US20110136683A1 - Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer - Google Patents

Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer Download PDF

Info

Publication number
US20110136683A1
US20110136683A1 US12/994,408 US99440809A US2011136683A1 US 20110136683 A1 US20110136683 A1 US 20110136683A1 US 99440809 A US99440809 A US 99440809A US 2011136683 A1 US2011136683 A1 US 2011136683A1
Authority
US
United States
Prior art keywords
expression
prostate cancer
seq
nos
sequences
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US12/994,408
Inventor
Elai Davicioni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Veracyte Inc
Veracyte SD Inc
Original Assignee
GenomeDx Biosciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GenomeDx Biosciences Inc filed Critical GenomeDx Biosciences Inc
Priority to US12/994,408 priority Critical patent/US20110136683A1/en
Assigned to GENOMEDX BIOSCIENCES, INC. reassignment GENOMEDX BIOSCIENCES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DAVICIONI, ELAI
Publication of US20110136683A1 publication Critical patent/US20110136683A1/en
Assigned to CRG PARTNERS III - PARALLEL FUND "A" L.P., CRG PARTNERS III L.P., CRG PARTNERS III (CAYMAN) L.P. reassignment CRG PARTNERS III - PARALLEL FUND "A" L.P. SECURITY INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GENOMEDX BIOSCIENCES INC.
Assigned to DECIPHER BIOSCIENCES, INC. reassignment DECIPHER BIOSCIENCES, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: GENOMEDX INC.
Assigned to GENOMEDX INC. reassignment GENOMEDX INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: GENOMEDX BIOSCIENCES INC.
Assigned to DECIPHER BIOSCIENCES, INC. reassignment DECIPHER BIOSCIENCES, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: CRG PARTNERS III - PARALLEL FUND "A" L.P., CRG PARTNERS III (CAYMAN) L.P., CRG PARTNERS III L.P.
Assigned to VERACYTE, INC. reassignment VERACYTE, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: Veracyte SD, Inc.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Definitions

  • This invention relates to the field of diagnostics and in particular to systems and methods for classifying prostate cancer into distinct clinical disease states.
  • Prostate cancer is the most common malignancy affecting U.S. men, with approximately 240,000 new cases diagnosed each year.
  • the incidence of prostate cancer is increasing, in part due to increased surveillance efforts from the application of routine molecular testing such as prostate-specific antigen (PSA).
  • PSA prostate-specific antigen
  • prostate cancer is a slow-growing, organ-confined or localized malignancy that poses little risk of death.
  • the most common treatments for prostate cancer in the U.S. are surgical procedures such as radical prostatectomy, where the entire prostate is removed from the patient. This procedure on its own is highly curative for most but not all men.
  • RNA-based e.g., gene or non-coding RNA expression
  • protein-based e.g., protein expression or modification
  • FFPE-derived RNA is typically degraded and fragmented to between 100-300 bp in size and without poly-A tails making it of little use for traditional 3′-biased gene expression profiling, which requires larger microgram quantities of RNA with intact poly-A tails to prime cDNA synthesis.
  • An object of the present invention is to provide systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer.
  • a system for expression-based assessment of risk of prostate cancer recurrence after prostatectomy comprising one or more polynucleotides, each of said polynucleotides capable of specifically hybridizing to a RNA transcript of a gene selected from the group of genes set forth in Table 3 and/or 6.
  • a nucleic acid array for expression-based assessment of prostate cancer recurrence risk comprising at least ten probes immobilized on a solid support, each of said probes being between about 15 and about 500 nucleotides in length, each of said probes being derived from a sequence corresponding to, or complementary to, a transcript of a gene selected from the group of genes set forth in Table 3 and/or 6, or a portion of said transcript.
  • a method for expression-based assessment of prostate cancer recurrence comprising: (a) determining the expression level of one or more transcripts of one or more genes in a test sample obtained from said subject to provide an expression pattern profile, said one or more genes selected from the group of genes set forth in Table 3 and/or 6, and (c) comparing said expression pattern profile with a reference expression pattern profile.
  • kits for characterizing the expression of one or more nucleic acid sequences depicted in SEQ ID NOs: 1-2114 comprising one or more nucleic acids selected from (a) a nucleic acid depicted in any of SEQ ID NOs: 1-2114; (b) an RNA form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114; (c) a peptide nucleic acid form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114; (d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c); (e) a nucleic acid comprising at least 25 consecutive bases having at least 90% sequence identity to any of (a-c); or (f) a complement to any of (a-e); and optionally instructions for correlating the expression level of said one or more nucleic acid sequences with the disease state of prostate cancer tissue.
  • an array of probe nucleic acids certified for use in expression-based assessment of prostate cancer recurrence risk comprising at least two different probe nucleic acids that specifically hybridize to corresponding different target nucleic acids depicted in one of SEQ ID NOs: 1-2114, an RNA form thereof, or a complement to either thereof.
  • a device for classifying a biological sample from a prostate cancer as recurrent or non-recurrent comprising means for measuring the expression level of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6; means for correlating the expression level with a classification of prostate cancer status; and means for outputting the prostate cancer status.
  • a computer-readable medium comprising one or more digitally-encoded expression pattern profiles representative of the level of expression of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6, each of said one or more expression pattern profiles being associated with a value wherein each of said values is correlated with the presence of recurrent or non-recurrent prostate cancer.
  • FIG. 1 A) Principle components analysis (PCA) of 2,114 RNAs identified to be differentially expressed between tumors from patients with differing clinical outcome (see Table 2 for comparisons evaluated), PCA plot of 22 prostate cancer tumors shows tight clustering of samples by clinical outcome of patients (circles, NED; diamonds, PSA; squares, SYS).
  • PCA Principle components analysis
  • Table 4 Two-way hierarchical clustering dendrogram and expression matrix of 526 target sequences (Table 4) RNAs filtered using linear regression (p ⁇ 0.01) to identify RNAs that followed either SYS>PSA>NED or NED>PSA>SYS trend in differential expression.
  • FIG. 2 Histograms showing distribution patient's tumor expression levels of a ‘metagene’ generated from a linear combination of the 526 RNAs for each clinical group. The histograms bin samples with similar metagene expression values and significantly separate three modes of patient metagene scores (ANOVA, p ⁇ 0.000001) corresponding to the three clinical status groups evaluated.
  • FIG. 3 Scatter plots summarizing the mean ( ⁇ standard deviation) of metagene expression values for tumor samples from patients in the three clinical status groups (NED; PSA; SYS). Metagenes were generated from a linear combinations of 6 ( ⁇ ), 18 ( ⁇ ) or 20 ( ⁇ ) RNAs and demonstrate highly significant differential expression between clinical groups (ANOVA, p ⁇ 0.000001).
  • FIG. 4 Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using an 18-target sequence metagene (Table 7) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between NED and PSA (*) as well as between PSA and SYS (**) clinical groups (p ⁇ 7 ⁇ 10 ⁇ 7 and p ⁇ 1 ⁇ 10 ⁇ 6 , respectively).
  • FIG. 5 Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 10-target sequence metagene (Table 9) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p ⁇ 4 ⁇ 10 ⁇ 10 ).
  • FIG. 6 Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 41-target sequence metagene (Table 10) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p ⁇ 2 ⁇ 10 ⁇ 11 ).
  • FIG. 7 Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 148-target sequence metagene to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p ⁇ 9 ⁇ 10 ⁇ 12 ).
  • the present invention provides a system and method for assessing prostate cancer recurrence risk by distinguishing clinically distinct disease states in men with prostate cancer at the time of initial diagnosis or surgery.
  • the system and methods are based on the identification of gene transcripts following a retrospective analysis of tumor samples that are differentially expressed in prostate cancer in a manner dependent on prostate cancer aggressiveness as indicated by long-term post-prostatectomy clinical outcome.
  • These gene transcripts can be considered as a library which can be used as a resource for the identification of sets of specific target sequences (“prostate cancer prognostic sets”), which may represent the entire library of gene transcripts or a subset of the library and the detection of which is indicative of prostate cancer recurrence risk.
  • the invention further provides for probes capable of detecting these target sequences and primers that are capable of amplifying the target sequences.
  • the system and method for assessing prostate cancer recurrence risk are prognostic for a post surgery clinical outcome selected from no evidence of disease (‘NED’), biochemical relapse (two successive increases in prostate-specific antigen levels; (‘PSA’) and systemic prostate cancer systemic metastases (‘SYS’).
  • NED no evidence of disease
  • PSA prostate-specific antigen levels
  • SYS systemic prostate cancer systemic metastases
  • the target sequences comprised by the prostate cancer prognostic set are sequences based on or derived from the gene transcripts from the library, or a subset thereof. Such sequences are occasionally referred to herein as “probe selection regions” or “PSRs.”
  • the target sequences comprised by the prostate classification set are sequences based on the gene transcripts from the library, or a subset thereof, and include both coding and non-coding sequences.
  • the systems and methods provide for the molecular analysis of the expression levels of one or more of the target sequences as set forth in SEQ ID NOs: 1-2114 (Table 4). Increased relative expression of one or more target sequences in a ‘NED’ Group corresponding to the sequences as set forth in SEQ ID NOs: 1-913 is indicative of or predictive of a non-recurrent form of prostate cancer and can be correlated with an increased likelihood of a long-term NED prognosis or low risk of prostate cancer recurrence.
  • Increased relative expression of one or more target sequences in a ‘SYS’ Group corresponding to the sequences as set forth in SEQ ID NOs: 914-2114 is indicative of or predictive of an aggressive form of prostate cancer and can be correlated with an increased likelihood of a long-term SYS prognosis or high risk of prostate cancer recurrence.
  • intermediate relative levels of one or more target sequences in a ‘PSA’ Group corresponding to target sequences set forth in Table 7 is indicative of or predictive of biochemical recurrence. Subsets and combinations of these target sequences or probes complementary thereto may be used as described herein.
  • polynucleotide refers to a polymer of greater than one nucleotide in length of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), hybrid RNA/DNA, modified RNA or DNA, or RNA or DNA mimetics, including peptide nucleic acids (PNAs).
  • the polynucleotides may be single- or double-stranded.
  • the term includes polynucleotides composed of naturally-occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as polynucleotides having non-naturally-occurring portions which function similarly.
  • backbone backbone linkages
  • Such modified or substituted polynucleotides are well-known in the art and for the purposes of the present invention, are referred to as “analogues.”
  • Complementary or “substantially complementary” refers to the ability to hybridize or base pair between nucleotides or nucleic acids, such as, for instance, between a sensor peptide nucleic acid or polynucleotide and a target polynucleotide.
  • Complementary nucleotides are, generally, A and T (or A and U), or C and G.
  • Two single-stranded polynucleotides or PNAs are said to be substantially complementary when the bases of one strand, optimally aligned and compared and with appropriate insertions or deletions, pair with at least about 80% of the bases of the other strand, usually at least about 90% to 95%, and more preferably from about 98 to 100%.
  • substantial complementarity exists when a polynucleotide will hybridize under selective hybridization conditions to its complement.
  • selective hybridization will occur when there is at least about 65% complementarity over a stretch of at least 14 to 25 bases, for example at least about 75%, or at least about 90% complementarity. See, M. Kanehisa Nucleic Acids Res. 12:203 (1984).
  • Preferential binding or “preferential hybridization” refers to the increased propensity of one polynucleotide to bind to its complement in a sample as compared to a noncomplementary polymer in the sample.
  • Hybridization conditions will typically include salt concentrations of less than about 1M, more usually less than about 500 mM, for example less than about 200 mM.
  • the hybridization can be done in solutions containing little or no salt.
  • Hybridization temperatures can be as low as 5° C., but are typically greater than 22° C., and more typically greater than about 30° C., for example in excess of about 37° C. Longer fragments may require higher hybridization temperatures for specific hybridization as is known in the art.
  • hybridization conditions which may be controlled include buffer type and concentration, solution pH, presence and concentration of blocking reagents to decrease background binding such as repeat sequences or blocking protein solutions, detergent type(s) and concentrations, molecules such as polymers which increase the relative concentration of the polynucleotides, metal ion(s) and their concentration(s), chelator(s) and their concentrations, and other conditions known in the art.
  • Multiplexing herein refers to an assay or other analytical method in which multiple analytes can be assayed simultaneously.
  • a “target sequence” as used herein refers to a region of the genome against which one or more probes can be designed.
  • a probe is any polynucleotide capable of selectively hybridizing to a target sequence or its complement, or to an RNA version of either.
  • a probe may comprise ribonucleotides, deoxyribonucleotides, peptide nucleic acids, and combinations thereof.
  • a probe may optionally comprise one or more labels.
  • a probe may be used to amplify one or both strands of a target sequence or an RNA form thereof, acting as a sole primer in an amplification reaction or as a member of a set of primers.
  • NED describes a clinically distinct disease state in which patients show no evidence of disease (‘NED’) at least 5 years after surgery
  • PSA describes a clinically distinct disease state in which patients show biochemical relapse only (two successive increases in prostate-specific antigen levels but no other symptoms of disease with at least 5 years follow up after surgery; ‘PSA’) and ‘SYS’ describes a clinically distinct disease state in which patients develop biochemical relapse and present with systemic prostate cancer disease or metastases (‘SYS’) within five years after the initial treatment with radical prostatectomy.
  • the term “about” refers to approximately a +/ ⁇ 10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.
  • the system of the present invention is based on the identification of a library of gene and RNA transcripts that are differentially expressed in prostate cancer in a manner dependent on prostate cancer aggressiveness as indicated by the post-prostatectomy clinical outcome of the patient.
  • relative over expression of one or more of the gene transcripts in a prostate cancer sample compared to a reference sample or expression profile or signature there from may be prognostic of a clinically distinct disease outcome post-prostatectomy selected from no evidence of disease (‘NED’), biochemical relapse (‘PSA’) and prostate cancer disease systemic recurrence or metastases (‘SYS’).
  • the reference sample can be, for example, from prostate cancer sample(s) of one or more references subject(s) with a known post-prostatectomy clinical outcomes.
  • the reference expression profile or signature may optionally be normalized to one or more appropriate reference gene transcripts.
  • expression of one or more of the gene transcripts in a prostate cancer sample may be compared to an expression profile or signature from normal prostate tissue.
  • Expression profiles or signatures from prostate cancer samples may be normalized to one or more house keeping gene transcripts such that normalized over and/or under expression of one or more of the gene transcripts in a sample may be indicative of a clinically distinct disease state or prognosis.
  • the Prostate Prognostic Library in accordance with the present invention comprises one or more gene or RNA transcripts whose relative and/or normalized expression is indicative of prostate cancer recurrence and which may be prognostic for post-prostatectomy clinical outcome of a patient.
  • RNA transcripts that showed differential expression in prostate cancer samples from patients with clinically distinct disease outcomes after initial treatment with radical prostatectomy are shown in Table 3.
  • the library comprises one or more of the gene transcripts of the genes listed in Table 3.
  • the library comprises at least one transcript from at least one gene selected from those listed in Table 3. In one embodiment, the library comprises at least one transcript from each of at least 5 genes selected from those listed in Table 3. In another embodiment, the library comprises at least one transcript from each of at least 10 genes selected from those listed in Table 3. In a further embodiment, the library comprises at least one transcript from each of at least 15 genes selected from those listed in Table 1. In other embodiments, the library comprises at least one transcript from each of at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60 and at least 65 genes selected from those listed in Table 3. In a further embodiment, the library comprises at least one transcript from all of the genes listed in Table 3. In a further embodiment, the library comprises at all transcripts from all of the genes listed in Table 3.
  • the library comprises at least one transcript from at least one gene selected from the group consisting of [NM — 001004722]; [NM — 001005522]; [NM — 001013671]; [NM — 001033517]; [NM — 183049]; [NM — 212559]; 5′-3′ exoribonuclease 1; A kinase (PRKA) anchor protein (yotiao) 9; AarF domain containing kinase 4; Abhydrolase domain containing 3; Aconitase 1, soluble; Actinin, alpha 1; ADAM metallopeptidase domain 19 (meltrin beta); Adaptor-related protein complex 1, gamma 2 subunit; Adenosine deaminase, RNA-specific, B2 (RED2 homolog rat); Adenylate cyclase 3; ADP-ribosylation factor GTPase activating protein 3; ADP-rib
  • Anthrax toxin receptor 1 Anthrax toxin receptor 1; Antizyme inhibitor 1; Arachidonate 12-lipoxygenase, 12R type; Arginine vasopressin receptor 1A; Arginine-glutamic acid dipeptide (RE) repeats; ARP3 actin-related protein 3 homolog (yeast); Arrestin 3, retinal (X-arrestin); Arrestin domain containing 1; Aryl hydrocarbon receptor interacting protein-like 1; Aryl hydrocarbon receptor nuclear translocator; Ataxin 1; ATM/ATR-Substrate Chk2-Interacting Zn2+-finger protein; ATPase, Class I, type 8B, member 1; ATPase, Na+/K+ transporting, alpha 1 polypeptide; ATP-binding cassette, sub-family F (GCN20), member 1; Autism susceptibility candidate 2; Baculoviral IAP repeat-containing 6 (apollon); Basonuclin 2; Brain-specific angiogenesis inhibitor 3; Bromodomain
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Ankyrin repeat domain 15; UDP-glucose ceramide glucosyltransferase-like 2; Hypothetical protein FLJ12949; Chromosome 22 open reading frame 13; Phosphatidylinositol glycan anchor biosynthesis, class O; Solute carrier family 43, member 1; Rabaptin, RAB GTPase binding effector protein 1; Zinc finger protein 14 homolog; Hypothetical gene supported by AK128346; Adenylate cyclase 3; Phosphatidylinositol transfer protein, beta; Zinc finger protein 667; Gremlin 1, cysteine knot superfamily, homolog; Ankyrin 3, node of Ranvier (ankyrin G) and Maltase-glucoamylase (alpha-
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Ankyrin repeat domain 15; Hypothetical protein FLJ12949; Solute carrier family 43, member 1; Thioredoxin-like 2; Polymerase (RNA) II (DNA directed) polypeptide L; Syntaxin 5; Leucine rich repeat containing 16; Calcium channel, voltage-dependent, beta 4 subunit; [NM — 001005522]; G protein-coupled receptor kinase interactor 2; Ankyrin 3, node of Ranvier (ankyrin G); Gremlin 1, cysteine knot superfamily, homolog; Zinc finger protein 667; Hypothetical gene supported by AK128346; Transmembrane 9 superfamily member 2; Potassium channel, subfamily K, member 1; Chromodomain helicase DNA binding protein 2; Microcephaly, primary autosomal recessive 1; Chromosome 21 open reading frame 34 and Dual specificity phosphatase
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Ankyrin repeat domain 15; Ankyrin 3, node of Ranvier (ankyrin G) and Maltase-glucoamylase (alpha-glucosidase).
  • activator 1 Replication factor C
  • Tripartite motif-containing 61 Tripartite motif-containing 61
  • Citrate lyase beta like Citrate lyase beta like
  • Ankyrin repeat domain 15 Ankyrin 3, node of Ranvier (ankyrin G)
  • Maltase-glucoamylase alpha-glucosidase
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Ankyrin repeat domain 15; Hypothetical protein FLJ12949; Solute carrier family 43, member 1; Thioredoxin-like 2; Polymerase (RNA) II (DNA directed) polypeptide L; Syntaxin 5; Leucine rich repeat containing 16; Calcium channel, voltage-dependent, beta 4 subunit; [NM — 001005522]; G protein-coupled receptor kinase interactor 2; Ankyrin 3, node of Ranvier (ankyrin G); Gremlin 1, cysteine knot superfamily, homolog; Zinc finger protein 667; Hypothetical gene supported by AK128346; Transmembrane 9 superfamily member 2; Potassium channel, subfamily K, member 1; Chromodomain helicase DNA binding protein 2; Chromosome 9 open reading frame 94; Chromosome 21 open reading frame 34; and Dual specificity phosphatase 5.
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Citrate lyase beta like; Phosphodiesterase 4D, cAMP-specific; Ectodysplasin A receptor; DEP domain containing 6; Basonuclin 2; Chromosome 2 open reading frame 3; FLJ25476 protein; Staphylococcal nuclease and tudor domain containing 1; Hermansky-Pudlak syndrome 5 and Chromosome 12 open reading frame 30.
  • the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Adaptor-related protein complex 1, gamma 2 subunit; Kallikrein-related peptidase 2; Phosphodiesterase 4D, cAMP-specific; Cytochrome P450, family 4, subfamily F, polypeptide 11; Ectodysplasin A receptor
  • Phospholipase C beta 1; KIAA1244; Paraoxonase 2; Arachidonate 12-lipoxygenase, 12R type; Cut-like 2; Chemokine (C-X-C motif) ligand 12; Rho guanine nucleotide exchange factor (GEF) 5; Olfactory receptor, family 2, subfamily A, member 4; Chromosome 19 open reading frame 42; Hypothetical gene supported by AK128346; Phosphoglucomutase 5; Hyaluronan binding protein 4; NECAP endocytosis associated 2 Myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4; Signal transducer and activator of transcription 1; Chromosome 2 open reading frame 3; FLJ25476 protein; Staphylococcal nuclease and tudor domain containing 1; Transmembrane protein 18; Hermansky-Pudlak syndrome 5; Chromosome 12 open reading frame 30;
  • the invention also contemplates that alternative libraries may be designed that include transcripts of one or more of the genes in Table 3, together with additional gene transcripts that have previously been shown to be associated with prostate cancer systemic progression.
  • the publication and sequence databases can be mined using a variety of search strategies to identify appropriate additional candidates for inclusion in the library.
  • search strategies for example, currently available scientific and medical publication databases such as Medline, Current Contents, OMIM (online Mendelian inheritance in man), various Biological and Chemical Abstracts, Journal indexes, and the like can be searched using term or key-word searches, or by author, title, or other relevant search parameters.
  • databases are publicly available, and strategies and procedures for identifying publications and their contents, for example, genes, other nucleotide sequences, descriptions, indications, expression pattern, etc, are well known to those skilled in the art. Numerous databases are available through the internet for free or by subscription, see, for example, the National Center Biotechnology Information (NCBI), Infotrieve, Thomson ISI, and Science Magazine (published by the AAAS) websites. Additional or alternative publication or citation databases are also available that provide identical or similar types of information, any of which can be employed in the context of the invention. These databases can be searched for publications describing altered gene expression between recurrent and non-recurrent prostate cancer.
  • Additional potential candidate genes may be identified by searching the above described databases for differentially expressed proteins and by identifying the nucleotide sequence encoding the differentially expressed proteins.
  • a list of genes whose altered expression is between patients with recurrent disease and non-recurrent prostate cancer is presented in Table 6.
  • a Prostate Prognostic Set comprises one or more target sequences identified within the gene transcripts in the prostate prognostic library, or a subset of these gene transcripts.
  • the target sequences may be within the coding and/or non-coding regions of the gene transcripts.
  • the set can comprise one or a plurality of target sequences from each gene transcript in the library, or subset thereof. The relative and/or normalized level of these target sequences in a sample is indicative of the level of expression of the particular gene transcript and thus of prostate cancer recurrence risk.
  • the relative and/or normalized expression level of one or more of the target sequences may be indicative of an recurrent form of prostate cancer and therefore prognostic for prostate cancer systemic progression while the relative and/or normalized expression level of one or more other target sequences may be indicative of a non-recurrent form of prostate cancer and therefore prognostic for a NED clinical outcome.
  • one embodiment of the present invention provides for a library or catalog of candidate target sequences derived from the transcripts (both coding and non-coding regions) of at least one gene suitable for classifying prostate cancer recurrence risk.
  • the present invention provides for a library or catalog of candidate target sequences derived from the non-coding regions of transcripts of at least one gene suitable for classifying prostate cancer recurrence risk.
  • the library or catalog of candidate target sequences comprises target sequences derived from the transcripts of one or more of the genes set forth in Table 3 and/or Table 6. The library or catalog in affect provides a resource list of transcripts from which target sequences appropriate for inclusion in a Prostate Cancer Prognostic set can be derived.
  • an individual Prostate Cancer Prognostic set may comprise target sequences derived from the transcripts of one or more genes exhibiting a positive correlation with recurrent prostate cancer. In one embodiment, an individual Prostate Cancer Prognostic Set may comprise target sequences derived from the transcripts of one or more genes exhibiting a negative correlation with recurrent prostate cancer. In one embodiment, an individual Prostate Cancer Prognostic Set may comprise target sequences derived from the transcripts of two or more genes, wherein at least one gene has a transcript that exhibits a positive correlation with recurrent prostate cancer and at least one gene has a transcript that exhibits negative correlation with recurrent prostate cancer.
  • the Prostate Cancer Prognostic Set comprises target sequences derived from the transcripts of at least one gene. In one embodiment, the Prostate Cancer Prognostic Set comprises target sequences derived from the transcripts of at least 5 genes. In another embodiment, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 10 genes. In a further embodiment, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 15 genes. In other embodiments, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60 and at least 65 genes.
  • target sequences can be identified by screening for target sequences that have been annotated to be associated with each specific gene locus from a number of annotation sources including GenBank, RefSeq, Ensembl, dbEST, GENSCAN, TWINSCAN, Exoniphy, Vega, microRNAs registry and others (see Affymetrix Exon Array design note).
  • target sequences can be further evaluated for potential cross-hybridization against other putative transcribed sequences in the design (but not the entire genome) to identify only those target sequences that are predicted to uniquely hybridize to a single target.
  • the set of target sequences that are predicted to uniquely hybridize to a single target can be further filtered using a variety of criteria including, for example, sequence length, for their mean expression levels across a wide selection of human tissues, as being representive of transcripts expressed either as novel alternative (i.e., non-consensus) exons, alternative retained introns, novel exons 5′ or 3′ of the gene's transcriptional start site or representing transcripts expressed in a manner antisense to the gene, amongst others.
  • sequence length for their mean expression levels across a wide selection of human tissues, as being representive of transcripts expressed either as novel alternative (i.e., non-consensus) exons, alternative retained introns, novel exons 5′ or 3′ of the gene's transcriptional start site or representing transcripts expressed in a manner antisense to the gene, amongst others.
  • the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #2 of Ankyrin repeat domain 15; in exon #1 of UDP-glucose ceramide glucosyltransferase-like 2; in exon of #19 of Hypothetical protein FLJ12949; in intron #4 of Chromosome 22 open reading frame 13; in exon #2 of phatidylinositol glycan anchor biosynthesis, class O; in exon #15 of Solute carrier family 43, member 1; in exon #1 of Rabaptin, RAB GTPase binding effector protein 1; in intron #38 of Maltase-glucoamylase (alpha-glucosidase); in intron #23 of Ankyrin 3, node of Ranvier (activator 1)
  • the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3; in intron #2 of Ankyrin repeat domain 15; in exon #19 of Hypothetical protein FLJ12949; in exon #15 of Solute carrier family 43, member 1; 313,721 base pair 3′ of Thioredoxin-like 2; in exon #2 of Polymerase (RNA) II (DNA directed) polypeptide L, 7.6 kDa; in intron #10 of Syntaxin 5; 141,389 base pair 5′ of Leucine rich repeat containing 16; in intron #2 of Calcium channel, voltage-dependent, beta 4 subunit; 5,474 base pair 5′ of [NM — 001005522]; in intron #14 of G protein-coupled receptor kinase interactor 2; in intron #23 of Ankyrin 3, node of Ranvier (ankyrin G); 71,333 base pair 3′ of Gremlin 1, cysteine knot superfamily
  • the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #2 of Ankyrin repeat domain 15; in intron #38 of Maltase-glucoamylase (alpha-glucosidase); and in intron #23 of Ankyrin 3, node of Ranvier (ankyrin G).
  • the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; in intron #2 of Ankyrin repeat domain 15; in exon #19 of Hypothetical protein FLJ12949; in exon #15 of Solute carrier family 43, member 1; 313,721 base pair 3′ of Thioredoxin-like 2; in exon #2 of Polymerase (RNA) II (DNA directed) polypeptide L, 7.6 kDa; in intron #10 of Syntaxin 5; 141,389 base pair 5′ of Leucine rich repeat containing 16; in intron #2 of Calcium channel, voltage-dependent, beta 4 subunit; 5,474 base pair 5′ of [NM — 001005522]; in intron #14 of G protein-coupled receptor kinase interactor 2; in intron #2 of Ankyrin 3, node of Ranvier (ankyrin G); 71,333 base pair of 3′ Gremlin 1, cyste
  • the Prostate Classification Set comprises target sequences derived from in intron #3 of Citrate lyase beta like; 210,560 base pair 5′ of Phosphodiesterase 4D; 189,722 base pair 5′ of Ectodysplasin A receptor; 3,510 base pair 3′ of DEP domain containing 6; in exon #6 of Basonuclin 2; in intron #1 of Chromosome 2 open reading frame 3; in intron #1 of FLJ25476 protein; in intron #10 of Staphylococcal nuclease and tudor domain containing 1; in exon #22 of Hermansky-Pudlak syndrome 5; and in exon #24 of Chromosome 12 open reading frame 30.
  • the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #1 of Adaptor-related protein complex 1, gamma 2 subunit; in intron #2 of Kallikrein-related peptidase 2; 210,560 base pair 5′ of Phosphodiesterase 4D; 3,508 base pair 3′ of Cytochrome P450, family 4, subfamily F, polypeptide 11; 189,722 base pair 5′ of Ectodysplasin A receptor; in intron #2 of Phospholipase C, beta 1; in intron #10 of KIAA1244; in intron #2 of Paraoxonase 2; 11,235 base pair 3′ of Arachidonate 12-lipoxygenase, 12R type; in exon #22 of Cut-like 2;
  • the potential set of target sequences can be filtered for their expression levels using the multi-tissue expression data made publicly available by Affymetrix at (http://www.affymetrix.com/stipport/technical/sample_data/exon_array_data.affx) such that probes with, for example, elevated expression across numerous tissues (non-specific) or no expression in prostate tissue can be excluded.
  • each target sequence suitable for use in the Prostate Cancer Prognostic Set may be validated to confirm differential relative or normalized expression in recurrent prostate cancer or non-recurrent prostate cancer.
  • Validation methods are known in the art and include hybridization techniques such as microarray analysis or Northern blotting using appropriate controls, and may include one or more additional steps, such as reverse transcription, transcription, PCR, RT-PCR and the like. The validation of the target sequences using these methods is well within the abilities of a worker skilled in the art.
  • individual Prostate Cancer Prognostic Sets provide for at least a determination of a minimal expression signature, capable of distinguishing recurrent from non-recurrent forms of prostate cancer.
  • Means for determining the appropriate number of target sequences necessary to obtain a minimal expression signature are known in the art and include the Nearest Shrunken Centroids (NSC) method.
  • a standardized centroid is computed for each class. This is the average gene expression for each gene in each class divided by the within-class standard deviation for that gene.
  • Nearest centroid classification takes the gene expression profile of a new sample, and compares it to each of these class centroids. The class whose centroid that it is closest to, in squared distance, is the predicted class for that new sample.
  • Nearest shrunken centroid classification “shrinks” each of the class centroids toward the overall centroid for all classes by an amount called the threshold. This shrinkage consists of moving the centroid towards zero by threshold, setting it equal to zero if it hits zero.
  • centroid of 3.2 would be shrunk to 1.2
  • centroid of ⁇ 3.4 would be shrunk to ⁇ 1.4
  • centroid of 1.2 would be shrunk to zero.
  • the new sample is classified by the usual nearest centroid rule, but using the shrunken class centroids. This shrinkage can make the classifier more accurate by reducing the effect of noisy genes and provides an automatic gene selection.
  • a gene is shrunk to zero for all classes, then it is eliminated from the prediction rule. Alternatively, it may be set to zero for all classes except one, and it can be learned that the high or low expression for that gene characterizes that class. The user decides on the value to use for threshold.
  • PAM does K-fold cross-validation for a range of threshold values.
  • the samples are divided up at random into K roughly equally sized parts.
  • the classifier is built on the other K ⁇ 1 parts then tested on the remaining part. This is done for a range of threshold values, and the cross-validated misclassification error rate is reported for each threshold value.
  • the user would choose the threshold value giving the minimum cross-validated misclassification error rate.
  • minimal expression signatures can be established through the use of optimization algorithms such as the mean variance algorithm widely used in establishing stock portfolios.
  • This method is described in detail in US patent publication number 20030194734.
  • the method calls for the establishment of a set of inputs (stocks in financial applications, expression as measured by intensity here) that will optimize the return (e.g., signal that is generated) one receives for using it while minimizing the variability of the return.
  • the method calls for the establishment of a set of inputs (e.g., expression as measured by intensity) that will optimize the signal while minimizing variability.
  • Many commercial software programs are available to conduct such operations. “Wagner Associates Mean-Variance Optimization Application,” referred to as “Wagner Software” throughout this specification, is preferred.
  • This software uses functions from the “Wagner Associates Mean-Variance Optimization Library” to determine an efficient frontier and optimal portfolios in the Markowitz sense is preferred. Use of this type of software requires that microarray data be transformed so that it can be treated as an input in the way stock return and risk measurements are used when the software is used for its intended financial analysis purposes.
  • the process of selecting a minimal expression signature can also include the application of heuristic rules.
  • such rules are formulated based on biology and an understanding of the technology used to produce clinical results. More preferably, they are applied to output from the optimization method.
  • the mean variance method of portfolio selection can be applied to microarray data for a number of genes differentially expressed in subjects with cancer. Output from the method would be an optimized set of genes that could include some genes that are expressed in peripheral blood as well as in diseased tissue.
  • heuristic rules can be applied that are not necessarily related to the biology in question. For example, one can apply a rule that only a prescribed percentage of the portfolio can be represented by a particular gene or group of genes.
  • Commercially available software such as the Wagner Software readily accommodates these types of heuristics. This can be useful, for example, when factors other than accuracy and precision (e.g., anticipated licensing fees) have an impact on the desirability of including one or more genes.
  • the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of target sequences shown to have a positive correlation with non-recurrent prostate disease, for example those depicted in SEQ ID NOs:1-913 or a subset thereof.
  • the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of those target sequences shown to have a positive correlation with recurrent prostate cancer, for example those depicted in of SEQ ID NOs: 914-2114, or a subset thereof.
  • the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of target sequences shown to have a correlation with non-recurrent or recurrent prostate cancer, for example those depicted in SEQ ID NOs:1-2114 or a subset thereof.
  • the Prostate Cancer Prognostic Set comprises target sequences for detecting expression products of SEQ IDs:1-2114. In some embodiments, the Prostate Cancer Prognostic Set comprises probes for detecting expression levels of sequences exhibiting positive and negative correlation with a disease status of interest are employed.
  • a combination target sequences useful in these methods were found to include those encoding RNAs corresponding to SEQ ID NOs: 1-913 (found at increased expression in prostate cancer samples from NED patients) and/or corresponding to SEQ ID NOs: 914-2114 (found at increased expression levels in prostate cancer samples from SYS patients), where intermediate levels of certain target sequences (Table 7) are observed in prostate cancer samples from PSA patients with biochemical recurrence, where the RNA expression levels are indicative of a disease state or outcome. Subgroups of these target sequences, as well as individual target sequences, have been found useful in such methods.
  • an RNA signature corresponding to SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21 915-917, 920, 922, 928, 929, 931, 935 and 936 (the 21-RNA′ signature) and/or SEQ ID NOs: 1-11, 914-920 (the ‘18-RNA’ signature) and/or SEQ ID NOs: 1-4, 914,915) (the ‘6-RNA’ signature) and/or SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935 and 936 (the ‘20-RNA’ signature) and/or SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022 (the ‘10-RNA’ signature) and/or SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920,
  • Exemplary subsets and combinations of interest also include at least five, six, 10, 15, 18, 20, 23, 25, 27, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 750, 1000, 1200, 1400, 1600, 1800, 2000, or all 2114 target sequences in Table 4; at least five, six, 10, 15, 18, 20, 23, 25, 27, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, or all 526 target sequences in Table 7; SEQ ID NOs:1, 4, 915, 6, 916, 9, 917, 920, 922, 14, 15, 16, 928, 929, 18, 19, 931, 20, 21, 935, 936, or combinations thereof; SEQ ID NOs:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 914, 915, 916, 917,
  • Exemplary subsets of interest include those described herein, including in the examples.
  • Exemplary combinations of interest include those utilizing one or more of the sequences listed in Tables 5, 7, 8, 9 or 10. Of particular interest are those combinations utilizing at least one sequence exhibiting positive correlation with the trait of interest, as well as those combinations utilizing at least one sequence exhibiting negative correlation with the trait of interest. Also of interest are those combinations utilizing at least two, at least three, at least four, at least five or at least six of those sequences exhibiting such a positive correlation, in combination with at least two, at least three, at least four, at least five, or at least six of those sequences exhibiting such a negative correlation. Exemplary combinations include those utilizing at least one, two, three, four, five or six of the target sequences depicted in Tables 5 and 6.
  • increased relative expression of one or more of SEQ IDs:1-913, decreased relative expression of one or more of SEQ ID NOs:914-2114 or a combination of any thereof is indicative/predictive of the patient exhibiting no evidence of disease for at least seven years or more after surgery.
  • increased relative expression of SEQ IDs:914-2114, decreased relative expression of one or more of SEQ ID NOs:1-913 or a combination of any thereof is indicative/predictive of the patient exhibiting systemic prostate cancer.
  • Increased or decreased expression of target sequences represented in these sequence listings, or of the target sequences described in the examples, may be utilized in the methods of the invention.
  • the Prostate Cancer Prognostic Set can optionally include one or more target sequences specifically derived from the transcripts of one or more housekeeping genes and/or one or more internal control target sequences and/or one or more negative control target sequences. In one embodiment, these target sequences can, for example, be used to normalize expression data.
  • Housekeeping genes from which target sequences for inclusion in a Prostate Cancer Prognostic Set can be derived from are known in the art and include those genes in which are expressed at a constant level in normal and prostate cancer tissue.
  • target sequences described herein may be used alone or in combination with each other or with other known or later identified disease markers.
  • the system of the present invention provides for combinations of polynucleotide probes that are capable of detecting the target sequences of the Prostate Cancer Prognostic Sets.
  • Individual polynucleotide probes comprise a nucleotide sequence derived from the nucleotide sequence of the target sequences or complementary sequences thereof.
  • the nucleotide sequence of the polynucleotide probe is designed such that it corresponds to, or is complementary to the target sequences.
  • the polynucleotide probe can specifically hybridize under either stringent or lowered stringency hybridization conditions to a region of the target sequences, to the complement thereof, or to a nucleic acid sequence (such as a cDNA) derived therefrom.
  • polynucleotide probe sequences and determination of their uniqueness may be carried out in silico using techniques known in the art, for example, based on a BLASTN search of the polynucleotide sequence in question against gene sequence databases, such as the Human Genome Sequence, UniGene, dbEST or the non-redundant database at NCBI.
  • the polynucleotide probe is complementary to a region of a target mRNA derived from a target sequence in the Prostate Cancer Prognostic Set.
  • Computer programs can also be employed to select probe sequences that will not cross hybridize or will not hybridize non-specifically.
  • nucleotide sequence of the polynucleotide probe need not be identical to its target sequence in order to specifically hybridize thereto.
  • the polynucleotide probes of the present invention therefore, comprise a nucleotide sequence that is at least about 75% identical to a region of the target gene or mRNA.
  • nucleotide sequence of the polynucleotide probe is at least about 90% identical a region of the target gene or mRNA.
  • nucleotide sequence of the polynucleotide probe is at least about 95% identical to a region of the target gene or mRNA.
  • nucleotide sequence of the polynucleotide probes of the present invention may exhibit variability by differing (e.g. by nucleotide substitution, including transition or transversion) at one, two, three, four or more nucleotides from the sequence of the target gene.
  • the probes can be designed to have ⁇ 50% G content and/or between about 25% and about 70% G+C content.
  • Strategies to optimize probe hybridization to the target nucleic acid sequence can also be included in the process of probe selection.
  • Hybridization under particular pH, salt, and temperature conditions can be optimized by taking into account melting temperatures and by using empirical rules that correlate with desired hybridization behaviours.
  • Computer models may be used for predicting the intensity and concentration-dependence of probe hybridization.
  • a probe in order to represent a unique sequence in the human genome, a probe should be at least 15 nucleotides in length. Accordingly, the polynucleotide probes of the present invention range in length from about 15 nucleotides to the full length of the target sequence or target mRNA. In one embodiment of the invention, the polynucleotide probes are at least about 15 nucleotides in length. In another embodiment, the polynucleotide probes are at least about 20 nucleotides in length. In a further embodiment, the polynucleotide probes are at least about 25 nucleotides in length.
  • the polynucleotide probes are between about 15 nucleotides and about 500 nucleotides in length. In other embodiments, the polynucleotide probes are between about 15 nucleotides and about 450 nucleotides, about 15 nucleotides and about 400 nucleotides, about 15 nucleotides and about 350 nucleotides, about 15 nucleotides and about 300 nucleotides in length.
  • the polynucleotide probes of a Prostate Cancer Prognostic Set can comprise RNA, DNA, RNA or DNA mimetics, or combinations thereof, and can be single-stranded or double-stranded.
  • the polynucleotide probes can be composed of naturally-occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as polynucleotide probes having non-naturally-occurring portions which function similarly.
  • Such modified or substituted polynucleotide probes may provide desirable properties such as, for example, enhanced affinity for a target gene and increased stability.
  • the system of the present invention further provides for primers and primer pairs capable of amplifying target sequences defined by the Prostate Cancer Prognostic Set, or fragments or subsequences or complements thereof.
  • the nucleotide sequences of the Prostate Cancer Prognostic set may be provided in computer-readable media for in silico applications and as a basis for the design of appropriate primers for amplification of one or more target sequences of the Prostate Cancer Prognostic Set.
  • Primers based on the nucleotide sequences of target sequences can be designed for use in amplification of the target sequences.
  • a pair of primers will be used.
  • the exact composition of the primer sequences is not critical to the invention, but for most applications the primers will hybridize to specific sequences of the Prostate Cancer Prognostic Set under stringent conditions, particularly under conditions of high stringency, as known in the art.
  • the pairs of primers are usually chosen so as to generate an amplification product of at least about 50 nucleotides, more usually at least about 100 nucleotides. Algorithms for the selection of primer sequences are generally known, and are available in commercial software packages.
  • primers may be used in standard quantitative or qualitative PCR-based assays to assess transcript expression levels of RNAs defined by the Prostate Cancer Prognostic Set.
  • these primers may be used in combination with probes, such as molecular beacons in amplifications using real-time PCR.
  • the primers or primer pairs when used in an amplification reaction, specifically amplify at least a portion of a nucleic acid depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), an RNA form thereof, or a complement to either thereof.
  • a nucleoside is a base-sugar combination and a nucleotide is a nucleoside that further includes a phosphate group covalently linked to the sugar portion of the nucleoside.
  • the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound, with the normal linkage or backbone of RNA and DNA being a 3′ to 5′ phosphodiester linkage.
  • polynucleotide probes or primers useful in this invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages.
  • oligonucleotides having modified backbones include both those that retain a phosphorus atom in the backbone and those that lack a phosphorus atom in the backbone.
  • modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleotides.
  • Exemplary polynucleotide probes or primers having modified oligonucleotide backbones include, for example, those with one or more modified internucleotide linkages that are phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′ amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkyl-phosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′.
  • Exemplary modified oligonucleotide backbones that do not include a phosphorus atom are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages.
  • Such backbones include morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulphone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulphamate backbones; methyleneimino and methylenehydrazino backbones; sulphonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH 2 component parts.
  • the present invention also contemplates oligonucleotide mimetics in which both the sugar and the internucleoside linkage of the nucleotide units are replaced with novel groups.
  • the base units are maintained for hybridization with an appropriate nucleic acid target compound.
  • An example of such an oligonucleotide mimetic which has been shown to have excellent hybridization properties, is a peptide nucleic acid (PNA) [Nielsen et al., Science, 254:1497-1500 (1991)].
  • PNA peptide nucleic acid
  • the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone.
  • LNAs locked nucleic acids
  • the nucleobases are retained and are bound directly or indirectly to aza-nitrogen atoms of the amide portion of the backbone.
  • the present invention also contemplates polynucleotide probes or primers comprising “locked nucleic acids” (LNAs), which are novel conformationally restricted oligonucleotide analogues containing a methylene bridge that connects the 2′-O of ribose with the 4′-C (see, Singh et al., Chem. Commun., 1998, 4:455-456).
  • LNA and LNA analogues display very high duplex thermal stabilities with complementary DNA and RNA, stability towards 3′-exonuclease degradation, and good solubility properties.
  • LNAs form duplexes with complementary DNA or RNA or with complementary LNA, with high thermal affinities.
  • the universality of LNA-mediated hybridization has been emphasized by the formation of exceedingly stable LNA:LNA duplexes (Koshkin et al., J. Am. Chem. Soc., 1998, 120:13252-13253).
  • LNA:LNA hybridization was shown to be the most thermally stable nucleic acid type duplex system, and the RNA-mimicking character of LNA was established at the duplex level.
  • Introduction of three LNA monomers (T or A) resulted in significantly increased melting points toward DNA complements.
  • Modified polynucleotide probes or primers may also contain one or more substituted sugar moieties.
  • oligonucleotides may comprise sugars with one of the following substituents at the 2′ position: OH; F; O—, S—, or N-alkyl; O—, S—, or N-alkenyl; O—, S— or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C 1 to C 10 alkyl or C 2 to C 10 alkenyl and alkynyl.
  • Examples of such groups are: O[(CH 2 ) n O] m CH 3 , O(CH 2 ) n OCH 3 , O(CH 2 ) n NH 2 , O(CH 2 ) n CH 3 , O(CH 2 ) n ONH 2 , and O(CH 2 ) n ON[(CH 2 ) n CH 3 )] 2 , where n and m are from 1 to about 10.
  • the oligonucleotides may comprise one of the following substituents at the 2′ position: C 1 to C 10 lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH 3 , OCN, Cl, Br, CN, CF 3 , OCF 3 , SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , NH 2 , heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties.
  • 2′-methoxyethoxy (2′-O—CH 2 CH 2 OCH 3 , also known as 2′-O-(2-methoxyethyl) or 2′-MOE)
  • 2′-dimethylaminooxyethoxy (O(CH 2 ) 2 ON(CH 3 ) 2 group, also known as 2′-DMAOE)
  • 2′-methoxy (2′-O—CH 3 )
  • 2′-aminopropoxy (2′-OCH 2 CH 2 CH 2 NH 2 )
  • 2′-fluoro 2′-F
  • polynucleotide probes or primers may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar.
  • Polynucleotide probes or primers may also include modifications or substitutions to the nucleobase.
  • “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U).
  • Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substitute
  • nucleobases include those disclosed in U.S. Pat. No. 3,687,808; The Concise Encyclopedia Of Polymer Science And Engineering, (1990) pp 858-859, Kroschwitz, J. I., ed. John Wiley & Sons; Englisch et al., Angewandte Chemie, Int. Ed., 30:613 (1991); and Sanghvi, Y. S., (1993) Antisense Research and Applications , pp 289-302, Crooke, S. T. and Lebleu, B., ed., CRC Press. Certain of these nucleobases are particularly useful for increasing the binding affinity of the polynucleotide probes of the invention.
  • 5-substituted pyrimidines include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. [Sanghvi, Y. S., (1993) Antisense Research and Applications , pp 276-278, Crooke, S. T. and Lebleu, B., ed., CRC Press, Boca Raton].
  • nucleotide sequence of the entire length of the polynucleotide probe or primer does not need to be derived from the target sequence.
  • the polynucleotide probe may comprise nucleotide sequences at the 5′ and/or 3′ termini that are not derived from the target sequences.
  • Nucleotide sequences which are not derived from the nucleotide sequence of the target sequence may provide additional functionality to the polynucleotide probe. For example, they may provide a restriction enzyme recognition sequence or a “tag” that facilitates detection, isolation, purification or immobilisation onto a solid support.
  • the additional nucleotides may provide a self-complementary sequence that allows the primer/probe to adopt a hairpin configuration.
  • Such configurations are necessary for certain probes, for example, molecular beacon and Scorpion probes, which can be used in solution hybridization techniques.
  • the polynucleotide probes or primers can incorporate moieties useful in detection, isolation, purification, or immobilisation, if desired.
  • moieties are well-known in the art (see, for example, Ausubel et al., (1997 & updates) Current Protocols in Molecular Biology , Wiley & Sons, New York) and are chosen such that the ability of the probe to hybridize with its target sequence is not affected.
  • Suitable moieties are detectable labels, such as radioisotopes, fluorophores, chemiluminophores, enzymes, colloidal particles, and fluorescent microparticles, as well as antigens, antibodies, haptens, avidin/streptavidin, biotin, haptens, enzyme cofactors/substrates, enzymes, and the like.
  • a label can optionally be attached to or incorporated into a probe or primer polynucleotide to allow detection and/or quantitation of a target polynucleotide representing the target sequence of interest.
  • the target polynucleotide may be the expressed target sequence RNA itself, a cDNA copy thereof, or an amplification product derived therefrom, and may be the positive or negative strand, so long as it can be specifically detected in the assay being used.
  • an antibody may be labeled.
  • labels used for detecting different targets may be distinguishable.
  • the label can be attached directly (e.g., via covalent linkage) or indirectly, e.g., via a bridging molecule or series of molecules (e.g., a molecule or complex that can bind to an assay component, or via members of a binding pair that can be incorporated into assay components, e.g. biotin-avidin or streptavidin).
  • a bridging molecule or series of molecules e.g., a molecule or complex that can bind to an assay component, or via members of a binding pair that can be incorporated into assay components, e.g. biotin-avidin or streptavidin.
  • Many labels are commercially available in activated forms which can readily be used for such conjugation (for example through amine acylation), or labels may be attached through known or determinable conjugation schemes, many of which are known in the art.
  • Labels useful in the invention described herein include any substance which can be detected when bound to or incorporated into the biomolecule of interest. Any effective detection method can be used, including optical, spectroscopic, electrical, piezoelectrical, magnetic, Raman scattering, surface plasmon resonance, colorimetric, calorimetric, etc.
  • a label is typically selected from a chromophore, a lumiphore, a fluorophore, one member of a quenching system, a chromogen, a hapten, an antigen, a magnetic particle, a material exhibiting nonlinear optics, a semiconductor nanocrystal, a metal nanoparticle, an enzyme, an antibody or binding portion or equivalent thereof, an aptamer, and one member of a binding pair, and combinations thereof.
  • Quenching schemes may be used, wherein a quencher and a fluorophore as members of a quenching pair may be used on a probe, such that a change in optical parameters occurs upon binding to the target introduce or quench the signal from the fluorophore.
  • a molecular beacon Suitable quencher/fluorophore systems are known in the art.
  • the label may be bound through a variety of intermediate linkages.
  • a polynucleotide may comprise a biotin-binding species, and an optically detectable label may be conjugated to biotin and then bound to the labeled polynucleotide.
  • a polynucleotide sensor may comprise an immunological species such as an antibody or fragment, and a secondary antibody containing an optically detectable label may be added.
  • Chromophores useful in the methods described herein include any substance which can absorb energy and emit light.
  • a plurality of different signaling chromophores can be used with detectably different emission spectra.
  • the chromophore can be a lumophore or a fluorophore.
  • Typical fluorophores include fluorescent dyes, semiconductor nanocrystals, lanthanide chelates, polynucleotide-specific dyes and green fluorescent protein.
  • Coding schemes may optionally be used, comprising encoded particles and/or encoded tags associated with different polynucleotides of the invention.
  • a variety of different coding schemes are known in the art, including fluorophores, including SCNCs, deposited metals, and RF tags.
  • Polynucleotides from the described target sequences may be employed as probes for detecting target sequences expression, for ligation amplification schemes, or may be used as primers for amplification schemes of all or a portion of a target sequences.
  • amplified either strand produced by amplification may be provided in purified and/or isolated form.
  • polynucleotides of the invention include a nucleic acid depicted in (a) any one of SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (b) an RNA form of any one of the nucleic acids depicted in SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (c) a peptide nucleic acid form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c); (e) a nucleic acid comprising at least 25 bases having at least 90% sequenced identity to any of (a-c); and (f) a complement to any of (a-e).
  • Complements may take any polymeric form capable of base pairing to the species recited in (a)-(e), including nucleic acid such as RNA or DNA, or may be a neutral polymer such as a peptide nucleic acid.
  • Polynucleotides of the invention can be selected from the subsets of the recited nucleic acids described herein, as well as their complements.
  • polynucleotides of the invention comprise at least 20 consecutive bases as depicted in SEQ ID NOs:1-2114, or a complement thereto.
  • the polynucleotides may comprise at least 21, 22, 23, 24, 25, 27, 30, 32, 35 or more consecutive bases as depicted in SEQ ID NOs:1-2114, as applicable.
  • the nucleic acid in (a) can be selected from those in Table 3, and from SEQ ID NOs:1, 4, 915, 6, 916, 9, 917, 920, 922, 14, 15, 16, 928, 929, 18, 19, 931, 20, 21, 935, and 936; or from SEQ ID NOs:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 914, 915, 916, 917, 918, 919, and 920; or from SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935 and 936; or from SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022; or from SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971,
  • the polynucleotides may be provided in a variety of formats, including as solids, in solution, or in an array.
  • the polynucleotides may optionally comprise one or more labels, which may be chemically and/or enzymatically incorporated into the polynucleotide.
  • solutions comprising polynucleotide and a solvent are also provided.
  • the solvent may be water or may be predominantly aqueous.
  • the solution may comprise at least two, three, four, five, six, seven, eight, nine, ten, twelve, fifteen, seventeen, twenty or more different polynucleotides, including primers and primer pairs, of the invention. Additional substances may be included in the solution, alone or in combination, including one or more labels, additional solvents, buffers, biomolecules, polynucleotides, and one or more enzymes useful for performing methods described herein, including polymerases and ligases.
  • the solution may further comprise a primer or primer pair capable of amplifying a polynucleotide of the invention present in the solution.
  • one or more polynucleotides provided herein can be provided on a substrate.
  • the substrate can comprise a wide range of material, either biological, nonbiological, organic, inorganic, or a combination of any of these.
  • the substrate may be a polymerized Langmuir Blodgett film, functionalized glass, Si, Ge, GaAs, GaP, SiO 2 , SiN 4 , modified silicon, or any one of a wide variety of gels or polymers such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, cross-linked polystyrene, polyacrylic, polylactic acid, polyglycolic acid, poly(lactide coglycolide), polyanhydrides, poly(methyl methacrylate), poly(ethylene-co-vinyl acetate), polysiloxanes, polymeric silica, latexes, dextran polymers, epoxies, polycarbonates,
  • Substrates can be planar crystalline substrates such as silica based substrates (e.g. glass, quartz, or the like), or crystalline substrates used in, e.g., the semiconductor and microprocessor industries, such as silicon, gallium arsenide, indium doped GaN and the like, and includes semiconductor nanocrystals.
  • silica based substrates e.g. glass, quartz, or the like
  • crystalline substrates used in, e.g., the semiconductor and microprocessor industries such as silicon, gallium arsenide, indium doped GaN and the like, and includes semiconductor nanocrystals.
  • the substrate can take the form of an array, a photodiode, an optoelectronic sensor such as an optoelectronic semiconductor chip or optoelectronic thin-film semiconductor, or a biochip.
  • the location(s) of probe(s) on the substrate can be addressable; this can be done in highly dense formats, and the location(s) can be microaddressable or nanoaddressable.
  • Silica aerogels can also be used as substrates, and can be prepared by methods known in the art. Aerogel substrates may be used as free standing substrates or as a surface coating for another substrate material.
  • the substrate can take any form and typically is a plate, slide, bead, pellet, disk, particle, microparticle, nanoparticle, strand, precipitate, optionally porous gel, sheets, tube, sphere, container, capillary, pad, slice, film, chip, multiwell plate or dish, optical fiber, etc.
  • the substrate can be any form that is rigid or semi-rigid.
  • the substrate may contain raised or depressed regions on which an assay component is located.
  • the surface of the substrate can be etched using known techniques to provide for desired surface features, for example trenches, v-grooves, mesa structures, or the like.
  • Surfaces on the substrate can be composed of the same material as the substrate or can be made from a different material, and can be coupled to the substrate by chemical or physical means.
  • Such coupled surfaces may be composed of any of a wide variety of materials, for example, polymers, plastics, resins, polysaccharides, silica or silica-based materials, carbon, metals, inorganic glasses, membranes, or any of the above-listed substrate materials.
  • the surface can be optically transparent and can have surface Si—OH functionalities, such as those found on silica surfaces.
  • the substrate and/or its optional surface can be chosen to provide appropriate characteristics for the synthetic and/or detection methods used.
  • the substrate and/or surface can be transparent to allow the exposure of the substrate by light applied from multiple directions.
  • the substrate and/or surface may be provided with reflective “mirror” structures to increase the recovery of light.
  • the substrate and/or its surface is generally resistant to, or is treated to resist, the conditions to which it is to be exposed in use, and can be optionally treated to remove any resistant material after exposure to such conditions.
  • the substrate or a region thereof may be encoded so that the identity of the sensor located in the substrate or region being queried may be determined Any suitable coding scheme can be used, for example optical codes, RFID tags, magnetic codes, physical codes, fluorescent codes, and combinations of codes.
  • the polynucleotide probes or primers of the present invention can be prepared by conventional techniques well-known to those skilled in the art.
  • the polynucleotide probes can be prepared using solid-phase synthesis using commercially available equipment.
  • modified oligonucleotides can also be readily prepared by similar methods.
  • the polynucleotide probes can also be synthesized directly on a solid support according to methods standard in the art. This method of synthesizing polynucleotides is particularly useful when the polynucleotide probes are part of a nucleic acid array.
  • Polynucleotide probes or primers can be fabricated on or attached to the substrate by any suitable method, for example the methods described in U.S. Pat. No. 5,143,854, PCT Publ. No. WO 92/10092, U.S. patent application Ser. No. 07/624,120, filed Dec. 6, 1990 (now abandoned), Fodor et al., Science, 251: 767-777 (1991), and PCT Publ. No. WO 90/15070). Techniques for the synthesis of these arrays using mechanical synthesis strategies are described in, e.g., PCT Publication No. WO 93/09668 and U.S. Pat. No. 5,384,261.
  • Still further techniques include bead based techniques such as those described in PCT Appl. No. PCT/US93/04145 and pin based methods such as those described in U.S. Pat. No. 5,288,514. Additional flow channel or spotting methods applicable to attachment of sensor polynucleotides to a substrate are described in U.S. patent application Ser. No. 07/980,523, filed Nov. 20, 1992, and U.S. Pat. No. 5,384,261.
  • polynucleotide probes of the present invention can be prepared by enzymatic digestion of the naturally occurring target gene, or mRNA or cDNA derived therefrom, by methods known in the art.
  • the present invention further provides methods for characterizing prostate cancer sample for recurrence risk.
  • the methods use the Prostate Cancer Prognostic Sets, probes and primers described herein to provide expression signatures or profiles from a test sample derived from a subject having or suspected of having prostate cancer.
  • such methods involve contacting a test sample with Prostate Cancer Prognostic probes (either in solution or immobilized) under conditions that permit hybridization of the probe(s) to any target nucleic acid(s) present in the test sample and then detecting any probe:target duplexes formed as an indication of the presence of the target nucleic acid in the sample.
  • Expression patterns thus determined are then compared to one or more reference profiles or signatures.
  • the expression pattern can be normalized.
  • the methods use the Prostate Cancer Prognostic Sets, probes and primers described herein to provide expression signatures or profiles from a test sample derived from a subject to classify the prostate cancer as recurrent or non-recurrent.
  • such methods involve the specific amplification of target sequences nucleic acid(s) present in the test sample using methods known in the art to generate an expression profile or signature which is then compared to a reference profile or signature.
  • the invention further provides for prognosing patient outcome, predicting likelihood of recurrence after prostatectomy and/or for designating treatment modalities.
  • the methods generate expression profiles or signatures detailing the expression of the 2114 target sequences having altered relative expression with different prostate cancer outcomes. In one embodiment, the methods generate expression profiles or signatures detailing the expression of the subsets of these target sequences having 526 or 18 target sequences as described in the examples.
  • increased relative expression of one or more of SEQ IDs:1-913, decreased relative expression of one or more of SEQ ID NOs:914-2114 or a combination of any thereof is indicative of a non-recurrent form of prostate cancer and may be predictive a NED clinical outcome after surgery.
  • increased relative expression of SEQ IDs:914-2114, decreased relative expression of one or more of SEQ ID NOs:1-913 or a combination of any thereof is indicative of a recurrent form of prostate cancer and may be predictive of a SYS clinical outcome after surgery.
  • Increased or decreased expression of target sequences represented in these sequence listings, or of the target sequences described in the examples, may be utilized in the methods of the invention.
  • intermediate levels of expression of one or more target sequences depicted in Table 7 indicate a probability of future biochemical recurrence.
  • the methods detect combinations of expression levels of sequences exhibiting positive and negative correlation with a disease status. In one embodiment, the methods detect a minimal expression signature.
  • any method of detecting and/or quantitating the expression of the encoded target sequences can in principle be used in the invention.
  • Such methods can include Northern blotting, array or microarray hybridization, by enzymatic cleavage of specific structures (e.g., an Invader® assay, Third Wave Technologies, e.g. as described in U.S. Pat. Nos. 5,846,717, 6,090,543; 6,001,567; 5,985,557; and 5,994,069) and amplification methods, e.g. RT-PCR, including in a TaqMan® assay (PE Biosystems, Foster City, Calif., e.g. as described in U.S. Pat. Nos.
  • nucleic acids may be amplified, labeled and subjected to microarray analysis.
  • Single-molecule sequencing e.g., Illumina, Helicos, PacBio, ABI SOLID
  • in situ hybridization bead-array technologies
  • bead-array technologies e.g., Luminex xMAP, Illumina BeadChips
  • branched DNA technology e.g., Panomics, Genisphere
  • the expressed target sequences can be directly detected and/or quantitated, or may be copied and/or amplified to allow detection of amplified copies of the expressed target sequences or its complement.
  • degraded and/or fragmented RNA can be usefully analyzed for expression levels of target sequences, for example RNA having an RNA integrity number of less than 8.
  • quantitative RT-PCR assays are used to measure the expression level of target sequences depicted in SEQ IDs: 1-2114.
  • a GeneChip or microarray can be used to measure the expression of one or more of the target sequences.
  • Molecular assays measure the relative expression levels of the target sequences, which can be normalized to the expression levels of one or more control sequences, for example array control sequences and/or one or more housekeeping genes, for example GAPDH. Increased (or decreased) relative expression of the target sequences as described herein, including any of SEQ ID NOs:1-2114, may thus be used alone or in any combination with each other in the methods described herein. In addition, negative control probes may be included.
  • Diagnostic samples for use with the systems and in the methods of the present invention comprise nucleic acids suitable for providing RNAs expression information.
  • the biological sample from which the expressed RNA is obtained and analyzed for target sequence expression can be any material suspected of comprising prostate cancer tissue or cells.
  • the diagnostic sample can be a biological sample used directly in a method of the invention.
  • the diagnostic sample can be a sample prepared from a biological sample.
  • the sample or portion of the sample comprising or suspected of comprising prostate cancer tissue or cells can be any source of biological material, including cells, tissue or fluid, including bodily fluids.
  • the source of the sample include an aspirate, a needle biopsy, a cytology pellet, a bulk tissue preparation or a section thereof obtained for example by surgery or autopsy, lymph fluid, blood, plasma, serum, tumors, and organs.
  • the samples may be archival samples, having a known and documented medical outcome, or may be samples from current patients whose ultimate medical outcome is not yet known.
  • the sample may be dissected prior to molecular analysis.
  • the sample may be prepared via macrodissection of a bulk tumor specimen or portion thereof, or may be treated via microdissection, for example via Laser Capture Microdissection (LCM).
  • LCD Laser Capture Microdissection
  • the sample may initially be provided in a variety of states, as fresh tissue, fresh frozen tissue, fine needle aspirates, and may be fixed or unfixed. Frequently, medical laboratories routinely prepare medical samples in a fixed state, which facilitates tissue storage.
  • fixatives can be used to fix tissue to stabilize the morphology of cells, and may be used alone or in combination with other agents. Exemplary fixatives include crosslinking agents, alcohols, acetone, Bouin's solution, Zenker solution, Hely solution, osmic acid solution and Carnoy solution.
  • Crosslinking fixatives can comprise any agent suitable for forming two or more covalent bonds, for example an aldehyde.
  • Sources of aldehydes typically used for fixation include formaldehyde, paraformaldehyde, glutaraldehyde or formalin.
  • the crosslinking agent comprises formaldehyde, which may be included in its native form or in the form of paraformaldehyde or formalin.
  • One or more alcohols may be used to fix tissue, alone or in combination with other fixatives.
  • exemplary alcohols used for fixation include methanol, ethanol and isopropanol.
  • Formalin fixation is frequently used in medical laboratories.
  • Formalin comprises both an alcohol, typically methanol, and formaldehyde, both of which can act to fix a biological sample.
  • the biological sample may optionally be embedded in an embedding medium.
  • embedding media used in histology including paraffin, Tissue-Tek® V.I.P.TM, Paramat, Paramat Extra, Paraplast, Paraplast X-tra, Paraplast Plus, Peel Away Paraffin Embedding Wax, Polyester Wax, Carbowax Polyethylene Glycol, PolyfinTM, Tissue Freezing Medium TFMTM, Cryo-GelTM, and OCT Compound (Electron Microscopy Sciences, Hatfield, Pa.).
  • the embedding material may be removed via any suitable techniques, as known in the art.
  • the embedding material may be removed by extraction with organic solvent(s), for example xylenes.
  • Kits are commercially available for removing embedding media from tissues. Samples or sections thereof may be subjected to further processing steps as needed, for example serial hydration or dehydration steps.
  • the sample is a fixed, wax-embedded biological sample.
  • samples from medical laboratories are provided as fixed, wax-embedded samples, most commonly as formalin-fixed, paraffin embedded (FFPE) tissues.
  • FFPE formalin-fixed, paraffin embedded
  • the target polynucleotide that is ultimately assayed can be prepared synthetically (in the case of control sequences), but typically is purified from the biological source and subjected to one or more preparative steps.
  • the RNA may be purified to remove or diminish one or more undesired components from the biological sample or to concentrate it. Conversely, where the RNA is too concentrated for the particular assay, it may be diluted.
  • RNA can be extracted and purified from biological samples using any suitable technique.
  • a number of techniques are known in the art, and several are commercially available (e.g., FormaPureTM nucleic acid extraction kit, Agencourt Biosciences, Beverly Mass., High Pure FFPE RNA Micro KitTM, Roche Applied Science, Indianapolis, Ind.).
  • RNA can be extracted from frozen tissue sections using TRIzol (Invitrogen, Carlsbad, Calif.) and purified using RNeasy Protect kit (Qiagen, Valencia, Calif.). RNA can be further purified using DNAse I treatment (Ambion, Austin, Tex.) to eliminate any contaminating DNA.
  • RNA concentrations can be made using a Nanodrop ND-1000 spectrophotometer (Nanodrop Technologies, Rockland, Del.). RNA integrity can be evaluated by running electropherograms, and RNA integrity number (RIN, a correlative measure that indicates intactness of mRNA) can be determined using the RNA 6000 PicoAssay for the Bioanalyzer 2100 (Agilent Technologies, Santa Clara, Calif.).
  • Reverse transcription can be performed using the Omniscript kit (Qiagen, Valencia, Calif.), Superscript III kit (Invitrogen, Carlsbad, Calif.), for RT-PCR.
  • Target-specific priming can be performed in order to increase the sensitivity of detection of target sequences and generate target-specific cDNA.
  • TaqMan® RT-PCR can be performed using Applied Biosystems Prism (ABI) 7900 HT instruments in a 5 ⁇ l volume with target sequence-specific cDNA equivalent to 1 ng total RNA. Primers and probes concentrations for TaqMan analysis are added to amplify fluorescent amplicons using PCR cycling conditions such as 95° C. for 10 minutes for one cycle, 95° C. for 20 seconds, and 60° C. for 45 seconds for 40 cycles. A reference sample can be assayed to ensure reagent and process stability. Negative controls (i.e., no template) should be assayed to monitor any exogenous nucleic acid contamination.
  • the nucleic acid portion of the sample comprising RNA that is or can be used to prepare the target polynucleotide(s) of interest can be subjected to one or more preparative reactions.
  • These preparative reactions can include in vitro transcription (IVT), labeling, fragmentation, amplification and other reactions.
  • mRNA can first be treated with reverse transcriptase and a primer to create cDNA prior to detection, quantitation and/or amplification; this can be done in vitro with purified mRNA or in situ, e.g., in cells or tissues affixed to a slide.
  • amplification is meant any process of producing at least one copy of a nucleic acid, in this case an expressed RNA, and in many cases produces multiple copies.
  • An amplification product can be RNA or DNA, and may include a complementary strand to the expressed target sequence.
  • DNA amplification products can be produced initially through reverse translation and then optionally from further amplification reactions.
  • the amplification product may include all or a portion of a target sequence, and may optionally be labeled.
  • a variety of amplification methods are suitable for use, including polymerase-based methods and ligation-based methods.
  • Exemplary amplification techniques include the polymerase chain reaction method (PCR), the ligase chain reaction (LCR), ribozyme-based methods, self sustained sequence replication (3SR), nucleic acid sequence-based amplification (NASBA), the use of Q Beta replicase, reverse transcription, nick translation, and the like.
  • Asymmetric amplification reactions may be used to preferentially amplify one strand representing the target sequence that is used for detection as the target polynucleotide.
  • the presence and/or amount of the amplification product itself may be used to determine the expression level of a given target sequence.
  • the amplification product may be used to hybridize to an array or other substrate comprising sensor polynucleotides which are used to detect and/or quantitate target sequence expression.
  • the first cycle of amplification in polymerase-based methods typically forms a primer extension product complementary to the template strand.
  • the template is single-stranded RNA
  • a polymerase with reverse transcriptase activity is used in the first amplification to reverse transcribe the RNA to DNA, and additional amplification cycles can be performed to copy the primer extension products.
  • the primers for a PCR must, of course, be designed to hybridize to regions in their corresponding template that will produce an amplifiable segment; thus, each primer must hybridize so that its 3′ nucleotide is paired to a nucleotide in its complementary template strand that is located 3′ from the 3′ nucleotide of the primer used to replicate that complementary template strand in the PCR.
  • the target polynucleotide can be amplified by contacting one or more strands of the target polynucleotide with a primer and a polymerase having suitable activity to extend the primer and copy the target polynucleotide to produce a full-length complementary polynucleotide or a smaller portion thereof.
  • Any enzyme having a polymerase activity that can copy the target polynucleotide can be used, including DNA polymerases, RNA polymerases, reverse transcriptases, enzymes having more than one type of polymerase or enzyme activity.
  • the enzyme can be thermolabile or thermostable. Mixtures of enzymes can also be used.
  • Exemplary enzymes include: DNA polymerases such as DNA Polymerase I (“Pol I”), the Klenow fragment of Pol I, T4, T7, Sequenase® T7, Sequenase® Version 2.0 T7, Tub, Taq, Tth, Pfx, Pfu, Tsp, Tfl, Tli and Pyrococcus sp GB-D DNA polymerases; RNA polymerases such as E. coli , SP6, T3 and T7 RNA polymerases; and reverse transcriptases such as AMV, M-MuLV, MMLV, RNAse H ⁇ MMLV (SuperScript®), SuperScript® II, ThermoScript®, HIV-1, and RAV2 reverse transcriptases.
  • DNA polymerases such as DNA Polymerase I (“Pol I”), the Klenow fragment of Pol I, T4, T7, Sequenase® T7, Sequenase® Version 2.0 T7, Tub, Taq, Tth, Pfx,
  • Exemplary polymerases with multiple specificities include RAV2 and Tli (exo-) polymerases.
  • Exemplary thermostable polymerases include Tub, Taq, Tth, Pfx, Pfu, Tsp, Tfl, Tli and Pyrococcus sp.
  • GB-D DNA polymerases are commercially available.
  • Suitable reaction conditions are chosen to permit amplification of the target polynucleotide, including pH, buffer, ionic strength, presence and concentration of one or more salts, presence and concentration of reactants and cofactors such as nucleotides and magnesium and/or other metal ions (e.g., manganese), optional cosolvents, temperature, thermal cycling profile for amplification schemes comprising a polymerase chain reaction, and may depend in part on the polymerase being used as well as the nature of the sample.
  • Cosolvents include formamide (typically at from about 2 to about 10%), glycerol (typically at from about 5 to about 10%), and DMSO (typically at from about 0.9 to about 10%).
  • Techniques may be used in the amplification scheme in order to minimize the production of false positives or artifacts produced during amplification. These include “touchdown” PCR, hot-start techniques, use of nested primers, or designing PCR primers so that they form stem-loop structures in the event of primer-dimer formation and thus are not amplified.
  • Techniques to accelerate PCR can be used, for example centrifugal PCR, which allows for greater convection within the sample, and comprising infrared heating steps for rapid heating and cooling of the sample.
  • One or more cycles of amplification can be performed.
  • An excess of one primer can be used to produce an excess of one primer extension product during PCR; preferably, the primer extension product produced in excess is the amplification product to be detected.
  • a plurality of different primers may be used to amplify different target polynucleotides or different regions of a particular target polynucleotide within the sample.
  • An amplification reaction can be performed under conditions which allow an optionally labeled sensor polynucleotide to hybridize to the amplification product during at least part of an amplification cycle.
  • an assay is performed in this manner, real-time detection of this hybridization event can take place by monitoring for light emission or fluorescence during amplification, as known in the art.
  • amplification product is to be used for hybridization to an array or microarray
  • suitable commercially available amplification products are available. These include amplification kits available from NuGEN, Inc. (San Carlos, Calif.), including the WT-OvationTM System, WT-OvationTM System v2, WT-OvationTM Pico System, WT-OvationTM FFPE Exon Module, WT-OvationTM FFPE Exon Module RiboAmp and RiboAmp Plus RNA Amplification Kits (MDS Analytical Technologies (formerly Arcturus) (Mountain View, Calif.), Genisphere, Inc.
  • Amplified nucleic acids may be subjected to one or more purification reactions after amplification and labeling, for example using magnetic beads (e.g., RNAClean magnetic beads, Agencourt Biosciences).
  • magnetic beads e.g., RNAClean magnetic beads, Agencourt Biosciences.
  • RNA biomarkers can be analyzed using real-time quantitative multiplex RT-PCR platforms and other multiplexing technologies such as GenomeLab GeXP Genetic Analysis System (Beckman Coulter, Foster City, Calif.), SmartCycler® 9600 or GeneXpert(R) Systems (Cepheid, Sunnyvale, Calif.), ABI 7900 HT Fast Real Time PCR system (Applied Biosystems, Foster City, Calif.), LightCycler® 480 System (Roche Molecular Systems, Pleasanton, Calif.), xMAP 100 System (Luminex, Austin, Tex.) Solexa Genome Analysis System (Illumina, Hayward, Calif.), OpenArray Real Time qPCR (BioTrove, Woburn, Mass.) and BeadXpress System (Illumina, Hayward, Calif.).
  • GenomeLab GeXP Genetic Analysis System Beckman Coulter, Foster City, Calif.
  • SmartCycler® 9600 or GeneXpert(R) Systems Cepheid, Sunnyvale, Calif.
  • an “array” is a spatially or logically organized collection of polynucleotide probes. Any array comprising sensor probes specific for two or more of SEQ ID NOs: 1-2114 or a product derived therefrom can be used. Desirably, an array will be specific for 5, 10, 15, 20, 25, 30, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 1000, 1200, 1400, 1600, 1800, 2000 or more of SEQ ID NOs: 1-2114. Expression of these sequences may be detected alone or in combination with other transcripts.
  • an array which comprises a wide range of sensor probes for prostate-specific expression products, along with appropriate control sequences.
  • An array of interest is the Human Exon 1.0 ST Array (HuEx 1.0 ST, Affymetrix, Inc., Santa Clara, Calif.).
  • the polynucleotide probes are attached to a solid substrate and are ordered so that the location (on the substrate) and the identity of each are known.
  • the polynucleotide probes can be attached to one of a variety of solid substrates capable of withstanding the reagents and conditions necessary for use of the array.
  • Examples include, but are not limited to, polymers, such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, polycarbonate, polypropylene and polystyrene; ceramic; silicon; silicon dioxide; modified silicon; (fused) silica, quartz or glass; functionalized glass; paper, such as filter paper; diazotized cellulose; nitrocellulose filter; nylon membrane; and polyacrylamide gel pad. Substrates that are transparent to light are useful for arrays that will be used in an assay that involves optical detection.
  • array formats include membrane or filter arrays (for example, nitrocellulose, nylon arrays), plate arrays (for example, multiwell, such as a 24-, 96-, 256-, 384-, 864- or 1536-well, microtitre plate arrays), pin arrays, and bead arrays (for example, in a liquid “slurry”).
  • Arrays on substrates such as glass or ceramic slides are often referred to as chip arrays or “chips.” Such arrays are well known in the art.
  • the Prostate Cancer Prognosticarray is a chip.
  • Array data can be managed and analyzed using techniques known in the art.
  • the Genetrix suite of tools can be used for microarray analysis (Epicenter Software, Pasadena, Calif.).
  • Probe set modeling and data pre-processing can be derived using the Robust Multi-Array (RMA) algorithm or variant GC-RMA, Probe Logarithmic Intensity Error (PLIER) algorithm or variant iterPLIER.
  • RMA Robust Multi-Array
  • PLIER Probe Logarithmic Intensity Error
  • Variance or intensity filters can be applied to pre-process data using the RMA algorithm, for example by removing target sequences with a standard deviation of ⁇ 10 or a mean intensity of ⁇ 100 intensity units of a normalized data range, respectively.
  • one or more pattern recognition methods can be used in analyzing the expression level of target sequences.
  • the pattern recognition method can comprise a linear combination of expression levels, or a nonlinear combination of expression levels.
  • expression measurements for RNA transcripts or combinations of RNA transcript levels are formulated into linear or non-linear models or algorithms (i.e., an ‘expression signature’) and converted into a likelihood score.
  • This likelihood score indicates the probability that a biological sample is from a patient who will exhibit no evidence of disease, who will exhibit systemic cancer, or who will exhibit biochemical recurrence.
  • the likelihood score can be used to distinguish these disease states.
  • the models and/or algorithms can be provided in machine readable format, and may be used to correlate expression levels or an expression profile with a disease state, and/or to designate a treatment modality for a patient or class of patients.
  • results of the expression level analysis can be used to correlate increased expression of RNAs corresponding to SEQ ID NOs: 1-2114, or subgroups thereof as described herein, with prostate cancer outcome, and to designate a treatment modality.
  • Factors known in the art for diagnosing and/or suggesting, selecting, designating, recommending or otherwise determining a course of treatment for a patient or class of patients suspected of having prostate cancer can be employed in combination with measurements of the target sequence expression. These techniques include cytology, histology, ultrasound analysis, MRI results, CT scan results, and measurements of PSA levels.
  • a certified test comprises a means for characterizing the expression levels of one or more of the target sequences of interest, and a certification from a government regulatory agency endorsing use of the test for classifying the prostate disease status of a biological sample.
  • the certified test may comprise reagents for amplification reactions used to detect and/or quantitate expression of the target sequences to be characterized in the test.
  • An array of probe nucleic acids can be used, with or without prior target amplification, for use in measuring target sequence expression.
  • test is submitted to an agency having authority to certify the test for use in distinguishing prostate disease status and/or outcome.
  • Results of detection of expression levels of the target sequences used in the test and correlation with disease status and/or outcome are submitted to the agency.
  • a certification authorizing the diagnostic and/or prognostic use of the test is obtained.
  • portfolios of expression levels comprising a plurality of normalized expression levels of the target sequences described herein, including SEQ ID NOs:1-2114. Such portfolios may be provided by performing the methods described herein to obtain expression levels from an individual patient or from a group of patients.
  • the expression levels can be normalized by any method known in the art; exemplary normalization methods that can be used in various embodiments include Robust Multichip Average (RMA), probe logarithmic intensity error estimation (PLIER), non-linear fit (NLFIT) quantile-based and nonlinear normalization, and combinations thereof.
  • Background correction can also be performed on the expression data; exemplary techniques useful for background correction include mode of intensities, normalized using median polish probe modeling and sketch-normalization.
  • portfolios are established such that the combination of genes in the portfolio exhibit improved sensitivity and specificity relative to known methods.
  • a small standard deviation in expression measurements correlates with greater specificity.
  • Other measurements of variation such as correlation coefficients can also be used in this capacity.
  • the invention also encompasses the above methods where the specificity is at least about 50% or at least about 60%.
  • the invention also encompasses the above methods where the sensitivity is at least about 90%.
  • the gene expression profiles of each of the target sequences comprising the portfolio can fixed in a medium such as a computer readable medium.
  • a medium such as a computer readable medium.
  • This can take a number of forms. For example, a table can be established into which the range of signals (e.g., intensity measurements) indicative of disease or outcome is input. Actual patient data can then be compared to the values in the table to determine the patient samples diagnosis or prognosis.
  • patterns of the expression signals e.g., fluorescent intensity
  • the expression profiles of the samples can be compared to a control portfolio. If the sample expression patterns are consistent with the expression pattern for a known disease or disease outcome, the expression patterns can be used to designate one or more treatment modalities. For patients with test scores consistent with systemic disease outcome after prostatectomy, additional treatment modalities such as adjuvant chemotherapy (e.g., docetaxel, mitoxantrone and prednisone), systemic radiation therapy (e.g., samarium or strontium) and/or anti-androgen therapy (e.g., surgical castration, finasteride, dutasteride) can be designated.
  • adjuvant chemotherapy e.g., docetaxel, mitoxantrone and prednisone
  • systemic radiation therapy e.g., samarium or strontium
  • anti-androgen therapy e.g., surgical castration, finasteride, dutasteride
  • Such patients would likely be treated immediately with anti-androgen therapy alone or in combination with radiation therapy in order to eliminate presumed micro-metastatic disease, which cannot be detected clinically but can be revealed by the target sequence expression signature. Such patients can also be more closely monitored for signs of disease progression.
  • adjuvant therapy would not likely be recommended by their physicians in order to avoid treatment-related side effects such as metabolic syndrome (e.g., hypertension, diabetes and/or weight gain) or osteoporosis.
  • Patients with samples consistent with NED could be designated for watchful waiting, or for no treatment.
  • Patients with test scores that do not correlate with systemic disease but who have successive PSA increases could be designated for watchful waiting, increased monitoring, or lower dose or shorter duration anti-androgen therapy.
  • Target sequences can be grouped so that information obtained about the set of target sequences in the group can be used to make or assist in making a clinically relevant judgment such as a diagnosis, prognosis, or treatment choice.
  • a patient report comprising a representation of measured expression levels of a plurality of target sequences in a biological sample from the patient, wherein the representation comprises expression levels of target sequences corresponding to any one, two, three, four, five, six, eight, ten, twenty, thirty, fifty or more of the target sequences depicted in SEQ ID NOs: 1-2114, or of the subsets described herein, or of a combination thereof.
  • the representation of the measured expression level(s) may take the form of a linear or nonlinear combination of expression levels of the target sequences of interest.
  • the patient report may be provided in a machine (e.g., a computer) readable format and/or in a hard (paper) copy.
  • the report can also include standard measurements of expression levels of said plurality of target sequences from one or more sets of patients with known disease status and/or outcome.
  • the report can be used to inform the patient and/or treating physician of the expression levels of the expressed target sequences, the likely medical diagnosis and/or implications, and optionally may recommend a treatment modality for the patient.
  • the articles can also include instructions for assessing the gene expression profiles in such media.
  • the articles may comprise a readable storage form having computer instructions for comparing gene expression profiles of the portfolios of genes described above.
  • the articles may also have gene expression profiles digitally recorded therein so that they may be compared with gene expression data from patient samples.
  • the profiles can be recorded in different representational format. A graphical recordation is one such format. Clustering algorithms can assist in the visualization of such data.
  • Kits for performing the desired method(s) comprise a container or housing for holding the components of the kit, one or more vessels containing one or more nucleic acid(s), and optionally one or more vessels containing one or more reagents.
  • the reagents include those described in the composition of matter section above, and those reagents useful for performing the methods described, including amplification reagents, and may include one or more probes, primers or primer pairs, enzymes (including polymerases and ligases), intercalating dyes, labeled probes, and labels that can be incorporated into amplification products.
  • the kit comprises primers or primer pairs specific for those subsets and combinations of target sequences described herein. At least two, three, four or five primers or pairs of primers suitable for selectively amplifying the same number of target sequence-specific polynucleotides can be provided in kit form. In some embodiments, the kit comprises from five to fifty primers or pairs of primers suitable for amplifying the same number of target sequence-representative polynucleotides of interest.
  • the primers or primer pairs of the kit when used in an amplification reaction, specifically amplify at least a portion of a nucleic acid depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), an RNA form thereof, or a complement to either thereof.
  • the kit may include a plurality of such primers or primer pairs which can specifically amplify a corresponding plurality of different nucleic acids depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), RNA forms thereof, or complements thereto.
  • At least two, three, four or five primers or pairs of primers suitable for selectively amplifying the same number of target sequence-specific polynucleotides can be provided in kit form.
  • the kit comprises from five to fifty primers or pairs of primers suitable for amplifying the same number of target sequence-representative polynucleotides of interest.
  • the reagents may independently be in liquid or solid form.
  • the reagents may be provided in mixtures.
  • Control samples and/or nucleic acids may optionally be provided in the kit.
  • Control samples may include tissue and/or nucleic acids obtained from or representative of prostate tumor samples from patients showing no evidence of disease, as well as tissue and/or nucleic acids obtained from or representative of prostate tumor samples from patients that develop systemic prostate cancer.
  • the nucleic acids may be provided in an array format, and thus an array or microarray may be included in the kit.
  • the kit optionally may be certified by a government agency for use in prognosing the disease outcome of prostate cancer patients and/or for designating a treatment modality.
  • kit Instructions for using the kit to perform one or more methods of the invention can be provided with the container, and can be provided in any fixed medium.
  • the instructions may be located inside or outside the container or housing, and/or may be printed on the interior or exterior of any surface thereof.
  • a kit may be in multiplex form for concurrently detecting and/or quantitating one or more different target polynucleotides representing the expressed target sequences.
  • the devices can comprise means for characterizing the expression level of a target sequence of the invention, for example components for performing one or more methods of nucleic acid extraction, amplification, and/or detection.
  • Such components may include one or more of an amplification chamber (for example a thermal cycler), a plate reader, a spectrophotometer, capillary electrophoresis apparatus, a chip reader, and or robotic sample handling components. These components ultimately can obtain data that reflects the expression level of the target sequences used in the assay being employed.
  • the devices may include an excitation and/or a detection means. Any instrument that provides a wavelength that can excite a species of interest and is shorter than the emission wavelength(s) to be detected can be used for excitation. Commercially available devices can provide suitable excitation wavelengths as well as suitable detection components.
  • Exemplary excitation sources include a broadband UV light source such as a deuterium lamp with an appropriate filter, the output of a white light source such as a xenon lamp or a deuterium lamp after passing through a monochromator to extract out the desired wavelength(s), a continuous wave (cw) gas laser, a solid state diode laser, or any of the pulsed lasers.
  • Emitted light can be detected through any suitable device or technique; many suitable approaches are known in the art.
  • a fluorimeter or spectrophotometer may be used to detect whether the test sample emits light of a wavelength characteristic of a label used in an assay.
  • the devices typically comprise a means for identifying a given sample, and of linking the results obtained to that sample.
  • Such means can include manual labels, barcodes, and other indicators which can be linked to a sample vessel, and/or may optionally be included in the sample itself, for example where an encoded particle is added to the sample.
  • the results may be linked to the sample, for example in a computer memory that contains a sample designation and a record of expression levels obtained from the sample. Linkage of the results to the sample can also include a linkage to a particular sample receptacle in the device, which is also linked to the sample identity.
  • the devices also comprise a means for correlating the expression levels of the target sequences being studied with a prognosis of disease outcome.
  • Such means may comprise one or more of a variety of correlative techniques, including lookup tables, algorithms, multivariate models, and linear or nonlinear combinations of expression models or algorithms.
  • the expression levels may be converted to one or more likelihood scores, reflecting a likelihood that the patient providing the sample will exhibit a particular disease outcome.
  • the models and/or algorithms can be provided in machine readable format, and can optionally further designate a treatment modality for a patient or class of patients.
  • the device also comprises output means for outputting the disease status, prognosis and/or a treatment modality.
  • output means can take any form which transmits the results to a patient and/or a healthcare provider, and may include a monitor, a printed format, or both.
  • the device may use a computer system for performing one or more of the steps provided.
  • FFPE Formalin-fixed paraffin embedded
  • RNA Extraction RNA was extracted and purified from FFPE tissue sections using a modified protocol for the commercially available High Pure FFPE RNA Micro nucleic acid extraction kit (Roche Applied Sciences, Indianapolis, Ind.). RNA concentrations were calculated using a Nanodrop ND-1000 spectrophotometer (Nanodrop Technologies, Rockland, Del.).
  • RNA Amplification and GeneChip Hybridization Purified RNA was subjected to whole-transcriptome amplification using the WT-Ovation FFPE system including the WT-Ovation Exon and FL-Ovation Biotin V2 labeling modules, with the following modifications. Fifty (50) nanograms of RNA extracted from FFPE sections was used to generate amplified Ribo-SPIA product. For the WT-Ovation Exon sense-target strand conversion kit 4 ug of Ribo-SPIA product were used. All clean-up steps were performed with RNAClean magnetic beads (Agencourt Biosciences).
  • Microarray Analysis All data management and analysis was conducted using the Genetrix suite of tools for microarray analysis (Epicenter Software, Pasadena, Calif.). Probe set modeling and data pre-processing were derived using the Robust Multi-Array (RMA) algorithm. The mode of intensity values was used for background correction and RMA-sketch was used for normalization and probe modeling used a median polish routine. A variance filter was applied to data pre-processed using the RMA algorithm, by removing target sequences with a mean intensity of ⁇ 10 intensity units of a normalized data range. Target sequences typically comprise four individual probes that interrogate the expression of RNA transcripts or portions thereof.
  • RMA Robust Multi-Array
  • RNAs Target sequence annotations and the sequences (RNAs) that they interrogate were downloaded from the Affymetrix website (www.netaffx.com).
  • Supervised analysis of differentially expressed RNA transcripts was determined based on the fold change in the average expression (at least 2 fold change) and the associated t-test, with a p-value cut-off of p ⁇ 0.001 between different prostate cancer patient disease states. Linear regression was also used to screen differentially expressed transcripts that displayed an expression pattern of NED>PSA>SYS or SYS>PSA>NED and genes were selected with a p-value cut-off of p ⁇ 0.01 for two-way hierarchical clustering using Pearson's correlation distance metric with complete-linkage cluster distances.
  • NED no evidence of disease
  • PSA patients with rising PSA or biochemical recurrence
  • PSA systemic or recurrent disease
  • RNAs RNA levels for RefSeq, dbEST and predicted transcripts
  • Table 3 displays the number of target sequences identified in two-way comparisons between different clinical states using the appropriate t-tests and a p-value cut-off of p ⁇ 0.001. At total of 2,114 target sequences (Table 3) were identified as differentially expressed in these comparisons and a principle components analysis demonstrates that these target sequences discriminate the distinct clinical states into three clusters ( FIG. 1A ).
  • FIG. 1C depicts a two-way hierarchical clustering dendrogram and expression matrix of 148 target sequences and 22 tumor samples.
  • FIG. 2 shows a histogram plot of the metagene expression values for the summarized 526 target sequences in each of the three clinical groups. This 526-metagene achieved maximal separation between clinical groups and low variance within each clinical group. Metagenes comprised of smaller subsets of 21, 18 and 6 target sequences were also generated ( FIG. 3 , Tables 7 and 8). The distinctions between clinical groups with respect to the metagene scores were preserved, although increased within-group variance was observed when using fewer target sequences ( FIG. 3 ).
  • POP Patient outcome predictor
  • NSC Nearest Shrunken Centroids
  • T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (indicated in the figures) and show that increasing the number of target sequences in the metagene combination increases the significance level of the differences in POP scores.
  • the data generated from such methods can be used to determine a prognosis for disease outcome, and/or to recommend or designate one or more treatment modalities for patients, to produce patient reports, and to prepare expression profiles.
  • RNA transcripts identified from comparison tests described in Table 2. Sequence listings are annotated with the Affymetrix Human Exon 1.0 ST probe selection region ID, proximal annotated gene from RefSeq, and overlap with coding sequence (CDS). SEQ ID Gene No Affy.
  • RNA transcripts used to plot hierarchical clustering and expression matrix (‘heat map’) in FIG. 1B.
  • the 526 RNA transcripts represent a subset of the differentially expressed transcripts (Table 3) between patients in the three clinical status groups (i.e., ‘SYS’, ‘PSA’ and ‘NED’) disease using linear regression and a p-value cut-off of p ⁇ 0.01. Weighting factors were from the regression coeffecient values; positive and negative values indicated transcripts correlated to increased expression in ‘SYS’ and ‘NED’ disease, respectively with intermediate expression values in the ‘PSA’ disease group. Weighting factors were used to derive 526-metagene values in FIG. 2.
  • RNA transcripts used to plot hierarchical clustering and expression matrix (‘heat map’) in FIG. 1C.
  • the 148 RNA transcripts represent a subset of the most differentially expressed transcripts between patients with clinically significant ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) disease. Weighting factors were from the test statistic values; positive and negative values indicated transcripts correlated to increased expression in recurrent and non-recurrent disease, respectively. Weighting factors were used to derive 148-metagene values, which were converted by scaling and normalizing into ‘POP’ scores depicted in FIG. 7.
  • CHEK1 Chromogranin A (parathyroid secretory protein 1) CHGA Chromatin accessibility complex 1 CHRAC1 Ceroid-lipofuscinosis, neuronal 5 CLN5 Clusterin CLU Calponin 1, basic, smooth muscle CNN1 Cannabinoid receptor 1 (brain) CNR1 Collagen, type XVIII, alpha 1 COL18A1 Collagen, type I, alpha 1 COL1A1 Collagen, type IV, alpha 3 (Goodpasture antigen) COL4A3 COMM domain containing 5 COMMD5 Catechol-O-methyltransferase COMT Coatomer protein complex, subunit beta 2 (beta prime) COPB2 COP9 constitutive photomorphogenic homolog subunit 5 COPS5 ( Arabidopsis ) Cytoplasmic polyadenylation element binding protein 3 CPEB3 Cysteine-rich secretory protein 3 CRISP3 V-crk sarcoma virus CT10 oncogene homolog (avian)
  • MSH6 Microseminoprotein, beta- MSMB Macrophage scavenger receptor 1 MSR1 Macrophage stimulating 1 receptor (c-met-related tyrosine MST1R kinase) Metastasis associated 1 MTA1 5,10-methylenetetrahydrofolate reductase (NADPH) MTHFR Myotrophin MTPN 5-methyltetrahydrofolate-homocysteine methyltransferase MTR Metastasis suppressor 1 MTSS1 Mucin 1, cell surface associated MUC1 MAX dimerization protein 1 MXD1 MAX interactor 1 MXI1 V-myb myeloblastosis viral oncogene homolog (avian) MYB V-myb myeloblastosis viral oncogene homolog (avian)-like 2 MYBL2 Myosin
  • PARD3 PAS domain containing serine/threonine kinase PASK Pre-B-cell leukemia homeobox 1 PBX1 Proliferating cell nuclear antigen PCNA PCTAIRE protein kinase 1 PCTK1 Platelet-derived growth factor alpha polypeptide PDGFA Platelet-derived growth factor receptor, alpha polypeptide PDGFRA Platelet-derived growth factor receptor, beta polypeptide PDGFRB Protein disulfide isomerase family A, member 5 PDIA5 PDZ and LIM domain 5 PDLIM5 Phosphatidylethanolamine-binding protein 4 PEBP4 Phosphatidylethanolamine N-methyltransferase PEMT Placental growth factor, vascular endothelial growth factor- PGF related protein Phosphoglycerate kinase 1 PGK1 Progesterone receptor PGR Phosphatase and actin regulator 2 PHACTR2 PHD finger protein 20-like 1 PHF20L1 P
  • RNA Peroxisome proliferator-activated receptor delta PPARD Peroxisome proliferator-activated receptor gamma PPARG Protein phosphatase 2 (formerly 2A), regulatory subunit A, PPP2R1B beta isoform Papillary renal cell carcinoma (translocation-associated) PRCC Peroxisomal proliferator-activated receptor A interacting PRIC285 complex 285 Protein kinase, cAMP-dependent, regulatory, type I, alpha PRKAR1A (tissue specific extinguisher 1) Protease, serine, 8 PRSS8 Prostate stem cell antigen PSCA Proteasome (prosome, macropain) 26S subunit, non- PSMD1 ATPase, 1 Patched homolog 1 ( Drosophila ) PTCH1 Patched homo
  • RAD21 RAD23 homolog A S. cerevisiae ) RAD23A RAD50 homolog ( S. cerevisiae ) RAD50 RAD54 homolog B ( S. cerevisiae ) RAD54B V-raf-1 murine leukemia viral oncogene homolog 1 RAF1 V-ral simian leukemia viral oncogene homolog B (ras RALB related; GTP binding protein) RAP1, GTP-GDP dissociation stimulator 1 RAP1GDS1 RAP2A, member of RAS oncogene family RAP2A Retinoic acid receptor, alpha RARA RAS p21 protein activator (GTPase activating protein) 1 RASA1 Retinoblastoma 1 (including osteosarcoma) RB1 Retinoblastoma binding protein 6 RBBP6 Retinoblastoma-like 2 (p130) RBL2 Retinol dehydrogenas
  • SEC14L1 Sema domain immunoglobulin domain (Ig), short basic SEMA3F domain, secreted, (semaphorin) 3F Serpin peptidase inhibitor, clade B (ovalbumin), member 5 SERPINB5 Serpin peptidase inhibitor, clade I (neuroserpin), member 1 SERPINI1 Splicing factor 1 SF1 Secreted frizzled-related protein 4 SFRP4 SH3-domain binding protein 2 SH3BP2 SH3 domain containing ring finger 2 SH3RF2 Sonic hedgehog homolog ( Drosophila ) SHH Seven in absentia homolog 1 ( Drosophila ) SIAH1 V-ski sarcoma viral oncogene homolog (avian) SKI SKI-like oncogene SKIL Solute carrier family 14 (urea transporter), member 1 (Kidd SLC14A1 blood group) Solute carrier family 20 (phosphate transporter), member 1 SLC20A1 Solute carrier family 14 (urea
  • TRMT12 Transient receptor potential cation channel, subfamily M, TRPM8 member 8
  • Trichorhinophalangeal syndrome I TRPS1 Tuberous sclerosis 1 TSC1 Tuberous sclerosis 2 TSC2 Tetraspanin 13 TSPAN13 Tetraspanin 14 TSPAN14 Tissue specific transplantation antigen P35B TSTA3 Tetratricopeptide repeat domain 29 TTC29 Thymidylate synthetase TYMS TYRO3 protein tyrosine kinase TYRO3 Ubiquitin-conjugating enzyme E2, J2 (UBC6 homolog, UBE2J2 yeast) UBX domain containing 3 UBXD3 Vesicle-associated membrane protein 2 (synaptobrevin 2) VAMP2 Vav 1 guanine nucleotide exchange factor VAV1 Vav 2 guanine nucleotide exchange factor VAV2 Versican VCAN Vascular endothelial growth factor A VEGFA Vestigial like
  • WEE1 WNT1 inducible signaling pathway protein 1 WISP1 Wingless-type MMTV integration site family, member 10B WNT10B Wingless-type MMTV integration site family member 2 WNT2 Wingless-type MMTV integration site family, member 2B WNT2B Wingless-type MMTV integration site family, member 5A WNT5A Wingless-type MMTV integration site family, member 8B WNT8B Werner syndrome WRN Wilms tumor 1 WT1 Xanthine dehydrogenase XDH Xeroderma pigmentosum, complementation group A XPA Xeroderma pigmentosum, complementation group C XPC X-ray repair complementing defective repair in Chinese XRCC1 hamster cells 1 X-ray repair complementing defective repair in Chinese XRCC4 hamster cells 4 X-ray repair complementing defective repair in Chinese XRCC5 hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80 kDa) X-ray
  • the 6-RNA metagene is a subset of the sequences listed in Table 7, also depicted in FIG. 3.
  • 18-RNA metagene scores were scaled and normalized to generate ‘POP’ scores depicted in FIG. 4.
  • Weighting factors were from the linear regression coefficient values; positive and negative values indicated transcripts correlated to increased expression in ‘SYS’ and ‘NED’ disease, respectively with intermediate expression values in the ‘PSA’ disease group.
  • RNA transcripts used to derive 10-RNA metagene values, which were converted by scaling and normalizing into ‘POP’ scores depicted in FIG. 5.
  • RNA transcripts were identified using Nearest Shrunken Centroids algorithm with leave-1-out cross-validation to distinguish ‘recurren’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) disease from Table 3 RNA transcripts. Weighting factors were from the test statistic values; positive and negative values indicated transcripts correlated to increased expression in ‘recurrent’ and ‘non-recurrent’ disease, respectively. Seq ID Weights 3 ⁇ 5.48 36 ⁇ 4.93 60 ⁇ 5.72 63 ⁇ 4.79 926 4.61 971 4.68 978 5.27 999 4.74 1014 4.86 1022 6.29
  • RNA transcripts used to derive 41-RNA metagene values, which were converted by scaling and normalizing into ‘POP’ scores depicted in FIG. 6.
  • RNA transcripts were identified using Nearest Shrunken Centroids algorithm with leave-1-out cross-validation to distinguish ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) disease from Table 3 RNA transcripts. Weighting factors were from the test statistic values; positive and negative values indicated transcripts correlated to increased expression in ‘recurrent’ and ‘non-recurrent’ disease, respectively.

Abstract

A system for expression-based discrimination of distinct clinical disease states in prostate cancer is provided that is based on the identification of sets of gene transcripts, which are characterized in that changes in expression of each gene transcript within a set of gene transcripts can be correlated with recurrent or non-recurrent prostate cancer. The Prostate Cancer Prognostic system provides for sets of “prostate cancer prognostic” target sequences and further provides for combinations of polynucleotide probes and primers derived there from. These combinations of polynucleotide probes can be provided in solution or as an array. The combination of probes and the arrays can be used for diagnosis. The invention further provides further methods of classifying prostate cancer tissue.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application is a continuation of Application No. PCT/CA2009/000694 filed May 28, 2009, now pending, which claims priority benefit of U.S. Provisional Application No. 61/056,827, filed May 28, 2008, the entire contents both of which are incorporated herein by reference.
    • FIELD OF THE INVENTION
  • This invention relates to the field of diagnostics and in particular to systems and methods for classifying prostate cancer into distinct clinical disease states.
    • BACKGROUND
  • Prostate cancer is the most common malignancy affecting U.S. men, with approximately 240,000 new cases diagnosed each year. The incidence of prostate cancer is increasing, in part due to increased surveillance efforts from the application of routine molecular testing such as prostate-specific antigen (PSA). For most men, prostate cancer is a slow-growing, organ-confined or localized malignancy that poses little risk of death. The most common treatments for prostate cancer in the U.S. are surgical procedures such as radical prostatectomy, where the entire prostate is removed from the patient. This procedure on its own is highly curative for most but not all men.
  • The vast majority of deaths from prostate cancer occur in patients with metastasis, believed to be present already at the time of diagnosis in the form of clinically undetectable micro-metastases. In these patients, it is clear that prostatectomy alone is not curative and additional therapies such as anti-androgen or radiation therapy are required to control the spread of disease and extend the life of the patient.
  • Most prostatectomy patients however face uncertainty with respect to their prognosis after surgery: whether or not the initial surgery will be curative several years from the initial treatment because the current methods for assessment of the clinical risk such as the various pathological (e.g., tumor stage), histological (e.g., Gleason's), clinical (e.g., Kattan nomogram) and molecular biomarkers (e.g., PSA) are not reliable predictors of prognosis, specifically disease progression. Routine PSA testing has certainly increased surveillance and early-detection rates of prostate cancer and this has resulted in an increased number of patients being treated but not significantly decreased the mortality rate.
  • Despite the controversies surrounding PSA testing as a screening tool, most physicians confidently rely on PSA testing to assess pre-treatment prognosis and to monitor disease progression after initial therapy. Successive increases in PSA levels above a defined threshold value or variations thereof (i.e. ‘Rising-PSA’), also known as biochemical recurrence has been shown to be correlated to disease progression after first-line therapy (e.g., prostatectomy, radiation and brachytherapy). However, less than a ⅓ of patients with ‘rising-PSA’ will eventually be diagnosed with systemic or metastatic disease and several studies have shown that after long-term follow up, the majority will never show any symptoms of disease progression aside from increases in PSA measurement. The limitations of using the PSA biomarker and the absence of additional biomarkers for predicting disease recurrence have led to the development of statistical models combining several clinical and pathological features including PSA results. Several of these ‘nomograms’ have been shown to improve the predictive power for disease recurrence in individual patients over any single independent variable. These models (see Citation #14) are used routinely in the clinic and are currently the best available tools for prediction of outcomes, although they do not provide high levels of accuracy for groups of patients with highly similar histological/pathological features or those at ‘intermediate’ risk of disease recurrence after prostatectomy.
  • The use of quantitative molecular analyses has the potential to increase the sensitivity, specificity and/or overall accuracy of disease prognosis and provide a more objective basis for determination of risk stratification as compared to conventional clinical-pathological risk models (see Citation #13). The PSA test demonstrates the deficiencies of relying on the measurement of any single biomarker in clinically heterogeneous and complex prostate cancer genomes. Therefore, genomic-based approaches measuring combinations of biomarkers or a signature of disease recurrence are currently being investigated as better surrogates for predicting disease outcome (see Citations # 1-13). For prostate cancer patients these efforts are aimed at reducing the number of unnecessary surgeries for patients without progressive disease and avoid inadvertent under-treatment for higher risk patients. To date, genomic profiling efforts to identify DNA-based (e.g., copy-number alterations, methylation changes), RNA-based (e.g., gene or non-coding RNA expression) or protein-based (e.g., protein expression or modification) signatures, useful for disease prognosis have not however resulted in widespread clinical use.
  • There are several key reasons explaining why prior genomic profiling methods for prostate cancer have not yet been incorporated in the clinic. These include the small sample sizes typical of individual studies, coupled with variations due to differences in study protocols, clinical heterogeneity of patients and lack of external validation data, which combined have made identifying a robust and reproducible disease signature elusive. Specifically for gene or RNA expression based prognostic models; the mitigating technological limitations include the quality and quantity of RNA that can be isolated from routine clinical samples. Routine clinical samples of prostate cancer include needle-biopsies and surgical resections that have been fixed in formalin and embedded in paraffin wax (FFPE). FFPE-derived RNA is typically degraded and fragmented to between 100-300 bp in size and without poly-A tails making it of little use for traditional 3′-biased gene expression profiling, which requires larger microgram quantities of RNA with intact poly-A tails to prime cDNA synthesis.
  • Furthermore, as <2% of the genome encodes for protein, traditional gene expression profiling in fact captures only a small fraction of the transcriptome and variation in expression as most RNA molecules that are transcribed are not translated into protein but serve other functional roles and non-coding RNAs are the most abundant transcript species in the genome.
  • This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.
    • SUMMARY OF THE INVENTION
  • An object of the present invention is to provide systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer. In accordance with one aspect of the present invention, there is provided a system for expression-based assessment of risk of prostate cancer recurrence after prostatectomy, said system comprising one or more polynucleotides, each of said polynucleotides capable of specifically hybridizing to a RNA transcript of a gene selected from the group of genes set forth in Table 3 and/or 6.
  • In accordance with another aspect of the present invention, there is provided a nucleic acid array for expression-based assessment of prostate cancer recurrence risk, said array comprising at least ten probes immobilized on a solid support, each of said probes being between about 15 and about 500 nucleotides in length, each of said probes being derived from a sequence corresponding to, or complementary to, a transcript of a gene selected from the group of genes set forth in Table 3 and/or 6, or a portion of said transcript.
  • In accordance with another aspect of the present invention, there is provided a method for expression-based assessment of prostate cancer recurrence, said method comprising: (a) determining the expression level of one or more transcripts of one or more genes in a test sample obtained from said subject to provide an expression pattern profile, said one or more genes selected from the group of genes set forth in Table 3 and/or 6, and (c) comparing said expression pattern profile with a reference expression pattern profile.
  • In accordance with another aspect of the present invention, there is provided a kit for characterizing the expression of one or more nucleic acid sequences depicted in SEQ ID NOs: 1-2114 comprising one or more nucleic acids selected from (a) a nucleic acid depicted in any of SEQ ID NOs: 1-2114; (b) an RNA form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114; (c) a peptide nucleic acid form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114; (d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c); (e) a nucleic acid comprising at least 25 consecutive bases having at least 90% sequence identity to any of (a-c); or (f) a complement to any of (a-e); and optionally instructions for correlating the expression level of said one or more nucleic acid sequences with the disease state of prostate cancer tissue.
  • In accordance with another aspect of the present invention, there is provided an array of probe nucleic acids certified for use in expression-based assessment of prostate cancer recurrence risk, wherein said array comprises at least two different probe nucleic acids that specifically hybridize to corresponding different target nucleic acids depicted in one of SEQ ID NOs: 1-2114, an RNA form thereof, or a complement to either thereof.
  • In accordance with another aspect of the present invention, there is provided a device for classifying a biological sample from a prostate cancer as recurrent or non-recurrent, the device comprising means for measuring the expression level of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6; means for correlating the expression level with a classification of prostate cancer status; and means for outputting the prostate cancer status.
  • In accordance with another aspect of the present invention, there is provided a computer-readable medium comprising one or more digitally-encoded expression pattern profiles representative of the level of expression of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6, each of said one or more expression pattern profiles being associated with a value wherein each of said values is correlated with the presence of recurrent or non-recurrent prostate cancer.
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • These and other features of the invention will become more apparent in the following detailed description in which reference is made to the appended drawings.
  • FIG. 1. A) Principle components analysis (PCA) of 2,114 RNAs identified to be differentially expressed between tumors from patients with differing clinical outcome (see Table 2 for comparisons evaluated), PCA plot of 22 prostate cancer tumors shows tight clustering of samples by clinical outcome of patients (circles, NED; diamonds, PSA; squares, SYS). B) Two-way hierarchical clustering dendrogram and expression matrix of 526 target sequences (Table 4) RNAs filtered using linear regression (p<0.01) to identify RNAs that followed either SYS>PSA>NED or NED>PSA>SYS trend in differential expression. C) Two-way hierarchical clustering dendrogram and expression matrix of 148 target sequences (Table 5), a subset of the most differentially expressed transcripts between patients with clinically significant ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) disease as filtered using a t-test (p<0.001). For B) and C), sample and RNAs were optimally ordered using Pearson's correlation distance metric with complete-linkage cluster distances and the expression of each RNA in each sample was normalized in the heatmap by the number of standard deviations above (blacker) and below (whiter) the median expression value (grey) across all samples.
  • FIG. 2. Histograms showing distribution patient's tumor expression levels of a ‘metagene’ generated from a linear combination of the 526 RNAs for each clinical group. The histograms bin samples with similar metagene expression values and significantly separate three modes of patient metagene scores (ANOVA, p<0.000001) corresponding to the three clinical status groups evaluated.
  • FIG. 3. Scatter plots summarizing the mean (±standard deviation) of metagene expression values for tumor samples from patients in the three clinical status groups (NED; PSA; SYS). Metagenes were generated from a linear combinations of 6 (▴), 18 (♦) or 20 (▪) RNAs and demonstrate highly significant differential expression between clinical groups (ANOVA, p<0.000001).
  • FIG. 4. Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using an 18-target sequence metagene (Table 7) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between NED and PSA (*) as well as between PSA and SYS (**) clinical groups (p<7×10−7 and p<1×10−6, respectively).
  • FIG. 5. Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 10-target sequence metagene (Table 9) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p<4×10−10).
  • FIG. 6. Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 41-target sequence metagene (Table 10) to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p<2×10−11).
  • FIG. 7. Box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group using a 148-target sequence metagene to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (**, p<9×10−12).
    •  DETAILED DESCRIPTION OF THE INVENTION
  • The present invention provides a system and method for assessing prostate cancer recurrence risk by distinguishing clinically distinct disease states in men with prostate cancer at the time of initial diagnosis or surgery. The system and methods are based on the identification of gene transcripts following a retrospective analysis of tumor samples that are differentially expressed in prostate cancer in a manner dependent on prostate cancer aggressiveness as indicated by long-term post-prostatectomy clinical outcome. These gene transcripts can be considered as a library which can be used as a resource for the identification of sets of specific target sequences (“prostate cancer prognostic sets”), which may represent the entire library of gene transcripts or a subset of the library and the detection of which is indicative of prostate cancer recurrence risk. The invention further provides for probes capable of detecting these target sequences and primers that are capable of amplifying the target sequences.
  • In accordance with one embodiment of the invention, the system and method for assessing prostate cancer recurrence risk are prognostic for a post surgery clinical outcome selected from no evidence of disease (‘NED’), biochemical relapse (two successive increases in prostate-specific antigen levels; (‘PSA’) and systemic prostate cancer systemic metastases (‘SYS’).
  • In accordance with one embodiment of the invention, the target sequences comprised by the prostate cancer prognostic set are sequences based on or derived from the gene transcripts from the library, or a subset thereof. Such sequences are occasionally referred to herein as “probe selection regions” or “PSRs.” In another embodiment of the invention, the target sequences comprised by the prostate classification set are sequences based on the gene transcripts from the library, or a subset thereof, and include both coding and non-coding sequences.
  • In one embodiment, the systems and methods provide for the molecular analysis of the expression levels of one or more of the target sequences as set forth in SEQ ID NOs: 1-2114 (Table 4). Increased relative expression of one or more target sequences in a ‘NED’ Group corresponding to the sequences as set forth in SEQ ID NOs: 1-913 is indicative of or predictive of a non-recurrent form of prostate cancer and can be correlated with an increased likelihood of a long-term NED prognosis or low risk of prostate cancer recurrence. Increased relative expression of one or more target sequences in a ‘SYS’ Group corresponding to the sequences as set forth in SEQ ID NOs: 914-2114 is indicative of or predictive of an aggressive form of prostate cancer and can be correlated with an increased likelihood of a long-term SYS prognosis or high risk of prostate cancer recurrence. Optionally, intermediate relative levels of one or more target sequences in a ‘PSA’ Group corresponding to target sequences set forth in Table 7 is indicative of or predictive of biochemical recurrence. Subsets and combinations of these target sequences or probes complementary thereto may be used as described herein.
  • Before the present invention is described in further detail, it is to be understood that this invention is not limited to the particular methodology, compositions, articles or machines described, as such methods, compositions, articles or machines can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention.
    • DEFINITIONS
  • Unless defined otherwise or the context clearly dictates otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In describing the present invention, the following terms will be employed, and are intended to be defined as indicated below.
  • The term “polynucleotide” as used herein refers to a polymer of greater than one nucleotide in length of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), hybrid RNA/DNA, modified RNA or DNA, or RNA or DNA mimetics, including peptide nucleic acids (PNAs). The polynucleotides may be single- or double-stranded. The term includes polynucleotides composed of naturally-occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as polynucleotides having non-naturally-occurring portions which function similarly. Such modified or substituted polynucleotides are well-known in the art and for the purposes of the present invention, are referred to as “analogues.”
  • “Complementary” or “substantially complementary” refers to the ability to hybridize or base pair between nucleotides or nucleic acids, such as, for instance, between a sensor peptide nucleic acid or polynucleotide and a target polynucleotide. Complementary nucleotides are, generally, A and T (or A and U), or C and G. Two single-stranded polynucleotides or PNAs are said to be substantially complementary when the bases of one strand, optimally aligned and compared and with appropriate insertions or deletions, pair with at least about 80% of the bases of the other strand, usually at least about 90% to 95%, and more preferably from about 98 to 100%.
  • Alternatively, substantial complementarity exists when a polynucleotide will hybridize under selective hybridization conditions to its complement. Typically, selective hybridization will occur when there is at least about 65% complementarity over a stretch of at least 14 to 25 bases, for example at least about 75%, or at least about 90% complementarity. See, M. Kanehisa Nucleic Acids Res. 12:203 (1984).
  • “Preferential binding” or “preferential hybridization” refers to the increased propensity of one polynucleotide to bind to its complement in a sample as compared to a noncomplementary polymer in the sample.
  • Hybridization conditions will typically include salt concentrations of less than about 1M, more usually less than about 500 mM, for example less than about 200 mM. In the case of hybridization between a peptide nucleic acid and a polynucleotide, the hybridization can be done in solutions containing little or no salt. Hybridization temperatures can be as low as 5° C., but are typically greater than 22° C., and more typically greater than about 30° C., for example in excess of about 37° C. Longer fragments may require higher hybridization temperatures for specific hybridization as is known in the art. Other factors may affect the stringency of hybridization, including base composition and length of the complementary strands, presence of organic solvents and extent of base mismatching, and the combination of parameters used is more important than the absolute measure of any one alone. Other hybridization conditions which may be controlled include buffer type and concentration, solution pH, presence and concentration of blocking reagents to decrease background binding such as repeat sequences or blocking protein solutions, detergent type(s) and concentrations, molecules such as polymers which increase the relative concentration of the polynucleotides, metal ion(s) and their concentration(s), chelator(s) and their concentrations, and other conditions known in the art.
  • “Multiplexing” herein refers to an assay or other analytical method in which multiple analytes can be assayed simultaneously.
  • A “target sequence” as used herein (also occasionally referred to as a “PSR” or “probe selection region”) refers to a region of the genome against which one or more probes can be designed. As used herein, a probe is any polynucleotide capable of selectively hybridizing to a target sequence or its complement, or to an RNA version of either. A probe may comprise ribonucleotides, deoxyribonucleotides, peptide nucleic acids, and combinations thereof. A probe may optionally comprise one or more labels. In some embodiments, a probe may be used to amplify one or both strands of a target sequence or an RNA form thereof, acting as a sole primer in an amplification reaction or as a member of a set of primers.
  • “Having” is an open ended phrase like “comprising” and “including,” and includes circumstances where additional elements are included and circumstances where they are not.
  • “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not.
  • As used herein ‘NED’ describes a clinically distinct disease state in which patients show no evidence of disease (‘NED’) at least 5 years after surgery, ‘PSA’ describes a clinically distinct disease state in which patients show biochemical relapse only (two successive increases in prostate-specific antigen levels but no other symptoms of disease with at least 5 years follow up after surgery; ‘PSA’) and ‘SYS’ describes a clinically distinct disease state in which patients develop biochemical relapse and present with systemic prostate cancer disease or metastases (‘SYS’) within five years after the initial treatment with radical prostatectomy.
  • As used herein, the term “about” refers to approximately a +/−10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.
  • Use of the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “a polynucleotide” includes a plurality of polynucleotides, reference to “a target” includes a plurality of such targets, reference to “a normalization method” includes a plurality of such methods, and the like. Additionally, use of specific plural references, such as “two,” “three,” etc., read on larger numbers of the same subject, unless the context clearly dictates otherwise.
  • Terms such as “connected,” “attached,” “linked” and “conjugated” are used interchangeably herein and encompass direct as well as indirect connection, attachment, linkage or conjugation unless the context clearly dictates otherwise.
  • Where a range of values is recited, it is to be understood that each intervening integer value, and each fraction thereof, between the recited upper and lower limits of that range is also specifically disclosed, along with each subrange between such values. The upper and lower limits of any range can independently be included in or excluded from the range, and each range where either, neither or both limits are included is also encompassed within the invention. Where a value being discussed has inherent limits, for example where a component can be present at a concentration of from 0 to 100%, or where the pH of an aqueous solution can range from 1 to 14, those inherent limits are specifically disclosed. Where a value is explicitly recited, it is to be understood that values which are about the same quantity or amount as the recited value are also within the scope of the invention, as are ranges based thereon. Where a combination is disclosed, each subcombination of the elements of that combination is also specifically disclosed and is within the scope of the invention. Conversely, where different elements or groups of elements are disclosed, combinations thereof are also disclosed. Where any element of an invention is disclosed as having a plurality of alternatives, examples of that invention in which each alternative is excluded singly or in any combination with the other alternatives are also hereby disclosed; more than one element of an invention can have such exclusions, and all combinations of elements having such exclusions are hereby disclosed.
    • Prostate Cancer Prognostic System
  • The system of the present invention is based on the identification of a library of gene and RNA transcripts that are differentially expressed in prostate cancer in a manner dependent on prostate cancer aggressiveness as indicated by the post-prostatectomy clinical outcome of the patient. For example, relative over expression of one or more of the gene transcripts in a prostate cancer sample compared to a reference sample or expression profile or signature there from may be prognostic of a clinically distinct disease outcome post-prostatectomy selected from no evidence of disease (‘NED’), biochemical relapse (‘PSA’) and prostate cancer disease systemic recurrence or metastases (‘SYS’). The reference sample can be, for example, from prostate cancer sample(s) of one or more references subject(s) with a known post-prostatectomy clinical outcomes. The reference expression profile or signature may optionally be normalized to one or more appropriate reference gene transcripts. Alternatively or in addition to, expression of one or more of the gene transcripts in a prostate cancer sample may be compared to an expression profile or signature from normal prostate tissue.
  • Expression profiles or signatures from prostate cancer samples may be normalized to one or more house keeping gene transcripts such that normalized over and/or under expression of one or more of the gene transcripts in a sample may be indicative of a clinically distinct disease state or prognosis.
    • Prostate Prognostic Library
  • The Prostate Prognostic Library in accordance with the present invention comprises one or more gene or RNA transcripts whose relative and/or normalized expression is indicative of prostate cancer recurrence and which may be prognostic for post-prostatectomy clinical outcome of a patient. Exemplary RNA transcripts that showed differential expression in prostate cancer samples from patients with clinically distinct disease outcomes after initial treatment with radical prostatectomy are shown in Table 3. In one embodiment of the invention, the library comprises one or more of the gene transcripts of the genes listed in Table 3.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from those listed in Table 3. In one embodiment, the library comprises at least one transcript from each of at least 5 genes selected from those listed in Table 3. In another embodiment, the library comprises at least one transcript from each of at least 10 genes selected from those listed in Table 3. In a further embodiment, the library comprises at least one transcript from each of at least 15 genes selected from those listed in Table 1. In other embodiments, the library comprises at least one transcript from each of at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60 and at least 65 genes selected from those listed in Table 3. In a further embodiment, the library comprises at least one transcript from all of the genes listed in Table 3. In a further embodiment, the library comprises at all transcripts from all of the genes listed in Table 3.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of [NM—001004722]; [NM—001005522]; [NM—001013671]; [NM—001033517]; [NM—183049]; [NM—212559]; 5′-3′ exoribonuclease 1; A kinase (PRKA) anchor protein (yotiao) 9; AarF domain containing kinase 4; Abhydrolase domain containing 3; Aconitase 1, soluble; Actinin, alpha 1; ADAM metallopeptidase domain 19 (meltrin beta); Adaptor-related protein complex 1, gamma 2 subunit; Adenosine deaminase, RNA-specific, B2 (RED2 homolog rat); Adenylate cyclase 3; ADP-ribosylation factor GTPase activating protein 3; ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited); ADP-ribosylation factor-like 4D; Adrenergic, beta, receptor kinase 2; AF4/FMR2 family, member 3; Amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65); Anaphase promoting complex subunit 1; Ankyrin 3, node of Ranvier (ankyrin G); Ankyrin repeat domain 15; Ankyrin repeat domain 28; Annexin A1; Annexin A2; Anterior pharynx defective 1 homolog B (C. elegans); Anthrax toxin receptor 1; Antizyme inhibitor 1; Arachidonate 12-lipoxygenase, 12R type; Arginine vasopressin receptor 1A; Arginine-glutamic acid dipeptide (RE) repeats; ARP3 actin-related protein 3 homolog (yeast); Arrestin 3, retinal (X-arrestin); Arrestin domain containing 1; Aryl hydrocarbon receptor interacting protein-like 1; Aryl hydrocarbon receptor nuclear translocator; Ataxin 1; ATM/ATR-Substrate Chk2-Interacting Zn2+-finger protein; ATPase, Class I, type 8B, member 1; ATPase, Na+/K+ transporting, alpha 1 polypeptide; ATP-binding cassette, sub-family F (GCN20), member 1; Autism susceptibility candidate 2; Baculoviral IAP repeat-containing 6 (apollon); Basonuclin 2; Brain-specific angiogenesis inhibitor 3; Bromodomain containing 7; Bromodomain containing 8; Bromodomain PHD finger transcription factor; BTB (POZ) domain containing 16; BTB (POZ) domain containing 7; Calcium activated nucleotidase 1; Calcium binding protein P22; Calcium channel, voltage-dependent, beta 4 subunit; Calcium channel, voltage-dependent, L type, alpha 1C subunit; Calcium channel, voltage-dependent, L type, alpha 1D subunit; Calcyclin binding protein; Calmodulin 1 (phosphorylase kinase, delta); Calsyntenin 1; Carbonyl reductase 3; Cardiolipin synthase 1; Carnitine palmitoyltransferase 1A (liver); Casein kinase 1, delta; Casein kinase 1, gamma 1; Casein kinase 1, gamma 3; Caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase); CD109 molecule; CD99 molecule-like 2; CDK5 regulatory subunit associated protein 2; CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2; Cell adhesion molecule 1; Cell division cycle and apoptosis regulator 1; Centrosomal protein 70 kDa; Chloride channel 3; Chromodomain helicase DNA binding protein 2; Chromodomain helicase DNA binding protein 6; Chromodomain protein, Y-like 2; Chromosome 1 ORF 116; Chromosome 1 ORF 52; Chromosome 10 ORF 118; Chromosome 12 ORF 30; Chromosome 13 ORF 23; Chromosome 16 ORF 45; Chromosome 18 ORF 1; Chromosome 18 ORF 1; Chromosome 18 ORF 1; Chromosome 18 ORF 1; Chromosome 18 ORF 17; Chromosome 2 ORF 3; Chromosome 20 ORF 133; Chromosome 21 ORF 25; Chromosome 21 ORF 34; Chromosome 22 ORF 13; Chromosome 3 ORF 26; Chromosome 5 ORF 3; Chromosome 5 ORF 33; Chromosome 5 ORF 35; Chromosome 5 ORF 39; Chromosome 7 ORF 13; Chromosome 7 ORF 42; Chromosome 9 ORF 3; Chromosome 9 ORF 94; Chromosome Y ORF 15B; Chymase 1, mast cell; Citrate lyase beta like; Class II, major histocompatibility complex, transactivator; C-Maf-inducing protein; Coatomer protein complex, subunit alpha; Cofilin 2 (muscle); Coiled-coil domain containing 50; Coiled-coil domain containing 7; Coiled-coil-helix-coiled-coil-helix domain containing 4; Cold shock domain containing E1, RNA-binding; Collagen, type XII, alpha 1; Complement component 1, r subcomponent-like; Core-binding factor, runt domain, alpha subunit 2; translocated to, 2; CREB binding protein (Rubinstein-Taybi syndrome); CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 2; CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-like; CUG triplet repeat, RNA binding protein 2; Cullin 3; Cut-like 2; Cyclin F; Cyclin Y; Cysteine-rich with EGF-like domains 1; Cytochrome P450, family 4, subfamily F, polypeptide 11; Cytoplasmic FMR1 interacting protein 2; DAZ interacting protein 1-like; DCP2 decapping enzyme homolog (S. cerevisiae); DEAD box polypeptide 47; DEAD box polypeptide 5; DEAD box polypeptide 52; DEAD box polypeptide 56; Death inducer-obliterator 1; Dedicator of cytokinesis 2; DEP domain containing 1B; DEP domain containing 2; DEP domain containing 6; Development and differentiation enhancing factor 1; Diacylglycerol lipase, alpha; Diaphanous homolog 2 (Drosophila); Dickkopf homolog 3; Dihydropyrimidine dehydrogenase; Dipeptidyl-peptidase 10; Discs, large homolog 2, chapsyn-110; Dishevelled, dsh homolog 2; DnaJ (Hsp40) homolog, subfamily C, member 6; Dpy-19-like 3; Dual specificity phosphatase 5; Ectodysplasin A receptor; Ectonucleoside triphosphate diphosphohydrolase 7; EGFR-coamplified and overexpressed protein; ELL associated factor 1; Emopamil binding protein (sterol isomerase); Enabled homolog; Ephrin-A5; ER lipid raft associated 1; Erythroblast membrane-associated protein (Scianna blood group); Erythrocyte membrane protein band 4.1 like 4A; Etoposide induced 2.4 mRNA; Eukaryotic translation initiation factor 4E family member 3; FAD1 flavin adenine dinucleotide synthetase homolog; Family with sequence similarity 110, member A; Family with sequence similarity 114, member A1; Family with sequence similarity 135, member A; Family with sequence similarity 40, member A; Family with sequence similarity 80, member B; F-box and leucine-rich repeat protein 11; F-box and leucine-rich repeat protein 7; F-box protein 2; Ferritin, heavy polypeptide 1; Fibronectin type III domain containing 3A; Fibronectin type III domain containing 3B; Fibulin 1; FLJ25476 protein; FLJ41603 protein; Forkhead box J3; Forkhead box J3; Forkhead box K1; Forkhead box P1; Frizzled homolog 3; Frizzled homolog 5; G protein-coupled receptor kinase interactor 2; GABA A receptor, delta; GATA binding protein 2; GDNF family receptor alpha 2; Gelsolin (amyloidosis, Finnish type); Genethonin 1; Glucose phosphate isomerase; Glucose-fructose oxidoreductase domain containing 1; Glucosidase, beta (bile acid) 2; Glutamate dehydrogenase 1; Glutaminase; Glutamyl aminopeptidase (aminopeptidase A); Glutathione reductase
  • Glycogen synthase kinase 3 beta; Grainyhead-like 2; Gremlin 1, cysteine knot superfamily, homolog; GTPase activating protein (SH3 domain) binding protein 1; Hairy/enhancer-of-split related with YRPW motif 2; Heparan sulfate 6-O-sulfotransferase 3; Hermansky-Pudlak syndrome 5; Heterogeneous nuclear ribonucleoprotein C(C1/C2)
    Hippocalcin-like 1; Histocompatibility (minor) 13; Histone cluster 1, H3d; Histone deacetylase 6; Homeobox A1; Homeobox and leucine zipper encoding; Host cell factor C1 (VP16-accessory protein); Hyaluronan binding protein 4; Hyperpolarization activated cyclic nucleotide-gated potassium channel 3; Hypothetical gene supported by AK128346; Hypothetical LOC51149; Hypothetical protein FLJ12949; Hypothetical protein FLJ20035; Hypothetical protein FLJ20309; Hypothetical protein FLJ38482; Hypothetical protein HSPC148; Hypothetical protein LOC130576; Hypothetical protein LOC285908; Hypothetical protein LOC643155; Iduronidase, alpha-L-IKAROS family zinc finger 1 (Ikaros); IlvB (bacterial acetolactate synthase)-like; Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta; Inositol polyphosphate-4-phosphatase, type II; Integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor); Integrin, alpha 6; Integrin, alpha 9; Integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51); Integrin, beta-like 1 (with EGF-like repeat domains); Inter-alpha (globulin) inhibitor H3; Interleukin enhancer binding factor 3, 90 kDa; Intestine-specific homeobox
    Intraflagellar transport 172 homolog; Janus kinase 1; Jumonji domain containing 1B; Jumonji domain containing 2B; Jumonji domain containing 2C; Kalirin, RhoGEF kinase; Kallikrein-related peptidase 2; Karyopherin alpha 3 (importin alpha 4); Keratinocyte associated protein 2; KIAA0152; KIAA0241; KIAA0319-like; KIAA0495; KIAA0562; KIAA0564 protein; KIAA1217; KIAA1244; KIAA1244; La ribonucleoprotein domain family, member 1; Lamin A/C; LATS, large tumor suppressor, homolog 2; Leiomodin 3 (fetal); Leptin receptor overlapping transcript-like 1; Leucine rich repeat containing 16; Leucine-rich repeat kinase 1; Leucine-rich repeat-containing G protein-coupled receptor 4; LIM domain 7; Major histocompatibility complex, class II, DR beta 1; Malignant fibrous histiocytoma amplified sequence 1; Maltase-glucoamylase (alpha-glucosidase); Mannosidase, alpha, class 2A, member 1; Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase; MBD2-interacting zinc finger; Melanin-concentrating hormone receptor 1; Methionyl-tRNA synthetase; Methyl CpG binding protein 2; Methyl-CpG binding domain protein 5; Microcephaly, primary autosomal recessive 1; Microseminoprotein, beta-; Microtubule-associated protein 1B; Microtubule-associated protein 2; Minichromosome maintenance complex component 3 associated protein; Mitochondrial ribosomal protein S15; Mohawk homeobox; Monooxygenase, DBH-like 1; MORN repeat containing 1; Muscle RAS oncogene homolog; Muscleblind-like; Myelin protein zero-like 1; Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4; Myocyte enhancer factor 2B; Myosin IF; Myosin, heavy chain 3, skeletal muscle, embryonic; N-acetylgalactosaminidase, alpha-; N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits; Nascent polypeptide-associated complex alpha subunit; NECAP endocytosis associated 2; Necdin homolog; Neural precursor cell expressed, developmentally down-regulated 9; Neuregulin 1; Neuron navigator 1; Nibrin; Nicotinamide N-methyltransferase; NIMA (never in mitosis gene a)-related kinase 6; NLR family, CARD domain containing 5; NOL1/NOP2/Sun domain family, member 3; NOL1/NOP2/Sun domain family, member 3; NOL1/NOP2/Sun domain family, member 6; Nuclear receptor coactivator 2; Nuclear receptor coactivator 6; Nuclear receptor subfamily 2, group F, member 2; Nuclear receptor subfamily 3, group C, member 2; Nuclear receptor subfamily 4, group A, member 2; Nuclear transcription factor, X-box binding-like 1; Nucleolar and coiled-body phosphoprotein 1; Overexpressed in colon carcinoma-1; PAN3 polyA specific ribonuclease subunit homolog; PAP associated domain containing 1; Paraoxonase 2; Paraspeckle component 1; PCTAIRE protein kinase 2; Peptidase D; Pericentrin (kendrin); Peroxisomal biogenesis factor 19; PHD finger protein 8; Phosphatidic acid phosphatase type 2 domain containing 3; Phosphatidylinositol 4-kinase, catalytic, alpha polypeptide; Phosphatidylinositol glycan anchor biosynthesis, class O; Phosphatidylinositol transfer protein, beta; Phosphodiesterase 4D, cAMP-specific; Phosphoglucomutase 5; Phosphoglycerate mutase family member 5; Phosphoinositide-3-kinase, class 2, beta polypeptide; Phospholipase A2, group IVB (cytosolic); Phospholipase C, beta 1 (phosphoinositide-specific); Phospholipase C, gamma 2 (phosphatidylinositol-specific); Phosphorylase kinase, beta; Plasminogen activator, tissue; Platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45 kDa; Pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 3; Pleckstrin homology domain containing, family A member 7; Pleckstrin homology domain containing, family G (with RhoGef domain) member 3; Pleckstrin homology domain containing, family H (with MyTH4 domain) member 1; Poly (ADP-ribose) polymerase family, member 16; Poly (ADP-ribose) polymerase family, member 2; Poly(A) polymerase alpha; Poly(A)-specific ribonuclease (deadenylation nuclease); Polymerase (DNA directed) nu; Polymerase (DNA directed), gamma 2, accessory subunit; Polymerase (RNA) II (DNA directed) polypeptide L; Polymerase (RNA) III (DNA directed) polypeptide E; Polymerase I and transcript release factor; Potassium channel tetramerisation domain containing 1; Potassium channel tetramerisation domain containing 2; Potassium channel tetramerisation domain containing 7; Potassium channel, subfamily K, member 1; Presenilin 1; PRKR interacting protein 1; Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2; ProSAPiP1 protein; Prostaglandin E synthase 3 (cytosolic); Protease, serine, 2 (trypsin 2); Protein kinase, Y-linked; Protein phosphatase 1, regulatory (inhibitor) subunit 9A; Protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform; Protein phosphatase 4, regulatory subunit 1-like; Protein tyrosine phosphatase, non-receptor type 18 (brain-derived); Protein tyrosine phosphatase, non-receptor type 3; Protein tyrosine phosphatase, receptor type, D; Protein-O-mannosyltransferase 1; Proteolipid protein 2 (colonic epithelium-enriched); Protocadherin 7; Protocadherin gamma subfamily A, 1; PRP6 pre-mRNA processing factor 6 homolog; Putative homeodomain transcription factor 1; RAB GTPase activating protein 1-like; RAB10; RAB30; Rabaptin, RAB GTPase binding effector protein 1; RAD51-like 1; RALBP1 associated Eps domain containing 2; Rap guanine nucleotide exchange factor (GEF) 1; Rapamycin-insensitive companion of mTOR; Ras and Rab interactor 2; Receptor accessory protein 3; Reelin; Replication factor C (activator 1) 3; Replication protein A3; Rho GTPase activating protein 18; Rho guanine nucleotide exchange factor (GEF) 10-like; Rhophilin, Rho GTPase binding protein 1; Ribonuclease H2, subunit B; Ribonuclease P 14 kDa subunit; Ring finger protein 10; Ring finger protein 144; Ring finger protein 44; RNA binding motif protein 16; Roundabout, axon guidance receptor, homolog 1; Roundabout, axon guidance receptor, homolog 2; RUN domain containing 2A; Scinderin; SEC23 interacting protein; Sec61 alpha 2 subunit; Septin 11; Serine/threonine kinase 32A; Serine/threonine kinase 32C; SGT1, suppressor of G2 allele of SKP1; SH3 and PX domains 2A; Signal peptide peptidase 3; Signal transducer and activator of transcription 1, 91 kDa; Single-stranded DNA binding protein 2; Small nuclear ribonucleoprotein polypeptide N; SNF8, ESCRT-II complex subunit, homolog; Sodium channel, voltage-gated, type III, alpha subunit; Solute carrier family 1 (neutral amino acid transporter), member 5; Solute carrier family 16, member 7 (monocarboxylic acid transporter 2); Solute carrier family 2 (facilitated glucose transporter), member 11; Solute carrier family 2 (facilitated glucose transporter), member 11; Solute carrier family 24 (sodium/potassium/calcium exchanger), member 3; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; Solute carrier family 30 (zinc transporter), member 6; Solute carrier family 39 (zinc transporter), member 10; Solute carrier family 43, member 1; Solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2; SON DNA binding protein; Sortilin-related VPS10 domain containing receptor 3; Sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2; Spectrin repeat containing, nuclear envelope 1; Sperm associated antigen 9; Splicing factor 3a, subunit 2, 66 kDa; Splicing factor 3b, subunit 1, 155 kDa; Staphylococcal nuclease and tudor domain containing 1; Staufen, RNA binding protein, homolog 1; Suppression of tumorigenicity 7; Suppressor of variegation 4-20 homolog 1; Synapsin III; Syntaxin 3; Syntaxin 5; Tachykinin receptor 1; TAO kinase 3; TBC1 domain family, member 16; TBC1 domain family, member 19; Testis specific, 10; Tetraspanin 6; Tetratricopeptide repeat domain 23; Thioredoxin-like 2; THUMP domain containing 3; TIMELESS interacting protein; TOX high mobility group box family member 4; Trafficking protein, kinesin binding 1; Transcription factor 7-like 1 (T-cell specific, HMG-box); Transcription factor 7-like 2 (T-cell specific, HMG-box); Translocase of inner mitochondrial membrane 13 homolog; Translocated promoter region (to activated MET oncogene); Translocation associated membrane protein 2; Transmembrane 9 superfamily member 2; Transmembrane emp24 protein transport domain containing 8; Transmembrane emp24-like trafficking protein 10; Transmembrane protein 134; Transmembrane protein 18; Transmembrane protein 18; Transmembrane protein 29; Triadin; Tribbles homolog 1; Trinucleotide repeat containing 6C; Tripartite motif-containing 36; Tripartite motif-containing 61; TRNA methyltransferase 11 homolog; TruB pseudouridine (psi) synthase homolog 2; Tubby like protein 4; Tuftelin 1; Tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin); Tumor necrosis factor receptor superfamily, member 25; Tumor necrosis factor, alpha-induced protein 8; Tyrosine kinase 2; Ubiquinol-cytochrome c reductase core protein I; Ubiquitin specific peptidase 47; Ubiquitin specific peptidase 5 (isopeptidase T); Ubiquitin specific peptidase 8; Ubiquitin-like 7 (bone marrow stromal cell-derived); UBX domain containing 6; UDP-glucose ceramide glucosyltransferase-like 2; UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2); Unc-93 homolog B1; UTP6, small subunit (SSU) processome component, homolog; Vacuolar protein sorting 8 homolog; V-akt murine thymoma viral oncogene homolog 1; V-ets erythroblastosis virus E26 oncogene homolog; Viral DNA polymerase-transactivated protein 6; WD repeat domain 33; WD repeat domain 90; Wingless-type MMTV integration site family, member 2B; WW and C2 domain containing 1; Yip1 domain family, member 3; YTH domain family, member 3; Zinc finger and BTB domain containing 10; Zinc finger and BTB domain containing 20; Zinc finger and SCAN domain containing 18; Zinc finger homeodomain 4; Zinc finger protein 14 homolog; Zinc finger protein 335; Zinc finger protein 394; Zinc finger protein 407; Zinc finger protein 608; Zinc finger protein 667; Zinc finger protein 692; Zinc finger protein 718; Zinc finger protein 721; Zinc finger, CCHC domain containing 9; Zinc finger, matrin type 1; Zinc finger, MYND domain containing 11; Zinc finger, ZZ-type containing 3; Zinc fingers and homeoboxes 2; and Zwilch, kinetochore associated, homolog.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Ankyrin repeat domain 15; UDP-glucose ceramide glucosyltransferase-like 2; Hypothetical protein FLJ12949; Chromosome 22 open reading frame 13; Phosphatidylinositol glycan anchor biosynthesis, class O; Solute carrier family 43, member 1; Rabaptin, RAB GTPase binding effector protein 1; Zinc finger protein 14 homolog; Hypothetical gene supported by AK128346; Adenylate cyclase 3; Phosphatidylinositol transfer protein, beta; Zinc finger protein 667; Gremlin 1, cysteine knot superfamily, homolog; Ankyrin 3, node of Ranvier (ankyrin G) and Maltase-glucoamylase (alpha-glucosidase).
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Ankyrin repeat domain 15; Hypothetical protein FLJ12949; Solute carrier family 43, member 1; Thioredoxin-like 2; Polymerase (RNA) II (DNA directed) polypeptide L; Syntaxin 5; Leucine rich repeat containing 16; Calcium channel, voltage-dependent, beta 4 subunit; [NM—001005522]; G protein-coupled receptor kinase interactor 2; Ankyrin 3, node of Ranvier (ankyrin G); Gremlin 1, cysteine knot superfamily, homolog; Zinc finger protein 667; Hypothetical gene supported by AK128346; Transmembrane 9 superfamily member 2; Potassium channel, subfamily K, member 1; Chromodomain helicase DNA binding protein 2; Microcephaly, primary autosomal recessive 1; Chromosome 21 open reading frame 34 and Dual specificity phosphatase 5.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Ankyrin repeat domain 15; Ankyrin 3, node of Ranvier (ankyrin G) and Maltase-glucoamylase (alpha-glucosidase).
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Ankyrin repeat domain 15; Hypothetical protein FLJ12949; Solute carrier family 43, member 1; Thioredoxin-like 2; Polymerase (RNA) II (DNA directed) polypeptide L; Syntaxin 5; Leucine rich repeat containing 16; Calcium channel, voltage-dependent, beta 4 subunit; [NM—001005522]; G protein-coupled receptor kinase interactor 2; Ankyrin 3, node of Ranvier (ankyrin G); Gremlin 1, cysteine knot superfamily, homolog; Zinc finger protein 667; Hypothetical gene supported by AK128346; Transmembrane 9 superfamily member 2; Potassium channel, subfamily K, member 1; Chromodomain helicase DNA binding protein 2; Chromosome 9 open reading frame 94; Chromosome 21 open reading frame 34; and Dual specificity phosphatase 5.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Citrate lyase beta like; Phosphodiesterase 4D, cAMP-specific; Ectodysplasin A receptor; DEP domain containing 6; Basonuclin 2; Chromosome 2 open reading frame 3; FLJ25476 protein; Staphylococcal nuclease and tudor domain containing 1; Hermansky-Pudlak syndrome 5 and Chromosome 12 open reading frame 30.
  • In one embodiment, the library comprises at least one transcript from at least one gene selected from the group consisting of Replication factor C (activator 1) 3; Tripartite motif-containing 61; Citrate lyase beta like; Adaptor-related protein complex 1, gamma 2 subunit; Kallikrein-related peptidase 2; Phosphodiesterase 4D, cAMP-specific; Cytochrome P450, family 4, subfamily F, polypeptide 11; Ectodysplasin A receptor
  • Phospholipase C, beta 1; KIAA1244; Paraoxonase 2; Arachidonate 12-lipoxygenase, 12R type; Cut-like 2; Chemokine (C-X-C motif) ligand 12; Rho guanine nucleotide exchange factor (GEF) 5; Olfactory receptor, family 2, subfamily A, member 4; Chromosome 19 open reading frame 42; Hypothetical gene supported by AK128346; Phosphoglucomutase 5; Hyaluronan binding protein 4; NECAP endocytosis associated 2
    Myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4; Signal transducer and activator of transcription 1; Chromosome 2 open reading frame 3; FLJ25476 protein; Staphylococcal nuclease and tudor domain containing 1; Transmembrane protein 18; Hermansky-Pudlak syndrome 5; Chromosome 12 open reading frame 30; Splicing factor 3b, subunit 1; Cofilin 2; Heparan sulfate 6-O-sulfotransferase 3; Enabled homolog; Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase; Solute carrier family 24 (sodium/potassium/calcium exchanger), member 3; Inositol 1,4,5-triphosphate receptor, type 1; CAP-GLY domain containing linker protein; Transglutaminase 4; MOCO sulphurase C-terminal domain containing 2; 4-hydroxyphenylpyruvate dioxygenase-like; and R3H domain containing 1.
  • The invention also contemplates that alternative libraries may be designed that include transcripts of one or more of the genes in Table 3, together with additional gene transcripts that have previously been shown to be associated with prostate cancer systemic progression. As is known in the art, the publication and sequence databases can be mined using a variety of search strategies to identify appropriate additional candidates for inclusion in the library. For example, currently available scientific and medical publication databases such as Medline, Current Contents, OMIM (online Mendelian inheritance in man), various Biological and Chemical Abstracts, Journal indexes, and the like can be searched using term or key-word searches, or by author, title, or other relevant search parameters. Many such databases are publicly available, and strategies and procedures for identifying publications and their contents, for example, genes, other nucleotide sequences, descriptions, indications, expression pattern, etc, are well known to those skilled in the art. Numerous databases are available through the internet for free or by subscription, see, for example, the National Center Biotechnology Information (NCBI), Infotrieve, Thomson ISI, and Science Magazine (published by the AAAS) websites. Additional or alternative publication or citation databases are also available that provide identical or similar types of information, any of which can be employed in the context of the invention. These databases can be searched for publications describing altered gene expression between recurrent and non-recurrent prostate cancer. Additional potential candidate genes may be identified by searching the above described databases for differentially expressed proteins and by identifying the nucleotide sequence encoding the differentially expressed proteins. A list of genes whose altered expression is between patients with recurrent disease and non-recurrent prostate cancer is presented in Table 6.
    • Prostate Cancer Prognostic Sets
  • A Prostate Prognostic Set comprises one or more target sequences identified within the gene transcripts in the prostate prognostic library, or a subset of these gene transcripts. The target sequences may be within the coding and/or non-coding regions of the gene transcripts. The set can comprise one or a plurality of target sequences from each gene transcript in the library, or subset thereof. The relative and/or normalized level of these target sequences in a sample is indicative of the level of expression of the particular gene transcript and thus of prostate cancer recurrence risk. For example, the relative and/or normalized expression level of one or more of the target sequences may be indicative of an recurrent form of prostate cancer and therefore prognostic for prostate cancer systemic progression while the relative and/or normalized expression level of one or more other target sequences may be indicative of a non-recurrent form of prostate cancer and therefore prognostic for a NED clinical outcome.
  • Accordingly, one embodiment of the present invention provides for a library or catalog of candidate target sequences derived from the transcripts (both coding and non-coding regions) of at least one gene suitable for classifying prostate cancer recurrence risk. In a further embodiment, the present invention provides for a library or catalog of candidate target sequences derived from the non-coding regions of transcripts of at least one gene suitable for classifying prostate cancer recurrence risk. In still a further embodiment, the library or catalog of candidate target sequences comprises target sequences derived from the transcripts of one or more of the genes set forth in Table 3 and/or Table 6. The library or catalog in affect provides a resource list of transcripts from which target sequences appropriate for inclusion in a Prostate Cancer Prognostic set can be derived. In one embodiment, an individual Prostate Cancer Prognostic set may comprise target sequences derived from the transcripts of one or more genes exhibiting a positive correlation with recurrent prostate cancer. In one embodiment, an individual Prostate Cancer Prognostic Set may comprise target sequences derived from the transcripts of one or more genes exhibiting a negative correlation with recurrent prostate cancer. In one embodiment, an individual Prostate Cancer Prognostic Set may comprise target sequences derived from the transcripts of two or more genes, wherein at least one gene has a transcript that exhibits a positive correlation with recurrent prostate cancer and at least one gene has a transcript that exhibits negative correlation with recurrent prostate cancer.
  • In one embodiment, the Prostate Cancer Prognostic Set comprises target sequences derived from the transcripts of at least one gene. In one embodiment, the Prostate Cancer Prognostic Set comprises target sequences derived from the transcripts of at least 5 genes. In another embodiment, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 10 genes. In a further embodiment, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 15 genes. In other embodiments, the Prostate Cancer Prognostic set comprises target sequences derived from the transcripts of at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60 and at least 65 genes.
  • Following the identification of candidate gene transcripts, appropriate target sequences can be identified by screening for target sequences that have been annotated to be associated with each specific gene locus from a number of annotation sources including GenBank, RefSeq, Ensembl, dbEST, GENSCAN, TWINSCAN, Exoniphy, Vega, microRNAs registry and others (see Affymetrix Exon Array design note).
  • As part of the target sequence selection process, target sequences can be further evaluated for potential cross-hybridization against other putative transcribed sequences in the design (but not the entire genome) to identify only those target sequences that are predicted to uniquely hybridize to a single target.
  • Optionally, the set of target sequences that are predicted to uniquely hybridize to a single target can be further filtered using a variety of criteria including, for example, sequence length, for their mean expression levels across a wide selection of human tissues, as being representive of transcripts expressed either as novel alternative (i.e., non-consensus) exons, alternative retained introns, novel exons 5′ or 3′ of the gene's transcriptional start site or representing transcripts expressed in a manner antisense to the gene, amongst others.
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #2 of Ankyrin repeat domain 15; in exon #1 of UDP-glucose ceramide glucosyltransferase-like 2; in exon of #19 of Hypothetical protein FLJ12949; in intron #4 of Chromosome 22 open reading frame 13; in exon #2 of phatidylinositol glycan anchor biosynthesis, class O; in exon #15 of Solute carrier family 43, member 1; in exon #1 of Rabaptin, RAB GTPase binding effector protein 1; in intron #38 of Maltase-glucoamylase (alpha-glucosidase); in intron #23 of Ankyrin 3, node of Ranvier (ankyrin G); 71,333 base pair 3′ of Gremlin 1, cysteine knot superfamily, homolog; 1,561 base pair of 3′ Zinc finger protein 667; in exon #4 of Phosphatidylinositol transfer protein, beta; in intron #18 of Adenylate cyclase 3; and in exon #2 of Hypothetical gene supported by AK128346.
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3; in intron #2 of Ankyrin repeat domain 15; in exon #19 of Hypothetical protein FLJ12949; in exon #15 of Solute carrier family 43, member 1; 313,721 base pair 3′ of Thioredoxin-like 2; in exon #2 of Polymerase (RNA) II (DNA directed) polypeptide L, 7.6 kDa; in intron #10 of Syntaxin 5; 141,389 base pair 5′ of Leucine rich repeat containing 16; in intron #2 of Calcium channel, voltage-dependent, beta 4 subunit; 5,474 base pair 5′ of [NM—001005522]; in intron #14 of G protein-coupled receptor kinase interactor 2; in intron #23 of Ankyrin 3, node of Ranvier (ankyrin G); 71,333 base pair 3′ of Gremlin 1, cysteine knot superfamily, homolog; 1,561 base pair of 3′ of Zinc finger protein 667; in exon #2 of Hypothetical gene supported by AK128346; in intron #11 of Transmembrane 9 superfamily member 2; in intron #1 of Potassium channel, subfamily K, member 1; in intron #2 of Chromodomain helicase DNA binding protein 2; 22,184 base pair 5′ of Microcephaly, primary autosomal recessive 1; in intron #4 of Chromosome 21 open reading frame 34; and in intron #2 of Dual specificity phosphatase 5.
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #2 of Ankyrin repeat domain 15; in intron #38 of Maltase-glucoamylase (alpha-glucosidase); and in intron #23 of Ankyrin 3, node of Ranvier (ankyrin G).
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; in intron #2 of Ankyrin repeat domain 15; in exon #19 of Hypothetical protein FLJ12949; in exon #15 of Solute carrier family 43, member 1; 313,721 base pair 3′ of Thioredoxin-like 2; in exon #2 of Polymerase (RNA) II (DNA directed) polypeptide L, 7.6 kDa; in intron #10 of Syntaxin 5; 141,389 base pair 5′ of Leucine rich repeat containing 16; in intron #2 of Calcium channel, voltage-dependent, beta 4 subunit; 5,474 base pair 5′ of [NM—001005522]; in intron #14 of G protein-coupled receptor kinase interactor 2; in intron #2 of Ankyrin 3, node of Ranvier (ankyrin G); 71,333 base pair of 3′ Gremlin 1, cysteine knot superfamily; 1,561 base pair 3′ of Zinc finger protein 667; in exon #2 of Hypothetical gene supported by AK128346; in intron #11 of Transmembrane 9 superfamily member 2; in intron #1 of Potassium channel, subfamily K, member 1; in intron #2 of Chromodomain helicase DNA binding protein 2; in exon #8 of Chromosome 9 open reading frame 94; in intron #4 of Chromosome 21 open reading frame 34; and
  • in intron #2 of Dual specificity phosphatase 5.
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from in intron #3 of Citrate lyase beta like; 210,560 base pair 5′ of Phosphodiesterase 4D; 189,722 base pair 5′ of Ectodysplasin A receptor; 3,510 base pair 3′ of DEP domain containing 6; in exon #6 of Basonuclin 2; in intron #1 of Chromosome 2 open reading frame 3; in intron #1 of FLJ25476 protein; in intron #10 of Staphylococcal nuclease and tudor domain containing 1; in exon #22 of Hermansky-Pudlak syndrome 5; and in exon #24 of Chromosome 12 open reading frame 30.
  • In one embodiment, the Prostate Classification Set comprises target sequences derived from 382,253 base pair 3′ of Replication factor C (activator 1) 3, 38 kDa; 58,123 base pair 3′ of Tripartite motif-containing 61; in intron #3 of Citrate lyase beta like; in intron #1 of Adaptor-related protein complex 1, gamma 2 subunit; in intron #2 of Kallikrein-related peptidase 2; 210,560 base pair 5′ of Phosphodiesterase 4D; 3,508 base pair 3′ of Cytochrome P450, family 4, subfamily F, polypeptide 11; 189,722 base pair 5′ of Ectodysplasin A receptor; in intron #2 of Phospholipase C, beta 1; in intron #10 of KIAA1244; in intron #2 of Paraoxonase 2; 11,235 base pair 3′ of Arachidonate 12-lipoxygenase, 12R type; in exon #22 of Cut-like 2; 143,098 base pair 5′ of Chemokine (C-X-C motif) ligand 12; in intron #6 of Rho guanine nucleotide exchange factor (GEF) 5; 15,057 base pair 5′ of Olfactory receptor, family 2, subfamily A, member 4; 6,025 base pair 3′ of Chromosome 19 open reading frame 42; in exon #2 of Hypothetical gene supported by AK128346; in exon #11 of Phosphoglucomutase 5; in exon #9 of Hyaluronan binding protein 4; in exon #8 of NECAP endocytosis associated 2; in intron #20 of Myeloid/lymphoid or mixed-lineage leukemia; 1,558 base pair 3′ of Signal transducer and activator of transcription; in intron #1 of Chromosome 2 open reading frame 3; in intron #1 of FLJ25476 protein; in intron #10 of Staphylococcal nuclease and tudor domain containing 1; 84,468 base pair 3′ of Transmembrane protein 18; in exon #22 of Hermansky-Pudlak syndrome 5; in exon #24 of Chromosome 12 open reading frame 30; 95,745 base pair of 3′ Splicing factor 3b, subunit 1; in exon #4 of Cofilin 2; in intron #1 of Heparan sulfate 6-O-sulfotransferase 3; in intron #1 of Enabled homolog; in intron #2 of Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase; in intron #8 of Solute carrier family 24, member 3; 32,382 base pair 3′ of Inositol 1,4,5-triphosphate receptor, type 1; in intron #9 of CAP-GLY domain containing linker protein 1; in exon #14 of Transglutaminase 4; in intron #4 of MOCO sulphurase C-terminal domain containing 2; 21,555 base pair 5′ of 4 hydroxyphenylpyruvate dioxygenase-like; and in exon #26 of R3H domain containing 1.
  • In one embodiment, the potential set of target sequences can be filtered for their expression levels using the multi-tissue expression data made publicly available by Affymetrix at (http://www.affymetrix.com/stipport/technical/sample_data/exon_array_data.affx) such that probes with, for example, elevated expression across numerous tissues (non-specific) or no expression in prostate tissue can be excluded.
    • Validation of Target Sequences
  • Following in silico selection of target sequences, each target sequence suitable for use in the Prostate Cancer Prognostic Set may be validated to confirm differential relative or normalized expression in recurrent prostate cancer or non-recurrent prostate cancer. Validation methods are known in the art and include hybridization techniques such as microarray analysis or Northern blotting using appropriate controls, and may include one or more additional steps, such as reverse transcription, transcription, PCR, RT-PCR and the like. The validation of the target sequences using these methods is well within the abilities of a worker skilled in the art.
    • Minimal Expression Signature
  • In one embodiment, individual Prostate Cancer Prognostic Sets provide for at least a determination of a minimal expression signature, capable of distinguishing recurrent from non-recurrent forms of prostate cancer. Means for determining the appropriate number of target sequences necessary to obtain a minimal expression signature are known in the art and include the Nearest Shrunken Centroids (NSC) method.
  • In this method (see US 20070031873), a standardized centroid is computed for each class. This is the average gene expression for each gene in each class divided by the within-class standard deviation for that gene. Nearest centroid classification takes the gene expression profile of a new sample, and compares it to each of these class centroids. The class whose centroid that it is closest to, in squared distance, is the predicted class for that new sample. Nearest shrunken centroid classification “shrinks” each of the class centroids toward the overall centroid for all classes by an amount called the threshold. This shrinkage consists of moving the centroid towards zero by threshold, setting it equal to zero if it hits zero. For example if threshold was 2.0, a centroid of 3.2 would be shrunk to 1.2, a centroid of −3.4 would be shrunk to −1.4, and a centroid of 1.2 would be shrunk to zero. After shrinking the centroids, the new sample is classified by the usual nearest centroid rule, but using the shrunken class centroids. This shrinkage can make the classifier more accurate by reducing the effect of noisy genes and provides an automatic gene selection. In particular, if a gene is shrunk to zero for all classes, then it is eliminated from the prediction rule. Alternatively, it may be set to zero for all classes except one, and it can be learned that the high or low expression for that gene characterizes that class. The user decides on the value to use for threshold. Typically one examines a number of different choices. To guide in this choice, PAM does K-fold cross-validation for a range of threshold values. The samples are divided up at random into K roughly equally sized parts. For each part in turn, the classifier is built on the other K−1 parts then tested on the remaining part. This is done for a range of threshold values, and the cross-validated misclassification error rate is reported for each threshold value. Typically, the user would choose the threshold value giving the minimum cross-validated misclassification error rate.
  • Alternatively, minimal expression signatures can be established through the use of optimization algorithms such as the mean variance algorithm widely used in establishing stock portfolios. This method is described in detail in US patent publication number 20030194734. Essentially, the method calls for the establishment of a set of inputs (stocks in financial applications, expression as measured by intensity here) that will optimize the return (e.g., signal that is generated) one receives for using it while minimizing the variability of the return. In other words, the method calls for the establishment of a set of inputs (e.g., expression as measured by intensity) that will optimize the signal while minimizing variability. Many commercial software programs are available to conduct such operations. “Wagner Associates Mean-Variance Optimization Application,” referred to as “Wagner Software” throughout this specification, is preferred. This software uses functions from the “Wagner Associates Mean-Variance Optimization Library” to determine an efficient frontier and optimal portfolios in the Markowitz sense is preferred. Use of this type of software requires that microarray data be transformed so that it can be treated as an input in the way stock return and risk measurements are used when the software is used for its intended financial analysis purposes.
  • The process of selecting a minimal expression signature can also include the application of heuristic rules. Preferably, such rules are formulated based on biology and an understanding of the technology used to produce clinical results. More preferably, they are applied to output from the optimization method. For example, the mean variance method of portfolio selection can be applied to microarray data for a number of genes differentially expressed in subjects with cancer. Output from the method would be an optimized set of genes that could include some genes that are expressed in peripheral blood as well as in diseased tissue.
  • Other heuristic rules can be applied that are not necessarily related to the biology in question. For example, one can apply a rule that only a prescribed percentage of the portfolio can be represented by a particular gene or group of genes. Commercially available software such as the Wagner Software readily accommodates these types of heuristics. This can be useful, for example, when factors other than accuracy and precision (e.g., anticipated licensing fees) have an impact on the desirability of including one or more genes.
  • In one embodiment, the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of target sequences shown to have a positive correlation with non-recurrent prostate disease, for example those depicted in SEQ ID NOs:1-913 or a subset thereof. In another embodiment, the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of those target sequences shown to have a positive correlation with recurrent prostate cancer, for example those depicted in of SEQ ID NOs: 914-2114, or a subset thereof. In yet another embodiment, the Prostate Cancer Prognostic Set for obtaining a minimal expression signature comprises at least one, two, three, four, five, six, eight, 10, 15, 20, 25 or more of target sequences shown to have a correlation with non-recurrent or recurrent prostate cancer, for example those depicted in SEQ ID NOs:1-2114 or a subset thereof.
  • In some embodiments, the Prostate Cancer Prognostic Set comprises target sequences for detecting expression products of SEQ IDs:1-2114. In some embodiments, the Prostate Cancer Prognostic Set comprises probes for detecting expression levels of sequences exhibiting positive and negative correlation with a disease status of interest are employed. For example, a combination target sequences useful in these methods were found to include those encoding RNAs corresponding to SEQ ID NOs: 1-913 (found at increased expression in prostate cancer samples from NED patients) and/or corresponding to SEQ ID NOs: 914-2114 (found at increased expression levels in prostate cancer samples from SYS patients), where intermediate levels of certain target sequences (Table 7) are observed in prostate cancer samples from PSA patients with biochemical recurrence, where the RNA expression levels are indicative of a disease state or outcome. Subgroups of these target sequences, as well as individual target sequences, have been found useful in such methods.
  • In some embodiments, an RNA signature corresponding to SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21 915-917, 920, 922, 928, 929, 931, 935 and 936 (the 21-RNA′ signature) and/or SEQ ID NOs: 1-11, 914-920 (the ‘18-RNA’ signature) and/or SEQ ID NOs: 1-4, 914,915) (the ‘6-RNA’ signature) and/or SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935 and 936 (the ‘20-RNA’ signature) and/or SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022 (the ‘10-RNA’ signature) and/or SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402 and 1425 (the ‘41-RNA’ signature) are formulated into a linear combination of their respective expression values for each patient generating a patient outcome predictor (‘POP’) score and indicative of the disease status of the patient after prostatectomy.
  • Exemplary subsets and combinations of interest also include at least five, six, 10, 15, 18, 20, 23, 25, 27, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 750, 1000, 1200, 1400, 1600, 1800, 2000, or all 2114 target sequences in Table 4; at least five, six, 10, 15, 18, 20, 23, 25, 27, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, or all 526 target sequences in Table 7; SEQ ID NOs:1, 4, 915, 6, 916, 9, 917, 920, 922, 14, 15, 16, 928, 929, 18, 19, 931, 20, 21, 935, 936, or combinations thereof; SEQ ID NOs:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 914, 915, 916, 917, 918, 919, 920, or combinations thereof; SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935, 936 or combinations thereof; SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014, 1022 or combinations thereof; SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402, 1425 or combinations thereof; at least one, two, three, four, five or six of SEQ ID NOs:1, 4, 6, 9, 14, 15, 16, 18, 19, 20, and 21 and at least one, two, three, four, five or six of SEQ ID NOs:915, 916, 917, 920, 922, 928, 929, 931, 935, and 936; and at least one, two, three, four, five or six of SEQ ID NOs:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 at least one, two, three, four, five or six of at least one, two, three, four, five or six of SEQ ID NOs:914, 915, 916, 917, 918, 919, and 920 and at least one, two, three, four, five or six of SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935, 936; and at least one, two, three, four, five or six of SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014, 1022; and at least one, two, three, four, five or six of SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402, 1425.
  • Exemplary subsets of interest include those described herein, including in the examples. Exemplary combinations of interest include those utilizing one or more of the sequences listed in Tables 5, 7, 8, 9 or 10. Of particular interest are those combinations utilizing at least one sequence exhibiting positive correlation with the trait of interest, as well as those combinations utilizing at least one sequence exhibiting negative correlation with the trait of interest. Also of interest are those combinations utilizing at least two, at least three, at least four, at least five or at least six of those sequences exhibiting such a positive correlation, in combination with at least two, at least three, at least four, at least five, or at least six of those sequences exhibiting such a negative correlation. Exemplary combinations include those utilizing at least one, two, three, four, five or six of the target sequences depicted in Tables 5 and 6.
  • In some embodiments, increased relative expression of one or more of SEQ IDs:1-913, decreased relative expression of one or more of SEQ ID NOs:914-2114 or a combination of any thereof is indicative/predictive of the patient exhibiting no evidence of disease for at least seven years or more after surgery. In some embodiments, increased relative expression of SEQ IDs:914-2114, decreased relative expression of one or more of SEQ ID NOs:1-913 or a combination of any thereof is indicative/predictive of the patient exhibiting systemic prostate cancer. Increased or decreased expression of target sequences represented in these sequence listings, or of the target sequences described in the examples, may be utilized in the methods of the invention.
  • The Prostate Cancer Prognostic Set can optionally include one or more target sequences specifically derived from the transcripts of one or more housekeeping genes and/or one or more internal control target sequences and/or one or more negative control target sequences. In one embodiment, these target sequences can, for example, be used to normalize expression data. Housekeeping genes from which target sequences for inclusion in a Prostate Cancer Prognostic Set can be derived from are known in the art and include those genes in which are expressed at a constant level in normal and prostate cancer tissue.
  • The target sequences described herein may be used alone or in combination with each other or with other known or later identified disease markers.
    • Prostate Cancer Prognostic Probes/Primers
  • The system of the present invention provides for combinations of polynucleotide probes that are capable of detecting the target sequences of the Prostate Cancer Prognostic Sets. Individual polynucleotide probes comprise a nucleotide sequence derived from the nucleotide sequence of the target sequences or complementary sequences thereof. The nucleotide sequence of the polynucleotide probe is designed such that it corresponds to, or is complementary to the target sequences. The polynucleotide probe can specifically hybridize under either stringent or lowered stringency hybridization conditions to a region of the target sequences, to the complement thereof, or to a nucleic acid sequence (such as a cDNA) derived therefrom.
  • The selection of the polynucleotide probe sequences and determination of their uniqueness may be carried out in silico using techniques known in the art, for example, based on a BLASTN search of the polynucleotide sequence in question against gene sequence databases, such as the Human Genome Sequence, UniGene, dbEST or the non-redundant database at NCBI. In one embodiment of the invention, the polynucleotide probe is complementary to a region of a target mRNA derived from a target sequence in the Prostate Cancer Prognostic Set. Computer programs can also be employed to select probe sequences that will not cross hybridize or will not hybridize non-specifically.
  • One skilled in the art will understand that the nucleotide sequence of the polynucleotide probe need not be identical to its target sequence in order to specifically hybridize thereto. The polynucleotide probes of the present invention, therefore, comprise a nucleotide sequence that is at least about 75% identical to a region of the target gene or mRNA. In another embodiment, the nucleotide sequence of the polynucleotide probe is at least about 90% identical a region of the target gene or mRNA. In a further embodiment, the nucleotide sequence of the polynucleotide probe is at least about 95% identical to a region of the target gene or mRNA. Methods of determining sequence identity are known in the art and can be determined, for example, by using the BLASTN program of the University of Wisconsin Computer Group (GCG) software or provided on the NCBI website. The nucleotide sequence of the polynucleotide probes of the present invention may exhibit variability by differing (e.g. by nucleotide substitution, including transition or transversion) at one, two, three, four or more nucleotides from the sequence of the target gene.
  • Other criteria known in the art may be employed in the design of the polynucleotide probes of the present invention. For example, the probes can be designed to have <50% G content and/or between about 25% and about 70% G+C content. Strategies to optimize probe hybridization to the target nucleic acid sequence can also be included in the process of probe selection. Hybridization under particular pH, salt, and temperature conditions can be optimized by taking into account melting temperatures and by using empirical rules that correlate with desired hybridization behaviours. Computer models may be used for predicting the intensity and concentration-dependence of probe hybridization.
  • As is known in the art, in order to represent a unique sequence in the human genome, a probe should be at least 15 nucleotides in length. Accordingly, the polynucleotide probes of the present invention range in length from about 15 nucleotides to the full length of the target sequence or target mRNA. In one embodiment of the invention, the polynucleotide probes are at least about 15 nucleotides in length. In another embodiment, the polynucleotide probes are at least about 20 nucleotides in length. In a further embodiment, the polynucleotide probes are at least about 25 nucleotides in length. In another embodiment, the polynucleotide probes are between about 15 nucleotides and about 500 nucleotides in length. In other embodiments, the polynucleotide probes are between about 15 nucleotides and about 450 nucleotides, about 15 nucleotides and about 400 nucleotides, about 15 nucleotides and about 350 nucleotides, about 15 nucleotides and about 300 nucleotides in length.
  • The polynucleotide probes of a Prostate Cancer Prognostic Set can comprise RNA, DNA, RNA or DNA mimetics, or combinations thereof, and can be single-stranded or double-stranded. Thus the polynucleotide probes can be composed of naturally-occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as polynucleotide probes having non-naturally-occurring portions which function similarly. Such modified or substituted polynucleotide probes may provide desirable properties such as, for example, enhanced affinity for a target gene and increased stability.
  • The system of the present invention further provides for primers and primer pairs capable of amplifying target sequences defined by the Prostate Cancer Prognostic Set, or fragments or subsequences or complements thereof. The nucleotide sequences of the Prostate Cancer Prognostic set may be provided in computer-readable media for in silico applications and as a basis for the design of appropriate primers for amplification of one or more target sequences of the Prostate Cancer Prognostic Set.
  • Primers based on the nucleotide sequences of target sequences can be designed for use in amplification of the target sequences. For use in amplification reactions such as PCR, a pair of primers will be used. The exact composition of the primer sequences is not critical to the invention, but for most applications the primers will hybridize to specific sequences of the Prostate Cancer Prognostic Set under stringent conditions, particularly under conditions of high stringency, as known in the art. The pairs of primers are usually chosen so as to generate an amplification product of at least about 50 nucleotides, more usually at least about 100 nucleotides. Algorithms for the selection of primer sequences are generally known, and are available in commercial software packages. These primers may be used in standard quantitative or qualitative PCR-based assays to assess transcript expression levels of RNAs defined by the Prostate Cancer Prognostic Set. Alternatively, these primers may be used in combination with probes, such as molecular beacons in amplifications using real-time PCR.
  • In one embodiment, the primers or primer pairs, when used in an amplification reaction, specifically amplify at least a portion of a nucleic acid depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), an RNA form thereof, or a complement to either thereof.
  • As is known in the art, a nucleoside is a base-sugar combination and a nucleotide is a nucleoside that further includes a phosphate group covalently linked to the sugar portion of the nucleoside. In forming oligonucleotides, the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound, with the normal linkage or backbone of RNA and DNA being a 3′ to 5′ phosphodiester linkage. Specific examples of polynucleotide probes or primers useful in this invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. As defined in this specification, oligonucleotides having modified backbones include both those that retain a phosphorus atom in the backbone and those that lack a phosphorus atom in the backbone. For the purposes of the present invention, and as sometimes referenced in the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleotides.
  • Exemplary polynucleotide probes or primers having modified oligonucleotide backbones include, for example, those with one or more modified internucleotide linkages that are phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′ amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkyl-phosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms are also included.
  • Exemplary modified oligonucleotide backbones that do not include a phosphorus atom are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. Such backbones include morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulphone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulphamate backbones; methyleneimino and methylenehydrazino backbones; sulphonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts.
  • The present invention also contemplates oligonucleotide mimetics in which both the sugar and the internucleoside linkage of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. An example of such an oligonucleotide mimetic, which has been shown to have excellent hybridization properties, is a peptide nucleic acid (PNA) [Nielsen et al., Science, 254:1497-1500 (1991)]. In PNA compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza-nitrogen atoms of the amide portion of the backbone. The present invention also contemplates polynucleotide probes or primers comprising “locked nucleic acids” (LNAs), which are novel conformationally restricted oligonucleotide analogues containing a methylene bridge that connects the 2′-O of ribose with the 4′-C (see, Singh et al., Chem. Commun., 1998, 4:455-456). LNA and LNA analogues display very high duplex thermal stabilities with complementary DNA and RNA, stability towards 3′-exonuclease degradation, and good solubility properties. Synthesis of the LNA analogues of adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil, their oligomerization, and nucleic acid recognition properties have been described (see Koshkin et al., Tetrahedron, 1998, 54:3607-3630). Studies of mis-matched sequences show that LNA obey the Watson-Crick base pairing rules with generally improved selectivity compared to the corresponding unmodified reference strands.
  • LNAs form duplexes with complementary DNA or RNA or with complementary LNA, with high thermal affinities. The universality of LNA-mediated hybridization has been emphasized by the formation of exceedingly stable LNA:LNA duplexes (Koshkin et al., J. Am. Chem. Soc., 1998, 120:13252-13253). LNA:LNA hybridization was shown to be the most thermally stable nucleic acid type duplex system, and the RNA-mimicking character of LNA was established at the duplex level. Introduction of three LNA monomers (T or A) resulted in significantly increased melting points toward DNA complements.
  • Synthesis of 2′-amino-LNA (Singh et al., J. Org. Chem., 1998, 63, 10035-10039) and 2′-methylamino-LNA has been described and thermal stability of their duplexes with complementary RNA and DNA strands reported. Preparation of phosphorothioate-LNA and 2′-thio-LNA have also been described (Kumar et al., Bioorg. Med. Chem. Lett., 1998, 8:2219-2222).
  • Modified polynucleotide probes or primers may also contain one or more substituted sugar moieties. For example, oligonucleotides may comprise sugars with one of the following substituents at the 2′ position: OH; F; O—, S—, or N-alkyl; O—, S—, or N-alkenyl; O—, S— or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C1 to C10 alkyl or C2 to C10 alkenyl and alkynyl. Examples of such groups are: O[(CH2)n O]m CH3, O(CH2)n OCH3, O(CH2)n NH2, O(CH2)n CH3, O(CH2)n ONH2, and O(CH2)n ON[(CH2)n CH3)]2, where n and m are from 1 to about 10. Alternatively, the oligonucleotides may comprise one of the following substituents at the 2′ position: C1 to C10 lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH3, OCN, Cl, Br, CN, CF3, OCF3, SOCH3, SO2 CH3, ONO2, NO2, N3, NH2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. Specific examples include 2′-methoxyethoxy (2′-O—CH2 CH2 OCH3, also known as 2′-O-(2-methoxyethyl) or 2′-MOE) [Martin et al., Helv. Chim. Acta, 78:486-504 (1995)], 2′-dimethylaminooxyethoxy (O(CH2)2 ON(CH3)2 group, also known as 2′-DMAOE), 2′-methoxy (2′-O—CH3), 2′-aminopropoxy (2′-OCH2 CH2 CH2 NH2) and 2′-fluoro (2′-F).
  • Similar modifications may also be made at other positions on the polynucleotide probes or primers, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked oligonucleotides and the 5′ position of 5′ terminal nucleotide. Polynucleotide probes or primers may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar.
  • Polynucleotide probes or primers may also include modifications or substitutions to the nucleobase. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808; The Concise Encyclopedia Of Polymer Science And Engineering, (1990) pp 858-859, Kroschwitz, J. I., ed. John Wiley & Sons; Englisch et al., Angewandte Chemie, Int. Ed., 30:613 (1991); and Sanghvi, Y. S., (1993) Antisense Research and Applications, pp 289-302, Crooke, S. T. and Lebleu, B., ed., CRC Press. Certain of these nucleobases are particularly useful for increasing the binding affinity of the polynucleotide probes of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. [Sanghvi, Y. S., (1993) Antisense Research and Applications, pp 276-278, Crooke, S. T. and Lebleu, B., ed., CRC Press, Boca Raton].
  • One skilled in the art will recognize that it is not necessary for all positions in a given polynucleotide probe or primer to be uniformly modified. The present invention, therefore, contemplates the incorporation of more than one of the aforementioned modifications into a single polynucleotide probe or even at a single nucleoside within the probe or primer.
  • One skilled in the art will also appreciate that the nucleotide sequence of the entire length of the polynucleotide probe or primer does not need to be derived from the target sequence. Thus, for example, the polynucleotide probe may comprise nucleotide sequences at the 5′ and/or 3′ termini that are not derived from the target sequences. Nucleotide sequences which are not derived from the nucleotide sequence of the target sequence may provide additional functionality to the polynucleotide probe. For example, they may provide a restriction enzyme recognition sequence or a “tag” that facilitates detection, isolation, purification or immobilisation onto a solid support. Alternatively, the additional nucleotides may provide a self-complementary sequence that allows the primer/probe to adopt a hairpin configuration. Such configurations are necessary for certain probes, for example, molecular beacon and Scorpion probes, which can be used in solution hybridization techniques.
  • The polynucleotide probes or primers can incorporate moieties useful in detection, isolation, purification, or immobilisation, if desired. Such moieties are well-known in the art (see, for example, Ausubel et al., (1997 & updates) Current Protocols in Molecular Biology, Wiley & Sons, New York) and are chosen such that the ability of the probe to hybridize with its target sequence is not affected.
  • Examples of suitable moieties are detectable labels, such as radioisotopes, fluorophores, chemiluminophores, enzymes, colloidal particles, and fluorescent microparticles, as well as antigens, antibodies, haptens, avidin/streptavidin, biotin, haptens, enzyme cofactors/substrates, enzymes, and the like.
  • A label can optionally be attached to or incorporated into a probe or primer polynucleotide to allow detection and/or quantitation of a target polynucleotide representing the target sequence of interest. The target polynucleotide may be the expressed target sequence RNA itself, a cDNA copy thereof, or an amplification product derived therefrom, and may be the positive or negative strand, so long as it can be specifically detected in the assay being used. Similarly, an antibody may be labeled.
  • In certain multiplex formats, labels used for detecting different targets may be distinguishable. The label can be attached directly (e.g., via covalent linkage) or indirectly, e.g., via a bridging molecule or series of molecules (e.g., a molecule or complex that can bind to an assay component, or via members of a binding pair that can be incorporated into assay components, e.g. biotin-avidin or streptavidin). Many labels are commercially available in activated forms which can readily be used for such conjugation (for example through amine acylation), or labels may be attached through known or determinable conjugation schemes, many of which are known in the art.
  • Labels useful in the invention described herein include any substance which can be detected when bound to or incorporated into the biomolecule of interest. Any effective detection method can be used, including optical, spectroscopic, electrical, piezoelectrical, magnetic, Raman scattering, surface plasmon resonance, colorimetric, calorimetric, etc. A label is typically selected from a chromophore, a lumiphore, a fluorophore, one member of a quenching system, a chromogen, a hapten, an antigen, a magnetic particle, a material exhibiting nonlinear optics, a semiconductor nanocrystal, a metal nanoparticle, an enzyme, an antibody or binding portion or equivalent thereof, an aptamer, and one member of a binding pair, and combinations thereof. Quenching schemes may be used, wherein a quencher and a fluorophore as members of a quenching pair may be used on a probe, such that a change in optical parameters occurs upon binding to the target introduce or quench the signal from the fluorophore. One example of such a system is a molecular beacon. Suitable quencher/fluorophore systems are known in the art. The label may be bound through a variety of intermediate linkages. For example, a polynucleotide may comprise a biotin-binding species, and an optically detectable label may be conjugated to biotin and then bound to the labeled polynucleotide. Similarly, a polynucleotide sensor may comprise an immunological species such as an antibody or fragment, and a secondary antibody containing an optically detectable label may be added.
  • Chromophores useful in the methods described herein include any substance which can absorb energy and emit light. For multiplexed assays, a plurality of different signaling chromophores can be used with detectably different emission spectra. The chromophore can be a lumophore or a fluorophore. Typical fluorophores include fluorescent dyes, semiconductor nanocrystals, lanthanide chelates, polynucleotide-specific dyes and green fluorescent protein.
  • Coding schemes may optionally be used, comprising encoded particles and/or encoded tags associated with different polynucleotides of the invention. A variety of different coding schemes are known in the art, including fluorophores, including SCNCs, deposited metals, and RF tags.
  • Polynucleotides from the described target sequences may be employed as probes for detecting target sequences expression, for ligation amplification schemes, or may be used as primers for amplification schemes of all or a portion of a target sequences. When amplified, either strand produced by amplification may be provided in purified and/or isolated form.
  • In one embodiment, polynucleotides of the invention include a nucleic acid depicted in (a) any one of SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (b) an RNA form of any one of the nucleic acids depicted in SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (c) a peptide nucleic acid form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114, or a subgroup thereof as set forth herein; (d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c); (e) a nucleic acid comprising at least 25 bases having at least 90% sequenced identity to any of (a-c); and (f) a complement to any of (a-e).
  • Complements may take any polymeric form capable of base pairing to the species recited in (a)-(e), including nucleic acid such as RNA or DNA, or may be a neutral polymer such as a peptide nucleic acid. Polynucleotides of the invention can be selected from the subsets of the recited nucleic acids described herein, as well as their complements.
  • In some embodiments, polynucleotides of the invention comprise at least 20 consecutive bases as depicted in SEQ ID NOs:1-2114, or a complement thereto. The polynucleotides may comprise at least 21, 22, 23, 24, 25, 27, 30, 32, 35 or more consecutive bases as depicted in SEQ ID NOs:1-2114, as applicable.
  • In some embodiments, the nucleic acid in (a) can be selected from those in Table 3, and from SEQ ID NOs:1, 4, 915, 6, 916, 9, 917, 920, 922, 14, 15, 16, 928, 929, 18, 19, 931, 20, 21, 935, and 936; or from SEQ ID NOs:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 914, 915, 916, 917, 918, 919, and 920; or from SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21, 915-917, 920, 922, 928, 929, 931, 935 and 936; or from SEQ ID NOs 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022; or from SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402 and 1425.
  • The polynucleotides may be provided in a variety of formats, including as solids, in solution, or in an array. The polynucleotides may optionally comprise one or more labels, which may be chemically and/or enzymatically incorporated into the polynucleotide.
  • In one embodiment, solutions comprising polynucleotide and a solvent are also provided. In some embodiments, the solvent may be water or may be predominantly aqueous. In some embodiments, the solution may comprise at least two, three, four, five, six, seven, eight, nine, ten, twelve, fifteen, seventeen, twenty or more different polynucleotides, including primers and primer pairs, of the invention. Additional substances may be included in the solution, alone or in combination, including one or more labels, additional solvents, buffers, biomolecules, polynucleotides, and one or more enzymes useful for performing methods described herein, including polymerases and ligases. The solution may further comprise a primer or primer pair capable of amplifying a polynucleotide of the invention present in the solution.
  • In some embodiments, one or more polynucleotides provided herein can be provided on a substrate. The substrate can comprise a wide range of material, either biological, nonbiological, organic, inorganic, or a combination of any of these. For example, the substrate may be a polymerized Langmuir Blodgett film, functionalized glass, Si, Ge, GaAs, GaP, SiO2, SiN4, modified silicon, or any one of a wide variety of gels or polymers such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, cross-linked polystyrene, polyacrylic, polylactic acid, polyglycolic acid, poly(lactide coglycolide), polyanhydrides, poly(methyl methacrylate), poly(ethylene-co-vinyl acetate), polysiloxanes, polymeric silica, latexes, dextran polymers, epoxies, polycarbonates, or combinations thereof. Conducting polymers and photoconductive materials can be used.
  • Substrates can be planar crystalline substrates such as silica based substrates (e.g. glass, quartz, or the like), or crystalline substrates used in, e.g., the semiconductor and microprocessor industries, such as silicon, gallium arsenide, indium doped GaN and the like, and includes semiconductor nanocrystals.
  • The substrate can take the form of an array, a photodiode, an optoelectronic sensor such as an optoelectronic semiconductor chip or optoelectronic thin-film semiconductor, or a biochip. The location(s) of probe(s) on the substrate can be addressable; this can be done in highly dense formats, and the location(s) can be microaddressable or nanoaddressable.
  • Silica aerogels can also be used as substrates, and can be prepared by methods known in the art. Aerogel substrates may be used as free standing substrates or as a surface coating for another substrate material.
  • The substrate can take any form and typically is a plate, slide, bead, pellet, disk, particle, microparticle, nanoparticle, strand, precipitate, optionally porous gel, sheets, tube, sphere, container, capillary, pad, slice, film, chip, multiwell plate or dish, optical fiber, etc. The substrate can be any form that is rigid or semi-rigid. The substrate may contain raised or depressed regions on which an assay component is located. The surface of the substrate can be etched using known techniques to provide for desired surface features, for example trenches, v-grooves, mesa structures, or the like.
  • Surfaces on the substrate can be composed of the same material as the substrate or can be made from a different material, and can be coupled to the substrate by chemical or physical means. Such coupled surfaces may be composed of any of a wide variety of materials, for example, polymers, plastics, resins, polysaccharides, silica or silica-based materials, carbon, metals, inorganic glasses, membranes, or any of the above-listed substrate materials. The surface can be optically transparent and can have surface Si—OH functionalities, such as those found on silica surfaces.
  • The substrate and/or its optional surface can be chosen to provide appropriate characteristics for the synthetic and/or detection methods used. The substrate and/or surface can be transparent to allow the exposure of the substrate by light applied from multiple directions. The substrate and/or surface may be provided with reflective “mirror” structures to increase the recovery of light.
  • The substrate and/or its surface is generally resistant to, or is treated to resist, the conditions to which it is to be exposed in use, and can be optionally treated to remove any resistant material after exposure to such conditions.
  • The substrate or a region thereof may be encoded so that the identity of the sensor located in the substrate or region being queried may be determined Any suitable coding scheme can be used, for example optical codes, RFID tags, magnetic codes, physical codes, fluorescent codes, and combinations of codes.
    • Preparation of Probes and Primers
  • The polynucleotide probes or primers of the present invention can be prepared by conventional techniques well-known to those skilled in the art. For example, the polynucleotide probes can be prepared using solid-phase synthesis using commercially available equipment. As is well-known in the art, modified oligonucleotides can also be readily prepared by similar methods. The polynucleotide probes can also be synthesized directly on a solid support according to methods standard in the art. This method of synthesizing polynucleotides is particularly useful when the polynucleotide probes are part of a nucleic acid array.
  • Polynucleotide probes or primers can be fabricated on or attached to the substrate by any suitable method, for example the methods described in U.S. Pat. No. 5,143,854, PCT Publ. No. WO 92/10092, U.S. patent application Ser. No. 07/624,120, filed Dec. 6, 1990 (now abandoned), Fodor et al., Science, 251: 767-777 (1991), and PCT Publ. No. WO 90/15070). Techniques for the synthesis of these arrays using mechanical synthesis strategies are described in, e.g., PCT Publication No. WO 93/09668 and U.S. Pat. No. 5,384,261. Still further techniques include bead based techniques such as those described in PCT Appl. No. PCT/US93/04145 and pin based methods such as those described in U.S. Pat. No. 5,288,514. Additional flow channel or spotting methods applicable to attachment of sensor polynucleotides to a substrate are described in U.S. patent application Ser. No. 07/980,523, filed Nov. 20, 1992, and U.S. Pat. No. 5,384,261.
  • Alternatively, the polynucleotide probes of the present invention can be prepared by enzymatic digestion of the naturally occurring target gene, or mRNA or cDNA derived therefrom, by methods known in the art.
    • Prostate Cancer Prognostic Methods
  • The present invention further provides methods for characterizing prostate cancer sample for recurrence risk. The methods use the Prostate Cancer Prognostic Sets, probes and primers described herein to provide expression signatures or profiles from a test sample derived from a subject having or suspected of having prostate cancer. In some embodiments, such methods involve contacting a test sample with Prostate Cancer Prognostic probes (either in solution or immobilized) under conditions that permit hybridization of the probe(s) to any target nucleic acid(s) present in the test sample and then detecting any probe:target duplexes formed as an indication of the presence of the target nucleic acid in the sample. Expression patterns thus determined are then compared to one or more reference profiles or signatures. Optionally, the expression pattern can be normalized. The methods use the Prostate Cancer Prognostic Sets, probes and primers described herein to provide expression signatures or profiles from a test sample derived from a subject to classify the prostate cancer as recurrent or non-recurrent.
  • In some embodiments, such methods involve the specific amplification of target sequences nucleic acid(s) present in the test sample using methods known in the art to generate an expression profile or signature which is then compared to a reference profile or signature.
  • In some embodiments, the invention further provides for prognosing patient outcome, predicting likelihood of recurrence after prostatectomy and/or for designating treatment modalities.
  • In one embodiment, the methods generate expression profiles or signatures detailing the expression of the 2114 target sequences having altered relative expression with different prostate cancer outcomes. In one embodiment, the methods generate expression profiles or signatures detailing the expression of the subsets of these target sequences having 526 or 18 target sequences as described in the examples.
  • In some embodiments, increased relative expression of one or more of SEQ IDs:1-913, decreased relative expression of one or more of SEQ ID NOs:914-2114 or a combination of any thereof is indicative of a non-recurrent form of prostate cancer and may be predictive a NED clinical outcome after surgery. In some embodiments, increased relative expression of SEQ IDs:914-2114, decreased relative expression of one or more of SEQ ID NOs:1-913 or a combination of any thereof is indicative of a recurrent form of prostate cancer and may be predictive of a SYS clinical outcome after surgery. Increased or decreased expression of target sequences represented in these sequence listings, or of the target sequences described in the examples, may be utilized in the methods of the invention.
  • In one embodiment, intermediate levels of expression of one or more target sequences depicted in Table 7 indicate a probability of future biochemical recurrence.
  • In some embodiments, the methods detect combinations of expression levels of sequences exhibiting positive and negative correlation with a disease status. In one embodiment, the methods detect a minimal expression signature.
  • Any method of detecting and/or quantitating the expression of the encoded target sequences can in principle be used in the invention. Such methods can include Northern blotting, array or microarray hybridization, by enzymatic cleavage of specific structures (e.g., an Invader® assay, Third Wave Technologies, e.g. as described in U.S. Pat. Nos. 5,846,717, 6,090,543; 6,001,567; 5,985,557; and 5,994,069) and amplification methods, e.g. RT-PCR, including in a TaqMan® assay (PE Biosystems, Foster City, Calif., e.g. as described in U.S. Pat. Nos. 5,962,233 and 5,538,848), and may be quantitative or semi-quantitative, and may vary depending on the origin, amount and condition of the available biological sample. Combinations of these methods may also be used. For example, nucleic acids may be amplified, labeled and subjected to microarray analysis. Single-molecule sequencing (e.g., Illumina, Helicos, PacBio, ABI SOLID), in situ hybridization, bead-array technologies (e.g., Luminex xMAP, Illumina BeadChips), branched DNA technology (e.g., Panomics, Genisphere).
  • The expressed target sequences can be directly detected and/or quantitated, or may be copied and/or amplified to allow detection of amplified copies of the expressed target sequences or its complement. In some embodiments, degraded and/or fragmented RNA can be usefully analyzed for expression levels of target sequences, for example RNA having an RNA integrity number of less than 8.
  • In some embodiments, quantitative RT-PCR assays are used to measure the expression level of target sequences depicted in SEQ IDs: 1-2114. In other embodiments, a GeneChip or microarray can be used to measure the expression of one or more of the target sequences.
  • Molecular assays measure the relative expression levels of the target sequences, which can be normalized to the expression levels of one or more control sequences, for example array control sequences and/or one or more housekeeping genes, for example GAPDH. Increased (or decreased) relative expression of the target sequences as described herein, including any of SEQ ID NOs:1-2114, may thus be used alone or in any combination with each other in the methods described herein. In addition, negative control probes may be included.
    • Diagnostic Samples
  • Diagnostic samples for use with the systems and in the methods of the present invention comprise nucleic acids suitable for providing RNAs expression information. In principle, the biological sample from which the expressed RNA is obtained and analyzed for target sequence expression can be any material suspected of comprising prostate cancer tissue or cells. The diagnostic sample can be a biological sample used directly in a method of the invention. Alternatively, the diagnostic sample can be a sample prepared from a biological sample.
  • In one embodiments, the sample or portion of the sample comprising or suspected of comprising prostate cancer tissue or cells can be any source of biological material, including cells, tissue or fluid, including bodily fluids. Non-limiting examples of the source of the sample include an aspirate, a needle biopsy, a cytology pellet, a bulk tissue preparation or a section thereof obtained for example by surgery or autopsy, lymph fluid, blood, plasma, serum, tumors, and organs.
  • The samples may be archival samples, having a known and documented medical outcome, or may be samples from current patients whose ultimate medical outcome is not yet known.
  • In some embodiments, the sample may be dissected prior to molecular analysis. The sample may be prepared via macrodissection of a bulk tumor specimen or portion thereof, or may be treated via microdissection, for example via Laser Capture Microdissection (LCM).
  • The sample may initially be provided in a variety of states, as fresh tissue, fresh frozen tissue, fine needle aspirates, and may be fixed or unfixed. Frequently, medical laboratories routinely prepare medical samples in a fixed state, which facilitates tissue storage. A variety of fixatives can be used to fix tissue to stabilize the morphology of cells, and may be used alone or in combination with other agents. Exemplary fixatives include crosslinking agents, alcohols, acetone, Bouin's solution, Zenker solution, Hely solution, osmic acid solution and Carnoy solution.
  • Crosslinking fixatives can comprise any agent suitable for forming two or more covalent bonds, for example an aldehyde. Sources of aldehydes typically used for fixation include formaldehyde, paraformaldehyde, glutaraldehyde or formalin. Preferably, the crosslinking agent comprises formaldehyde, which may be included in its native form or in the form of paraformaldehyde or formalin. One of skill in the art would appreciate that for samples in which crosslinking fixatives have been used special preparatory steps may be necessary including for example heating steps and proteinase-k digestion; see methods
  • One or more alcohols may be used to fix tissue, alone or in combination with other fixatives. Exemplary alcohols used for fixation include methanol, ethanol and isopropanol.
  • Formalin fixation is frequently used in medical laboratories. Formalin comprises both an alcohol, typically methanol, and formaldehyde, both of which can act to fix a biological sample.
  • Whether fixed or unfixed, the biological sample may optionally be embedded in an embedding medium. Exemplary embedding media used in histology including paraffin, Tissue-Tek® V.I.P.™, Paramat, Paramat Extra, Paraplast, Paraplast X-tra, Paraplast Plus, Peel Away Paraffin Embedding Wax, Polyester Wax, Carbowax Polyethylene Glycol, Polyfin™, Tissue Freezing Medium TFM™, Cryo-Gel™, and OCT Compound (Electron Microscopy Sciences, Hatfield, Pa.). Prior to molecular analysis, the embedding material may be removed via any suitable techniques, as known in the art. For example, where the sample is embedded in wax, the embedding material may be removed by extraction with organic solvent(s), for example xylenes. Kits are commercially available for removing embedding media from tissues. Samples or sections thereof may be subjected to further processing steps as needed, for example serial hydration or dehydration steps.
  • In some embodiments, the sample is a fixed, wax-embedded biological sample. Frequently, samples from medical laboratories are provided as fixed, wax-embedded samples, most commonly as formalin-fixed, paraffin embedded (FFPE) tissues.
  • Whatever the source of the biological sample, the target polynucleotide that is ultimately assayed can be prepared synthetically (in the case of control sequences), but typically is purified from the biological source and subjected to one or more preparative steps. The RNA may be purified to remove or diminish one or more undesired components from the biological sample or to concentrate it. Conversely, where the RNA is too concentrated for the particular assay, it may be diluted.
    • RNA Extraction
  • RNA can be extracted and purified from biological samples using any suitable technique. A number of techniques are known in the art, and several are commercially available (e.g., FormaPure™ nucleic acid extraction kit, Agencourt Biosciences, Beverly Mass., High Pure FFPE RNA Micro Kit™, Roche Applied Science, Indianapolis, Ind.). RNA can be extracted from frozen tissue sections using TRIzol (Invitrogen, Carlsbad, Calif.) and purified using RNeasy Protect kit (Qiagen, Valencia, Calif.). RNA can be further purified using DNAse I treatment (Ambion, Austin, Tex.) to eliminate any contaminating DNA. RNA concentrations can be made using a Nanodrop ND-1000 spectrophotometer (Nanodrop Technologies, Rockland, Del.). RNA integrity can be evaluated by running electropherograms, and RNA integrity number (RIN, a correlative measure that indicates intactness of mRNA) can be determined using the RNA 6000 PicoAssay for the Bioanalyzer 2100 (Agilent Technologies, Santa Clara, Calif.).
    • Reverse Transcription for QRT-PCR Analysis
  • Reverse transcription can be performed using the Omniscript kit (Qiagen, Valencia, Calif.), Superscript III kit (Invitrogen, Carlsbad, Calif.), for RT-PCR. Target-specific priming can be performed in order to increase the sensitivity of detection of target sequences and generate target-specific cDNA.
  • TaqMan® Gene Expression Analysis
  • TaqMan® RT-PCR can be performed using Applied Biosystems Prism (ABI) 7900 HT instruments in a 5 μl volume with target sequence-specific cDNA equivalent to 1 ng total RNA. Primers and probes concentrations for TaqMan analysis are added to amplify fluorescent amplicons using PCR cycling conditions such as 95° C. for 10 minutes for one cycle, 95° C. for 20 seconds, and 60° C. for 45 seconds for 40 cycles. A reference sample can be assayed to ensure reagent and process stability. Negative controls (i.e., no template) should be assayed to monitor any exogenous nucleic acid contamination.
    • Amplification and Hybridization
  • Following sample collection and nucleic acid extraction, the nucleic acid portion of the sample comprising RNA that is or can be used to prepare the target polynucleotide(s) of interest can be subjected to one or more preparative reactions. These preparative reactions can include in vitro transcription (IVT), labeling, fragmentation, amplification and other reactions. mRNA can first be treated with reverse transcriptase and a primer to create cDNA prior to detection, quantitation and/or amplification; this can be done in vitro with purified mRNA or in situ, e.g., in cells or tissues affixed to a slide.
  • By “amplification” is meant any process of producing at least one copy of a nucleic acid, in this case an expressed RNA, and in many cases produces multiple copies. An amplification product can be RNA or DNA, and may include a complementary strand to the expressed target sequence. DNA amplification products can be produced initially through reverse translation and then optionally from further amplification reactions. The amplification product may include all or a portion of a target sequence, and may optionally be labeled. A variety of amplification methods are suitable for use, including polymerase-based methods and ligation-based methods. Exemplary amplification techniques include the polymerase chain reaction method (PCR), the ligase chain reaction (LCR), ribozyme-based methods, self sustained sequence replication (3SR), nucleic acid sequence-based amplification (NASBA), the use of Q Beta replicase, reverse transcription, nick translation, and the like.
  • Asymmetric amplification reactions may be used to preferentially amplify one strand representing the target sequence that is used for detection as the target polynucleotide. In some cases, the presence and/or amount of the amplification product itself may be used to determine the expression level of a given target sequence. In other instances, the amplification product may be used to hybridize to an array or other substrate comprising sensor polynucleotides which are used to detect and/or quantitate target sequence expression.
  • The first cycle of amplification in polymerase-based methods typically forms a primer extension product complementary to the template strand. If the template is single-stranded RNA, a polymerase with reverse transcriptase activity is used in the first amplification to reverse transcribe the RNA to DNA, and additional amplification cycles can be performed to copy the primer extension products. The primers for a PCR must, of course, be designed to hybridize to regions in their corresponding template that will produce an amplifiable segment; thus, each primer must hybridize so that its 3′ nucleotide is paired to a nucleotide in its complementary template strand that is located 3′ from the 3′ nucleotide of the primer used to replicate that complementary template strand in the PCR.
  • The target polynucleotide can be amplified by contacting one or more strands of the target polynucleotide with a primer and a polymerase having suitable activity to extend the primer and copy the target polynucleotide to produce a full-length complementary polynucleotide or a smaller portion thereof. Any enzyme having a polymerase activity that can copy the target polynucleotide can be used, including DNA polymerases, RNA polymerases, reverse transcriptases, enzymes having more than one type of polymerase or enzyme activity. The enzyme can be thermolabile or thermostable. Mixtures of enzymes can also be used. Exemplary enzymes include: DNA polymerases such as DNA Polymerase I (“Pol I”), the Klenow fragment of Pol I, T4, T7, Sequenase® T7, Sequenase® Version 2.0 T7, Tub, Taq, Tth, Pfx, Pfu, Tsp, Tfl, Tli and Pyrococcus sp GB-D DNA polymerases; RNA polymerases such as E. coli, SP6, T3 and T7 RNA polymerases; and reverse transcriptases such as AMV, M-MuLV, MMLV, RNAse H− MMLV (SuperScript®), SuperScript® II, ThermoScript®, HIV-1, and RAV2 reverse transcriptases. All of these enzymes are commercially available. Exemplary polymerases with multiple specificities include RAV2 and Tli (exo-) polymerases. Exemplary thermostable polymerases include Tub, Taq, Tth, Pfx, Pfu, Tsp, Tfl, Tli and Pyrococcus sp. GB-D DNA polymerases.
  • Suitable reaction conditions are chosen to permit amplification of the target polynucleotide, including pH, buffer, ionic strength, presence and concentration of one or more salts, presence and concentration of reactants and cofactors such as nucleotides and magnesium and/or other metal ions (e.g., manganese), optional cosolvents, temperature, thermal cycling profile for amplification schemes comprising a polymerase chain reaction, and may depend in part on the polymerase being used as well as the nature of the sample. Cosolvents include formamide (typically at from about 2 to about 10%), glycerol (typically at from about 5 to about 10%), and DMSO (typically at from about 0.9 to about 10%). Techniques may be used in the amplification scheme in order to minimize the production of false positives or artifacts produced during amplification. These include “touchdown” PCR, hot-start techniques, use of nested primers, or designing PCR primers so that they form stem-loop structures in the event of primer-dimer formation and thus are not amplified. Techniques to accelerate PCR can be used, for example centrifugal PCR, which allows for greater convection within the sample, and comprising infrared heating steps for rapid heating and cooling of the sample. One or more cycles of amplification can be performed. An excess of one primer can be used to produce an excess of one primer extension product during PCR; preferably, the primer extension product produced in excess is the amplification product to be detected. A plurality of different primers may be used to amplify different target polynucleotides or different regions of a particular target polynucleotide within the sample.
  • An amplification reaction can be performed under conditions which allow an optionally labeled sensor polynucleotide to hybridize to the amplification product during at least part of an amplification cycle. When the assay is performed in this manner, real-time detection of this hybridization event can take place by monitoring for light emission or fluorescence during amplification, as known in the art.
  • Where the amplification product is to be used for hybridization to an array or microarray, a number of suitable commercially available amplification products are available. These include amplification kits available from NuGEN, Inc. (San Carlos, Calif.), including the WT-Ovation™ System, WT-Ovation™ System v2, WT-Ovation™ Pico System, WT-Ovation™ FFPE Exon Module, WT-Ovation™ FFPE Exon Module RiboAmp and RiboAmpPlus RNA Amplification Kits (MDS Analytical Technologies (formerly Arcturus) (Mountain View, Calif.), Genisphere, Inc. (Hatfield, Pa.), including the RampUp Plus™ and SenseAmp™ RNA Amplification kits, alone or in combination. Amplified nucleic acids may be subjected to one or more purification reactions after amplification and labeling, for example using magnetic beads (e.g., RNAClean magnetic beads, Agencourt Biosciences).
  • Multiple RNA biomarkers can be analyzed using real-time quantitative multiplex RT-PCR platforms and other multiplexing technologies such as GenomeLab GeXP Genetic Analysis System (Beckman Coulter, Foster City, Calif.), SmartCycler® 9600 or GeneXpert(R) Systems (Cepheid, Sunnyvale, Calif.), ABI 7900 HT Fast Real Time PCR system (Applied Biosystems, Foster City, Calif.), LightCycler® 480 System (Roche Molecular Systems, Pleasanton, Calif.), xMAP 100 System (Luminex, Austin, Tex.) Solexa Genome Analysis System (Illumina, Hayward, Calif.), OpenArray Real Time qPCR (BioTrove, Woburn, Mass.) and BeadXpress System (Illumina, Hayward, Calif.).
    • Prostate Classification Arrays
  • The present invention contemplates that a Prostate Cancer Prognostic Set or probes derived therefrom may be provided in an array format. In the context of the present invention, an “array” is a spatially or logically organized collection of polynucleotide probes. Any array comprising sensor probes specific for two or more of SEQ ID NOs: 1-2114 or a product derived therefrom can be used. Desirably, an array will be specific for 5, 10, 15, 20, 25, 30, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 1000, 1200, 1400, 1600, 1800, 2000 or more of SEQ ID NOs: 1-2114. Expression of these sequences may be detected alone or in combination with other transcripts. In some embodiments, an array is used which comprises a wide range of sensor probes for prostate-specific expression products, along with appropriate control sequences. An array of interest is the Human Exon 1.0 ST Array (HuEx 1.0 ST, Affymetrix, Inc., Santa Clara, Calif.).
  • Typically the polynucleotide probes are attached to a solid substrate and are ordered so that the location (on the substrate) and the identity of each are known. The polynucleotide probes can be attached to one of a variety of solid substrates capable of withstanding the reagents and conditions necessary for use of the array. Examples include, but are not limited to, polymers, such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, polycarbonate, polypropylene and polystyrene; ceramic; silicon; silicon dioxide; modified silicon; (fused) silica, quartz or glass; functionalized glass; paper, such as filter paper; diazotized cellulose; nitrocellulose filter; nylon membrane; and polyacrylamide gel pad. Substrates that are transparent to light are useful for arrays that will be used in an assay that involves optical detection.
  • Examples of array formats include membrane or filter arrays (for example, nitrocellulose, nylon arrays), plate arrays (for example, multiwell, such as a 24-, 96-, 256-, 384-, 864- or 1536-well, microtitre plate arrays), pin arrays, and bead arrays (for example, in a liquid “slurry”). Arrays on substrates such as glass or ceramic slides are often referred to as chip arrays or “chips.” Such arrays are well known in the art. In one embodiment of the present invention, the Prostate Cancer Prognosticarray is a chip.
    • Data Analysis
  • Array data can be managed and analyzed using techniques known in the art. The Genetrix suite of tools can be used for microarray analysis (Epicenter Software, Pasadena, Calif.). Probe set modeling and data pre-processing can be derived using the Robust Multi-Array (RMA) algorithm or variant GC-RMA, Probe Logarithmic Intensity Error (PLIER) algorithm or variant iterPLIER. Variance or intensity filters can be applied to pre-process data using the RMA algorithm, for example by removing target sequences with a standard deviation of <10 or a mean intensity of <100 intensity units of a normalized data range, respectively.
  • In some embodiments, one or more pattern recognition methods can be used in analyzing the expression level of target sequences. The pattern recognition method can comprise a linear combination of expression levels, or a nonlinear combination of expression levels. In some embodiments, expression measurements for RNA transcripts or combinations of RNA transcript levels are formulated into linear or non-linear models or algorithms (i.e., an ‘expression signature’) and converted into a likelihood score. This likelihood score indicates the probability that a biological sample is from a patient who will exhibit no evidence of disease, who will exhibit systemic cancer, or who will exhibit biochemical recurrence. The likelihood score can be used to distinguish these disease states. The models and/or algorithms can be provided in machine readable format, and may be used to correlate expression levels or an expression profile with a disease state, and/or to designate a treatment modality for a patient or class of patients.
  • Thus, results of the expression level analysis can be used to correlate increased expression of RNAs corresponding to SEQ ID NOs: 1-2114, or subgroups thereof as described herein, with prostate cancer outcome, and to designate a treatment modality.
  • Factors known in the art for diagnosing and/or suggesting, selecting, designating, recommending or otherwise determining a course of treatment for a patient or class of patients suspected of having prostate cancer can be employed in combination with measurements of the target sequence expression. These techniques include cytology, histology, ultrasound analysis, MRI results, CT scan results, and measurements of PSA levels.
  • Certified tests for classifying prostate disease status and/or designating treatment modalities are also provided. A certified test comprises a means for characterizing the expression levels of one or more of the target sequences of interest, and a certification from a government regulatory agency endorsing use of the test for classifying the prostate disease status of a biological sample.
  • In some embodiments, the certified test may comprise reagents for amplification reactions used to detect and/or quantitate expression of the target sequences to be characterized in the test. An array of probe nucleic acids can be used, with or without prior target amplification, for use in measuring target sequence expression.
  • The test is submitted to an agency having authority to certify the test for use in distinguishing prostate disease status and/or outcome. Results of detection of expression levels of the target sequences used in the test and correlation with disease status and/or outcome are submitted to the agency. A certification authorizing the diagnostic and/or prognostic use of the test is obtained.
  • Also provided are portfolios of expression levels comprising a plurality of normalized expression levels of the target sequences described herein, including SEQ ID NOs:1-2114. Such portfolios may be provided by performing the methods described herein to obtain expression levels from an individual patient or from a group of patients. The expression levels can be normalized by any method known in the art; exemplary normalization methods that can be used in various embodiments include Robust Multichip Average (RMA), probe logarithmic intensity error estimation (PLIER), non-linear fit (NLFIT) quantile-based and nonlinear normalization, and combinations thereof. Background correction can also be performed on the expression data; exemplary techniques useful for background correction include mode of intensities, normalized using median polish probe modeling and sketch-normalization.
  • In some embodiments, portfolios are established such that the combination of genes in the portfolio exhibit improved sensitivity and specificity relative to known methods. In considering a group of genes for inclusion in a portfolio, a small standard deviation in expression measurements correlates with greater specificity. Other measurements of variation such as correlation coefficients can also be used in this capacity. The invention also encompasses the above methods where the specificity is at least about 50% or at least about 60%. The invention also encompasses the above methods where the sensitivity is at least about 90%.
  • The gene expression profiles of each of the target sequences comprising the portfolio can fixed in a medium such as a computer readable medium. This can take a number of forms. For example, a table can be established into which the range of signals (e.g., intensity measurements) indicative of disease or outcome is input. Actual patient data can then be compared to the values in the table to determine the patient samples diagnosis or prognosis. In a more sophisticated embodiment, patterns of the expression signals (e.g., fluorescent intensity) are recorded digitally or graphically.
  • The expression profiles of the samples can be compared to a control portfolio. If the sample expression patterns are consistent with the expression pattern for a known disease or disease outcome, the expression patterns can be used to designate one or more treatment modalities. For patients with test scores consistent with systemic disease outcome after prostatectomy, additional treatment modalities such as adjuvant chemotherapy (e.g., docetaxel, mitoxantrone and prednisone), systemic radiation therapy (e.g., samarium or strontium) and/or anti-androgen therapy (e.g., surgical castration, finasteride, dutasteride) can be designated. Such patients would likely be treated immediately with anti-androgen therapy alone or in combination with radiation therapy in order to eliminate presumed micro-metastatic disease, which cannot be detected clinically but can be revealed by the target sequence expression signature. Such patients can also be more closely monitored for signs of disease progression. For patients with test scores consistent with PSA or NED, adjuvant therapy would not likely be recommended by their physicians in order to avoid treatment-related side effects such as metabolic syndrome (e.g., hypertension, diabetes and/or weight gain) or osteoporosis. Patients with samples consistent with NED could be designated for watchful waiting, or for no treatment. Patients with test scores that do not correlate with systemic disease but who have successive PSA increases could be designated for watchful waiting, increased monitoring, or lower dose or shorter duration anti-androgen therapy.
  • Target sequences can be grouped so that information obtained about the set of target sequences in the group can be used to make or assist in making a clinically relevant judgment such as a diagnosis, prognosis, or treatment choice.
  • A patient report is also provided comprising a representation of measured expression levels of a plurality of target sequences in a biological sample from the patient, wherein the representation comprises expression levels of target sequences corresponding to any one, two, three, four, five, six, eight, ten, twenty, thirty, fifty or more of the target sequences depicted in SEQ ID NOs: 1-2114, or of the subsets described herein, or of a combination thereof. In some embodiments, the representation of the measured expression level(s) may take the form of a linear or nonlinear combination of expression levels of the target sequences of interest. The patient report may be provided in a machine (e.g., a computer) readable format and/or in a hard (paper) copy. The report can also include standard measurements of expression levels of said plurality of target sequences from one or more sets of patients with known disease status and/or outcome. The report can be used to inform the patient and/or treating physician of the expression levels of the expressed target sequences, the likely medical diagnosis and/or implications, and optionally may recommend a treatment modality for the patient.
  • Also provided are representations of the gene expression profiles useful for treating, diagnosing, prognosticating, and otherwise assessing disease. In some embodiments, these profile representations are reduced to a medium that can be automatically read by a machine such as computer readable media (magnetic, optical, and the like). The articles can also include instructions for assessing the gene expression profiles in such media. For example, the articles may comprise a readable storage form having computer instructions for comparing gene expression profiles of the portfolios of genes described above. The articles may also have gene expression profiles digitally recorded therein so that they may be compared with gene expression data from patient samples. Alternatively, the profiles can be recorded in different representational format. A graphical recordation is one such format. Clustering algorithms can assist in the visualization of such data.
    • Kits
  • Kits for performing the desired method(s) are also provided, and comprise a container or housing for holding the components of the kit, one or more vessels containing one or more nucleic acid(s), and optionally one or more vessels containing one or more reagents. The reagents include those described in the composition of matter section above, and those reagents useful for performing the methods described, including amplification reagents, and may include one or more probes, primers or primer pairs, enzymes (including polymerases and ligases), intercalating dyes, labeled probes, and labels that can be incorporated into amplification products.
  • In some embodiments, the kit comprises primers or primer pairs specific for those subsets and combinations of target sequences described herein. At least two, three, four or five primers or pairs of primers suitable for selectively amplifying the same number of target sequence-specific polynucleotides can be provided in kit form. In some embodiments, the kit comprises from five to fifty primers or pairs of primers suitable for amplifying the same number of target sequence-representative polynucleotides of interest.
  • The primers or primer pairs of the kit, when used in an amplification reaction, specifically amplify at least a portion of a nucleic acid depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), an RNA form thereof, or a complement to either thereof. The kit may include a plurality of such primers or primer pairs which can specifically amplify a corresponding plurality of different nucleic acids depicted in one of SEQ ID NOs: 1-2114 (or subgroups thereof as set forth herein), RNA forms thereof, or complements thereto. At least two, three, four or five primers or pairs of primers suitable for selectively amplifying the same number of target sequence-specific polynucleotides can be provided in kit form. In some embodiments, the kit comprises from five to fifty primers or pairs of primers suitable for amplifying the same number of target sequence-representative polynucleotides of interest.
  • The reagents may independently be in liquid or solid form. The reagents may be provided in mixtures. Control samples and/or nucleic acids may optionally be provided in the kit. Control samples may include tissue and/or nucleic acids obtained from or representative of prostate tumor samples from patients showing no evidence of disease, as well as tissue and/or nucleic acids obtained from or representative of prostate tumor samples from patients that develop systemic prostate cancer.
  • The nucleic acids may be provided in an array format, and thus an array or microarray may be included in the kit. The kit optionally may be certified by a government agency for use in prognosing the disease outcome of prostate cancer patients and/or for designating a treatment modality.
  • Instructions for using the kit to perform one or more methods of the invention can be provided with the container, and can be provided in any fixed medium. The instructions may be located inside or outside the container or housing, and/or may be printed on the interior or exterior of any surface thereof. A kit may be in multiplex form for concurrently detecting and/or quantitating one or more different target polynucleotides representing the expressed target sequences.
    • Devices
  • Devices useful for performing methods of the invention are also provided. The devices can comprise means for characterizing the expression level of a target sequence of the invention, for example components for performing one or more methods of nucleic acid extraction, amplification, and/or detection. Such components may include one or more of an amplification chamber (for example a thermal cycler), a plate reader, a spectrophotometer, capillary electrophoresis apparatus, a chip reader, and or robotic sample handling components. These components ultimately can obtain data that reflects the expression level of the target sequences used in the assay being employed.
  • The devices may include an excitation and/or a detection means. Any instrument that provides a wavelength that can excite a species of interest and is shorter than the emission wavelength(s) to be detected can be used for excitation. Commercially available devices can provide suitable excitation wavelengths as well as suitable detection components.
  • Exemplary excitation sources include a broadband UV light source such as a deuterium lamp with an appropriate filter, the output of a white light source such as a xenon lamp or a deuterium lamp after passing through a monochromator to extract out the desired wavelength(s), a continuous wave (cw) gas laser, a solid state diode laser, or any of the pulsed lasers. Emitted light can be detected through any suitable device or technique; many suitable approaches are known in the art. For example, a fluorimeter or spectrophotometer may be used to detect whether the test sample emits light of a wavelength characteristic of a label used in an assay.
  • The devices typically comprise a means for identifying a given sample, and of linking the results obtained to that sample. Such means can include manual labels, barcodes, and other indicators which can be linked to a sample vessel, and/or may optionally be included in the sample itself, for example where an encoded particle is added to the sample. The results may be linked to the sample, for example in a computer memory that contains a sample designation and a record of expression levels obtained from the sample. Linkage of the results to the sample can also include a linkage to a particular sample receptacle in the device, which is also linked to the sample identity.
  • The devices also comprise a means for correlating the expression levels of the target sequences being studied with a prognosis of disease outcome. Such means may comprise one or more of a variety of correlative techniques, including lookup tables, algorithms, multivariate models, and linear or nonlinear combinations of expression models or algorithms. The expression levels may be converted to one or more likelihood scores, reflecting a likelihood that the patient providing the sample will exhibit a particular disease outcome. The models and/or algorithms can be provided in machine readable format, and can optionally further designate a treatment modality for a patient or class of patients.
  • The device also comprises output means for outputting the disease status, prognosis and/or a treatment modality. Such output means can take any form which transmits the results to a patient and/or a healthcare provider, and may include a monitor, a printed format, or both. The device may use a computer system for performing one or more of the steps provided.
    • CITATIONS Patents and Published Applications
    • 1. US 2003/0224399 A1 patent application Methods for determining the prognosis for patients with a prostate neoplastic condition 2003 Dec. 4
    • 2. US 2007/0048738 A1 patent application Methods and compositions for diagnosis, staging and prognosis of prostate cancer 2007 Mar. 1
    • 3. US 2007/0099197 A1 patent application Methods of prognosis of prostate cancer 2007 May 3
    • 4. US 2007/0259352 A1 patent application Prostate cancer-related nucleic acids 2007 Nov. 8
    • 5. US 2008/0009001 A1 patent application Method for Identification of Neoplastic Transformation with Particular Reference to Prostate Cancer 2008 Jan. 10
    Publications
    • 1: Cooper C S, Campbell C, Jhavar S. Mechanisms of Disease: biomarkers and molecular targets from microarray gene expression studies in prostate cancer. Nat Clin Pract Urol. 2007 December; 4(12):677-87. Review.
    • 2: Reddy G K, Balk S P. Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer. Clin Genitourin Cancer. 2006 December; 5(3):187-9. Review.
    • 3: Nelson P S. Predicting prostate cancer behavior using transcript profiles. J Urol. 2004 November; 172(5 Pt 2):S28-32; discussion S33. Review.
    • 4: Bibikova M, Chudin E, Arsanjani A, Zhou L, Garcia E W, Modder J, Kostelec M, Barker D, Downs T, Fan J B, Wang-Rodriguez J. Expression signatures that correlated with Gleason score and relapse in prostate cancer. Genomics. 2007 June; 89(6):666-72. Epub 2007 Apr. 24.
    • 5: Schlomm T, Erbersdobler A, Mirlacher M, Sauter G. Molecular staging of prostate cancer in the year 2007. World J Urol. 2007 March; 25(1):19-30. Epub 2007 Mar. 2. Review.
    • 6: Mendiratta P, Febbo P G. Genomic signatures associated with the development, progression, and outcome of prostate cancer. Mol Diagn Ther. 2007; 11(6):345-54.
    • 7: Reddy G K, Balk S P. Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer. Clin Genitourin Cancer. 2006 December; 5(3):187-9. Review.
    • 8: True L, Coleman I, Hawley S, Huang C Y, Gifford D, Coleman R, Beer T M, Gelmann E, Datta M, Mostaghel E, Knudsen B, Lange P, Vessella R, Lin D, Hood L, Nelson P S. A molecular correlate to the Gleason grading system for prostate adenocarcinoma. Proc Natl Acad Sci USA. 2006 Jul. 18; 103(29):10991-6. Epub 2006 Jul. 7.
    • 9: Stephenson A J, Smith A, Kattan M W, Satagopan J, Reuter V E, Scardino P T, Gerald W L. Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy. Cancer. 2005 Jul. 15; 104(2):290-8.
    • 10: Bueno R, Loughlin K R, Powell M H, Gordon G J. A diagnostic test for prostate cancer from gene expression profiling data. J Urol. 2004 February; 171(2 Pt 1):903-6.
    • 11: Yu Y P, Landsittel D, Jing L, Nelson J, Ren B, Liu L, McDonald C, Thomas R, Dhir R, Finkelstein S, Michalopoulos G, Becich M, Luo J H. Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. J Clin Oncol. 2004 Jul. 15; 22(14):2790-9.
    • 12: Feroze-Merzoug F, Schober M S, Chen Y Q. Molecular profiling in prostate cancer. Cancer Metastasis Rev. 2001; 20(3-4):165-71. Review.
    • 13: Nakagawa T, Kollmeyer T M, Morlan B W, Anderson S K, Bergstralh E J, Davis B J, Asmann Y W, Klee G G, Ballman K V, Jenkins R B. A tissue biomarker panel predicting systemic progression after PSA recurrence post-definitive prostate cancer therapy. PLoS ONE. 2008; 3(5):e2318.
    • 14: Shariat S F, Karakiewicz P I, Roehrborn C G, Kattan M W. An updated catalog of prostate cancer predictive tools. Cancer 2008; 113(11): 3062-6.
    EXAMPLES
  • To gain a better understanding of the invention described herein, the following examples are set forth. It will be understood that these examples are intended to describe illustrative embodiments of the invention and are not intended to limit the scope of the invention in any way. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental error and deviation should be accounted for. Unless otherwise indicated, parts are parts by weight, temperature is degree centigrade and pressure is at or near atmospheric, and all materials are commercially available.
    • Example 1 Identification of Target Sequences Differentially Expressed in Prostate Disease States
  • Tissue Samples. Formalin-fixed paraffin embedded (FFPE) samples of human prostate adenocarcinoma prostatectomies were collected from patients at the Mayo Clinic Comprehensive Cancer Center according to an institutional review board-approved protocol and stored in the Department of Pathology for up to 20 years. For each patient sample four 4 micron sections were cut from formalin-fixed paraffin embedded blocks. Pathological review of FFPE tissue sections was used to guide macrodissection of tumor and surrounding normal tissue. Patients were classified into one of three clinical disease states; no evidence of disease (NED, n=10) for those patients with no biochemical or other clinical signs of disease progression (at least 10 years follow-up); prostate-specific antigen biochemical recurrence (PSA, n=10) for those patients with two successive increases in PSA measurements above an established cut-point of >4 ng/mL (‘rising PSA’); and systemic disease (SYS, n=10) for those patients that had ‘rising PSA’ and developed metastases or clinically detectable disease progression within five years after initial prostatectomy. Clinical disease was confirmed using bone or CT scans for prostate cancer metastases.
  • RNA Extraction. RNA was extracted and purified from FFPE tissue sections using a modified protocol for the commercially available High Pure FFPE RNA Micro nucleic acid extraction kit (Roche Applied Sciences, Indianapolis, Ind.). RNA concentrations were calculated using a Nanodrop ND-1000 spectrophotometer (Nanodrop Technologies, Rockland, Del.).
  • RNA Amplification and GeneChip Hybridization. Purified RNA was subjected to whole-transcriptome amplification using the WT-Ovation FFPE system including the WT-Ovation Exon and FL-Ovation Biotin V2 labeling modules, with the following modifications. Fifty (50) nanograms of RNA extracted from FFPE sections was used to generate amplified Ribo-SPIA product. For the WT-Ovation Exon sense-target strand conversion kit 4 ug of Ribo-SPIA product were used. All clean-up steps were performed with RNAClean magnetic beads (Agencourt Biosciences). Between 2.5 and 5 micrograms of WT-Ovation Exon product were used to fragment and label using the FL-Ovation Biotin V2 labeling module and labeled product was hybridized to Affymetrix Human Exon 1.0 ST GeneChips following manufacturer's recommendations (Affymetrix, Santa Clara, Calif.). Of the 30 samples processed, 22 had sufficient amplified material (i.e., >2.5 ug of WT-Ovation Exon product) for GeneChip hybridization.
  • Microarray Analysis. All data management and analysis was conducted using the Genetrix suite of tools for microarray analysis (Epicenter Software, Pasadena, Calif.). Probe set modeling and data pre-processing were derived using the Robust Multi-Array (RMA) algorithm. The mode of intensity values was used for background correction and RMA-sketch was used for normalization and probe modeling used a median polish routine. A variance filter was applied to data pre-processed using the RMA algorithm, by removing target sequences with a mean intensity of <10 intensity units of a normalized data range. Target sequences typically comprise four individual probes that interrogate the expression of RNA transcripts or portions thereof. Target sequence annotations and the sequences (RNAs) that they interrogate were downloaded from the Affymetrix website (www.netaffx.com). Supervised analysis of differentially expressed RNA transcripts was determined based on the fold change in the average expression (at least 2 fold change) and the associated t-test, with a p-value cut-off of p<0.001 between different prostate cancer patient disease states. Linear regression was also used to screen differentially expressed transcripts that displayed an expression pattern of NED>PSA>SYS or SYS>PSA>NED and genes were selected with a p-value cut-off of p<0.01 for two-way hierarchical clustering using Pearson's correlation distance metric with complete-linkage cluster distances.
  • Archived FFPE blocks of tumors were selected from 30 patients that had undergone a prostatectomy at the Mayo Clinic Comprehensive Cancer Center between the years 1987-1997, providing for at least 10 years follow-up on each patient. Twenty-two patient samples had RNA of sufficient quantity and quality for RNA amplification and subsequent GeneChip hybridization. Three clinical categories of patients were evaluated; patients alive with no evidence of disease (‘NED’, n=6), patients with rising PSA or biochemical recurrence (defined as two successive increases in PSA measurements) (‘PSA’, n=7) and patients with rising PSA and clinical evidence of systemic or recurrent disease (e.g., determined by bone scan, CT) (‘SYS’, n=9) after prostatectomy. No statistically significant differences between these three clinical groups were apparent when considering pathological factors such as Gleason score or tumor stage (Table 1). As samples from older archived FFPE blocks are typically more degraded and fragmented than younger blocks, the distribution of block ages was similar in the three clinical groups so as not to skew or bias the results due to a block age effect. Fifty nanograms of RNA extracted from FFPE sections was amplified and hybridized to whole-transcriptome microarrays, interrogating >1.4 million probe target sequences measuring RNA levels for RefSeq, dbEST and predicted transcripts (collectively, ‘RNAs’).
  • Table 3 displays the number of target sequences identified in two-way comparisons between different clinical states using the appropriate t-tests and a p-value cut-off of p<0.001. At total of 2,114 target sequences (Table 3) were identified as differentially expressed in these comparisons and a principle components analysis demonstrates that these target sequences discriminate the distinct clinical states into three clusters (FIG. 1A).
  • A linear regression filter was next employed to statistically rank target sequences that followed a trend of either increased expression with poor prognosis patients (i.e., SYS>PSA>NED) or increased expression in good prognosis patients (NED>PSA>SYS, alternatively decreased expression in poor prognosis patients) (Table 4). FIG. 1B depicts a two-way hierarchical clustering dendrogram and expression matrix of top-ranked 526 target sequences and 22 tumor samples. Patients in the ‘PSA’ clinical status category displayed intermediate expression levels for genes expressed at increased levels in SYS (n=313) and NED (n=213), respectively (Table 4). FIG. 1C depicts a two-way hierarchical clustering dendrogram and expression matrix of 148 target sequences and 22 tumor samples. These target sequences were a subset of the differentially expressed transcripts (Table 3) filtered using a t-test to query ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) patient samples (Table 5).
  • The expression levels of these genes were summarized for each patient into a ‘metagene’ using a simple linear combination by taking the expression level and multiplying it by a weighting factor for each target sequence in the metagene signature and combining these values into a single variable. Weighting factors were derived from the coefficients of the linear regression fit analysis (Table 4). FIG. 2 shows a histogram plot of the metagene expression values for the summarized 526 target sequences in each of the three clinical groups. This 526-metagene achieved maximal separation between clinical groups and low variance within each clinical group. Metagenes comprised of smaller subsets of 21, 18 and 6 target sequences were also generated (FIG. 3, Tables 7 and 8). The distinctions between clinical groups with respect to the metagene scores were preserved, although increased within-group variance was observed when using fewer target sequences (FIG. 3).
  • Next, Patient outcome predictor (‘POP’) scores were generated from the metagene values for each patient. For the 18-target sequences metagene, this entailed scaling and normalizing the metagene scores within a range of 0 to 100, where a value of between 0-20 points indicates a patient with NED, 40-60 points a patient with PSA recurrence and 80-100 points a patient with SYS metastatic disease (FIG. 4). In contrast, Gleason scores for patients could not be used on their own to distinguish the clinical groups (Table 1).
  • Using the Nearest Shrunken Centroids (NSC) algorithm with leave-1-out cross-validation, smaller subsets of RNA transcripts were identified that distinguish ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’ (i.e., ‘PSA’ and ‘NED’) disease (Tables 9 and 10). NSC algorithm identified 10- and 41-target sequence metagenes used to derive patient outcome predictor scores scaled and normalized on a data range of 0-100 points. FIGS. 5 and 6 depict box plots showing interquartile range and distribution of ‘POP’ scores for each clinical group. A 148-target sequence metagene (Table 5) was similarly used to derive ‘POP’ scores depicted in FIG. 7. T-tests were used to evaluate the statistical significance of differences in POP scores between ‘recurrent’ (i.e., ‘SYS’) and non-recurrent (i.e., ‘PSA’ and ‘NED’) patient groups (indicated in the figures) and show that increasing the number of target sequences in the metagene combination increases the significance level of the differences in POP scores.
  • The data generated from such methods can be used to determine a prognosis for disease outcome, and/or to recommend or designate one or more treatment modalities for patients, to produce patient reports, and to prepare expression profiles.
  • TABLE 1
    Clinical characteristics of different clinical status patient groups evaluated.
    Note Chi square tests for homogeneity reveal that the three clinical groups
    do not show significant differences in terms of patient composition based
    on known prognostic variables such as pathological TNM stage or Gleason
    score. Also, the block age of the samples was not different between
    clinical status groups; so that sample archive age effect is mitigated
    (i.e., older samples have more degraded, fragmented nucleic acids that
    could skew or bias results if not evenly distributed in clinical status
    patient groups).
    NED PSA Systemic X2 Tests for
    (n = 6) (n = 7) (n = 9) Homegeneity
    Pathological T2N0 2 3 3 p < 0.07
    Stage T3aN0 1 4 1
    T3bN0 0 0 3
    TxN+ 3 0 2
    Gleason Score 7 2 7 4 p < 0.06
    8 3 0 2
    9 1 0 3
    Block Age 10-14 3 4 5 p < 0.9
    Group (years) 13-15 1 1 2
    16-20 2 2 2
  • TABLE 2
    Comparison of differential expression between patient clinical
    status groups. Two-way comparisons for differential expression
    using the following statistical criteria: a) at least 2-fold mean
    difference in expression between comparison groups;
    b) expression levels >50 intensity units of a normalized data
    range (approximately the mean expression level across all
    transcripts in all samples) and c) significance cut-off of
    p < 0.001 determined using a t-test.
    Clinical Differentially
    Status Comparison Expressed RNAs*
    NED vs PSA 316
    PSA vs NED 442
    NED vs SYS 213
    PSA vs SYS 194
    SYS vs NED 269
    SYS vs PSA 323
    SYS vs NED & PSA 310
    NED & PSA vs SYS 77
    *Differential Expression is indicated by at least 2-fold change expression between mean of clinical status variable and comparison variable; also mean value >50 intensity units of a normalized data range and p < 0.001 calculated using a t-test
  • TABLE 3
    Differentially expressed RNA transcripts identified from comparison
    tests described in Table 2. Sequence listings are annotated with the
    Affymetrix Human Exon 1.0 ST probe selection region ID, proximal
    annotated gene from RefSeq, and overlap with coding sequence (CDS).
    SEQ
    ID Gene
    No Affy. ID Symbol CDS RNA Sequence
    1 3509278 — NO ctggtccctctcctgatagagtttcaggtttgccctgatgatctagatgaagcaaagtgtggtgacacttcgctgaatgctctgtcagtgtgcctagaaatagag
    tctctatcagggccgtttgcttcctatcacactc
    2 2750440 — NO ggcatgatctaggctaactccctggc
    3 3498665 — NO tgggcaagagcttttgtatgtttccag
    4 3159532 — NO cccaacacggtgcagccgatttatttatttttccctcagcatttttaggtggattgactgggatgctttattcaactcagggacgcaccacgaatatgttttttg
    5 3521600 UGCGL2 YES tggcgccagcgaaagccacgaacgtg
    6 3820597 — NO gctgggcgcagcgttctgaggggatgtggggtctgggaggtgtctcgaggtgagagctccaagtcacgg
    7 3955349 — NO gtggcgcaatattgcaatacagctcactgctacagccccaggcttaagtgatcttcttgcctcagtctcccgagtagctggaaccacaatctcataccaccac
    gccccacgcctggtaaatttttaaatgtttttgtaaagacagggtactgctgtgttgcccaggctggtctctaattcctagtctcaagcgatccttccgctttggcc
    tcccaaagcactgggattacaggtgtgagccactgtgcccagccctgctctaggttttcatttggatttgctgcctagtggaaggcacaggatggggcagtg
    ccttctgccagtgagggaggctccaggtagatgtcattgctgaactggagctcccctgg
    8 3204523 PIGO YES tgcttcctcttctacgctggcattgccctcttcaccagtggcttcctgctcacccgtttggagctcaccaaccatagcagctgccaagagcccccaggccctg
    ggtccctgccatgggggagccaagggaaacctggggcctgctggatggcttcccgattttcgcgggttgtgttggtgctgatagatgctctgcgatttgactt
    cgcccagccccagcattcacacgtgcctagagagcctcctgtctccctacccttcctgggcaaactaagctccttgcagaggatcctggagattcagcccca
    ccatgcccggctctaccgatctcaggtt
    9 3373899 SLC43A1 NO agccatggccgtagatttataaataccaagagaagttctatttttgtaaagactgcaaaaaggaggaaaaaaaaccttcaaaaacgccccctaagtcaacgct
    ccattgactgaagacagtccctatcctagaggggttgagccttcttcctccttgggttggaggagaccagggtgcctcttatctccttctagcggtctgcctcct
    ggtacctcttggggggatcggcaaacaggctacccctgaggtcccatgtgccatgagtgtgcacacatgcatgtgtctgtgtatgtgtgaatgtgagagaga
    cacagccctcctttc
    10 3707645 RABEP1 YES atggcgcagccgggcccggcttccc
    11 3860354 LOC100127980 NO ttcagattcacgagggtaatccagatgaaggtatatcattgtacctggcccgcatcactcagtaactgtcacctttgatttattgatttacttgagatggagtttggt
    tctgtccccgaggccggagtgcaatggcgtgatctctgctcactacaacctctgcctcccaggttcagagtgattctcctgcctcagcctctttagctgggatt
    acaggcacccaccaacatgcccagctaatttttgtatttttagtagagaggagctttcaccataatggccaggctggtcttgaacctcaaatgatctgcccacct
    tggcctcccaaagtgctaggattacaggctggagctacagagcccagcctgtcaccttgatttaaatgaatgcagctttcttggtgtcttgatgtttgtgaatttct
    gtggagtttgatactgctccttttgctgcttgtttttccagagtccccttatcacttgacgtgctgttata
    12 2406772 MRPS15 NO tgtcgtgacagcctctctttggggccagcttctgcttttgcccccatctttgcagtacagggggtaaattaaacaagaggatgcctgaatgaacgatatcctgg
    gttcttgagagacaagtgggagctgataattctgaaaattcattagtcaaagcatggagataaaggtggcagcaggaaggggagaggcaaggagtagacc
    cgtgacagttttagaatcttatttgtgccaaaatactttactgcattggcttggacctctaatacaatgttgaattgttaaccatgatagcactgtatcctggtctaatt
    cctgaattgaatggctagtcttaccattaagaatgctatttgcggccaggc
    13 3881324 HM13 YES ttatgaatttgacaccaaggacctggtgtgcctgggcctgagcagcatcgttggcgtctggtacctgctgag
    14 3271321 — NO aggagcaggtcgtcaagtccaccaggatggaatgctcagtaggagaaattgcgctgtggggccatttgaggcgcctgtccatgcgggtccgtcctggccc
    ttctgaa
    15 3316374 — NO aggcattacgccagctcccggatgcctcagcctcgtgaattcggggtaggacgctcagggcccatggtcagcacagcgggtgggtgggtttcagcgtggt
    cacttctccaggggtgcataattgagcagcttctcgatcaggtccacgtg
    16 3333695 — NO gttgaggagcttgatgctgcagtgagattgtgccactgcactccagcatgggtgacatagcaagactgcctcagggggaaaaaaaaaaaaaaacaccaaa
    aaaaaaggtatatggaccctagttttggccaggctg
    17 3930855 — NO gtggctcactgtagcgtcagtctcc
    18 2945934 CMAH NO ggacgattcgtttctatttgacccaagactgatgctgcgtggtgaaggagaggaactgcgttccaggcagaggaagtccagatgcgcaagagcagagatg
    ggagggacagcacagtggcttctcagaattgaatatggtgttagacttctaaaagagctgtggtagagggagaaaactgtcaaaggaaatcagtaactgtta
    aaggaaaataccttaaacgtcctgttttcaggctgactaatgccttaggggagcaaatgagcaaca
    19 2581405 — NO ttggtatgtagggttcgtatgaatgaaacgtgactaccagggcagataatgaaaggctttcaatcccagagtaagagatatagggccaggc
    20 2465840 — NO atgtggcacaatttacgaaaaccaaagagaggctatgctgagtccctacaccaccaagaccgtgatgttctgcccactcgcctcctgatggcctgtggggat
    agaccagcttccagatttcacacagatgggctgtatggaggaggc
    21 3431367 — NO cgatctctcatggtgggctcaagtgatcctcccatctcagcctcccaagcacctgggactacaggtgcacatcaacacacccggataatt
    22 3458114 NACA NO gggccactgttcctcaagcatctaaagggcttccagcaaagaaaggccccacagctctgaaagaagtacttgttgccccagctccagaaagcacgccaat
    catcacagctcccactcggaaaggtccacagaccaaaaagagttctgctacttcacctcctatatgcccagatccctcagctaagaatgg
    23 3875254 — NO ttctccctcagaccaagttaaactgtttttttcccaagagctaggaatcatatctgatcacactgggacttcccttcactgtcagtctaagagtttgcatttttgaggt
    ttaggaaaagggaaaaaaaaggaagaaagaaagaaattgtatctgagaacaaagaagctgccacatggtccctcggtatca
    24 2515646 ITGA6 YES tgtgctcaccgatatgaaaaaaggcagcatgttaatacgaagcaggaatcccgagacatctttgggcggtgttatgtcctgagtcagaatctcaggattgaag
    acgatatggatg
    25 3202904 — NO tgagggcgttggaccacacacccttgaaaaaggcctcgccccgctcatctctgaagatcttcctccaacagtcgacggtgcccgtgtacatgatgtcagctc
    ctttgcgccgggactgcatcatcgtccgccgccgcactgtgtcgaagggttag
    26 2768304 NFXL1 YES ctgtccaccttgtgatcaaaactgtggacggactttag
    27 3736631 — NO aaagcggtcactggccatatgatgcggagatggttttatctgaggcctgagaaccaacagatgtgcctgcgccctggcctgtgcagctgtgggcagatgtg
    tccccaggggcctgccctcactcgtgaccatgcaataccctgcaacataaacattttcttttccaaggatctgcaggggtggacatgatgctccaggcacag
    agtaggaagaaaagggggtgacctggggttcccagcaaacaggtccacctcatgctcactgcgtt
    28 2787529 INPP4B YES tgtgccctggtatgtgaatgtacagccccggaaagtgtgagcggaaaagataacttacct
    29 2980188 — NO tttccccacaaattgctgatgtacc
    30 3273235 — NO caatattcactgtgaggtcaagctcctagaggtaaaaactcaaaactgtggcagccctcccccgtgactgggtccctctgaagtttctaactctcagagttgtc
    catactgggcatctagcgattcat
    31 3402918 USP5 YES gaggaaaagatcaagtgcctggccacagagaaggtgaagtacacccagcgagttgactacatcatgcag
    32 3529227 — NO cgaagtgggtctccaaattccgcgcccaccccaccgcccgagaagcccactacgcatgcgtccgcaccccaccggcgccccttcctattgagcatgcgc
    gggagccccacctatttctctctaccgtttcctccccctacctggtaccccatccctagctcagccattgcttttttttccacgaccctccgctgtttcttccgcga
    gcttcct
    33 3839571 KLK2 NO ggagggaatggctgtgtcccacaggaataacagcgggatgcttcc
    34 2697538 CEP70 NO gagactcgttgggtgatcatttcattgagatcaacctgaatgaccaggtgtaaagtgcaagagtaatatgctatgactga
    35 2521076 — NO ggatccatgccagacaacgcacattctgcagacactggttactccagtggctccttactggaaacatataatatcagtgataagtgctgtgaagaaaataaaa
    caatgatgtgctggtatggatttttaacttttttatgtgatgaaccacagaatgatggttttaaatgtatgaaatacatagaattgcaacagaaaccagttatgaaat
    aatgaagatattaaatatgacatctatattttagtaaagcattagtgaggactgtaaatgatctttaaagaatttggcttaaatttaatctaaaattgctatcaggtatt
    tcacatcgctgtaatttttgcctgcattcgtaactgaagagataagtaaatgtcagaggttaagataaatctttttctttttttacctgtccatatttacaaacattctgc
    gttccgtacatagacgcctggataagaacccctgtgcaagaatgactttggtgctactttaaaaaaagtggttggggaagacctcataggaaatgacatcaat
    aatagattgcatgataacctatactagttcttactgttaccaatttaaattctaactgcttaaaagctaacacggtccttccctttttttgagcacctgatttgaagtac
    tttgagtaggcctcaagtgtcgtatgcaagta
    36 2811029 — NO ctgagttctgatttggagcagcctgtcgcaataccaaatcacctttgaataaacttatcctctcagcttttattgttcagaattgatttcgaggatagaaattccattt
    ccttgtcatatatacctgagccgttgcatcaaattgtcaga
    37 2735920 — NO gggtgtagcgcaccaagcatgagctgaa
    38 3843767 ZNF135 NO aataacctagcatggggcggcactaaatggctgcaggaaagccgagtcttcttccacatccggcggctcccctcggatgcgagcgctggcccagggtgt
    gtttacagaggtgagggcttcccgtggacccttctcgttgggagcgcttagcctcaggagcggattcagggcacaggcagaggacgtccacaaacacca
    caggaagccgccacccaggggcgtggaaaggcccaatgcctcgtctgggattcacggccggcaaagcggcccctccggaacgggacagcacagcg
    gctcacctctgcgcctctgggggtgcggggggagcctcgccctccacgctctctgggggaccgcccgccctagcccccgcctgggcttcgcgggtgga
    cggttgggggccccgggcgccccccagcgcgtagcttttctccttctcgtgggtcttctggtgctcggctagggccaggctgaagtggaaggtcttccagc
    agccctgacaggcgtagcgcttccggccgccatggctgctgtggtgctccatcaggtgcgagagccacgcgaaggcctccccgcactcgccgcaggca
    tagggcttcccgcgggacaagcccggctcgtcagccccagggccctgcccggcctccagccctgcgctgtcgccggagctagagacgccctcgaggct
    ctgcccgtccccatcctcggggtgcggcctcttggttcccagtttcgccgtgcccctgtccggggcaggctgctggatgacggactgcctctgcgatccggt
    ggcagagtcggactccgcgtcctgggggtcctgcgggtccggggccttcccaggctgctcttcctcctcctcagtggtgcccgacgggggatcggcaag
    ggcgtccccagggggcgcctccgtaggcagctcaggcagcacccccgcgggggcggcctcctcgcaggcgcacccagcgctctcctgccgcctccc
    gccttctggaacaaggtcagagccctagcgtgagcgccc
    39 3895275 ProSAPiP1 NO tgggcactcggcattttgacacatgtcctgtcaaaaggccagagtccccagtgtcccctcccctccatctctcttccccatagaccccataaccccagaccaa
    agaggttctctaagcagctgtgaccaggttcctccctccccacctgccctcctagctccagcactgcccccgtggcagcccacttggacccccctaaaagg
    agggaataggaggagggcagggtgagtgggggcaatcctaggtggtgggggagtcatgctccctttctcggcacccccttgttggagatggaggcagca
    gacgtgcagtgccataaggtgccccagtccttctggaggcctgggctgctactgttggccaccctgtgtctagtgatgctctctgtgctcacctcctaggccat
    ggagcctgagggggcctgcaccaggtttgctgaaactgacagagcctgggctccagacctctctccctcctacagtgctctccctccctgggcagattggc
    aggacaagtgggagcagatggcctgcctttggctgagagggctacctgcccagcccctcccccaacaagatctcttggactcaggcctcagagcctggc
    ctggttgtgagtgtgtgtccctgtgtgtgtgttgcgggaggggaggactggggctggaagtccagcacccagggaagatctgtcctcctgttcttgggaagc
    gttgcctgacggcttctcggctctaccctcacccttctggccaggatcccgcagggcaacagccccatctgcttggctgaccccacacccaggaccactgt
    ccggctctaacacagctattaagtgctacctgcctctcaggcactctcctcgcccagtttctgaggtcagacgagtgtctgcgatgtcttcccgcactctattcc
    cccagcctctttctgctttcatgctcagcacatcatcttcctaggcagtctcttccccaaagtctcaccttttcttccaatagaaaattccgcttgacctttggtgcac
    40 4031098 CYorf15B NO tcacttaacatagtgccagggcatgcaattttgtttcttactctctggatgtgggatatgcgagtgtgtgtgtgtgtgtgtgtgtgtgtgtattaagctttctgtttctg
    atgaaattttcatatgaaatttactggagataagattaaattagtggaaaaacaagataattttgctttctatgtagtggtcaccaagttaaagaattgtgccagtta
    ttaggcaagataggctttgagatttagggacagttaaattttacaccaacttagtgaacatgagacttctacctagtgttacatttcatttttaaataagcaatttaaa
    aattggtaaatgatttgtttactttgattatattctggtataattttctgacaaaattatctgtgtcttggtcagcattgttgctagaatatgtattcagattttgtctgtcca
    taattgagaacacagaaaaaatctaatttgactatacccatttacccccatggaaatgaaactatattctatgaatgaaaaatgattttaataatgtggtgtattaca
    ttttcttcattcaagtaatgtaggccctgagtagagcatgttatgaatatttagttccttagtgttttctcattcaagcctctcatattgaatgagtctagggtttggag
    agatgtttcacacagcatgtctcttcagtgcaagctgacagatatcagtgcacaattaaagaaacttaattgcacctttcaacttggagtataaattttgtatgtatc
    tatgtatatctatgtgtgtattttgtggtttaaggcttatttacataatatgtgacattttacctcagaaattcagtgactgaatttcacagctgcttcccatgcatcttta
    ttatctatgtttctgaaaaactcaaatactaactaatctcttttcttcccttagctgttcctttcctgtggttttaaaaaagtgaccagaaactaggtctctattttcattg
    ctttgctgcatattcttttaacctgcttttatc
    41 2927637 KIAA1244 YES gtcccacaggatttcgggaatcaag
    42 3839575 KLK2 YES ttctgaagcatcaaagccttagaccagatgaagactccagccatgacctca
    43 2566620 TSGA10 NO atccattgatggtttgatagtgggctgggaaggaaagctgtgttcctccacattaggcagcaaa
    44 2959903 LOC728052 NO tcatttatttgacagtgcatgtctgcaatgccgtgctcatcaatgat
    45 3100926 — YES agtaacagctatccaccaatgtcaatccatac
    46 3853655 — NO gcaggcaatatctccgcacctttaat
    47 3947544 — NO ctgctggaacgacaccaactctttgcctcccatccttggttggatatgatttgaaatttggtaatgtgtctctacttgaaacagatgcactgtttggatgttttcagg
    tcggtgatctacttgtccagtttgatcgctaccagaag
    48 2466070 ZNF692 NO ggattagtccgctccactcactgtcagcattaagtgggggtgcccaagacggggtggatggggggcgccctccagacctctgaccacggcctcaccgcc
    actcgacccaactatgaagagcgcccccagctgcacgccaggacacgacctttccttcccctagaaaccagtaaaggccgctgccctattcaagatgaaat
    gtgtggaccgcccccagcccagttgaaatttcccgtgaaagtctctcgccccttccccacagctccacttcagtggactggagggcgcaggcctttgttctg
    actgcttctgtctgcctgcctcccacccgacgacactcacatggtagcgctgagcttcaacaccctgta
    49 3065818 RELN YES ttcgataggtttgaggggaagctcagccctctgtggtacaagataacaggtgcccaggttggaactggctgtggaacacttaacgatggcaaatctctctact
    tcaatggccctg
    50 3332183 STX3 NO ctgatttcactccagactggtgtggccacccttgtcttcagatgagaat
    51 3681410 PARN YES ctgtcaataccagcaaatatgcagaaagctatcggatccaaacctatgctgaatatatggggagaaaacaggaagagaagcagatcaaaagaaagtggac
    tgaagatagctggaaggaggctgacagcaaacggttaaacccccagtgcataccctacaccctgcagaatcactattaccg
    52 3873342 — NO gccacaggagggtttaaacacagcagtaatgagactttatttctgctgggaaaacattgccgttattgccc
    53 2572055 — NO gtgcctgagagaaaacggcctaatcgaaaacgtccgcggcatacatccattcttaaaacttgagtggctgcttttctgggtggaaaagagcggtatcagaca
    gggtgagcagtcggggaacggatgaacaaagacttgcaccgtggccctgatgcctttgttccgagttctattcagttgtacttgtgcgttgttacaggacttta
    gaatgcagccctgccccccaacccccacctcccagggccgacctgtgctcctaggaaggcaaacctc
    54 3434549 MLEC NO tggcacctcttgcatccaggcagtcttgtgagatgggggcacatagcactggggaaagcagaactccattctcacctctattttgagcttcagtgctttatttca
    gtatgaggaaaaacaacaacaaactgaagtgcgctttccgtcctttcaaaggacaactgtcgggaagggagagccgagttgcgaggtaggaggggagca
    ctggcagggagagacattcttgactcctctcttccctggtgtgttgtgatccagggaatgaaaagaaatttgaccctggattggttctctccttggacttaagga
    atcttaccttttccttccacaaagttctcccaggcaaggaccagctgcccattctgagcccagggcagcctcttcaaccattattgg
    55 4007482 — NO tccaagcaggtcttcgtagtagagaacgaaccagccctcgatcaccaggtgaatgaacccacacactgcaaaccagcacagggacagtcgccgccaagt
    ccccaatgggacaaccgcagcacgacctgacaacagccatgtggtcacgactaagacccctgtgacagagaagaggccagccagtatatgccaggtgg
    ggcggtcattaggtacaaagttgtc
    56 2751391 CLCN3 NO cccgagttagagcatggattcagttttagtcttaagggggaagtgagattggagatttttatttttaattttgggcagaagcaggttgactctagggatctccaga
    gcgagaggatttaacttcatgttgctcccgtgtttgaaggaggacaataaaagtcccaccgggcaaaattttcgtaacctctgcggtagaaaacgtcaggtat
    cttttaaatcgcgatagttttcgctgtgtcaggctttcttcggtggagctccgagggtagctaggttctaggtttgaaacagatgcagaatccaaaggcagcgc
    aaaaaacagccaccgattttgctatgtctctga
    57 2871645 — NO ctctgtggggttcggttccactttgtagttcgggtttgtaatgtaaagaataatgggaaactggtctaattatgagagttaagagagtagaggcctgtagttg
    58 3629576 PARP16 NO ttagccataatagggcccggtacgatttgggagtgacatttctgtaaagaagaggaaaaatcatttttctataatttgtaaagttgtgaaagagccactaccaca
    gtttttacattgattattggaacatttc
    59 2545930 IFT172 YES tggtggctacaacattggcaccgtcagccatgagagccgtgtggattggctggaacttaatgagactggacacaagctcctcttcag
    60 2569734 — NO ttcccttggctttggacatgtgagggaagtaggtatccgctgcctggggaaagtcaacaggacccctcctccccgtacctcttggtatacaaagctgagcgg
    tg
    61 2832639 PCDHGA10 YES ttactttgaagtttgcggcatgatggtggaaagtgtaaatgctaaaacactgatgagtagaatttg
    62 3113343 — NO ggctgattgaccttgactggcctcatgtatgtgtctcaaagttggctggggctgtcggctgaaattccttagttctactccacatggcctttccccatggccagc
    ccaggctgagatctgagattgaagagggtgagaacagaaagtacaagatcttcttttgacttgaaagctagcccagaatcgagggaaataaaccccaccttt
    tgatggaaggagcttcaaagaatttgtagtcatttccaatccacgaagagtaggtacccactatttgttgaataaagccctattgaaagctttttagctatccaga
    tgcaaattactggccaacctttgggtagaattataaaattctgcccaaaattctaccaaattactggtacttgtaaaattctaccaaataactggccaacttttggg
    tagaattgtaaaaattaagttgtaaataaagcctattgcctaacaggaacttcaaagtcagagaatcctaaaatgattgtgctacacagggccacatagagcac
    agctttgtctttttttttttgagatggagtctcgctctgtcccccaggctgaagtgcagtggcgcaatctttgctcaaggcaacttctacttcccaagttcaagcaat
    tcttctgtttgagcctcctgagtagtgggactgcaggcatgtgccactatgccccattatgtatttttagtagagatgagatttcaccagattggccaggctggtc
    tcgaactcctgacctcaaatgatctgcctgcctcggcctcccaaagtgttgggattataggcatgagccaccatgcccgcccgcttcgtcttttcactggacta
    atgaagatacaggtgtggaatggtttcacagcatgcccaacctcatgaggcttgttgggtcagagcttgtgccagatgccagtcttctgccttccagtcttata
    gttgttacgctatagccttctgcagtggatggtaacgtggccaaaataagcctttggttttggagtattcgtaaaatg
    63 3875673 — NO gggaactaacgccttccagaacagaaatatgtggtccgatgagtattgaatgcaacttaaaatctagttggaatgtgatggataagaagagacccaaagtcat
    caacaagccttctcatgaactttcagtcattaaccttcctatatagtaaggacagaaatgatgatttaagccatcttaggcaaggcagtgctaacaatatgctttt
    gtaaagtcaccatccggtg
    64 3959071 — NO ttctctaattctaggcctgccgtttttctctgtgagtggacctgatctccttttgctttggctcccagagttccctattcgcttctccttgtcccctgagtcctgctctcc
    ctcctctggataaccccttccagcccttcacttctccctcctgttatttgctggaatggctaattggctgacccccccacccagtccccatgggagaccccctcc
    agcaccagaagaggcagactaacattttctttggtagcagaatgtaaaattgtaaaatgtgaaagataggagagaaacatcattaactgttctgttatttattaac
    attttaatttatagaattatagacttaacagcaaaaattcaaacactgagggtcatcggtgaaaata
    65 2864793 — NO gcctattggcttcaagttgtttacgctttggtaggttttggcttgttccctcaaaggatcccttcttcatgtcctcccatgatgttgcaggcaagggtctcttgttatat
    gtggtactaactcgggcccacctggtcataatttc
    66 2976430 — NO gctcctacagtaacactcaatcaattcaccccactccagtgttcttcctgcaacatcactgatttagatggcccactctg
    67 3862771 — NO gggaatctattaatagtggaggaagtatttagtgggtggga
    68 3192159 BAT2L NO tggatatatggcattgacccgcttgctttgatacgaaacaaaaaagcagacgactccttcatcccatctgctcctaccgtgactgtgga
    69 3062031 — NO gggtttgtcatgctacgctgtgccattcatgtgtttttttgctcatgctgttccttgtgcctggaaattctccccctaattcccctgagcagtggatgcagtggatac
    cctccccagatcccccccaacttccctgagtgttggctaccaaaagctctgagtgcacccagggagctaagtcctcctgcccacaggcaataatggactga
    cacggggtagacttaaagaaataagaggcacatcaatcaattgaaatgtgtgggaccttacctggactctgaatta
    70 2505555 PTPN18 YES gagcagtacaggttcctgtaccacacggtggctcagatgttctgctccacactccagaatgc
    71 2361309 — NO gagccggacttccttgtcccaccag
    72 3569829 — NO gtactcgcctcctgcatggagcacgctcaggggtgg
    73 2946327 — NO ttactgttgctgtccgtaaactggaacctctgttcactcaag
    74 2751432 — NO ggaactcctcagaacttataatatgttgatattctttgattcccagatgaggggatgggtaataggatacatggttttccagacttgtttgaaaatgcaactattttt
    gggttgcagggaaggatatagtagaactcatgggaactggtgtttcttggaacatgctttggaaatgctgggttatgccctgttaactcttacatcattagttttta
    gcccaaaaggaaacagcaaataatgttttatatgagccacattttgcgttgattttcc
    75 3907608 ZNF335 YES ggacgtctacggaagtggagcacctccaccaagagccaagaggaagagggaccagaggaggaggacgatgatgacattgtagacgctggagccattg
    atgacctgga
    76 2316543 — NO atgagacctcagacaaagccaccagga
    77 2453070 C1orf116 NO tgcgaccagtacagaccctgtcctggctgaacaagaagagacacatgctccacttgggagcctttgccaccacgcaactcagggctcaagatgaatggga
    gggagagatttgagtccaagcatacatttatattcagtgttgtgccattgagttcccatgtggatcattctgaaggtgatctccacaagagggtgtgtgtgtgtgt
    gtttggtgtgtgtgtggagggggggccgctggatacatcactgaagctattgatataacacaatgagtcactgttcagaattttgctcttgttagatgttttcttac
    attgggtagagtccagcc
    78 3119603 RHPN1 NO tccagctggcagcaagcaccgagcatgccctccccacccagaggacctccgggcaatgcctgtcccgcctcatgctggaggctgcctcgggcacctgcc
    tgcccattaaagactggtcagacctgt
    79 3908801 STAU1 YES cactgcagaaggaacgggcaccaacaagaaggtggccaagcgcaatgcagccgagaacatgctggagatccttggtttcaaagtcccgcaggcgcag
    cccaccaaacccgcactcaagtcagagga
    80 2525664 — NO gaagctgttttaatggaggccgagagttggacaattttgtgttatggagaattctgggaagaaggaaagacccggatgggactgtttattaaggcttatgactg
    gactggagata
    81 2395926 CLSTN1 YES tacgggaaagaacatcaatataagctgaccgtcactgcctatgactgtgggaagaaaagagccacagaagatgttttggtgaagatcagcattaagcccac
    ctgca
    82 2571145 ANAPC1 YES ctcaaaagtgtttattacatctgacctatgtgggcaaaagttcctgtgctttttagtagagtcccagctcca
    83 2836006 — NO ggatgtacactgatttggccctttaaatgacattataccaagaagttggtataagggagtaggagatgagaaaactttttgaaaaatcatttggtgcatgctaag
    gtagcttgtaggacatgtggttttaaaaaattcatggattttgaagaaggatagggtggaagtaaaatttagctgatagcatagggatcatttgtgatttatataga
    aaataattatatttttgagtgagaagcatcagacttaaatttttttcttctattttggttattaccaaaaggaacagagaaactctcagaattctttgaatcatagaatg
    ttagtgctggaaaggactaggaagtgacttgtacaaccccttcattttacaaaggatcagagagaattggttagtagagtcccaaatctgcttttagaagtaata
    tggtgatcatcagtttagattcactgtaggaagggcagccctgttaaagtttgtcaggagaaaaagggaaggtatcactttttgtatgttcacccagttgcttctg
    tagttttcatacccctgttttctcaattttcttagaactgtctttaatggcccagctctaccagggcttgttgtctaaggacattaacttgtgctcccctcagggatgg
    gtttactactagctgtcagaaagctattgggtatcctaatgtgttaatagctgaaactcagctgtaatttctcctaaatacttcagcattttgcattctgtacattgtgg
    tgctttttccaccttgtattgttgtaactgtaagctcctagggggcagcaatttggtcttaggcgtgtaccctgtttagtgcctggcaatgccatgtttatatcaagg
    tcttaatattacttttgagttatttctcccactcttcatggaagtgatgctccagccttgctaaaacactgagggtcctcccgataagccaggcattgtgattccttg
    gcttcaagtgccttctgtcttccccgaaggtccactgagatctacaatcccccctt
    84 2517773 — NO tagcggagaatgacctacctacttgattaatgatgtctgcatgggcttactaagagggtgtggggaatggtggcaggggtaactatcatcgagaatataggg
    caatgggtatattctaactttgcataactttgctagattatatatatctttactcacaataagcaaagttgaacaacttaaaattgattccctgttttctgttttcactatc
    caactaggatgaactcttaagttcatacatatactttaaaatgggaacaaacatagcctgtcatgtctttatttaggctaagtgcatatgtatgtataagtaatgtgt
    atatccttcacttattaatagtgccttcatgaattcaaagacccttgtcacatggtgctcaggaaaaaaaaagtgccaatattctttttttttttttctctaagaagtact
    agtttaggtaagtgaaattcaatagcatatcagtgctttaccttagtcactttttgtgttttgatcacccttagtcatcactggagagaagagtttgaattcatttgtgg
    ttttgctttagtggcaaacctccttacagggatgagttgccctccattctccttgccatatttggttaatctaggccatgacctttgaggggaaaaggcacagatt
    gcaacttttctttcctgcttttgtgaatcaggccatgttcacgcagggtccttgaaggtgacttgagtgaggaagctatataccgatgacttaccaatttttggtctt
    ataacattctctctctttttttttttttttttttgtagcatatggcttcctctactgtatgttggcatttgccacttttggggatttgactcctgcaggtattttt
    ttttttttcttttgggggagtgtgacggcagtggatatagtcttagatgatgtttttaatagttcaagtccattagtgtcttactctagagaaaacg
    aaagactcactgtgtgagttttcttgccctctggttttcagaattctgtgtagtttctcaacat
    85 3064957 — NO aaatccacagccacatctttgaatg
    86 3239181 KIAA1217 YES tcattctcaccgcagagtcaaaatggccgagcaccccctc
    87 3629017 CSNK1G1 NO tcaccatctataaggtctcagagcagaggattattcatggtaataagtgggggtgtggtgcagccattccagtaacaccca
    88 3709453 — NO ggtgggacttacaggtctcgctatagcaccagataaaatccatactacaccctatcattacctgggaatgagggtacaggagaaaacagtaaagcctcaaa
    aggaggaaattcgtaaagagtccttaaaaaccttaaatgatttccaaaaattattaggggacgttaattggataagacctactttaggaattcccacctaagcaa
    tgtctaaactgtttgctttgctgagatgggatccaaattcatgtagcaaaagaactctgatgcctgctgcagctgaagagttacaaatgattgaggaaaaaattc
    aaagtgctcaagtccgtagaagagatcctagtgttccattacagctcttagtgttccctactctccattctcctataggagtgattgttcaaaatgttgacttagtta
    aattgtcctttttaacgcacagtacgactagaactttctcaatttatttagatcaaatagctattcttataggccaaatacaactgagaatagtcagactcattggca
    ccgatcgagataaaaatgtagttcctttaaacaaagcacaggttcgacaagcctttattaattcgtcagaatggcagtcaaatctggctgattttgttggcagtat
    agatattcattaccctaaaactaaaatgtttcagttcctaaaaattgactacctaaattttacccaaaataactagttccattcctttggagggagccgtaactatctt
    ta
    89 2732012 FAM47E YES ccttataagccaaagtgggtgaagatgaggtatggagcatggtatttgaaccccaagttgtggaaaaagcaaagagtagacgagcctctggttgaccctga
    ggtctcacata
    90 2787588 — NO ggttgctgcccttgagcattttgcc
    91 3630110 — YES atggagcacctgttcgtgtacctcc
    92 3738711 — NO gtagctaaacatatgcgtggggataaaaatcgggtggacaaggccagatacatgaagacatgctccactctcatctgtgaa
    93 3675240 — NO cccggactgatgtgatttctttgacaattacaaaaaacaaaaaacaaacaaacaaaaaaacgcaaagcaatagcagggaaaggacagtttgagaagacct
    gcaaggcctgccaggcggctcgcttgtgcagacacaaccgggacggctttgaggggacgtgcacacccaag
    94 3458922 CTDSP2 YES gggacctgagaaagaccctcatcctgg
    95 2694337 — NO gaggaagacttgtgcgcccggcccacacgaaccatagagccgatctccggg
    96 2990414 — NO ccctccacacgtgttcagttaaagtgtgaggaataccctccccagacaaacatcacagatttccgaaatcaaacacgctccagcaagtgttctgcacacccc
    actg
    97 3190328 — NO cttctcagttgggtcaagtccattgacctttctgttacagcttgagttttgtgtcttacgtagaaaaggtgcccctgctctcactttctgcacagctatcaggtccag
    ctcatagcagttcttcta
    98 3745435 MYH3 YES ctgagattgcaggatctggtggataaactgcaagtgaaagtcaagtcctacaagaggcaggcgga
    99 3110076 LOC100134128 NO gtaaaagcgcggcaccgacaccagctgtgtgcagcagtggcggcggcggccgaaggagaaatagaacagcgcaggcaaaagaagaaaggcgcgg
    gctgg
    100 3471539 — NO cacgggtccgctagctttaagtacaacaggatttccgtgttcaaaagactatactaagtgcttaatcaaatcccgtcacactaaagccaaatttagttctctagg
    aatcggagtctgcgtata
    101 3918710 SON YES cagagcagcctgtagacgtaccatcggagattgcagattcatccatgacaagaccgcaggagttgccggagctgcctaagaccacagcgttggagctgc
    aggagtcgtcggtggcctcagcgatggagttgccggggccacctgcgacctccatgccggagttgcaggggccccctgtgactccagtgctggagttac
    ctgggccctctgctaccccggtgccagagttgccagggcccctttctaccccagtgcctgagttgccagggccccctgcgacagcagtgcctgagttgcca
    gggccctctgtgacaccagtgccacagttgtcgcaggaattgccagggcttccagcaccatccatggggttggagccaccacaggaggtaccagagcca
    cctgtgatggcacaggagttgccagggctgcctttggtgacagcagcagtagagttgccagagcagcctgcggtaacagtagcaatggagttgaccgaac
    aacctgtgacgacgacagagttggagcagcctgtggggatgacaacggtggaacatcctgggcatcctgaggtgacaacggcaacagggttgctgggg
    cagcctgaggcaacgatggtgctggagttgccaggacagccagtggcaacgacagcgctggagttgccggggcagccttcggtgactggggtgccag
    agttgccagggctgccttcggcaactagggcactggagttgtcggggcagcctgtggcaactggggcactagagttgcctgggccgctcatggcagctg
    gggcactggagttctcggggcagtctggggcagctggagcactggagcttttggggcagcctctggcaacaggggtgctggagttgccagggcagcct
    ggggcgccagagttgcctgggcagcctgtggcaactgtggcgctggagatctctgttcagtctgtggtgacaacatc
    102 2792431 TMEM192 YES tccttggatatcacccagagtattgaagacgacccacttctggatgcccagcttctcccacaccactcattacaagctcactttagaccccgattccatcctctt
    cctacagtcatcatagtgaatcttc
    103 3828963 DPY19L3 YES gaagtggagcgagaaatctcattcagaacagagtgtggcctgtattactcctactacaagcagatgctgcaggctccaaccctcgtgcaa
    104 3874927 CDS2 YES gttcattgtccccatatcttgtgtgatctgtaatgacatcatggcctatatgtttggctttttctttggtcggaccccactcatc
    105 3012468 AKAP9 YES ctggggtcagggaatttatcttacacacagtcagggatttgacatagcatcagaaggccgaggag
    106 3541309 PLEKHH1 YES gatgtcatccggaaacctcaaggccaagtggatctgaactcccgctgccaaattgttcgaggggagggttcacagacgtttcag
    107 3543492 PSEN1 YES gcaagtgacaacagcctttgcggtccttagacagcttggcctggag
    108 3878896 — NO aacgtgctcagggagaatcagctggtttct
    109 2669445 — NO atggctaaaactccaatagacagcatgtagtgcttgggtgacagactttgggacaatcacagccactacaaagtgaaaggggagaatccagaaagtacag
    agccagaaagggagagccccaaattctatgtaaaaactgcccaaatctttggctgaccactgaactatgcatgcatggggcagacgctaagcaacctagct
    aaggataaaataactaagccgagaattgaggtagtgcctc
    110 3953763 PI4KA YES gagcaacctggacataactgtcggctctcggcaacaagccacccaaggctggatcaacacataccccctgtccagcggcatgtccaccatct
    111 3529048 — NO gcccagtacctctccaagggttgtatatccggtgggggtggagggatcggcagaggtggtgtctcagccctttcgttcaaggagcgggttgatggtggtgg
    tgtaggaattgctgggtcttggaaactaggggcaccaggtactgcgttgtcccgaaaccactttagttgcccatgcttcaaggcatagcgtgtgtcaccaaac
    cactgaatgatctcaggccgaggtaaaccagtgatctgttctaacttttggtaatcctcacgccgtgcccactggcactgtaaaaaaaaggatttaaggatagc
    cagctgctctttggttttgcgcttggtctttcgctggcgttgcatatctggggaaaggtactctgtggggccaactctacctggtactga
    112 3691111 — NO ttgacgtggcttatcaacctttgtctcttacgtgctctttgttccggccatcgtcttgtttaacaaa
    113 3845902 TIMM13 NO gggtccgcatgtacgtactgcctgcccggggcttaggagggtggcaccggtgctgggacacacgggactgtgtcctcgccaccccccgccctgccccct
    gccagccagtgcagcttggatctcgggggtgtggggccctgtgccttcctgaagtgctggcagcccagtggcacctccttcaggcctttggggtattcccct
    agtgtgcccaagtcagcctcatattctgggcggacagcttgtctggacttcggagttgggggtggtcagacaccacaggagctgtcacctcctgcggatgg
    gcaaataaatt
    114 4009521 PHF8 YES gaccctgctttgaaatctcgacccaagaaaaagaagaattcagatgatgctccatggagtcc
    115 3817782 — NO catgcccggcccagtaattaggtttttttttaaaaagccccaaaccttaattttatttgcccctcatttcacggagctcccagcgtagtggggagaagctggccc
    agagaaccccacgtcctgcacagtgagggccagcccttggggaccccatgtcctgcacggcgggggccaggccctggggccacgtgtgttcccccccc
    acccctattttctgccgcgtgctcgttctgctgcacgtggctgtcacttgaatgggaatttaaaaatataacttaatgcacactgacttcccttgattggtgcaatta
    attatttgaaaagaaaaatatcacagtgttcttaaggactggcatttttccaagctgtgtcagttttgattgatgtctgacgccgtggctggcttctgaaagcctca
    ccagttctgatggcttattggcgacttcagtgtatccagcaatctctgctcatctttctgggggaatatataatgatcagcaggcctgagaactcctacaaatca
    gagataagaaaacaaatggcccgatgaattcggcgtgaggggcttgagcagacgcgttacgaaggagctgcaggaacgaaagccatggttcagtgccc
    agcatcggtagaagtcagaggcagccagctgggagacaccgccagccccaggacggccacgtcagaacaccgccaccagatgccagtgaggaggg
    cgcagctgcacgctgctcccagccggggtggatgcagggcggtgccatggccatggaaaaccgttcggcattttcttggaaacggaagcatgtaccctgt
    gccccagcgatgccactctgtgcatatttactcaggagaaatgaaaacatatgtctccagaaagattggtacataagtgttcttagcagttttcttcacgagagc
    cccaaactggaaacagcccgcacgtccatcaacaggaggatagataaataaataaccatagatccacgcgcaaccgagtactgtttagaaatgaaaagga
    gcg
    116 3948736 — NO cgttgatcccacctccttgatctggtttctaagacctcatacaaactgggcccgttagtctttgctccctgatactatctgataccatctggtctcac
    117 3104724 ZBTB10 NO ctggtcggacggaaacgctccgccggctttattgtcgcttcgttatgtggcggagccgagcagtttagcgtgcctctcaccctcagcgcctgcgaagccggc
    118 3364565 PLEKHA7 NO actggcctgtgctacttattaccgggcttgtaatagcggttcttgtctccatagcctgttgagtgttcccagatgtgactcacctttctgctgccctatcatgcag
    gcctactga
    119 3540221 — NO atgaggccggaaagatggcgaatttgcagggctgg
    120 3458075 — NO ccaaattttagttgtgaggaaacagacataccaagtattctttttagcaatgagcattagttctgtttttcttaacagtgaggcaaactatgtatatttacattttgtag
    aatatttcctccaaaattggtttctgcatactttttgtttttgctatcactgtttgggcttagagtagtatccttgaggctcgtctcatcttttttatttgttttgtttttttgttt
    gtttggttttgttctttgagactgctgcagtacaatggagcgatcccggc
    121 3773290 — NO caggctcatcattccttgttggatttcttcctggacttatttaaaagttgttatagctattatgaatgagcttttttaaaaattgtaattcctaactatattactggtgtag
    aagaaaactacagagctggtatccagctactttattgatttcttactgtttctattggcttttatttttcattagtagaggttgagaatttcagtatttcattcccagatcc
    atatctcatttctttctcttgttttctttgcgttgctggagcctccaaaacagtctggggtaactgctatgctagcaggcctcctcatc
    122 2835195 FLJ41603 NO ttatcggtgtagcagagaggttcccaagactcttgactggtcctgggagtgggtgtgaccaagtcatagttctggaatgtgtgtaggcaaattcagaggctgtt
    ccagggaagaggggattttgatactgtgttaggtggggtgtgtgaggctgttggcagcaggtgaacagctactgctgtgttctcaggactagggaacaaag
    gggtatgcaaatcatagaggaaactctgggaaggcggtgataaggcctggtgggtggggaggttagggaatggcttgctttcctgtttctggttagaaggg
    gagccagggggaacccccagtggtttcaggtggcccctgaggtcctggaggcagccgtggatgtgatgcaattggctgtgggaccttagatgtaggaca
    caacttcagtgttcccatccagaaagacctcactcacagggttgtgctgagaatgacgtggggctaagcatgcagagctccctgtaaactgtgaagtgtgat
    acaaatgtaaatgacagcagtgatctcggggtggcccccggcatgctgccctcccccacgcccatgcctgtggcagcaaaccttgttcatcagtatagcttt
    ctttcctgtaacccaggatctaccttggggggcttctcaatactgcattctatgtagccagcctctttaacttggtaagtgagccaccccattctagaacctggaa
    attggagcccctcaaaaacagttcctgttcaaggaggactgacctgctggggcaatgttgggtgcagtgcagtccctgcttggggtggtcatgtctaggctgt
    tgctctgggcaaagataagagcaagattcacagaaatgggaaaatgtgaccaagtgtgatcttaacaactgacaaagtttgtaaccaacccaagttagaatg
    tgtgtcaaacaggaggtagtttagatatgcttccaagaacatgtctgtgttataaccatagtgcctaagcagtgagctctggtttttgaagggcttttaagaa
    123 2988321 FOXK1 NO aggctctccgggcaaatcagaaggccacgagagagagaggagcggggagagtggtgaggaggattcgtctctgactgatgaacctcgccgtgcctgtc
    tgtcacatccaagtctgtgccagctgctgggaggtcagactcctgccctgagaa
    124 3632941 UBL7 NO cccagcaagttgcagaggctactgcccttgggaggcactcatgaaggtgcctccatctctccatccccaatatacctgatggtcaactctc
    125 3855574 — NO ggcagcaggggtcagattttcctcatggcctctccagcaggccagcccgggtttctcctggtggctgggagccaggagagcggctcccatgcagagtgct
    ggtttcacatttgtgggtggcccatccgttgaggccagtcacgtggccaggcccaggaccagatgggagaggaccgcacaagtgcagcgtgagctgtgg
    gaggtgtggctgaccacgcttagagagtgtggtgccaggaaagatctgatgtgtcaccattctatatctgtgatgggcagacgcaggcaggtcaaagggg
    ccctggggacttaccgagcccctgcctattggccaggcactgtgattgtcctcggtgccatgtgccatggaagccctctcagaggtcgaggggaggcagg
    tggagacagagcctctgtaggcctttcaagctgtagccccagagcccagaggcagccgaattcatgtgtgcagtcagagagcacttagtgggcactgtagt
    caatcagtgagcgcttactggacaccacaggcagcaagcatttactgagtacctctggcagttgatgcatacttcctgagtacctgttcatagcaggcttagct
    ctggatgtggggtggtgaggaatcccacaggctgaggggtggcctgggagctttccagggggcctgaagcaggaggggctgcctgagtgggtcagca
    gcccagcccagtgccctacgcagccctgcccacacccccaacccagcctctgtctccccagtcccatcccccacaccctggtccctcctactttgtgcctcg
    aggacactgccccgctgccctcctcacttcccagcgtctgctgtcccctccgctgctgctgcccggcaggattgctctgtgtctcatccacgtttgtccctgca
    gagttcctcgcctctccctggaaccgccagcctcatgccgcatctcagaggctttttttttctctcttttttttttttttgagatggagtctcactctgtcacccaggct
    agagtgc
    126 2648215 — NO tttcgcagttgccaaaaatggtgccgtaaggctttcctggaattaagtagtcagaggtatttggttagcagatgctttgtaaaacctaatatattcccactatatttc
    ctttaaaaatcaagggggggttaacacctttagattgtcatgttttattgagaaaaatccacttctctgaaactccctattactg
    127 2714009 — NO atctgaggccaaggataaattcatcaactgggtagccaccactatagaagaagccaaccacaatcaatgtcggctatgcgtccagctgccagaggccgcc
    aggaatgagctaccttgaagaatcgtccgtgacaacatttctgaatggctatgtcactatcaatggggccacaacaacaacacttgcaatccaacctgaactt
    cctatgaccaaaccaagcaatctatttatgcccaagtcaagtgaaaggtgaactccaccttcaccatgcatcaaaagccttggtatcctgcccaatatgcctgg
    aacggtatatattgggaacctgctgtgctggtggccggattccatatagctcc
    128 3342827 — NO gagcaggcagttggcaaaccggaaag
    129 3494235 LMO7 YES ggaaagaagccgcaggatcagcttgttattgagaga
    130 3816344 SF3A2 YES ggagctacctggcacatacgcaggggaagaagc
    131 2340361 DNAJC6 NO cggcggcttcgcctcgcccggcgaagcttctctccggtggccgctccttcttttccctcctctttgcgtcatgtcgggcacttaatttttt
    132 3557286 HOMEZ YES agagcagctggctatccttaaatccttttttttacagtgccagtgggcacggcgtgaggattaccaaaagttagaacagatcactggtttacctcggcctgaga
    tcattcagtggtttggtgacacacgctatgccttgaagcatgggcaactaaagtggtttcgggacaacgcagtacctg
    133 3911399 — NO attttcctgcattcacgatggcctcc
    134 2612381 EAF1 YES cagcagtaaaatccaggcccgaatggaacagcagcccactcgtcctccacagacgtcacagccaccaccacctccaccacctatgccattcagagctcca
    acgaagcctccagttggacccaaaacttctcccttgaaagataacccctcacctgaacctcagttggatgacatcaaa
    135 3354739 — NO tttgagaggttatttgtccatgggatgctcgtgttaaaacaaaaa
    136 3434425 RNF10 YES taatcgcaaacgtgaactttcctaccccaaaaatgaaagttttaacaaccagtcccgtcgctccagttcacagaaaagcaagacttttaacaagatgcctcctc
    aaaggggcggcggcagcagcaaactctttagctcttc
    137 3734620 KCTD2 YES aggaagcggagttttacaacatcgcgtcccttgtgcggctggttaaggaaaggatacg
    138 3802333 LOC728606 NO ttcagctacgttgtcccagcacttcactggttaaccttttatgtccaccatttgtggatttcacagctacttgtcaatggtgaatattgatcatcatcattatctactga
    gctgctaccatatcccagctactccttgcatgttgttcattattttctcaacactcagcatatttgcaatatgttatgtaatatcacagacaaggaaactgaacgca
    gaaatgttttatttcttgccaaacatcacatgaggatgaacaatgaaaccgatttgaaaccaggattgtctgattccaacatctctgggtctttttcactctgatatg
    139 2896736 — NO aggatctagctctcttgctcaagctggagtgcagtggtatgatcaaaactcactacagcctgcaactagtgatcctcctgcctcagctatagctaaaactatag
    140 3053930 — NO ttggcacactaactccacttctagacatctatcctaagataataatcaacatataaaaatgcacatacaaatattgactataagaataaaaaaatttcagcatttaa
    gctgtacaggtgaatgtttaaattatggtacacccatttgtgttatttattttaaaaaatttttttgaagtataactatgtagaaaactgtcctagcataatgttaagcat
    cgttcccaatgtgttt
    141 3459700 — NO ctaaggtgagacaggtctgtgaatccggggtctctgtcacttggggaaaaaaaacgggcagaaaagctctgaagtttgaaacacataaggaaaatctgcta
    tctgtacccccaccctcccaaaatatagttgacgcccccgcgtgatgaagagtttatgggggtggaggcttggaggagatgtcactgcgcctgggagcttgt
    gtccgattccgggaggtggccgtgtccgagtgcgtggttgtacatttccgaaggtctcagtttctctcactttcagcccgcga
    142 3223562 MEGF9 YES gtctgccagttgcgatgccctcacag
    143 3888086 ARFGEF2 YES ggaaaggccttgacatggcaagacggtgtagtgtgacgtccatggagtccacagtgtcctcggggacccagacaactgttcaggatgaccctgagcaattt
    gaggtcatcaa
    144 3378887 TMEM134 YES ggattccagccgaacttccatccgcag
    145 3280240 — NO acctttccctgaggttggataggcactgctccccttctctgtgcccctggctcccacatctaatgactcctggcacttacgacactctcattcaaattttctagcc
    atgcaccttaagccc
    146 3379391 — NO ttttgtacatgcacttgcagtattgaggttaatca
    147 2351210 FAM40A YES gcagcacccacctcaaaagccaaaacagactcaatcaacatcctagcggacgtcttgcctgaggagat
    148 3758440 — NO gtttcactatcgagagtcggactgcttttggatttacgtggctttgtgggatgcggtatgaagatcgttgcattcaagtttaccgcctctacttcactgcagaatct
    gactgccgtcagatctgtatgac
    149 2617213 ITGA9 YES tattgggctggaaccatcaaagtgctgaaccttacggacaacacctatttaaaactgaacgacgaagtgatcatgaacaggcggtacacc
    150 3677835 CREBBP YES aaccagaggagttacgccaggccctcatgccaaccctagaagcactgtatcgacaggacccagagtcattacctttccggcagcctgtagatcc
    151 2332491 — NO atccactaagaggcgcaagttggctgcctttccagaatcctctgattttcgttgatccaaggggctggaactgagcttcctttttcatgccaagtagggtccaaa
    caacagagaaacataaagctcttcctttctccccaacctcaccagcccttaccatggctggcttcccagtgattcattcaaggcaaca
    152 2932426 RBM16 YES tggggtccggccatctaatgtttccagtagttctgggattattgcagcccaaccaccaaatattctaaataactctggaatattgggaatacagccacccagtgt
    gtcaaatagttctggacttttgggagtgctacccccaaatatacctaacaattctggacttgtaggagtacagccaccaaatgttccaaatactcctggacttct
    gggaacacagccaccagctggacctcaaaacttaccccctttaagtatccctaatcaaaggatgcccacaatgccaatgttagacattcgtccgggactaat
    accacaggcacctgggccaagattccctttaatacagcctggaattccaccccaacggggaatcccacccccatcggtacttgattcagctcttcatccacc
    accccgtggaccttttcctccaggagatatttttagtcaaccagaaagaccttttttagctcctggaagacaaagcgtagacaatgttactaacccagaaaaaa
    ggataccacttgggaatgataacattcaacaggaaggagatagagattaccggtttcctcctatagaaaccagggaaagcattagtagacctccccctgtgg
    atgttagagatgtggttgggcggcctatagatccaagagaaggtcctggacggcctccactagatggtagggatcattttggaagacctcctgtagatataa
    gagagaatcttgtgaggccaggtatagatcatcttggtcgaagagaccactttggctttaatccagagaagccctgggggcatagaggagattttgatgaga
    gagagcatcgggttctaccggtctatggtggtccaaaa
    153 3273785 ADARB2 YES taaagtaagcatattgtcaaccttcctcgctcattcaagcacctgagtcctggcatcacaaacacggaggatgacgacaccct
    154 4015409 TSPAN6 YES tgagaaggctttgaagcagtataactctacaggagattatagaagccatgcagtagacaagatccaaaa
    155 2428715 PHTF1 YES ggccacagcgttcagttgatgtggttgtatcctcggttttcctactgacactttcgattgctt
    156 3261500 NOLC1 YES gtctgccaaggtcccagagcgaaagttacag
    157 3144008 NBN YES cagacttttgactggcgttgagtacgttgttggaaggaaaaactgtgccattctgattgaaaatgatcagtcgatcagccgaaatcatg
    158 3527425 PARP2 YES atctgtgaaggccttgctgttaaagggcaaagctcctgtggacccagagtgtacagccaaggtg
    159 3836942 — NO taccaggagcccatggatggcgtgacccagcaggcagcacagaatgtacttgccaaggcgggcaaagagtaaacc
    160 2746889 — NO ggagtcaaacgtcagagcctgagacctttgatgaagggtcacatcgccagagctcagtgg
    161 2853401 — NO gctgagagctagctttgctttataattttgtacttactaaaaaattaaataacttataaatggaggaaaacttggatcagttgatagattttgggggagttagtgaaa
    tttcttgaggggattttcaatcgaatgcttttattttctgtggcagtaatgatctggttggtttatctcataaataactgatgctgctgctttttgtgttctttgatgtctca
    ccttatgtttttactaagtaaggacagcaatggattggcactgatgc
    162 3593678 USP8 YES tgtcctgcgcaatgagcctttggttttagagggaggctatgaaaactggctcctttgttatccc
    163 2466363 — NO tgataattggtgacgacaaggaaattaagacgattgctcaaagagatgca
    164 2961018 — NO gatcttccacacaaagatcaggtgaagaaatctatgcagctatacatgctaggacctgagtacaccatccctgcaa
    165 3307825 — NO ctgaggaatcttaaatctgggtataaacgtgaaatggttttattttttccttactgggtctccagtcatacagtgtaaaacactcctaacctctgtactttcctctgca
    gtgcagtcctttaagaatcccttggtccgatgtaactttgccgccact
    166 3375666 FTH1 NO gacccgcagggccagacgttcttcgccgagagtcgt
    167 3510380 C13orf23 YES gcagctgccaccgtttctggaatgaacctgctgaatactgtccttcctgtgttcccagggcaggtctcctcagccgttcacacacctcagccatcaataccaaa
    cccaacagttatcagaaccccttcattgcccactgcacctgttacatccatccacagtacaaccaccactcctgttccttccattttttctggcctagtgtcactgc
    caggtccttctgccactcctaccgcagccactcctaccccaggacctacaccacggtccactcttggttccagtgaagcatttgcttctacttctgcacctttca
    ctagcctccccttttccaccagctcttctgctgcttctaccagcaacccaaattctgcttcattgtcatcagtttttgcagggctccctttgcccttaccaccaacat
    cccaaggcctatccaacccgactcctgtaattgctggtggctctactcccagcgttgccggtccacttggtgtgaacagtcctcttttgtctgcgttaaaaggttt
    tctgacatccaatgacaccaatttaatcaactcctctgctttatcctctgctgtcacaagtgggctggcttca
    168 4026959 HCFC1 YES caagccagccaacaagcggcccatgtcctc
    169 2888352 RNF44 YES agagcagctcccgtcgtaccgctttaacccggacagccatcagtcggagcagacgct
    170 3320634 USP47 YES gagaaattgagcgcaatacatgcaag
    171 3752442 — NO taggtgcatgacactgctcagtttgatgtgctaatctgattccagtaaagagaattgctgatttaatgttgaggcccgatcttccacaggtcctaaatgtttcccaa
    aatacatggatagcatacgactgggtttttttaaaattatcccaggtcaagcatgagtatctc
    172 3188731 NEK6 YES caggactgtgtcaaggagatcggcctcttgaag
    173 3303115 — NO ctggaccaaccactacttccgtgtttcaagttcatttttagcacatgaacatgatcactgttagccagtgaagtagcttctgactagatcattgattagatctcaca
    aaaaaccaaaaatagtatatggaaaccaagatgagagcaaaagaaaacgttacctgagtaggcagctaaaacatattttgacattatttttaagcagcattcat
    aaggttcacgga
    174 3820685 ILF3 YES ggttctggcatttatgacccttgtgaaaaagaagccactgatgctattgggcatctagacagacagcaacgggaagatatcacacaga
    175 3882554 — NO ataatgggatggcaaatagtctccccagcccagagttcaatatcctcctggttgctggctgagcttagactagaattatgttgagtttccaggacacccatttta
    cgaatgttattttgaattgcctgttgtatgtgataata
    176 3054154 — NO ctacacgctgccgaggaaaacgcaacagacatggcaggtgcctcacgacaagaaacacttacaaatagaatcaaaactgattcaagtcataca
    177 2624472 CACNA1D YES atccgcgtaggctgccacaagctcatcaaccaccacatcttcaccaacctcatccttgtcttcatcatgctgagcagcgctgccctggccgcagaggacccc
    atccgcagccactccttccggaacacg
    178 3652530 POLR3E YES gactgctgtgtaagctatggtggcatgtggtaccttaaagggacagtacagtcttga
    179 3980537 ARR3 YES actaccacggagaacccatctctgtcaatgt
    180 2808239 — NO cacaggtgaattgtctgggaagtcaggatgttgcacagaagctatgcaagtcatagattagaaaagcaagaatccacattcatgctttccagcatagatgag
    gagatactttttctccaccttcttagattcagtggctgggcagagagtgctgtgaattcatctgacaacaggcagattaacacgagaaaaggaatataagtttttt
    attttttatttttttatttttttgttttgagacagagtgtcactctgtctcccaggctggagtgcagtggctcactgcaagctcccacctcccgggttcacaccattctc
    ctgcctcagcctcccaagtagctcagactacaggcgcccgccaccatgtccagctaattttttttattttttagcagagacagggtttcacctcccaaagtgctg
    ggattacaggcattagccaccgcgcccagccaagttttttaatgtttaatctaatgtgcatggaggcatcatagaaagaactgaatatccaaaagtgtggtgaa
    atttgagactttagataccatcttaatgatagtggcaggaggcagacaaatcctagggagacaagggtgggtccctggtgaaaccccaccttcaaaccaaa
    gacagatttaagcatgaaagccaagctacaagtctccagtaaatccatggaccggattaagaatctctc
    181 2811059 — NO ccatcagcttgtgactcatggcttagctggtctcaatggggaacaaaccagagagtctatggatcaacacaaagctataactgc
    182 2858392 — NO ggcccagcttcatggatatacaaactatacattcacatgggttccacacctagatgggctcttacatcatgtagctggtcctacctgggagagagc
    183 2779739 — NO tctgttcacggagcttagttctacttcctga
    184 3298972 — NO gttaactataggtaggggacagagaaaggagcagagttaatgtatgctattgaagctgagttgctatcagtctgaactagactttgaactcagcatg
    185 2933580 TULP4 YES gaaactggccacgtgcgatgcggacggaggcatattcgtgtggattcagtacgagggcaggtggtctgtggagctggtcaacgaccgcg
    186 3528128 TOX4 YES caactaggccaaaccagtacagctactatcc
    187 3528025 — NO cggcgctacgttaacttcgactatattaatgagcatcacgatcttcattttcatgatcccgtagtcctcgcggtcgtagaaaatgaaaggaaagcagccgttaa
    cacaggaagagcgaaaaaaggacattttccctggcgatcgtggc
    188 3581134 AKT1 YES gatgatctctccacggtagcacttgaccttttcgacgcttaacctttccgctgtcgccccaggccctccctgactccctgtgggggtggccatccctgggccc
    ctccacgcctcctggccagacgctgccgctgccgctgcaccacggcgttttttta
    189 3676391 — NO tgggccatctcctcggtacaggtcagctgccgccggcggagctcctcatctgtctcct
    190 2319003 — NO ccaagagcccggaattttcattacaactttcaaagagagcaagaggaggagggaaaaagatttcacaaaagcattatcaaggccccaacccaggatgccc
    tgctgtacaaccaaaatttgtaagaggtcagcctttcagggagtcaaaaacccagcatgtgga
    191 2858313 — NO ctgcagagcaaaatatagaggcactaattttgttatatttgcagcccacatactgtaataccagatttgctcctgttgttct
    192 3048750 — NO cgggaaacttcggaagacagctgtgcctggctctgtggctgcatgcagtgcttcacttggccagcagaggtcagctgtgccgagctgccccagccatgag
    aagagaagcctgcccttgctggcaggtggctatggccggcccagagccttcctgcccagctcctgcagccctgctgcctgggatcaggctgggagatgg
    gccttcctgaccgccagccttcctctccccgagcacacgcacatgtagattcggggggaagctgcctgctcttccttagaggagccggggcagctatctgc
    tggtccctttctgaacaactgttga
    193 3360848 APBB1 YES tgaggaggggacgttgaccttccca
    194 3387192 CWC15 NO gccaagagtggtaatggcgtctgtatgatcttcggagcctgctgcatcggacctcggc
    195 3893880 — NO actccgcagggctggcacttcctgagggagtgggggctcaggcttcagacggactttattaaaatgtgtagtttgtgtgaatcatttcagtcaaaagtttcagct
    atactcggccgttaagacaacttaatga
    196 2393792 KIAA0562 NO ggaagggctgccatagttgccgcagt
    197 2395248 RERE NO tcacagcagcgagcatccagggtttgcagggacgatgttacagactctgttttctgcctggcgtttcacttgtgtctgctcctagcctgtgctctgccagcagc
    acagacatctgctccatcagacctcttccattttgcacagggagtgcaggaggtgaatgttcactttctgttctccagtgtcactgttctgtttccacgggatgga
    aagcgcatgggcctgtgtccattgtagatttccttctagatttctgtgtacacacacttgattgttctggatgaatgtcttttttaatactccgaaaatttcatcatcta
    agaaaatgattccatacaaataactcagcacacaagtgacccaggacatatgcctgccaaagggatgtgttagaaggctgccttctcatgcgcattgtcactt
    ggatcttgtggtgaggacggccccatctttcttgccacagattgaggccacttttgagcaagggagatcctggagttaagacaggtgttgggggcagcctgt
    attttaccctaggggcaggtctgcatggtgaccccacattgcactggtaaaccatttgagtcccactcttcatcctggaagtgggaactggagtcccacccac
    agtgcattcagaaagcatgctgtgtgggggctgcttctcaggaggccaggcccttctgagcggaaccgtcctggagagagcctgccctcgtttccaggctg
    cagccgtaacgcactttc
    198 3403226 UNQ2963 NO ctcacccttgaggcccgggcacttc
    199 3920956 — NO cccaaatgtgagttgcatcaaattcggtaaatgtagagtatgtttgttttctctgtacacaatactgacgtcagtgctagtgcctgcctaaactcagacaccagta
    gatccttttccaga
    200 3970256 REPS2 YES tttgaaaagtactatcaatgaagccttaccaaaggacgtgtctgaggatcca
    201 2724115 — NO gcaggccttacttatttccacaggaccttataagctcatacactctattgcttattacgttactggaatctatctaagcagaaagaggctggcccaccttctgttat
    ctatgtttctatactctttggacttgcta
    202 3351955 MIZF YES caaccacatgcgctttcgtcacagtgaggaccggccctttaaatgtgactg
    203 3133234 PLAT NO ggaattctgcttcactcgcttaacatatacacaacacctgtaacatacaaggcaatgggctaggtgctccagaccgggaaaaggagggacaggaatgcttg
    gtctgatgggctaatatggcatttagagaagtaccaaggtacagtggagccggtcacaaaagggcagacttgt
    204 2723089 — NO tttgtggctgttaataggaaggatgctggt
    205 3102652 — NO tgtggcaaactaccacggcagatgtttacctatgtaacaaaactgtacatcctgcatgtgtacccctgaacttaaaaagttgaaaaaaaaaaaaaaagaaaca
    aataggctgggcatggtggctcaatgcctgtaatcccagcactttgggaggccaaggtgggaggattgcttgaggtcaggagttcaagacctgatatagtg
    agacc
    206 3392531 — NO ttggacttgaatgactaggagaatgactactctaatgaacaaaaatgtaaatgttatatgtgggtttagtaagggaatgcaatgaacttggttttggatatgttaaa
    cttgagttatcactggaacattcaggtagaaatgtttagaaagcagtttgaaataagagtttagtagaaaggttgagagcagcgctgcagatacagatttgaaa
    gtcatctgcaaagagatgtgtcttagcgttctc
    207 4015009 — NO tggaggcggccctacacctggcaatggaggt
    208 2596170 INO80D YES gatgagttgccggatgacattgccaatgagatcactgacattccacatgacttggaattgaaccaggaggacttttcagatgtcctgccacggctacctgatg
    acttacaaga
    209 3591676 — NO aaaacctggaatgctgtaggacatgtacccactgaggcggatgcaaggagcgatggagaggaagga
    210 3680412 — NO tttaccccttctcggtgacatttgc
    211 3906169 CHD6 NO ctgcttgacttactgggtgatattgggctacaactgagactcactttgctcctgtgtaaagtggggcaacagcatctaccacggagggttgaagatttacgga
    gatcatgctaagacagtttgttccaaactcaaaggaaatcatttgcaaacaacagaaaaggtcagaaaccgtatacctggccaagagagatcccttttacgct
    ttgtttaatgtttcatgttgtattttgggttttcccatttactggattctgagctccaaaacaggaatcacattttatgttttcttattttaaaagcaataataataactagt
    acttattgagtgcctactgcttaccatgttcaaggctttacatgattatcttgtttgttcctcacaaccactctgaagatgggctttgttattcccattttataggtgag
    gaaaataaggctttaaagcattaaataatttccccaagattatccagctagtaagtgacaaagcaggaaaccaaaccaaggacctttttctctaggggctgaga
    212 2803102 — NO ctatatgtagctaccctgtggcctccccctaaggtaaccactttactttttagtagtgaagaatgtctaaaatataataaaggtatatctagaacacaaacctcca
    agcaggaacaacccattatctctcctttgcatgccctgtcaatggcttcaaggtcaaagctagctaagtctctgagtgtgtagggagctgacatcttggtgaaa
    agtccttcagtacatgctagatcatagctgacttgcactatccttccaaactttggaatatctctctggtattggattggttacaatggaaacagaaagattctgat
    catacaaaataaagattttcatttgtgagctcaaccattggatctgtcatcttccattagtagaaaaaatgaggaaatcaaatactttgttttgtttttaaccacgcag
    agaaggaagagagtagagtgtgggaaattgatatatctgccttactgccccagcccctccctctggagtgtgcaagtggtcagaagtcagcaaattacttttc
    catcatatttggccccaaactaccctggtgagtgaggagaaagggaatcatttgataaggtttggaaaatagcatctgtttttcttagtgtttctggatgaatttat
    caggcatccggtaatttgtactttctgttgaaaactataatagaataccgtgcatagacatgaaaccttttggtattagtcagaagctacatactgactgctgttgg
    agaagaccacatttacagtcaagggtagaatcatctgaaatagtttcccctggaaaaaaaaaaaacatggccatatatgcctacatagatctcctctttgcttca
    tgaatttggaactaaacctgggtgtttagataattccagttctaggattttctcaccttgagtttattccccttattcttactagttcagtttggccactgtacatatgga
    gcttactagaggcaaagcactctgtgaggggcaatggttataca
    213 4025793 — NO ttgtgtctgctccaagtgcgaaccctccatgcactgcagagaacaccagaaggagaggagcactacctgagcttctccttccgggtctaaaggtggaacttg
    ctttgcagcacccagcatttcactgtactgattcctttttttggatcaccacctcctgcgtttagcagcccatatgctgggctcactcagctatacactgcttg
    214 2616236 FBXL2 YES aattttggaggctgcccgatgctcccatttgactgacgcaggttttacactttta
    215 2959832 LOC100128757 NO tccggtgcttacctctaactgataaaactagctccaacccaccaccctccactgacttccttcgcactcagcccactcgcacccgggtgaataaacagccttt
    gttgctcacacttagcctgttcaagttgtctcttcaattagatgctcgcataacatttggtgccgaaagcccgggataggggaactcctccggcagacctctcct
    ctatcctcccggtacccacgttctcccatgcaagagacttccctcgccctcaggacctcagaccagctccgcgagcactccggcctctgtctatgga
    216 3072195 — NO ttagtgtcgtcaggagactccctccatcagaattactcaggctgattgttttgagtcctgggacccagttggtatccagaatcttggcttgtttgcctaggaacc
    217 3757471 ACLY YES gggtgtcaacgagctggcaaactatggggagtactcaggcgcccccagcgagcagcagacctatgactatgccaagactatcctctccctcatgacccga
    gagaagca
    218 3986531 — NO gagggaggaattacgtggtgaaggatgaagtgaacagcggtgcttggcatataagccagccctcaaacaag
    219 2696767 MSL2 YES cttcctgtagctggtgcaaagactatgagcagtttgaggaaaacaagcagttaagcatcctagtgaactgctacaaaaaactatgcgagtatataacacagac
    tacactggcacgggatataatagaagcagttgactgttcttctgatattttggctttgcttaatgatggatcattgttttgtgaggagacagaaaaaccctcagatt
    catcctttactttgtgtttgacacattcccctttaccttcaacctcagaacccacaactgatcctcaagctagtttatctccaatgtctgaaagcaccctcagcattg
    ctattggcagttctgttatcaatggtttgcctacttataatgggctttcaatagatagatttggtataaatattccttcacctgaacattcaaatacgattgacgtatgt
    aatactgttgacataaaaactgaggatctgtctgacagcctgccacccgtttgtgacacagtagccactgacttatgttccacaggcattgatatctgcagtttc
    agtgaagatataaaacctggagactctctgttactgagtgttgaggaagtactccgcagcttagaaactgtttcaaatacagaggtctgttgccctaatttgcag
    ccgaacttggaagccactgtatccaatggaccttttctgcagctttcttcccagtctcttagccataatgtttttatgtccaccagtcctgcacttcatgggttatcat
    gtacagcagcaactccgaagatagcaaaattgaatagaaaacgatccagatcagagagtgacagtgagaaagttcagccacttccaatttctaccattatcc
    gaggcccaacactgggggcatctgctcctgtgacagtgaaacgggagagcaaaatttctcttcaacctatagcaactgttcccaatggaggcacaacacct
    aaaatcagcaaaactgtacttttatctactaaaagcatgaaaaagagtcatgaacatggatccaagaaatctca
    220 3188391 — NO caggggtacacccacatctattgtattagacaaatcacagagggattgcaacagaacacagatttttctcactgttttttctctggttgatcgggatgcattatcc
    accagaaaacactgtagacgactcactcaccaggaaaagagcatatgccagttggaataaataaaggggaagagtaaggaagaggctgtagaattatttta
    taaattatcaagtcttatgagccaggtgc
    221 3846196 — NO tctggccaatgcatattacttaagggcaatgtcgtggccagctgtggtggtctgggctctccctctgtatcgcctggggaggctgctgaggtgactttttggaa
    gaaaacacgggatgagtgtatgatggtggctgtggagaccacccaaaatcccggggttgggggcaatagtgaatgaatgggaccatctgcgtgggtccct
    acacgagatgcttg
    222 3070747 — NO gagctcattctgcgtttcttattgcttg
    223 3821522 — NO gtagataaccatttgtcgctgctttttctgttaagtgttcaccacttgtatcattggctggcaatacctggtttgtcatagttt
    224 3875001 — NO agctcctccccagaataccatgctc
    225 3279450 C10orf97 YES ccaaagtttaattaatctcctgctgacgggacatgctgtttctaatgtatgggatggtgatagaga
    226 3541293 PLEKHH1 YES tctttctctggcctggtctacaagaatgtcac
    227 3547709 TTC8 YES cctggaacgtctttgaaactccctggaactaatcagacaggagggcctagcc
    228 3875261 — NO gccaaccttggtttgtgcagtttaaggaaaaaagccatctccataacatggaagtgcaagatgaagcagcaggcactagtggggaagctgcagcaagttat
    acagaaaatctagctaatgatgagggtggctacactaaaaacagattttcaatggagacaaaacacccttctattggaagaagatgccctctaaagctttcata
    ggtagagagaggtcagtgcatgggcttgaaagaacaggctgattctcttgctagaggccaatgaagccagtgagttta
    229 2584791 — NO cactggaagaatataggttggctcagacagtccataggaaggctaaataaccacgctcaggaaatgggccttagagagtgggaagagaaaatgtatctaa
    acttatatctcagtaacagcttgataggacattgtcactagcagtgccaccactaggtcctca
    230 3204563 KIAA1539 NO ttgccagcactctgaacccatgcgggctaatgacctgcccatcctg
    231 3356165 APLP2 YES cgagactctggatgttaaggaaatgattttcaatgccgagagagttggaggcctcgaggaagagc
    232 3650891 — NO tacactccctcagggacagtcttgccatttcccgtttttcattcttataaacaatgccctggtgcaggggtcagcaaacttttctataaggagtcagataatctttttt
    ttttttttgtattcccttttggcaatttgtttaattgagataaaattcacataacttaaaactcacccttttggtgtatacgattcagtgctttttagtatattttcaagattgt
    gcaaccaacaccactatctaattccagaacatttttatcaccccaaaaaggagccctgtgccaattagctatca
    233 3829699 GPI YES actgaagcccttaagccatactcttcaggaggtccccgcgtctggtatgtctccaa
    234 3971251 CNKSR2 YES cctcttatacctagaagtcccacaagcagcgttgccacgccttccagcaccatcagtacacccaccaaaagagacagttctgccctccaggatc
    235 2359255 — NO agttgtggaggcatgtttataagcagatctgagttttgccacactggaatttatttat
    236 2811000 — NO ctgggtctaggaagccaggtactttgtgctgtttcaacaagagctcttctgctttaactagttt
    237 3391986 — NO gctggagaagttcgtctgggacaaagagctctggcctcatgcctgtgggtccagcagtcaaactgggacagactatgtgaaaagggacccac
    238 3888361 — NO agcagcctcccgcttagcggagagtgggatgagcacatgcgcggccgacagggaagagtgaatccagagcagaagtcaagggcaagactcgtgggg
    gggggaagaaagggacagaagccagctcccagcaataaaggtcgggttattttgttcttttgtgacatgccctatatc
    239 3897502 — NO tctcctggggacttacatagctgtttggtttttcaacttgattgaagaaagttattcgggggatctgtccaattcacaccttctgttccctgatcaaatactttagggt
    caaacataaggttttattgatttttgctcaagcaaagaattaacatttttgataaggaactgtaatggcaattataaggtaatatggtgtatggtaatattatgctgcc
    agaggaaacatttgactatgattaaattcaagcccagtactgggtagctctagataattaaagataattttatccattcaagtcccctctgttaagctgcacattga
    ca
    240 3235381 DHTKD1 YES acagtatattgtgagcatggtcataaagctgccaaaatcaaccccctcttcaccggacaagccctgctgg
    241 3286657 — NO tccagtgaggccacatcatgacttcccccatgaagacatcgaattcacggctgccttcacctttgtcctgtcaatgtctgatctttcctttcaattacagcacgag
    gctggggttcca
    242 2714224 MYL5 YES tggaccagatgttccagttcgcctccatcgatgtggcgggcaacctggactacaaggcgctcagctacgtgatcacccacggggaggaga
    243 3331851 GLYATL1 YES tgaaagtagagcattcgagagcactcctcttggttacggaagatattctgaagctcaatgcctccagtaaaagcaagcttggaagctgg
    244 3356559 — NO gccatggttctcttgtggtcagctcttgttctaatccttagcgcccatttggaaaccagttatggggaaagcacaatgtaggactcttgggactctgcacctgac
    tggctggctttccaagatcactgagatggctcttcctccagcatagaaattgatggctggttatccagacagcaacctcttttgcccatgtgcttggtgctctgtc
    atggcgggaaaagtaactatgcacagatcatgattatggtattagattgggtacacatgaaattgctagtatgcacctattttgatgtatgaaaatatcattttcat
    gagattcatcctaatttatgctatgtatggggcctgattgccctaacagctcatc
    245 3636325 — NO atcagacaccgcctattcaccagctcatctataaaaccccctgcatttcaccgcagaactggaacctatt
    246 2539613 — NO tccattcttgcgcttaaaaactgtacctaactccctcccatagcagacagaataggataggcttcttccctacctggtgttcaagttctaccactgccctcctccc
    ttcccccatttacctctctagaattaccaggtatctatgcatacatgaattctctgcttccattagatttacttgtcattccccaaatacaccatgcacttgcatattag
    caaagccaagtttgtctttcacaaatgcagaggttaaataagagttaaggatgaaggtaaaccaaactttatttatatactatattttaccaaatatgatttaaggat
    ctctaggcagtgttgtctta
    247 2860647 — NO gcaatgtggaccagaccatcgacaacccctatgccacctttgtcaagatgctaccggataaggattgcctctacgccctctatgac
    248 3143676 MMP16 YES cccgatgcggtgtacctgaccagacaagaggtagctccaaattt
    249 3492475 — NO tgggctgaccacagactttaccacaaa
    250 3698355 ZFHX3 NO gtccgagcctccgtactgggtgcaatgaaagc
    251 3364564 — NO attggcgtggttcttccccaggataccttatagagtctagtgaacttttcctgtttgtggaaacaatcaggctgggtttaaatgaggacttgtctctatttggagcat
    ttgtgagcgtgtaaggaaatgagtgttt
    252 3101645 ADHFE1 YES agggagcttttgatgcctatgttgctgtcggtggtggctctaccatggacacctgtaaggctgctaatctgtatgcatccagccctcattctgatttcctagattat
    gtcagtgcccccattggcaagggaaagcctgtgtctgtgcctcttaagcctctgattg
    253 3015159 ZKSCAN1 YES agttcatggacctgagatgctcgcaagggggatggtgcctctggatccagttcaggagtcctcgagctttgaccttcatcacgaggccacccagtcccactt
    caaacattcgtctcgg
    254 2686624 IMPG2 YES atacctttcaagctgcatggccctcagcagatgaatccatcaccagcagtattccaccacttgatttcagctctggtcc
    255 2897644 — NO atgttgggtcccaccttacatttagtttcatgtccccttagtttcctccaatctgtgacagtttcttaattttttcttgtcttctgtgaccttgacacttctgaagaaaaca
    tttccttgatatttctgatgaaaatgattattatgtagaatgtccttcaacttgaattggtctttttctcatgattagaatgaggttctgggtttttggcaagcagagaac
    agaagcgatactatatttttctcagtgcgtcatatcggggtcatgatgtcagtgtgtcttatactggtacactaacccatgtctgctaggtttctttccaatacagtca
    256 3909740 — NO ggtggagcaagagccctgttggctgatgg
    257 4049026 — NO ggcacagaagggcaaattccgcacattctcatttgtggg
    258 2321582 — NO atggagccagaaaaacgcgtgcagcagctcatc
    259 3304498 ARL3 YES ggcttgctctcaattttgcgcaagttgaaaagtgcaccagaccaggaggtgagaatacttctcctg
    260 3533002 — NO tactgaatgtgcttggttttggacag
    261 3568039 PPP2R5E YES ctcttgctgccgctgcagatccagtcttcctcc
    262 3764440 RNF43 NO tgcggaatttctcggcacctacctgtagtatggggcacttggtttggttgcagagtaagaaggtggaagaatgagctgtacttggttaagcagttgaaacctttt
    ttgagcaggatctgtaaaagcataattgaatttgtttcacccccgtggattccagtgggcccgaca
    263 3790080 NEDD4L YES ttgggaaagcagataaccctgaatgacatgga
    264 2658005 — NO gtattatcacatgactgccaggtgc
    265 3029676 — NO gtctgtgggtggatagatccattaatggataagtaaatgagcaatgcttcctgggttgaggttttggattactgtggtcatgcactgcattggagatgaggtgga
    aaaaccatc
    266 3390272 — NO gagtgggcactaggaaacggattcaaagaggcgatgaataatctgagttttacaggtttaacaggaaggcataacattgtaagcaaagaaagaaaagatatt
    ccagacaaagcatatgtgg
    267 2642810 DNAJC13 YES ctggatggagtaagagcctctggtaatagagatgtttgtgtaaaaatgacaccaacccataaaggtcagcgatgggggttactcagcatgcctgttgatgag
    gaagtagagagccttcacctcaggttcttagctacgcctccaa
    268 2811129 — NO gatgagatattaactgctgcactgg
    269 3070222 AASS YES tgagaaaatggtggatcatagaggagtacgggtagtggcatttggaca
    270 3907114 TOMM34 NO cctgcctgaccttacccagagaagccatgggccacctgctctgtgcccgctcctgaaaccca
    271 2790942 — NO atgttcccataagcaacagcctgtaaattgtcacatgtaagtcatctaataagtttagaacaatgaacaactcattttctgaactgggacaaacaaggaagctaa
    attca
    272 3043075 — NO aatcagtgttgcctggtggatagcaaatcaagtttcaaggttacaga
    273 2354095 WDR3 YES ccatggtgaaatggtgggaccttgatactcagcactgctttaaaacaatggttggccaccggactg
    274 2713294 — NO tggattgcgtaaaggtggggacctccagatcttccacgggaaaggtacgtttttcttgttgatattgtgaagtgtgtatggggttgtactttggcaccttgtagtg
    agtcagtttccccccattggtgatcattgccaaatca
    275 3220577 KIAA0368 YES agatgttgcatcaaagggccttgggttggtttatgaactaggcaatgaacaagatcaacaggaattggtttctacacttgtggaaacacttatgactggcaaaa
    276 3531076 SCFD1 YES tgttactcgtattttggacaatcttatggagatg
    277 2505303 RAB6C NO gcaggaagaaaacttcgagttacaggtcaggaaaagc
    278 2644040 PCCB YES gagatcatgcccaattatgccaagaacatcattgttggttttgcaagaatgaatgggaggactgttggaattgttggcaaccaacctaaggtggcctcag
    279 2938530 — NO gagaatgccggtggggccttcagcagcagcatcctaacagtgttgca
    280 3625346 CCPG1 YES gaggccctactatgcaaaatgatggaaggaaagaaaagccagttcactttaaagaattcagaaaaaatacaaattcaaagaaatgcagtcctgggcatgatt
    gtagagaaaattctcattctttcagaaaggcttgttctggtgtatttgattgtgctcaacaagagtccatgagcctttttaacacagtggtgaatc
    281 2971361 — NO ctgcctagtattgtgctacagtaccagacaaaatcactttagggttttggggttttgtttttttaaacaaactggtatgtaatataaacttaggaaccaccaccac
    catctcgagtatcaatgtttcagaatggaggcatagttcagtgaaaaaaatgccggcattggttttagttttgattcttgtttcaccagaaagcatggtggttggg
    ggagctgtcaaagtactccggatagactcagcgccattaaataagctcaggcatatacggccaggagcaa
    282 3026661 TRIM24 YES aagtgtgagcgcctacttttatttct
    283 3108906 — NO ctgcatcgaaccagcgacctgggtgcctccccacccaagacggacctccacatcgggaa
    284 3649134 MKL2 YES ccagcagccctttatcaataaggcctccaacagtgttcttcaatccagaaatgctccgcttccatccctgca
    285 3729183 CLTC YES ttattgaagttggcacaccacctacagggaaccagccct
    286 3900156 C20orf74 YES tcccaacaaaatcgtggcccaggtagcttgcgatgtccttcagttgctggtttcctactgggagaagcttcagatgtttgaaacctctctgcctcggaaaatggc
    287 3907653 NCOA5 NO tttcctctttggaactcttgtgttgtt
    288 3102604 — NO ttggtcttcacgcactgggtgtgtctgtaaatacagcgctgtccacggtgtctgtcctgcttccatcccaaattcaggctttagcttaaaacatctttagtttaatttt
    ttaaaaaattcttttctttcccccagataaaatcttaatcttttgcactagactgttagccagggaaa
    289 3863282 — NO gaagtgtttccagacatcccaattc
    290 2920506 — NO gcttcttcgtggtcttttccattat
    291 2319069 — NO ctgaagcagggtgcccgtttctacaccaaagagcggcaaaatgaagaa
    292 2573693 CLASP1 YES gcttctgggcctgcagaacttactgaa
    293 3022667 SND1 YES gtgcccgagtagagaaagtcgagtctcctgccaaaatacatgtcttctacattgactacggcaac
    294 3570810 — NO atgtgggtggagatgatctttgctttgagaacaggattcattatgtgggctggtcaggagtgggaacaagagcaggaaggccacaggggattgagagtact
    tctgtccccaacacactcatcaaggacgtgcaatcgggggccaaggctcattatggtgattttca
    295 3847162 — NO tggccagctccctagtttgtgcttactatacctggccacgcctccctacctaaggccgctggcttaaccctaggggcaggcagtgttagatcagacccagac
    cttctcatcccaccctcatcacatcggggagaggggactccaggggcgggaaggcaggcgtccctccatttggccagggtgggcggcgaggaggggg
    tcactctgcaggaacactgagctctgaacacctct
    296 2535304 — NO tcaacaacatgaatggcggcaacactaggagacatcc
    297 2697615 — NO tgcagtggtactattttagctcaatgcagccttagattcttggact
    298 2931795 — NO agatggcatgctgcacaagggattcatggttacagcgggcttgtgggactggggctctccaatacgtggttgggtttgtaaagaaatcaga
    299 3011882 STEAP2 YES caggttattgaacttgcccgccagttgaatttcattcccattgacttgggatccttatcatcagccagagagattgaaaatttacccctacgactctttactctctg
    gaga
    300 3464921 — NO cctgataataagaggaacgaggacagctcagaaagtacaagtcaagaagccctgagaggggagtgaattcaggaaaccggacatttcaggtttgcctca
    gcattgcatgagtttgaggaacaagaaaagatgaggatggattgtgaatgatctcgaatgtgttttgaaggtttttggaggtatttggattcaccctaaga
    301 3541610 — NO aggtcgatgggctcagaattcactgacaggttcagatccagccgagaagtggagcatgtatggtattagtggcatttgaaggtcattagtggcataactattgt
    agtgtaaattcaagttttattggtatattgtgtatagccctgcaga
    302 3872499 — NO ttaggagccatcaacgagttcacgccggagaaagacctttcaagtgtggagaatgtgtgaaatctttcagtcataagcgcagccttgttcaccatcagcgagt
    tcacagtggagaaagaccttatcagtgtggagaatgtgggaaatctttcagtcaaaagggcaacctcgttctacaccagcgagttcacactggagcaagac
    cttatgagtgtggagaatgtgggaaatcatttagttcaaaaggacatcttaggaaccatcagcaaattcacactggggacagactttatgagtgtggagagtgt
    gggaaatcttttagtcataaaggcaccctcattctacatcagcgagttcaccctagagaaagatcttatgggtgtggagaatgtgggaaatcttttagttcaatc
    gggcaccttaggagccatcagcgcgttcata
    303 2470335 — NO aaggcgttcgttatgtgggatatgctgttaccactgaacttgaagttatcaaagaagt
    304 2887649 — NO ggtaagtggattgacctctaaactccctagaagggctgtagctttgaaggtggacatttattgggctcgcacgtgacacttattggggctaa
    305 3522210 — NO gtgagaacctacatgttgggtgcccacc
    306 3674221 — NO agtgagcgtttgagtgaaccagccacagtctctacgtgtcatccaaggagcccggcacagaccccgtgtcacccccatgtcacccgcagaccccgcgtca
    cccatagatacgcaca
    307 2560167 — NO gggacacagagcagttgaggatatctcttttctttcactctgttctgaaatctgcctcttcccaaaggtactccatgacccctaagatactcactctg
    308 3041159 — NO ttaattcagcacaactcaccattcccactggaaacatactggcaattcacatcttccaaacaagg
    309 3183335 FKTN YES gaggcactcaggccaaaacaggaaaaa
    310 3204049 — NO gggcgccatcggatggggcaaagagatccctgaaaacgtattgccgggggacggggacttgcaggacaagaaaaccgtgggagaat
    311 3393003 KIAA0999 NO gttgattgtaaacccacagtatctagcagcgttgtgccaaattgcccttgtgtttctctccacccaaaatatcacagctgctttcctcacatttggttcatccgtgtg
    ctgttctttt
    312 3598130 — NO gccaagtacaaagtgctgtcccatatattacctttatcatcatgacaagcacttgagatggtaattaacaactccactttaagtctgagaataatgaagcaactg
    acccaaggctccaaagacagtgaatggcagagatgagattcaaacccaggtctccctgactcgaaagcccacgctttcccccaacaccatgttcttttccttc
    cctgtcagaaagggaaataccaaaaacaaatgagggtatgtatgagggtttggctggagccccagtcagccaaagtctgattccaagtggactgcagggt
    ccgtgttatctcccttgggcacaatctcaaaagcccagaattcagctgccttgctaaccttccatcccagtcttagtgagaagctaaactaacttctgggcctca
    attacagcagatta
    313 3681604 LOC728138 NO tgccatagaccctcacgtgtttgttgcattaattggataattcaaaatataaagtattatccagtttcaggataatattaagatctaaaccaatgaatgctctatgaa
    aagttgtagattaactgatcccttaaaactaaaaacagcgtcttcataagcttctactgggggcagctaccactttcttcatcacatttcttatcctcaatagctgtg
    ggcaatgccaaaatagc
    314 2410882 ATPAF1 NO gttggcccttcacctagttgactcagccctcgatagtctagagcccaccccctcctcaggaactcaagagctcagcatttataatgagcagttggtaatgagtt
    gccctatgtgcttgtcgcaagcagtcacagagatgagccctattacttgatattcaggaacaaaggtacctgaacattctgataattatctcagcatacttgagg
    tttccttttttaagtgttcgaggttataacaagagacagccaaggacctacaagacagttgacttgattttgcacagtgtaacagcgcagttgcattctggccact
    ttgaccttatagctcccaaatgatgagtttgtcatctttatgaactcatgacaggataataagcttgaagacctgctgtagttagatatgggctttaatccttcccag
    gcaccagtcagctgaacaaaagcataagccaaacatcctgtttaaactgtagaataaccagatattcccatcaggttaaagacttcatctagatgatgccccc
    cagagatgcctttagtgtaagtagctggcttggggtatcagcaaatttcaggtatagttagataaacaggtacagggcctgcatactattaaaccatagtttgtg
    gcacccgcttttcta
    315 2821250 CAST YES agggccagatgatgctatagacgccttgtcatctgacttcacctgtgggtcgcctacagctgctggaaag
    316 3134070 PRKDC YES gattggagcaatgatgtaagagctgaactagcaaaaacccctgta
    317 3888286 — NO agctccagttacatgggcctgttaacatggcagctttgtctataagcaaacccaggagagaaagacatagcagagatggatgtttgaagtctataccttccac
    cccctttaaagagaaagtaacaccactccttttctgtgtcccttggggacactacctccatgtctggtcacatggctggactttacagcagataagcatactgtg
    gcctgagaccatgattgtatgctttccttctgctgacctttacaatccctcaataaattgagctaacacagggaagcttttttaccaaataactgtgttgcatcatcc
    tccagtttgcctggtgtccttaatcaatggaaggggaataagcaaactgagttttcttacaccttttgagtatagtgtttttgccatcatagatgtggctcctcataa
    ttctccaacttttatattaaaaaaccaaaacctcaaaaattgtagttcatgtcagtcagtgatgactcatcttagaagtattttgtttttggatgtgtgaatgtgcatag
    ttcttaaagtccaacattcatgtaataagacatcttgcatataacaatgacccttacgtctaagatgttaaatagatcctaagcctggtataactttattcaagtatcc
    ttatttgcccctaaaatgtctttaatacacattacttgggttatttcttgaatgaacatacaggtatcccaatttctgatttttaagagaatggggtcttgctctgtcaccc
    aggctggagtgcagtggtgcagtcatggcttactgcatccatgatcctcctgcctcagcctcccaagtagatgggactgaaagcacacactgccatccctgg
    ctaatgttttcatattttgtagagttgcagccttgctacgtgacccaggctggagtgtagtagctattcacaggcatgattgcttgaaactcatggcttcaaggga
    aactccca
    318 3919790 — NO gcagggagtgcagaaaccttggagaaagtgagagattttccagccaaagggaactttgtgtttccctggctgggactcttggggatctttttcaggttttctgca
    gtttttctgaattgagctttaaggcaactggatggattttgaact
    319 3948965 — NO cttagctgttccagcggcccatgtttaaaagaatgtgcttctttttccaagtatttctgccgcttgcatgcactgagcttctttggaaaggagcaccatgcaggca
    tattttccagacaggaccggatttgctcgttactcaga
    320 2738676 — NO ctgagacctgaagcacgagagccaagtgtgtaagcaagtcgatgggattgggaagaagtttaggctgctaaaaaatttttacataaagcttgataagaggg
    gatattgcatgtgaaataaacagaaattcagtaaatatggtggaagtgcaggatttaggggatggaaaaaaatactagtttcaaaaattgaggctagaagtga
    aggtaggggccagattatgaaaagccttgtaagcaatgctaagaaacaatagatgtcagaaggacatgccaccatctaaaaagcagtcttgagaacaagta
    attggataaaggtgacctgactaggtatttgtttttttaagtaaattgtgttaattttgttaggtgtaaaaatggcattagggtcatgttggggaaaaaagaatctctt
    tcttacagatgaaattacatggtctctgagactgcttccaaaaa
    321 2929182 — NO tgggtgtaaacattgatgatccttctaatactctgtcctcttaatttctctaagttctctttctagtgatcttgtctcccagtgtggtgggtatattctggctagaccag
    gtcattgtttatggtggcagcccctctgtcatctgaatttaagcgtcccattttttcggtactagcatggctcactgc
    322 3004581 — NO gcaaatgttttaatgggccctcctaccttacctgacataagataattcatactagaaagaatacctacaaatgtgaagaatgtggcaaaagctttagtgtattctc
    aacctttactaatcataaagcaattaatactggagagaaatcttacaaatatgttgaatgtgacaatgtttttaactaggctgcaactcttgctg
    323 3300811 C10orf4 YES tttggatttaggtggcgagtagaaaaa
    324 3426258 — NO atggagattaagcaggaacttcaagaaagccaagctcttcttggtagcacaccagagtctgaagg
    325 3645807 — NO agtggaatctctgaaactcaggtgtggcatcaacaaag
    326 3976960 — NO caaatcccgggtggcagccataatccccaaagatgacccccaccccaagattccaaagaagctagtggtggtggaagcaaaaggaatgcagcaaggtc
    agggtttcattgtccaagccggcctgacacctgccgccctgcccttgcccagtgcacaccctagaccctgggccggcctccatgcagctggaggccagaa
    gacagcaacccatatctttgcaccctcctccatgccccatggcctgcctgcccagaaagatgccaccttcacagagccagtgctgtcgtctatatcattt
    327 3981121 OGT NO ccgtcgccgccatttcaagaccgtactag
    328 2391399 CPSF3L NO gtatgcaccggcttatgaacccaccaggctctgtccgagcggcattgaaatggccagagtgggacaggctggtgccctcagagcgcttggagcggccag
    agactcgctggagctcccggggtgttgccgggcagggaggcaggggctggaggggagatgggccagctctggagggtgcctggttctgggtgtgggt
    cagggaagaagtgaaggttaaatcagcgagtgacaggtgaaattccatttctgacaaagattatgggtttgtctgtgtctcactcgaatctctggg
    329 2748879 GUCY1A3 YES tgcgaattggactgcactctggatcagtttttgctggcgtcgttggagttaaaatgccccgttactgtctttttggaaacaatgtcactctggctaacaaatttgag
    tcctgcagtgtaccacgaaaaatcaatg
    330 3063716 — NO gtgagtggttagagaacaatggcaaacaaagggcgaggcgtttaagcttctgtagagagg
    331 3361874 TRIM66 NO tgggcttccgtgatcccgttttctagtttggggtaactgagtcttgaatgctttactagtccggcaatctttggacttaggcttctgccctttgagactcacatgact
    ttctggtttggggtctggtcatttccctttcaatttttgaatctccttctctgttcagttggcttggcaaagtaccctctgttctcatg
    332 2812780 — NO tctggaatgaaacagcgtaatgagatgagccctga
    333 3065419 — NO ctacaaggatactcaggtcagaaaggcccaggagtacctacctcattcagcaacagtccagtcaaaatcttcctccccgacaatggcctatgaccagcctgt
    tctacacattcctctctgg
    334 3077669 — NO aagagcccttctcaatggcttaacccatagagccc
    335 3652961 — NO aagcggaggttggaggaagccgtgattgtacc
    336 2895678 SIRT5 NO aaagcagccgtggagacaaccatctt
    337 2978057 — NO ctgtgttgtctcagtcaagcctagaactgaagctacctgacatcaagccaattgtccaggaccagcatttccagcacttccagttgtccatatctgcacttccag
    gagtaaacaggca
    338 3595946 RNF111 YES caaggccacttcatcatcaagcttctgcctgcccgcattctcatggaaacccccctcctcagactcagcctccgcctcaagtggattatgttattcctcatcctgt
    acatgctttccattctcaaatatcttctcatgcaacatctcatcctgtggcacccccaccaccaactcacttagccagtacagctgcaccaatccctcagcatctt
    cctcctacacaccagccaatttcgcaccatattccagc
    339 3628693 HERC1 YES tataggaaatcatcaggagccaagtgtgtttatcagctgcggggacacatcactcctgttcggactgttgcctttagttctgatgggttggccctg
    340 3734777 MRPS7 NO gtgagctactgccacgctgaaaactacctgtgggttaaggatgtagttcctttgtaagggtgggcaggcctcgtaagaaagatgtagcagcatattcactatc
    cgttaatccttctttctttgaggctggaacttgctctctctgcccctatttccttgtaaagagggagcacattgacttgggaatttcctccaggaaactcagggctg
    tttt
    341 2806269 DNAJC21 YES acagagctggatgactatggccaatttggagaaagag
    342 2849121 DNAH5 YES atgaatcccaaagcgattactgccccacagatgtttggtcggctggacgttgccacaaatgactggactgatgggatattttctacgctttggagga
    343 3012989 — NO tcttattcttggccacgggaccaaccctcacaggggcactctatgcagaagcttccttcctaaattggaactcccactttgaccactctccttt
    344 3184655 — NO ttgcaaggcccacaccacgtggctgagaagtcaactactacaagtttatcacctgcagcgtccaaggcttcctgaaaagcagtctaacagcaaaagaaaag
    cttatattaaataaatagttaaatattaaaccttcaaaagaaagactcgacacaatgacacaaagcacattctggaggtcctc
    345 2428776 RSBN1 NO gctgcccaagatgttggaacaccatgtgcaataaagggcttcgtcttggattttggccttattaccacaaccag
    346 2502833 DBI YES acggcccgggatgttggacttcacgggcaaggccaagt
    347 2608589 — YES ttccattgatgaattggataatgctgag
    348 2781610 — NO cttacaggagaaatcgaaacacagctgctac
    349 2810989 — NO ttagagtttatggaccttgctcttggtta
    350 2489148 — NO cctctgccttcgctcgcgccgctctccttcagtctccccagggcctgtttcatggatagggtccccttgcccgcgtgaaagtctcattcctc
    351 3239162 — NO ccactggctaataagcaggtctttattgagtgcccaacactgagtttagtcacaggtgcttattctggataattaatctcagtagattaaccttcttcagaatgacc
    atgtatatcagacttctcttatccccaattctgggtccttattaacctcttccagggctaagtatttacccttccataaatcggatgttttcttaagcattttttctcctgt
    catcactgaaactccagcctagttcttcacttgtatgcaattttcttgtaaccctgtctctcgttttggttttattgtccatatgcctattgagtgcttttccagttg
    352 3573019 POMT2 YES ctgataggtcttgctggctacctgagtggatatgatggtacctttttgttccagaagcctggggataaatatgagcatcacagctacatgggaatg
    353 3937196 DGCR8 YES ttgtgcccccaaaaagaggcgaacagaggaaaaatatggcggagacagcgaccatccgtccgatggagagacaagtgtgcagccgatgatgaccaaga
    354 3154331 NDRG1 NO tgctgggcgtcaagcttgcataatgccgtactttgagggcggttgtcacaagtatcacaaaatgggtggcttaaagcaacagatatttattcccttttagttctgg
    aagctaaaagtccgaaatcaaggtgtgggcagggccgtgctccctctgaaggtgctaggggagaatgctgcctgcctcttccagcttctggtggctgctgg
    ccacacttggttcaccttagctagtagacacatcactccagtctctgcctccatcctcactcagcactctcccgattgtatctctgcgtctatgtccaaatttccttc
    ttcttttaataacatcagccgttagctttagggcccgctctaatccaatatgacctcatcttaacttgattttacctgcaaagaccctatttccaagtatagccacag
    tgataggtactggggttaggacttcagtatgtctattttggggacacaattcaaccacaacctacagcaaagggtaggtggcctgactgaggtggggtggcc
    gatttgatggtagatccagaaacagaactcacttaggcctgattctggagacttccacagcgtcagtctaatgtgctgagtgccccgcctggaggaaaaattc
    gggcatc
    355 3697772 PHLPPL YES tcccagcgaatcagtaccgtggatctctcgtgttacagcctcgaggaggttcctgagcatctcttctatagtcaagatattacctacctcaacttgcgacacaac
    ttcatgcagttagaaagacccggaggcctcgatacactctacaa
    356 2611934 SLC6A6 YES gctatgacctcgctggggagctacaacaagt
    357 3127807 — NO caaggaagcgagtctccgtgacacgtggtacaatatcatgcagtacacacggaaccagaaccaagaagaaatggctggaaaagatgaaagaaaaaaaa
    agttgatatagtctcaaatgtagtgaaaaaacatcaacttatagattcaaaaagttcataaacccctcataaaaataaatgtaaagaaaaccctacctggacaca
    tcatagtcatcatacagagcaaattttgtgcattcacaggtaacaaagatatgaacgacagctgactcaaaacaatggaggctcaggatgtgtgaaatggtga
    aagaaagctgttgactcactattcacactcattgagaatatcctttaaaaatagtaagtgaagacgttgtggcaggttgaactttcc
    358 3909039 SPATA2 NO agggctacatcaaccgacctttcgggtttcacggtgaagaagtactaacgcattgatctcagaggcggaggcctgcacttgaccatgtaggtggcagagat
    cgtgggctggctgtgtccacgtgggagttcacttagcgactcagatatctcaaccaatggctgctttgttgtctgacaagggagaaggtggcacttccgttca
    gattcattttgctaatctctccactccctgttcagttggttctttttttggggttttgttttgttttgttttgttgttttgttttttcctttaaagaggatttctgtctctgggacc
    ctcgctgcacctacccctcccattgcaaagccaacttggactgggaagggcccttcaggtcaccaaacatccacctggagcggcgagctagaggcctgtt
    ggcttgtgaaatgagccctcctgccacacggggcctctcccaaaggctcatcccttggccgcccccttcctaaacacaaggatccccagctggactcccca
    ccccctggcttccccacctctccaggtgtcaaaggtgaaccgagtccagtattagctgaatgtcatttcgtacaccacagctcagtcagcccatggccttcgt
    gaactttgctcc
    359 2412620 NRD1 NO gtttctttgaggaacgcagcctgaa
    360 3220615 KIAA0368 YES gaccctaaactactgtcaatggcatattcag
    361 3521230 — NO tgctgctgacatcacgggccctgggtt
    362 2327492 SNHG3 NO gacaatctttggcagacttggagcaaaagattgaggtgcatttcatgcctcctt
    363 3557645 AP1G2 YES tgtcaacattcttggtcgcttcctactcaacagtgacagga
    364 3709227 — NO tgccgtcctcagtgaatcacagcagcttcaaaggactcaactggcaagatttcccacag
    365 4021348 ZDHHC9 NO gagagcaagtaagctgtcccttttaactgtttttctttggtctttagtcacccagttgcacactggcattttcttgctgcaagcttttttaaatttctgaactcaaggca
    gtggcagaagatgtcagtcacctctgataactgg
    366 3030989 ZNF862 NO agggcttgaccctgcctagatcctccttaccaagaaagggctgaaaagagagggcatctggcatgctttttgccacttctgtttctaggttatgtacttcatgga
    atatctgggcattgcttagaaacctgtgtcataaattggctttgggcaagaggctttgagttggaagaaaaggtggaaagaaagtgcttgggggcggagttc
    agggatttgacgggattgccagcgcttccaggccgtgtcatccaagaccagtgtggttgtgggcacattagcttggagacagtggcagcctcttgggacta
    acatcttt
    367 3035657 — NO agtccggtggcttagatgacaaatggaggtagaggacgcattctcgcctgttatttcgatttttttctctcctcaccctgaccgtcacgttctcaccttttccacctc
    aatccccagtcacactagcttcccaggattaaaatggtctct
    368 3626930 — NO tgctttcacttaaggcagggctgttgagtcggtgaggggatgagggcatctcaaaagaaggctggctttcaggattgcacagagatgttcctgctcccagca
    gactggggtaaaatttcctgggaatgagggcatttctga
    369 3091396 — NO caagtgagagtgattttgttacatgggatacattgcatagtagtaaagtctgggcttgtagtgcaaccatcacccgaata
    370 3323928 — NO cagtgcatcccggaaaaaagagagcaaa
    371 3326853 TRIM44 YES tggccaagaggaagtgtccggaccatgggcttgatttgagtacctattgccag
    372 3402333 — NO caaagtcctttgcaagtctcacccttaagcgcgtggggactgtgt
    373 3796317 — NO tcacgttgctggctaccctcatatgtgtgatgactgttagttgtacaattacatttaagaaagaggattacattgctagctggaatttcttctactattataaaaatag
    aactgttttaccaacaagtctcttctccgagtgggacttgatggtaactataactgggatagggcaaatcaacgtcatgggtccacaggttttgctttaa
    374 4020467 — NO tcccaacaagttgaaccttgcgttacgataaaagcagatgtggcatccaatcctaccacccagcaaagagaaaccccaggcattcaactgcagc
    375 3180404 — NO catcgctgtgtgcatctaactcttgattcacggtctgaccgacgccttggtttctggagaactgccctcgtttatggaagagtcactgtcatcaggagccatccc
    agggagaggctcagtgggaagtgtaaaggtggagcaagtaaaccggctccagaagagaaggcgaagaaggactatttctgtttagatttgcttaaccgca
    ttttcactttcttgggaacccctgatggagttcaaggtcatagaagagaagaaatcagacactgctacaggactcttgctcttggtt
    376 3781848 — NO gaggaagtgtctggtccggtccctagagcatggcaggtatgcactcaatgct
    377 3868844 KLK11 YES tcaaggcattatctcctggggccaggatccgtgtgcgatcacccgaaagcctggtgtctacacga
    378 2396267 — NO tggggacggcaacaccgcgctgcaagtcgttatcattccg
    379 2862752 GFM2 YES tggtggatgtagtaatgaaagaaaa
    380 3869672 — NO ggagttgcatccttgcttgactaaaatggaagccgtattgattttgaaatgaaaagcttcatgatgtagcatctggactttcactgtcc
    381 3876038 PLCB4 NO taaggatttcaacacacgtaaggccatgtttctgatgttatag
    382 3879228 — NO ggggagggacatgacttcctgttacgggatgaggaagtagaggttcatggagga
    383 2399914 — NO ttagacttgaaagaacctcgttcacctgccacatgctatcctagggaattaatagcttcccatgtggacactcactctatgt
    384 3142073 — NO ggggaacgaagcctgacaactcctaagtttctggcttctacaaccatttagtgaaggtttcattaatggcaggcaggagtacagttttagaaggtctggactgg
    agagacatttgggggaatcatccgtgagtatcgagagttaaagacatgccaggaatagtgtatacaattaaaatagacaggggcttgggaaatgccagttcg
    cagatatatatttgtcataagtgaactaaagaaaaggtatatggttggatgagcttaaacccagcatg
    385 3777286 ARHGAP28 NO cgcagttcatgacttgtaccagtgaaggtagcaaggtctgtgtgttggtgatgaatttgcaggggatcaggctgaagaaacaagacttgggagagaggatgt
    gagacctttttatgacatgcatagagttggcacctcagcctttgcatggtagggagctagctgaaggctacctccatgacagatgtacactttgaaaagacag
    gccgggtgcggtggctcacgtctgtaatcccagcattttgggaggctgaggtgggcaaatcacttgaagtcaggagttagagatcagcctggccaacaca
    gtgaaacctggtctctactaaaaaaaataaaataattagccaggcatggtggcgcacacctgtaatcccaactattcgggaggctgaggcagaagaattgct
    tgaacacgggaggcggaagttgcagtgagctgagatggcaccaccgcactccagcctgggcgacagatcaagactccatctcaaaataaaggaagata
    cagctaatctatatttctttcaccagagatcaccaccactaacaattcatactggtcgtttttccctgaatgttttacctatgtaggaaaattttacatcccaatttttaa
    tttaacactatgaaaagcatttctttttataataaagacactctattagtatacttttgatggcttcaaaactacttttgtatagatgcaaaattaaaatatcaaattgttt
    cttttgtttgtttgtttttttgttttttttttgagacagagtctcactctgtcgcccaggctaaagcacagtggcatgatctcggctcactgcaagcttttcctcccaggt
    taaagtgattctcatgccgcagcctcccgagaagctgggactacaggtgtgcaccaccacccccggctaattttttgtatttttacaaaacacaaagagagac
    ggggtttcaccatgttgggcaggctggtctcaaactcctgacctcaggtgatccgcctgcctcagcctcccaaagtgctggg
    386 3851492 — NO ttttttacggattcagtgatctggacgggcacatactaccat
    387 2712928 — NO gtgagtaaaccatggcgtgtttgttggccaaaagccgcaagtctttgaaaaggtgaatcatcacttttccattta
    388 3060349 — NO ctctggaggcttcttgtcagtactagaaactaatacttggtgaatatccttttctgcttccattaccttgtatgaaactggttccatttatacactgagattagaagca
    ttcataagtgatgcggcaccacaaacacagaagatcaaactactcacagtgtggagaaccatgtcttttataagtgtgatgtgcctaaaaccatcatc
    389 3504762 ZDHHC20 YES aaaccccaaaactgtccaggcatgg
    390 3543824 — NO agtcttttataagtgttggctatcattttttctcatctatttccttgcttctggttttgcacactttaccatccacactgccatcagagtgatcacacctctcttcagtagc
    tcccatcatctactgcataaagctgagactgttagctagactgttaggcacctttcccacacgatctggctctgccccacttcccagcctcagcccacatggct
    aaacaa
    391 3781951 LAMA3 YES gatttgggcttaccacctactgaccacctccaggcctcatttggatttcagacctttcaacccagtggcatattattagatcatcagac
    392 3216926 — NO aacactgatctccacgagcacaatcatccaaacggagatgggaacccctgttctaactctctcagaggcctgaa
    393 3448246 — NO ctctttggtatattattgcagatgttgttatttcacagttaggtaaattagacataaaaaggtcaaacgacttgaacgtgctaccataaaaggtcagtgataaagc
    cagaagtcatttctcagtgtccatcataagccacc
    394 2693224 OSBPL11 YES ggagatggctgggtttatcataaaccactttggaaaataattccaacaacacaaccagcagagtga
    395 2672926 SMARCC1 YES tatgttcatgcggatgctcctaccaataaaacactggctgggctggtggtgcagcttcttcagttccaggaagatgcctttgggaagcatgtcaccaacccgg
    cctt
    396 2914136 — NO ccatccgttcttttagctgacttgaatgactctaatgcagtgggttgcaggtttggctacttacctatgtactctgtaaacatccagaggcccagggatattctga
    gccactgtgtgtgaatggagtttggccatctgtagatttccgcagtctctccaggtgatcgcactgtgcagcctcattgctc
    397 3210858 — NO tttgctctgaaaggcagtttctgtataggttcctccgagtgaagatcagaatgttatcagacactggctgtagctcagatgaca
    398 3853401 AKAP8L YES acttggaactctgggacaaatagag
    399 3605225 — NO tggacccatctcagcagtgctcaaaccaatgcccaaactctcctgcttaggacacttctccactggccaccctgaggccaccacacctcactggccactcct
    cctctatcttctctgctggctcttcctcctctatggccacctaaaggatgggtgttacacactcaatcct
    400 2377461 — NO tggagttggccttgttaactattaaacacaaaagcatgtgatagttacctgagagatccatgcaggggagagtccaggggaaggtgactgatcactgcttcc
    cagggggaggcagaaaatgcttcctggaggagatgatgggtggattaaggaagatgagttgagcaggagttgtagctaccagccagggaggaagggta
    ttcagagcagaggaagcaaggtgagcaaaggcaccaagatgtgacactactggactgccaagcta
    401 2934549 — NO gtgtgctactggcttatggctgatacgtaagagaatctcatctatctctaaatgttctgccttaagccgcacaaagga
    402 3185031 — NO tggcacatgtggattctataccttaattaaagccactcccttacatacacacatttaggtatcgccagactcgcctgatgaggaataattattctttcctccatattt
    cttaactcctgtcttttccatgaaacggcttggcattaaactccttcccaga
    403 3560964 — NO gtaatgtggcggtcaaaaccggcgctggaaccacgggacatgtt
    404 2732616 MRPL1 YES aacgtggagccatttaccagtgttcttagtttgccatacccatttgcttccgaaatcaataaagttgctgtatttacagag
    405 3150536 — NO gccactcattcatggttgttctatgttccatgaactctaatagcccaacttatacatggcactccaaggggatgcttcagccagaaagtaaagggctgaaaaag
    tagaacaatacaaaagccctcgtgtggtgggaactgtggcctcactcttacttgtccttccattcaaaacagtttggcacctttccatgacgaggatctctacag
    gtaggtta
    406 3774169 — NO atcgctgtaccattctggggcactggagatggcagctgagaagcagagaagctggagacctgaagcctccacccttggctgtggctgccgagagaggcc
    cctgcagagggagccccaggccacacccagacaccacagccagctcacagtgcggccagagggcacaggctgcttggggggtgagggtccccattc
    ctgccacctctcacagaccatgacccacagggctgggggcttcccctgggagaaagtccttccctccccatggcccagccctggggaaagaaagcagag
    actaactcagggactgcagtaggctgaggacaagggaggtgggcttggggtgaaggccccccctcactcgcagagaagggacactaccggcagtaga
    ggacagggaggcaggacgacggcagttagagacgaggcgtttcaggtgaactgtatgtagtgttactccggacgtgagcatggcctgggtcagtcgaat
    gaaatgagctgggcctcgctgccctgtgccggcggcccctgtgcctgcggttgctgggccacggggggctgctgctgggggggaccgccagagggtg
    ccatctgtgcaggaggaaagcaggcatggccctggtcctcccttccccagcccagggaggaaggcttttgtcccagcagagccacagacccacaagtgc
    ttgtaatccatgtccacggactgcagctcatg
    407 2987860 — NO cccgtgtttcgtgtacaacatatgatacatgtgacagttgacaagagtgcctgagtctcagagcaggaagagttatcctgcctccacatgcattgaagggaat
    atatgtcacacgttactagccaggctcagaggagaacacatctcatttacaagttcaaatctgaaagggagaaatgtgctagtatttagtggatcttgaggaaa
    ctagggatgtgttacccatctgtgcaggaacattagatctagatggggctctcctagtcaaaacgctga
    408 3829652 — NO atgtgactttacaaccctcggtgtcctcctggctgctgggccccagcctcctgactgttcagctcacacacgtgaacctaacacctgccttggtcccctgctcc
    atcttctagacaactcatgctgaggaccagcccacaggaggaggcctccgagttctctcttgacgtcttcaccttgaccattttttgccaccattttagtctgtcca
    ggc
    409 3900228 C20orf74 YES gaccaaagcctgtgtacattactaccactcgagacaatgagaacatttacagtacaaagattccatatatggcagctcgtgttgtttttattaagtggattgtaac
    cttctttttggaaaaaaagtatctaactgcaacacaaaacactaaaaatggagttgatgtattgcctaaaatc
    410 2858280 — NO ataaaatacaaactctccaacaagaccttttggccatcaggaacgcagca
    411 3088555 ATP6V1B2 YES aactgcccggttcttcaaatctgac
    412 3850502 LOC147727 NO gactgtttgccaatggttgtatttagtaagatttgtagactctgtttttcttttgacacagctgcaaggccaacagctgtgcaaagccacaagttatgctaagtcag
    cagttatgctatagattacatgacctgtgactgtatcattaactgcttttgttttgcttctgtaagtttgcctataaaaaccacactcagtctttgttcaatggtcagctt
    ttcagatacaaatccactgagccggtgtacatctaaataaa
    413 3946288 TNRC6B YES tgtggacaagcgagcgatgaatctcggggattttaatgatatcatgaggaaggatcgatctgggttccgtccacctaattccaaagacatgggaaccacaga
    tagtgggcctta
    414 3430162 POLR3B YES agtctggttgaatatttagatgtgaatgaagaaaatgattgtaacattgcactgtacgaacacacaattaata
    415 3751732 — NO gaatatgcatctttacaagcatccacag
    416 2347259 — NO tggctgcctgacattattgggtgct
    417 2421262 — NO ctccctgcttggcttgatgaccttt
    418 3886689 PABPC1L NO gtatggtcttgggtttctgctgagaaatggcttgtaggtggggggttaaagttcctcacacctctcctgaacgggaggaagctgctgttcaccagtttccagtg
    ctcaatgcgggcaggtggggcatctgtgcgtttggtaaatacatgatgtt
    419 3951993 — NO ttgagcccagtggcgggactccacgacgtagacctctctccttctgcc
    420 3966982 — NO ttcctgctgaccaacctaattctggtttcatacagggcagccaggtgcccacctaaaagactgcacttctcaacttccagttgtttctatggataatggttggaag
    cagaaattgggttggggcttccagataatcccccctcacagggactgcttcaagagaaagggatgccctttggttctttctcctttccactgcctggaatgtgat
    gtctgacactgtggcagccatactggcataatgaggccaactctctgccatgctaagagtggcagagctgggaattgaaaagagcctgctagccttgggtt
    gcttccccttgatcggctcattacttggaa
    421 2756515 MFSD7 NO tgagcgccttgtagtccaggttgcccgccacatcgatggaggcgaactggaacatctggtccacctgcgggcgggggcgaaagggctccttgcgggctc
    cgggagcgaattacaagc
    422 3261869 — NO tttttgtattctagtcgttcagccccctcccctcccatcttccagcgcttctgaacaactcctactgttctcttcc
    423 3391839 — NO ccctatagattgtttgaggaccctattaaatattgtatagcctctaggaataagcctttccattgacttgctgtgataaacagatcttttgtcagcgactcttaaaata
    caaaacagccttgggcagtagagtaccac
    424 2437406 C1orf104 NO gcttccctgacctagacagtcctgactgatggtccaacctcaatcccacttatttttggctaggccttcctgggagtcataaaagagatgaatccattctagagg
    tgcacagcctgtctcttccctcacaaatgtcagtccccaagtcattctgatccaccttcctaatatttttgccacctccaacttctttcaagatgaaaaggaaatgt
    agagaagcaaggtcagggtagacacttaatcccactgactgtctttaatccactcttctccctctcaacctggatgatctccacactcctatccatactcagata
    caggatatattgttcccctattatgtgctaagcactttcatatcccttgccttgcttaatctttacagtcctgtgaagtaggaattttatccccagctgaggaaagag
    actgagcgagaccgacttgctcaaggtcacacagtttttcaccaggggtagcagtgttcacg
    425 2802671 — NO tagagttagagtcagggccctggtccctggtgctctttcctggtcgcttctcatagccaggacgcttgcttacattagttctcaaccccactgggaccaatcatttt
    tattgccaatctattttggggctctgttctcgtggcaataaatcattctttcagagctccctatttaaccttgtgagagcgtgtgtgtgtggtggaggtgcttacata
    aatgcagtatttttaacctgcctggcacgctttaggttggcgtta
    426 3415835 ZNF740 NO aagtagggcacgctctcagagaccaggatagagagtcagggaacctgggaaagagtagtgccagttccgggtaggctgctgcaccaggccctaccagc
    tcaggctataaacagtctgctttgccccaagtttttccgtccacccccaacagccttgtcatcacttagctactgatcacgcccatggcttgacattggagggt
    tacattagtggagtccgccacagcttcgaaccctctccccagatgccctttgcctctgctgtggccctggggttttatcaactg
    427 3764797 — NO tgggactgtcaatcattggctctgcctctctgaccacagactaaatatatgaccagtctaacctgttaagcataacaatatggacactgggagagaagcctctt
    gaaatcctttgctgaacggatcatgtacaagctgccaagagttcatctc
    428 2431813 — NO tgatgcacagtttaggagcaggaaagccatgtcttggatccagga
    429 2468734 — NO tgcccaagtccttgaatcctacagaccttgctaatggctccgttcacgacacccaactggtcctgaactcttaggattaacccgtttgcttatggctgaggaa
    430 2512616 — NO cctaactaggagagtgttttcaagggagagattgctatagcatcagcctcagggtaggagaatgagcttaaccatgagatttaggtttgagcatgtttactata
    agtaaaaagcattttcctggagtctggcaaatattgtggaagatgtac
    431 3242348 — NO aagagaatgggcaaagggagcgggtaggatggcggccgcaccaccagccacggactgggagaggcccttctgtgtttccagatgagaagagagctca
    aggaatcccaggaatagactccatggaaaagaatgaaaaaaatcagagaaaagccaaatatccaaaagag
    432 3316358 CD151 YES tgggtgagttcaacgagaagaagacaacatgtggcaccgtttgcctcaagtacctgctgtttacctacaattgctgcttc
    433 3473828 TAOK3 NO tcccactagcgatcagctgacattcctaactgaaggctgcaatgtgttgcttattcattttgtaccgtgggagctgcggggactagcagagagctaaacta
    434 2453074 C1orf116 YES cccggaagctgccacctaatattgttctgaagagcagccgaagcagtttccac
    435 3144603 C8orf83 NO caggaatgcaagcactgctacctaactaaagaccttggctttggaaacatcttaccccttggcagctctccagagtttagacttggcagcatcaaagac
    436 3035937 GNA12 NO agcactcctcccacgggcctgggaaggcaaatgtgttttctgaactgtgttgagaccgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgttggggtgt
    cttgtgaagtcctgctaacctcttgtcagcagaatattcgagaaatgc
    437 3854106 C19orf42 NO cttcaaagtggagtagtggcacagagaccatatggcctgcagaatggaaaatgtcacctgtttggcctcttaccagaaaaatttgccaaccgctcaactagg
    gtgtgatggagaatcccaaggtgtcccttccctcccaaagccactcagggaatcatctgtacc
    438 2604179 USP40 YES ttgcaatggggagtgacgttcaacctgggacagaaatggaaatcgtagtagaagaaacaatatctgt
    439 2625696 PDE12 NO tagtgggacttttaagcatctctgaaataaaaaacttctttttacagacaagcattatagtttgagttacagacaacagtgtgtatatatgtaatatatatatagtaaa
    atgaaatttaaatatgaagccaaactttttaaaattagaaactacaaatggttatactgattagtgtctagcctagagtggtaaccatgctttactaattcagttatg
    aaatacattatttataatgcattagctgtattagctgttgcttttttgatgttcaggataactatgttatctcatttctgcatttaattaatagctcgagtattaaaagccc
    actcccttcaagaaaagctttgattttccccagtcatgaaagcccttgtttcaaattctttaatctctgaacctagtatcataagaatttcctattttgataacatctgta
    ctttcatattctgctcactatcaaatgtattgttaacacttagtaagtttgaaaatgaaggggttttatctgcatttgacattgaaccttgaagtactttaagtactcca
    aggggaaaattaaagtggaagtttcttcggatcttgttta
    440 2410545 POMGNT1 YES catgtggatgcggatgcctgaacaacgccggggccgagagtgcatcatccctgacgtttcccgatcctaccactttggcatcgtcggcctcaacatgaatg
    441 2545098 HADHA NO atgtgtgtgcagaattctaggcagcaccttagggagggactgggatgagagaaagtgggacctggtgggctcaaccacacacacctgtctgtgcagatgc
    tttgcccaggcttctcaccacggtgtaccgggatatta
    442 2749561 ETFDH YES atgctggtgccgctagccaagctgtcc
    443 2849125 DNAH5 YES ttcttcggaccttgggagcagcaaaaagagccaatccaatggatacggagtccacgattgtcatgcgtgtactacgggacatgaatctttcta
    444 3022356 — NO gaacacctgcccaatgtcagctatacttcagctctcatttgcactattcaaacttataaagttgaagagcaacctacgcctgttg
    445 2474026 — NO gtggtagcagttttccagatgtggatgcttcatgatctggtg
    446 3160004 — NO tgctttgttgagggtgtaaggggaa
    447 3795785 — NO aatgggaatgaaatacatgcctttttgtttttaggggtgctcagttataaatatgaaaggctgagaaaatgctaattgtacagtaagatcaactggacttgttttaat
    aagacaataatttgaaattagtaaactattttatacaaatagtgctaaaactttggaaggtcctcaacctcctgg
    448 2990169 — NO cttgggtatcacacaagcattactgacattgagttcatggaaaatacagaaaatatatacaaaattaatgccacagaacatgacaaatggctgtgaggggag
    gacttttgatcaattgcttgatcttaaacttactttagaagaggtggccagtgcctgccaattggctgccatgtggatacttcttatgcttgatcttaagtgcttttgt
    gtgtgacagctctacacaattccctagttaagagttacttctcaccaaccaaagg
    449 3858632 — NO gctgactgcagattcaaccttctgagctcacgaa
    450 2481311 KLRAQ1 YES gctgagttgcaggggaagtaccagaagctg
    451 3726479 RSAD1 YES tggccctggggctacgcaccgatgtggggatcactcaccag
    452 3847164 — NO ccatgcgaagtaccaagccctagttgttctccatccaggaggccgtgtggctcatcccttacccacagaccctcactcaccaccttcgtccctaccatccaca
    gcacccgctggccctgaagtgattccttggtcctggacctggggttttgcattttgtctctgaggaggaggtcgcatggagggggaggggatggggatgtg
    ggtgtatggacgggtggtgggtaggggcacgtctgatccactgtcacggcacctctggtgagttgtaatgcgttcgtgactccaactgactggtcttcaccta
    acctgcttatttctctgccaacacctgggatgggggtttgtaaatccagcagggctca
    453 2945519 GPLD1 YES cttcccatgaccacacacaggagtggggaaaccttacttgtacttcatcggttttcttccaaatcagcgacgggagtaacatttttattcctatcaccaaaccac
    ctgaaaaatggactcctaaacttcctcatatgacatcacattaggctaatcatgtaccctcaatatcatcagggtaagtgtatttattctgttattattacatttgtagt
    gcaagagctggacactctagaatcttccatgcacactactttgggagg
    454 2960606 — NO ctaaggctggatctccgtttctttccacctgctccaactgtacccacagctgtgtctgactggctgccgtcattatgctccagtgtgtacatctctccactgacact
    ggtgctctt
    455 3275073 — NO gaggaggttgactcaggagaacttggg
    456 3392454 — NO gatgctgaattgaactgggatcttcttgtctgtcaagcccttgaacagctttccctttaagcaacaaagatgacaagtttttgctattttggattagtgagagtgtac
    gaaatggtttccctttccttccaggcaaaaataccaacagaatctggcttcggaatgaaagtgctaatttcatttggtgactttcagatttgaaatacgggcttga
    acaggcattgtgcattagtcagctgaggcagtggaggttatttttacgatgctaattattatttcctgacagtgatttactttatgttgtctactgttttacgcccccaa
    actagccattgttttaggaacagaattggttgggttgtcatgctcttttcaaagacaaatcttactattttatgcatagaaatactttcctgtaataaagaagaaagct
    ttattgaagagaatcttgcatatgaaatgtaatctggataaatattcaaaactaataggtttatattttagtcttgatttttaaagtatatttttctgacatcctaaccacc
    ttgctttatgtgcattaaagttaaatctgttttactgggatgcggctgaat
    457 3428624 MYBPC1 YES catttgagatgcagatcatcaaggccaaagataactttgcaggaaattacagatgcgaggtcacctataaggataagtttgacagctg
    458 3869530 — NO ccattacagcagcaggatccagtgacccgggatgctcacatctctccctgacgtgggcggagtagccccttcctcccaaggtcactgtcctgtccaacccc
    gtgctcccctagcccgttgggaggtggacagtgagacatcttccca
    459 3180781 — NO tattgggagtcctgtcagaagctgcctgctacagggtctttagctttccttagattttcaaagaggtttgtgatccaagaagaatagagttttgaatctagattttat
    actaaacgatcactttagattttcaggagtgtgtgcctagtttgtgattaagtta
    460 3319155 PPFIBP2 YES ccacagtgctgctagtaatgaaacctaccaggaacgcttggcacgtctagaaggggataaggagtccctcatattgca
    461 3428631 MYBPC1 YES cttgatcctgcatatcaggttgacaaaggaggcagagtgaggtttgttgtggagctggcagatccaaagttggaggtgaaatggtataaaaatggtcaagaa
    attcgacccagtaccaa
    462 3435265 LRRC43 YES agccgaaagccgtgattccgatctacgaaggcgattaccaccctgagcccctgaccgtagaggtgcagatccagctgaaccagtgccgctcggcggagg
    aggctctgcgcatgttcgccgt
    463 3697431 — NO ggaaagcggggcagacaaagtatccaaaagt
    464 3928125 — NO gggcactcacccaagtaatgtccaaacaatatttttccatgtcccccctcccccagaacacacacaggcaaaggcagagatgtttactgtgaggtcacatgg
    catgaagcaaatgcagccttatctgtttattattacaacagccagttagcattggcaaatgtgctttggttacaaacatggtttctgctaataatttcatgaagaag
    cttttaggatatgtgaccatttattcttagtataatcaatcattgaaggataaaaatcagagtataaaagtttatactctggcaaatataaatacatgcacagaagttt
    ctgacagtttaaatttgagcatatttgaaatattaaaggcatgaaatttaaaaatacacatacgtgaaactatggtgaacatgttatgggtttgtcccatggtttaac
    tctgctcagcccacgattcttagctgggtcagtcaatagtctatttttatcattttctaccctgttgtacagcatgatcatatc
    465 2769166 — NO gtggggtcagagaagatattaggaaa
    466 3545551 C14orf178 NO tggcgcatatcagcagacggcggtcactactgtggctcatttaaatctgtgttcagctccgggcctcttttttcaggaatccttgtttcgggacacccagtggaca
    467 3899443 — NO gacttacctggagagcgcgagaactggtgtagcttacgtggagtgagaagagatggggaacatgtgaatgaggtcagagcggttgcaggaaacggactg
    ctgctgtaggccattttaaagacttttgattttcctctgaactgccgagtattttcagcagaggagtaacatgatctcacttatttttaacgggcttactctggctgc
    468 3182036 — NO aagattgaggagaagagtagtgacaa
    469 3063084 — NO gagctgggtacagagtgcttcatgctgagcctccgggcatgcttcgtgtacactccgcacactctccacacacacacgttacatggcagcagtcc
    470 3387617 MAML2 NO gaaagcctgtgtatcgccgtgactccgggcgcgagccagtgtcagcaaagcggctaacaacagacgagaaagagaaaggaaaatacaagctacttttttt
    ttccatctataaagcggagcaaatacaggagatagaaccagattgcttattgcgagtccagaccctcagatccactggccggggatggaatgtacaaaagt
    ggacagaaaagtggctggacatgactcggtgcaatttgctggaagtttgtaagtttgaccatcgtttgtaaattactctcggaagagtttgtctctcttgatactgt
    attagaatagagccgggggtgaggaatagaaacgtaagcgggaaagaaaaaaatgtgttgaaggatctctctcagtggctagcga
    471 3566496 — NO cctaagtcacgcctctggaactttggcaagttctatagaagagtcagcagcaggtgtgggtcaaggtcccaattcacttcctgcagctgtaccatcccttcctc
    gttctgcaaattttctcta
    472 3088581 — NO tgatctcatgatctcaaaacaaaggg
    473 3120740 — NO gagcttggtttttggtcagaagccaagaaaaaagatcggagaagaaaagaaggaatgacctcaacttgctctgcacggaggacggggacggctcagaga
    taaatagc
    474 3399570 NCAPD3 YES cctggacgccagtgagttactctcagacacgtttgaggtcctcagctcaaaggagatcaagcttttg
    475 4010188 SPIN3 NO tgtatcaaagtaatgtgtccaccggtgtgagcaccagcaactcacttcttcctcagacatctctaaagctggaaagattttgagggacaatatggtttccttcac
    cccacaccaatgttatgaatgagaccagcagaccaacagcaaacacctaga
    476 2638236 — NO tcagctctgcagccctacagttaccagctaaccttg
    477 3683253 — NO tgaatgaatatggtccctggggctaaaagtaagaaaggagaaaaaaataaagcaacccccaaatttgatgagaaccctatagtccctgactgattgtttcctg
    gccatcatcatcatcagcttcaactttgtcaacacacccttaatatgggtgtaccttgttttacagtttgccgagcactttcacacccattattggatatgacacaca
    acccggtgagagtgctctc
    478 2502720 MARCO NO ttcacttctctgctcccgaggtgtcctcgggctcatatgtgggaaggcagaggatctctgaggagttccctggggacaactgagcagcctctggagagggg
    ccattaataaagctcaacatca
    479 3378495 — NO aaaactgccctggaggatcggcacg
    480 2642712 — NO atcattttgctcaggccacggccact
    481 2798891 — NO catttcccagtgctgtatactcctatctcccagtgctgtttgctcccatttccca
    482 3428610 MYBPC1 YES agagaaggaggccggaactacaccagcaaaag
    483 3691119 — NO ggtctcgcgcgccgtcttctcgagag
    484 3821139 LOC126075 YES agaccattgtgatgattcccgactcccagaagctcctgcgatgtgaacttgagtcactcaa
    485 2349300 — NO gagaattgggaatcaagaatcagccctgtttccatcttagccacaccaacttatatctttatgattttcaaagcttttgccatgtgattctgcccccacaaaggcat
    cggtatttccta
    486 2638933 — NO tgcggatctccaaagcctagggatttttccgtaaaagagagtgggccgttctggttacccttttattagaagggtattccaccacagagagccggaggttttcc
    agatgtgtgtaagagagcaggtgcgcaaggcaagcaaatgagcgcaaacagtattatggaaaacatttgagaagttagctccatgaggactgtgggctcc
    acaagaggactcgactgggtagcctggtctgacacaggtacgtgaaagcagagtattgcttcaaagctggaaaccttccataggagcctcacactgttgga
    agatgtactgctgctggttaaggtcaacctggggtgcaatgctgctgtcttcatcttcggtcccgaagtaatgctcaataagatcaaaggccttttggtagatct
    cctg
    487 2661085 — NO ttcctcacaaactggccttccatttccagcagaggcaaatcaaattgccttttccgccctcatctctttg
    488 3037551 — YES ggcagtgaggagatcggtaacttgggagt
    489 3215176 — NO tggccgtctgtacagaacccacctgcaaccaccacaccctgagcccatgtggccgtctcacctctaagtcacccaa
    490 3410744 DNM1L YES gcattacaaggagccagtcaaattattgctgaaatccgggagactcatctttggtga
    491 3439960 — NO cagagcgccagcaagcggccacagaa
    492 3461262 — NO tcattttaactctgtgcagagtatcaaatccatccatt
    493 2316284 — NO atgccaacgccgacgtccctgcgggg
    494 3882865 — NO tcctagcagcacacatatgcagctctt
    495 3685651 — NO aggggagcttcgtgatcctgtgcaccaagtctccatgccccttgttgtacccagagcaccatgctccccgccagccccctgtccacccctgcttagttataca
    gccattgtccgttttgtgtagaacagtggctttcaagcttttgtcaccatgatccatattttaaattgcaaccctgttccctatgatacct
    496 2854135 — NO ccgaggactgttgaattgtggaacatctggtggaaaatagcaagaggtgacagaaatgctaatggggcagtgagatgtagacttcaggcagaattgttgtac
    ctgtcgagttggag
    497 3314277 — NO gtctaaggaaaacaacaggctgcgcgaaatcagccctcagggtaacactgaacctggcgctcttccggcaccacacaggaggcgacgcccgggaaag
    aagactgagcggctcctgtctgaagacgtctccatcagtccagcca
    498 3724236 NSF YES tgatggcgtggagcagctaaacaacatcct
    499 3746906 NCOR1 YES cacaggtatgaaacacctagcgatgctattgaggtgataagtcctgccagctcacctgcgccaccccaggagaaactgcagacctatcagccagaggttgt
    taaggcaaatcaagcggaaa
    500 3909730 ATP9A YES gaccacttcagattcgatcgtatgtgtacgcagaagagccaaatattgacattcacaacttc
    501 3428460 UTP20 YES ttggttgtacagttggcacgagatctgcagatggatttctacccacactttccagagttttttttgactatcacctcgatcctggagactcaggacacagagttgtt
    agaatgggctttcacctcgttatcatatc
    502 2751975 GALNT7 YES gggattatttgccattgaacgagagttcttctttgaattgggtctctatgatccaggtctccagatttggggtg
    503 3894100 C20orf96 NO tcccagcacctggagccttggatcatttacttccaggaccggatctccattcagaccctgatctacagtctccctgctccctctgcccttcctccctctttctttcc
    ctccctccctccctcccttcttccccccttcccttccctcctccttccttcctcctctccctccctccctcctttctttcttcctgtggttttttcctctcttcttcccttcttt
    ctggttggtgctgctgggccaggtgggaatttctgatta
    504 3908236 — NO accttcagggtgctttcacaaatgagctactggagtatttttcgtatctttggttgatgaaaaggctcatctccaaacttaatggttgtaccaaggtgttttcattcct
    tcaacaagtcactgagtgctttcttggaacacacagccttgcactgggggttatggggagggaggaagaggctggacagggttactgcatactgccggaa
    ggagattctcatttggctgcagagtgtcgcaca
    505 2407923 — NO gaggtctcccgtcactgggcatccagctgggtgctacggccgtggctcctgccttctgcagccctgtcagggcccaaggccttcctcatcagcacttgctcc
    agcctactcactggagttgtgttctgggtgggtgtgtagaatactcgcactcctacttggggcatcagggagctctctagcaatttc
    506 2571603 — NO ttggaagctaacctgccacattgacttaactgagtgaccccagttccaaggcagggcctctacaatttccagtttatctattgtttcctgtgtaagagcagatact
    tactgtaagtccgtaagtgctactcgtaggtcaaacaaccttgatgatatcacacttcaattgtcttataaatcccatctgaaccactcctaccctatggtatatga
    gccctgggtttgggtgctaatgcggggatccaccatctcatctcattgccgcctgagacacctacatggctt
    507 3634205 — NO agcagatgtcagcatccgggtcacctag
    508 3746967 NCOR1 YES ccactgtataaccagccatcagataccaaggtgtaccatgagaacatcaagac
    509 3675286 WDR24 NO ccgcctggtcttgtgcccgagacgggcggaggctggaacttgagacctcaataaaggaagtagag
    510 3809651 FECH YES agctggcaccattcatcgccaaacgccgaacccccaagattcaagagcagtaccgcaggattggaggcggatcccccatcaagatatgg
    511 2793478 AADAT YES catattgagcagaggaccaaaatcgatgatctccttggctggtggcttaccaaatcca
    512 3139792 — NO tgtgtcacttctgcattgcccagtattttgagttgggggaaaaatgaactcacctggccccacctcctgttccagtgtgaaatactgacacttgctgccagccca
    gcctcctcacataagcattagaaatatcagacagtccactaggttagagcacctcattcatgaggttctgttatttattcggctctcccactaaaatgcagggcat
    aaatttatgtgtctgctctaagactgcagctgtctgccccccctccaccctcctcctgcccttcctgtgtcagtgttacattcgctccccccacttttggtctcaggt
    ctgtctcctttttgtttttatgggtgatttgcagtgattcagacagggcatccttgcatgttggcacttcctggaggttaccaggaggcagccatccttccttggctt
    ggccaggcatccccgactccaccccactttccccttggtggtggaaaggtgggttggaggtgtgtactggggcacatagcccaggaatgttgctctgagaa
    gaggacatgtgcagtagacacaaaaatataaggaagcaattatgttcatcaagccgaaagttgcagattttgaggaaatgtgtttagataccactacataata
    aaagggaaaaccacttggcatttaaataacttacttcaagaggaaattatgatattttcagtctacaaatagagtggtttttaagccaaccttgagtaggtacaag
    caaattataaacagtctgctcaaatgattttactatacttagactagaaaatggctcctcttctctctccctctggtccctatgtcccagtgctgtccctcatatgtta
    caa
    513 3296171 — NO acatggctctggtcgaaatgtgactgaagctttgcat
    514 3470058 PRDM4 YES cttatttagctgacagaccacctcc
    515 2830812 — NO tgggtaacagaacgcaactttgtctccaaaaaataaataaataaattgttacaatgaaagtggctctgtgttagccgggagtgg
    516 3151504 — NO cttagggaatctgtttcggtggctcagagaaggatctgttgccaatcagccgatgccaggtctccggtgct
    517 2978822 — NO ggcaggtccaggaactgggtctggagccttgaaagcagaag
    518 3432174 — NO gtgcgatggaaaaggtatccaaagtgatactccctttgactctgagcatcagttgcccgtgtttcagtcacttcaa
    519 3922854 PDE9A YES gaccaactgcccctgtaagtacagttttttggataaccacaagaagttgactcctcgacgcgatgttcccacttaccc
    520 3225896 — NO ctggatctgccacctcttctttcggctgtggatggccctgggagacacgcctggcctcagatgccccttgacccaactggaggaagggtggggggcccag
    cagaaaagcctgcagcctccctgggcaccgtttcaaagctgatgctgctctccctgctctgggtctcagctcctcccctcttctgcattgttgaccaacagcct
    gggtctgacgcggaagcagaagaattcc
    521 3981141 OGT YES aatcacgcagtggtgcacggcaacctggcttgtgtatactatgagcaaggcctgatagatctggcaatagacacctacaggcgggctatcgaactaca
    522 3040366 TWIST1 NO cctctgcattctgatagaagtctgaacagttgtttgtgttttttttttttttttttttgacgaagaatgtttttatttttatttttttcatgcatgcattctcaagaggtcgtgcc
    aatcagccactgaaaggaaaggcatcactatggactttctctattttaaaatggtaacaatcagaggaactataagaacacctttagaaataaaaatactggga
    tcaaactggcctgcaaaaccatagtcagttaattctttttttcatccttcctctgaggggaaaaacaaaaaaaaacttaaaatacaaaaaacaacattctatttattt
    attgaggacccatggtaaaatgcaaatagatccggtgtctaaatgcattcata
    523 3847114 PTPRS YES gagtaccagttctgttaccaggcggcactggag
    524 3903914 — YES aattccagagaagggtttgagtttggagttttatctgttgtaaaatggccctgcttttag
    525 2545695 GTF3C2 YES attcattatattgacgctggttaccttggtttcaaggcctacttcactgctcc
    526 2468742 — NO ggaggttcgttcataacacaccctagaaaccatgaaaaacatggagagccaagtggagtgagtgacccgagtttacaaagcctgcaatgatcattcttttatt
    acctgacaggatttagggtaactagaaaaacaaatacaacttatcttaggcaatcacttctctatgatctcagggaggctata
    527 3332623 TMEM109 NO ctgtctggggttggctctcttaaccctttctctgctcccagcctgcctcaccagggaaggttggaggggcctccctctggcttctgcatctgcgccagcaaac
    atcactgccgttggtctctcatgacttaactggcttccctctgctgctgccttggcttcctcctaatgctcgtgctctcctgtccttctgaagttgctccttggccaa
    atctccagct
    528 3457669 — NO ggctttatcggatagggacagacgaggtaaggaaggttgtttaatgagaggccttgcttgccagcctaagcttttaaatttgatgccagtggcaacaataaag
    tgta
    529 3575429 EML5 YES gtggcagagatggttgtattcgtctttgggattta
    530 3676065 — NO atgggggacgaatgccggctggattcaag
    531 3541353 PLEKHH1 NO gggccctgcccagataaaattgttggtcttgtctgtaattagtattccaaaggttcaggtggtgttgcatctccgtatcaatgttcagctagtaggtaaagggaca
    tatttggagggaactaactctggcctagctactattatgctcttcactttttcttttttattctctcaagccccagcatcatgcagtcctcagttgggtgcttacgtgct
    cttctcttccttgcagcagtcctcaaggcagggcagattcctctttaaggtgctcgcatgttacccctgggttctgctgacccaacattagctacaaagtgggac
    agtcccacagtgctccctcttccttgttgtggggaagaccgcaaaaagacctcttttgctttagtgactttgttcctactcaatacaggaagtgttgaccagcaaa
    aataataattacaaaggctaagttctgatttattgttcctgactcccgtgtgattaactggaaaccctg
    532 2428388 — NO tggagctctccaaattaagaatgggtagtgacaaactttgaacaggtaacaaacaataaattcaaagtatatttaggattaaacagtcaatttctaaatgggagt
    ctatcatgtctcccctttgcaatactggccttcccaacaggaattctatacttgtccagtccaccataatgggta
    533 2883068 — NO tttctatctcttcaccttacacacac
    534 3686201 GTF3C1 YES agggctcgattccagcttctacggacacctcaagcgcaactggatctggaccagctacatcatcaaccaggccaaaa
    535 2933137 — NO atgagcaaggctggtatctggagttttgataaagt
    536 3098268 — NO agcctcagattctaccgaggcaggcgccccaaataccctccggacgctggcagcagttgcgtgcttcatctgtcct
    537 3804158 — NO cagtgtgccattgtaatttattggtggagtgctatcattggtaacaatatcatataaatgtatttaacccctcctagcttttgaagtaagattcatgttagagctagaa
    tttgtctgggtgc
    538 3570485 — NO tggaggggcaggattacacactgaatcattggca
    539 3666058 — NO ctcttggcttcaagtgattgatcctcccacctcagcctcccaaaatgctggaattacagacgtgagccactgtgcccagccagctcatcttcgaataataacag
    ttttacttcttccttcttaatttttatactttttcccccctttttcttgcttcattgtattgactaggatttctgatacattgttgattagaggtggtgatggaggacatccttg
    tctttttcccaaactcagggcaaaaaaggattcatagttgtgccattaagtaatttgctagggtttg
    540 3692317 — NO acaatgtggctgtgtttgatcccgcgacgtgtcacttggaatctcaatttattgccaatagacgacgttgtcaggcactaattttctggtggcgctccatc
    541 3749798 MGC33894 NO tcgggggtcacaagccaaagccacaccgctagaagggctcaggacccagcccagctcccgtcctcttggtggcatcaagcttgtgtgatatgaggtcttat
    gtc
    542 3965785 MAPK11 NO atggagctgatccagtaacctcggagacgggaccctgcccagagctgagttgggggtgtggctctgccctggaaagggggtgacctcttgcctcgaggg
    gcccagggaagcctgggtgtcaagtgcctgcaccaggggtgcacaata
    543 4051547 LOC100129722 NO tgaccttggcccagaatccaccagggcagggcctgtgaacagggccaacttggggccctcctccgccctctctggatgcctccccttcagcactgggcct
    gccaggcagacagatggacacgtgcttgaggaaacacgggttttatctgggcgaggggttcacgcctgtgctccggggcccctgcccaggttgtgccgg
    gttcagagttgactggctgccagtggaacagagtgtactttgctaatgaagcccttgtcattggacagataggctcctccaggtcctccctgccctgtaataaa
    cgttgccaccg
    544 2849256 — NO aagacaggctggtgctttcaaaatcagtattttattgtgaggtcaagcagaaatgtactagcagcacaaccacagatgacacttgtttggcttaaaacaagaca
    caca
    545 3166772 — NO tttcttgtctcttgagtggcggatcatgcgacacctcccgaccacagcatttgggcgagatatagacatgcctctaaa
    546 3886907 PIGT YES acaacgagacattagaggtgcacccacccccgaccactacatatcaggacgtcatcctaggcactcggaagacctatgccatctatgacttgcttgacaccg
    547 2474079 — NO agggcacagagagttcaacaaacactgaaacttaagtttgtcctggacatcttcagcatccgactttctggtggaaag
    548 2661946 — NO gccatcttcctatcctggtcctgat
    549 2963039 — NO ttggtctctatctgggcacagtctctttggtactgtgtgttaggactagatgtttttaacatgaatgaaaacgtggactcaaaagaaacacttttcaggtgtctataa
    atcttcttattttcaagtttacttagtatttggtcctggggtgtctacatgtcactcagttttgaggaaaaaatgagatgaccttagaaataacatagaaattaatgtg
    attgatgaatatccttagaaatttaatgagatttatacttggaatatggcaattacaatattttattgaaaaatgaataggtcaccagcctggcc
    550 2991676 TWIST1 NO tgaatgcatttagacaccggatctatttgcattttaccatgggtcctcaataaataaatagaatgttgttttttgtattttaagtttttttttgtttttcccctcagaggaag
    gatgaaaaaaagaattaactgactatggttttgcaggccagtttgatcccagtatttttatttctaaaggtgttcttatagttcctctgattgttaccattttaaaatag
    agaaagtccatagtgatgcctttcctttcagtggctgattggcacgacctcttgaga
    551 3535849 — NO ctgaatgctacaacctcggagagagaataggggagtgttggtgtttgtggtgaatcggaaagcacgtgtttaaagaggacaatcacattaattcagttccagc
    tatgagattacattgtcaaatcatctgatttttcaagagaaatcacaaatttgaatttcttaaaatgagaaatctactttttaaataatgacgggattttcaagtatgtta
    aaaatactgtaggctaataccgaataagctaagcaaaacttttgtggatcaaaccgaaaccatgggctattttcttctcctcctcttcctcctccttctcataggaa
    taaaacaactaaatataatcctgtctttataatttccatataccaagctttaattatatttaatacccatcaaagttagttaaaatgaactctgagtaatttataccttat
    ggaaaaattacggtgttctaagtctgaccaaatgtgtagaaagtacc
    552 2488753 CCT7 YES agccagctatggtgcggatcaatgcgctgacagcagcctctgaggctgcgtgcctgatcgtgtctgtagatgaaaccatcaagaacccccgctcgactgtg
    gatgctcccacag
    553 2575232 SAP130 YES gtgatgtccagttctaaagtaaccacagtcctgaggccgacctcacagctgccaaatgctgctactgctcagccagcagtacagcacatcattcaccaac
    554 3076375 BRAF YES cacgccaagtcaatcatccacagagac
    555 3187656 CEP110 YES aatttgcagcagatatcccagcagcagaaaggggaaatagagtggcagaagcagctccttgagagggataaacgagaaatagaacgaatgactgctgag
    tcccgagctttacaatcgtgtgttga
    556 3286398 ZNF32 YES actgaagcccaccacaaatatgaccactct
    557 3840338 ZNF808 NO acagatgtcggccactttcgccatcctgttttttgt
    558 4019888 — NO ggaacagagtgtgccagaaccctcagggtgtttctcagctcttgtttacgggccaccag
    559 3831504 — NO tggtttgcgaatatgctcaagtctctggatgaattgtatgacagtgaaggggtatgtgattagactgttgtggctttgaggttgatgtgtatgttttaaaggattatg
    attgagttggagatca
    560 2540638 — NO ctccttctatcccaatcggacagtgatatgaccctggggatgttccatgaatcatttgttcctctttggccccatctgattgtgtacttatctccttacacagtccttc
    tgaccttgaaatgatccagaaaagatgtaaaagagtaaattctatagtcagtttaaaaggcagcaggaaaggattgggaagcattttggacaaggggtctag
    gagacaggcccagctctgcacttttccgtgggacaaaggcctttgcattctctcctgta
    561 3229612 UBAC1 YES acgaggatgagcgtgtggacgaggctgccctgcggcagctcacggagatgggctttccggagaacagagc
    562 3839570 KLK2 YES ctcatccagtctcggattgtgggaggctgggagtgtgagaagcattcccaaccctggcaggtggctgtgtacagtcatggatgggcacactgtgggggtgt
    cctggtgcacccccagtgggtgctcacagctgcccattgcctaaagaa
    563 2380069 KCTD3 YES ggcagcaagtgtttacgagcccatatttggattggactatcgaacgagtagctttaaatgcaaaggtggttggagggccacatggagacaaagacaaaatg
    gttgctgttgcctcagagagtagcatcatcttg
    564 3428646 MYBPC1 YES tctgattgacaagacgaagttcaccatcacaggtctgccaac
    565 2998434 RALA NO agtaactgtccgctagaagtctgtccaaatttaaaatgtgtgccatattctggttcttgaaaataagattccagagctctttgatcgcttttaataaactgcaagttc
    attttaaatgaagggccagcatatatacttgcaagataattttcagctgcaaggattcagcaccagttatgtttgaatgaaccctccttttctctgagattctggtcc
    ctggaaatccctttctgctagtggtgagcatgtaagtgttaagtttttaatctgggagcagggcataggaagaaaatgtcagtagtgctaatgcattttgcacta
    gaacgcttcgggaaaatattcatgcttgccatctgttcatttctaaatttatattcataaagttacagtttgatacaggaattattaggagtaattcttttctgtttctgtt
    tataatgaagaacactgtagctacattttcagaagttaacatcaagccatcaaacctgggtatagtgcagaaaacgtggcacacactgaccacacattaggct
    gtgtcaccattgtgtggtgtacctgctggaagaattctagcatgctacttggggacataatttcagtgggaaatatgccactgaccgattttttttttttcctctttgc
    agtggggctaggacagttgattcaacaaagtatttttttcttttttctcagtcctaatttgaacaggtcaaagatgtgttcaggcattccaggtaacaggtgtgtatg
    taaagttaaaaataggctttttaggaactcactctttagatatttacatccagcttctcatgttaaatatttgtccttaaagggtttgagatgtacatctttcatttcgtat
    ttctcataggctatgccatgtgcggaattcaagttacc
    566 3544955 — NO gctttctcctcttccgggtcttggactg
    567 2981913 EZR NO cagctaagatgccatgtgcaggtggattccatgccgcagacatgaaat
    568 3013230 CASD1 NO agactgtctgcacctgtattcattgtggaacttcctctttcattggaaactttcttactcaagaatgacggcagtattgttttcttatatgtgcaatgaagtggaatga
    taaacagtatgcctttaatttatatgtgttcttgttctgatgttgtttcctgaaatgatttttcttcctaactgtggttttcgggtatgcaagcctaaatctttgtacactttg
    tctcacagaatagttctgaggctccatgacagggttttgtcattgttgatgttattgttgcttcgttttataaaaaagccaaaattttttttccaatccaaacgttcacct
    gtttcctttcctcaagctataccagtgtaataccagttaccctgtggatccatttaa
    569 3739279 — NO gtggcagtatctgtgacgatgggaagt
    570 2409084 — NO agattttttgccactgccttgaggatccctgattcctattgattttacctgcccttggacctgtccacctctatcttcacctccacctccctgatccggtctctaatca
    actctcacctggacaacagaaatggcagcccaaattgtctcccacat
    571 2848243 — NO tccacaggactagctggcagatctaacgttggggagagagacaaaggtggggtcacaggcagccccagcgtgttggcccaagttactggaagtttggag
    ttgccttgggaagtggaagcttgtgtctagcaccttagaccaccgggccatcctgccacacgcttggagttgctttgaactatgctggggaaggtgcaggcg
    gagctggctgggaaagtcagcatgggcatgtgaagtttgggtgtacatgacatcaggctggcagtggtgggtgagaaggagtctggggttcgggccaga
    gggtgggctggagatgtaggtttgttgggcatccgcacagatggagcctgggagtagctgagactccatggggagcacgaggatgagctgttgaaggca
    tgagctctggaccctggcattagaggtctaggaaattaggggcaaccagtaggacttgagaggggagcctggggaggaggaagtgccaggagtgagtt
    acactggcggcccagtgaaaccggggttcctggggggcgggatgtgtgtgtgtggcagggctgggttatcttatacctttcagaactatgtttaaagttttgta
    gatgtaattagaataggatgagttcatgccactttgaaacctataattgtatgaataattttgaattcattacgcagacatgacacatcacggcttctctttgcgtat
    gatatca
    572 3775781 — NO tgactgagctgtggaccgcaagcagtggcagccccttggctgctcgctattttgagtctggagagattgttcacgaggagcacaggctgtttggcaacatca
    gagct
    573 3990538 — NO ctgggtagtctacgagaaatgtcaattattatctctactacaactacttacatatatctaatgggaaaagagtggggcttaggtgtcagagtggatgggagaca
    aaggagaagctacactaataaatacaacaagtggaaggtacctgtcccattcctaaaaggatttgtgggcaatgctggcacttggtggccaggagaatcttc
    tgaccccactctccctcctcttcagtcctgaagaccccaagaacccagttaggatcccctggccagaggtctctgtgactgcctctggactcagcacgtgca
    gcagcttgggaggatttgagccagtctcaaaaacttttagccccagaatgagaccagtgaccccaagcaggagggctgggatctggagggaagagagg
    gggtccaaggggaccctgtggctgaggccatggagaaccagtgccagggcccaagagacccatttttccagttatcagaggtgactgacatcttctgcca
    ctgccttgagttcagaaatttaaaaaagcttgcagcaagaaaatgccagtgtgcaactgggtgactaaagacca
    574 2411004 KIAA0494 NO ggactgacgcgttcccactttcttactctgcacctccccactctcttcccattcaagaacgagtttctcttccctctccattggaaatcttgctccggaggtccgaa
    acacgtattttaagcgtgcccttcctcacctcctggagcacccttagaagtattgcctacttatccgggctgagaatccttcatttttgacctggcttttttttcgccc
    tttgggagataaaggtccctctccaccctctactaacactctgcacccaaggccttatcctttggggtcaccag
    575 2642748 — NO acaggggcgcatttgcctcacaaggaacatttggcaatgtcgggagatattctgggttatacaagtgggagattaggaatgctactggcatctagtgggcag
    aggccaggatactgtgaaacatcctataatgcacaggagagctccctacaacaaacaatt
    576 2661956 — NO atggacacccactttccatgcttag
    577 3307945 — NO aaaatccagtcccaactgcagatccctatgcactcccccaac
    578 3789999 — NO ctctcttcttgtggtaggtcccagaaacttctacttgggggtacatgaggcccagctgggattgggcacagaaggtcatggctctgcacctgaccctcacctt
    aggggtcaggagagagccaaggacacgagtgatgggttagggaggactcaggcaccatggaatactgtggccatccttccatagaggagaggtacagg
    tg
    579 3963093 EFCAB6 YES atggcgattataccagactggcttaggtcgcatcctcacacacgaaaatttacacattcaagaccccattcttcaccgtgtagagtatattca
    580 3589632 EIF2AK4 YES cagagaagctgacgaggagagaagt
    581 3816037 — NO tttccatcacccagcaaacgccgtcccgcagcacccgggaagctgcggagtcgggctggggccgccgcgttgcgcacatcggtccttg
    582 3417925 LRP1 YES cggtgaattcctcttgccgagcacaagatgagtttgagtgtgccaatggcgagtgcatcaacttcagcctgacctgcgacggcgtcccccactgcaaggac
    aagtccgatgagaagccatc
    583 3696235 RBM35B YES acccgctgatgactacaccagtctgatgcctgttggtgacccacctcgcactgtgttacaagcccccaagga
    584 3462998 OSBPL8 YES aagaagcttatccaacgccaaccaaagatttgcatcagccatctcttagtccagcaagtcct
    585 3962740 TTLL1 YES ctttgaatgctatggctacgacatcatcatcgacgacaagctgaagccctg
    586 2681997 — NO cccagagcgagacgactattccatggccctgagcagacaatttctcttttaaaaatggtggccctttaatgatgttattatgaggtttttaaatgacatatcaaaa
    gttgtttatatcacaaaaacccaacagtcatttaattatactaatgaaggtctttatacgtgtcagattttttaaaaaagacttctaatggccatgagaaatggactg
    ttgctgctgcttgcatcacagcagtggtggcagcattctttgtagaggaagaacatattttataatgtataagggaatttgcatttcgcttttcacggcaaacctttc
    tgtgttttttgtaaatctaacaattgcaacaacatggaatatttagttgggagatgtttggagtaagtgttgaaagcaactatgtttgcttgcttttttttttttatggtta
    gagaacaactgtggcgactttcacagattgaactagtacagttcaaaggaaaatcatcgactttagcacatctgatagctatataggcatggcagaggtgtctt
    gaaaaaac
    587 2743344 PHF17 YES ggtcctagaggaatttgagcagcgatgctacgacaatatgaatcatgccatagagactgaggaaggcctggggatcgaatatgatgaagatgttgtctgtga
    tgtctgccagtctcctgatggtgaggacggcaatga
    588 2992873 — NO ttcccaagcactgtacggggtattgggaaggtaagaacaaaaaagatgtagtccttgcccttacaggtctagttgaggaaagaaagggggattgttttccagt
    tgcactgaatatgaatcagaatgaggaagaaagtacttggaagcctctagctgactctggtaccattccacggggccatgatacctttcttagtc
    589 3568027 — NO acatattttatgctatgccctgggggtaaagggtgactaagacgtgtaaggcacttgcattctacaggccattgcttttcatgggtataggttttctctccccagtt
    agactgtaagccttgttt
    590 3830188 FXYD3 NO ctggagacttcctatgtgtgcattggggtggggcttggggcaccatgagaaggttggcgtgccctggaggctgacacagaggctggcactgagcctgctt
    gttgggaaaagcccacaggcctgttcccttgtggcttgggacatggcacaggcccgccctctgcctcctcagccatgggaacctcatatgcaatttgggattt
    actagtagccaaaaggaatgaaagagagctctaaccagatggaacactggaacattccagtggaccctggaccattccaggaaaactgggacataggatc
    gtcccgctatgatggaagtgttcagacagtttataatagtaagcccctgtgaccctctcacttaccccgagacctcactttattacaagatctttccaaataccca
    aatgtccctgcaagcccgttaaata
    591 4011203 OPHN1 NO tcccaggctcctatgcaagttttttttccccattatatcacacttatctagcaagggaccttgtggtttgtggctttagtggccatcatttctgggggttggcttttac
    ccttttttcttgaatatttgccaccaagtgaaaaatgttaggacataaacccttgccaggtccctttcatttgctatctctattattggaaaggacctaaaaattggtgt
    aatggggcagaaatctgaggaatggacatttctaattcctgtttgttgaagggaagttgctggaaagagcatcagtacttgtttctatgcagatgcctgggccg
    tagcttgtctgtagcgtctgtataattataatgttgcccagtgtgagggaaagagctttcctacttgcactcttctaccaaggccctgttagtgcactgattatagta
    ctgacagataaacctagataaagagatagagagtgagtacatgcacactcatgtgcaaacccactcagagatgcatttggaacagtgctactgaaaggcag
    tagtcattttcaagactgaattccaaacatggtttattggtgagttaggaacatgtaaggccaagtacactgagagcctttttgaaagtaattgagtggaaacttg
    atgccattctaaatcaaggcatatccaggtggcccggttgaactcactccactgtacccagtctcaaaggccaggttgctaagaaaccaggagtaaaagagt
    caagtgaccatcatttcacctgctgcttgcccccaatagtagtctctgtgaggccttactgacctcacctaggaagtgatttttgagcccttgtttcagggctgtg
    gcctccctgctctatcctgaataaagcagacaggtgtgcagattttggccatgaaagcatggctaatagggccacagtccctttaaagaaacatggtttgact
    ctggttttcttgggggaaaataccacaatcaccgatgcaaacattggaagattattgagagccctagaaagctgct
    592 3349796 — NO tgcagaaaaggtggataacccaactctggtggg
    593 3040457 TWISTNB NO tgcctcagccattctagttttgttgtgtgttggaggacagtctaatgaagacaggataaatgtgattctgactagtgggaaatttcagattactttttaatgattgga
    atgggctataagatattgtgctgaagagaaaacagttgttctgttcactgctttcattgagaaaatgtggaatgtctcttgactaattgacaaagtgtaatgaaatg
    acaagctggttgaagctggtaatcaatgcatggccatatttattcattttccacacacttgaccatctactttgtataacacattctgctaaggcccagggataca
    atggcaaacaagatagatgtagttccttcccttgtggcatgtcataagagaaacagatgtgcatatacacacaataaataagaaaattaataattgtattaagtg
    gtatgaaaaaaagggggaggattgttcactcactgttacctgtgttagtatctgcaaatgcatgaatggttgaactcccatgtcagcatttttgttgccatttattta
    gtaccagacatagtgctggtctcacagcttaatatttggtaatgaataaattctgctagtggtatatgttgatctgaacttacaatgatgggatatagaattggcag
    agtggcagatgttcacaattgtctacaagtagatgtgctagacaatggaaggatgcaggccaacctctttgattacaattgagattcatgtgactattgagccct
    ggaaatgtagcttgtcca
    594 3895503 — NO gtggcggaccgtagaagagcaagccca
    595 3907654 NCOA5 NO ccaggcccagctagccaagtttggaatggcatttgtcatgtcagtagccaccacctttgttcattgtgaacctaccaaggctttccagcttcatacacattgacc
    agagctcaagctcctgcctgcaactcctgcctagagttgaagaaaagcaaactggccttggcaggcacagtgtcatcataccctcaccccatatgtttgggg
    tctgcttgaggattcataaatcagccactctggattgttgaggaatggccatggcagccacagaaaaaagaatttttctctctgagccaaggttgttttttgtttttt
    tctcttttcttttttgttttcatttcattggaagatctccaatggactgaacagctccagtcagcagcagttaccacaaactgtgaatctgggccccaccactcttcc
    ctgttaaccagttctgtcagcatccccctctccagcagcacttccatgaagttggttctgagactctggccgtgaacacccgtttcttcagtgatttgttttgggct
    tttggctcaaaaccccaggctcttgtttttgtctagactcttattctgtttcctgagcagcaggaggtagggaccactttgatgtcagacttctggtagctggacat
    gttctcgagatgggtggctgttcgcgacttttgtaccagagtgaaattgttagaaggagggtttctggctgtggttctaaatggagccccaggaagctgccctc
    tccccagggtttgtgctcagtagagcc
    596 3679982 — NO aagagacacttttccctaagcaggaagttaataattaagttaaccaagaaatagaagtgcatgagtattgtttggaaatatggagaagggaagaagagtaga
    aacagctgaaaagattaaaagtgattgctttggcgaggt
    597 2858366 — NO agctacacaggaaataacaccaccaaaaataacacattcaaactcagagggcaatcttccctaa
    598 3048215 MRPS24 YES accatgccgcagagcgaacggtggaggatgttttccttcgcaagttcatgtggggtaccttcccaggctgcctggctgaccagctggttttaaagcgccggg
    gtaaccagttggagatctgtgccgtggtcctgaggcagttgtctccacac
    599 3168775 — NO atctgtagccgtagtaaattttggaagggcaaatcaatatggcgggtagaggctagttggtgaagcttattaacacagattcttttccaggctaaagttgtcttca
    gtggttaacctttgtttctcctagtagagaggtgggcaggataccttttgtctttgcaaatctatgtcttgatttaggcaagtggaaggcagagaggtttcttgcat
    ctgctccttcaaaactaccttcagta
    600 3643388 — NO ggaggtattactgagcgccacctggctg
    601 2927513 TNFAIP3 YES gtgacggcaattgcctcatgcatgccacttctcagtacatgtggggcgttcaggacacagacttggtactgaggaaggcgctgttcagcacgctcaaggaa
    acagacacacgcaactttaaattccgctggcaactggagtctctcaaatctc
    602 3911005 — NO atgcctgagggcatcgaccagaacgaaccagacacgagtccctgccctctggaagctcacgttccagcagaggagagg
    603 3942797 INPP5J YES ttcatcctgggctactatagtcacaaccacagcatcctcatcggcatcactgaaccctt
    604 2802457 — NO ggcctatggtaggattgtaggcataagtgctggatcaggagtcatccctcttctacctctgctgccttctgatgtttcttttgccaaccagcacgccggaccagc
    ccttcttgttttctcttttggttctaggtcacaactctttctc
    605 2874851 RAPGEF6 YES caacacctgagcgtctcataatgcatttaatagaagaacattccatcgtggatccaacttatatagaagattttctattaacttacag
    606 3147604 AZIN1 YES gaaattggctttacgatgaacatgttagacattggtggaggattcacgggaactgaatttca
    607 3822303 CCDC130 YES tgccatataacatctggtgcgatggctgcaagaaccacatcggcatgg
    608 2767313 — NO ctgtctttggattgatggctcagagaagatggcagcatagatctttaaagcagtttgagtggggaattcttggatcttggggtacttggccatgtggacaggatt
    ggctggagaaggagggtcaggtggcggtcctgctgccaaggtctgagggtaatactgctcctaag
    609 3159245 — NO tgtgtgtctcaaacttcaagaagtctctaggataacccaaaggcaacaagggagaccaaaacaaggacgctggagacattttagcctctgatactgacagct
    gcagcaaacagaaaacgcagcctaaccgcgggccagataaaaacctcaca
    610 3403122 PTPN6 YES gaagcagcggtcagcagacaaggaga
    611 3849599 — NO tgggcacccgttatcctagttactcgggcggctgaggcaggacaattgcttacccagaggccg
    612 3534950 KLHDC2 YES tgcctatgatcaccttgcatggacagcaatcctgtaaacatcacagagtggcatcatttgtataattatatgcattgttgtagtttgcacctgttggttttaatgtgca
    tgtgaatggcctagagaacc
    613 3631427 — NO ccctgttttgatatcctggttgtgaaatgtcttatgttttctgctaatctatttgtgttaaagtaagcagggttggtttacagtaccgtggctcaaaagctagtgtagg
    cagctttcctctcctg
    614 3779594 — NO acgccaagagtccagtgcaacgatccctgccacacggtcagccgaccccacttggtgccacagggtccagcctcggccactctgggctcaacctttccag
    cacgtctgggagcccaatgaggctatgggacagtgtgcatttccctcaaggcctccggaaagtcacctgccacccactgtgacctctgaggctgaaagga
    ctaaggactcctttccccatcatttcagctgggccagtggctggctaaaatcagcgcagcattcccattcttctgaaagccacagctgaaataatgcaccagct
    gaaaccacagtggacagactgagatggcctccctctgggcctctagttggcaactttctcacccgggggctcctctttctccttttcccgctccttgttccagtc
    cttaaggccttctggaagtgaggtgtcctcatccaagctgccagtgccttccacaaattcttcataggtagatttttccgcaaatggtctggggcccaaaa
    615 3931281 — NO cccgaggagcttgtgatgtcaccagtgtgccctgcgggatctggggaacaggagaagtaggccagagaagtcgggttgaaaggtgtgtcgtttgcgtcct
    ggatctcccttaatttaaccccataacattccattttacagataaggagactgatgctcactaagacactaatatgcccactcacacagcaagtcccaagtctct
    ccccaaaatgatttgagaattttgaggcacacaaaagggagaaaattgagtgcccgtgatccaacgactgcaactgtaggaaaccaggaaagtggagga
    gtggtagtacttctgaacccta
    616 3110077 — NO tgggaagaggattcggactcgtcacactgcagagcagcagagcgagaaaggatgagaagaggcagagaaggcgacggcagaagaaaaaaggaaaa
    actgcggccgcgatcagagcctga
    617 3419463 — NO gcgccctcgccctgggaaactcactggagtggggacagatctcaggcgtttggcagtcac
    618 3903370 — NO attgtatttctattggacgctgctgctctaggttactgagttt
    619 3609638 — NO agaatcaggaaaattggtgcagggattggcacactgcagggagaatgcatgggctccatg
    620 3227685 — NO tcttgggtactcaccttcagccctagagcattctttagcactcacagtttctcttctcgtcgggttattctttatattaatcttttcctgtccaaattactctctatgtctcc
    tgatcagtccttgactggaagcatcaag
    621 3349840 — NO cataacctctagagtagaaagtttcagaaggaagagattccccaaactgtgtaattcccttgtaaatctcattcattcaatgggatttgagaaccaaccacttgtg
    caggtgcccgcatccgaagataacttgcccccaggagacagcagataagaagagggcagagacaaaggaggtctttttgcgacttgcatc
    622 3035683 FTSJ2 NO cccatgtgtgccttgacgggacttcatcttatagactgttaaactgtcacacacaaacaggctttccacccctgctctgagagcaccacgcacagatttccagt
    tcttagtgtggctgtttaaagtagaaaatctgggggctgggtgaggccactcatgcctgtaaacccagggctttagaaggctgaggctgggggattgcttga
    agtcaggagttcaagaccaacctgggcaacatagcaacaccccccatgtctacaaaaatgaaaaaccaaaaagcaaaccaaaagaaaaatctgaaatttc
    catctggggattaacttctgtctttctggtgaacaatatagcaattcacgcattcttcaagcagcaaaagttcccggaacaattagggaagacgtatggtctgaa
    tttatccaggcagtgggtctgctttggtttttgctggaaatttatatcagtgtctgggctcccaagaacataaatgtaattgccaaagcaagcagtgatgtggtgt
    gtttattttcttttactcatctaggaacttgacgcagcttta
    623 3439354 ZNF84 NO tcaagaaagagtcccgattgtgttccagtacctggttcttctggtct
    624 2812078 — NO ggcagtgctgtagggagcttcattaattatgatagtctcgctgtgtcaaatggattacaaatggaaccacctgtggggagcctgcaaggttacggacagagg
    cta
    625 3038635 — NO gatatgaaaaagcacgcatgcaactaactactgttgatctgctttgcta
    626 3088092 — NO acaagagggcgggtacaaacgcacagcttccagggctgaaataca
    627 3337338 ALDH3B1 YES atgaaggacgagcgtgtgcccaagaacc
    628 3420557 — NO gtaagttgcctgtcgctcctctgaatttt
    629 3841267 CNOT3 YES atggcggacaagcgcaaactccaag
    630 2929962 STXBP5 YES tcaaggagccttgcacagcatattcctggccctggtggcattgaaggcgtaaaaggggcagcatctggagttgttggtgaattagcacgagccaggctggc
    actagatgaaagagggcagaaacttggcgatctggaagaaagaactgcggccatgttatcaagtgcagagtc
    631 2387074 MTR YES gttgaggattatgcattgaggaagaacatatctgtggctgaggttgagaaatggcttggacccatt
    632 3388958 — NO gtaggtgccgaacaccgcgagtctccgcgcccgacccgacctcgtgttcgagtgtgtgcacgctggcgtttatggagagactagaagagccgcccacgtt
    aagagtctacgtgccctgcagg
    633 3620562 — NO cccaaactgaaacatcatacctatta
    634 3870278 — NO gtttgacttctgactaaaggtcttg
    635 2833045 RNF14 YES tacctgcaagcggatgaggctaataaaag
    636 3030300 CUL1 NO gattgctgcactggacgactttagaacatccctcaca
    637 3767510 — NO agatcgaggacagtgttgagacaccaccacctc
    638 3039444 — NO gttcaaacagtagtttactcctgcctcag
    639 3067653 — NO agtatgggagaggggtaatgctgagca
    640 3139926 TRAM1 YES aattaacaggcgaatgcacttctccaaaacaaaacacagcaagtttaatgaatctggtcagcttagtgcgttctacctttttgcc
    641 3203423 B4GALT1 YES atgtctatatctcgcccaaatgctgtggtcgggaggtgtcgcatgatccgccactcaagaga
    642 3875984 — NO tctttctctgggttcatttcctaactgtctaactttggg
    643 2848542 — NO atggtgtggcaagttgactgtatcgtgatgttagccgtcttgtggcagaga
    644 3134299 — NO agaccacagaaactgggcgggcagcagatgcagacacagccatcctatgcatttag
    645 3538031 — NO tgaccacgtgcgcaaattatttttcttttttagtagaatggtgcattttttgcctttgtatttgaaatttagctaaattacaatagctatcagaactacaattgaccttagt
    aatttcaaaaccatagttataagggttttaagttgatttttaaaaatcttaagatatgatagggatttcaaaactatgtgtgtgtatctctgatagggaggggttggg
    gcacagactaataagtgtgccaaaaatctgtgaatccaaatgtgtaacaagtgttgtctgaataaatgtccacaaatccatgctattattg
    646 4037525 — NO tgtattagaatgtaatgaactttaatggaatgtactcgaatggattcgactggaatggaatgttctggaagtgaatggactccaatggaatggattcaaaagga
    atggaatcgtacgga
    647 2814589 BDP1 YES agcttctgacatctctggaggtttcagcaagaaaagattgtgtaggttccaaagagtctgctttggcaaaaatagatgcggaattagaagaagttggaccatc
    aagaagggttggagaggaaactgtaggagataattcaccatcttc
    648 2823139 — NO tcccaacctggcagtgctgagtggg
    649 3113389 COL14A1 YES ggacagaaccagctacaaccatagtgcctaccac
    650 2853728 C5orf42 YES cagcagtgagagtcgtccagtccatggctcgtttcatggctgcctatttcaccaatcagcagctttgcattttgccccctca
    651 3895815 RNF24 YES gctcggatttcccacattacaacttcaggatgcctaatattggattccagaatctgcctctcaacatatatattgtggtttttggtactgctatatttgtcttcatcctta
    gtttactcttctgttgctac
    652 4013748 BRWD3 YES ttgttgatttagattcagacggtcctggtacttcat
    653 3384440 — NO ttgtccttgggcaaacgtggtatactttctcagtggtggttggaaggaaatttgttgccctgtcatttcgcaagtatggaaaaagacctaaaggagaatttagca
    gctgcagccgctgtttttattgcgtactttactagcgccaactctttaataatcgcttgttagttgttacccctgttttatgggtcaagagactcaatatatcagtactt
    tggtaaggccaggcagc
    654 4026568 FAM58A NO aggccgggagtgtactgtgtgcagctgacccaaggcagccacatctgcgtttgtcctttgagaggactttgactacaatacaggcatgacatcaatgaaagg
    aaagtcatgaaatcgatgagactgaatccctacggatttcttaaaagccagatttgtagggagaatgaatgtgca
    655 2675946 WDR51A NO gccagggatttgtaccatgggacttgg
    656 2941689 — NO tctccaactgcagcgacctgtggctcttcagat
    657 2330052 EIF2C4 YES gaaggcagtcatgtgtcaggacagagcaacggccgggatcctcaggccttggctaaggctgtgcaaatccaccatgatacccagcacacgatgtattttg
    658 2726487 OCIAD1 NO cgcagtgaggtctgacgtcatttcc
    659 2902605 LY6G6D YES ccccagtgaccttgattcaccaacatccagcctgcgtcgcag
    660 2732332 — NO tcaaaagatttggagtctagagggcagaaattgaagaggttggtgctctgcacgtctgagtccgcccacagactgaataaat
    661 2329455 — NO ttcctggatcacaaagggctgtaggggttccagagatgctggagctctggtacaacaggagggccacaggc
    662 2373856 PTPRC YES gtatttgtggcttaaactcttggcatt
    663 2465069 SMYD3 YES aaaaagcttggccagaccacaagcgggaatgcaaatgccttaaaagctgcaaacccagatatcctccagactccgttcgacttcttggca
    664 3046899 VPS41 YES tgatggcagctgaaattagccaaaa
    665 3418387 GEFT YES ttgccgctttgcactgacctccagagggccagagggtgggatccagcgctatgtcctgcaggctgcagaccctgctatcagtcaggcctggatcaagcatg
    tggctcagatcttggagagccaacgggacttcc
    666 3568670 — NO ttcttgcagtagtgcgtgagctctcactcttgctctggggagtctggattagtccttgagggaatggattagttcctgcaagggtaggctgttataaagccagga
    tgctctcaggctctcctctgtttgcatgggttggcttcc
    667 2824307 — NO aggcacaggctcaattagtttttcaaactctagccaaggcagtatttcatttgggaaatcatgcaacagaactgctcaattcttaacttctcctgctgttaacattta
    cacttagactgccagcaacagttaacttaaattttggtctcaagggaacaaaaaaaaattgcattcagaatttaatatagtattttaaaactaattttagcctgtaag
    tcattatgagcaatagtaacttttgtacctcctcatcttgtctgataatatattctatatgctgtcaatctgattatatagtctatatgctagaagttgctgattttcattct
    gccaccaagaaaactgtacttttatttatgggaaaaggatttaaatactcctagatacttaaaatttttttaatctaaaagttgattttctcccaagaacaattttgtttg
    ctttctacaaagttttaagtttaataaaatgccggtaatcaccactgttttcctccccaaaataaatgctctgatccatattatattagagtgatactgtcacttagtat
    tgatatctttaatattttttacatcatgagacattgttatgatcttacctgattgttatctcaaggtgagctaatcatctttatttgccttaaaaaatactgtactggctgg
    atatttaatcttgttagtttagttatacacttgttttagtcgagtttaattcaaaaggactcttaacagtatggtgtaaaactcagattttctagtccagacaaattgctc
    tctataacgatttggcagatcaatggagacatccgttttaactttactgttctgtacttactatgtagtcatgtgcagcttatcaacacaaagaatacggatgaggg
    catttaaatggactacaagtgactctgacttgtaaactagggaagcctcttgtgtttgaccttaaaggccagagaaaaactgaagatagattgacttaactattg
    ccaagcagattatgggttactttatacttcctttcattc
    668 3204568 — NO agccctcaggccctaccaaccttgactgtcctgtccc
    669 3410647 — NO cccaggagtactagttgagggccaggctgctgagaagcagttgaagtagccttgaagcaaggatgggagattgctgggtgagatcaaagatacgctggg
    atgggggtgagtgaaagtgtgagcaatgagtagaggcaagattgtagatgctgcatttggaggaatatttctgactgcataatcagaggtcagaatggctag
    agaaattaatacagaggtacaaggctagatttagaagagtaagctaagaacagactgcaatgggcttttgaatg
    670 2555029 — NO catccacgtacacatatgagctgtacacatagatgttaatcaggttgcttttttcattttatttaaatattcaaaatattgtgtgattgtgatccattgagatcattgaag
    tagtattaatttagctgggaattagcagcttatgttgtgtgggcccagttcatcaatatgtgtgtcaaatatccaccctcagatatcagcagcctttgacttgcagt
    caga
    671 3238290 MLLT10 YES tagtaccttaattggcctcccttca
    672 3490689 — NO tatagaggaaacctatcagggcagggacagt
    673 3571835 — YES catccatggattgggcccactactcatagcagctcctgaggcaggtaaatggggcaaggactcacgccaaataccacacgcgtatgtcaaacacccaagg
    tcggattctggggcccctgccctcaggaggctgtcagactgttccccctaaacacacttctgaaggttgtagggaccttgccctgctgtct
    674 2318698 PER3 YES ggggcacccgttcattacttcgagaagcagctcacccttgcagttaaacttacttcaggaagagatgcccagaccctctgaatctccagatcagatgagaag
    gaacacgtgcccacaaactgagta
    675 2330382 — NO tggcccagctacatttgcaatgatgtgcacgtaaacactgttaagaggttaaagcttgtatacaatctgttactgtgaaataactaaattgggctttaaaaaaatct
    tagtatttattgatcttcattcacatatacagttgaaatttaaaataacagatggttattccaatgctgctgaaaccttttctaaaaaatacttgttttgttggttgaatgt
    gatgagaggcgcttctgggcagtctctcttctctcccacccgtctttcctcctccgagtaccccttctccagctttgtactagccatgtaaaacccaaggttttctt
    taaaacatcagaagagatctcgtcctccatgccccaaaaaagccaactcattggaggtgttaccc
    676 3837059 GRLF1 NO ttgggtgttgaagtggaatcgtttcatcccagcc
    677 2582942 — NO tcaatcaggtcaaccacaggtcatatgaaaccatcttcccaactcccccacctccactggttctgaagagtgggtgtaaacaatgggttaaacaatccaggat
    gcagacagctgttaatcataactggctccaca
    678 2876012 — NO tgtctcatctaccaattcctgctattataagatcaacttctgcaaaaaccttatccacctcaagtatccttagcagc
    679 3372066 NUP160 YES ctttgccttaacttccacggatatctgggccctgtggcatgatgctgagaaccaaacagtagtgaaatacatcaactttga
    680 3781765 C18orf8 YES gagatgcctcataaatttgtgatagccgtgctgatggaatacattcgttctcttaaccagtttcagattgcagtacag
    681 3278980 DCLRE1C YES ctggatcacaggtgcataccgccatgcc
    682 3435777 C12orf65 NO gttcaagtgcaatgacacacgcctataatcccagcaccttgggaggctaagacaggaagatcacctgagcccaggagctcaagattgcagtgagctatga
    acaccactgcactccacctgtccacttgttcttgtgtgacagaacaagaccctgtctctaaaaaataagataaaaccataaagaaacacagtcagtactataca
    agaataatggctacttctagagggaaggagttgtcattgtgatgaggcacttggaggggttctggggtgcctgacaaagttctgtttcttcacctgggtggtag
    ttagaagggtgtccccgtatttcaaattgtacctttgtgagattgtatg
    683 3524572 EFNB2 NO gctaggctgtctgcgaagaaggctaggagttcatagaagggagtggggc
    684 3790001 — NO cagaacaagtgcatctgctggcagccagcttaaggagttagcagccctcaattccaataacgaacgtgtaaatcagaattc
    685 3301881 TM9SF3 YES gaaggagatggataaagcagatgtttattggggcattccttatcccagctatggtgtgtggcactgccttcttcatcaatttcatagccatttattaccatgcttca
    agagccat
    686 2745373 LOC100130178 NO tggcagattatgtggaccatcaacaaactaccaaaa
    687 2774241 — NO tgcacagacaattccctttactaggtgtcaccatagctaccatcttcatctccttcaaatgttgctttggcattgaggcttaccctcacttccttatttaaaattacaa
    ccagctgggcgtggtggttcacatctgtaatcccagcaattttggaggccaaggtgggcagatcccttgagctcaggagttagagaccagcctgggcaaca
    tggcaaaaccccatctctataaaaaatacagaaaaaacttagctgggtaatggtggcacacacctgtagtcccagctattcgggaggctgagacgggagaa
    tcgcttgagcccaggagatccaagctgcggtgagtc
    688 2852754 AMACR YES tacgacttacaggacagcagatggggaattcatggctgttggagcaatagaaccccagttctacgagctgctgatcaa
    689 2390973 — NO tttgccagtagcctcataatgagcgtgaggtagtatctcattgtagtgttaatttgcatttacctaacaattcgtgatgtggagcatcttttcatgggcttgttggctg
    ctgtgtctcttctttggagaagtgtctgttgaagttgtttgacattttttaatcaagttgttggacaggttcccttgtttttaagtcagagtaggtgatgtttgtcttgaa
    ggttata
    690 3457600 ANKRD52 YES accaagagaggcgaactccattgcatgctgctgcctacgtaggcgatgtccc
    691 2853708 C5orf42 YES ccttattccagggatgctgacattccatttctaactagtttttctggaaagcttagagaacatgaacttaattctttactttttgatgtacatacaacattaaaacgac
    atcagagcaaaactaaaagccagaatgtgtttagagctggttcttgctttgttgttgctcctgagtcctatgaatcagaaaaatcatcctctttaaatgatgaatat
    ggcatgcatttagaaaaccagaaactttcatcatcagtactggttaatcaagggatca
    692 3055843 — NO cccagatggagacacccatagcagggcgccggatccaatctcttcctctcctccctcggccttcctctccccacaaaccccagggtctagaaagtagaagg
    ttctcccctcttctctccttcctcataatgaactcgatgg
    693 3139045 ARFGEF1 NO catggtttgcggaggttagatttactggaaatgtattcatactgtgaattgtgctctgatggttaaaagacaagattgtcaagcattccgtattaacagtggatgta
    gaaaattttttcagatggacaaaatgtatatggtacagatgtaaagttttctatgtaaaaaattctgtacaactttctgtacaatattgattcccatctggca
    694 3607791 WDR93 YES ctgcctatttgcaatgccaccggaagtcaagggccc
    695 2666907 SLC4A7 YES accaagaaagaaatacgtggatgctga
    696 3887309 — NO ccagcagggggttcccatccttcct
    697 2333654 DPH2 YES tggaagacgagggattgccatcgcctatgaggatgagg
    698 3333566 LOC751071 NO gtctgcggacgctgtataccctcctccac
    699 3278417 FRMD4A YES aagccagagaagctcgacaccgtcaagtgaaattggagccaccc
    700 3986088 NRK NO tcgacacggagcacccttctagcttcttcgtctccaggactgacgctcaggctcctctctcgccttagcccaacttgctttcccgcctcgcaaactccgg
    701 2558398 LOC100128333 NO tgcccaccagccaactagacagatgtggcctgcattgtccccctggaggcaaaggatgtgtgggtatttatttatttaagatagtaagttatggccaggtgtgg
    tggctcacgcctgtaatcccagcactttgggaggccgaggcgggtggatcacctgaagccaggagtttgagaccagcctggccaacatggtaaaccctgc
    ctccactaaaaaatacaaaaattagctgggcatggtggtgcatgcctgtaatcccagctactcgggaggctgaggcaggagaatcgcttgaacccaggag
    gcggaggttgcagtgagccaagatcgtgccactgcactccagcctgggcaacagagcaagactccatctctaaaataaataaataaataaataaataaata
    aataagacaataaattatataagcagtgctgaatacagcttcatcatttaaaaatccaaacagtttggaaatatatagacaagtatataaatgctcttcttgcaccc
    cttcccccatcctaaagcctaccatacaggtaggcactgttaattatttggtggaaatgtttacactttttgctttgcatttacacatgtgagtggcagggatagtat
    ctgagaaattaatttttttctctcctgaattttctctttttctgccctcacatttatggagctcattacctccagagcagcttttcaggttagaaaactgaatttatcttca
    ggcatctctggcttttgtgtgctgaaagcttaagcatttagggcaactccaggatttgctgagtggctcatcaaaggatgaggattctcttgcacagactgaa
    702 2830633 — NO gcattgtgtatgctgaagccatcatcactctcgctcacaggaggttcattatccatttctgacaagtagccttctccttgatcctcttccttaggc
    703 2546259 — NO tatacccacatcactaagctgggaggcacattt
    704 3615631 TJP1 YES ttccgtgttgtggataccttgtacaatggaaaactgggctcttggcttgctattcgaattggtaaaaatcataaggaggtagaacgaggcatc
    705 3729022 GDPD1 YES gagctcccaccttaccttggcaaactggatgtctcatttcaaa
    706 3729073 YPEL2 NO tgatggcctcttgtcaggagagcagtggcacgggggcgtgaggaagagggaaaggggaaactctaagggtcctggcgcggggaaggggtggaaggg
    tggaggtaggaacaaaattgcgccgctcctggagacctgataacttaggcttgaaataattgacttgtctaaaagga
    707 3043777 — NO tgcactacatcgctggcaagaattgttcagaaaggctggcctgctaacgacttctggggagattttc
    708 3080463 — NO aaggcacctacacaacatcaggccacttgg
    709 2969705 REV3L NO ttgctaataaatgtaggccggaggggatggcttagtggtctaagcatcagatttgaaatacctagagtccctggaactgcaggtttgaatgtcagcagagtca
    acccagc
    710 2904894 MAPK14 YES attctggattttggactggctcggcacacagatgatgaaatgacaggctacgtggccactaggtggtacagggctcc
    711 3421016 — NO atgcctccagtatcggatatgtgggcaggcacaa
    712 3724753 NPEPPS YES tgggttttatcggacccagtacagctctgccatgctggaaagtttattaccaggcattcgtgacctttctctgccccctgtggatcgacttggattacagaatg
    713 2600045 GLB1L YES tgttgtggagcgaaatatgagagacaaactatttttgacggggaaactggggtccaaactggatatcttggtggagaacatggggaggctcagctttgggtc
    taaca
    714 2893581 — NO tgcatttcagcttggagtgcgcagcatgaggcatttgtggttcagaaaagaggtcttcctttttcctcctcctgttttcttttccttccttctccccaactccccaaag
    gcttactgcctttcttctcaggccacgtgtgtagataacctttgaggaaaagatggtttccgtgctgggatatttggatattacctaaagggacaagatgagccc
    tttctttgccttgttttctttctctggcctcatcagagtgaattatatctgactgtgtgacagttaattgtaccatccatcccgtgtcctaagctgataagccc
    715 3712473 MPRIP NO gtgtgtcccatccaagttgagcacgcgccttccccagcttgcagcagcacaccccaagcgctgcttttcacctgtacctttgttttattattattattattattgctgt
    tgttgtcatcgttaactgtgggcatggaa
    716 3026735 — NO ccatgatgtgaaaggtcgggtgatatctgagagctgaaggaggttaagcggatccatgccaggctgacaaggggaacaggtgcctctgccctggactgg
    agcctacgcaaccatcttctgctttatctagctgctgtctgtctcctgtctctgcgtgagtgtgtg
    717 3603221 IDH3A YES agtcgtgcagagtatcaagctcatcaccgagggggcgagcaagcgcattgctgagtttgcctttgagtatgcccggaacaaccaccggagcaacgtcacg
    gcggtgcacaaagccaa
    718 3820895 CARM1 YES ccaggtggaccagaccggctccaagtccagtaacctcctggatctgaa
    719 3183801 RAD23B YES agaatgagaatttggctgccaattt
    720 3420741 CAND1 YES agaaaaaagtgtgaagacccgacagtgttgttttaa
    721 2356132 TXNIP YES cctgctatatggatgtcattcctgaagatcaccgattggagagcccaaccactcctctgctagatgacatggatggctctcaagacagccctatctttatgtatg
    cccctgagttcaagttcatgccaccaccgacttatactg
    722 2625835 SLMAP YES ctttcaaagagtggcggggactgcacttttattcatcaat
    723 2996070 AVL9 YES gtctgtcacctcgagatcttgtccttcatttt
    724 3175548 — NO cctcaatgggaaccctggtgcagaa
    725 3810034 — NO tagctgttcaggaaagctgtgtggctggagcagagaatatactggaaatcagagaggtcaaaaacaatgagcaggagatatcggaagaaatgttcctaacc
    acttcactcttc
    726 2767097 — NO agtatttcatgacaactctaagaaggacagcactcaggggcagaatccgcaaatatcacctatttccaattatacttcacatgtgcatatgtgcacacacgacg
    gctgtc
    727 2853747 — YES ttattctggggaatgcctgaagttaacatttctagcaattcggtggcatgagaatg
    728 3016374 — NO cgcagtttgtcagcatcgatgtgggactgggagaggaaggatattgccagttatggttga
    729 3845911 LMNB2 NO tttatggcctgggaaacaatttgcatttgtccccaaatacgcttagctgtgtgccgcttagaacgatgcgaaaccatccctctgtgtaagcccgtg
    730 2642763 — NO gtggcaggagtattttcaccaaagaaattaaatgctacaaatcctaccaccacaccactggtttgggctcatagaaagtttgttaagagtctgtgacatgaggt
    ggcctctaatacagtgagttcaatatttgaacttctgtaaagaaaaggattagatttattcagtatgatcttaaagagggatgctaggggcagcaggtaaaaattt
    cagggagacagattttcgttcagtgttgggaaactcctgaggtaagaagtgcccattaggctgggtggccactcaccttagaagagagatactacagagaa
    ggctgaaacatggaagattgtaggggttgagtggctcattagtttggccaccaaatc
    731 3642784 PDIA2 NO tgtcacccccgccatcactgctggacaggagccacccccttgggtaccagagggagctgtgcattgtgaataaaga
    732 3178621 SECISBP2 YES tgttaccgaggttttcaaacagtga
    733 3681988 KIAA0430 YES cgatcggtgcagtgaatagcctccacagatacaaaattggcagcaaaaagatcctggtctcacttgccaccggggctgccagcaaatcactctct
    734 2973750 — NO ggagcgtgggagttcatattttacactatgttggtacttaccatgcaaatgaacggccctgctgggaaaagaacctttatccagagaggggatccgaggaaa
    tagtaagagttgggttccgagaagctgtgctgcatcacgggagagctcggtgtta
    735 3284084 EPC1 NO atggtgcggaacctgctgttttatctatttattgtgccgtgtttacagttttttgtacactgtaccttcattggttcctgtgctgtagtaaatgtgttaggtagctgtgga
    ctccttggtattttgtaaatggtataacataacttggttcccctctgggtccttgagttttctgtgtatcatgtgaaaaaaaatggtgacatacatacagaattttaca
    aaaaaaaaaaaaaaaaaaaaggcatcagtttttttaaaaatggggaatgtactattaaatggggatcttcctggtctactatcattaggacaagtaacaagctaa
    aaatgaagtctcttgaatctttccatccccaacttgcccacaaagctgtgggtggtttctggtacttaaagcactaatattatgttgctgctctgcgaacagccca
    gtagtcccattt
    736 3642301 — NO ccacaggagacacgaggccgaggtggcgcagcacccaccctacacagcagtggccatgtgccaattacacgtgctgggaggag
    737 3133236 PLAT YES tgtgtctgaacgatggccgcatgactttggtgggcatcatcagctggggcctgggctgtggacagaaggatgtcccgggtgtgtacaccaaggttaccaac
    tacctagactggattcgtgacaacatg
    738 2858415 — NO gctggtaataatcgcgtttttggtaaaaacacctcatggaatttttttcctttctcataaaatagctgatactgtaaaattgagatagcctctcaagtctggaacacc
    tttcaattcatcaaaaagggacaacctaatattccaaagaagactcaatccttttaacacacatacattttagggccagtcaagagaagtggcctgttctgtagg
    aaaacatttcttggcacattattattttaagtgattgcaggagaccacagagggagagaaaagagacaacaacaacttctagcatgcctgggggatgacttgc
    tctttcatatttgtggaaccctatgtcaagagagaaaacatctaaaaataaaaacgcatttactcagattctctagggcaaggtgcaa
    739 3301253 — NO cttgtggcattgtgctaaagcaaaaaggaatggaatttgcaatgagagagcctttcaagttcaggctcagcctttagctgtgtgaacttgaaccactcacaattt
    ttctgaatctcaatttcctcatctgtaaagtttatctaatatgttggtggtgaggtaatcatattattatctcaaataggagattgtatatgaaagggctttggaaagg
    caaatcccattatttgtttaaatcaattttttcccctaaaaaagatagctcataaaagaatgtgaacttaatctgtatgtgtaatttctttcaagtcctatctgatgttgct
    tgtgac
    740 3068212 DOCK4 YES aatgcctgtagtgtccagtaccgacgaccctttggctgtgcagttcttagcatcgctgacctgctaacaggagagacaa
    741 3664307 — NO ccagcaattctgaggcagggaccaatcaga
    742 2357616 LOC388692 NO atgtggattgtctaactggaggttgggagtccagggtgcagaaggagaagcttggagtgcaggatttggtggtatgtgtgtggcagtaggcactatgttctaa
    ttgccag
    743 2824047 — NO atgaccagagtcataggtggtgatgt
    744 3348756 C11orf1 YES atttaagcgagagcctcactggttcccaggacatcaacctgaactggatcctccccgata
    745 3561991 — NO cttatttgatgggtggccaagatactgggtagggtggtgtgatttgctatactgagtagatcagtaaacaataaagtataaatcttgctttgtagttggaaggtca
    gttaacaaatatttagtcaatatgatgctggagttggctaatgtatcccccaggtctaattaatgaaaataatcttgcattggtctttaggaaaatcatttttattctctt
    tctgaatacttaaccatagttgtttacatgttttactgtggaagtaatatcttttatgaatgttttagagaaaacaattatggttcacttggaccattcagtaatttgtcc
    agcctggctagtttctagttatctga
    746 3051857 — NO agagaagaatcctccgacggcttcgttaccatcctgtctgaagcggattgcacgagccc
    747 3459696 — NO tgagcttcacatggggtcaaactggaaagtatctctttgctatgctcccatttaattaaattaggaaatctgcctaaaacttgaatcactcctcttttcagctggtgg
    ccaggcaggaatgctccctgaagagtactctttcaatagacttcagaatgtgttacctgaaaagtgctcatgatgaatcaagacatcactgtgttttccatacttc
    tgaagtagagattgtccactaacagcttagggaaagcagagtacccgctcagctgctctttttctggtgtggtcagaccagctgggtcctctgaaacatgaat
    ccatagtgcttcctttgttatactatttctgactcagttttctctaaacggctgtaaaatttaactgcctagctgtattttctttctgtggactttatgctctcatatttagg
    agaaagaataagagaacaccaacttacatctctgtagctctggatgattattaaggccctggtctaatgcttaaaggtaagcatctgttatctatattcaataaaa
    gaggaaaatgaaccccagagagaaatcaagttactttagaatcgcaggctgtcccatgaccctggtgaccatcactgaatta
    748 2614179 — NO gtgaagccatcagtgtctacagcttcagctattgcccgtgtgcagatggtgcttaatctctcttgtgccttccagacctgcatt
    749 3047613 — NO attaggtgatggtagcggactagccgacggagggcaggcaggggagggggagaggactttacagaaaaggaattctcggtcgagctctgcctggagat
    gactggcttacacttactaaacccagcgggtca
    750 3677890 CREBBP NO atcaacagccgccatcttgtcgcggacccgaccggggcttcgagcgcgatctactcggcc
    751 3177929 DAPK1 YES tgacaattcaagatagtttgcagcatccctgg
    752 3211613 TLE1 YES tcctggtcccagacagtctaagaggcacagataaacgcagaaatggacctgaattttccaatgacatcaagaaaaggaaggtggatgataaggactccag
    ccacta
    753 3452723 RAPGEF3 NO tgtgagaaggtgaagcccataaggcacagaaggagttcagtgagaccagtgacttcaggctcagtgtgggagaccaggggaaggatgggcatgcagg
    gggcgggggactaggctgtgggggaggcaggatgcatggaaggtagggaaggctgaggaggtggagccaaagtcggaggtgggagaagggctgtg
    ggtccctgtgggaccctcatggggctcaggggctggaatgaaggaggtagatgagagggtctaaagctggaacatcatgagttgagcatgggatg
    754 2845333 — NO ggggctaacatggacggtcaggagctacgt
    755 2852760 — NO tgaatgcctgaatctcaaacttgtacttcatcatggactccagtcttcctttcacatccaatttcaatgatcatcaatacagtcattttgctccttagcccactcggac
    tatttctctccatacctgctgcaactgccttgacactggtgtgacagccttttaaaaactggtgtttggggctggtatcactccagtggattc
    756 2750640 — NO caataagatagacggaaatataatatttaaggttagagaagaaggctgagtgtggtggctcactcctgtaatcccagcactttgggaggctgaggcaggaca
    atcacttgagctggggagtttgagaccactcagactcacttgagacca
    757 2807722 — NO ttcttatgcaaacaacaccatctgggctctggaacttcacaaaaggacactgttaagtcacac
    758 3338718 — NO tcatccatcaggctgtgtcagacgcacctgagccctc
    759 3482760 — NO tgaccccagacctagggttgctggtgga
    760 3884900 — NO tgcttcgattgctttcgagtcatgagttggtg
    761 3038653 — NO aaatgtgggcccgttaaagagcaagactctagaaaggaatctagccaaagaggacagcgttggtgggatggggataa
    762 3340340 RNF169 YES agtcagagctgtagtgacacagcccaggaaagagcgaagagcagagtcagagcagttccaggcaacaaagccaag
    763 3441973 — NO agtgctgtctacacgctgagtattaaatcctaaatgtgtatattagctgacaacctctcccttgaactctgcactcacataaccaacaatctaaacctctccctcc
    catatgctaccccatctcagtaaatggcaacttcattcttctagttgctcaagtcaaa
    764 3629351 SPG21 NO acccggtgtgttcttgtatagtcagtggcatcagcacccgtcagccggccttttccttcaggttcgtcaggctcaccg
    765 2611420 — NO gtgctggcaccatcgagccacaactcaggggcctcatc
    766 3371610 — NO acagttttgagacaggtggttcaggtg
    767 3795789 — NO gcctggctcttccttaccacccggattttgtttttgctttctgggtagagctctgatgttgccaaacagcctgtgctcctcgtgaacaatctctccagactcaaaat
    agcgagcagccaaggggctgccactgcttgcggtccacag
    768 3118031 — NO aggaaataactttacatgtgctcctct
    769 2976043 IL20RA NO tcctgtgcaaacaagtgagtcacccctttgatcccagccataaagtacctgggatgaaagaagttttttccagtttgtcagtgtctgtgagaattacttatttctttt
    ctctattctcatagcacgtgtgtgattggttcatgcatgtaggtctcttaacaatgatggtgggcctctggagtccaggggctggccggttgttctatgcagaga
    770 3330211 — NO attactgaaagtggcgtgcactgaca
    771 2397801 — NO atgccagagactgtgatgttggaaa
    772 2537317 TMEM18 YES aatacatcaatgaggcggctgcgat
    773 2875953 — NO caatagtgcaatatcacgaccaggatattaacattggtacagtcaaaatacggggcattaccatcaccacaaggatatctcatattgcccttataaagccaccc
    cacttccctcctacctcacccctcctgaactcctggtaaccacaaattatccatttgtataagttggtaattttgagaatcttacataaatggaataatacagtatgt
    aacttttgggattgactttttttcacttagcataattctctgaagattcacctaggttgttacatgtgtcaatagtttgttcctttttaaattttaacttttattttttcgagagt
    aagtcttgcactccaggc
    774 2882417 — NO aggaaagcatgagaggtcagcagca
    775 3095010 — NO catgcagtacattggatatgatataatttatggtttcttgtttgcagctgtttgtatctttttaatcccaaaccagacaaaattataaacattttatatacaatgttatctt
    ggaaaaagttagatgtaaataattcatcttaatctatatttgagaaatctgaggggtattaggaaactcatgagtgaatgaacatatagattggatcaaaggagg
    agagtatgagagtagggagaccaggtaaaaaggtatcatagtcatc
    776 3450794 KIF21A YES ggatgctcctttaaacagcccaggatcaga
    777 3627349 — NO tcttctggctcttccgtgacgcattacaacagcca
    778 2360857 FDPS NO gggagcagctgatcaggtttctgac
    779 3821204 PRKCSH NO gtgcggtggatactgacctttgctccggcct
    780 3665595 FAM65A YES tggaggatgaggacgtgcagactcgagtggctgg
    781 2852747 AMACR NO caggcccacggctcaagtgaatttgaatactgcatttacagtgtagagtaacacataacattgtatgcatggaaacatggaggaacagtattacagtgtcctac
    cactctaatcaagaaaagaattacagactctgattctacagtgatgattgaattctaaaaatggttatcattagggcttttgatttataaaactttgggtacttatact
    aaattatggtagttattctgccttccagtttgcttgatatatttgttgatattaagattcttgacttatattttgaatgggttctagtgaaaaaggaatgatatattcttga
    agacatcgatatacatttatttacactcttgattctacaatgtagaaaatgaggaaatgccacaaattgtatggtgataaaagtcacgtgaaacagagtgattggt
    tgcatccaggccttttgtcttggtgttcatgatctccctctaagcacattccaaactttagcaacagttatcacactagtaatttgcaaagaaaagtttcacctgtat
    tgaatcagaatgccttcaactgaaaaaaacatatccaaaataatgaggaaatgtgaggctcactacgtagagtccagagggacagtcagttttagggagcc
    tgtatccagtaactcggggcctgtttc
    782 3004680 — YES tggatgagtgtaagggacaccaaggaggt
    783 2722233 — NO tgaaattcataaaggcatgtgtgcca
    784 2805960 — NO cccagggcattagagtgacctcacaagagtatctcagaatatttaaaaatttgaacacacaaacacaatgaaactcaacatctgtcagacatcacgtgaacta
    ctagtgaggtagttcattctttcaacataagattgcactataatccttctgataatttcatatttttgtgagactgggttttccaggccatctgataaaaaatcaagta
    ctatatggacaccaacatggagcagaaaatgagggcagcagtgtccaatctcattccaggtg
    785 2952396 — NO aggaatggaattaataggttgtggcaatatcaa
    786 2612927 — NO caacccaatctacagttgtgggcagtggct
    787 2640231 — NO tgcccggcctgcaataagtatttctaaataagatcacattctcagctacaagaatttaggatttcaacatcttttgaggaggactcaatttaacccataagaatact
    atgtgggccacacatggtgcttcacatctgttatcccagtatttcgggaagttgaagcaggaggatcattgctcagggcctatggggacaccgggtgcataa
    gaccaca
    788 3371122 SYT13 NO agcaggaaatggaatatgcgggtcacactg
    789 2972930 — NO gctgtgacacaacagtgtggcgatgtcccacagacctgaaa
    790 3529011 — NO agcggctgcagcacgtagttggagaaggtgagggcgatgacagcctggttggtggggtagatcaccagcacagcaatcc
    791 3670860 LOC100129617 NO gagccagccaccacgttagattttagagtctcctggagcacgtgaaaacaactgaaaaagggtaaccacacatcatttcacttgtgatgtagcttgcctgtctc
    cacaccatgcccctgaagaatagtatatcacctacagccccttccccagtcaggaatggaagtgcatgacacatgtgctcctctaccccttccatgctcatgg
    cagacatcattaatcaattatagcactctttctgtagagccagagacagcatcacactctttcccctcctgcattccaggccaccactaccaactgaaatcgtgt
    tagtaccataatgaatgctatgtaccattctctaccctaagcgattgcaaactgtaaatgaattgttgctgatttctgagcccctcctagatttggggtaaattcattt
    cttgttttcagaacacaggggatagggacaccctgtgcagttctttctccaggacaaggagactccccactgggggatggggcggggtttctgccttaatttg
    ggcgctcatagtttcaaggaggagctctttctggctttggccagctagaaggaaaggtgccctgtttgttaactttaaaatcactacgggtgtagtgtatggagt
    gggctgtgccatgctggagttcagagcaaaggttcttcaggttttcttgcgaaggaccttaacttgtcaatggcagagccacacccccgggacatacttggc
    agaggaatgcctcttcaggcacataaacatttttgcatactccatgttagtcaataaaccgtttcataagggttctttgaggacatctgacttcaaagggaaaaa
    attcataattcagacaggctctcggggcttcaccatacaacgcctttcttgtatttggttagttttatgggcctggagtgttgaccatgtatta
    792 3844568 SHC2 NO ttcctccgcatgagcctctggcatggtccttcctccagctggccccgggctgggcagagcctcctcctgccggggcccctgcccaccccctcctttgcctgg
    agtgagggtgttcataccaaagacggaaccatttcgcctttaaagaaaatatatccagaagcagccgctgcctcggagccctggcccttgggtccccctctc
    gcctggctggttcggtctaacgccccggagagtcagggctcccaggaccctggggaggaggcggattccgggcctggctgggcttcctcttcccacctg
    aggactgggtgcacagttgtctttgaggggggacgcttaaggtgctttggggttctcaggccaggatacatgctggcgctgaagtgcaggcagccttgagg
    tcacctgggatctcggggtagccaggctgctccaagacagtggatatcgaggcagtcgtgaggcccctactccacctgggagcaggggaaggacgtggt
    tgcctggcctgggctgcgcccagcagcttccccccagtcctgccctcccagctgtcgacccagatgggatgttc
    793 2810517 GPBP1 NO cagcttacactgttttgcttgcagagtcatatctttttcgtacaatggaaatcctcaagtccactttgtgcggtctccctctccttcccccaaaaaacaacaacaac
    aaaacaaaaaccaaaaaggaaaatgtagcatgttggctaaaactggagcaaagtgcactaaaacaatttcctgaactcacctgttgtactattcaccttttaaa
    ccataaattgctctttagccatttgtagtgcagtaaatgttacaggaaaagacttggcacattttcttccaaattttaagaggtgattttcaaaagctttattggggta
    tgttgtcagaccagggttttcagagttgatggaaaagagtcttgtgagaaaacttattttgataaattattacacacgcagaaaaactgatcacactgactggat
    ctgtccacgacatggaaaa
    794 2377968 — NO gtaagacacgttcccagaggcaggac
    795 3020324 — NO tatgtaatgagcatgtgcatagtgtgtgtatgtgtttgtatgtgtttgtggggggtaatggtctc
    796 3133424 — NO cctgagctggcaggtggcatcccaggctcgtgccaggacccagcagggctggtttccatgggcctgaaaaggcccacatcagaattccagggcatagg
    cgaggattact
    797 3225212 RPL35 YES cttcctctttccctcggagcgggcg
    798 3731955 — NO tggaaccctcaggtgttcgcaggtgt
    799 4012443 — NO ggagtaggggtcaactggattttgccagc
    800 3145052 KIAA1429 YES ttgatgaccccagaaggagttggccttaccactgccttacgtgttctctgtaatgttgcatgcccaccacctc
    801 3542308 — NO gggacggtgcacatgtgcattcacatgtgttttatggatgctacagaggaatatcagaagagaggaagagggccccaaacagcccctttagctctgaaa
    802 2385170 — NO atggcaggccccaatgtggcgtgcattgag
    803 2617336 CTDSPL NO ggtagaactgcccatgccacaaatatttatttggaaaagtagtcattaaatgaacccactgccttaaatgtcttgaatgttgcagtcaagtgtctgtcatgtgttga
    tatccacacagaattaggccctaatgagagccttagaccctcaaccatgcccctttcgttggcatcacagggccttatttggaagagcgggcaaagaggat
    ggaaatcataaaatatttcatgggaatcgaacctagggatagtgctccacttctgacgatggagtgaagacacttggcagacttgagccagacacttcaccta
    gtagttcctgaaactgtgagcaccactgcactaagccagtgcggagctgttagggacgggcccagctcctgcaccacggacacagaatgtctggagagg
    gccagcaggccctctgagggttctggaatctgtgcaccttatttgaccacactccaaaattctgtttttattttaacccttgaatctgctttatgtacataatcaaaat
    atctatatctatatctatatctatatctatatatttttaatcatctacatgtaaatgaagcaatagaattctaacataaggccaagaaatgagacgaatgtttggggttt
    atgttttttaaggtaaatacgggtattgtttttaattattaccatgtattaaattgtgggctttgaaacctaatgaaacctgttagccacttctctgtgccatatacttcc
    catgttaccaaaatacccccaactctttagccaaaagagaaccctgacctcctgagtttccatgctcctttctgtaccaggtttaaatgtagtcttctggagaagt
    atttttgacattgagctctgggacaggacaccttgggtttgtggactgcagcccactatgatgttattacttctctggccaggcctccagtggaagtgcacagg
    cactcccaatgttgttaatgctctgtcttccatttgttctggaatcctacgtgttggtctgtggttccatgcat
    804 2982034 RSPH3 YES catggggaagacacacatcagtctccagaacccgaggatgagcctggtggtcctggagcaatgacagagtcactggaggcctctgaattcctggagcag
    agcatgtcacagacacgggagctgcttttagatggaggctacctacaaagaacaaca
    805 2335196 — NO gtacaggaatccagctgtgtggagcag
    806 3561721 — NO tccagctatacacccgtaacccaacagcggctcaaccctgggcgccaactaccgctgcgtcctccgccgcttttcg
    807 2819696 — NO gataatagtagtatggatggcagtggcat
    808 3408052 — NO catgatggttgtcttcactctcctactcccaatgattcctagaaaagaaactttaaaacatgtttctacttcccattctgcagtttagtaaaatgatttggttaactctt
    aaaactttttgtggaataatgttctgtgaattcaagtatacaaggcaggaggatcacttcaggccaggagttccataccagcttgggcaacatagcaagaccc
    cgtctctacaaaaaacaaaaagagaaaaaaaatatataatacttgaggtagttgaattgccgtgatttattgtcaccaatatttttaaatcttatatttattataataat
    acacattacatttttataactgggttataacattgattattctcacttattctagatgtgacttatttaaataagtttagaattatatattaaatacaattatattaaaaacat
    ttttgcttttatgtaaaacactatttgccatgacattttttgtcacgtaattttgtttttctttgtgtttgaatatgatcaaatacttcccaaaattaaacttacaaatgtatat
    caacatattataattcaaaagctgtttttatttgggaaataaataacaatgtgtaaagaccgggaatttgttctcctacctaagcctgatgattaaaagacagtgta
    actatgcaggtgttaaacattttctatattcttacagccatctctgttcatatatccatttttaactccacgcccctgtaagcctttgagtttgtgatccctggtgaaga
    cagtgacccacattgattttttttttttttaaggtttctctctcttttttgctttttctctcgaatataggacc
    809 3628699 HERC1 YES attcagcctcattgggtatctgccctggcttggccagaagagggtccggctacagcctggtcaggagagtctccagaattgttgttggtgggacggatggat
    ggatctctgggactgattgaagttgttgatgtgtccaccatgcaccgtcgagaattggagcattgcta
    810 3350729 — NO tgcagacgtgcacattcccagtccgtgccccagccgtcctgggtccccttacaagcccgggtctgccacttcacccttgtttttccccatcctccgggtccac
    atttcatatgcccctgccctcattcccttatgattccctagctgctggttccagagtcttctgggcttacagtctcccggc
    811 3380411 — NO aaagcaaggaaggtattgaagacacaaagtcacatgtgatgggctcaggagccagtgtgaggaagggctgctcatacagcacagtggaggat
    812 2377588 — NO cccatagagctcctaaccagatgcaacagtgactgcgtcaccattccccacttttcccaactacgcagtgacaaacctaccagctttacc
    813 3219836 — NO tgggagccgtggatgaaattgtgctc
    814 2737650 BANK1 YES catcatgaaagcaggaagacatacgggcagagtgcagatg
    815 2843633 — NO aggctcgccttctcaatagcgtgtatttggatgagatgagtttcactgtaaagagaaaaagatgttaaaacctcattgtctaaggcccctcatctgagaagtctt
    gtctgaccctctagcccagcaggaccaaggtgtggtgcctggtcccagcctgtcctctgctcccctgggctgcagttggcccagttgcctgcctccattagat
    acggagttgctctggggctgagatgcccatctcaagtgcattctgtcggaagggttctctgctggaaggcctttggttttagttgggattccatgagctttagcc
    caaaggtggcctcccatactagcatattt
    816 3478420 — NO ccactgtccacagaccatctggggccctggagggagcgggctgggccagggaggaacaactgggaaggggcagggaagaatcactgaacatcagtgt
    gaaggtggcctga
    817 2749415 TMEM144 NO agcttttcaagacacttcctgcatctctgacctgttgcacctctgttatcaggcacctctgttatcaagc
    818 2921363 — NO tgacgcgggtcttacctgggctaaattcaaggtgctggcaggaatgcattcctttatggaggttttggggtagggggcaaatccatttccagtttatttagttgtt
    ggcagaattcagttctttgcagttaaaggatcaaagtctcctttccttgttgtctgttagctgagggtctttactagcttctgaaggctgccttcattccttggctcat
    gatccccttttcttcagagcctgcaatagtgggtgaagtccctctcccattttgaatcattcctgttacactatcatccctctctctgacctacccttctgtcttccatt
    tccactgttaaatgtctatttgattactctgggcccactt
    819 2703246 KPNA4 YES tagttttgaactgtgatgctctttcacac
    820 3226615 WDR34 NO gctcgcagcctttcttcggagagtgg
    821 3373866 SLC43A3 YES attactttaaggatctgtgtggaccagatgctgggccgattggcaatgccacagggca
    822 2852746 AMACR NO ctggtagcaagttctggatcttatacccaacacacagcaa
    823 3023100 — NO ggctcctatccctacatttcaaatagcatttctctcacaattgattatgtattaaggcttgtcaacgaaaaggaaacttttttctctcagaatttctagaacttttttcttt
    aaaaagttttttattctgtagccagaaaaatttaaagtttgtgctgggttgctttggttatagaactaatgaagcttgagtaatagtttcagacattctcagggtttttc
    ttctgcagccagattttacacttctattatctcagctgtcttataaatgtattccctccatcacacaatataattagaatgtattgatgaacagatgtaacttcatcact
    agagagacgttaaataaattatgtgttggtatcatgacttttatcaaatcatgaaggatgccatcacttttatgtgatagtccattggtatagtactaaagtttgtaag
    taaagaatgtcagatagataacaagataacttcattttcgagatctcataacctgggcc
    824 3431525 ATP2A2 NO tggtaccatccagttaagcccgtgacaaaaatggaaatttctaaatagcccaagtctccagggcaattgggaacagctttgaacccactaagatggggtctg
    ctatgccaaaacatagatacagaattcacagtttgtcctgcattaggacattctcttcaactttgccactgtagaaagtggaggtaggtcagcggatggtgcca
    cattaacagccgccttactgaagtgtagtcca
    825 3695469 — NO tttatcctgatggaaagagtccagtagagaggaagagattgatgatgtaggagagagga
    826 3761535 HOXB13 NO ctgccaccgccactaacggagatggccctggtagagacctttgggggtctggaacctctggactccccatgctctaactcccacactctgctatcagaaact
    taaacttgaggattttctctgtttttcactcgcaataaattcaga
    827 3823884 NWD1 YES actgcagagccggtattccatatcctgggagatgcctctgatccttggatgtgcatggccgtgctggcctcccaggccacactgctgacagtgtccagggat
    ggtgtggtcagtctgtggagctcagctacgggaaaacttcaggggaagcaacatatgtccagcatcaaagaagaaacacctacctgtgccgtctcagtcca
    gaagc
    828 2475018 FOSL2 NO ctcagctctcacaggggtaatcatctcaagtggtatttgtagccaagtgggagctattttcttttttgtgcatatagatatttcttaaatgaagctgctttcttgtctttt
    atttctaaaagcccccttataccccactttgtgcagcaaagatccccgtgcaggtcacagcctgatttgtggccaggctggacaaattcctgaggcacaactt
    ggcttcagttcagatttcaagctgtgttggtgttgggaccagcagaaggcaaacgtccagccaacacacaggactgtaagaggactctgagctacgtgccc
    tgtgaagacccccaggctttgtcataggaggtcgttcagcttccccaaagtcagaggtgatttgatttggggaagactgaatattcacacctaagtcgtgagc
    atatcctgagttttacttccttatggcttgccctccaagttctctctctcatacacacacacacccttgctccagaatcaccagacacctccatggctccagctatg
    ggaacagctgcattggggctgcctttctgtttggcttaggaacttctgtgcttcttgtggctccactcgcgaggcagctcggaggtgtggactccgattgggct
    gcaggcagctctgggacggcacagggcgggcgctctgatcagctcgtgtaaaacacaccgtcttcttggcctcctggccagtctttctgcgaatagtcctct
    ccctggccagttgaatgggggaagctgctggcacaggaaggagaggcgatcccggctgaggcttaggaaattgctggagccggctccaagcagataatt
    cactggggaggttttcagagtcaaacatcattctgcctgtgttgggggccaggtgtgtcacacaagcatctcaaagtcaaaagccatctggggctgctgcttc
    tgtttctcaggctctggggaaaggaatctccctctcctctcacttgattccaagtgtggttgaattgtctggagcactgggactttttttc
    829 2987324 — NO gttggtgcccaacatatgcctgcca
    830 3379421 SUV420H1 YES cgcctttccttcgaggagctcaaggcattt
    831 3109159 — NO cattcagcactctcacgggatggacagagcagtgttcatgcag
    832 2480318 — NO ctctgacgcacttgaggggttggctc
    833 2841516 C5orf41 NO gcagggatctagacgtcaggccaactgagagctgacagggaagagagagctagctagtatagacatagacatgagaatcagctcagctgctgtaggaga
    aagtcactgacagacagtagcatccaaggcatccagcgttatatgacccacgaaaacccccaaaattaaatatacacaataaaaggtcaaatgtttttcttga
    acaaaagtatatttatattgaaaacaatcaggtgaagagtagaccctaatcgccagtattt
    834 3738805 FLJ35767 YES ggagcttcttacctgctcacactgg
    835 2771466 — NO aaaagagagcaatcctgcaagccaatcccgactctgaaaatcatcacta
    836 3322962 — NO tggtggtgatgcttatagtggagagcctctaccttgctgcagctc
    837 3906050 — NO tagatctccaaaatgacctctcacca
    838 3119642 — NO ccagagaaagccgctgacagggaggagaggccccagcccctattacaaacccagccatcaa
    839 3125570 — NO ccccaaaaccatctgcaacagccag
    840 3933835 — NO ctgatggaccttctggccgcttctatgtttcttctctgattg
    841 2802644 — NO gggatcacttgccacctgggatgtt
    842 2854122 — NO aagttctgtgttagatagtcaagtagggtgactgtagttagcatccatgtattatatatttcaaggtagctagaagacttgaaatgttcccaacacagaaatgata
    atactcatgagataatggata
    843 3147610 AZIN1 YES gcaagagttgggtgtacctccagaaaacattatttacataagtccttgcaagcaagtgtctcagataaagtatgcagcaaaagttggagtgaatatcctgacat
    gtgacaatgaaattgaattgaagaaaattgcacgtaatcaccc
    844 3398488 SNX19 YES gggtgaacaaatgccggctgagctggg
    845 3629947 — NO gaccagctctgatgggcaacccaaactcaagaagtgtaacttttctgcagaacccttcagaacttaaaagatcactgatgtaaggtcactagctggcacctctt
    cttataattacaattaaatgggcaataacttacccttacataatgacaactactattaaagagaaatcatggcatttgagaacaatgacataagattaaatcaagg
    caccatggctaactattcagga
    846 3677823 CREBBP YES ttttgtgtgcgacaactgcttgaagaaaactgg
    847 3101370 — NO taggtgccctgaaagttattgttgctttttttgttttttttttttcagtttgtgcgtgtcacttgaatcagaaaccaaacacatgtaaaaaaatatcatcctcaatgcccc
    ccattaactctctctccagaaggtgacaatgttagtgaactcaagactctcactgatgatggtattttacaatgaaaacacaaggaaaccctttgaggtccaattt
    tcacatcatattctccaaatagtaaaatagcagctctacatgttgatgaaaagaaatttcaatttcttcctatttgtttttactcatatcaacattaatatgtatctggatt
    tattaatttccaaaaagaaaattttagttaccaaatatttcagaaatttaataaagcattacatatatgtaattagcacttatctaccaaaaaaacatatgtgtatgtatt
    tatttatcttaccttcactgaagttcttttttctggctggacatgagaaacaggattaagtgatcaatgctggctttatttcttcataagcagtaatttgggtctttttcat
    tcaacacaacgcagcattttcataataaattcacaaaagacaatacaaagaaacacctactgaatagaactctgtcgagcaattcatgttttaaagttggactct
    ataccaaactggcattatggtattataggcatttgatttttgttttcttattttcagtttgtcagtttctttactaccattatttttttctagccggagataacgtataatca
    848 2977512 — NO gccaagattagcatatgtgagtggcaca
    849 2329726 — NO caagcacctcggtatagcattattactgaaaccacttaattcccagctttttgagttttttaaaaaaacccactgcactaagattcacaattcattgctacatacaaa
    ttaaagctagtaagaacacactaacgtcacaagtttctcattctaaagt
    850 3626942 — NO tgcatgctcacagtaacacgtatactaaaat
    851 3823576 RAB8A NO gcccacggccaccagaatgcaattgagaaatcgtttattttagtaactgtctgatctttttcaactttggagatggaataagttaaaaatttgctatttttcctgtaac
    atctgctgaacgggcccacccacacgttgtatattcagagagagagagggagtcaaggtgtgaccgtcgaccacagccagtgtcaggcctctgcctctgg
    gcctttgctttgtggcctcactgcaacacaaagctccaccaggaggctggttcacgtcccctaccacggaagcgaggtcccagaaggccagcggtggttc
    caggagcaacagctcccaaaccctgagcaaggcaaccgatcgccaggaccaggaagcatcacccaggagatttggcgcccacttc
    852 3837475 GLTSCR2 YES cggagcttcctacaatccatcctttgaagaccac
    853 2802804 — NO tcgagtactatgtcttttgtggcactgaaaccttataacactatgatagctctgcttccacagcagtgaaaaccgaaagagccgggctgggcacctgcctcttt
    gaggtggaactcgggtcag
    854 3410550 — NO atatctcgtctaacccctaccattgtgcctggccctttgaaatgtgtttcttgctgacgtgcttgtttctcct
    855 2808525 — NO aaacagagtagcagttcagcccttatttgccttcaaaaaaagaaaagtacaaagtgttctctaattctggcttttagaaagttctaggaagttaaatgaacactttt
    ttttcactatgaattatatgagtgaattcatcagaacggctgcttctaagaaggattttggtggttttagaaaggtaggtgtttattcctttgcctgggaagcctcac
    cagagatgttgactctacaacccatctcattcgttagtttttgtggacagcagttgcctcatcgggaatttttttttttcacttccttaccatgtttcccttcggatggat
    agactagcc
    856 3484743 — NO atttacactttaacaacttgctgggaatttaaacaacttgctgggaacatcctttgtgaggcactgtagcctttttttatttgaaactacttaaactccaagacaggc
    tcactaactctttttcaagtgcaacaacaaatgtgttagctgaaaatagctaatttaatgattatttgtgacacagacacgattatgtgagccaagaga
    857 3765643 INTS2 NO ccgaaggattttgcagtcctctgtcagtaacttccattgattaggcagacatattcaggtaaaccctaatcattaaaaaaaaattatcaatgtagaaagtaattcc
    cttttttctctctgagatatacctcaatcacacacttccccacccccacttgaaacagacctcttcacttgtgttttttttttttttttcctgaggtggagtcttcccctgtt
    gcccaggctggagtgcagtgggatgatcttggctcactgcaacttctgccacctgggttcaagggattctcgtgcctcaacctcctgagtagctgggactgc
    aggcacgcgccacctgtatttttgtatttttagtaaagacgggggtttgccatgttgcccagactggttttgaactcctggcctcaggtgatctgcccaccttggc
    ctcccaaagtgctgggattacaggtgtgagccaccgcacctggccagaccgcttcacttgtaaaagaaattaggctaataagaaggtgtagtttttgagaaat
    gaaatttaactttagccttttcactagtaaatagtcacatctcattttcttcctttgtaaaatggggttactactggccctacctcatattctatgagaatgagtttgtag
    ctgtttcaaatcatgaagtgcatagtatcacatgtgatagaatatttataactttttattagatgcttaatgttcaattaagtaattttgatgtgaaaaataaaagtaata
    aaagtatcttaaaaatagcataagaattttcatatttttaaacaaggcagttttgtagtcccttaagattaaatacaactgctccttttttttttaaactgaggccttgcg
    atattttgtg
    858 3810029 — NO ctggtctcagctggactatcgctgaacagaggcgttggccgcacatccccttggaaggactctttgcttccacattcggaacactgtcctgct
    859 2658003 — NO cttgaaatttgagcacatcccactgtattatttcactgtatggcaaaagtgaaggaggtaggcatgttctgtcatccttaattaagctttgggctgcttattgaagta
    tcattttttctatagattggaacatggtttatatagcagactatcttgtccactgacattgcccagtactgagttcc
    860 2788748 — NO atgtagtacatttatgggctgtgat
    861 3242486 — NO ctcagctacttaggcaggagaggca
    862 3540024 MTHFD1 YES aggggagtggatcaaacctggggcaatagtcatcgactgtgg
    863 3439941 — NO tgttgggaagcagcaacaatcagccatacagctttcaag
    864 3457676 CNPY2 YES ttgtggaggaatacgaggatgaactcattgaattcttttcccgagaggctgacaatgttaaag
    865 3843592 — NO gcctggccagttgtaactatttatcactgtctggactcataaacattttgagatgactttgggagtgcctggggagtttcattcagcctggtgcatatgggcagtg
    aaaaatatgctcatctgtgatagtagatgtggtttggttcacaaatccaggggctgggctttaaacggcattaggtggacagaggagggttgctacagctgag
    gtctcagctggtgcagcacaaaagtgaaatagggccatggctatctgaagccatatgtggttctgtgtggctatggagtcattccaggagacgttcacaggat
    gatttgggattaccactgctattgtaaaccatggaaattctgtgttaatattggatgctatttgtatttgtcaagcatagtctggatgcttatccacattttggtataag
    gccagaattgaaggcccaatatgatgtgtcactttgacatcttgtgaaagtgggacaaccttaaaaggtgtgagtacaaatctcattcccactctgctctcttga
    ataatgtatcctagcctaacagcccgttttatcaaggtgataaggcagggttccaggttgttatattttgtggtgggtttcaattccatccctaccagcagagttat
    ggaaacaaaccattgcatattcccaagggaatcatgggccgttata
    866 2518951 — NO gcaaccctgcagtggtagtagtggtg
    867 3187461 — NO cctgggaatattggcgctagagaacagtgatataatttgaggtgtctacaaatgttgtctaaaaaacctctctcctctcatcccatgtttcctctgactctactctta
    aaatctaggtatcactgggaagagtaacgcactaggcccacaggaccttagtattaatataaatgagctttagttttcaaatgtcatttttttctctataactggag
    aaattccattaataaaagaaccctaggggatagagggtagagggagcgagaggggagtaagggaggacacggacatacttaacactacctagggcacc
    taaccatcagaaatg
    868 3730738 — NO ggcagataaagtacccatactaaaaagatgtctttagcttggttgaaaaataattgtcagtcctaccactgtgagttcaaagaacttaagaaaatacagaacttc
    aagcagagatatagaggattg
    869 2898998 SLC17A4 YES gtgagaagagatacattgtgtgttc
    870 3397924 RICS YES atctaaagagctggtctacctcgtgcagattgcttgtcag
    871 2494772 — NO taaatgactgtggactagtgcgcgttttttgttttcag
    872 3322617 — NO catgacccaccgtacatgcatgggcatgatctgattttttttttaattaaagttgtcacagttatcaaagtctcatta
    873 3735156 — NO taaaattgaaatgcaggttgggcac
    874 2346360 — NO gtattctctttcatgtggtcagtgtatga
    875 3757401 — NO caccagtttagcctttgagtgtgcagagctctgccctccctcccacccctcagccccaaatccaagatttcatagccctaacacccacccaagcagcttccct
    cacacatgccctttgttttcttcctctcttctatggttccttagggaaaggagccttctttagggatgaaaagctaactacagcccagtctggcctccagcagccc
    agggtcagctcagcctccactggaggcgagggaggagggcaaagggcatgggagaggtagggctgccctccaggagccttccccttccctaggagcc
    agtcaggattggggaggaaggcagaggggtcctagggagctgtcacatagaggaaaaggggctgggagtggggatgacaagaagtacaaagaaaga
    gaaagtttggggagatggataacaagctcagctgtgtcagtgatgtggaggggaggtatggtgggggaccagccatggccctatccaaccccaggctcc
    acaggccccaaattggctttgcaaatccaaacattttaaggaagtggtttagggatggaagagaaacacggtagaggtctgtgctgtggattttcatctaggg
    tggtgggaacaccagagatgtctcctctgccattgttttagttggctcctggacctcatcccagcagagggagggtgactgtcagcaggtcagtcccaccgc
    cactgtccccctcgcagtgggcctctgtgtctcaggcctggccaggctccctgcccctcagagctcctcgtggacccgctcctcgtcctcatctgacttcagc
    ttgagctcgtcgactgtgatcttgccgtcctgg
    876 2386080 — NO gggcgcttttatgaggcatgagggaggcttgataggggctttgaaggcactgatggcaattggtgaagtagacttttatctaaagggggcagaga
    877 3013608 — NO tttgcctcttcgagcttggcagtgcgagccacaga
    878 3460675 — NO atgaacactcgcaggtggtcaggtg
    879 2564601 MRPS5 NO cacagcttgggatgttaccttgccttttgt
    880 2939374 SLC22A23 YES tgataatgcctggaaggtccatatcgctaagttctccttactggttggattaatctttggctacctaataactggatgcattg
    881 3320209 — NO ccaccatgattgtgcttgccgggag
    882 3852627 LPHN1 YES gtgtaacaaccgcacccagtgcgtggtggtcgccggctcggatgcctttcctgacccctgtcctgggacctacaagtacctggaggtgcagtacgactgtg
    tccc
    883 3349758 — NO aaacaggccatgtgactgaggagcaggtagcattcatattattcatatttcgagcttggtagatgtagaattttgcagtggaggccaggagaggatgtgagag
    ctgcaggacagaggcataggtttttggaggtggttgtggtgttccccgatggcaatcaacttcacggagagaagaggttattttctacttaggttgcctggagc
    cta
    884 3427503 — NO aggtccttcaggtgccattaatttttcttgttattcaacacatattattgagcctctgtaatgtcctaggcttgttcaagatgttcagaataaagcagtggatagaac
    aggctttaaagccctgtactttattgcccaagtcaacgtccttagaatacaggtacctcacaactaccttgaggcttttattatgttattttcttctgcattcaggaatt
    ccccagagccaataggatacaattttaaaatgtcaaaccatttttgatctcataccatttggcttcagtccttctttccaactgtatcattgtctatttctaaataggga
    tggtctacactgtaaggctgatttgctcattgcccccacaaaatttgtcttgcattttctctgttcattcctgcacctgaaataattttgccactgccttctcaaagcc
    ctcaaaccttcaatgtctgggtcaaagccgttggctcccaggaagcctgttttagaaattaaatccccaagttcttttatctgcattgattatttaacacctgacagt
    tgcaacaactaagatgatttgagcgagataatgctccacattttttaccgtgtctgtgtttgtaggtgtgcccaactgacatactggctaagagttcagggtccca
    885 3835463 — NO gtcctggatcatcaacttggttacaacatggtgttaacatgtgggactgattgtgtttcttgttaatatttctgtttctcccaaccacgctgaatatt
    886 2809576 — NO tcaaatctatggcttaccagagagaagaccagagcgcaatatctccgtggccttagtcctgact
    887 3601075 — NO atgggccaaagctggggcacaggaaa
    888 3864620 C19orf61 YES gacttatgttttccgggcccagagcgctgaaatgaaggaacgagggggcaaccagaccagtggcatcgacttctttattaccca
    889 3888182 CSE1L NO ggaagttctccttttgaacttgtcacgaattccatcttgtaaagg
    890 3558243 RIPK3 YES cttcgggatcctaatgtgggcagtgct
    891 3702633 — NO tttactcctaagcaccagtgatgacctcgtcaagcagggtgggctgcagggagatgacagcgggtatgaaagggtgtga
    892 3433106 — NO tagctcaatgcaaccgacgtttctgagcccccagaatctgatccagatcccggacatataaaccacgccaagaagacaggggctgtctctagcacattctct
    cgagggagtccggggccccttcccagacgcaactgcaaaaggaagggctaacgccatggcgggcccgtggtttattttatatccgacaaagtgcacggc
    agcctgaactggactggaatgaaaagacgtgtctgggacgggtctacggggacgcgctgcgggacctgtccggcttggcttccaagccgctaaccaacc
    gctggatgctctgcagttcgctggtggccgcctctttctccgcgcagagtttgggcgacaa
    893 3544695 TTLL5 YES ggggcggggcgtctacctgatcaacaat
    894 3219716 — NO gtggcatctctgcttggaagtcctattcttagtctcagcttcagtacaccctcaagctatcttatttgcttctaaaaatctcttctagtacttctgtttcagtctttgtata
    gttcctatctgttctttggatattaattatgtatagtcacgtatatatactgtgcagacttatttagaggctttttgtcatattttgcttaaacctgctactgtgcaatctta
    cattccagttctttcattagtatggtctttttttttcctttctcctctcttctacacttctattctacttttccttcttggtccctttgcgtagcatcttttgcctggccatctca
    gttttatcttttaagtcctttttctttgttcatcccctgcttcagtgagcttttgcttctctgaactttgataacaagtattactgaaccatttatttctgggtgtagaattca
    tccaaactgagcttttgagggaaccttattggttatctaattcattctcctggccagtacagctgtcattctctgaaacatccatgacagtatctacttgaatgtttaa
    tggacatctcaaatgtaacgtcagagactgaattccagaccttcctccagttgtctgttcttctcatagtc
    895 3442242 ZNF384 NO aaggagaaggaataagacggcaggagg
    896 3293761 — NO accctccttaccttgtccttagatgcttaacatttttgtttggttttcttataaaaataacagatcttatgaaggtagaggtcagatgctgaatgagcgtctggcaaa
    agtgggatctgagcagctgatgcgggctgccagggccaagccaaggttgtccccaaggcctggccttggagggtcccccccgaccggccctgtccctg
    cccttgctccctgggaggggacggtggatgggtgctgctcacacccacaaggcttccctgtctagtcacagctctgtgatctccaggggggtctccatgatc
    acgtcgcgaa
    897 3829701 GPI YES cccaggagaccatcacgaatgcagagacggcgaaggagtggtttctcc
    898 3539958 SYNE2 YES agtgagaactacagaaggcgaggagg
    899 3620286 EHD4 NO ccctatattattctatccgtcctccag
    900 3621069 — NO atgaatccacctaaaaggggcagaggca
    901 2496816 — NO ccacccatgggaagctgatgagttttgtgtattgaattcgaagagcagagaatgggggaaaaggagattcccccattgaaaacctagataatgagagaggc
    ggaaccaaaagcagactcagaacttcactgagaataatgggggtgtagtagtcaggtgagagagactggactaccaaatcatcgttgctatccagtta
    902 2644239 — NO tgaagaccagtcgaaggagtgcagaccaggaaaagcgggacgttgatttggatggga
    903 2832085 ZMAT2 YES tggactttcgccgaaagtgggacaaagatgaatatgagaaactcgccgagaagaggctca
    904 3757844 STAT3 YES tgctgaaccctcagcaggagggcag
    905 2943556 — NO cctcatctgctcctactaccttgca
    906 2459948 — NO aaacttttctcgatacccttctgtgatgactt
    907 3119958 GRINA YES ctttgtccgggagaatgtctggacctactatgtctcctatgctgtcttcttcatctctctcatcgtcctcagctgttgtggggacttccggcgaaagcac
    908 2567115 — NO cctgattagcatatcacagtgctctaggagtcctggaacgccttcctcttccatgtgcactgctgctgacatccaggccattttggaacctgcaaatgtctcttccc
    909 2893649 — NO taagtcttagtaactccgtgctggatgtgcattttgcattcagcttctttatcataagggaggaacaaagactggggctcctgctgacatctgcagacacaaag
    ctgagtcggaatttgtggtcttagcttcggttcagcaccaagtgtatttataagtttgcagtcataggttttgttgtccaaatcccaacaaagccctttcccacctcc
    accccaccccggaagttatatagggttccttgaagggacaaagcctctagaaaaagaaaagtcactgaaagttgtaatgtgaaaccagcaaagagaaaata
    catgtttggtttagttgtggtcacagtccatggtg
    910 2346547 — NO ccctgacagatctcggtctggggcacagga
    911 2852745 AMACR NO ctggagcttccctggactcaacttcctaaaggcatgtgaggaaggggtagattccacaatctaatccgggtgccatcagagtagagggagtagagaatgga
    tgttgggtaggccatcaataaggtccattctgcgcagtatctcaactgccgttcaacaatcgcaagaggaaggtggagcaggtttcttcatcttacagttgaga
    aaacagagactcagaagggcttcttagttcatgtttcccttagcgcctcagtgattttttcatggtggcttaggccaaaagaaatatctaaccattcaatttataaa
    taattaggtccccaacgaattaaatattatgtcctaccaacttattagctgcttgaaaaatataatacacataaataaaaaaatatatttttcatttctatttcattgtta
    atcacaactacttactaaggagatgtatgcacctattggacactgtgcaacttctcacctggaatgagattggacactgctgccctcattttctgctccatgttgg
    tgtccatatagtacttgattttttatcagatggcctggaaaacccagtctcacaaaaatatgaaattatcagaaggattatagtgcaatcttatgttgaaagaatga
    actacctcactagtagttcacgtgatgtctgacagatgttgagtttcattgtgtttgtgtgttcaaatttttaaatattctgagatactcttgtgaggtcactctaatgc
    cctgggtgccttggcacagttttagaaataccagttgaaaatatttgctcaggaatatgcaactaggaaggggcagaatcagaatttaagctttcatattctagc
    cttcagtcttgttcttcaaccatttttaggaactttcccataaggttatgttttccagcccaggcatggaggatcacttgaggccaagagttcgagaccagcctgg
    ggaacttggctggacctccgtttctacgaaata
    912 3659213 — NO acctccaaggttacagcactttctaagaatgtgcctatgtagcatgtctgtccccccactgcctccaccaaaattctgagaacaaagacactgtagggattgaa
    cctgaagagtattcgctggaatggtatgctaaggtttctttcctgctgtacacctcctctgccccaacaaggtgctttaagttctgttttttaatttaggaaacctgtt
    ctgctattatagaaggccatgaaaagagaccagtgatttatctaatcataagcaaaaatagtagaaggctattgtcttgtcacttaagttgaatgaatcccagtg
    attgtagttgcttcacgaaaaataaccaatttgttctacagaggtagtctgttcccagagattgaaaaaaaaaaagatgtaggaaagtttaaataaataaaattgt
    ttaaattcacaatggagggccaattcacatggccctctgcattttgatgtaattctaacagttttactagcagaatctaacaaattttgaaagtcagagcgtatgta
    tagatatatatacacatgcacacatttttttaatgatacgttatccacttaaaaaaaaaagtctcaagaatgtcataagaaactcccttaacctcaatgagcctcag
    gtttctaatccctaaa
    913 3296517 POLR3A NO ctcatgtaacctgggaagagccataaaggggtaccccccaccccaactgccttcctggaagcatgcctgggaagtaagctgtaggcctgatccgagccag
    gaccactgggatccgtgcaaaggccaggggagggtagaattgaatcataggagtgaactccggcacctgttgtcttctgcgggtgacgcacactttaaatgg
    914 3028090 — NO cttggtcgtcacattctgcttttag
    915 3291113 — NO aagatctttgagttgtacttggtgtgtgctgtttttgtttgagatgcagtgaatgtgcaaatagcccagccgtaaatagttacttaaaataatctcttggtactgggt
    agcagcagtagaaagttgatctgttta
    916 3616816 — NO gggccgaaactgctgccgtgcattagctctgtggaggggagtcataaattctggttgtcagcgttttccgtggctttgtg
    917 3842744 — NO ctccatatattagctggggctgccataacaaaacatcatagactgggtggcttaaacaacaatttacttctcacagttctgaagtctggaagtctgagaacagg
    tcgccagcatggttaggttctcgtagggttctcttcctgttc
    918 3956320 PITPNB YES tcccgagggctccttggtgtttcatgaga
    919 2473315 — NO ctgggctgccaatctcttgccttgggggcagagcctcatctctctggctactggggttagctaccttgttggagctggcaaagccattggtgttgacatcggg
    ggtgactcctgaagccgccatatacgtgctgccaatggttttgatcttggtgatcacccggaacttgggattgtccaggagctgaggccaggattcaggaaa
    gaattgtcagcagtcaagggagaggaatgacccaacccagtgacagatgtacctgtttacaaggaccccactaaacccaagagacactttcctatcaaagtt
    gttacttagtctaccgcttatctgccacatgatcctgggagaacttc
    920 2659117 — NO tgcctacatgctccttctagctttgtttccctgatgttccttgccacctgctactcctctctgagctacttttccaggttccacagggagaggttcagctgtccgtgg
    tagacatgagggtagagaatgaggtggttgggttccacttacctttctatcatcttgcagtatggatgtctcttgactggtaccgtgta
    921 2826873 — NO gatatttatttgggtgcatgtttcct
    922 3498544 — NO tggcgtctgatcaggaagggactctgctgcggctgtggatctgacctgggtatcagatggtgatgctttgtaaatagtgtgcctcataggggtctgttcttagtt
    aaaaggagcctgcttggtgattccttttg
    923 2756844 SLC26A1 YES caggccatcgcctactcattgctggccgggctgcagcccatctacagcctctatacgtccttcttcgccaacctcatctacttcctcatgggcacctcacggca
    tgtctccgtgggcatcttcagc
    924 3088854 — NO atgtgccctacccagacagtgcctg
    925 3173548 PGM5 NO cgggagatgcttcactgatgccttcttgctacctgtttgtgcctcttatgactttggaaaaacaaaagatattttgcttttgggggatagagggtgggtgggaaaa
    gaaaaaaaatccatttggttttggttttgtcctattcctccaaatgcagcagggcctttagttgtctgttaaagctgcactataatttggtatctacattttatcacaca
    aaggaacctccccttttgacaacaactgggctaggcagctgttaatcacaacatttgtgcatcacttgtgccaagtgagaaaatgttctaaaatcacaagaga
    gaacagtgccagaatgaaactgaccctaagtcccaggtgcccctgggcaggcagaaggagacactcccagcatggaggagggtttatcttttcatcctag
    gtcaggtctacaatgggggaaggttttattatagaactcccaacagcccacctcactcctgccacccacccgatggccctgcctcccccatcccatccccaa
    catccctgtaccaccttctctcacatcttctaaagctttgtacaaatcacaatggtgcacttccaacaaaatatatcaataggtgttttcctctcttattttgtaaatag
    tattattttagctattaagctggataccttctttcaaattcagccattcagttgtaaagttgggaagaagtttcttgacaagactctgcaattaaatgcttaaaatttgg
    aggggatccttccttgattacatcaagtatgttggtacatgggtttatacaagttcctcttgagaaggcaaaaagaccaccatgtgtgagagctctttgacttgg
    ccaataggggcctatcttaatgcacttgtttggacacatttctgatcttatttgtaaaggctgcaaaaggagaggatgaaatgctgtaaaagtaggaaatgaagt
    ggaagctggaagaaaatgtaattggtggtacagctatgggccagatggtggaggggagggtggggacccctgc
    926 3200057 BNC2 YES tccctcccaaccagtcccatcattccaaccagtggtaccatagagcagcaccc
    927 2974443 MOXD1 YES ggccatgagagtctggtgcaccacatcctgctctatcagtgcagcaacaactttaacgacagcgttctggagtccggccacgagtgctatcacc
    928 2385905 — NO tctaaaaggcgtggaaacatttataagaaataccaattatgcagtgttggtgtcagtgtggacttaactgccgagactgacttattgccag
    929 3639566 — NO acaggttatttctatggacaggctcttgacagaaactctgaacatggatattactgtccccttcattcaaatgaggctgaactgaggctcataagtatttaactctc
    acacctagttaacacagtaagatttgaaaccagatatatatgaatccacgaagtcttatctg
    930 3200565 — NO tggcatttcatgaggggaggcttatctgtgg
    931 3083781 MCPH1 NO atgtagtggcctatgttgaagtgtggtcatccaatggaacagaaaattattcaaagacatttacaacacagcttgtggatatgggggcaa
    932 3829376 — NO atggccgtcgtcaggagcattgtgga
    933 2359017 — NO gtaaccgggggatcttgcttgtcagtgcctggac
    934 3180982 HABP4 NO ggggagacttttccagctgggccaagggagtcagactctaagaacaatagatgttgcttttcccgtgtcatgtaaatttgttgcacttttttgggctgagctgtta
    gaggggcttctccagaggctcgagagcaggccatttcccaagaagatgaagaatggtgactgtgtttttattgaaggaatttcaaatgaagaataatgtttaaa
    atgtgtatatagagatagtatagactcctccgcggaagcatggagggaaaggaggttgtaaaatagactccatggagactcttaggaagcagtagattcccg
    ggggctgtgcctttagcgttagaggaaacacatagagctggaactgttaatggaaagcagtcacagctgagttttcggagaccaa
    935 3915249 — NO ccaagctgtagatcttcccaagatatttttcaggaacgaagcatgtaaacttacatgagtgaaagacagtggtaaaaaaaaaaaaaaacagtctattttgggct
    ttggctcctacctaaatctagcttgtt
    936 3263765 — NO tgcagagtcctacagctggttcaaggcagcatcaggctcagaacccctttctctcagctctctgttgtgattatttcaggaccttgttctgttttccacatggcctc
    taatctagacacctgacctggtgggagtaacctttca
    937 3303272 ERLIN1 YES ggagctcaaaaagtaccaggccattgcttctaacagtaagatctattttggcagcaacatccctaacatgttcgtggactcctca
    938 2683681 — NO ggtgacccaggcacgatagctaagaaggcaaagtcgcttgttctattagctgtttaggcatctttgcagccatccttgatttggagtttttgatcttgatctaattct
    atccctcaaaaccagcccttacaatctcacgtgcccacctcttccatgacagtccttgggcctagagggagggtgattgtatagttttagcagcagggcatttg
    cagtgaaaaacagattgggcccagtgggatgccaaatgagagagggtcgcatct
    939 2683865 ROBO1 YES tggtgtgtggcttcatacatttggggaccctatttccactccctcctcttggcatgagactgtatacaggatccacccgag
    940 3781116 — NO ggcagctgccctgtaatgttctaccagtacttcagactcaacatgcacgaagattaa
    941 3050281 — NO atgctgcccttcgatgaccatagtgaatgttccacagagtgtactacgagccacaaacaccagggagagaaccccagcatcagtggagtagaaacaaaaa
    ggtgttctgtgtttcgcacttgggtcctg
    942 3903591 — NO atcggcatagcctagatgggtcttctgtttcagggtctctcacaggaggtagtcaaggtgtcagccagggctggtgtctcatcttagcgcttggctggggaat
    aatctgtttccaaactaacttggttggtgacagaattctcttcttgaagggatgttgaattgaagggcttggtttctcactggctgatggctggaggttgctctgaa
    ttcctttccatgtagcttcttcaacatcacaaagctgagaaaggaatagcaagtctcctaggaagatggaaatcacaattttttataatcatggagtggcatccta
    tcacattttccatagtccgttagttagaagcaaatcaccaggccagtccatactcaggagga
    943 3115066 — NO gtctaggggttacaggatcatcatctaagttctgcttctgcctggacttgctgcgtaatttgaatgagtggctaaacctgactctttctcctcttg
    944 2509773 MBD5 YES cactaacagaaggtttggaagcctacagccgtgtccggaaaaggaacaga
    945 2322410 NECAP2 NO ttctctttggtggtttctaaagtgcct
    946 2837342 CYFIP2 YES ttttgtgcggactgccattcctttcacccaagaaccacaacgagacaaacctgccaacgtccagccttattacctctatggatcc
    947 2936910 — NO ttaaaggtgtagagtaagaagaatcaataccgtgtgttggatattaagcaattggtaattaatcttgcttcctttatcttgacaagatgtgctttttcacttac
    948 3958553 SYN3 YES atccttcaagccagacttcatcctggtccgccagcatgcctacagcatggccctgggggaagactaccgcagcctggtcatcggcctgcagtatggaggg
    ctgcctgctgtcaactctctctactccgtc
    949 2901722 — NO acagtaatggaagacgggagttgcagtgctcagtcatggaattcctccta
    950 3092902 NRG1 YES ccaaatgagtttactggtgatcgctgccaaaactacgtaa
    951 2437102 KRTCAP2 NO tgccacgtgctcagaaattcacagcagatgcaatctcatgtaaaaccctcatgtggtaaaacaaagatctatcatggttgcccttaatcttttctcttttttttttttttt
    tttttttgagacaaggctttactctgtcgcctaggctggagtgcagggatgtgatcactgaagccttgacctggtctcaagcaatcttccctcctcagtcttacca
    gtagctgggactaccagtgagtgccaccacacccagctactgttttaagtttttgtagagatggggtttcaccacattgcccaggctggtctcgaactcctggg
    ctcaagtgatcctcctatttcagcctcccagagtgctggaattacaggtgtgagccactgtgcctggctgccctcatttctttgcccccctctaggacttgctttct
    ccgcatagcccttttgcaggcttcagagttctttccatccagtagccccgggacttctctctgttaggttttg
    952 2657991 CCDC50 YES tatgccgagattttgctgtcctggag
    953 2520359 — NO ctttgagcgatgaaaacagtttttatctttttagcaaagttgtagttaggatcttctgtctgtttttaggggtctccactggtattaaaggcctga
    954 2592274 STAT1 NO gctgaggtttagctgtcagttctttttgccctttgggaattcggcatggtttcattttactgcactagccaagagactttacttttaagaagtattaaaattctaaaatt
    ctattaatctctcattaatagtatttaatataaagattcttaaaattactgacgttatgaattggtttgatgc
    955 2681309 — NO atcttctaagtgtccatgcagcttgaatcattgcacacagtcttctatgagttatgaaaataaataaaaccccctcttttccccattttatggttgtgaaactgacac
    agataacacaaaagggtagattagggaaagccatatcccctctgccacccacctccaatactgatccagctttcctggatcaggctagtagggcgttgaggc
    ttcttactagaa
    956 2961267 COL12A1 YES ttggaatccatctcctagtccagtgactggctacaaagtcatcctcacaccaatgactgcaggaagccgacagcacgctctgagtgtggggcctcagacaa
    ccacgctcagtgttcgcgacctctcagcagacacagaataccagatcagtgtttccgccatgaa
    957 2854242 RICTOR NO ggctgcatcctattaccacaatggggtgtgctataactgctggtattagagagggaactttggccctttcacgtttttcttaatgtttgtaacactacttcagaggtt
    tataacctcaaagcagaagaagagcctcaacaacccgggacttataagttatttttatgttactagacttgcataaagattcttgttttccaactcttcattttgttgc
    aatgtgttattacaggatatatgaaccaattaaggtttttcactacagttcttgaataaaatttaaaaatcattttttattttaattaaaaatatttcccatttatagaatgc
    atatatttgcaatggacttccactttcatcaactttccatctcatcgctttaaacaggaacttgaacaagcactgttagtttagacctaaaggataggaaagcatta
    aataatactttggatctcctgaggaaaagataagtttgcttgcaatttacacattccatggggaaagaagagccatatttccttaaaaaaaacattaataaagctt
    gttattgagaaaaattgtagtgaaaagccttaagtaccaaattttaaagcagcagtaacttaatttttatatcagtgtttttgttttgcacaaactaaatgcagtggta
    ggtgggtttatgagtatattaattgcctttatccatttgtgaagttaagttgatgagggcaaggtttttgtttgtttaatttgtatatgtctaaaggtatttggaacttttta
    caggaattaaacatatatgcaaatttgtatataaaaatagcatggccatcatttgaatgcttgtaaatgaaaggattatcttttttgagatctatatataaatagaaat
    agaaaatccagctggactgattaggattcttttttaattcatttgtgtataacatttttattacaattacacatcagttttgacacagtcatagcaacattaatattttccc
    atgatgcagatcctttttgtaatgggcttgttctttga
    958 2957263 — NO tggggaggcacataacagttttttattctgggaagagccagttccccactcaacatattcaataggcacagagaccaggggaccacggaaagctccagtga
    cccccgacccccgccaactcttcctaacaacatttgactccttgccctcctccgttggaactgtgcttcctggaaggaaagtgattgaagaagaagagatgta
    gttctgtaaaaggcataaaaacagcttgtttttttaaaaaaataatatttttctgttatgatgcaaattttttcatgactcttctttctctcactctccacagtcatttcatc
    ggcaggtcctgccagctctgcctcccaaacacattgagactgtctgctgctttctgcctgcaccaccaaccctagtctagtgacctttgaccaggggaga
    959 3429874 OCC-1 NO aacagaagaatccgtaacagaagatgaca
    960 3766915 — NO ctcctccattgaagcagattgattaaaacagcttaggaaagggcaaacttggatcacgagcagtggatttttttcatatctgatagtgaatttaactttttcatttct
    ggcgaaattaaagagatctgtgaccaaaagtggtcaagcactggagtctga
    961 2691040 — NO cgcactggcattggaacataataaactaaaattaaaatgtttctttactgtgcctcaccattgcacaatcaaaaaaaatttttttgcatacactgtggtgaaataatt
    tttaaaacttggacttgctactgtgaagactgatgtttaaagtttataactgtataaacattttctatgtccccccccacaccatggatttcttataacattggatatatt
    tttccttgctggactattctcttttggattga
    962 2824389 DCP2 NO agtgcactgctttcttacaggaagacaactcagaacacacagccataatctgctttggtgtcagtcacatcacagtggttatacatttgtcctgaatggtgattca
    ttcctttccatctaacttccttgtgacaaatagcatttactattgaaatagtcttaaaatagggaaaagagtgaaagttactcttatgcatgggagtgggcttaaag
    ggttgacttccaccagctgagtacaaacaagtgtaaagaaaaactatgataaagtatggaggtcttgagaattgttcataatgaaatctttaatctgggttatca
    gagtaatgaaatcaccaataaaaacattccatttatcttggatcttctgtggttagcagaggagtatggtctagctatgttagcagcttgaaggcacaacgtaaa
    aggaatgagctttcacaaggtgcttacgttagctgggtagtattggtcaaaggtactctgaagagtgaatgcagaaatcagttggctgtgtttgtaatcttgtcc
    cacatggaccctaacctttagtagacttcagtcttttagtccagtagaagacaatggccctgaatatgtgttttctgctttttggtggaaggtttcctgcaggtggtt
    gggtggtttttgggttattggctactgttcgttcagtgccatttgaagacctgttgtttcttaatcctttttcttggtgtgactggccaggaaaaagtccattgagtcct
    ttttttctccctggtgtcttaccccttctgtagaataatccatattttaaaatttgtttcacatcatttatagcaaacctgccacagacttgcaagcagtgattttatctttc
    cttcctgagaaggtgatctcacttttgatgtttgggtcacctgtggacacctgtgctcttttgagtctcaaggcttatagctttcacattggcttgggaacaacaga
    cttgtgtgtggttctagagtgaaatgggcagtgttctgctggtcctcagtctttgagag
    963 4054485 GABRD NO ctctgcaggatcgggatcagagcgtgggaggaggtgggggtggacgtccatccggtgaacagtga
    964 2871027 EPB41L4A YES cccggcctgatcagaatgtgacaagaagtcgaagcaagacttaccctaagcgaatagcacaaacacagccagctg
    965 3468170 — NO gctgagcccataacctgcgtcttctgctctagcctcttgtctgtctcattcctcctctgcatggattgtctctatttggaaggtccgtggtttttatgtgtaaaatgaa
    agctgccgtgttccctttccaacaccaagtctagttctctagctcccattctatcagtgtcatacctcccagcttaa
    966 2739471 ENPEP YES gatactgcattcaaacgaaacatgtggccattctctgtgcggtggtggtgggtgtaggattaatagtgggacttgccgtgggct
    967 3725508 — NO ccagtgctttgcactgtagctgctcaataa
    968 3946498 MCHR1 YES ttcgcggtcgtgaagaagtccaagctgcactggtgcaacaacgtccccgacatcttcatcatcaacctctcggtagtagatctcctctttctcctgggcatgcc
    cttcatgatccaccagctcatgggcaatggggtgtggcactttggggagaccatgtgcaccctcatcacggccatggatgccaatagtcagttcaccagcac
    ctacatcctgaccgccatggccattgaccgctacctggccactgtccaccccatctcttccacgaagttccggaagccctctgtggccaccctggtgatctgc
    ctcctgtgggccctctccttcatcagcatcacccctgtgtggctgtatgccagactcatccccttcccaggaggtgcagtgggctgcggcatacgcctgccc
    aacccagacactgacctctactggttcaccctgtaccagtttttcctggcctttgccctgccttttgtggtcatcacagccgcatacgtgaggatcctgcagcgc
    atgacgtcctcagtggcccccgcctcccagcgcagcatccggctgcggacaaagagggtgacccgcacagccatcgccatctgtctggtcttctttgtgtg
    ctgggcaccctactatgtgctacagctgacccagttgtccatcagccgcccgaccctcacctttgtctacttatacaatgcggccatcagcttgggctatgcca
    acagctgcctcaacccctttgtgtacatcgtgctctgtgagacgttccgcaaa
    969 2818169 — NO agacacagacgggtggacccaagcattgagggc
    970 3092610 UBXN8 YES ttttgctttgtggccggattttgctactgcttgctcttctta
    971 2560754 — NO gcccgctatctgcatctgccttttggactccttgggggaaataaaacaatcgtgtacagttgggaggctcttcgttttcaccatcagttgactccatcagt
    972 3850324 — NO gagttcagggagacgccagacaattgcagcagtttgtagagttatgtgggtcaggctaggattagttttgctgcaggaataagcaatccccccaaatcttaat
    caaggtttacctaaaatcggccgagcaca
    973 3209807 — NO cttctctgaaaagaccagcggccctatgactatc
    974 2639722 KALRN NO ccttcttctctactgggtgcaattcgaggttgctgagcttctctccaaagtctaaaatggtggggcagtagggacctgtgagaggcccaatggcccaatgtact
    tcccccagatcccactcagaacagcaggtacgcccaggctcctgctgccctagaggtctgcaacatgagtgaagaggttaattagagggacacacttatct
    ctgaagtttttctccaggctgaacatttctattatcagtggcccctaatctggaaaaacccatcattctaatctagcttgtatccccacatcatgagaaagaggga
    agaagaagaagggatgatgtgtggtagagaagatgagggttaactttagcctttcccaaacactggcaacaaccacttcctcaacaatttttctatttgcttcag
    cctactcagattttttcaggtttttctagctcctccataacctcactccctcccgaggtctctggttcaaagaccaccctaccagcccctatttgcttcaggttatcc
    tgttgagggtgggtgggaagagtgagaagatataaatgaaaaactggccacatgttgataattgttgaaactagatgatggtacgtggacattcattataccat
    tctccccacttctgtatttgtttgcaatttttcataataaaaaagttttaaaagtcctccagtttccaacacactcaagagagagccccaaccccaaacacagagtt
    tcatggaaaccccacaccaaggcaagaggcagagatgatgattccatttcatatatacactcattttctaactttttttaaaggcccactgctttattttcaatagat
    taaacctgatttctgagaggtcctgaagttgggcttatttccctggc
    975 2972483 — NO gtgatgactatgggccaggacaaca
    976 2518314 ITGA4 YES gcagttggtgcttttcggtctgattctgctg
    977 3680796 — NO tgtctgcttcaacctcacacttctctcag
    978 2329274 — NO ctgtgggaaggactcttctaggttttggactctctaattcttctgctgaacccagtgactgtgtaaacatccagaggcccaccccacccaaagaatgtcagactg
    979 3379673 CPT1A YES ttcaggcagcaagagccggcaacgccatccatgccatcctgctttacaggcgcaaactggaccggga
    980 3549257 — NO tgagtcctccattccaaactctcct
    981 2360474 FLAD1 YES gacatctagggcctctgaactttctccggggcgcagcgtgacggctggcatcatcattgttggaga
    982 2584988 SCN3A YES aaaataagatgcgggagtgtttccaaa
    983 3630231 LCTL YES tcacatgcaaatggttacggagatcgtggtacccactgtctgctccctctgtgtcctcatcactgctgttctactaatgctcctcctgagg
    984 3801606 — NO ctggtgccagggctcctctcactgccctacacttgcagggaggtggacttccctccc
    985 2476381 — NO agcatcacatattcaggggaccttgaaaagtttggtgtgcctgagcatagtgtagctggaaggtagtggtgggagatgagcctggagaggaaatcagggg
    ctagaagataaacaggaatatatcacagagttacttaccttaaaagtaatgttgagccactgaaaggttttcagcagctctcatcaggtttgcattatagaaaga
    tggtcttcaggtgtagttgaatggttggaggggaagttggaacaagaccaaactaccatggaagagactttcatctgttttgtctcagcagatagagctgtatat
    gtcttctccctgtcctactgttttgggggactgagattttggtactcatcagcactcttgctctcatattatgga
    986 2522188 LOC26010 NO ggtgctgacccaattcgctgccaaaagagtgtcaatcagaatatacaaatcccgtatggttgtgtcatcctctcttaatcatttttactaattctaataatcagctct
    agcttgcttcataattttcatggctttgcttgatctgttgatgctttctctcatcaagactttgcagc
    987 2673516 UQCRC1 YES atgccagtgtggtacgtgagatctgctccaagtacatctatgac
    988 3659195 — NO gaagaagcagtgcatctgggtggca
    989 2652475 — NO tctgtccctctgctagttagttctgtacagttatccccacagtcctcttcctaaagtagacattactttcttgttcaggtctagagttggttgccttcgcatgtagttaa
    agttctgtagcatggtgtataatatccataacactcaaccctgcttacctctcaagaggcacctttacctgtcaccccacagtctatgtgttaaatttctgttcccta
    gataccttgggcctctttctaaatacacactttcatgtccattatttccccctgtctggaatactctagagcctttcattgacaattcacttgttctttttggtgcccctc
    ctcaatgtgacccttttagaaccttcatcacagaaatagttgttctgttttttcagcatctgtgattctttccctccctgtcatagaataaaatgtgtatttatagtcatc
    accaagaactcatattgcctcatggggattgtatctcagcatc
    990 3198107 — NO atgaagcagcacaggtacgaggtgcaag
    991 2994022 — NO gtagattcgatgggcccgaggctcag
    992 3548367 — NO tcctgttttctgcattagctgtttgcatgtatttagtaggttagaggtgggaactagagatcagagaattgtttatggcagcagagttagcagtaacttgagaggg
    catagctaagtcaaagacctact
    993 2440185 COPA YES ccaaaaaggtacaggtgcccaactgtgatgagatcttctatgctggcacaggcaatctcctgcttcgagatgcggactctatcacactctttgacgtacagca
    gaagc
    994 3480073 — NO atggggcttatccttactcgcagtcacctaaaag
    995 3513910 KPNA3 YES ggtccaattgagtgctgtccaggca
    996 3978139 — NO gaaggcctcggcaaaggactgtgct
    997 2540091 — NO cagctccagggtgaaatggtgctag
    998 2896688 — NO tcccgagggctgatcactggaaacagggcaacctctggtgacctggtttttcatcaccagccagggcagaagaagtcaaagtgtgctcaagggctttgcac
    gctgctccctagaactgg
    999 3022504 — NO actgtcttggtgttggtcaggattaatataagggagtg
    1000 3104044 — NO atggcctgaaagctttaggtggtgcaacacagggtgaa
    1001 3939535 SLC2A11 NO caatcaatggtgagcgtggtattccaggctaaaggtaattaactgacagaaaatcagtaacaacataattacaggctggttgtggcagctcatgactgtaatc
    ccagcactttgggaggccaaggtgggaggatcaattgaggccagagtttgaaaccagcctaggtaacatagtgagaccccctatctctacaaaaaattttaa
    acattagctgggcatggtggtatgtgctaacagctctagctactcaggaggctgaggcagcaggatcacttgagtccaagagttcaaggtagcagtaagct
    acaatcacaccactgcatgccagactgggtgacagagggagacttcatctctttaaaacataataataataattacagactcaggaaatgcagtgaaagaaa
    aatacaggttggccaggtgaggtggctgatgcctgtaatcccagcactttgggaggccaagatgggaagattgctttgagaccagaagtttgagaccagcc
    tgggccacatagtaagatcctgtttctaccaaaaaaaaaaaaaaaaaaaattagctgggtgtggtggtacatgcctgtggtcccagctactcaggaggctga
    aatgggaggatcacttgagcctgggaggtcgaggctgcagtgagtcctaattgagccactgcactccagcctggacaacagaaagagaccatgtttcaaa
    aaaaataaatacaggttgtagtgggtatgggtatgcataccaggaggcccgacctcgtctgagaggggagtggtcagaaaagaattttctgaggaattgatg
    tttttaatcaactttattgaggtataatttatacataaccaactgcatccattttaagtatatatttggcgagttttgagttctaagtatagttttggtgagtgtatacactt
    gggaaacaccaccgtgatcaagatggaacctttaccctaccccaaggcacccacatgcccatttgctatcagtaacccaccccagtcccagacctggg
    1002 2420794 — NO tagatctccacatgataacctgttgaactttttgagtatctgttgatcaagaaaataaagtcaaaagctacaattaattagtaatgtgctcaaaataaatttgtatttt
    ataaatcataacatcttttccatgttactctgtctatatggagttcttaataccacacatttgcttagggagatggaattagcaactagtctgtgctaccctgtatttttt
    ttttaaccatgtagttggattttttaaaatacaataaaagagttcacttttccaggtttgacaacatttttatgaattggaaattttctgtggctacagatactattaacat
    tttggaaaggtgtaaagaacattgttttaatgtaaggctcttctctaacctccctcccctctccaaattctccataatatgaagtaggaagatatgtatttttctgttg
    ccattaaaatgttctggccatcgtgggagtggggatggggagggcggggatgggaattagaacttactagaataaaattccaaatagaggtttggggaaac
    ctacttgtgagtgctttttaacctcaaaataaggatttggggtgggtggagaaggtgatggggcagaagaagttgtttttggaggagagaaagcagattgaaa
    ggaaaaggacagctgatagccacttaaataatgtcatcgttagagtgatacctattttttgtaaaaagaaaacaatatgctccattcttacaaagcattgattgtat
    tttaatatatacaatgtaaatactatcatgcagtggtgtccaagggagagaatacagtcatgagttcttagtttctgttattggttgggccaataaagccccttcat
    catccttcttttctgcttatcactagagacagaaactaaaaaccatggcttcaggctgctaaaagcctaaaacaaaacagaacaacaacaacaaataaggcag
    gttggacaagcttgctgagtatttgggagcctttttc
    1003 2444781 — NO taatggggccaaaggggcaacacaaagcattgaaaacatcactggctcacaaaaacagtcaccttgttaccttctcagttgcatttgtttatttcacaaggcttc
    attcacacataaaaacaagatactaatccaattcaagttcataacgattataaaagtaaacatttgttgggacaatgtacaataaattgcactttttagacaagcat
    tacatttacatttatagagtgtactatacataatacatggaattacggaaacgtctaattggtcattg
    1004 2537266 — NO tgatacacacttcgaaccacagccagggtccaggcctgaacagatgtcagcatcttcagggagcttttgccaggacgccgcccagccacatggccaccacg
    ttcattcaaacacggggcttcctgtcaaactacactaga
    1005 3061935 — NO aagaggtcacccttgccgtttgatggaatgcctattatttgatagctgctgataccacgataacacagagattccctttcaattaaaagtgcctggacaccacag
    ccagacaacttctgtcccaccacatgtatactgaatttcagtcttcttacatctcatttcaaatatattttgaaatatatttccagtttatataaatagtataacacctaa
    caattcccatttatttgcaaatattattgtgaggatcgactgggacataaatg
    1006 3893061 — NO ttcctgtccagctaaagatgctgcctggccgtggcctccacgctctgtaaacatgacccacaccccccagggcactccacggaagccttggagataaggg
    acacatcacttctatgctcacctgaagtgaccccattgttaaaggacacagctcaactcaatcagggcaccagcagcgactccaagtcagggtgcaaactct
    ggaggctgctgtgtgaggggggcactagagatggtggtaaacagaaaggggggcttccttcaccagccaggtgaccccaggcaagtcacaaggaacc
    gctctgatcca
    1007 3996137 — NO ccatggaatcctgttggagctggtctacagaa
    1008 2424640 DPYD YES tgggagaattgttgctatgcagtttgttcggacagagcaagatgaaactggaaaatggaatgaagatgaagatcagatggtccatctgaaagccgatgtggt
    catcagtgcctttggttcagttctgagtgatcctaaag
    1009 2823618 — NO ttcctgctactggttggttaatgaggcactgagctaggaaccctgtaagtgttcaagtgttaaaattgtgttgttgtacctttaaatataaggagaagaaattggg
    agagatcagattaaaatattaaatacttatatggtttagaaaagtgacagcataagggagatcaaccaggtttaagggtaaatacttaggtgaccagaagatct
    acagtaaacttgaggacatatcccaccaagacccacaactcagctccagctgattgtttccacaataggactgaatgcctgc
    1010 2491474 — NO atctggcgtggagatcgttcaaaggtgggaaactacgggaggaaggtactcaggtgttgagtgcagccatggggccacttgaattagcatccaggcagcc
    cgcgcccctccccagagacaatcagcggtgtttca
    1011 3780190 — NO cccatgatgtctgtcgtgcagatgaatgtgtccacgcgtgctgggctagtacagaagatcg
    1012 3443271 — NO ccacagtatggtcattcagcgaaagaagtaccaagtatttctttctgttaatgagtcagaggtattaatatatgtatgtgagtcccccatttaccctgcgcaagat
    aagttcttttaaatgcaattagaatatcctaagataaattacaaactcctcttatgtatccttttctctgaggtgaaatgagacactgcacagatgagaggtactatt
    1013 3249840 — NO gcactgaacgctaatccctttttctatttccgcttctcacaggcacaggaacacaggcacaaatgcacaccacaca
    1014 3365366 HPS5 NO ggggctacttttgtcagtgtctgtacccttggcatcggcatctgtgactctttatccatgacctcagtgtttcttaaccaaagttgtactcagcatttcttaaccaaa
    gttgaattttgaaaagagtcagtccttgtttgctggaattagaatgttaatgtcctagtattattccgaactacagtattaactgcttgttgctagtggattagacaga
    ttcttttcttactgtggcttccatgttgggagcagaagcttttcatcctggtcacatgaagacagatggtattattgactggagagttgaattatttttatatcttgtctgg
    cacaatatggaaattactgaaataagacggtgtataatggaattaacacccaaaataagtagaacactgaagatttgaatttgatatttaagtaaaatgggactg
    ggtgcagtggctcaggcctgtaatcccaaccctttggaaggtaaagacgggaggatcacttgaggccaggagttcaagaccagcctgggcaacatagtg
    agaatgcatctctacaaaaaataaaaaaaattagctaggcatagtacctgaggccaggaggtccaggccgcaatgagatgtgttt
    1015 2883453 ADAM19 NO ctggctgtatggctgcatgtgacaagccacgtcccctcccacctctccccaaacccctgcatccctgtattcacacgggtcactctgactca
    1016 2924473 — NO agcagggactcagcgtgaggcttgaagcaaacagtggaatctttagaagcctgctttgtgtgc
    1017 3378661 — NO ccctgggtgtaacgaggccattttgcaactacatccagccaggctgaaaacacttactttattccgagtccatcagaattcttgaaaatcagaggatctctcaa
    gccaccccgctgaatatactctacattaaaatctgtcaccataggaaaatattagaaagataagtggtataattaaaaacgataaaaggaccataaaaaggat
    cctaagtaatacagtataaatggtgtttgttattctgtgtatatagttatgctgttagtcaataaaatatatgcttagtaagaagcatctcttagaaaatatggagagc
    acattgagaagcaacgcttgaggggttttcca
    1018 3754749 DDX52 YES aggctgggtgtcctgtaccagaatacataaaag
    1019 3150460 — NO gctgcccacgggactttgcaggagg
    1020 2664515 — NO ttctctttagacttaccagttaggctctaatttaggaaaaataaaacaaaaacttacatgggtttggagtaaaattagctggagtaaaatccaaggctagatttcta
    ttgaa
    1021 3123616 — NO aggagggcccaatatccctgggtcg
    1022 3432252 — NO agtggtcaaacccagatgagggtcccgcttctggtttatatacaataa
    1023 2593632 — NO ggagcgggaaggagattgactgttagtttctta
    1024 3054956 — NO tgtgccagccacagtacgatgtacctcctccaatctatgtgtccaaatcagcgcatcctttaaggccctactcagatggcacc
    1025 3096135 — NO gggacccagaagcaaccgttatgagcaacaaaaggaagacactggtttggatggacgggaagcggttgggtgggctggactgacggaggcccctttaga
    1026 3541539 — NO tgtgggctggccatctatatccatccatctatctattattccacccatccctccatccatccatccatttatttaattaagttatttttaacggttggctctggagttgac
    attcatttattttaaaagaacagtgaatcatagctcttttcctcaagatgcttgcttttatttgcatggtggcatattgattaagtactcagaacactatttgacatatgg
    taagccctcaataaaagtttgttattattatgactgtacttctcccctctaatgtatagaggtaaacattttggttcctattgtgacacgtgggttataatgagttagg
    gcctacttaagaagaaagtggaaagaaagcgggtaaaattgttgctcagatactagcatgtgggtgga
    1027 3762591 — YES ggggcggtggtcattaattctgctatcttagtatctctctctgttttgctgcttgtgcacttttctatttctaccggtgtgccagctct
    1028 3305557 — NO acctgccatcctcatagtcaccgggag
    1029 2394713 TNFRSF25 NO tggcaaaagagcaatctggatccgccttagccagatacataagggtatttgccttcactttcagccagcattccccccagcgatcctagccagatattac
    1030 2406204 — NO ctgatatgtatctgttgggcaagtagttccatgaggagtttgtttttgttcagaatgatctttaggaaaaatggaaataccacggtgaagggaaagaagtcagaa
    tatgtacacaaagccta
    1031 2722321 TBC1D19 YES tgtttttcccgggatacatctgtgttgagtcactttgcattcaacagtgcctcgccaccaaaatcatacataa
    1032 3532235 — NO atagtgttatatccgtgctgccatatcactaaaataggcttgccaaggcaggtgaggtgtatgaatgctcaagcctcacagaactgcaatcaagtgccaactat
    aaataatactgaaaaaagttgaccatctgaccagtggataatactttcaaggcattcaattagcttatcctttgcagtattctaagctattcacattgacgatcacat
    acattgtagtgcttgctgcaagggaggcatataaccagttgttttggctaaaatatgacaggaaggcattccttgggttctatataaaagtaacagtattcaaca
    gtctaatggcaatcactgataggctgcttaaa
    1033 3053937 — NO tgcacgctggaatcatggctcattgcagcctccaactcctaggctcaagggatccttccacctcagcctcccgagtagctgggagtacaggtgttcgtcccc
    accatgtctggctaatttaaaaaaatgtctttgcaggatgggatcttgctatgtttcccaggctggtctcaaactcctgggctcaagtgattttcccatcttggcct
    cccaaaatactgggattatacgtataagccaccacgtctggcctgagtcatctcttttgacccagaacaaaaccagtccaggagtggctgtactccccagga
    gtgtacactggggaggcccacagctccggggtgcagtggggctcttgcaatttaatgactgattcatcttcaaaaaagcacaatctcagccaggcg
    1034 3304915 — NO tgggagactgacctaactgagcatcaactatgccaagcactgcgcaaggtgtcgaggctataggaacgtgcctttctaccctagagaagtttgcagtctgct
    gtgggtgatgagctatatagaagaatgtactattagatggagggaagtgagggagcaacatggttacctgaggaagagcagtccaggccaagggcacag
    caagtgcaaaggccctggggtgacggtgtgtgctggctgctcatgatgcagtagggaggcctgtggctgggatgaagaatagtggagggtaaagtggaa
    agaggtgagagcagagatgtagctggcagtggggagggaatagggtgaagcagcaccatgtagggccttgcaggacattctaaggattttgactttcatc
    gagtgagatgaagattcactgaggggttctaagtagaggcagggacatgatctggcttcaatcatagaatgatggggattgactaggcaggatgggttatga
    tgtgcaaggtcgcagggggctgctagccaggtgagataggatgtgggctctggcagcagtggagggggcaaggcactgcgggtgttggacagactctg
    atgattggatgtgggcctcaagggagagtttgtgtgggagctgggaaacaactgcatcaggttgcctggggtcccactcttaggccgacaacttg
    1035 3545436 — NO gcggtcactcagctatccaatgggatgacacacagcaaatcagctcttcactgcctcaacagacagtcactaaaataatttctttaaaggtatataaatgttggc
    cagtgtaatcctctacaaaacacatttgcaaatataaaataatggaggtatgatgctgctcagagaatgggaatgctctggcagtccccaacatcctatcccac
    ttggggctttgctccgaggggaagagcaggtgcaggatatattgccctttgatgtgatgtagatgctactagggacccactgggaagagtcccgttccttga
    gttatgctactgtagggatagacccttggtgtgaggaatctaacaatgagtcaaaggaaacatcacaaagaaggtgacacctcagaggagacaaaggact
    ctgaaatcctggaatcacgggatatctctgattggttagggaattcctctgcactcaatctccagcaaatgggcagattccctcacaacttagaatttttcatggg
    gagtgctggactgtaccccaaacatggagtaaggtggcatcatccatctctgaagggccatactcctcgcaaagc
    1036 2632506 NSUN3 YES tgaatatgatagtctgagattgaggtggctaaggcagacgttggaatctttcatcccacagcctttgataaatgtaattaaagtgtctgaattggatggcaga
    1037 3333132 — NO cctgagttcctgggcactctttcctgagcttgcttggggctgatttgaattcag
    1038 3459329 — NO ctctggattttgccactcacacagttg
    1039 3597530 APH1B YES gccagtgaaggtttgaagagtataaacccaggtgagacagcaccctctatgcgactgctggcctatg
    1040 2757682 — NO aacagtgcaagaaaggacgcatcactctcttctggtgccgatgtgctctcttgttaa
    1041 2811303 — NO tcacgtggctttgtgtaccaggcgtccagggagcaattaggagggcaatctgttaagtcttttgcctcagggcagaaccattaggtgtgctgtgtatgtgcctc
    aaggggtgtaaataactaagctattcatgtactcatcagtttcctttcaaggcatctgtgaaacctttaatctgtggaagaatcagagaaagttgacctattgtatt
    attatcctccctcacctgaatattttga
    1042 3611032 TTC23 NO gagtccttttgtcctgcggtccatataagagggtctggatctggagacactgtagaacaccaagcagctatcatgaggctatggaagtgtcgctgagagcag
    gaaactaaggtctcccttgaatgagagaaagatgacctcattcttaggccctgctgtgatggaattagcatgctcctgggatgtctcctagtgactgacctttgg
    tttggatgttctgagggatctaggcaaaagtgaacagttttagcactatttcacaaaactctctgtgactatctgtatgcaaaaaatagatttaaaagtagtattttt
    aaaaataaaggcaagaaccttggtactgaccagaggatgggctccagtttctatttttaaatgtggcccttgttatagcctggaaaagatttaaaaaaatagtttt
    gttttttttgtaaacacatactctacttttattaatatataggctgtctatactcttgactacacagcaatgtcttagttattaggaaccaaatattcagcttatggacta
    cccagggctggctttggcttgatttctcccttctgcttactttaagtcttgccatttgattgcttgtagtaggctagggcaaatcaaggagaggagaaagattaaa
    gttgtgcccaaaatggccaaaataattttgagaaagaatgaggtggagaggtggaggaacttgctttactgaatgccaaagacccttttatttttttaaataaagt
    aattaagacagcatgtttgtcacccggggtagacaaaaagaccagtggaacagggcagagagcccaagccttgacagatgacagaaatggccttgcggg
    attggtgaggaagaggtgggctagtcaataaatgggtactgggaccgctggttttccaaatggaagaaaatggatcactaccccaaatcaaacacaaatatt
    aagctcaagaaagatttgaaggactaagtgtgaaatgcaaaacttggagcttttagatgaaaatactggaaaatatata
    1043 3977071 — NO gtggctggaccatgcggaactggat
    1044 3363301 DKK3 YES tgatggaggacacgcagcacaaattgcgcagcgcggtggaaga
    1045 3644748 — NO tgggccacgtggtgctctctgaagttagaa
    1046 3799937 — NO catgcagtccccaaggctatcggtcctcctcag
    1047 3336773 FBXL11 YES gaggagcttgccaacagcgatcccaagttagccctcactggagttcctatagtacagtggccaa
    1048 2822962 — NO tgtgagaacagactcggcagtgacatccactccaaatgga
    1049 3627325 — NO ccagacctgagccacgtagctatcaaacac
    1050 3780263 — NO catctgaaattaatgggactaatgtaaggattgatattttcatatttgctcaattgcatcctgggttaagcacattcaacag
    1051 2656010 VPS8 YES atggcgctatctctgccctcagtatc
    1052 3028587 — NO tcacccaggattctcctgtacctgctcccaatctgtgttcctaaaagtgattctcactctgcttctcatctcctacttacatga
    1053 2419066 ZZZ3 YES gttgcctttgagtgatggtccagaag
    1054 3081481 — NO atggccacctgtgttgacgtggaga
    1055 3935290 — NO atgatgaaagcgtggaggtaccagct
    1056 3051677 ECOP NO ttgatgtgtgaacgctgacctgtcctgtgtgctaagagctatgcagcttagctgaggcgcctagattactagatgtgctgtatcacggggaatgaggtggggg
    tgcttattttttaatgaactaatcagagcctcttgagaaattgttactcattgaactggagcatcaagacatctcatggaagtggatacggagtgatttggtgtcca
    tgcttttcactctgaggacatttaatcggagaacctcctggggaattttgtgggagacacttgggaacaaaacagacaccctgggaatgcagttgcaagcac
    agatgctgccaccagtgtctctgaccaccctggtgtgactgctgactgccagcgtggtacctcccatgctgcaggcctccatctaaatgagacaacaaagca
    caatgttcactgtttacaaccaagacaactgcgtgggtccaaacactcctcttcctccaggtcatttgttttgcatttttaatgtactttattttttgtaatgaaaaagca
    cactaagctgcccctggaatcgggtgcagctgaataggcacccaaaagtccgtgactaaatttcgtttgtctttttgatagcaaattatgttaagagacagtgat
    ggctagggctcaacaattttgtattcccatgtttgtgtgagacagagtttgttttcccttgaacttggttagaattgtgctactgtgaacgctgatcctg
    1057 2699603 — NO aaagaaggatctgtcagccaagtcttttct
    1058 2836754 — NO agtgtggccgtttgcattactgctggaattttgaagactactacatattccgtcagtgtcaggattttgttcttcagtgtggtacttttttttttttttttttaagatggagt
    ctcactctgtcgcctgggttggagtgcagtggtgtgatcttggctcactgcaacctccagctcccgggttcaagcgattctcctgcctcagcctcctgagtagc
    tgggattacaggcatgcgccaccacacctggcttatttttgtatttttagtagagacggggtttcactatgttggtcaggctgttcttgaactcctgacctcgtgat
    ccgcccacctcagcctcccaaagtgttgggattacaggcgtgagccaccgcacccggtagtgtggtacactcttaaaatcatagttcctgctgtctg
    1059 3504560 — NO gcatggccatggatcgggcaagttggttttact
    1060 3924596 PCNT YES agacctgaaggcacaatcacaagaagagatcaggcgcttgtggtcccagcttgattctgccaggaccagtagacaggaatt
    1061 2408919 — NO taggtgacggattgttaggtgcagtaaacc
    1062 3219942 PTPN3 NO ggaccaggcttctaccattaattcacatgctttaaaaaaattaaaaattaaaaaaatgaaaaataaaaaaacttaaaagattttacctatattcctggaacatagtt
    atcttaccccagctttgtagttcctgtttaaggaaattccctctgaaggaaattttagctctcaagagtcaaagaagatgtatagaggtggtatctgttagtttttgtt
    tgtttgttaaggatctaggcagagaggtcattacatttttctgaagttgaggtcacaggtggggtacccacaagagaggtcattacatttctgaagttaggcatc
    ccaggcatctcttctaaagaactatcctgtattctaattgttaaataaatatcttcttcattgtgagcctccacaactgctgtttctgataaatttagatcattctttgca
    gaattttatatactggcaatctcaaaactaggctccttcaagattcctaggaagtctcccaagctcgggttgggttccactattctag
    1063 3240958 DNM1P17 NO gtcaacaagaccttgctggacctcgtg
    1064 2830809 — NO gtgcagattgttaatccctagtgtgcagggatagggagggagaggaaatgtccacacagacgaggagaaggcctgtaaatgcaaatttcacactgttgatg
    gtttgtcctgttggttgaccagcattcccaagataaccaggtgag
    1065 3020549 — NO cctcatgcatgcttcgagatcattgtttgcttcatttccctaaaatctacagttcctttgaaagtagactctggcgttatcacctttccccggtctttttgcagtttcctg
    ttgacctctgagccattctccctcactcttgtttcactctgtttgcaacactacctcttcctgtatcctggcctctcatttctcacagatcatcatgctgttcttgaaac
    attttatttacttgattttagaaaactatactcttagtttccctaaaatctcataatctctttgcgggattttcctcatctttgtgacttccaaaatttgaagtgtcccctgg
    ccagtcctgggtggctacattcaatctc
    1066 3282482 — NO aaaagaagtcgtttattggtgcatgggacactctgggaggtagtatccatttggatgtcctgctgcggttggagacatggaacaaaa
    1067 3192070 — NO cctgtcggtggactgaatgggccaagtgttcagaagtccttgggaagaggatagtgtcctgaatcataatgtggtattttc
    1068 2473609 — NO aaagtgtcctattctcggggtggcagggaggggggcaggccacaaaggacatgagtgttaggaaaagaagaaagcacagggaattaaggcaggaagg
    gataggctaactactgttctgtgcaaatgcaattgggtttatgatcaggactgactgcccttacgtataaagttgctaacccccaagacctgaagggaaaagtc
    ttttgaagctgccagttttttgatcattcaacaagaagacctgaacactgagaatcctttttctggattggttccatcaatactttgtccctgaaatcaggaaatacc
    ttgccattatgggacagccctttaaagttcttttgatgttggacagtgcccctggccacccagaaccccatgagtttaacaccgaaaacattgaagtggtctact
    tgcccccgaacacagtctctaattcagcatctagatcaggggatcatgaggacctttaaggttaataacacacggtactctaacctcaatagaacatcatgaa
    aatctggaggaattacaccgctgaagatg
    1069 2814779 — NO actctgctgactgtaatggctctcacgcagttcctaatgggcactgtggaaccactcagcatagacaggcataggcagg
    1070 3558342 — NO gcccagtgaaggggtgacagaactagcc
    1071 3611698 LRRK1 YES atctcctgccagatcacggagctcgacctttctgccaactgcctggcgaccctcccctcggttatcccctggggcctcatcaatctccggaagctgaacctct
    ccgacaaccacctgggggagctgcctggcgtgcagtcatcggacgaaatcatctgttcc
    1072 3701429 — NO tgccgcttttccctccacttgtgtaacagcatactcaggtttataccaactgggagacacgcaggcatctcccctcacaagcagctgtctactcaattctgtagtt
    atgtctgctaagtaatcagaatgcacaataggtttttagcatctgtatctcatcctcagagtagagagtacctgttttacgagagaaaactgagaaaacggtctct
    cagggcctctggggcagccttcaattggacagcagtagaatttcggtccagttttcaaatcttttcttattgttggattgactatgccatcctgcaaaaggaaaat
    tactttaaattattatttcaaaaaaacaacacaacaggctggagtggaaacggaatgactgaaaacgagcacattttgtgaaatacttttaattaagagtttttcca
    tctagtgtcagcagtaagagaaaaagagtatgagtagattaaacgaaatgtggtgagaatactaagcaagactctaaaattctgcattcatttgaccattactg
    aattcctcttagtcaatttacattccagggagatgccccccttgtatgttcctaggctgtgaaatgctcca
    1073 3933333 C2CD2 YES ttccgccggcggcatcaacagaaagacccaggcatgagtcagtcacacaatgaccttgtgttcctggagcagccagagggttcccggaggaaaggcatca
    1074 3799749 — NO ttggattccactaatcacccgatcacccc
    1075 2487131 ANTXR1 YES gaaagctgcactccaggtcagcatgaacgatggcctctcttttatctccagttctgtcatcatcacca
    1076 3187719 — NO gggcaaacttcagcctcattagatagaggctggacttccggaagagctgggaagggggaccatagtttctggggaggggtggagaactcacatttaccta
    gctgctggccaggctattttcatacccacagaccgatttaattctcaactactgtactcatttagtagatgagaagaatgagacattgaaaacatgcacagtgga
    ggtgggaatgaaagccagctctccaactctccagtcctctttcctgtcactgcatcaggctgcagggtgaaggggaggtctgggatacaaagagaacttag
    aggtggagcagttggattctgtgcagtgctaggagggaggagaggggttggagtaggtgggaagtaggcctccttcagtttggatagcacttcccttaacc
    caatgactctagtgggagggtggagggatggggatgggaagggagcctgggagtgaggaggaaaggcaaactctgtcttcccccaggggagtcaatg
    aatagtacc
    1077 3474744 — NO ttagtgtacccttcggtgacaggtaagggctttctgaaacgcattgtctttttattatagccattctagtagtaaggtgtgaagtggtatctcatagtggtttgggtt
    gtatttccctgatattgggatgttg
    1078 2489696 — NO atgcagttacaaaatcggattcagcatcagaacag
    1079 3195395 ARRDC1 NO gtgagtcgacagccagggcttggca
    1080 3497381 — NO ggtggacagtgatggtttcaaaggggaaa
    1081 3130174 GSR YES tcattgttggtgcaggttacattgctgtggagatggcagggatcctgtcagccctgggttctaagacatcactgatgatacggcatgataa
    1082 3180421 — NO gagaggtggatctgtctggacttcaggctgtgagaacctcacagcacagataggatgtgagctttaccccttgtgttcaggccgctcgcacggagtcagctt
    gcggaagcacgttcccaggcctgctctgcgtgtaatggtggaatt
    1083 2384882 GALNT2 YES gaagtcggtgaagcacatggatttgtgccttactgtggtggaccgggcaccgggctctcttataaagctgcagggctgccgagaaaatg
    1084 2601621 — NO tctcctgcttcctagacgaaatctaagcaatattttatccacttctttttagtaaaagaaatacatattgcctgttggggtcatgagctatgtagggaatgaaaaaat
    tttttaaaggagaattataaagagaaggaggatacaagagaaaggaaaacgaaagctggtgggaagttgagccatgtttatctctagtggaatccttaccttg
    tgttt
    1085 2624206 ITIH3 NO tggatggcccggattttatggcatctggaac
    1086 2626149 RPP14 YES tcaagattgtggagttggactgaatgctgcacagttcaaacagctgcttatttcggctgtgaaggacct
    1087 3466862 — NO tgtcacttagtctactgccagtctactgtctgtgccaccatgggaaattgcatgagttcagacctgtgaaaaatcagaataaagataaaaacacattttttgaag
    gttacggaaattcttaagatcttggttttcttgaacttactactagtactactgatttagaaatggcctacctcctatagtaggaaagggcaaagaaaacaatagtt
    aatagggaaggcttaaaggagcttgagggctgtcctggcaataatagaagagatccttgttttttaaaggagagttaatgtacaaagattctgaaaagtctaga
    aacatgggtaaaatttttatgattgccgggcgcgg
    1088 3400762 — NO tcaatgaccagcgtagacagagctagtagcagcaatgagatgagtgactagagaggtagagagaaaaccaggaaagtgtggagtcatggaagctaagg
    aagatggtgttgggaatagaggtggtgaacagagtcccctgttcttgctgataggagaggtcaaatgagataaggacagaggcgtggcctttggattccga
    gatgtgttgatcaccggtgcacttggcaagcatgcca
    1089 3511392 KIAA0564 YES aatcccgcttccctgtactttatgaatatgactgggaaaagtggcttctttgtggacttttttgatatcttcccaagaacagccaatggcgtttggcacccttttgtg
    acagtggcaccgctgggaagtcctctcaaaggtcaagtggttctccatgagcagca
    1090 3762555 — NO tgcacatgtggtaagagcatccagcaggaaagaagagggcaagttgagtgtgcgtgggcatgaaggattcactgtacgcatcccagccctgctcatctca
    gccgcatggactgggcacacatttaagcatggagggtggtggttttcaggctgttttctagagctgtagaactcaaatgaaatgctctgagtctgtgaggggg
    ggaggagtcaataaagggtggctaagtgcatggagtttgaggtacccgctctgctgtaacc
    1091 3853067 ILVBL YES gcttgctgctctcacgggagaacgaggatcaggtggtcaaggt
    1092 4015570 — NO ttcatggttgcctagtgctgcgaggagtggggaatggggaatgagtgcttaatgggtatgggtttcttggggtgatgaaatgttccggcactaagttgtggtaa
    tgactgcatgactttgtactaaaactactaaattgtacactttaaatgggtgaattgtatggcatatgagttatt
    1093 2458440 — NO tgcacttttgcctccgaactctcgtgtttaatta
    1094 3333734 SLC3A2 YES atgggttccaggttcgggacatagagaatctgaag
    1095 3379257 — NO ggccgtgcagcttcttgacaaattgcaaaggtgcccacgagtttccaagt
    1096 3662461 NLRC5 YES ctcaacttgatcacgaggttcctgacaccgtccgagctcctttttgatct
    1097 3670791 — NO gtgcaggtctaatgggctccttccttc
    1098 2689662 — NO ctcatggcaacttcttccgcttcctagtttca
    1099 2698749 XRN1 YES gctgggatcactatggaagcaactatgcattgggggca
    1100 3940626 — NO tgcaggctttacctatgaccgaacatgcatggaaatgccctctgatggactcaggcatgatacatacatcaaacagccttgcacggtggta
    1101 2577438 — NO gagagcatggctacaacagcaatatttctggaaaccagttatcgggggaattcacagg
    1102 2885881 — NO atggactcatcccagaacaatcctcaggcactccgaaatgcagatgccc
    1103 3473848 TAOK3 YES atggctccagaggtgatcttagctatggatgaaggacagtatgatgggaaagttgatatttggtcacttggcatcac
    1104 3721713 — NO agaacctggtcgtgtcttgagaacccagtccaaacagaatcaggcctctggactgggagcaacactcccttcacccgcaaagattcaggaaaagcacccc
    aaggacaaggaaaccaatgaggtctgggctagctctgcagctttaggatactagctctagggaaggattttttcctttttaaacagcgtatcactctgttgccta
    ggatggagcacagaggcaccctcatagctcactgcagcctcaaactcctgggctctggcgatcctcccgcctcagcctcccaagtagctgagaccacagg
    cacgtgccaccatgctcctagggaaggagcttgagaagaaactgccaggagtgaaccagggctggctgctctgtgatgttctctccccacctcccctccag
    ctctcaacttggtggcagggccggcaccctgctctccctcctaactcccagcctgctgctgcccccttctgggaccctaattttctggactttgagaaatgggc
    tgcccctgggggtgcctccaagagcccatttgagggatcgggtggggctgacctctctgtcttctttggatcatcgccttctcacactgtcctccctcttgattct
    gaaaaatggtcctgctgcccatggagaaccacagtaagatagatttctcatgcagctagtgaggggacttc
    1105 2924660 — NO accatgtttttgcctccagtctgtc
    1106 3242466 — NO atggctatgggaatatcgggagttgaggaagaaaaaggctccagtggcactgaag
    1107 3268238 BTBD16 YES agcagctcaccaccggctgcgagaagtggctggaaatgaacttggttcctctaggggggacgcagatccacctccacaaaatcccacaggacctgctcc
    acaaagtgctg
    1108 3293847 SPOCK2 NO tgtggcatgcgctgacaaatgtgtccttgatccacactgctcctggcagagtgagtcacccaaaggccccttcggcctccttgtagctgttttctttccttttgttg
    ttggttttaaaatacattcacacacaaatacaaattgacaggtcaaaatcca
    1109 2416565 JAK1 NO aatcttgctttttgtggcctggggattggctgtgtgatcagcattgaaatgggttgttgcagtttgaagtctggaaggggtatgtccctgggttctaattctttccct
    ctaggtttctgtactcagctcagagtctagaatggtagcttttaggattggaaaagaccaaagttacctaattcaactctttcatttttttttcagtggaaaaactaat
    acccagaaaagggaagagagttaacccaaaaattacatctagtgaattgtctgattagctttacaattgaggcattgtagagctctttgaggcattagtcttggtt
    gtctgagtgcctggctattaaaggctgtctttgcctgttccctctttctgttagctgcctggaagtgcagggttgcttcacttttagcaccttgactctgtacctgac
    atggtgcttcaacaggatattgc
    1110 3198506 — NO gtctacgcagctgccatagaggagggggattgtttgggagaccttcccgtggcagaatcaaagctcgtagttcagctgcgggaatctggtgtacttaa
    1111 3384336 RAB30 YES gggaagacgtgcctcgtccgaagattcactcag
    1112 3649726 — NO ttgtgcaacagaaaactcaacccaa
    1113 2732288 — NO aggtttagttgtgtggccgtaatcacatccaacaccaagtcggccaaccatatgtgagcttaatcccacagaattcttatgttagacctccctcttcagataatag
    aggagattttttttaagtatacgtgcacagaggaagtgacttctttctgcgcactctgttgtcactggaa
    1114 3291868 — NO tacgaggaagtgaccagtgttcatctgaaacggatgccttgtttctcagaaatgtcattctctttatttcatcttcgtagttctgtgccttctctcagcaatttctgattt
    ctttatttactgccacacagatgacaaatgacatgcatgtccatgataccctttactcaattcacatgcgatttccaaggctggctataattcccaaa
    1115 3572359 — NO gtggggggctgtaatctacaaaagccatcttcagtaccaggtttaattccatcattgtttttcgggttttaggtctctggactattgtcctttaacaacaaca
    1116 3613987 — NO gcctgcctgttcatgccaaatatacatcctcacaatgcacagtacacaacatgggcacataggcacagaggctatgccgg
    1117 3768275 — NO ggctttgaagggcaactgaccaacttttttatacataaaggatataaactacaactattttcccactctgtgtagaatgtggaacggaaacagtgtgtggcacac
    tttaaatgatgctaaacttctacagtgtgtaaactggcttgttcaagaggccaaagtgcttctgttgagaaacactgatgaccaatctcctctttgtggtcctgtga
    tactgtgaaatatatatttgatcttcctccctgtttcccagcatacaattcctaaaaccctcagaatctgcaaaataagatttttttttaatgctaatgattgactgatg
    gctggaggctcctagagagcctcaggattggggctgattctcagggctttc
    1118 2367980 RABGAP1L YES gaccatcttctccaggtggactacctgaagaagatagtgttttatttaataaactgacctacttaggatgtatgaaggtttcttccccacgtaatgaagtagaggc
    tttacgggcaatggcaaccatg
    1119 3063344 ZNF394 YES gtgtgaagaatgcgagaagagcttc
    1120 3147137 — NO tttaggaaaaggctgctatactgtggacgaagtctcagatcagaa
    1121 3737089 CCDC40 NO acgggacgctttctctgggatgcattgagtcagggaatagaagatggggtgaatgatgtttctgacccacagaccgttgggatgcttttgctgtcactttccca
    tcatgctgcatgaggcatgacagcagctgt
    1122 2686311 FILIP1L YES tgccaagcatgcgatattcagagtctccccagaccggcagtcatcatggcagtttcagcgttcaaacagcaatagctcaagtgtgataactactgaggataat
    aaaatccacattcacttaggaagtccttacatgcaagctgtagccagccctgtgagacctgccagcccttcagcaccactgcaggataaccgaactcaagg
    cttaattaacggggcact
    1123 3307401 — NO gccactctgctcaaagttggcacgagttggaatgtaatcaccatctctgcactcaaggcatgcagaaatgaagtctacctcagccctcaaagacctcacctg
    agaaaaagacaaggctccaaacagaaggcaaaacagaatgagcatagaaagagaccactttttcacatacctttacaaagcactgctcacccctccttaac
    ctcgcacagacagagcatggggcctcagtgtcactgccactgccaccctcccactgactagctgtactctctga
    1124 3648042 CIITA NO ctctgaggacactaaccacgctggaccttgaactgggtacttgtggacacagctcttctccaggctgtatcccatgagcctcagcatcctggcacccggccc
    ctgctggttcagggttggcccctgcccggctgcggaatgaaccacatcttgctctgctgacagacacaggcccggctccaggctcctttagcgcccagttg
    ggtggatgcctggtggcagctgcggtccacccaggagccccgaggccttctctgaaggacattgcggacagccacggccaggccagagggagtgaca
    gaggcagccccattctgcctgcccaggcccctgccaccctggggagaaagtacttctttttttttatttttagacagagtctcactgttgcccaggctggcgtgc
    agtggtgcgatctgggttcactgcaacctccgcctcttgggttcaagcgattcttctgcttcagcctcccgagtagctgggactacaggcacccaccatcatgt
    ctggctaatttttcatttttagtagagacagggttttgccatgttggccaggctggtctcaaactcttgacctcaggtgatccacccacctcagcctcccaaagtg
    ctgggattacaagcgtgagccactgcaccgggccacagagaaagtacttctccaccctgctctccgaccagacaccttgacagggcacaccgggcactc
    agaagacactgatgggcaacccccagcctgctaattccccagattgcaacaggctgggcttcagtggcagctgcttttgtctatgggactcaatgcactgac
    attgttggccaaagccaaagctaggcctggccagatgcaccagcccttagcagggaaacagctaatgggacactaatggggcggtgagaggggaacag
    actggaagcacagcttcatttcctgtgtcttttttcactacattataaatgtctctttaatgtcacaggcaggtccagggtttgagttcataccctgttaccattttggg
    1125 2568862 — NO tcttcttctagcagtgctcagtgggt
    1126 3405549 DDX47 NO tggcgtgagcgagataaacctcctaacagtaggtttgtacaataaggccatagggcaccgatgcctgtttccataattgttgtaattttatgggctttgaagtgtt
    gctctagatacttactttctcctttcagggtagcgagaggctcccattagaatatttcatatgtacctgtctggtttgcaagctgttgagttgatttattcagccctag
    tggtaataatgactc
    1127 3479324 ANKLE2 YES aactgaaggagcggatcagagagtattta
    1128 3736140 — NO tggatgtctactttgcacgctgcgattgggagagctgtcccgctgcatgcgttccctctgtaatttcctcagagctcacatacgtacctctctcacgagtgaact
    cagattttccattgttttgctttattctatcatttgctttgtggttttgctgtaaatattgaaatcttaatcatcatcgagaggcacagccaagctttccagctctccacc
    cccgtggcccatccaagtctgttcatctggtaacttctgttgtctgggacggcagcaagaagatgccggggcttgcctggagtcctggcagaggagtgcca
    ctcacttttgcctagggtccagttggggcttaaaaaatatttggagagaagagtaatgaggattttttgtgtttcctagacattttatgcatctatttttgtaaaatcac
    cttcgctaactttcaccaagcactttgagcacagtggaacttcagaagcacaaccagcctaaccccagaatctcaggtggcacagctagaaattgagtccctt
    cctaggacactggccgtggccttcagggtgaccagtcagtgccaccgggttggcattggtgttacagacaggcctctgaagacaaaccgagcaccccag
    cggcccctcaaactaagcaaggatcttttttctgtctgcgctccctggggcaaggtcaaaggtggacccgcccactgtgggtcaattcatcgaaaagatgg
    gacccgcacccccgccacaggctggcccccccccacccatggggaaggtggtgtgctgctggctctgaccatactcttttggaaattgagaaggaaagca
    ttgagtgggacctaatccggagaagaaattaaagaccagaaaaagaaggaagctgggaatgaaactcaaaatgcacttgaacctggaagcggcaaccct
    cagctctgcgcggccgagcctcagcaagagttcgttt
    1129 3954953 — NO catggtctaaccacagaggggaatactactcagcaatacaaaggagtctctcctaatacgtgcaacaacattcatgaatcccaaaaactttatctggagccaa
    gccagacacaaatgtgtacatacagtacggaatgacttcagattctgaaaaaaggcaaatctgaccaattgaggcagaaagcaggtcagtggttccccagg
    tctgggactggggtgggttactgatagcaaatgggcatgtgggtgccttggggtagggtaaaggttccatcttgatcacggtggtgtttcccaagtgtata
    1130 2396759 FBXO2 NO tcgagggtagataggccttaacttagtccatagcgtcctcaccttccccaagccacacatcctcctcccatcccttgctccgatcccagcccctgagcaggga
    gagagaagttttgttggcataggtttgcttaggtagccggcttctagaatgtagatccgtgagggcgtgagcttggactggacccactgctgattccctgcac
    ctagcacagtgcttgccacaaagtgggctctca
    1131 2519281 ITGAV YES ggtgagcgggaccatctcatcactaagcgggatcttgccctcagtgaaggagatattcacacttt
    1132 3640619 — NO tctgttgtctcgcccttgctctgctcctacttcacccatcttctgagatccaagtcaaaatcatctgcacg
    1133 3976861 HDAC6 YES acctaatcgtgggactgcaagggatg
    1134 4048293 — NO ggggtagaacaatcaagcttattcctaaggattttcttttgacaaataaatgggtggtagtgttgtttattgagataggaaaaactatgggaggaaatgatttgaa
    gtgggtggtttgaaataaaagttttgtttaaatatgagatgattgattgacatttatgtggagaaatccgaaggtcaatggcatttaagagactcatggtgaggcc
    agggcttcaggtatttatgttggcagcagcaatacgtgtagtgtgttaaattccagggcgtg
    1135 2393657 KIAA0495 NO ccctgtttgtctgagccctttggagatttaggttgagtcatgagaaccggtcattggaacatacactttattatgttacaaaaacaaaaatccccactgaaacaca
    gctaaaaaaataacacattttcccaagattacattaccaaaaacagttgttatgtcattggagggcgtccattaatactgctcggagaagcacgatcttaca
    1136 3389355 CASP1 NO aggtttttggaattatgtctgctga
    1137 3584178 — NO attgtagtttgaagagctgcccttgggaactcatgggacaggcatcaggcctggaatgggatggacaagtggggcctccaggagaaggagcattgcagg
    agatgctggagagtggggagcagtacgtgcagcagatagggga
    1138 2365984 MPZL1 YES tcaccagttaagcaggctcctcggaagtccccctccgacactgagggtcttgtaaagagt
    1139 2468456 — NO aaagcaatcttaacagtgagggctatgaaaccgttgaaaattctcccaagggaagtgatggaaacctccttgcttgagtcatttcaaagtcgacaaaacaacg
    aaaaatacatggagggagggatcctgtagtgttggggagcagactcgatgatttcatagttcttttctgtctctgatttccatgttctgtgaaatagtattgcagct
    aagaaacatgaaatccttcactccgacagtatg
    1140 2954656 YIPF3 YES acctgcttcggctactggctgggagtctcatccttcatttacttccttgcctacctgtgcaacgcccagatcaccatgctg
    1141 3499189 ITGBL1 YES agatggcatattgtgctcggggaagg
    1142 3102170 PREX2 YES gaaggatattattacagagacaatgtttctgtggaagaatttcaagctcagataaatgcagcctcactggaaaaggtcaaacagtacaaccagaagctc
    1143 3151372 — NO caggcactgtatcaggtgctgcgtacttctgctagctcatctcacctggtcatgccgctctga
    1144 3153640 — NO ttcttccttgatgcaggatctgaggttgaag
    1145 3708351 — NO tcacattctggggttagaaggggcccaatggatgggaattcttcatataaaagaggaaatgcc
    1146 3793991 — NO tgcaacaatgggagctttttaactagtctctgtaaggcgttgtcatcacatctg
    1147 2840186 DOCK2 YES catgagttcatgagtgacaccaacctctcggagcatgcggccatccccctcaaggcgtctgtcctctctcaaatga
    1148 2945913 CMAH NO ttgcctcccggagtgtgtaaccacatgagaaatagagggaaggttctgtccttaagaagttaaaagtgtgactgggaaggtaaaacatacttattaagggtta
    actagcatcatgccattctgtgtgatggtgagtttgtgtgtgtgtgcacatgtgcgtgagtacacacatatacatttaaaaaggtcttgaatataccaaaatattat
    gtctaggtgatgggtagcttgtatattttttctgtatccttgtctgtgtttgtcaaattttatagaaacaataacagtaacagctctctgaccttctaccctgtatgttct
    gcgtcctgtctaattcctcaagttccttcactgcctgtcactctgatgcttgctatatatcagcccatcctgctttttgtttcttagacccaaagtgtcaagtgcacac
    ctgccctgggtctttgtgtttgctgtttccatttcctggagtgcagctggccctgatttgcatgtgaccagca
    1149 3706405 PAFAH1B1 YES tcgtcactggcagcgtagatcaaaca
    1150 3898481 — NO atggcggcagagtatctggttctctt
    1151 3962245 NAGA YES tgctcttgctgggacatgtggcccaggtgctgatgctggacaatgggctcctgcagacaccacccatgggctggctggcctgggaacgcttccgctgcaa
    cattaactgtgat
    1152 2877309 BRD8 YES cacagagccatggtccatccgagagaagctatgttt
    1153 2973720 — NO gtttggtgtctggtacttagagctccctgaaactgtggtgttt
    1154 3091762 FZD3 YES aatcatttgcctctcggccacattgtttacttttttaacttttttgattgatgtcacaagattccgttatcctgaaaggcctatta
    1155 3418179 — NO ctgagctcatccagtaaaactctcaaaagatgaatagatgcccttttccttgaggagccttctgcctgatttctttgtcactgagtttgggtccctggttggagtgg
    caggaggaaggggtccaccacgtcttctgac
    1156 2685385 — NO tttggtgtctttctgaagggattcggcccggag
    1157 2912792 — NO ggatgaaatcgtgcacgtccctcttcgtccctctcaggacagaaattcttttgtccagcatatatctatgttgcatataccaccagccaattagtcacttagtagct
    ggtgttggttatgagatcaactgtcatagtatcacagtgcttgtttcaggtaacccttatgttatttaatagtggcccaagagtgcaagagtactgttgctgacaat
    ttggattcacgagaagc
    1158 3590727 JMJD7 YES tctggtatgacatggaatacgacctcaa
    ///
    JMJD7-
    PLA2G4B
    1159 2363028 — NO gaaacgccgtcctgcggaaacatccaccatccggacc
    1160 2374733 — NO tagagactggatcatagaaggagttgtttgccatgcttacccttaaaggctttctgagcagtcatcctgggatggacagggcagggagtggagagaccagc
    gagcaggtttttgttacggttcgagtgagggttgaacacaggcagtggtggtggagatgggttgcagggataatcttgagagagatttaggagacaagattc
    acaggttg
    1161 2448301 TPR YES gagattcagcgattgcaggaggacact
    1162 2596900 — NO gaatggtgggaaatgtatgcttgactcaaaacagccag
    1163 2713805 ZNF595 YES ctatatgttctcctttcagccaagacct
    1164 3878694 — NO ggggtgtctgcgtggggagaaatcagttgtcggcattttaaatctctggataatgag
    1165 2434634 ARNT NO cggctgttgatacgattgtctgttatcgaacacattcagtgataaagctgggttactgctgcttttggtgctctcaccttatctggaagatctgcaaacattaccta
    aataggctggcaagataaacactttctggaacccgagacttggccataaagataatgctgcatttttctgtcagaatcacatatgatgtgtgttctgtagaggtta
    tttctgcatggaaactcaacttcttggattagccgtcccagtgaaaatcctcattgttggagtgtaaaccaaatacgaagccctcttgcaaagtagcctctttcat
    cccatactcaaaatacccagtttagcaagcaactgagatttaagtctctctggccctaagaggtttttcctctttgctccctccaatcttgagattgggttttgcttta
    gagtgcaagtatcataattccgtatgatagatggggcctggacacccatctcaacagggtcacttggtaattaacaatagccatataaatgcggatacaggtt
    actaccctcaccctttaccttcctcaggtaacagtcgtagataccagcttttttttttttttttttaaattggctttggccagtagctaaagtgcaagactgaattaatg
    agaagatatattaaatgtagtcataggggactgaggagcaagggtggccttgaagaggccaaaggaatgtccatttgctgagtttcccttccttatgtctccag
    tctggtgccaggtagtggagtaaaaaaggagacagtttatttttttattctatgtgcacacttacagtatacatatatatttatatcacaatttacgaaaccaaaaag
    ttgagtttccaatggaacccttgttttttaataatcgactttttaaatgtgatcaggactataatattgtacagttattatagggcttttggggaaggggaggatagc
    gagaagatgctctgggggttttgtttttgcttttccttcagggttttatttttgactgttttg
    1166 2502158 — NO tgcactttcccagcgtttctgtctgc
    1167 2511348 — NO agacaacagtaaagaaataccagcaatttgaagccctgtccctgaatcctactcctgttgccttcatatcgagagttccaagtgttggcctgcagttaagttctga
    1168 2697262 DZIP1L YES ggaactgcatgaagagcacatggctga
    1169 3829727 GPI NO gttctctgccaagtgctggccagaggcgcgtgtgttggtcctggtcccccgctttctcccccactgtcctgtccctcccctccccgtgcagctgctcag
    1170 2566885 — NO cctacgaggtccatggcagcgggtacttgaaggattta
    1171 2644609 — NO ggctttgaggatctctgtgccactttg
    1172 2681773 FOXP1 NO tccttacgaggctagagattttctgacaacagtatgttagtttcatttggtccgtgaatggagatggcagcaaatattctcagaccctcccagatctggctaaga
    catccccttatttaggaacgaccctcccctggcataccctactctccatcgcctgttggcaataaacgtgccttgtggatattccttaaaagccttcctgccatcc
    ctctagcagtcactgtaaagttcaaatctcaaagatgcttaggagccaagattctctctgctcgtgcccagcagcccctgctgtgagctcactgccttccccag
    cacgacctcctaggctgctgccttcctttctgttggagtctggagtcaggctaactcctaaaaatctgcagagaggtctctggagggaggacccaagcctgtt
    actacctaagccagaattttacacctagtttccttgaatagagaagtccaaccccagaggtgtgcacacacacccgccctgcaaatcagtgacggggagaa
    agcctgacttttcttgggttttgctagtgggggaaattgctcatttggaagggcaccagcaagctta
    1173 2941811 — NO gtgtcgcttttattctaactgctggaactatttgttgtacctctttctgaagatcagtttggggctaaattacaagctccatcagcacaggggccatggctgcctcc
    tgactgctgtaggctgagcacttggtagagcatcagccc
    1174 3037970 — NO tcacctaaaaggacgaatccatctgcttctgtctctggtactgagggctttttagattccggaggctttctgaaga
    1175 3235439 SEC61A2 NO acactttgacggatcgtttttgtcagatga
    1176 3670576 — NO ccaaggtcacacaatacgaggtggggtcagaatgcaaacccaggcagtgtgcctacctagcccagactcttaaccactaagatgtcactaaagaagca
    1177 2682104 — NO ggagatttggagtacttggagcatggag
    1178 3809910 — NO gggaccttgtccctctttgcatggagggatggtttctttaggtcctgggggatagcccaggccacttccactctgaagatctgtgttctttatcagtctttcaatct
    agtatatttgcatttaataggtgacaaatgggcctggaagctgtggtgggg atggagtgggaaaccagctctcagtctgacattgactcctggaggggagg
    gtcacctctgttcctgggcagcctttcagtggcgaaggccaccatcccccacagcgtgattgagaagcctggcacttctgcaatgagtactgtggagcctga
    cctttggctagtagcttggtctttattgacagggctgtc
    1179 2428310 — NO cccgggtctgtcataaccgcaaatttctataccactctgctgctttaagatatcaacaggcaaaagataaccactgtccaactcacataaaaataggacatcaa
    gttttgggggacttcatgtcctacctccagcttactaagcctgctatctctggagattccactactgcaaacctagttaggcaatgggtaatagcattacccatta
    agccaaatgtggagtgaacaataataataatcactaggacttggagagtcactaaataaagatttgttgagtaagtggaggaaggctgccttctaagctgtgt
    atcactttggccccaacctgcagtactccttcccactgtagccactgactcctgctcccagcttcaaaggctaggatcctctcataaagaattaccaaagccag
    agatccctacctgcctaatatatactgatgcctcatgtgggcccttga
    1180 2429289 — NO tgtggtttgattagtaactaccctggagtgtctcaacttt
    1181 3246430 — NO acccgatgttgacagtttctccctccctctctctctctgctgtttcctctatagagctaagtctggtttgcattgaaataagcatgcagtaatatgccttttgccttac
    caacttgtatttgcacacaggcagca
    1182 3314235 — NO gtgtcctaagcgggtgcatgtccag
    1183 2332841 ERMAP YES tggagaagagcccggttgcattttg
    1184 2452077 PIK3C2B YES catggtgatgcatattcggggcttg
    1185 2592323 — NO atagagggttcttgcagctgtccaaggtagaggcagtggaagcttgcgctcagtagaatcagtggaggtaggaagaggtggacagattcaggttatgcttt
    ggatgtgataccaatatagaaggatccttatgttgaaggattagatgcaggagtgagagcagaaagtcaaggatggctctacagcagctactagaacccctt
    gaaaaatggtaatgctgtacacggagctgggaaggcaaggagggggcaggggcaggagttttgtaggactcaataggtttgtggagagaaaaggaggc
    tgatgggaaaatcaagggctttgttttgagcaacatcaagatacctattaaatattcaaggcatcaaacagtaaatgagtcagagttgtactagtatcaagatttt
    tgatcattgttttattaatcctaatacaaaccttcctagttgtcagggttcagc
    1186 2895598 — NO atgttctcggaacaaggaaccagtaaagtacagacatctggccccaggattttgctggctccagggacgtcactataaacccactaacactaattgctttcac
    gtctgctcccatttcta
    1187 3578431 — NO catgcgaaagcaacagtctgatctccaggttatgaaaactataattaaaaagtcactacacagaaaaggtccaagtttccagcttggcaaaacttgggtgcag
    ttacatgaaacgtttaataaactgaattgttttccccaatgtgtaaacaaaatgacaagactaaatctgtgcctggtaatttcaatctaactctgaagctacacaaa
    acacacagacaccttgtacatttcacctgttagtatgaccatcttttttcttcggtggtggaaggaagggcaaggtgactgtgtaaagcaaagatgtgggaagt
    agaaatattgtttactagacattataaagtcatggtgaaaagaaagcttcgattaatgcatagcctaaggg
    1188 3590373 — NO tcttgtggttccttaacttgtggcagcataactccagtcttcacatgaagttcttcctgtgtgtgtatctgagtcctaatataaggagactagtcatattggattggg
    gtccatcctgctctgttaatgacctcatcttagctgctgacatctgtaatgactctattaccaaataaggtcacagtatgaggtagtaggggctaggacttttaac
    atacgaatattgggaggacacagttc
    1189 3277334 — NO tgcctgcttcacacaagtcgaactgcaactgggatcttggcttcttgtcaagtcagtagcatgcaagccagtttaagtcaaaagaggacacactcctcttactt
    gattccccttgccatctattttctccctcaatcttagccacttggagaagaatttaataccttttttttttccagagtccaaaggctgtggatctaagtggggcattttg
    tgctcaagcgaatctgccatgcactacggtttcaactc
    1190 2323027 — NO gagcggtatcttgaaggtggctttaagtttgggaagttcgggaagagcagtaaaggcacgatactgggactgagcccagtaggagt
    1191 2360843 HCN3 NO tgtcagcagatgtcttgggtcctgagt
    1192 2834307 STK32A YES gaataaacaaaagtgcgtggagcgcaatgaag
    1193 2890310 C5orf45 YES aagaagaaaacgtgggacaccagcaggc
    1194 2510000 — NO gataatgaagccaacgcaaaaatccacgtctccaggctaa
    1195 2575065 — NO tctttccagctcatgtctcccggggggctgggctgtctcctgtcctgcagccgcagcacttgatctcagcaggtggaatgcagagcagaggaatccgccag
    acattacagggatctatctgagtataaaacgggactgctctttccactaaattgcttttggagaataaagttaagtgaattaaaatttccccagtctcaattgctaat
    atggtaaatattcgcagttacaactctcattaacaaaatctcttaggagtcctcagtaatttgagactgtaaagacgtcttgatactacaatgcctgagaacgagt
    tctctggatcttacctgcccctcttacatgaggaggcaccctgatgtctgggtggcttaccctttggcctctggcgggcattcagcatgagtgaa
    1196 3336723 FBXL11 YES tttaatgtagagtatattcagcggggtggcttgagagatcctctgattttcaagaattctgatggactcggaataaa
    1197 3660063 — NO catgctctgacgctctatgccactgctgcacct
    1198 4029263 — NO taaaagactgaacaagaagggcacagtgttcacggagattgaagtgaacaagaaa
    1199 2663789 CHCHD4 NO gatgaagatttggacccttccattcataatccctttctaagtgaagggagaggctggcttggctgttccttgttattccgaaagccctggtttggggcccatgttc
    acactggctctcagtctagtcaggtgca
    1200 3743045 — NO gccactctcgtgctgcttgagctgc
    1201 2826559 — NO agcaaagactctcgggaacaccctattacaggaaaatctctcatacctgacctctgcttaacccactcgtgagattaaatgatagtcttcattctctctgtagaat
    ttgctgactgatgctcatgctacattgaatgacagtagactattctttagttttatcttgaacttttattccccccagttactgtagacttaccaagaaacatttgtgttt
    gtacccaacacactgttatggcacttgatgttgtaatcacatagtttaatgaattattattcagtgaactctgaagataaaaaggcgtttgtatgagaaccaattgg
    ctactttgaaatcaagtgagtagccaaaatcaattatggttgaaatagatgagggttaaataattttaaatgattagggaaaaaaaaacaaaaaacacctaacg
    atctaaaaaaatctgcaataatattatttttcacgtttgtaaaatgtctttctgtgtttaagaaacagaaactggaaatcacaggtgttgttttatgggggtagtttttg
    caagaaaaaggaaatagaactttcttcgatagacccacactgga
    1202 2882611 FAM114A2 YES gtgagccagccaagaattctgagtctgttgaccaaggtgccaaaccagagagtaaatcagaacctgtagtttccactcggaa
    1203 3044784 — NO gacccacggcaattttgaatacttggaagagcagtctaagtaccctcacacaa
    1204 4016017 ZMAT1 NO tgtaggtattcccatggtttcatccttgaccttactctacaaacacgatttctatttccctgatttcatttctcatctgtatgcttatgacctttctgtcaagtattagattc
    acatatccaaatggcagctactgcttcacctggatgcctcatagcca
    1205 2872559 — NO ttggtgatgctttatcgacctctgagaatccctttgtgatctgcagtgctactgtggttcacaaaatctgtgttcttgctctccctgatagcatctgacatttgtcatc
    aggggttggcaatc
    1206 2810393 MAP3K1 YES tgctagtgcaactactgctccatcgatcccttcacatttgtctcctggtttacgagatgtggcttcgttgtttagaacttc
    1207 3309863 — NO aagtgtagcggcaggcatcctggga
    1208 3349873 NNMT NO gaatgctgttagcctgagactcaggaagacaacttctgcagggtcactccctggcttctggaggaaagagaaggagggcagtgctccagtggtacagaag
    tg
    1209 3849058 — NO gtacatcattacccggcacagacaca
    1210 2609601 — NO cccctcaaatcttacagctgctcactc
    1211 3489275 — NO tctcttgattagtctaggtggtggtttagttctgttctgattttttatttgttttagagatggcatcttgcgatgttgcctaagctggactcaaactcctgggctcaagt
    gatcctcccacgtcagcctcccaagtacctgggactgtaggtgtgcaccactgcacctggctgtctgctctgatctgcaccactgcacctggctgtctgctct
    gatctttattatttcttccactaattttggatttggtttgttcttgcttttgtagttcttgagatgtgcattgctagattgtttatt
    1212 3490771 — NO tctccgtattgcttagggtggtctcgaacttctgacctcaagcagtccttcggccttggcttcctgaagtgctagagttacaggcgtgagccacagcacctggc
    ctacatattacatttaagtctgtgatgcttttagaatttttatgtcaagtgtgagatttaacttgaggttcctttttgtggggtggatagtatgttcgggtgttctggcac
    ctatcttttctcattgaattgatttgcacctttcttaaaaatcagttgagcgtatttgtgtgagtctatttctaagttccccactgtgttagattgagctgtatgtgatcta
    tatgtatgttcctctgtcagtcccactgtcttaagctgtagctgtttaagtctgaaattgggcagactcattcctcctacttta
    1213 2353513 — NO taatgtcatcatcagtgggcaagtctagaaccctaatatcctggtgctcaaaattagtgttatcaattcagtcttctccacattaaacaatttccaattcctttgagg
    cctggtgtgatggattctgtctttcaaatgctttttttctttcagtgactctatcgttcataaatgttaaataaaaccctcactctgttataaaaatatagactttaaaaat
    tttccaaagtaaacactccagagaaaggtaggcgggctgaataggctgctgttgtccttcttactgccca
    1214 2610157 CRELD1 YES catctgtgtgaaggagcagatccca
    1215 3092298 LEPROTL1 YES tggggagcttgtgcacttgttctcacaggaaacacagtcatctttgcaactatactaggctttttcttggtctttggaagcaatgacgacttcagctggcagcagt
    1216 3241630 CCDC7 YES taaagaaaatcgaccagaagcagtgaaaagttg
    1217 3489976 — NO ctctgaggtttaggcctcgatattcaggagagtggtgtaggaggaagatgaaccactgggttttagacacatggaggcttagttcagggctttgggcctccc
    ggttagtttgtttagtcttgttgatctaggaggagatcacaccagatga
    1218 3671050 PLCG2 NO ggagaacgtgccctattcacactctgggaagacgctaatctgtgacatctttctttctcaagcctgccatcaaggacatttcttaagacccaactggcatgagttg
    gggtaatttcc
    1219 2476149 — NO gtcagttagacagagtccacaagggagtcg
    1220 2670672 — NO gaactcacggtcttcagccttcctgc
    1221 2792848 — NO tggccatggtgaaacagtgcctcta
    1222 3168127 — NO ttccaatcagcagtatcatggattaaat
    1223 3227785 — NO gggcagtttgactatgtcgcatccagcttcccatgccgtccatccctaggagtctgtctcaccatacaagggcgcagacaggccagcttgagggtgttcatc
    aacgcagcattgtttgaagagcagaagttagaatctattcattcgggggcctgactgcataaatacactgtggttgccgtccagca
    1224 3367153 — NO cttgtatgaccctttgtctcggttgactagttgtttgctctaagaatatttcatgttttgctgtttctttcagtttgtaggtgctaagctattgaaaggtttagagactaat
    ctaggtctttctaaattatggctgcttgcagttttattcctggagaaatggtttaacagcacttctttgagttggcactcttctgcctgtctcagctctaactttcccgc
    ctccttttcagtagtccctctttcaccctccactccccaagcctgaaatggaaagaacttgctttgttactgatgataatatttaagctctaaaattttaacagtgttt
    cagttgcaaataaatggaaattgtgtattctgtttaatgtgtttcagaaaatccctgctattttttttttctttaaatacaagaaaacaggcgtgtaatgcctcattgaa
    aa
    1225 3483227 — NO tttagtcaagtaggttgagagcaccagggatcattttttcttcacaaccttttagctcagtgatacccagagcaatgtgcctactcagtggagaagatagtatttgtgt
    gaataaatttactgttctgtgtgttacatgtctagttaggagtggtcctctaattctgta
    1226 3766878 POLG2 YES aaaatgtggttccttgtgttctctctgtaaatggggacctagaccgaggcatgctggcctacctctatgattctaccagctg
    1227 2555150 — NO tgggcgtgaataaggaagcaaaactcaattataataacattactattgttcaaacttcacatggcacttgcaaccggaggctactttgtctgcctgtctccatact
    catgctgtcttatgctcatgttcttca
    1228 2601747 DOCK10 YES gataccacttcccactcgtcttccaaggggggtggaggagcgggaggaactggtgttttcaagtccggctggctctacaaggggaattttaacagcaccgt
    gaaca
    1229 2664745 — NO ttatccaccgcacatgaaagagagctcagcgccaactgccagtccactgaagggtgtcgcagtgatatttgtttga
    1230 2698409 — NO atgtgctactaacaggtcaggagcccagatcaaagagctggtttgggaggtggataatgaaggttgtgaagtctgtgctccctctgagaagcctgaggaaa
    atgcaggtggctccctcaatcaacagacatccaaaatgg
    1231 2704917 PHC3 YES atcagcagattcctcttcattcaccaccttccaaagtttcccatcatcagctgatattacaacag
    1232 2823922 CAMK4 YES aaatgggattgtccatcgtgatctcaaaccagagaatc
    1233 3717013 — NO ggtctatatgtctgtacttatgctggtaccac
    1234 3498270 — NO atgtccagcgcaaggacactgtccagccttctcttcctgcacatcagctgcctcccgtcagtcctgctgaacggggatccttcccagatttc
    1235 3737381 — NO cttcaaagggtgtccagatgctatgaagcattgggttcgacttggggtccacgtggtttgtgcctcagggtccaaaaccacctgcattctaccggtggcgtct
    gcagaagacgaatggcttgaaggagctggcactccgccggctagatgatccaaaccatttcatttctttgtcgtgtggaaaaggccctctgtgatgcacttct
    gttctctgga
    1236 2512319 LOC643072 NO ctgtagctttgagtttgcaccgttccttgtcccaggaaaaagttaagaaacttaaaatgttttgttttgctttaaagaagacaggacagaaaacgggatttaaaa
    cttagtttttaaaaaaacaaaagctacagagtagggagcataggtcaaccatctccacctaaattttttttgttcctaaactcagaattctacaacccaactaaatt
    aatatgccaagattttgcggatgttaaaactcaaaaaaagcagtatgcaagacggtcccggggtaaaattctactgcctttccacggacaagtta
    1237 3596425 — NO agtcctcgctgtagcatggggtaaagccaggatatgacttcacatagtttaactccagaacttacactgtcatcttgttttgtttttctgttctcttgtgtgtcaaaa
    gaattcctccttagttgttctcatatggggcaaccattaaattaggcagtgtaaaaaacaagttatgcagaataaagtagcaagagcaatctactctgaaattag
    tgttttccctcactttagcacctttagctgacccagcttcctaccgcccagactttttacaaaatctctctctggagttgcctcctgatctggattaggagtcacata
    1238 3809494 — NO ctgtgtttaacacggctgtgctacttcaggctcccatctcgctgagggtgcccatgtcagccaatgacctt
    1239 2442446 — NO gtcttttgcagtaggtcagggctaagaggactaatccctcaagagtgaagaaaaaaactattgatggtggcttgaaagagtcaactgctgtagcttttcttgga
    gatgatcacaaaatggggagcagaaaacaggttgaaattacagaagattaattagtaagaaaagatgggttaaagatgtaaattagaggcaaagttaagaa
    gaatttggtttcttcattatactcagaaaggtaaggatggaaaagttgatggagcaagattgtgaagtatcttatatgcaagactaagaagtttggactagattct
    gaagacttaggagaaccagtgaagaaatcttaatagaggaatcggattagatcttagggtcagaacaattattagcaagcagggtaggtgaagttcctgttg
    acccactttg
    1240 3281111 — NO agcatctgtcgctggtgagaccctcaggaagcttcactcatgaggaaggcagtagggagctggcatggcttggcgagaggcaaggaaggagagggga
    aggctcttttccataagcagttctccctatggcaccaagccatttatgagggacccacccccatgacccagtcacctcccaccgagcaccacctccaacattg
    gggatcacattgcaacatgaggtttagaggggacaaatattcaaactgtatcactgggagatggggctaccggaagtcaagccattcc
    1241 3770080 — NO ctgtactaagtgctgatgtgccagcgctatg
    1242 3821078 — NO acagatgtgatcaaaaggcctaatatatgtgtaattggagtcccaggagtgaagagtgaaaatgaggcagaaaaaaattcaagtgagaatggctaagaattt
    ccccaaactgatgaaaggcatccacccacaaatcccaattttgtacttccaaccactgttataccacccccctcaacaatgcctataaatgtttgttgaaaatga
    gtgaatgaatgtactccaatcattttctcacttggatgttccctactttttgc
    1243 2531265 SP140 YES ataatagcaaagccgacggccaggtggtctccagtgaaaagaaggcgaacgtgaatctgaaagacctt
    1244 2719554 CC2D2A YES actggtggctcgatatgtgtccttgattcccttcttgcctgacactgtctcatttggtggtatctgt
    1245 3342924 — NO tgaggtccacaaatcagtcaagttgaataaagaggaaattctaaggaaaatattaaaaattacagaaagaggaagctggggacactgagcataaactttgat
    gacatcaattttaccgtgtgcctatccactattcctccacttagtttctcagatcttgccagcaaccttagggcttgcatcctccatttc
    1246 3811421 — NO gtacgtgtgagtgcgctgtataaagtctggaaccacaattag
    1247 2448106 — NO ttgtgtgattgcaatgctgaatttgtc
    1248 2661177 — NO ccttgttcccacatcggcacattatc
    1249 2748212 — NO aggcattttttgtccacacacttgctttggggatttttattaggtagacggtaattagaggtgtcagtcatatgaaagtaaatcactagtctttcgtattactgttttct
    cagtggtccttatcagttttttttgttgctctgtaatcattcatatggtaagacttaacttttagtcatgtaaatttgtttagggacaatttaaactattttgtcaaattagtc
    gttttattccaagttgtacgtcttatgcatttatttagtatagtgaaagccttatatacacatttaatataattagtctctggatatttggattattttttagtagtactttttta
    gagtgtgggttttttcttttcttttctgtttttgagacagtgtctggttctgtcacccaggctggagttcggtagcccagtctt
    1250 3081649 — NO cacctttgtgcatgtatatacttcaagttgtatgaatttctttatgcaaagagcctttaaaatataaactgtgatttttgtttctaattttttactttggattgacagggcct
    tttttcaagtgttggaatttccttttagatttcttatcagagtttatcttgattttactgaaattcatttagctatatgaaattcctttagccatagtcttgattcagatcccc
    ccacctgagtctttccaggaccttgtgccatctgttattgccattgttgtattcacttacagcctcttctccatgagtacaagcccaccatcatgctc
    1251 3415065 — NO gagccattcctttggcaactcttgctgtcagccatcttccaaagagctttg
    1252 3436225 — NO tgtctaccatgttgggcagcacagatctaaagcatttagaaccatggctagagctatgtgtttactatcattgcttcaatatggagagtcatccaaacaggtttca
    tttgctcccagataaactgtcatgggacctgccgtggccagtgctcaccttgtactgctggaataatttaacaatttttttcaactgccatcatcatcatgccatttt
    atgtcttcgtagcatttatcactatctaaaggtaggtcgctta
    1253 2546677 — NO ctcccaaactcttgaggacatgtggggaactacagctgg
    1254 2723423 — NO aaggtagtgtgcaaagcgaaaagagggcacagaccaaaatcatgcaaaa
    1255 3291647 — NO gtgggttacatgttcctgcctggca
    1256 3449366 IPO8 YES ggacctcaaccggatcatccaggcgctgaagggcaccatcgacccgaagttgcggattgcagccgagaacgagctcaaccag
    1257 2935290 — NO gttttacaacacccaaagcaacagaaa
    1258 3296065 KCNMA1 YES gttatggtgatctgttctgcaaagctctgaaaacatataatatgctttgttttggaatttaccggctgagagatgctcac
    1259 3414403 SMARCD1 YES tacggtgtactgtcctactgatgctggattacca
    1260 3611215 — NO ctagtctagggatagtggtagaagtacgtaatgtagatg
    1261 2997513 — NO cctttgctctctcatatgcatccggcacagcagc
    1262 3180413 — NO ttcaagggcataggcgtcggaattgtgatttcgtgcgtgttt
    1263 3732510 — NO gaaccactttgttgaccttctgctgcaa
    1264 2572597 CCDC93 NO ctggacggtgtctatcaaaagtgcaaatgcataagctctttgaactagcaatgctactcctaagaattgtacctgtgtacaaggtacttgtgtacaagagtttttgt
    tgaaacattgtaatagcaaaaagttggagagtgccaccaatacaggggaatggttaaatacattatggccagcttaaacaatggaatagtttgtagaaatttaa
    aacaatggatcctgtgtgtgtgtactaccatagaatgggccccaagatgcatgattaagtgaggaaaaaagcccatggtatcctaatgtttggaatggagaaa
    gtgtgtagatgtatgtgtgtgcatatgttttcacacagacgtatacacgtgtatatcatatgtccacctgcatatgcctaggatgtctctgggaggatatctagca
    gcccggcagcctgaattgcctctgggaa
    1265 3216409 — NO aggttctgaagtcccaggcaaatgtaatagggggtaggcagaggacttacttagagagatggtggtgaaagtctcaaactgcagatttctagaacaaacag
    gttacttgtaagaagcagacagagatacttagatcagtaaaatacttctgtaacactagaagtgagaagacatgagaacgttatctagaaactatcaagagga
    aatgactgcagaccaaaaatcctacgc
    1266 3294290 — NO tccacagctcgatttggccaatttcgagttgaaaggatggtactggacccaggcctcataagtagcttgtcatcaagatctctagtagccaaatcagaaaccc
    acaatgaagtaaagatcagtatgtcaaggaagacaagactaacggggtaaaaagccttagactagaaactacatttagggggaaataaagcaaaaataaa
    aacctttcaataagtaacactagtttccagatggtactctagctcaggcatgagaatctgttcttaaaagtgggacattatttcaatcataaacataatttactaga
    atggacatttggcaaagcaagtccattatccacctgccatcacagtcacttttttagtcaccagtgaaggcaagcctgaaggacacctactccaaagtgcttcc
    caaaaatttgccacaggggctgattcctactctgtttgaggcattcttttgtgctgaaagattgtcaccagaaagacaactgaaagacaaatattgctgcttggg
    agcagttgtggcaccagtgtggctcccactgtagcaattaaag
    1267 3446505 — NO gtcttgtagcactcaaacctttgtctttcccacaagactgaaaactccatgacacaggaatatttcttatcctgtgaacctttgtgtcataccacctatagtagtgttt
    agtataaaataaattaattgtttggaaatctatcctaaaaaaaaaaacctagattcagtaaaagctctgtggccaaggatgtttgtgttacagtgaacaccttcga
    gcacttcagg
    1268 3616936 — NO ctcatagcatggtggtctcgcagtagttagccttcttacatagttactggcttt
    1269 3628351 MGC15885 NO cctccgttacccgtcagcccagcatccggctttgcttccataa
    1270 2745112 — NO gcaaaattggtctggtatctgtctaaattggtcaatacaagtgttattctggaatcatgtaaaaatcacttactttcataactgtttagaaccccaaatgttttcccttt
    gaaggggaacatctgtggaatatgattttgaatagaggacttctatgaaatatatttcaaatcttaaaaatatttttaatacttcctaaagtggtataggatttaccct
    cgctgactatgccttccatttaagaacagtcttgcatttgtggcttttca
    1271 2824232 APC YES tgtccctccgttcttatggaagccgggaaggatctgtatcaagccgttctggagagtgcagtcctgttcctatgggttc
    1272 3101817 SGK3 YES agttctggtttcagtgggaagaagtg
    1273 3129414 — NO cctagctgtctgtcaggtagaatgagggtgaaggagatctaggatgcttcaggcattgcgcttgaacttaaaaaacaggatcagcaggccctgacttcataa
    ggcccataaatacaaatgactagctccctttctcaaggtcattgaaaatatacagtagtttcagacatcacatgggtttgggcaaagggggcagatttccaagc
    taggtcacttaatggtatc
    1274 3576514 — YES gtggccgggaggcaaaacttctctatgagtggaaacgtttgaagaatacatcacccattacgattttgctaatcttaggtttcagacaccacagacacattgatt
    ctatttggaaagatagccatcaatcagccagc
    1275 3650814 COQ7 YES ataaagaaatttcgggatgaagagcttgagcaccatgacataggcctcgaccatgatgcagaattg
    1276 3723777 — NO gccaaagagcatgtagagcaaactaggctctattcagcatttccatttcttaatgtatctatttgatttcaataaaatttcatcattttgaagatctctcccattagctt
    gggaaactacagaaacatgcacataactactgagaaggtatcaagtgttcctacactagtttaaaaaaatcattcaacacccacataaattctgatatgcacta
    ggctgaacagctgttaaccactgagaagctgggcactgcatcctctccctgggtcaaaactctatatgct
    1277 2550931 — NO atgcacatgggacagtctaagatggtagtggtgg
    1278 2681842 — NO accaagtgacattttgcattcagcctt
    1279 2868846 — NO gctctagtgccacaggaagctgcct
    1280 2880139 PPP2R2B NO agccaagggagaacccaagacagagaa
    1281 3309073 — NO attgaatgattgtttagaggcagtgtga
    1282 3636536 HDGFRP3 YES gcaattcagcaacagagctcttcagaa
    1283 2347802 RWDD3 NO gggatacattcaggtctcagttgttgaggctgttgagcagcaatccaggtatgaaaatgggaaagatttgactgcttctctcatgcaggggaataaagcaaag
    gc
    1284 3202177 PLAA YES tcctgcacttgacattcttcggttgtcaattaaacaccccagtgtgaatgagaacttctgcaatgaaaaggaaggggctcagttcagcagtcatcttatcaatctt
    ctgaaccctaaaggaaagccagcaaaccagctgcttgctctcaggactttttgcaattgttttgttggccaggcaggacaaaaactcatgatgtcccagaggg
    aatcactgatgtcccatgcaatagaactga
    1285 3945822 — NO aaggaagcgagagacttggcagtcctgtaggctttaatggaatcagcaatggacgctcg
    1286 2682207 — NO ggggctttaattcttaatcgctgtgaggattgttatccgtgggatgtgagctgtcttagtggtattcaatcaagtgtccacttagccatgactggaagtaattgctc
    ccaagtgggcc
    1287 3263773 DUSP5 NO agccattacgggagcacagcatgtgctgactactgtacttccagacccctgccctcttgggactgcccagtccttgcacctcagagttcgccttttcatttcaa
    gcataaggcaataaatacctgcagcaacgtgggagaaagaagttgctggaccaggagaaaaggcagttatgaagccaattcattttgaaggaagcacaat
    ttccaccttattttttgaactttggcagtttcaatgtctgtctctgttgcttcggggcataagctgatcaccgtctagttgggaaagtaaccctacagggtttgtagg
    gacatgatcagcatcctgatttgaaccctgaaatgttgtgtagacaccctcttgggtccaatgaggtagttggttgaagtagcaagatgttggcttttctggatttt
    ttttgccatgggttcttcactgaccttggactttggcatgattcttagtcatacttgaacttgtctcattccacctcttctcagagcaactcttcctttgggaaaagagt
    tcttcagatcatagaccaaaaaagtcataccttcgaggtggtagcagtagattccaggaggagaagggtacttgctaggtatcctgggtcagtggcggtgca
    aactggtttcctcagctgcctgtccttctgtgtgcttatgtctcttgtgacaattgttttcctccctgcccctggaggttgtcttcaagctgtggacttctgggatttgc
    agattttgcaacgtggtactact
    1288 3497166 — NO cgccagcataccagctcatgtttcagaatttctgtcacaaaaaggaacacaatattttaagttgactactgtgggaaagctatgatcattcaataacctacctttct
    gatagctctttctcagataatataagctataaaccaaaatagtcagccttcacctgatttacagtgccctttgaaacttcctaagttttctagcccagtaaatgctga
    gctaccagttctacttccaagctagagaacctgtttactaaagttagaagtctagtgacttcctctgtcagactgtcccagaatgctctccctacccccaacaact
    gtgtaagaaccgtcattagccatctccaaattgccaaagtgctcagtcccttcg
    1289 3618874 — NO gtaacatgcatctgtgtgggaacct
    1290 3202840 — NO tttcactgctactgcgaactggtcctgaaggtgcagatctcttagaaggaggactcccacttcttggtggtggtcctctttttactggatgtggtcccctggaag
    aactcatgttaaaattcatggaatatccaccgtcatccatgtgtcctccccgtgagggaggtccccttgttcctccacttcctcctcttccacctctaagacctctt
    ggagggcctctacttcttggaggtggaggcggtccacgtctaccactttcaaatgatggtttgttggcttgttccacctcgatggcttttccatctaatgactttcc
    attcatgtctctggctgcatccttagcatctgctgggctttcaaaggtgacaaaagcaaatcctcctgatttgttggtttcatggtctttcaccaagagtacttccac
    tattcgtccatatttgccaaatactgcttcaagagctttctcatttgtttccgtgttaagcccaccagtgaacggctttcctgggcaatctgc
    1291 3755656 — NO cattaggggaccctgcctgaatctttgccaacctgcaaggaaactc
    1292 2469949 — NO tgccagtgacatccagggttattcgtatacctcatgctttagattcgcttctggttcatggtgccagcccttagaaactctgggttcctacctgaagccggtcttat
    caaaacgccacccctggttccagtttgatcagggtaaccttgtgaattagcaagcagcagtccccagtgtgtgctgacatggaggttggagagaaaatagat
    atgtcccatgcctggtttccagccaatactgatgtcgcgggttagtccagcaggctgaggctgaggcctgtgacaaagtccctgcatggaggtcttcctgcgt
    cagagcctagccctgttcaata
    1293 2830605 — NO gagctttctaatgggggtgggaaga
    1294 3235906 — NO ttggggttgatacccatcatcgctcttagactcggggttgatactcgtcatcgctgttacactcagggccgatacctgtcatca
    1295 3616555 — NO aggcagacatcaaccctctaagacatttttttcctatcctctgggaatattactttttggacaatcttggtccattggtaagctcatgggaatttgtcagagtttttttg
    tttcttttggctcatgtttagcatcgattggcagagtgtttggagtcatcc
    1296 3369121 ELF5 YES caggaattttggagcgggttgaccg
    1297 3908978 — NO tcccatcagcaacatccgtcataccctgacgccc
    1298 2338495 — NO aagagcaggggacctatgatgcagaaagtcctttgctggagctcacaggtcgaatttcagggaagctgcccaagggcttgaacatccctgctttcaggttcc
    ag
    1299 2452931 — NO ccacatagtacggtgtataacaaggagtggtcaaagagttgtggctggtggtttccttggcaaagccaaagtcagtgagtttcaggatggcgttgggcctttt
    ggaggtgtataagagattctc
    1300 3448040 — NO tgttaagccttcctgagatcacaccaaatgtccttgatgggaattgtaaacaacccttacttctggtttctaatgatattccaggaaaggagcctaactagagtca
    1301 2823916 CAMK4 YES gattgtggaaaagggatattacagtgagcgaga
    1302 3799998 — NO gggcatcaagaatttggacatactggtgtctggtatcgaggttcttcagctactcaatgcacgtgatgatggtgatgatcatgatggtaacaacagac
    1303 2978095 SHPRH YES tcatgaatattggatggctctgaggaatcgtgtgtctgctgttgatgaacttgcaatggctacagaacgactaagagtgcgtgatcctagggagccaaagcct
    aatccgcctgttcttcatatc
    1304 3475634 — NO gacacctcaggtgacatgctttatagttggcctgagccttgacccagtggttcaacctgagtttggtcttggtaccattcaggtgtttgtgagctgagactgatg
    agtaggaacaggtgttttatatctcgtcttttgtcaaaagtaaagactcattcctttggtaacccaaccaaatcaggatcag
    1305 3683092 SMG1 YES gtattctgagcacacccaactacag
    1306 4022048 RAP2C NO cgccaagtctctgggctattttttatttttgcaaatgtgctttctaatagccattgccaccatgttgtttacctaatcagcatatttttgtctgaatacttgaacattttaa
    cagtaacgcaggtgtagaatcagaaaggaaacttatgcagagtaatattttggttcagttttaacatcgtgacaatgagggctttttctagcaatgatttttaaatt
    gtgtaagtttgacagtattttattgttgggtttttatttgattttagttgtgtgcttttcatttgcagaagttagtaactgcagctcacctactgcaccaaagttctcgattt
    taggagcccagctttagtcatttgaacatgcttctaaataaaataaaacaaaaccaaaactatacttttgatctataataagagctcaataactttgtcaaggaaa
    gctctaatatatgcagtgatggtttatgaaagggtgtggcaattttaaatttatattgtgtgtgatgttcaaataaagtggtatctacattcatgtgatttatgggtca
    gcatgaccattaattactgagtagaaattgactaaactttgatttcctttttttaaatcgtgttgcatttgattcctgagcaaattccctcaaagtgaactcttgttctta
    aattttgaattttatggtgagattgtaaagatagaggcaattgaaacattgttccttatttatgaactgcttgaagtgaatacttaatttaagtttgcactttaatacca
    aacttaaaaccaaacactcatttaaaagtaggttaagtgatcatggatcattgttattagctttgtggctttgtgaaattctaaaggaatcaaataattcatcatgatt
    taaattttctagagattttgatttttttataatgtttctttcctgtagattgtgttcttgtttctctctctctctctctctctctctctct
    ctctctctctctctctctctctctctcaaaattacagtgttcattgtcattgacc
    1307 3153356 — NO ttttctgaggaatagggctcaatggtgggcttagaatattgagtacaccatgctgtaaacagatatgctgtcatctaggctttgttgtaccatttagagagcacag
    gca
    1308 3529618 PSME1 YES gtggatgtgtttcgtgaagacctctgt
    1309 3830025 — NO aattcattcgcctccggtacttgcaagcctcgctcagtcttaagcaagaggggatggattcgcccgcagcactgagaatccaggggcaggcgggatggcg
    ttcaggcgctgttgctagaaatctctgtctttactctgttttgaaggcagcatggcagggtgaacacaagcacagactgaaggcagcttgccgcggttcacat
    cctggtcacaccacttcctgaccatgtcacgtgggcaaatta
    1310 3866580 KPTN NO agggatgatcccattccaccctgtccactctggatgagaattggccacctgatggttatttatacgtccagaagaac
    1311 2620390 TGM4 NO gccacctgctgacgacccttgagaagctgccatatcttcaggccatgggttcaccagccctgaaggcacctgtcaactggagtgctctctcagcactgggat
    gggcctgatagaagtgcattctcctcctattgcctccattctcctctctctatccctgaaatccaggaagtccctctcctggtgctccaagcagtttgaagcccaa
    tctgcaaggacatttctcaagggcca
    1312 2693884 — NO cagtctgagttcctgcacccttcag
    1313 2724817 — NO gatgatgctggacaaactgcaaatcctgaacttagagactgttgcagcaataaccattttgactgtgataatatcattctgctcaagttg
    1314 3718581 SLFN5 YES ccagtgacccggaaaaccttcatgaaaaacaactttgaacacatccagcacattatcattgatgacgctcagaatttc
    1315 2645299 — NO ctggcagcctgctcaacactttaaattttatcagtttagtacctgctgatgcgtctaaaactgttggtcccattctagttttatacttacatatgtagtattaaaagcac
    ttaagagaaatgtagaatatataatctttataaaagtattaaaggaattatttaaattgaatttgtatcccatttatcttgcttgctaaatagatttaattggagcatcca
    tttgtataacgtctggctatttctacaatgttaaaacagtgggttgaggaagtaaaatttgagttactcagttactgacatagaaaagaaccctgtgagaccaaat
    tcagctttggaaacaatttagtgtaattattttgcatatgtagatacacctttgaaagccaagaaaggtttatgattggatctgtactatattaatttaaaaacaaatta
    ttcttaagtatattgtagcatttctgttcctgtaagtactttactcatcttaaatgtactgatcattagccacctttataaaaagaatgtgcctgacccactagtatttga
    tagaaatattaaaacagttaagatccttaaacatttctgcatataattttttattgagtaaatgtaacttaacgtaagtagttctatgaagtctgtgtaaattaaaaccc
    tgttttgtgtagatgaagcaatctttataagtttctgtcatcaagactgtattttgtgtgctatttttccatagctaggaaggtggcaagtaaaacatatgcactatcct
    agaaacatactgttccaggtagatcttaatttactacctggaatgagccatcttaggtgaccacca
    1316 2927067 — NO aatctgtagttgtaatgtagccttctacctaaataaaagagatcctaacataatggttctcattacttaagcctcattatgatcaagctcttcccaaataatctgacc
    aa
    1317 2434911 — NO ctgagacgatgattagtagaactgagaagtgcccattggttttggtgagatagaggtcagacattaccttagcactttttggg
    1318 2916250 C6orf162 YES ggctcagaggggtgcgcacaacaaccttat
    1319 3152957 — NO tctggcaaaacccaggtgcggtaaccctgcagcagcttccactcactcctgcaatgcctgaca
    1320 3190622 SPTAN1 YES gaagcttttgagacagacttcaccgtccacaaggatcgcgtgaatgatgtctgcaccaatggacaagacctca
    1321 3508990 — NO ggatttctatgccacactacccgtaactttgaaaaataactttaggctgcagttttcagcaaacaggacagtccttagctgccacatagctcaacataaagtgca
    caaaaaacttcacggtgggacagtgaatcataaattcccaaactgacgtgtgtctacagaacagatg
    1322 3567717 — NO ttttccatagcttggttctcaggggttatagatgcaagaagttcctggaaagagctctaaaccagaaaataacagtctgctggtcaaactcaaaactgtcttggt
    tgatatatgagctggctgtctttactgttacctcctgtcatgatcattttgctaattttctgctataactagaggggaatgtc
    1323 3780094 — NO tgcgttagaagacctgccgacaggccggataaggccaatgagagagggaacggagaagaggggcacctgggttcacaggccttaagaaagaatttagt
    tacttatttaacaaattaaacaatgtgtgtcacgcatgtaggtctgggaaatgcattattaaaaacacacagtgcagaggtgcagcaccagcatacgggtgga
    tt
    1324 3799938 — NO ggacaccctcaaccagtaacacacactctccttcttcaatgacgtttgtgttcctagaatccattttcctcagtcag
    1325 3932154 — NO tcttgccatacccaagtagggaatcacttccaggaaaacaagtcctcaagcactcaatgactttgtaaacccatgactgaaacaagactcatctgaggcagta
    ggactggtgggattctactgacttcttagtatcacatggcaccatcacaaatgcattgttagagcagcaacatccagagttcttaagcttgtaccctaaca
    1326 2534308 — NO cctcacagtgacacgcgatgttttcaaaagtccatctttccacaggatgtttacagcacccagcgggtaggcagtgctatttattaaccctgttgtactgatgaa
    caaaccagccggctcagggcagggggtgagcttgatcaagatcacagacaggaagtgacagcggggtctcagcccaggccatgcctgacacccacac
    tcttctctggtgggggcgcttccacctttgtccctggaagcccagcctgacagcttctgcagtgcctctggcagccgcccacaaacccagccaggcaaaat
    cccagggtgccagacaccaggagaaatttccaggggaatttggccatttggctgtctcttcacttccctgaaaagccaaacagagaatggatttcttatcaca
    ctgtagcaaggcaatcaactggaaaagagacaggaggagaagtgtgaggaccaacagtcacagggacccaggaatcgtgttagccaca
    1327 3696944 — NO gctcccaaggcccaatcagatacagctctccaaacctgccagtgctggtgaacgcgctgctgggagcact
    1328 3712853 — NO ggccgtgaaggaagaatgcggtgtt
    1329 3916807 — NO ttcaccaggatacgactgttggaccagctgctggagatggacctgctacccctcagcagcctccccaccacaagacaagtgatctcaatgtccccaaacct
    gtgggaccctgttctacacacctcatttttgttccggcgtttcatcctccttgtgtgattgtactgattttcatgagacacaagttacttctttacatccatattcccaa
    agcagggttacatggtaggaaagaaaggaagttggaggtactaagctcattgtgtctcctc
    1330 2381295 — NO aggaagtaactagagccggcatttgggggtgttgcggacgattcttacgaatccagacaatttgctcttttaaacgcggccttgcggttgtctaacagtgaga
    atagatgactaactgaatttgtcagactccctgccttctgtcataataacgacgcagaattgccaccgttatgtgtc
    1331 2608169 — NO gtatggggagaacgaggatgtgata
    1332 2363544 — NO ccacaagaagggctagagaaatacagagatatttgaagagtgtgaggaagagtattaacacaccagttttcttgatcaatag
    1333 2407863 — NO acatccttcttttcggccttgaatcctttcttgctttgcaaggaacaattttcttcctactataaactacagcactaaggtatggaccttagaaattatatagtctaatt
    ctctgctgacacacaaatcccttcaacaacaaagaatcataagttcacattgaaaggtctctccaaatctcccataaatctacaatattcttgatgtttaaaattta
    ggataatagagaattcactaattcataagacaaagtaccaatgtaataattctataaaatgtcataatctgctttccttgtaacttctgcctattgactc
    1334 2920969 FIG4 YES aggatcctcgggcttatttcgagcggtttcagcttttggtg
    1335 2949119 LTB YES tgcgtggtgcgagtgcgtgaatattgggggcccggacgccca
    1336 3241194 — NO cattgggccttccatcatcagaaagctcctcatgccacatcttgacacattattcccgtcctcctg
    1337 3447084 — NO aggatgtgagactgccgtggatatcagggaagggagacttataagaaggagaaatttggtcaactgtgtcaaatgcttcagcgatcaggatgagtaatgag
    gaacggccatttgatttgatttgatcattcagatatctttaaagacctttaagagggcagtttcagt
    1338 3626136 — NO acgaccatgcgcactgagaaacaggcaccaggatgtcgagaacggcaatgtatttgctcacaaaaagctctacttcacacaccacctgtgcatgagcgtgc
    cacatcaaaatga
    1339 3800039 — NO cataatcaggtcctctgcaagtgggagtccaactgtgacgcagcccccccacgttcaaagcatcccttcagcttccggcaatctcctctccagg
    1340 3887175 — NO gccctggttgcaactctgctggtct
    1341 4011861 — NO atgaggggaacggtagctgacaatagcagaggagggttttgcagggtctttaggagtaaaggatgagacagtaagtaatgagagattacccaagagggtt
    tggtgatggaaggaagccacaggcacagagaacacagaatcactttatttcatatgggacaactgggaga
    1342 2320367 FBXO44 NO ggtacaatggcatggcttctgtctaaggtacagaggggttggcatttcaggaaccaggccatcacagaaacaggttcatgggcagacccctcagtgagctg
    caggtatctcacctggcagccgtccagtactgctggcttcctctggaggcccagccacaggctggggttggggtgtgtggacatctctgggcagctcttga
    gtccaccttgtgccagatcagcagtgccaccc
    1343 2680360 — NO gagctgggtcagttgctccattatgtactttggtttgcag
    1344 2866718 ARRDC3 YES actcgctacctcattcgaaggccgacatggcagtgtgcgctattgggtgaaagccgaattgcacaggccttg
    1345 3251759 — NO gacaaccttcaatgcactggtactttgtaccctgacctctactgtgatgaacactcaacttgggcaagga
    1346 3742688 NUP88 YES tgtgttgagttggagcttgctttgaa
    1347 3772092 LOC100131096 NO tggctgtgcctctcgatgatgattaagatttcaatatttacagcaaaaccacaaagcaaatgatagaataaagcaaaacaatggaaaatctgagttcactcgtg
    agagaggtacgtatgtgagctctgaggaaattacagagggaacgcatgcagcgggacagctctcccaatcgcagcgtgcaaagtagacatcca
    1348 2596545 — NO gacagcagagctatctatcagttcctctgaacttgttctgaatgagcttttcttactgttcagtattcactctcctattactgttttgcttcctcatagaattccagatta
    gtgggcccctggaagttcagctggtagatgagaaaactgagcccattgaagttaaagtcacccagctagtcagggttgatcttcccaactcagagtcccctg
    cttacttaaacttttatatccaacaggtttacttcccctggaaacttatttggtattttttattttccatctccatgccctcgataggtttc
    1349 2928626 — NO cagccgccaaagacgcctgagagcggcaggggagtgtgttgccttaggacaatagcaaactgggacgtggtagagtctgtaaattccaagcactggg
    1350 4035053 — NO catggtatcatgtgcctgtaatgtc
    1351 2487210 ANTXR1 YES cagggtcaagaacaaccagccagcc
    1352 2891955 — NO ggcccttgacaaatgcctgaaatct
    1353 3061185 ERVWE1 NO ctcttcaaacaacaaccaggaggaa
    1354 3104349 — NO atggacaagttaggccctccacttcgaacgggaagacttgtgcaaaggttgtatgacagtgatacaaaatcagacagtgcc
    1355 3915245 — NO aattgggttcttgaggtggattggaggagaacagcctctggatgtctgctgggcagtgacgatgtgtctggaggctttgacattggattcattaggcattgcta
    atgtacacaaaaaatgtagcaaaaatgatgcctgtttctgggtgagaacatctg
    1356 3961553 — NO ctcccaggtttacaggtcttgactcagtacttcatcagcaataggttgtggtcacaggaaatggaagctgcctcaggacctgtagcaacttgcctgcatgctg
    ggttatgttatcttttgagtggtgcccaatacgaggtgtctaggggaaagtcttaagtggttggagcccatgaca
    1357 2523501 NBEAL1 YES tctcacagtggaattcgtccctttctt
    1358 3601127 — NO gtgtgtttgtgcaagcatgttaagcatttctctgtcttgtgttcatt
    1359 3892321 — NO tgcaggggtgtccagacggcctggtgcaggatccctttgatgtggagga
    1360 3087823 — YES ggaggatgttcggactatagattcagctgtgggatctggttctgtagctgagagcacatcgctaaacatagatgtgcagtctgaggcttca
    1361 3337295 — NO aaggctacaactgtgctcttagaggcaaaagaagaaaatgagactgccaggcatgaataatgagaaatctttgatggaattagccatgcagaacagata
    1362 3528558 TRA @ NO tctttggtcccggaaccagattgtccgtgctgccct
    1363 3536444 — NO cttttctctgtagttggcggaatcagctcagttacattttttactaagttacccacattctgacactccttgacagttttaagatcttcttctaacacacttgaatagaat
    ggatactggaatctattttgacagctgttgaaaatctattctgttgttacaggaggttaaggaggttatttgtaacactgggattatttaatgaaccttttgaaaagg
    tgtgcagactgttcaggcaaatagtattttttagaatttaaatgattttggttttcacagttaaattatcaaatgtaatgcttttaagaattatacacctagtaatatttttc
    attaattttctccaccagtgtagtaatagtacattacaatgttctcaattaccggtgccttctaaaatgcaggtgtagagtctttaaatacagctagtctattgccag
    ctgtcccatagataaccttctttaaaagtgacctttgagcaatttcataaagaataaatatttctagttttttgttgctgaactgctaaaagatggttctatacatgt
    aacaggtggctttagttgggttgctt
    1364 3823557 RAB8A YES atggcgaagacctacgattacctgttcaagctgctg
    1365 2707806 — NO cagacccttgtggtcgagttgtttactttggtaattaagtacctgactctgctggacgctcttcgcgtttcagaagcgctgtttggcattgtacagtctgagcgtga
    gttgaattcc
    1366 2849541 — NO gttcttcataaatcctccactcacaagcttgcagcctttcctatcacagtcatatccaatctcaattcccctgcccagtataatgggactcga
    1367 3795889 — NO acgctgaccagtgaccgaggacacagttgtgtgttaggctccatcacctgctgtactttgagttgggaaattttcatcatcttagaaactgggtcattttatcaga
    gtctagagtcagatatagaaaaagtttgtggctatttctccaatttatatgactaaggtcgggtatctttttcaaagtgtctaattgaaattgaaaaggcagcaattt
    aaagttgctattgcaagggcagaaaatggtcttaagaaagccagctttcaaattgaataaacatgactgcgttcactttttgagc
    1368 3895772 — NO gaaacaaactgacaatactcgtgaaatcaacacccagatgaggtagaccagcactcca
    1369 2920915 — NO ccaactcacaccatagcagcgctcatt
    1370 2971825 MAN1A1 YES ctggaggcagcagtattctggcagaatttggaaccctgcatttggagtttatgcacttgagccacttatcaggaaaccc
    1371 2990655 — NO ggtttcttgataactgctccacttagagaaatgagctgtgatctgtgtagattttggaaaatgggtagctggggggatcatctttaaacaatctttttcatgctcatca
    cgaaatgcttttacaataggtttattttgactttgtgtttagaatttttttttttttttgctttttgctatagactctttaaaaaagttgttgttctggatattattgatagatgga
    acaaaattcatgtccttgcttgaatcttttagcgagctattcagagattctatatccccatttactcatggttttttcaaggtgaatgaaacaacataccctgct
    1372 3198975 MPDZ NO tgcactggtcctgacaatttttatgctgtgttcagccgggtcttcaaaactgtaggggggaaataacacttaagtttctttttctcatctagaaatgctttccttactg
    acaacctaacatcatttttcttttcttcttgcattttgtgaacttaaagagaaggaatatttgtgtaggtgaatctcgatttttatttgtggagatatctaatgttttgtagtc
    acatgggcaagaattattacatgctaagctggttagtataaagaaagataattctaaagctaaccaaagaaaatggcttcagtaaattaggatgaaaaatgaaa
    atataaaataaagaagaaaatctcggggagtttaaaaaaaatgcctcaatttggcaatctacctcctctccccaccccaaactaaaaaaagaaaaaaaggtttt
    ctaatgaaaatctttaaaaaatactgtcagtattttaaaattttcaacagtattataaaaacattgcatctccccacctctaatatgcatatatatttttcctgctaaaatt
    ggtttctacaattgagtaaatggcaaatacatgaagcaatgtccctaaattttataaagaaattatatttaatgcacatttcaattttcattcttattttgaccttttgta
    aaatattttcatgttgctataagtaaatgatgatgccaccccatgttgactatggtttttctagaaagcaactatgctgctaaccatagaggaacatagaagggtt
    ccagaatctttagtgctggttttaacaaccgatgcaacattaaaaatgtgttagtgtgctgtgcaattggttttcaattcatattaatcttaatgacagagaacaatg
    tgttactaattattttggttgtatgccattagtaaattgatagaaaaattaaggggattaacataacttcatttcattgacttatattaacatcttataatacaatagttta
    agactaagggaaacagatggagctgtttattgagacaactggtga
    1373 3652974 — NO ctgacatggtgtgtcacaaagagctcc
    1374 3680296 LOC388210 NO gtagaccctacaccattcctcagcc
    1375 2530462 COL4A3 YES ttccctgggttaatgggtgaagatggc
    1376 2550272 — NO caggggcaagagctagttagaaaactgagctcgccctgtctctaatgtctggtgagctgctctcctctctctacaatatatcacgggtagtttcatgtcaacaaac
    1377 3118585 — NO gaatatgttgttaagtgggcagcat
    1378 3403090 C12orf57 YES taagtttgctcgcttggtcaagtcctacgaagcccaggatcctgagatcgccagcctgtcaggcaagctgaaggcgctgtttc
    1379 2524930 — NO tgtgaacttgggttgtgtcgtagaaaatgtgagtgtcagagag
    1380 3125787 CNOT7 YES ggttacgactttggctacttaatcaaaatcctaaccaactct
    1381 3171102 — NO ccaaggactggcaggacgtcagtgatgctggg
    1382 3250113 KIAA1279 YES cctgagcatataggggaagatgttcttcgccctgccatgttagctaagtttcgagttgcccgtctctatggcaaaatcattactgcagatcccaagaaagagct
    ggaaaatttggcaacatcattggaacattacaaatttattgttgattactgtgaaaagcatcctgaggccg
    1383 3747008 — NO ggtgactggaccacgcaggtagtttctcatgaatgatttagcactgtccccctactgctgtctcgtgatagagttctcatgagatttggttgcataaaaagtgtgt
    agcacctcccctctcttttcctcttgctctagccctgtgaagatacctgctctggctttgccttttgccatgagtaaaagctccctgagacctccccagtcatac
    ttcctgtacagcccatggaaccatgagccaattaaaccttttttctttataagttacccagtctcaggcatttctttatagcagtgtgagattgaaccgatacagac
    aacaataacaaaaagtagataaatatgaaggccagagaaatggcaacttcttcacgaagggaagctgcttatcctcaagcaagtcagttgaggactatcctg
    tgagctattttccgtgccttgttttccactcatacagggaagtatgccctggtgtctcacagttgcttcagttcttctttactgggaccctaaatataataacacact
    gaaccactcaacttctcagaccttcaatatccctggggctttttctcaaatggacacagcatagctttcagaaagctgaataatgtagacaaaagaagtctccct
    caccctttgattatggaaaaccaaagatttattcagtgccaaggataagaaaggaaggacttgatcaacaaccactgttaagattttgacccattcactacttca
    cgtgaactcccagggaaatggaaaatgaaagaaggtctccgcggtagagggataacaatg
    1384 2406715 — NO acagagccctgattccacatacatgagctcccatgtgtggctggggctctgctgggtcctgggggcaggaggaggatggagaggcaggccctaccatgg
    aggaggttgtgatctaggggcaggctcctaaccagttaacatgtgcacagtttggcaagtctctcacagaagtctatagcatgtgggggaacccagtggaa
    gaagtgatcgagctctaggatgaggaggagactggggagaacttcagagagcccttagaacttgaactgggactgggcac
    1385 2808962 ISL1 NO cctccttggctgaaagagtcctttcaggaaggtggagctgcattggtttgatatgtttaaagttgactttaacaaggggttaattgaaatcctgggtctcttggcct
    gtcctgtagctggtttattttttactttgccccctccccactttttttgagatccatcctttatcaagaagtctgaagcgactataaaggttttgaattcagatttaaaa
    accaacttataaagcattgcaacaaggttacctctattttgccacaagcgtctcgggattgtgtttgacttgtgtctgtccaagaacttttccc
    1386 2849483 — NO cctgttggtgtgtcgataatggcaaggtctgcagtgacccagcagtggctgaggtggggctggggctgagaacctgatccctgagaggccatttattgtaa
    gaacaggcaacatggcagggaagtgaccaggaactaggacaggcagtaagtgggagagaatgacggcaagcctggagctgtcccagaggtgactga
    cggatgctgtacaaggtggaa
    1387 2868168 ERAP1 YES atttgccctacagatggtgtaaaagggatggatggctttgctctagaagtcaacattcatcttcatcct
    1388 3082899 ARHGEF10 YES atggagttcgagtgaatttgaaagttacgaagagcagagtgactcggagtgcaagaatgggattcccaggtccttcctgcgcagcaaccacaaaa
    1389 3505964 CENPJ YES gctgagaacgcatctttagctaaacttcgcattgaacgag
    1390 3522535 DOCK9 YES caaagctaattgagccactcgactatgaaaatgtcatcgtccagaagaagactcagatcctgaacgactgtttacgggagatgctgctcttcccttacgatga
    cttt
    1391 3404455 — NO cactagacagcaattcagagcctccaaaataaagaatattcataaaagtaacaatagaggtaaatataaaacccagaattactacatgtgtcatatagtttataa
    cttctcctatttatagctttctatatttatatttatctataacttcataggcaaatgaataaaaattataaatatgatagtggtcatataatgtataaagatgcaatctgtg
    acagtcttatgaagcagggatgaagacatataggatcaaaatgtttgcatagttattgaagctatgttgatattatgaaattatattgttacaagtttaagatgctaa
    ttataattctcaaggtaaccactaataaaattaccaaaattatgcagaaaaggaaaaaagaaaaacaatacactataaaaaaccaattaaatacaaaaaaagtc
    agtaacagacaacttgagaaacaaagacatataagatatagagaaaacaaatgattaaatggcaaaagtaaatcttgttttagtaatcacattaaatagaaaag
    gatgaagccatcctattaaagggctgagactgacaagttggctaaaaactaaaataaattaaaaagaaaaacaagactcatctacatgctgtctataagagac
    ttgccttagatataaggacacaaagaagttgaaagtaaaaggactgaaaaagatattccatacaaacagtagtaaccaagatagtgccgagtggctatattttt
    gtcaaacaaaataaactaaagtaaaatttacaagagaaaaagaagggcattatgcattgacaaaaattttgacatagccaaataattatgttataaaatatatgt
    acttaataatacagcctcaaaatatatgaagcaataattgctataatttaagggagaaaagaacagttctatgaaaagttagagaatgaaatattccactttcaac
    atgagattaaacaactagacataagatcaataaggaaatagaaaatttgaacaacactataaaccaattatcc
    1392 3309338 — NO ttccagctcatcggcgttgaggtgcac
    1393 2475878 — NO gctgctgagtctcaaaacagccaaa
    1394 3032635 — NO gaggctcctcttcctatggatttgcttcaaggaggtcagggc
    1395 3475556 VPS33A YES attacattgaggattgtatcgcccaaaagcactcgttgatcaaggtgttaagactagtttgcctccaatccgtgtgtaatagtgggctcaaac
    1396 2930679 — NO gatcaacattcttaatgacataagagaagggagttgcaggtggatctaagggaaaactgttccagtagtaaaggagcagcaaatccgatagccctaaggga
    1397 3489376 CDADC1 YES ggatcataaaacaggagttggggcag
    1398 3933755 — NO gtttgcatttgaccatgtcgtgggcaggaga
    1399 2430088 — NO tcattcttaaggctaaggtggcaagataa
    1400 3420474 — NO atggaagcatgttggcgtcatcagcagagacagggaaattgggaaggagaggagagcataattagtgtgcagaaacttggaaatgctgacattggactcc
    tggcaga
    1401 3956302 PITPNB YES gactgtccccagatgtgtgcctataagctggtgaccatcaaattcaagtggtggggactgcaaagcaaagtagaa
    1402 2334264 hCG_1820661 NO ctgctcgctgagatagacacatacctgattgcctcctttggagaggcttgtcagaaacaaaataatgcaaccatttgtctctcagctacctgcgacctggaagc
    cccctccccacttcgagttgtccccgcctttctggacggaaccaacgtacttcttacatatatcgattgatgtctcatgtctccttaaaatgtatgaaaacaaactg
    tgccctgaccaccttgggcacatgtcgccaggactccctgaggctgtgtcacgggcacgcatcttcaaccttggca
    1403 2358760 SCNM1 NO cagcctggtgccctattaataagactgtcaaaaagaggtctttgcccttcatgttgtctgcctgcttctccactaccactcaaagtcctttcccccttcaaatcaca
    taaggactgcaggtaggcactagggggacctggccacatctggaaacagggctgtggctaagttccctgtgaaagtagaagagtcaaaaggcattggca
    gggttatggggaacaccaagggagggaacacccccacctcctcctagtaacctgaacctccctgcctgctgatccccagagtataaataatcccctggtga
    actggcagtaacccttgggggttagcgccaagattctcaccccaaagcccaaggaaggaggcaggcaaaatggatagaagggcttttatttacaggaaag
    gaggacagatgaggatttaagtgtccagtgctcccagcgctagttggtaaagggaaatgcagtgttatctcttcttttgctggcgacctgtaa
    1404 4005886 CASK YES tcatcacaaagcacccagaccggtttgcgt
    1405 2440191 — NO ctcctcacccgcatcataactcctcttcaag
    1406 2561968 SUCLG1 NO aactgtggaatggatcacgtagacatgtaacccagcagcagtttgcttctgttgtccactgattaatcagcctatgtgcctgacactggtcttgca
    1407 3216427 — NO atgttgagaaagcatatgcatgtgacagggcggatttgttagaagc
    1408 3235909 — NO gttagactcggggttgatatctgtcatcgctgt
    1409 3469137 — NO agcaacagaaagctcgtggtgttcctctgcctcaaaggccaaacgtctgtgggttttttgtcttggctgccgaccgcagcacgtcacactgtttgaaatttgca
    gctgcgatcatttatcttcaggggacaggggt
    1410 2343471 — NO gacagattgaaagaggtggtgaagc
    1411 2464386 — NO ggtacacacattaggagactgcagttttggtgagaggtgatggaagctcgagactagtgaggaaaagggaggtgtcaacatgagccctagattcttggagt
    ccagaacttgaaga
    1412 2672266 ALS2CL NO gtgtgagcatgcacaggttagggtgggctg
    1413 3730349 — NO tgggcctttcaaattgagtctaagtttaaaagatataaagaggtgtgggggaagggcattcctggcagagggaagagcatatgcaaaggtgtggaggccta
    gaactacactgcagctttaaggggtggtgagtgatggccgggcaccgtggctcacacctataatcccagcactttgggaggccaaggcaggaggattgct
    tgagctcagtagttcaagaccagcctgggcaacatagcgagaccctgtctctgcaaaatatttttaaaaaattagctgagtgtggtgatgcacgcctgtctact
    aggga
    1414 3755723 MED1 YES ggctcctccatagcagagaaatcttatcagaatagtcccagctcagacgatggtatccgaccacttccagaatacagc
    1415 3861643 — NO ctggcaagcagacgggtttggaatagacattggaagaagcttttagggcatcctagacagcgttgcgatgcttggggcaggggcaggaaaaagccactg
    atggactttcagggcagagctgtaatcgagttgatgtttcagatttagtcgaagggtgtgagagggctgagacggagaaagtggtgtggcagaagaggttg
    ctggtggccatgggtcggggtgcagattatgagagaactc
    1416 3542787 PCNX YES tttgatcctatgtgggagcgactgaaaatagaatgagcttggttaagcacctctcctttgcc
    1417 2468417 RNF144A NO tgccaccaaaggcatggctgtgggc
    1418 2520238 NAB1 NO gggaggaacatttaagctgatggaagtggaagtggaagttgctgtacattggcagcaaggcctccgagttagcttttgaatgcagttaactggtttctcttaac
    tgtggaattcattgaaaagtcagactccgagtggtcgttccaggatatctt
    1419 3129693 — NO cagcctgtgtgtactcatttccttctcttgagtaccactaatttgatagttcacgtatcctctactaagaggtagagtgagacagcttagggacatcagaagtact
    actttcggttcttccacatggaaacatgaggaacgaggaataagtattctttccctaacacttacagtgcacttaagacaaagttttttttttttttggactgaatata
    cgtcgatggacacaggcccagatatggagaaagggcaggtttcctctaggcaagatttgcacggggaacctga
    1420 3845840 — NO cctggatccctgaagactgctctgagatcgatcagccagagagaaacagagagaaagctggctcagccctgaaggctttgagcaaaagtttcagaagga
    gctggaaggagacaacagcccgttctccctgagctgtggccgggagggcccaggccagcaccacgatgtacagatggcccagggggctcgacatgag
    tgagggctgaagttcgtgcaaccccaaccgccacccctgaattgggcagaaccaatttttttcttagcacctgtctgactctgcttaccatgacaaccccaag
    ggccccccagaattgatatccaagtgcctttagcctatcaaagacaggagggggtgcattctcggccaggttagggttcacagagcatccgtatatta
    1421 2621185 NBEAL2 YES ggctgtagacctggaccatgtgacagatgagcgggaacggaaggctctggagggcattatcagcaactttgggcagactccctgtcagct
    1422 2871234 — NO tttgctgccatccatagtcttttcctaagtatcacaaaaggatatgcctgccaatctcttaaaaaatgacaatgcagacttgtgctcaaaatgaagctacagattta
    gaacctcagattcaatgaactaaaaggagaatatattaaatgttaaatttgacctcagaaattccactatactaaggatgttgcctaagacctctcaaagactga
    ggaccagcagaacactgcccatttcactctagaaccacacacaagtctgttgttcccaagccaatgtgaaagctataagccttgagactcaaaagagcaca
    ggtgtccacaggtgacccaaacatcaaa
    1423 2904825 C6orf127 YES ccaggggctcactttctccaacaaaa
    1424 3133366 — NO gtgtcagtacagccgcgtggcagagctga
    1425 2577848 — NO ggcttgcatcagcacacattgtacagccttgcaaattacacagaaattgaaaagaaggttccttgttcataagtgcaatgaatctttgatgtccagtgatccgct
    gcaaacaatgaaaacaaactgtaaagcacttaagaagtttccagcactcatcaaatgcatttccttaggtgacaaaaaatccacaaggagaatgcaaataagt
    ggcatttagttattagagagatacttgaaaaaaaaaaagtggaagtattttcctgcttagaatgatttctgttcccctttgaatgtaagtggtttaagaggcattaag
    aacataatttattttatacttaatgttcacactacctaaatgaataaggaaagggccctacaaggaagagttatgtattttttggtaattgtttctgagtttagagattc
    aggggaagagtaatcctctatttgtgggctcttcttagcatccctaacccccaaggagatagtacatggttttgacttggttatttcactcctgcattctttttcccc
    caaattttaagttgggtcacattgtgctggctgcaaaa
    1426 3332349 — NO ggggatgtctgcaatgtcagcactgattgcagcaccaaactcaaagacaataccactcatgccactgccaacatacccctggcttcctcaacaactttagaat
    tattatattgccctaagtgcatctagaata
    1427 2416733 — NO ggaaaagtacatgccagaagtcagctgtgcagtaacctatgagagagctactcctgtttcaccccagatcatcacctcgattccaaag
    1428 2437457 ASH1L YES aagcaccagttgagattcccagtccttctgaaaccccagctaaaccttctgaacctgaaagtaccttgcagcctgtgctttctctcatcccaaggga
    1429 2704212 — NO gagattgatgtggttgtcagctaaacctgctctttcagtagtggaaatt
    1430 3888795 — NO gttgtttgccttgacagtgcggctgcgcttcggcctgctcgggttaccagggaacaaggc
    1431 2556326 — NO ttgcctcagctgactttaccaaaaattccctttcccttccctgctttaagtcatttcatgtaggttagtcttcatttattcttttgcctctctacagtagttattgctttgtgc
    tgtacatttgggttaaaggagttgtatatgtgtatggtgacagcataatgcctctgaagcccaggacctagctacttcttagctcctaacgtaatttcatccatg
    1432 2878702 — NO gtcagagtgtataaggtgaaatgccgttctgtttttggag
    1433 3328538 — NO gccatccggatgtcagctctgtggacattgactgctggttttcctggggcctcggttttcctctctggcctggcatggactgcctcttgccttggagttgctggg
    atggtggggtgtgtgtgtgagtgagagtgtgttgttggggggcagtgccctggagaggacttcatagcct
    1434 3496801 — NO aggactgtgtggcggactatgcagcatagt
    1435 3668198 — NO tccacagggcagaaactattgcagagttcac
    1436 3764547 4-Sep YES agcagtatttccgagacgagagtggcctgaaccgaaagaacatccaagacaacagggtgcactgctgcctgtacttca
    1437 2544277 ITSN2 YES ggagtgctagcaagtctggagcatcaaataaa
    1438 2581567 — NO agcagtttggcagccacatggattga
    1439 2612556 — NO gcctgggggaatccgtgaacgccta
    1440 2894809 SYCP2L YES ggtgtattcatttccgtgtattgctgcttt
    1441 3956007 — NO gacagtcttcagaaaagggcagctgg
    1442 2407214 GNL2 YES gaaacacacgtgtgattaagcagtcatcattacaaaaatttcaagaggaaatggatacagttatgaaggatccatacaaagttgtcatgaagcaaagcaagtt
    accaatgtctcttctccatgatcgaatccggcctcat
    1443 2948537 KIAA1949 NO tctttctcacatcctagagacggtctttaatacgcattaaccctgtgctgccacatctggctcctgccctcattgcctccaatccggactcttcctctcacatca
    1444 3991159 — NO acaggtggactgcagggtcgtcttacaaaatgacaag
    1445 2444356 — NO tagaccctgacattcagctccaataatggatgtcccagtatgccctgaatccaaacaaatgcctgactgcaataa
    1446 2480997 MSH2 YES agacaggttggagttgggtatgtggattccatacag
    1447 2671526 — NO atgttccttccaaatctcacattgaaatgtaatcttctatgttggaggtgggcctgttgggaggtgactggatcgtgggggtagatttctcatgaatggcttatcgt
    catcctcttggttctgtccttgtgatagtgagttctcgtgagatcatgttgtttaaaagtgtgtggtatccctctgccttgctcttg
    1448 2673140 — NO aagaccacattgagccacctatctccatctgtgcttatgtactctgcttccttcttgttaggatgaacaatgggcgaaccttccaagttcctatttaaagttacccc
    aatctgtgcagaagatcctgtctcctcccacctactcaaggcattactctggca
    1449 3394422 THY1 YES catgaaggtcctctacttatccgccttcactagcaaggacgagggcacctacacg
    1450 2485881 — NO ggggtgacattcagattcaatcggtctacggatgagaaa
    1451 2572007 — NO aggcttctttgacaatcgtttctgatctttagctgagtctagatggtaaaagtgaactagtgaaagggaagaatgagttttgttttggatggcatctcattattttttat
    tttctttttatttatatatttgtttttcttatttttttttctttttgattttaatacctccaccctacttacagatattttttattttcttgacaactctgataaatg
    atggattggaggatcagacttgttgacatcactgatgaggcttgtcttgttgcttgtcttctctggctaacattccttagtaaaaatatttct
    atatttttttctttattttatttggtcattatttcattttgagcttttttcatttattactagataagcgagttttgagtgtcaaatttgcacttaatttgttttt
    ggtactgtcataaggactgtagcatacacagcatactacaactgtaactttttacgaaaatatacattttttgaagatgacttcagaaa
    ctgagggagagagacccacttgagactaggcagcaaacagtgaagaagaaatgagcaacatggtgtgcaggagca
    aagtttcctactgtatatctctactctaagtgtacaatgccta
    1452 2804366 — NO gatacttcatctagtaattcctgcccaggttttgaaacctcatgctggaccctcctgtgcaaggctgccctgctcattctgctctcatctgatcctctcactgggcc
    agtc
    1453 2369480 FAM20B NO tcggcaattgctcattctagggagggcatcatagttggtcagtcttaattcccatgccaaaggacaaacaggtgtgacatttggatagatgaatactgggattg
    gctctggagcatgtgttttgagttgaaccttgcagtcctttctctacgcccgtggattttgtggaaaca
    1454 2556336 — NO agtcctgtctagtggtcagtcctaacagtgtggttaaaggggagctaaatttcaactttcaggggtcagctgagacaaccacctagattttccaagttagttcca
    atttcaagtacaataatcctttgacaacatagaaaagaattatagttagcaaaattgcaattgtcacagtcaaggtcttgttggtaatagagggttggggaaaaa
    gttaaaacagcattaaatgaatatatttttaacataacaaaagttcccagaagacatccacttcaaattcaagccatattcatcaatgttaaaaaccttactcttctc
    cctgatagtgtgaggaaaa
    1455 2589618 TTN YES cctatccctgtaaagcctgtcccagaag
    1456 3405368 — NO ctggggcataaaaaagcaagtgttctcactgagggatgaatagtctactagcaactgtaagacagttgcacgaataatgatgatacaaagaggtatccgatg
    aatataatgtagcaggataaacaaaatggcagtggaaaacaggagtaaaaccaaagggaaggattctgagaagactatttataatgggaactaaaattgtca
    gctgaagctcagatggcggtagaggcattccagatggagtatagaaaatgaatgaagaccaaggacaggacagaaatatctggggtgcactcactaggt
    gagtgtgtccagacattgaaagaggatgagcagaggaagagaacaggagaggtaagaactaaaaaggtggtattaggtcctggaaggtcttaaatatcaa
    gctaaagagttttactgccaagctacagaactttatcaaatgccatactgagaagactgatcgatttattaaagcaaactcctaaaggatctcttcttggaaaca
    attcattagtggttagtgtggaatctcagtgtggcacggaataaagtaaagtacatgggtaacggccccagaaaaaccagagcacagcccagcgcattacc
    actcatcgcctgggtgatcttg
    1457 3447472 — NO ttttaaggagggttgcagaaagtga
    1458 2331932 — NO tgccggtgcagttccttggtatactga
    1459 2413973 USP24 YES tacgtcgatggagttcagcacaagcacgagaatttgggaatcttcacaatacagtggcgttacttgttttgc
    1460 2972147 — NO aagtcaggagggttcagtgaccaga
    1461 3568132 — NO ttaggtatttcgagtttgaagtgtctataagtcatctggagctgtccaggagatggttctatacatgaagatcaggaccagtttcttgtcatca
    1462 3593984 — NO ccaggtggtctagcgctcctaacaaacaccttatgattatccttcattcaacagaggaggagactgcaggcatgcttcagtcagtggtaagaacaggaagaa
    aaacccaaatcagcaacattttcttccttaatttggtataaacgtccttttcattatttcaagttactaatttgctaatctcaaatgttttctgaatcaggtttgctaaatg
    ctgtaaagaatagctatccttcatacaatactaggttttattttttttagtatgtcagcataataaggtacatgcgcattcattccaccaacctgtttagataatactca
    gcttgggtcatattcaaattctacacagagattctctgttttcaatacaactgcttagaaagcagaattgcctagtgatgactgta
    1463 3878647 — NO gcagcccatcccgaagtgcttattacattagaacatttagtgcttttaaagatggtgtgtgtgtgtgtgtgtgtgtgtgtgcgtgcgtgtgtgtgtgtgtgagaga
    gagagaaagcatatctaaatgttggtaccaaatcataccccattggaaagattcaattttctgaaattccacctaagaatttttgtatgtatatatgaaggcaattgt
    gaaattatagagaattagcaaagtttatttagaatttgaggggtttggagtgcagttttacagattttctgactctcttttctttaatgtccatgcagagactaacata
    attgacttttagatctttatccagagagtcaatccaattcaattcaaaaatgtttattgccagtccactctgaaca
    1464 3271123 — NO gtgagtccctgggtcagtgagcaca
    1465 3291284 TMEM26 NO gaaagtggcttatttgaggttgttggtgctgttggtattattgccatagttgttatttaattgcttgattaaactcagtcaaatatccttccta
    1466 3859781 DMKN NO caaggagccaccagattggatgggagcccccacactccctccttaaaacaccaccctctcatcactaatctcagccttgcccttgaaataaaccttagctgcc
    1467 2326309 — NO ccttcacggatttggttggggtcagagaga
    1468 3091040 BNIP3L NO agtgcattgtgctctttccaagttcagcagcagttctatcagtggtgccactgaaactgggtatatttatgatttctttcagcgttaaaaagaaacatagtgttgcc
    ctttttcttaaagcatcagtgaaattatggaaaattacttaaaacgtgaatacatcatcacagtagaatttattatgagagcatgtagtatgtatctgtagccctaac
    acatgggatgaacgttttactgctac
    1469 3823592 HSH2D NO ggggtgcttcatgtcatagcttctcagaaagcagcagtaactgaggctgtggatctgagaacgggagctgctagccaagcaatgagtgaagcttttgtccgt
    agtggcatgttttatctgaggccagcctttgtactcctgtgtta
    1470 3551323 CCNK YES ctacaccacaagtgccgcaagtacagcagtcacagccgtctcaaagctccgaaccatcccagccc
    1471 3602745 RCN2 YES atggatttgttagtttggaagaatt
    1472 2332284 — NO cccggcgcgtatcgtaggcagtgtaccgtggccgtgccgtcagagtgtgcgtgtgcgtgtgtgccgtgtcgaggctgtgtag
    1473 2689891 — NO ctagaactatattagctgctcagtgagttgggcaattggatatttttggttttatgatttcagattttatagaccagtggaatacaggccttgtgcatatgaagatca
    ggtgacaagtttgc
    1474 2952713 — NO tgtttgttgtttggttatgatcttgctt
    1475 3181289 TMOD1 NO cggtggagtccatgcctttgaactggatgtgttctattgatgacctgtgctctgcaggggaaaccagaaggcaaaatgctggcagcatgaaacccttttgtgg
    ttcagttctttatgcactaaggttttaggttgactagtggttgtagttgaaaattttataaaataccgttaatgtgaagtttttctttagtcacagaagttgaatctggtt
    attatttaaaaactagaagcccccaaaccagcagatcttactgaagatgatgttccagcagcagcgacttagccccaggagcccagtttcaatggccttgctg
    tgtggtgtttcaagtgcatttaaaatgtgtgacacagaaacggcacactcttc
    1476 3412443 — NO acctttgacatctctagcacacggagcaattctagatggttgataaaagagcataaatcaatcgacacaaatatccccttaaaccttgtctttcatgtccagtatt
    1477 3886313 TOX2 YES atgagtgacggaaacccagagctcctgtcaaccagccag
    1478 3976557 RBM3 NO atgggacgtttgtagaacctgagtatttttctttttaccagttttttagtttgagctcttaggtttattggagctagcaataattggttctggcaagtttggccagactg
    acttcaaaaaattaatgtgtatccagggacattttaaaaacctgtacacagtgtttattgtggttaggaagcaatttcccaatgtacctataagaaatgtgcatcaa
    gccagcctgaccaacatggtgaaaccccatctgtactaaacataaaaaaattagcctggcatggtggtgtacgcctgtaatcccagtgacttgggaggctga
    ggcaggagaatcgcttgaacccgggaggcggaggttgcagtgagctaagatcgcgccactgtactccagcctgggcaacagcgagactccatctcaaa
    aaaaaaggaaatgtgtatcaagaacatgattatccagcggtattttctaattcagatcatcaaactgattatatagaagagttggctttaaaatgtttgcaaatgtc
    tttttttttttaatactggaagaaaaaatattctgttgtgtctcatacagtgcttaggatgtctttc
    1479 2635686 PVRL3 NO ttccatagctgtagctggagcggtaattggagctgttcttgcccttttcatcattgctatctttgtgactgtgctgctgactcctcgaaaaaaaagaccatcctatct
    tgacaaagt
    1480 2680971 — NO agttggcttacaacctgtgctgtattga
    1481 2715956 HTT YES ttgagttgtacagccgctggatcctgccgtccagctcagccaggaggaccccggccatcctgatcagtgaggtgg
    1482 2452913 — NO ctgtgcacaggactcctcaaatattttccgtt
    1483 2667796 — NO caagagaaggtgagcatataacaggtaaataacagaagctctgattttttttttctttttatagtttgggactattcatccagcaagagaaggacgcttaaaagta
    gatt
    1484 3602153 C15orf39 NO aagggattctgatgagccgatgggccctggaggcagcccattaaagcatctgg
    1485 3752031 CRLF3 YES taccaaaaaggcctcgcacattcagttggacag
    1486 3765307 APPBP2 YES ggaaactgaacagaggctgcttcaagaagctcatgatttgcacctgtcttcactccaactagctaaaaaagcttttggggaatttaatgtacagactgcaaaac
    actatggaaaccttggaagactt
    1487 3956644 — NO gtacatgcaaacgggatgggagcag
    1488 2345202 — NO tgatgcccgcgttgtcttttcagactctgttttttgcctttagcatgccttgtaatttttttttttttttttgataagctggatgtgacataaggggtaaaaagaactgaga
    taaacaggcctttagtgtggcctagaggcctatctggctaggagttaggctgtgtttactgtttgatgtagctttggtgtcagagattaaaatttcctctcgtgtaa
    ctgcttttgtctcctttgttgtctttgggtttccctaataactccttcataagtaggttccgaggcttgtagttatttaagctgtaagtccctgttattacacaggagcc
    ctattgatgtggtgtgtgtgtgtgtaaaagtgttctataatcttatgattagctcttagtgagcctgtgtctttggactgtgaccttcatgagtgctttttagc
    1489 2655521 ABCF3 YES aaaggagagtcggttggaatcatctggcaagaacaa
    1490 2920283 — NO gcaggacatacgctaaaaccggagcaatacagagaagattagcatggccctcacccaaagatgacacgc
    1491 3102056 — NO agattacaaactcacatttaatgttataaatgcagaaaaaggccaaaaacacaaaaagagtggcaacgagggacag
    1492 3161310 — NO tgaagaccttcacgctttctctgtaagttttcattcaaaacatctttcaatttcttttttttctttttcttcttttttgccctcattttagttagtttgagtttcttgtggctctgta
    gtgactgctctaatagaatatcccttacaactttgtggcagttaatttctggatgatcactgtgacttccatttacatgtatttgg
    1493 3289083 — NO acaggtaaattaggacggcactgcgggtactctgtgttccgcctgctcaagttctagacttctggtgtccatagcaacccagcaga
    1494 3304760 — NO cggggaggaaagacagctctaccag
    1495 3895434 C20orf194 YES tctttcctgggcacttatctaacag
    1496 3406522 — NO tggttttgtggataggggaaatctagtagatattaaatatttttatctgcaaaaagcatttggtaaggttctcaatgggagattaatgactaaaataaagaatgagg
    cattaggagataaatttgcttatgagcaagagacagatactaacagtagaaggaaatactttttagattggaaaggagtgacatatagcacaagccaggaatc
    agttttgggaccta
    1497 2692051 — NO gtatcggattaagctcaaaacgggaggaggaaacaaggatgactggagtcaaggaa
    1498 2835105 LOC728264 NO ggcaggggttgggacaagtgctaagtatgcaagactcaagggaagagct
    1499 3935012 — NO cttctccaggccagatttaaccacataaacacatcaaatcccagct
    1500 4038282 — NO tggctgggtgagttctaaaaatgcccaagacctccaagactaggtgagatctgaagtaatgaaatgcctccattcactaaaggcctgaaattgtcctgactgc
    ctcag
    1501 2856770 — NO atgttcaaccagatgatgggccatgattgt
    1502 3579731 — NO cccatgtgtatgctttgagccgttccttagttgagtaggtgattgaccataccagcagcactggtgccaattaagcggtctgcttggttcacacagcctttcattc
    ctgttctagcatggctctgtcttaaatctgcatgcatgtatttattccttaatatattacctctcttcctttcttcctttttacatttcttcccattttttattgtttctctctctct
    cactctctcactcattctctcttgcactttgtcttcggagctcattgccatggagtggcttggctgtacgcatcaaaaagccacccgcaaacgtccatccttggc
    cgtgcggttccacgtctcactcattacttccttcctgcattcatagcatccttccttcctgcttgctctctttttattaggcatttattcctctattagtggagtcaggtg
    cccttatgacaagtcctagc
    1503 3636549 — NO ctactgaaagcatgtcctgtgaatgttacttgtcagtgacaaaataggtacagaaattgaaataagagtttagaaatttttagagccgtttgatggagtagctttgt
    gaatctaataattgaggcttacattttgtatgtctttatttttctcataatttatttttattttataaacatgtctgtttgcaactcattagaactttaaaaaaaaaaactagt
    cattcactctaggtagagtagaagtactgactatgaaggatctttaaaggtcaatagtggtcctaatacgtaaaataatttgctcatatggtgtatttaaactattg
    gcaactatgtaaaagggggaatgggttgaccttcatgttacaaatattaatttctcctgcataaaagtaccctcattg
    1504 3653150 — NO tttcatgagatctacacctgggctgggcacgcctgttggttttttactgacaacgcataatttttcgaggagtggtaatcagaggcaaccgttctagtgacagtg
    attcaggcgtaaacacttggctttggcccagaggttgcactgtgtgagaccacaggtgaacactagaatgtttacactcttccggagtctgtaggtggatgcca
    1505 4011856 IL2RG NO cagggtcctgtagccctaagtggtactaactttccttcattcaacccacctgcgtctcatactcacctcaccccactgtggctgatttggaattttgtgcccccat
    gtaagcaccccttcatttggcattccccacttgagaattacccttttgccccgaacatgtttttcttctccctcagtctggcccttccttttcgcaggattcttcctcc
    ctccctctttccctcccttcctctttccatctaccctccgattgttcctgaaccgatgagaaataaagtt
    1506 2351151 — NO aaatagctgggtctcagtgtctcttt
    1507 2577491 — NO gttctccctagttttctctacaacagtggaaaacaaagcagtgctctctatgccaggacagtacatttggacggcgacaccttgtttgcagaatcct
    1508 2693258 — NO atctacattttcacactgacaccca
    1509 3156385 — NO agtcacacccttggggatctcattgtgtttcatgacttaattatgctgctgactctcagattgttatcttagtttttcagacttctttcttgaactccagacccgtggcc
    actatgttctcgccatgtggaatctgatgtctcataagcatttcagacttaatatactcaaaaggaactgatattcacgccaagcctgcttctctccccttctccact
    cactaaatggcactactttccttctggctgg
    1510 3175668 VPS13A YES cttggaggtattatagcagaagtgaatttggccgagcattctacagttattacatttttagattatcatgatggagcagctacattcctcttaataaatcacacaaa
    gaatgaacttgttc
    1511 2389740 — NO atgagtgattcattctgccctgtggacacttgggaacagaaggcgactcttgagctgggttttccaggcttattaggcgctcagtgggttaacagaatgagctg
    gtccaggaagagatcagcctgtgaaagccgtggctgggatattattggagat
    1512 3224499 — NO atctcttaggtcatatgtcatcgcattacctttaaaaattgtatggtctaaatgtaaaatagttatttttcaacatttgttttaatacccttgtaactgctttttactcaaga
    cagacatttcacttacactaagtgtgtgtgtgtgtgtgtgtgtgtgtagaaacttaggatataacacgtatgtaaattacacacacatacctgtttaaatgtaagaa
    ttcagtgataggaacagttcatctaagaagattttaatgacagggcactcttttggccaaagcagtggaatttcctaagcagcaaggttggtaatagtgctggta
    ggatctgtatgtgtaagctgttacacaagctgaggatcaaagtgccaatttctcaaggagaaaaacttctccgagaaatgaaagtctctgatctgtgttgtatgc
    cctaa
    1513 2807754 C7 NO gggccagaacacactctacaaaatgactaggataacagaaagaacgtgatctcctgattagagagggtggttttcctcaatggaaccaaatataaagagga
    cttgaacaaaaatgacagatacaaactatttctatcctgagtagtaatctcacacttcatcctatagagtcaaccaccacagataggaattccttattctttttttaat
    ttttttaagacagagtctcactttgttgcccaggctggagcgcagtggggtgatctcatctccctgcaacctccgcctcctgggttcaagcgattcttgtgcctc
    agcttcccaagcagctgggattacaggtgcccgccaccacgcccagctaatttttgcatttttagtagagatggggtttcaccatgttggccacgctcgtctcc
    aactcctgacctcaggtaatccgcctgccttggcctcccaaagtgctgggattacagacatgaaccaccacgcctggctggaatacttactcttgtcgggag
    attgaaccactaaaatgttagagcagaattcattatgctgtggtcacaggggtgtcttgtctgagaacaaatacaattcagtcttctctttggggttttagtatgtgt
    caaacataggactggaagtttgcccctgttcttttttcttttgaaagaacatcagttcatgcctgaggcatgagtgactgtgcatttgagaatagttttccctattct
    gtggatacagtcccagagttttcagggagtacacaggtagattagtttgaagcattgaccttttatttattccttatttctctttcatcaaaacaaaacagcagctgt
    gggaggagaaatgagagggcttaaatgaaatttaaaataagctatattatacaaatactatctctgtattgttctgaccctggtaa
    1514 3929304 C21orf59 NO tccacacagtgagagtccagggctcagggctgctcaagaccaaggcttcccttgatgcttcacttcgggtgatcagacatgggggacctgtttatctttagta
    gccggcaaaggcaatcgtaaaacatttgttgtaacttcaggattgtcactctaagaacacc
    1515 3947636 TSPO YES gtacggctcctacctggtctggaaa
    1516 2748234 — NO cgaggtttatgttgtgttaggctcatgagaaggcaagaaattttattatttaaatgttttctccagtaatgtattggattcaagccattgagatttggggagtgtttca
    gtgacttatttgggcaaaacagaatatttgaaattggcattgtctcagaatctggc
    1517 3630746 ITGA11 NO gactgtaaatacgaacccaatctgcacactccaggcctctagttccagaaggatccaagacaaaacagatctgaattctgcccttttctctcacccatcccacc
    cctccattggctcccaagtcacacccactcccttccccatagataggcccctggggctcccgaagaatgaacccaagagcaagggcttgatggtgacagct
    gcaagccagggatgaagaaagactctgagatgtggagactgatggccaggcaagtgggaccaggatactggacgctgtcctgagatgagaggtagccg
    ggctctgcacccacgtgcattcacattgaccgcaactc
    1518 3004500 — NO ctcatgcttcaaaggcatattctcaagaaacaggtgtaatttgtgcagataatcacacctgggaagggatcacagagaaggagaaaaagaaagaaatggct
    tattctgaggtgaatgtgtc
    1519 3552925 DYNC1H1 YES tgccaccttgatgacgcagtgcaaagagggggcacagaaggaaggcctgatgctggactcgcacgaggagctctacaagtggttcactagccaggttat
    ccgcaacctccacgtcgtgttcaccatgaacccgtcctcggagggactcaaggaccgggcagctacatcacc
    1520 3649810 — NO cagcaagaggtgcaggttgagtatttggaggtggtatatttggccagactttagccgcatcgattatgctatttcttgctggctgttttaaattttttttaaaaagga
    ggaggtgtcagatacatcatttca
    1521 2782685 — NO aaaactagggctgtccaggcttaca
    1522 3166121 — NO caaaagcctgctgctgggtagatag
    1523 2524769 — NO agtgtagtgcagcattgcctctggaactggcctgattcttgcctcataaaattcttgtgaccaataaatgaaattctacacatttttatgtgtctaaaatcccaagac
    tagtatctgacacatggttagctctcaatatattttagctactgctattatcattattggtagtactattaaacattttgaaacagaaaatcacttggggctggtcacg
    gtggcacacgcctgtaatcctagcatgtggagaggccgaggcaggtggatcactggagctcaggagttcaagaccagcctgaccaaatggtaaaatcctg
    tctctaccaaaaaaatacaaaacttagatgggcgtgatggcatgcccctgtagtcccagctactcaacagggtggggtaaa
    1524 3101675 ADHFE1 NO ttaactgaaagaattaccgctggccattgtagtgctgagagcaagagctgatctagctagggctttgtcttttcatctttgcgcataacttacctgttaccagtata
    ggtgggatatacatttatcttgcaggaaattccccaaagctcagagtccagttccttccataaaacaggctggacaaatgaccactatgttagacccccaggc
    tcgacttcaggggtcagtgttcctgtcccaaaccccacacagaatactctgcctctgtttcatgtagcaaatga
    1525 3633418 SIN3A YES cacctctcacttgcgtatgaagacaaacaaatactggaagatgctgctgctctgattatccaccatgtgaagaggcagacaggcattcagaaggaggacaa
    atataagataaaacaaatcatgcatcattttattccagatttgctctttgcccaaagaggtgatctctcagatgtggaggaagaggaagaagaagagatggatg
    tagatgaagccacaggggcagttaagaagcacaatggtgttgggggcagtccccctaagtccaagttactgtttagtaacacagcagctcaaaaattaaga
    ggaatggatgaagtatacaacctcttctatgtcaacaacaactggtatatttttatgcgactgcaccagattctctgcctgaggctgctacggatttgttcccaag
    ccgaacggcaaattgaagaagaaaaccgagagagagaatgggaacgggaagtgctgggcataaagcgagacaagagtgacagccctgccattcagct
    acgtctcaaaga
    1526 3904327 — NO ttccaaaggtcgctaaagatactgttactactattgagatattattggctacttcacgtttacatagtaaatgtttgcagcatataacattacagactcataaaccca
    taattaacttataagtgttaatggacaactgtgctttgatttttgcctttagtgataagaaaacaaagtagtgaaatgggtcactcctcaaagcatggaacattttaa
    ctttgcctagtaaggaaaaacaaaacaaaatatagcaattacatgtggaaccgtaacctgcaaaagtaacacaaatattgtctcaaaaggtacaaataggttgt
    acctggaccttaagcagcatg
    1527 2652509 FNDC3B YES gcaccaattgacaacggttcaaaaatcaccaactaccttttagagtgg
    1528 2441680 — NO aggcaagagccctttcgtgcaagtaagcaattttgctgcctcccattttttttttttttttcaatctgtttgggactttgagggctggggtgggaaggtagtggaatg
    gaatagataaacagccagtcaagagctgtggggaggttgacagaattggggtgcaggtacatgtaggatacacagaagctttgtgtctgtggaggctgtat
    gagtctgtgggtgagcagcatgtctaagtgggtggaaa
    1529 2694895 — NO atgccttggagacgagcccagaaggag
    1530 3048170 C7orf44 NO tcctatcatagctggcaccgtgttcatgcctgtggtattccctgtatccctattcctgggaagcagcccaggagggggattcccttggcctctccagggtcagg
    tcacctttcccttcattagtgtgatgggaccttcagaagagaagcactttctgcggccaaactg
    1531 3085948 — YES gaggccggtagtgctgaatggacatggggctggatgaaaagacttccgcctgcctctctcagccccggaatcgccatgagctgctatt
    1532 3300246 CPEB3 NO ggcctttccttggtgtgacacttgaactagtcgattttttgaaggctataacctaacctcgactatttgttgttatgtgca
    1533 3822344 MGC3207 NO ttggagacaccatgttagtcgtggctggtctccaactcctgacctcgggtgatccgcgccccgcggcct
    1534 2345520 — NO aagcctgtttgagagcaggactgat
    1535 2549493 — NO gctccggccgagagaagccaccattcctttc
    1536 2788417 ZNF827 YES gaagagttactggaagcggcacatggtgattcacacaggtttaaaaagtcatcagtgtccgctctgtccattccggtgtgctcgcaaggacaatctc
    1537 2544515 ADCY3 YES actatgtgaccttcatggtgggggag
    1538 3329911 NDUFS3 YES ccactgtcagaccacggaatgatgtggcccacaagcagctctcagcttttggagagtatgtggctgaaatcttgcccaa
    1539 3467685 — NO cagggagctgcatgtccaactgttctcaggggagaaagtttggccttctctaggaacagacggagagaaggcaagggatcctaagggagatggtgcaag
    ggcttttggggagtttggggtttatccaaaatgtagtagagaagagggttcttgaagagttttcagcagggatgggacatgtgggatttgtgtaaagcaggga
    gcaaactatggctcaagggcctgctttggctcactgcctgtttttggaaacaaagttttattggatcacagacacaccattagttttcttaggagctacaaaggc
    1540 2535364 — NO atcaaggaagtcgagtaaaacacttct
    1541 2979944 SYNE1 YES gcagcaaataggtgaaagattgaatgaatgggcagtcttcagtgaaaagaacaaggaactctgtgagtggttgactcaaa
    1542 3210881 — NO atggctctacagcaccggattttgcatcagaatccttcgagtttcttatcttcaccatctgtagcatttagattgaaaaggcttacctgggttttctttttttgtgtttt
    atgatctcaagctattgggagtagaccaattcgtgtggctcaatatgagagttaaagttacgtcagaaggtaatgaaagctgattttgcccttttattaactatagt
    attttaatcctggtatgtaaaattattactcatttgtgcctaatgcagataatgggaagcagctcactgtggtaaagtaggggcattaagcacaggtgcaac
    1543 3984493 — NO ccagggaaatatgggaactgtgagaggcagcaggcaagttatgggcagaggcagatacaatgagttcatgtgggaaattt
    1544 3294206 — NO ttttttctgcactcccattgcttta
    1545 2389550 — NO atgtattggtggacagcatctaggaagaga
    1546 2593736 — NO gctgtaacactttactatgtctatgcaaatacacatttaaacaatataggaagatttcaataaccaaactaactgtacaaaaaataaacaaattaactttattacatt
    gctacttcaacttcagtccttacattgatttgttttttaaaaaataccagtttgaaacacattactgaaagtgagtgtacacaataaatagaaaatagggatgcata
    gtgctggagacattcaaccaacttatcttcatctgttgcctactgttg
    1547 3315642 ATHL1 YES gaatgcagacgggtcaggcgctgtgaacttcct
    1548 2638195 — NO gtcaacgaggggaatccactctgcc
    1549 3973655 — NO cagtttggcaaagagcatgccactgttcctgctgtctatcaaag
    1550 2409486 — NO tctgaaatccgacatcccagtgtccattctggggcacagcttcccctcctttcaagtctctctcttcctccctctccacaacacagaggcctttagctccccagc
    ccttactgttcagtgcgtccacccctccttgtctagaccctgaagtatattacatcagctactctcttgtgagctcctccagtactctgccccttgtccttctattgcc
    ctagtctagg
    1551 2635963 PHLDB2 YES cctgcctgtccggaaggaagactttgatttgcggagccatgtagagactgctggccacaatattgacacctgttaccatgtatcaatcacagagaagacctgc
    cgaggattcctcatcaaaatgggtgggaaaattaaaacgtggaaaaaacgttggtttgtttttgatcggaacaagcgaacattctc
    1552 3730508 TANC2 YES tccacaatgttgctgccttgctctgccgctcacctcagctgacagcctatcgggagcagcttctcgggaacctcacctgcagagcatgctgagccttcgttc
    ctgtgttca
    1553 2512118 — NO ggcatatgtttggtatctctggtccttagttcctgaacaattctgggctaatgctgtagtca
    1554 3181032 — NO tgcttctaacaaatccgccctgtcacatgcatatgctttctcaacattcactgtcaaaaatgccctaccaggacacaacatagtgacaataacacattcaatttaa
    ggataatggttgagagggaaccagctaagaacttacaata
    1555 2401404 ASAP3 NO aggcctctggatggcagaaggaaag
    1556 2496802 MAP4K4 YES tgatctttggtcttgtggcattacagccattgagatggca
    1557 3048180 — NO tcagatttactttcccggagtagtcacaggactgggcagtga
    1558 3436406 — NO ctctgtgccttatcaggagagggtgactctgtgccgactttacaaggctatgggaaggacac
    1559 3840203 LOC400713 YES gctgtcgtagagtggcaatcatcagtggc
    1560 2633650 NIT2 YES ctggctgaaatacgccagcaaatccccgtttttagacagaagcgatcagacctctatg
    1561 2835873 — NO tgatcaaatagtgccgtctgcctggagtacagcatgggggaagaggtttggctgtgttttgatgtagtcactgcccatagtgttgtagttgcttcattttgatgtgt
    catacagctaaagatgctccctttaggtcatttttgttgccgctgcctctgcggcttgttactactgtt
    1562 2849540 — NO agaagacaagaggaagccgttctgctggcatttcgtcgggatgaagacaacacagcca
    1563 2986834 — NO ctggccgtgtttcctgtgagttttgagg
    1564 3222790 — NO tgctgttctgcttctcccattcttgcatagagtaatggagttagtgaaaatgggctttcttttacaacacaaagtgttgctcttctttctcctagggagaaagtagta
    agctctgtgggtgtaggaggaggaaaatagcaggagcttagccaaggagggtgctgcagcacatgtgggtcttcatagtccggaagggtgagtgacac
    1565 3317133 — NO ccaaaaggactgtcgtggcagagcagccatggccaagtggactcagggttcattttcggaacccctttaagcttatagaaagtccccatcatcacccagctc
    ggccccggggcaccgagtccgtctggtgtggggcgtcctttcgacagagcctcctccacaaacccagactctggcttccaccagggccccggacacctg
    cttcctcagggcagacagagaggggtgacacactgcaccctgtggctgggaaaaggggcctgggactgtgcccgtctgggacggagcagagccacca
    tcccatgcaggcactatcaccgcaggcaaa
    1566 3600340 — NO agggccactcaaccatgcgctctgggaggagtgggctgagatggggctgcttggtcagccctgactgtgttttgatctttgggcgtcacc
    1567 3929187 — NO ctggccaccagggaacagttacgtaaattatttgatgtgtctttttaacaagatattaggaagtgctcggcattgttaggattttttttggccacgtggaaaaacac
    acatgatataaagcaaaggaaaataaggcagtctgcaaatggatctgcttagaactgccattacgtaa
    1568 3989061 — NO cttgctctgtcataccttgtggaaatgtaaaagatcaatgacagctagcctttcacacaattatttatgcctcggccctctaattgacacagttacccctagcact
    catcgttgtgatcacctgcagccaagacgctgattttctgctcctatagcctggcaaccttgtggtacatgggactacgtccttta
    1569 2735839 MGC48628 NO tatacatatgtctgcctctaataaa
    1570 3660480 — NO tgagaccgcaattccagcacgcattggcaggacct
    1571 2655657 — NO tgggaggaggacgtctttgggattccttctcttcatgagctgc
    1572 2848543 — NO agcataaagaaagttggcctgggttttcgtgactcggcagggtccactcagtttaaaatgc
    1573 3397172 — NO ctgccgtgggcccattgaccagagcgacctgctgtctgatgcc
    1574 3790842 — NO atgtggcgaatgggtagaagaatgt
    1575 2824108 — NO ttttctgattcactaccactgctggtgttacagcgtgaacgtgacctgaagacaa
    1576 3361136 — NO agaagcaggtataagccaaatgttgagagttagagaatgccagcctgcagttgtcatcacccaggcttagtacc
    1577 3971846 — NO atgttcactcaggctccttggtgtg
    1578 3294447 ANXA7 YES gtgagttttccggatatgtagaaagtgg
    1579 3850170 S1PR2 NO gttgcactatttggggcacagaataatcaccaaaagtgagaaaaacgagtttgggtggctggggaggactttgggactcttgatgcaaggcgcaacttgag
    aaaattctgggtgtgatatttgcacagacaccctcctttcaaaaacagccaccccccaagctattctcagctccacacctgcagccccagctaaggtaccag
    gtctcctgagcaaggcagagagaagccttgagccttctctgtgtcttctttcaagaaccccgctgtgtcttctttcaagattttttttttgagacagtttcaagattttt
    gttttgtttttgagatggagtctcactgtgtcacccaggctgaggtggcagtggttcaatctccgttcactgccacctccacctcccgggttcaagcgattctcct
    gcttcagcctctcgagtagctgggactacaggcacctgccaccatgtctggctaatttttgtatttttagtagagacagggtttcactacgttggccaggctggt
    ctcaaactcctgacctcaagtgatccgcccgcctcggcctccccaattgctgggattacaggcgtgagccactgtgcccggccttcttctttcaagttatatag
    aatggagcatgggggtggcagtggctagggacatttcctggggacactctcccctaaccccccagaaggacttcacaaaaacctgtggataatggaaggg
    atgttacggtacaaacgtatatttatgtgtgtgtgtgtgtatgtgtgtgcgcgcgcgcgtgtgcacataggcgtgatgtctgtgaccctc
    1580 3918219 — NO tgcggattcgtctgctccacgcagggtgctctgacgtactctgtgtggcctggagctcagaaacctgtgctggactcagtg
    1581 2370552 — NO gttggggtgaactgaacctgtccattt
    1582 3476124 — NO gagcgggatcgaggcgtttttaataattcgagttgggaagacccggatggttcatcaaaatgatggtgttgagcacccgggaggcagacattgggtatttgtt
    cacaattttgcacctgtaagaaaatgttcctttataactttcaaggattgccgtgagcgtctttggggccttttcattcatgtacaagtttcattcattactattcaactt
    ggtagacttggtgaaaaatgtaaaagcattctgtatttggatcagtcttgggaactaaatttgtcgtgaattggggcctgtcacagattgcctccagtgtgcatcc
    tccacgcagaccctccttgctcagtctccctctggcgcccatggggaagccgtgctgtggttggcagtgcggccatctgggctgccgcaacgtggcaggg
    caccgtccagcaagactgccccttagtgcagggctaagcaaggaaaagaagaagcccaaaaaggcgggttctttttgatacttgtaattcaggcgtcctcc
    agagtg
    1583 3929424 C21orf66 NO ctgttgctgattttggtgacacatctctgttgatatcagtaaatatcaattgataagtaaaaaaatatgcaagtcttaacttggatgtatttcatcttgcatgtgctcac
    ctccctcccctctcacccagtcgtttgggttgtttgcctccccttactgtcatatcttcatagtgtggaactaaaacgtagaaatgagggaagtatagtggacag
    atgtttcccccaccccttcttttacctaggcaagagattaggggagtcttttttgattaaagagagtaggtccaaaataaagaccctgaaacactaaaatctggg
    gatccccaacaaaagaactggctcagtacctagtgatccgacggagacacctctgttagacagctcctgcccacacacacagcttccagtcttgctatctat
    atgaacaggcagttaacgatgatcataaggaccaacctgagcagcagaaccaaagggactgaggaaacagacagtgctggtacaagtatgcaagttttct
    gtaaacagattactttcaaacagttgggagccccagggagataatagaaggtatcctactcaacaggagtatatagaatgctgtagaagaggaatattgtaa
    gaacaagaactatctcttgaaaactaaaaatatgataactgaaatataaatttaaataggattggaagctaaagctaggaaattaccctagaatgttttagagaa
    atggaaaatacgaagaccaaaaaaataaaataaaactatgctgtgaaagagaaagattagcatttgagaaggcggaagttggtcctgctcagatgcggtttt
    cagatgcc
    1584 2418445 — NO aggtttcaacccaactggacctgcttg
    1585 2977983 EPM2A YES aattctaccaaatatctggctgggtag
    1586 3074397 CNOT4 YES ttcatccaatcacagtgcacggtccccttttgaaggggcagtaacagagtcacagtcgttattctcagacaattttcgccatcccaaccctatcccaagtgggc
    ttcctcctttccccagctccccacagacatccagtgactggcctacagcaccagaa
    1587 3320669 USP47 NO cggtggagcctcatgatctcttatcttttgaggctgaggcaggtcacatgcaacaaattgtgaccctgctccccacaagtcatgcaaaggttttgaagagctttt
    accgtggggcagatgaacttgtgtcaaccatgcacaccctgtgagaaccaagtacctgtgtttctaaggcgggcactcaaggtgaggggtgcattctggcc
    aaagaaacaaaagctgtggtttcaggaccatgccgtgtgtagctgatctgtacgggacgtgtatgtaaggaagagcaatcatgatagataagaacagtgtgt
    gaagcagccttcacactagagtgtttggtcatctcttataatgtaagggaaggtactttaaaattctgggaagatgcgatgaactcatgtcccagtcagaaaata
    atccaatgaaataagcattggttgccaggccacagttaggaattgta
    1588 3562057 — NO gagcaaaaatattgtcaggtttcttgctgtggttctggatgttcagtagcaggctcatttg
    1589 3924690 DIP2A YES gggcctcgtggagcattcgtactttgagcgtccacaggtggcttctgtgaga
    1590 3029146 — NO agtcaactcggggagtcaaattaggaaaggcttcgaaggatgggcaggacgtaagaatccagagaggagagggatgtttggagaacagaaagtggaag
    gttcctgtaggaaaatgatagagctatacttggagaggcaagcggggc
    1591 2480430 — NO tcttcactgaaggtgccagcctatgggtggactcgtgatctagacctaaagggttagtgtgagttcctagaggaaaagaaagccatgaggcagattgtggaa
    ggctttgaaggccaggtggagggccttgaactttattccatagacaatggggagctattga
    1592 2923442 — NO ctgggaagaacttcaggctgttgttcagggcatggatatcaccactgtcca
    1593 3393487 FXYD6 YES cctctggaacctgaggcggctgcttgaacctttggatgcaaatgtcgatgcttaa
    1594 3879288 — NO gctttcaagaatacggccatgtctgcattgttggcttacacgcagacacacgctcgggtttttcatttggcagggtg
    1595 2889490 AGXT2L2 NO catctcatccaaatacacgctattgagaaggcgagcctgacctccctcttacagataaagtcagctttcagaggctcagggtgggggggcctgcccgaggc
    cataatgctacccaccccctcctcctaaccactggtctgttggaataaccca
    1596 2915334 DOPEY1 YES agattggttgagagtctccgtttgccacaggtgccaactctccattctcaagtgttcctgtttttcagagtgttacttttaagaatgtctccccaacatcttacctcac
    tctggcctaccatgattacagaactt
    1597 3186622 — NO ctcatattaggatgtggacctgtccaaatcttcagggagtcctccctccccaggccaggcaatttctccagcaccaaggtaaccactgttttgttctctattgcta
    tggattggttttgcttatttgtaaatttatttgtagacttggtccctatcactacgaattggttttgcttatttgtaaacttcatataattagaaatcatgaggcattttcat
    aagtgtgttttcaacttctataaagagaaacacaatgtaccttcttttttgtgtcctaaaccttctttttctcagtccccttccctgtacatgcacttttcaaagtgatta
    gaggtacagagaactcttcctctaatctaataaacaaaatgatacaaactcaataataggtggaaatgcccctcaggttcaatgctagagagaaactgcagg
    gaatggtggggactatggcaaactatggaaa
    1598 3720992 — NO catttctatggttattcgtggaatgactctttgaccacgcggagaaggcaaaacttcagccatttgtgtttttttccccttggccttcccccctttcccaggaagtcc
    gacttgttca
    1599 3916840 — NO tggcaatttcaacagttcgtcactgcacgctgcctcttaaagg
    1600 3959370 — NO catgggcttctcagatccaggtgatgccca
    1601 2571999 SLC35F5 YES tggtttcactcagcgcaggcgaatggctcttgggattgttattatctgcttgttgatgtgatatgggttgcttcctctgaacttacttcg
    1602 3757901 — NO tatttccttattacatgttccagacaggagtgctagccca
    1603 4002896 — NO ctttcatggagcaccgctgctcacgacctgttacagtctagaaaaatggaaaaactgaaaatgggtatctatgccacctaa
    1604 4013965 — NO aaaatctactgtggagggagtgcaaa
    1605 2327098 — NO atacttgagagtaaatgaactgctcttgttactttactatgtcaattacaaagcttaaaattcacacaagccacacgacatatttaagaatgcatgtgagggcca
    ggtgc
    1606 2381607 — NO gacatcagagtggaacttgggcgatgctgccaacatga
    1607 2995272 C7orf41 NO cactcccgcttcagtggggtttctatggagttgtcttggtagcctttgccattttgaatttagagtccattttgtggctgactattctcttaagtttatgttggagaatta
    acattcgctgactcgaatgtagagaactctgaatgtattaaggataggttttgagtcctcacaggtgaccttactgagggaaagcatggcagagaagaaatgc
    agtctgcactttttatgtactttttaagtgtccgtaagtgaaaggttttgcttataaagcatgaattttaatatctagtcattaaactgcacaagtgcaaatacaaggg
    caggaaaggataatcacttagctttggactaagagggtaagagaggcccagaagcctttaagtgttttgccattactgagttacctgggtatgtagcgactgg
    ttc
    1608 3261789 SUFU YES gctccaacctgagtggtgtcagtgccaagtgtgcctgggatgacctgagccggccccccgaggatgacgaggacagccggagcatctgcatcggcaca
    cagcc
    1609 3934119 SIK1 NO tgtgcgcgtgcattgattactatccatttctttagtcaacgctctccacttcctgatttctgctttaaggaaaactgtgaactttctgcttcatgtatcagttttaaagca
    gcccaggcaaagatcatctacagattctaggaattctctcccctgaaatcaaaacctggaagacttttttttcttattttagttgagaagtttcataaactgctcaag
    gattagttttccaggactctgcggaggaacggcaggaagaacctcagagagggcagaggtgacttcaaagtgctggggactccgtcctgagggtcacttg
    gccctgagcccctgcgtgcccttgcggaagcccagaagcttcttcctgctgcacctcccgtttccgctgctgctgacgtttatgcatttcatgatggggtccaa
    caagaacacctgacttgggtgaagttgtgcaatattggaggctgactgtagggctgggcagctgggagacaggctcatggctcatggctcatggctcagg
    gcggtgcctgccctgggccgggacccccctccccaccccccacctaggctttttgggttttgttcaaggaaggtaaagtgagaggtttaggtcagtgttttta
    agtttttgttttttttttaaagcaaatcctgtatatgtatctacatgggagacaggtagacactacttatttgttacattttgtactatacgtttgtgttccaggtttcagct
    tccctcgctcctgttgttaagaagcgtccctgtcagcacaggtgtgcattgaggaaggggccccagggccttcgctccctcagcactggggtggaggcgg
    caggaaggggcggcccttacctggcaggtctgggcgcacctttagcaggtggactccgtggggctccaccagccagaagcctctggaaggcaacgaag
    gcaatgctgctccctgagtccagtccccgcccccaaacccagcccaggtgccttcagctacttcggcttcttaaaccctgcagtgtt
    1610 2748304 — NO actcaaggtctgtccatgctggtgacttagagtagtgggatttaaaccagaggatgcacacttggaggcacttgaagatgtttcaagggacatgcaggcattg
    aatatttaaaggaaattaattgccgattcttagatcttgagtgttaatcagttctaacactgaccgtcctgagaaaatgcctatggcccaggtgacctgctggtttt
    cctttcacaccttctctttcatgattaccattctttaaagggaagacatacctttcacctaccccttatcagagtgccaagtagggggataattaaaatactgctgg
    ggctgctgggaaagtgagtgactcta
    1611 2358329 TARS2 YES ctccagcacccatgtcctgggggcagcagctgaacaattcctaggtgctgttctctgca
    1612 2636804 — NO tcttatcacaacactgcggcgggaaaatcaggaaatgggttcacctttcagcagtcaccacagtaaacttcattgagaacatacatgcccagatatctcttctg
    tgcacatgtatatgttaacagctagccattcagccaacaggta
    1613 2907584 KLHDC3 NO cagggaagtcactaatgggagagtgggaggtatttgaaaagggggtttcgtgggtagtttttgtcctactttcatctctcttttgatcccgacag
    1614 3185561 — NO gcgagtcgactcacctacctcttttcaagccggcctagccccttcccggaacctcggctcccccccaacgaaactactgctaagccaactggactacacttcc
    1615 3752751 — NO atgggttcaagacctgtttatgtgcgagaacaacaggctttggtgctggtgactcaccaagatgggaaatacaggaaaagaagcagggatgtggtagcag
    agtgt
    1616 2366872 — NO ttcccatccctgctctagcagcctg
    1617 2389086 — NO tgagagaggtttctattgttcactttagaaaaatgtaggtcaatgtaatgggtgatatctgttcttaattattctaagaattaaatcctgtatgttatcagtcacctatta
    tatggcacaccctcagggg
    1618 2523976 — NO aggcaaggggtaaagtccaggatgaggc
    1619 3394423 THY1 YES gcagttcacccatccagtacgagttcagcctgacccgtgagacaaagaagcacgtgctctttggcactgtgggggtgcctgagcacacataccgctcccg
    aaccaacttcaccagcaaataca
    1620 3510096 POSTN YES agggagaaacggtgcgattcacatattccgcgagatcatcaagccagcagagaaatccctccatgaaaagtt
    1621 2974447 — NO atggattacgggcttttatgtgggcagcaacttgtgcctcag
    1622 3000375 — NO gtcacttttgtggcctcttggctgtaccttccctgggacaggacacggtcctttct
    1623 3498077 — NO gcagttatgtatacacagggcaatcatcagaccataatcattactgttcgaggccagaacagagacgactagctctctgtgtgcctttcccaagtctcaccgtg
    atggactgtcctctc
    1624 3670758 — NO gtcttcagagctagccggctgtgtcttctccccgtttctttcactggtgaataacctttcgtttgaaccagccttgattgttctctccatgttccactgtggctcccca
    tggacactgctaggtggaatctctgagaaaacaggcacttcgcagtcggcgcatctttctctgccagcttagggattgccgtcaaggtggaggaagggtatt
    ttggccatgttcggagtcgttgttttta
    1625 3418194 — NO cagttagctgtagagatgtgatttagcaaagttggttataaagtgggtttttgtaaattgatttccttattactgttctttgtagaattgaagatgtattctctcccagcaa
    aatagttcacctgcagatcattgaaaagtttggctgaagaaaggggttattttggtgtgggggtaggaggcttctgtgggctgggcatggtggcttacatttgt
    aatcccagcactttgggaggctgaggcaggaggatcacttgaggccgggagttcaagacttgcctgaccaacataatgaatctcccatctctacaaaaaga
    atcagccaggcgtggtggcgcacacctgtagtcccagccactcaggatgctgaggcgggatggtctcttgaacttgggagattgaggctgcagtggagca
    gtactcgtaccc
    1626 3687863 ZNF764 YES gaggtggcgaaatgtcagacacaaacggac
    1627 2438168 — NO gggaatatagagaggctgctgagag
    1628 3059966 KIAA1324L YES ggctctctgtaccaacaatataacagactttacagtaaaagaaatagtggcagggtcagatgattacacaaatttggtaggggcatttgtatgccagtcaacaa
    ttattccttctgaaagtaagggtttccgagcagccttatcatcacaatc
    1629 3281916 — NO aaaaagtaaggtggatatgtgcagtggct
    1630 2838994 — NO gtagaaaggggaatgtgtactgctagaggttacgggctttga
    1631 2724513 UBE2K NO gtgtaccaagactagcaagagtttgcttcaggattttgttgaataattaagataatattttgagtgtgtcagggccattcaaattgttggtgttgcatcacagctac
    cttaactgatttttaacatggatcctctgtgcctgtgaatttacttgcatgcttgtacttgacttcttaggatgggtagctgaaaagaccaccattttaagcatttgaga
    attcttaaatatgaaatttattcagaattgaagatggtgacctattcagagcctttttgtccttgtcaacagactgggacagtgtctgattcccccttcacccccccc
    acccccgccttgccacacacagctaatattctaatggtaaatttctctgtatcaggtggggaaatgtgctgaaggacagtatgtatcccttgcttcatttttaggtc
    gtaggtttggaatgtcttgtcccagttcttcaaacactcttaaattttttcttaagtaatgtaaaaatggaactgccaattttatttctcttgcaaaaatagtaaatacttg
    atgttacattattcccaggtttaatgaaagaacccaacttagtttttcagtgaatttgacacctattttttagtgatgaaatttttctttgagaactggcaaggatgcag
    tcagctgtttgcagtttttagcctga
    1632 2415597 — NO ccctgttaatcttgtggtcaccatacactcttgggttagctgtcaaattagggtttctccaccctgcttttgtataatgaagtttctaatcctaaatgcaggatgccc
    cattctgagcctgtttgtatttaacagaaaatagggattttcgtcccatttttatcttaccaattcactccccaactgtgccagaatgcccagaggtaatagcctttt
    ggaaggagctttcccatgctacattccagcagggtaaaacaatctgaaaatgttcttgccccttttatcactgagttctccatatcccaggctattttataaataga
    atttttccctacagaaaatatgtaaagccattgcgaagagaaaacttttctacacatagaaaacatgataatttctcattagttttggaacaatacaggtctactcta
    agttgtttcttattctggagtacaaaatttgcattttataatgtaaattgggacactgtatactagctttctc
    1633 2818227 — NO cactatgtcaactgggtgtctttgctaagtttggcatcaatatggtgacctctcgggagcaggggaccactaggttacataaggaggggtgaactggcccag
    attggaaatggagcaggtcaaaactcccatgctaaccagtagtgagatggagcct
    1634 3412324 IRAK4 NO atatacacctatctcaaccatttttttaactgatttttttcctaaatattcttctttacctttaacaaggcataggctgttgcaggacagtggttattaaagcatgggttg
    aacttccaaaatata
    1635 3598210 ANKDD1A YES gtcggggccatatggctgtgctgcagcgacttgtggacatcgggctggacct
    1636 3728164 — NO cttgctaacgctcgccagagaaatattccgtggaggtgttaaaacaagactagtggaaagaaatggtaacttaaaaagaaagaaaatccatggcagtgaag
    aacagatttcatattagtactgtcataatattctctaatgtatcatataaataaaaatctgtttagaccagaattttaataagtcaccaaaggaaggttttgaatccta
    cagtttatgtatccccctttgcgatgtaaatgttcacatctcaagtgaagtagagtggggagacgcttcggagactagaggctgttaattagtgaggtatattttg
    atcagggcaagaagactggttcattctatatcttcgtatttctctggatgattatttcattttgtaaaatatgtaagagttcccccccagccccttatctttttaaaaatt
    aaaatggtcatgctcttctaaaaagatgacttaatttgaaggctttggagacatgaggatgatggggatccatcactccctgttctttgctccctttggactggag
    tgttggctgtctggaagagttttgcttgagctcgtgggttattttcttctatgtggaggaaccaagagactctttagcatctttcagcaagagcgaggtctgggtg
    tactcaccatctgtcttaattatccttgtgtataagaaaacattcccatcttttcccaattgccatttccttccttaacttttagaggccagaacctcatctgttgatgca
    gggagatctcacttctttaacctatttctagttgccttcagtcacagcggggtggccaggggcgagtcacttaagcctccccaaggctcagtttcctcctttgta
    aaagagggagaattatagtactcactgcctgcagttagttgtttggaggataaatgcaaaattcttcactgggagtctggcataaaacagcactccgcaaatgt
    ctgttgatcttattattatagaattattatttttattattattatttttaagacggagcctcact
    1637 2779706 — NO acctggtaaagtgagaagagtgatcaggagaagataatttgcatagtatatatagatttctattccatttatataaaacccttgaatggtaccttagtagaaacaat
    ataaaataaagctaatatgggttagatgataatgtggttaagtggatttttttttcctgtctgaacaaaagaactgacaatttaatcaatagacccctgtcagtctgg
    agagatgcttctagtggtcagcacggcactctggtctttgtg
    1638 3394582 — NO aacagctcaacatgtgtcgggatgtccagggaa
    1639 2429120 TRIM33 YES catattttgaaagcacggtgtgatcctgtccctgctgctaatggagcaatacgtttccattgtgatcccacctt
    1640 3428756 — NO cagctaaggtaaatctgcttggtccaaacaaaacaaaacaaaacaaaacaccagactgcaacaataacaggaaaagatcctcttcagtgatttatgttgttct
    cttactttcataactagtttgaatgcaaggctggtaaagggatacacagagaatcattattttaaataacaaaagccattcaaaactctctctacctgtcaaggat
    gttttatgctcccattcttatttgtttggcagtaaacataccttgcccacagtcgccagcatcaaacccacaggacaagacattgcatgcttggtcacagaactta
    tcagcgagccaggaattcgcacatc
    1641 3595186 — NO ttgtttaggcaaagcacgttatggctttttcttgcctagtttaggtctgtgcttaatgactactggaatagcagcaaacataacatcctgataacatttgggaggaa
    aagccatatttgaaaattggtgaaatgcaataatctttaaaccaggaatcatcagtttgctaataaaaggtatatggctccaagttacgtattttgtcagggtcctc
    tggcattttcactagtcattttgctagtgtgtacaatgattcctatcttgctgtaaaacttggtgatttttttatattgttgaactaggtgacatgaatattgagtcagatc
    acataatcttagagtaacacataagtgattatgtagcgttgtgggtggaaacaattctggataaaaagtgcatgacagttcagaactactgtgcaggcagcctg
    tctgaaatcaggtttaaaaattggccctgtctccagctgactcgttttgtc
    1642 3959259 — NO ctcaagcacagtcatgattggttttgtattttcttctccaggctacataataattttttgacctggttttcttgatgccttataattctgaatgctggacttgtctctttatta
    cctgccagttagc
    1643 2604457 — NO acagcaggaatctgtcagtgtccctga
    1644 2843218 PRR7 NO ggcgcgcgcacgacttgagacctgccacgggcagcccccggccgcgggtccccgagtgacgctggcggcacctgagagtgtggcgcgggcccggg
    gccacgcagcggagcccagtgtccagtgaagcgtctgaggacccgccgcc
    1645 3039818 — NO gctgacctattgctgaggactatgagaaaaaagttattacagaatgagtcatatggaaaacacttgcaaac
    1646 3483658 — NO gcagacaatccccatcagcttaaggttcccgtcaccagggtttcccttcatcgaaactttgccacagtca
    1647 3605805 SCAND2 NO tgtagtattcactactccagacctttttcaagttgaattttttttctttttccctatgtctgttcttacgtattttttttaaacttttatttcagtagtgtttggggaacaagtag
    tgtttggttgcatggaaaagttcttcagtggtgtttctgagttttggtgcacccatcacccaagggtagtcttttttatccatcaagtctgtacccaatgtgt
    1648 3659197 — NO agagagcctagcctgaatatgccacagccgcacagagtttctcct
    1649 3775146 — NO cagttaagtgcagctcggtgagtcccggcagttccttcccggcactggctcgtccctgggttctcaaggttccatgcggccacagcgtccgtccacctgtcc
    acgcgagccacatgctgaaatggaggtggataaaattcatcaggcagctgctgtaacacggaaatgtgcagatgccagagtagcttcgtc
    1650 2534837 — NO tgtgcacgcatgcagcactgcgataacggggcagggggagttaggtgattgcttaaagcacaagtgtgtagggaagaaacaaaggcaggaggggccat
    taaggagcctgtagagtgtttgggtcgggggctcacatttgtacagagtgagctga
    1651 2705269 — NO aaagctacaagcatggccgcctgtggtatcgaggtgttgcaaacaatatctgtgttgcgcttcctgttttaacctacctcgttttgtttgtttttgtttcactgttcatc
    acagcagtgttatctccaggagacatatagagagctcaaccggcaatctcaggtgcatttaacatttttaaaacgaaacagtagttgaccaatttttcttcttaa
    aaaattggaagtggggggaatccaatgacaaaaactaatgtggcttgtttctggagaaaataattactgtaaatggaacaacaacaacaaaaaaaactacga
    tcttactgactttgcctaaatacacaagcagctgatgtactattaatgagaacgaaatacacattaggaaaatggagccatttcaatctagtggtttgggcaaga
    tggggaagagaaggggaaacattctagtttctggattacattattatgcccctcctgaaaaggtggttgtcatttgcatttatttaaagcaggtaatatgcaggaa
    tgtaactgaggattatcttcaggcaatcagcaagatatcctcctcatggtccctttagctctcaaaagcaatgaaatcctcctgttctcatttttactgctgtggttgt
    gctgctgaacaatactatcttctcaaattccatgccacaaattcagcaataactttttggattgaatttaacaactactgtaattggatgctgatgtggacaaaatat
    attgatttcgatttcactcccgaatgtgattgccaccagctc
    1652 3479382 GOLGA3 YES tcagcaaacagcccgtgggaaaccaag
    1653 2320890 — NO gtttcatgagacagcgatctgcctaaccattcactcctcctagaagcaaaagctaccgtgatcattgaggcacagccggtcttcatatatcctcaaaggaggg
    ggattagcttccacatcccttctctattcctggaggtgccagtagtgggagagtcatggcagaagttaccagaggcaagtggggcagaggcaagtagggta
    tatgtttggatcagtggatcagtgtcctttattgtgcagaaaaagctaaaattacagattcttctgaagggatacatagcagccgtttcaccaatgtccctcagtc
    catttgtccaggtccaga
    1654 2824597 — NO tgtaggtgctgctttaatgcttggactgatgttattgttgtgggagtggattagttattgtgagcatgggttggttataaaagcaaggtcaaggctggg
    1655 3916352 — NO taatgggcctgagtgtcaccaagag
    1656 2900984 HLA-F YES ggaatgaatggctgcgacatggggcc
    1657 3003162 GBAS NO ccctatgccgatgttgtcctggattaccttttttgtcctgtcttatcacttcgtctcctgtctcgggtttctggctgtctgttcctatttctatttgatgttgtgctctcactt
    cacacccagcatgtagaatcaccttgctcttccaacttccctgtctgtgccactcaccttgttttactcagcccgttccttagttctctgtggtgaatctgtcaccta
    agctgtgcattcttcatcggacatgtattttggttctcttgtttccttctccatctctctctccaagcctctcgagccccattcccaagtagcttttttttctgactaccttt
    ctgggctccaagctatacctgtgtctccttcctgccctgcaatacattaccccaaagtttgtcagattgatctgcttgagttctgttttcttttttcatcacgttttttcttt
    tctctgaaactttcagcagctccctgtttgcagaacataaagacttaactcctgcctggtttttaggggtcccaataatgggattctgcccaacccatccagttct
    gggtacaagtactgcctgccttacaatctccattcaggtaaggccagggctcctaagagcaggtttggggtccccagcaaagaggagtggctacaaatcca
    tgcgtgactttgtgttggtgaaaaacctgggccccgttgccaggcccctttctggaccccacctgaatcatgtgtactgggcttcctcctgggcactgcctcca
    atgcagggttgtctattcctgctcatgtcatgcgacgaaaaggaaatgttggacatacatttccctagcagaatccctctttccctgtcctcgattttcattgatcc
    catgttatttctgaacattcatgagtcacgcatcagatacatttaatatcagatcctaatttaaaaagtaaatgctactcttccaaaagtacacatgatgtggtcact
    atactgggtcataaagatgtatgggttttcagttagttagacttagaccgt
    1658 3743421 — NO ggaacaggagaagccccaattttcagaagagaggggagttgattgagaagtgtaagattgttacttgagaataatcttgagggtatgaaggtagggtaagg
    gagaatggtgataaactc
    1659 2949593 DOM3Z YES ctggcggcccagtcaccgtgtctgtacaccaagatgcaccttacgccttcctgccc
    1660 3824798 MAST3 YES acggcagaagatggtccctcgcgtctctcccatcttccggctatggaaccaacacac
    1661 3933890 — NO tctccgtaaccctataacagtccgata
    1662 3340811 — NO catttatttatgatcaaccagagagactaaacagtggactcatgggtttggactctattgcaattcaa
    1663 3888249 DDX27 YES gatgaagaactcaccaacacaagcaagaaggccct
    1664 3932432 — NO atagggaatgtgctttgagctgttt
    1665 3941419 — NO caggaaaagagttggcctggacctgca
    1666 3976987 CCDC120 NO gttgactgcgtgtccattgttgttatagttggttgaatctgtcccattaattctccttcc
    1667 2892314 — NO acatggccagtactgtttcaggggaatattgggtggcgctgg
    1668 3379157 — NO gggccagagaactttacaatgattatgaagatcaaagggcattagaatcaagctataaagagccactgtttgatgttgggatgtgaggatgctgcaggtggat
    gtctgcacgttgatggtgagaacatggtcaccctggccctgctgggtctttgctaaagagactgtgctctgttcttggggccgttttcatcacctgatta
    1669 3830022 — NO aggacggtcggcgtgcagagttcctggagtgctggggggcctgagatggttgtatgacgtctggaggattcaggagggtgtatggggtctcaaggacac
    1670 3904149 CPNE1 YES ccttggttcagctgtccatttcctgtgaccatctcattgacaaggacatcggctccaagtctgacccactctgcgtccattttcaggatgtggg
    1671 2408020 — NO tgaaccatccattgcctaaaactccagcaaccctaaaaggacccaatcaaccagaagaaaaaatactaatacctcatatcatacagcaacctaacatttcaaa
    gtgctttcacatgtgttagttcatgcacacctgacaacagtttaactgagggagccagggc
    1672 2437930 MEX3A NO ccctgggtccagtagaatgtataaaagttgtaaggaaaagataaatagaggagggaagtggctgagtccaccctgagttgcccaatcttcagataccaggg
    ttggatcaggttgctagtttaagattgggagcttccagtctgctggggttgattctgagaatccttggatttttaaattgtaggacaaagaaatgaggggttcattt
    cccagggtcttggaaaggatgcacactgatcatctcaataagacaggggctgggttgggggcagcagaggaggccaagcacattcacctgcacccctag
    tacctgggcagcccatactccaatgtggta
    1673 3264854 — NO ctccacctctttttgtgcgagggcggcctc
    1674 2701275 — NO acttgctggaaaaagtacatgctctcc
    1675 3017578 — NO tatctctgatggagctagtgaacattaagccctcaatatttgtttaatcagtgctatcaaagtggtttaaatggatgtagtctccaggggtctctg
    1676 3625878 — NO ctacttcagtgagtgggactttagcctgagca
    1677 2438152 — NO cagctccctgagatagatgtaaatcctaagcattgtgggtgttttggtttgatgggactggattgaaagatttacagacttaaattgtaaaggaaggtaatttaga
    gagaggaaggaaataaacattatgttggtttggttataaccactggcttgtctccactgacatggcctgggggtgagtggtgtatttgcaaagctcctttcaggt
    ctgcattaatctctggcattagttggctgtgaccgattagcctcccagttaaagtatgtagtcagttcttagtgatggtaaatgggttactgaggccttcttattaca
    tccaattatgaggtgactatataatttatcttgcaaactgttgagtgtgttctaaacagtatgctgtgggggcgctatcactaattatgctgga
    1678 2786550 — NO gtacccaggaggtttggcatcactcaagaccctcagaatgcttcctctgctttaaatgcttggagtggctctctgtccaaactgtattaccccatccaaactaaat
    cacctctcactatgtggatgaagcaaacaacagatcttttgtttcgaaatgatttcatgttaactatattccaggatattaagatcttacttaaggaaactgctttgc
    agtgccagggatctaagctatata
    1679 3122495 ANGPT2 YES cagggacagccggcaaaataagcag
    1680 3252241 — NO cttctccgcaccacatcgcccttactctaaaattgaccacataattggaagtaaaacactcctcagcacaagcaaaataata
    1681 2806568 — NO agagcactcaattcgactatccgtccagctttcacagaatttacttctgagcccacaagactcaaattgtataaggatagagtctgtttcattcatcaacatatcc
    agcacctgacatagttttacatggcacagagtgggtgttcaataaatatttgtcaatgattgaacagaaattttcagcaccaaatgaaagaaacacatgactttg
    aacaacggcacgagaataccaactgtttgattatgcaacgacaggatcttttggc
    1682 3385452 — NO agttcctaaatgggaacactgccttatgga
    1683 3968192 — NO gatcaacgcttaattcaaaaccaggctgtagaagaagaagaagaagagctaagaaggttcttagtgctgatggggagaagagaaggttctggagctgtgc
    catccccgggtggaaagagggaatgtgttctttcttcccttgacacttctgtgcagatgaatcaggcaggaatcaagagcggttg
    1684 2397794 — NO cttctgatcaccaagccacatgtgatgactcctgggcccttcttcctgggacaactgcaccagcttctaatcagctcgcccatctcagcctgacccctctctgc
    agcctgaagtccagactctctagcctggcaccatagtcctttccttctctctgacctaatcattaaccataaccc
    1685 2412877 ZCCHC11 YES cgatgtgacattggggatgcttccaggggaagtttatcttcatatg
    1686 2904959 MAPK13 YES gtgggctgtatcatggcagagatgct
    1687 3367083 — NO acagactgacagaggtgcatggtggag
    1688 2762520 — NO tttaccatcgtttcattccatccatcc
    1689 3463535 — NO tgcctgtagctccatacctgtataatcaacagctattaaatatctgctaagcaaactaaactaagcattttcaaaagtaaacttgtgaaacctgatggatttcagta
    gttgacatcagcatctacttttgctgaagtcagtagcctggacattatttatgacacttatttttttttcccatcttgcccttatccattcattcaccaagccttgttgagt
    ttatcactgagtatctcattgccatcacaccaatctaggacaccatcatctcttacataggtgattacaatagcctccacactggcctccctgtctccgtttagctc
    atctcccaatatattttataaaaatgatactgttactttctctgctttaatggcttaccattacctttaaatggagtctgaatcagtggtctccaaaggggggtgatat
    ataagataatctgctagggtgcaggaggaaaatattggaacttttattcatatttacctttttatttgaaaaacactaaggcattaatatttaaaagctactactgtgt
    aatagttatttagtcattccttctttgctctatgtgtcagatggtcatttggtactaaaggtgtcctgagggaagcatgctttgttcactttctgcatgttgcacaatac
    tataatttgaatgtccatctatgcggatttatgagttatctagtttaactattacaaaatatgtaagtctgggattagggaatttgtggagaaaatcaagtgtttaact
    gcaaataagatcacattgttgttcagctggtaagatatacaaaatcaaatctgttctcatgaattaagaaaaattacgctgattttgaggttttaagtgaaacttttta
    aaaaattctcatttttttgtaaggcatccctttctgctttgatagccattaaaaatcaaatattcaaactgatgttagaactagatctttgaatctctgtatcacacggt
    gttaagatcttcagaaataatgaagcatattcaatatttta
    1690 3533262 — NO tgggggagggaggatactactgagcaa
    1691 3651809 — NO caaagatgagaggtgcgaagttgtccaagtccaacagctcaactgaactttcctaagtggaattgtta
    1692 3719905 MLLT6 NO ggttttgcatctcatttacttctccattggttcaggataaag
    1693 3744442 — NO ctgagcgtgccatctcccagtggcc
    1694 3994048 — NO gcaagcagcttgtcagacgtgcatgtggtttgga
    1695 2566874 — NO ttccctccaaagtggaagtgagctggagagatctctgggtctgaaagtcacctgctatgttggaggagggtcaggctttttgaggactactctggtcaaggtc
    tgcagacttgatccctcctttaacccaaatcttattattatggctacacatgtgccacacattatagctccagatactcacgcaaggttc
    1696 3788902 — NO agtttcttttggcaggtggtccagaa
    1697 2684832 VGLL3 NO aacacaaccatttacgatctcagtcagcagatttactctactcaaggaaaaaaagaaacaatcttattggaagcagatgttgacactgtgtcagttattgaagac
    ggaaggagttcacttgagccattgcagttacaaaggggtattgatggcagt
    1698 2808743 — NO ggccaactgtcaagatgttttgaaggccaatctggaagtatatgttaaaataaagatgtgcataatttctaactgagcaactctactttgtggtatttatcctagag
    aaacattcacaattatgcccagagagatatatgtagggtatcccttgctacatggtttataacaaaaaaatatattagccaactagggtccattagg
    1699 3311746 — NO tttcctcagtgcattcttggtggtgagattgattggtgagcatcgtataacccactctgggagcatagcctatttgtatttgtgtatgtctatactttgtgaggtttag
    cccacttc
    1700 2398939 — NO atgaaatggtttggaaaggagcctt
    1701 2948399 — NO agagggcgatcaggtctcattaggccccagggtgtctgaggggtgatctctgccagtggcggtgggcaaggcagaagaggcgtctgctgcagtggaag
    gatcatgacagcctgagttaaattccacctcttctcagctgtgaggtcttgagtaagtgattttgctactctgagtcttagttactttg
    1702 2974531 — NO tctcattttgattctggcagtgggcccaaatgctaagtgtcttgcccaaagtagaaatttccagttgctacttccatggtgtgccgcacaggcaatggctgagtt
    ctt
    1703 3385006 CREBZF NO tctggatgattagcacatggataaaggagatttctggaatataaaatggattgtttttgaaatttctaggtttggctctatttactgtaatggttgaaaacaatttagt
    atttgggtgacccttttgtttttcttctaaatgtgcctctggtaaaatacagaactagactaaagatgtagctttttaatatttgtcttttgatggtggcaggagttcata
    cattaattgaactaacacatcatattttgacctactatttctatcatattgacttactgtttctgcacttctttgaccagacttatc
    1704 3777967 — NO gcgagtgactccgtttctttggacctgcggttgagctggcagcagaatggaggggtccgagaaacgggtgagtgtgaatcccttgcagaaatgctctctgg
    gggtctgcccttgaatgttaggcggcatgacaagtcaaatgcagtccaccagggtc
    1705 2446212 TOR1AIP2 YES atggccgacagtggacttagggaacctcaagagg
    1706 2527475 — NO ccatttgagatgttctccgaggtgg
    1707 3110892 — NO ttggtttcaaatggacagcagcaaa
    1708 3229044 BRD3 NO gatgtttctggtaatcatggacccttctcc
    1709 3518549 MYCBP2 YES caggaccaggttctcggttgtcatctcctaagccaaagactctcccagccaataggtctagcccatcgggtgctagttctccacgctcctcctcaccacatgat
    aaaaatctacctcaaaaaagtactgctcctgttaagacaaagcttgatcctcctcgggaacgttctaaatcagactcttacacacttgatccagataccctccgc
    aagaagaaaatgcccctcacagaacctttgagaggacggtcaacgtcaccaaaaccaaaatcagtaccaaaggattctacagattcccctggatctgaaaa
    tagagctccctctccccatgtggtacaggaaaacctccacagtgaggtggtcgaagtctgcacctcaagta
    1710 3701324 — NO caaattacaattcaggttctgtttgaggtgctcctgagaagaggaaaagagtcagaaacctacacaaagatgtatagaagattaggtcctgagag
    1711 2941831 — NO ttgcgtttacatgacttgagtggcctgtcagtcccgctagtaaagtctcctcatccatccactctgtttaaacaatcaaactctgaaacctgtgtctcctggaccat
    cctataatccctaaaataggctgttatgcttttcacctctgccctactctgttagcactaccaacttattgacctctttcaatcaaatcgttatctaaaggatacctgt
    aactcagataggttgcctactgggcctgtttagtttta
    1712 3403963 — NO ttttttctgcactatggcttgggccc
    1713 2337265 C1orf175 YES gaaaggcaacaacaagcagtcacagggg
    1714 2774211 — NO catcaggagtgtggattctgccattagtacccaacagatcaatgcccagtgtttc
    1715 3626362 ALDH1A2 YES gcttcagaaaggggacgtctgttggataagcttgcagacttggtggaacgggacagggc
    1716 3760869 — NO gagcgtctctccttcaaatacctggatttttttttttttgtacactggttcatagatcggcacttgactttgaacctggcaccaaaaggcacaatatctgataccctgt
    acaagagctattagagatgctgccatatggatgggcaaaactgagccaatcccacttaggaatggaaggcttggacatggaagggaggatataaacgagg
    agttggagaaaaacgcaagcccagtttttgctagagtggaaatgaaagtgggaatgagggtcttgtttttagtcctctaaggaccaggaagcaattttaaaact
    tccttggtttttctgaaagcagcatattcaaaatgccagcaaaaactcctaacaactgcaaaaccaaaagaggatcaaagctcaccaacatcccttcttattgct
    gaaaggctctaaaattcaggatgccctgttcccttgtaaaagggaaaataattaagtctgatttatggtaatcataccacatcacacttctaaaaaaatattcaag
    tgtgtgaccaggggacgtttgacaccatt
    1717 2772067 — NO cctcaaagtgtctaggaggcggtttgatatgcagactaaagtgaga
    1718 3350159 — NO tttacatcatggtgtgtgacaaaacaattgcttccccctcctccctgcccttccccacccctgacttctaagataacta
    1719 3946034 — NO aggtctgcccatcccaaacctgggt
    1720 2699092 — NO gcttcaaacattggcccttcacgtacaacaaactctatcattcgatgtatcagggcgagcaaattcctacaacaacaacacagttaaagaaaatggattcaga
    cctaccactatataaaactacacttgacctaagttactataattgtgcagaaaatgattattctgctgactaacaccgaatttaataccaaaaaagtaacctggag
    catatgttaatgccttgtgcattaagagggtgtggggcagtgggagtagggaagtgggaggggatggaaaggtgagggagggtaggaaaccacaataca
    gcctcatagtaatatttaattttctaaatgtcacttattttccaaaagtaaaacattaaattataaatcacaactaattagaaagctgcaaatattgatatataaaatca
    gtaacttagagcctgcatgttattacagccatcta
    1721 3027187 — NO gttcacggcagctcccaacaggtctgaggtaagacgccgctattatcctcgtttgctgggagaagactcgggcttagagcctctgattacacagctgcactct
    aaccatttcctaata
    1722 3496668 — NO tctcatgtacctcgtagtatacctactatatacccagaaaaattaaaaattaaaaactaaagaaagaaataattgcaaaatgtaataatgtctttgaggggaaaat
    aaaaacttcagtgaaatactctaagaggggtttgatgcagagctgggggatgtgggaaagtagagataggaaagttgaggagggagggatgggttacagt
    ttgccaaggacagaattacttgagagggtgggagcaggacacacatgtcagggcctctggaacaggaagaggttggtttatggcagaaattgaaagaatg
    ctctcatacacagctcactttcctccttgctttttgtctgcatagcattattcaatatgtagcataatataagttgaaatcatatatcacctttgtggtcttctcccacca
    gaaatcaggcattatgaaggcagaagggcagaggtatttgtcgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtttgacttttgtatttttgctgc
    cgtattcctggtacctggaatagcacttggcagacaaatgtatgcaaagttattcaaatccagtgggaccagaccacagtg
    1723 3718614 — NO cagtggggatgtagaatgtgtccaaa
    1724 3759098 — NO ggggcagcacaggtactctgattttggggccacgagggccaaatccgcgcctgcacgtag
    1725 2721510 — NO tattcctggactatagccgctgatctcattgatgcccttcttc
    1726 2938424 — NO ctcaagagtgaacccggaaaggctcctaaggaggtccctgcctcagtccaggcaaggctgtggcctagacgaggtggcg
    1727 3606484 AKAP13 NO tgctgctgcccgcatgggatgcgcaggggaggcgtggggatccgcaggagggtggttgggatacaccggatacctctgctctcattgcttgtttgcaaatg
    ctctatggacatttgtgtgctaaatccta
    1728 3750237 — NO ttcacccacatacaaaatagtgcgcgttttggctacttcagcctcttcccttctctagaaataactcctccttgtacttagtaaaggcacacattcacttcaagagt
    agg
    1729 3320010 — NO caggaggcccgaccaaaagcagatcaaataggagtgacagagttcagagctgcctgggacaaagttttaaattttattttcactgcaacccataggaagata
    aacattttatatcatgacccagcacacaca
    1730 3907649 — NO aggaatgggccgcatggactacctgggggtccccaaggccccagctcctctcctttccgcgccttctcccaacctttattgcagcgtctcctccggcgagac
    gaggccgggcttagaaaaagggcagcgaagacccaggggccaaactggcactgaggagctctggtctctgcgcggcggggcgccctctccgaatcag
    ccccaacaggcgtggcctccgggcttcaggcagcggggtaaggggccaggacacgggcacagggtctgtatgtaaacggtgacagcggc
    1731 2546923 — NO ggctgtgtcacgtggacagtgtcacatctgcgggtggggataacaaggcacctgagtgcgtgaaggagga
    1732 2788764 — NO ccatgggaacagtcttgcagtgatggacggtttccatcccccatcactgacgcgggaataactgtgctgt
    1733 2886332 — NO cttttggcaaaaatgcgggccatggggtgtcaaag
    1734 3307785 — NO aacttcaaactgtgctcatgtgggcacagaagcatcgtgcagggctgcactgtcaccagccccagcagccacagggcagtttgtcaccagctccctgaga
    atcaactccagtgtgatggaggtgaccc
    1735 2339825 — NO tctttaagcgagaagtagatgtggggaggggttgttgcatttttaaagattcctgtattaggccgggtgc
    1736 2922550 — NO gtgaactttgtacttacgtgtgcttttgtggtagcaagtatcatctttctgtttccttttagcatttttggtgtactggtcta
    1737 3319874 IPO7 YES tagcgcacagtttgacatgtcaacaag
    1738 3571362 — NO tgggtactcgagcactgaagcattctcatcacttcccatgaagacactaatcccattaaactaggcattcctctttccctgaggttcgttgatagttgtatcttttgt
    catttcccatagtgggaaaactaaggtccgtggagggggatgtgaatccataatttctcttcaacaaacaggcagcagagccattgtggaatttctagcctaa
    gccataagatttgtggtttgtcctgatgtaagtgcattcactg
    1739 2562256 — NO acaggcgggtatggtaatagcaatctcaggagggctcttctgttgctgtgtagaaaatgaaccaagtagcatagaatcgtgaccagctttccacacctggctg
    gagcactcctggggccttcagtagggacagttac
    1740 2599272 — NO ggaagttactgcttcccctggtgtctgttcttctggcttcagcttcgctggggatggattc
    1741 3019543 — NO gtggccttttaggaactgtagagtaacttaatataagagacattatttggtgggcagaattaagatcttgggagccattgctggtgcaatcctcacttgggaaaa
    tttaacaaaatatagttagaccttttccaggtctcacccattccatt
    1742 3316144 TMEM80 NO gagggccacattcggagcctccgtccactccagttttatcagcttttgccttttgcacggagtgctaaacaaattctagctctgtgtttttttcccattcccagattt
    actatcagttctccttaaaaagtatctaagctgttacagtagctttcccttcacttgattctattgtgtgttttctatgtttggaataattacacccaaatatctagatattt
    tctcttcaccgcattttgtaaata
    1743 3808909 TCF4 YES gtctatgctccatcagcaagcactgccgactacaatagggactcgccaggctatccttcctccaaaccagcaaccagcactttccctagctcc
    1744 2360953 — NO acattctatcagagagtacatgatatcaccatgccttatcattggtgaagttaaccttgaacttggttaaggtgctgtctgccaggcctcttcactgtaaagttact
    gcttttccctcttcatactctgttcttt
    1745 2458084 WDR26 NO cagctgttctaggatcttgtcatttttactgaaagtctcgtgcacatgtgaagtgccctctgagtttaaggtttggttaatactggtatatttttataagattgaaattgt
    gtccccatctttaacttaaacattttcattatcagggtcaatgtgctagaactgaattgtaacatttttaggcacagatggaaaaaaatgttattggctccttgaaaa
    tgtgtgtgtgtggcgaggggaatagatccacaaaagcatgtatgtacttacaaaccaagctgtagagatcaagaaaagaacttaagtgttgatctcaagatttc
    taaattgtcaagatttacatggcattgtggtggaactagttaac
    1746 2775432 — NO tggagaccagataatggatgctggcaagatctgggaatcaaagccatggaaagggtgccattggtcag
    1747 3577885 DICER1 YES tagataatatgttaatggggtcaggagcttttg
    1748 2413468 TMEM48 YES gctggaggatagttgcaagtattgtttggtcagtgctatttctacccatctgcaccacagtatttataattttcagcaggattgatttgtttcatcctatacagtggct
    1749 2478883 — NO tgaacagacctcaatgtcagacaagccaggggagcctgc
    1750 2783808 — NO atatttttaatggtgtcagccaggcaaa
    1751 2406967 — NO ctcctgtgactcagagccctcggctt
    1752 2436718 UBE2Q1 NO tgctgtatttggatctcacgctgcctctgtggttccctccctcatttttcctggacgtgatagctctgcctattgcaggacaatgatggctattctaaacgctaagg
    aaaaaaaacaaacacagaactgtttcaagtactcaagactgacttacagaccaaccaaccaccttgctggaacccttgctagcaggcattcttataaaagaaa
    ctttcgagcctccttatattgctggaaactcagctgtgctccagactagagcctccttacctatgctatgga
    1753 2663594 — NO ggcatcttatttcacgcaccacaggcccttgttcttcccagatgtcagcaggctttctccaataaatgcttcttcatttgctgttgcccttggaatcatcccagaga
    ttttaaacggctgtgtgtatgtttcatggggaagtctgtggcctccttacactgtcctgcagaactggcacctccggctgtttt
    1754 2854791 — NO tttagaattgactgaggagcggccgggtgcggaggctcacatctgtaatcccacacgccttgggaggctctgaggcgggtagatcacctgaggtcaggag
    tttgagaccagcctggccaacatggcgaaaccccgtctccactaaaaatacaaaaattagccaggtgcagtggcacacacctgtaatcccagctactccga
    aggctgaggcaggaggatcacctgagcccaggaagttgagactgcagtgagctgagattgcaccactgcactccagcctcagtgacagcgagactgtct
    caaaaaaagaaaaaagtgactgaggaggaagaggccaggtggcaaatggaacagaatcaccaaagggtgaacaggactaaggcaatgtagtgtatgg
    ctcagctacgtcagagtggaaaaggtgttattagagcagaaactatggtccctgcgtcacagggaagcaacctacagagaagcagcagctccccaagag
    aggagagataagaagccagaagcctcagagtgaacaattgtccta
    1755 3350791 SIDT2 NO tcagagtttggtgtattagaggaactgccagttgttcatactggctaggcagggccttacatttgaggggagaagggtgagagattgagctgggtggagga
    ggacatgaaggcctttgggtgccat
    1756 3447872 KRAS NO catcttcagtgccagtcttgggcaaaattgtgcaagaggtgaagtttatatttgaatatccattctcgttttaggactcttcttccatattagtgtcatcttgcctccct
    accttccacatgccccatgacttgatgcagttttaatacttgtaattcccctaaccataagatttactgctgctgtggatatctccatgaagttttcccactgagtca
    catcaga
    1757 3709501 — NO gtccagtgcctcataacatggtctcaagctcttaacaaatggagcccaggattcaaaaatctgaactctaataatggcttgtcattctggtttcttacccttgagg
    aacctgtgaggtgttaaccaacctgtaagctgcattccagcactggcaaacctggcctctcaaatatccagccaattctaagtttggtgccagga
    1758 3606344 — NO gaaaaaattgtcagttgcagggatacatttctcactaatgaagaaacatggaaaatatctgtgtaaggggatcacgctgtttcttaagttcagattattggaaga
    gggtggtgatgtaggtgtgtactcttcctgaggttg
    1759 3884906 FAM83D YES ttctgtctggccaagtggttgaacactttgatctggagttccgaatcctgtatgcccagtccaagcccatcagccccaaactcctgtctcacttccagagcagc
    aacaagtttgatcacctcaccaaccgaaaaccacagtccaaggagctcaccctgggcaacctgctgcggatgcggctggctaggctgtcaagtactccc
    1760 3919041 SLC5A3 NO ttggaaacagaaacgaggcttattgctattgcagaaatcccaaactggcaaaggccagtatatatggtattccataatataaccagcttttgaaatttatgtgttt
    ggattagtgccttctggttaccagtattgactctgctagtttgcacctttccgttctta
    1761 2847683 — NO ctgggaggctttcagatgcagcatccaccaaggaatacaccgactaacacacatgacagcctgaactagcaacctgcatcaacacccctgcagaaaagca
    gtgcatttcaactgctcatttaataagtatttgaattcataattacaaaacatcttctgtaattaaaccaccatatgcatttaaaatattttggggacaaagagtagca
    aagaattatattggatattgactaaaaacacttatgaatatcaataatttgctcctcctcccttttcatcatagactctttacaatgatactgaccttggggttg
    1762 3776975 — NO tttgcaacccaacctgctggaagtgcaaagttcagaccagcagcaagaactcttgccccatgcttctgctgacat
    1763 3543413 RBM25 YES atctcgaaccagtggagcgcactcgtaacctggatcccagaaggtcgcgaaggcagtaccgtttcctcagcggc
    1764 3653407 — NO ttgagtgtggtagtgtccgtctgtagtcccagcaactcaggaggttggggcaggaggatcacttgagcccaggagttcaaggctgcagtgagctataattgc
    accattgcactcaagctcaggcaacagagtgagaccttgtctcaaaaaaaaaaaaaaaaatttaaacaagcgacagtaatatttcattagaaatgtgatgaat
    gctatgaaggtgtagaggatgtctttagaatatataactgggagggagaccttttgagttaaggcaggtgctggtcaggaaagtcctgaggaagttacatttg
    gattga
    1765 3670580 — NO gtgaaagactaaacagacgacttcaaaactctcatccaacatccaagagttctgccatttccaagattcagcaatcctc
    1766 3767260 — NO taccagttagtacaaagatcacagccaatatagaacctaaaagtattcacaatgaaaatgacaatgtagttgtcgttttgagctgcatggtacttaaatctg
    1767 2456432 — NO cacctgctccgagggtcagggctaagtggtttgagcaagtggcaagctcacaggtccagttggctgagggcctgacccatgacgatccattt
    1768 2750681 — NO tatgacactgaatacgggaaagtgatgggagtgaggctggttaaaatttttcacccacgcagtctccctgtgtt
    1769 3071991 LOC653852 NO cacgtggtcactgacactcccatggc
    1770 3436046 ATP6V0A2 YES actcggatccgcaccaacaaattcaccgagggatttca
    1771 2383133 — NO tcagccctgtgaagatgtcattccattatcttctgtcttctattgtttctgtggagatggtagctctcagacaaattgttggttgctcgtttgtacatactccccactcc
    catcctgccctgggtactctaacattttttcactttgtgtttagtttcagcagttttaagataacgtgcctaggtcgggc
    1772 2434773 FAM63A NO actttccagccgcagagtagtgcag
    1773 3338526 PPFIA1 YES gtttggagcaatgatcgagtgattcgctggatcctgtcaattggccttaaagaatatgcaaacaatcttatagagagtggtgttcacggagcacttctggcctta
    gatgaaaccttcgacttcagtgcactggcactgctgttacagatcccgacgcagaa
    1774 3671856 KLHL36 YES caggcagacgcgagtgtctcggccatacaagatcagcgaatcatca
    1775 3060641 — NO ctcccatggctggataaaccaaatctgatacatccacatttaaggttgttttccaagttggtttccataaaaggcctttaacaataataggcttttaacaacaaaaa
    ggtatccctcccatcacaatgagagcttgatgagggctcaaaagtgacttcaaaaactgtaaataattattttccttggacggctttaaaaacagctactgatag
    caaatcagaaacactaaagaaaaaagacaataaggaaacagctgtttgtctagtgaatccataataaataccaatttgaggctatagattacaaagccaaaat
    attcttataggaaagttaatgtttatatttacaatcccatggactaaaaaaactgtctaatatcttaaagactg agtctacctttatttaacattgtttatacacaaaga
    cccaagggatggtagaattcttgatccttctggacaaaagcatagtgagaggggactgaaattaacaaaaagggaaaattaacattaatctcaaaattctacc
    catcgttgtcttaaaatgatcaagactcagctacatctgagaaaaaggaaaaggatcagaagtgaaagaaatcagaagccagtaattaaaaaaatcataacc
    ttgtgtgctttctactgacggcatttaaa
    1776 3379623 MTL5 NO ctgtgcctaggctgttgacaacttttgctgagttggacagaataagactgtgggccatgctgcttgcttcactctctgggtgtgatggatcggtgagggtgcag
    ttgctatgattgtaattggtcatctcatcatggctgttaacatttctggaccaaacaaaaatgacttcagctacttccagattctgctgatacattacacaggatgat
    ctaaaaggctacagttctgaagatactcatctttcttgtaatctgggggcatctggtcaatagtattgcctctgtgctgtattgtgtctagaacattcaaggacattt
    gatacttctcatactttaattgcgtgctctcccagttgcagcaccctctgaggcttctatgtgttgcagccgatgggcatttgcacagagcagcagtcatgacag
    cgttttcagggcagctatttctccttttcccccttttcctctcccccggcttcccattctcctcctcctccttcctcttctcgtcccctcctcctcctctttgttctcctcc
    ccctgctcttcttcctctctccttttcctccttctgtgtctatactagattattttcaatcagtcacatgtttttctttattttgaatgttacaaaatatttctctattgtaaacg
    gtgtgccaggaaaaacatgagatgtgtatttgtattttttatgcacataattacttaatccaatgcctctccacttaattgggcctgatga
    1777 3547548 — NO ccagtgttgggtgcaaatatacctaggata
    1778 2779848 — NO atgagaagggtattggatacgattaggttagaagctcctagctcctcagtgaagtggtacataagggctctctctgc
    1779 2869655 — NO ttctttttctaccctcactgtcctct
    1780 2964686 — NO tctgagcacacctgtccagagagctc
    1781 4004181 DMD YES ccttcagaaccggaggcaacagttgaatgaaatgttaaaggattcaacacaatggctggaagctaaggaagaagctgagcaggtcttaggacaggccag
    agccaagcttgagtcatggaaggagggtccctatacagtagatgcaatc
    1782 2432028 PDE4DIP YES atgtctaatggatatcgcactctgtcccag
    1783 2443375 F5 YES tactcaagatcaagaagataacggcaattataacacagggctgcaagtctctgtcctctgaaatgtatgtaaagagctataccatccactacagtgagcaggg
    agtggaatggaaaccatacaggctgaaatcctc
    1784 2736714 — NO ttccagagtttgcagggacagttagagtcaatatgaattctcagaataagcactgccagatagtccggaagccctttacaaggaaagtgacatttttgctgtgtt
    ttgaatagtgaacaagaatgtgcaggaagagaatgaaaggatatcactagcagaagaaatgcctctttgtaaaaccatagaaaataactctgagttgccatat
    aggacatatgagaatttcagtgttactgaaacaaaagcttttggaaaaggtatggtgattaaattgggtatacaatctgaaaggtaaattgaggacaacttgtgt
    gccagtttgca
    1785 2969491 — NO ttgtagctgttagaagggatagttctacaaggtatccaaatttcctaagtatatttctttaaattttccttttattgaattttctgtttactggcattagtctcatatcagttt
    tggctacctttagctgcttttgttgaattctatttaataaaggcactgcaagtataaaattattaaaaatagacaagcacaatcctttctctgctaaacaagcttatga
    aaaacctggtgatacccaaagagctacaaaggaaactctcacacttg
    1786 3417650 RBMS2 NO ctgcacttgtggaacatcacatggcaaaaacaggagttttttcgctagactttttttttctttttaaccttattaaaaatgagattggtcctaa
    1787 2586174 — NO ctttgcttataatgttctgtagtgctgatggactgcctgattgtaga
    1788 3777613 — NO aatgctgcaggcatcagtgggagag
    1789 3888166 CSE1L YES tgacatcccgtcttcctatatggccttatttcctcatctccttcagccagtgctttgggaaagaacaggaaatattcctgctctagtgaggcttcttcaagcattctt
    agaacgcggttcaaacacaatagcaagtg
    1790 2332174 CTPS YES tgaattctcaagaaacgtgctgggatggcaag
    1791 2684865 VGLL3 NO agaaccaactacagtcacctctgctacctcagcatgggctggagcctttcatggaacagtagacatagtgcccagcgtgggattcgatacag
    1792 2756426 — NO aggcaatggcgattttaggctctccaggtgattacaatatgcaaccatgctcccaaatgtctgctgtaaaccaacatctttcggaggaccagttgaaaataatat
    ttctcaaattaatgtgaaaagtgtttgctgttgagttgcggcctttcagtcccgcctttgttctctactcaccactgttgagttgtggcctttcagtcccgcctgtgtt
    ctctactcacctctactgcttgttttgctcctgattcaaaccagttccacacatactaagcccactgtgctaggtggcctgaccgtggtgaatattattgtggagg
    aaggactttgctgtaagaaattgcattccccaaaactgaaaccatgatatttactcaactgaggtaaaaaatgaaagactaagggggactcccaagggtcag
    ggcaagaataaataccttggaatattaatacccatctcatgatgcctgagtgtaaatgctcc
    1793 3309131 C10orf46 NO ggaaatgctaatttgagcttcattcataggggaacctactatatattgcatccctgctggttggaaattatcttcatctctggactgcattgtttagaaaaatgttaat
    ggcttacaattctgagaactttattgtgtggctctg
    1794 3435688 ARL6IP4 YES ctgacggatgagcagaagtcccgaatccaggccat
    1795 3544550 LOC731223 YES tggaaagctttgaagacggcggttctggg
    1796 3737293 KIAA1618 YES tgaaggcattgtctgcatttccaagaagcacctagataaatacattccttacaagtacgtcatttataatggggaatcttttgagtatgagttcatttacaagcacc
    agcagaagaagggcgagtacgtcaacc
    1797 2769855 — NO ttagtttgggtctgatctttgtttc
    1798 2914869 — NO cttccttgtggaagttggcttgatg
    1799 2754682 — NO acagagcccgagcttttgtcctgcaggctcaagcttctagattcgtcttctcgttaatgcggggacggac
    1800 2353146 — NO ttccagcaggcaccgaaaaagccctgtgagcttctctctgagcggtggagaactgcacatgtatggatgttgctgcttcc
    1801 2685210 — NO atatttgagtgtcttattggacttggaacttccaccagtatctccagaattattgtctgtctgcag
    1802 2774664 — NO agttttggttccgacaagctgcaccattccaactgcc
    1803 2517907 — NO tacacaaattgaacgcggtagggtgggggaggaagtagggagataaagcctatgctgctgattcctcaattataggagcagtctctaaaagccctcgtcaat
    ctagtgatgtgt
    1804 3156168 — NO gtgcaagctgtgtagtggatcattgagtgt
    1805 3359979 NUP98 YES ggactctttggaaccacaaataccacctctaatccttttggcagcacatctggctccctctttgggccaagtagttttacagctgctcctactgggactactatta
    1806 3701355 — NO tcaataaaagttgtattgagatgtgattcacatactgtacaatttatccctttaaaatatgcaattcggtagtttttagtgcattcacagagttgtgcagccattatcgt
    aatcagtt
    1807 2329396 HMGB4 YES gtcagctagaaaccggtgcagagggaaaag
    1808 3290788 CCDC6 NO tccatgctcaagagccattgtaagagattaaggggtttctaggtttttggtgattttttgtttgtttttttctttgttttttttgggtttttttttcttctttaattttttgattaaaa
    catacacacagctgttagcataaagtcgtggggggcattttctggaatgctcagcagttctgattaactgccaagcccaggttgcctctcatgaggcaactga
    aaaaatcctgtgtcttgatagcatgggtgc
    1809 3449856 — NO ctttgactccattgtctgctttggct
    1810 3573894 DIO2 YES aggggaaccagagcgcacaagggaa
    1811 3670649 — NO ccacgttgtcaagcacagaactataaaaacaatggattcagtgggtgaaggtaggagaaggggttcaagagattcagacttacagtaggaaagttatttttcc
    aatctcagtaagttttttagggttatgaagattgagcactgacgacgctgaaataccacagtgcaaatgcttccgtagattccctgggctctgcactcaccagat
    ccatttctatgataaagcacagagctcctcaaacagaacagtcgagttgcaggctcagcagcctccttgtcagtgtcctgctcaactcagc
    1812 3851066 — NO tgcagtgcctggatcataactctggatcatcactgaaacct
    1813 3912092 SYCP2 YES tccttgggagacctggcaaaatgaat
    1814 2626159 RPP14 NO tctacttttaatcaggcgtggcagc
    1815 3448099 BHLHE41 NO caccagctgtaaaagatcctatgcgaaagacactggctcttttttttaatcccccaaataaattttgcccccttttaggccatgttccattatctcttaaaattggaa
    cctaattcgagaggaagtaagaagggtctgttctgtggctgagctaggtgaaccccggggtaggggaaagatgttaacacctttgacgtctttggagttgac
    atggaacagcaggtagttgttatgtagagctagttctcaaagctgccctgcctgttttaggaggcgttccacaaacagattgaggctcttttagaattgaatttac
    tcttcagtattttctaatgttcagctttctaaaaggcatatatttttcaaagaagtgaggatgcagtttctcacgttgcaacctattctgaagtggtttaaatggtatct
    cttagtaacttgcactcgttaaagaaacacggagctgggccatcgtcagaactaagtcagggaaggagatggatgagaaggccagaatcattcctagtaca
    tttgctaacactttattgagaaattgaccatgaattaatggactcatcttaatttcttctaagtccatatatagatagatatctatctgtacagatttctatttatccatag
    ataggtatctatacatacacatctcaagtgcatctattcccactctcattaatccatcatgttcctaaatttttgtaatcttactgtaaaaaaaagtgcactgaacttca
    aaacaaaacaaaaaacaacaacaacaaaaaacaagtccaaactgatatatcctatattctgttaaaattcaaaagtgaacgaaagcatttaactggccagtttt
    gattgcaaatgctgtaaagatatagaatgaagtcctgtgaggccttcctatctccaagtctatgtattttctggagaccaaaccagataccagataatcacaaag
    aaagcttttttaataaggcttaaaccaagaccttgtctagatatttttagtttgttgccaaggtag
    1816 3872452 ZNF552 YES agcacgagagactgctccctacagaagaaccttctgtgtggtgtgaatgtgggaaatcctctagcaaatatgacagc ttcagtaatcatcaaggagttcacac
    tagagaaaaaccttatacgtgtgggatatgtgggaaattatttaacagtaagtcccacctccttgtacaccagagaattcacactggagagaagccatatgagt
    gtgaggtttgtcagaaattttttaggcacaagtaccacctcattgcacaccagagagttcacactggagaaaggccatatgaatgcagtgattgtgggaagtc
    atttacccacagctctacattccgtgttcataagagagttcacactggtcagaagccttatgagtgcagtgaatgtgggaaatcttttgccgaaagctccagtct
    cactaaacacaggagagttcacactggagaaaagccttacgggtgcagtgaatgtgaaaaaaaatttaggcaaatctcttcacttcgtcatc
    1817 2489627 POLE4 NO gtgttctgcataagtggcttcctga
    1818 2934111 — NO tcaagattatatatggcagatgaggataa
    1819 3181290 TMOD1 NO gtaatggcccagcttagagacttcagctactgatctcatcacttattagacaaattgctgctgaccttacgcctgtatattaagcctccgcaggatgccggacaa
    tggtgaagaaactccagatatcaaggaattgggaaatcctggccaaaccaccccaagatgattacactgaaatgtagtattagtactgctgccagatctcttttt
    aacatcatgtgcgtctcttgggatccagcaaaagtgttaagccacaatgcccttgtgccttttaatataccacagtgccagttaaactaatatttttgtttgttgcttt
    tgggagttattttcattagtgatttcagcaaatctcatgataaaggacaaggtcaagaactccagagcactgagcagagaggctggtgatgaaaaggtgaag
    gcctgcgcactgaactgtaa
    1820 3487237 AKAP11 YES aatgttccctgtgccaagttcacaagtg
    1821 4009127 JARID1C YES tgagtgtccccccacagtagtggtgaaggaggagttaggtggggatgtgaaggtggagtcaacatcgcctaagaccttcctggagagcaaggaggagct
    gagtcacagcccagaaccctgcaccaagatgaccatgaggctacgga
    1822 2750647 — NO tgagtacagcccactgattgacattcaagacccattggaaaaatcaggagacacaagagtgggaagagtgcagattggagcagctatccaaaaataca
    1823 2916198 ZNF292 YES gggctggacttgctacctgtatagaactgtgtgtaaaggctcttcgcttggagtctacagaaaatactgaagtgaaaatatctatttgcaagaccatttcatgttt
    gttgcctgatgatctggaagttaaacgtgcttgtcaactgagtgaatttcttattgagcctacagtagatgcgtattatgctgtggaaatgttgtataatcagccag
    accagaaatatgatgaagagaatcttccaataccaaattctttacgctgtgagctgttacttgtattgaaaactcaatggccctttgatccagaaactgggattg
    gaaaaccttgaaacgacaatgtcttgcattaatgggagaagaagcatccattgtgtcttcaatagatgaactaaatgacagtgaagtatatgaaaaagtggta
    gactaccaagaagagagtaaagaaacttctatgaatgggctttctggtggagttggtgctaattctggccttcttaaagacattggtgatgaaaagcagaaga
    agagagagataaaacagttaagagagaggggatttatatctgctcggtttaggaattggcaagcctacatgcagtattgtgtgttgtgtgacaaagaattcctt
    ggtcacagaatagtacgacatgctcagaaacattacaaagatggaatttatagttgccccatatgtgcaaagaactttaattctaaagaaacttttgtccctcatg
    tcacactgcatgttaaacaatctagtaaagagagactagcagctatgaaaccattaagaagattgggaaggcctccaaagatcacaactaccaatgaaaatc
    agaagactaatactgtggctaaacaggagcagcgacctataaaaaagaatagtctctattcaacagattttatagtgtttaatgacaatgatggttcagatgatg
    agaatgatgacaaagataaatcctatgagccagaagtgattccagtccagaaaccagtacctgttaatgaatttaattgccc
    1824 2984592 SFT2D1 YES tggcttccgggcggcataaagctttttgcagtgttttataccctcggcaatcttgctgcgttagccag
    1825 3123564 — NO cagttcattccgtttccacctggcagctgctccctctgacacccaaggactcgcagggagtggccgttggacctgcagacc
    1826 3165879 TEK NO gtagcagccagtcccgtttcatttagtcatgtgaccactctgtcttgtgtttccacagcctgcaagtcagtccaggatgctaacatctaaaaatagacttaaatct
    cattgcttacaagcctaagaatctttagagaagtatacataagtttaggataaaataatgggattttcttttcttttctctggtaatattgacttgtatattttaagaaat
    aacagaaagcctgggtgacatttgggagacatgtgacatttatatattgaattaatatccctacatgtattgcacattgtaaaaagttttagttttgatgagttgtga
    gtttaccttgtatactgtaggcacactttgcactgatatatcatg
    1827 3887555 — NO tccattccaggattggtgctgaagcacatgtgtcctgaagttcaggacgtcagggtaattgacacagaagaaa
    1828 2356740 — NO tataatctagaaacattcttcagcgttttttttctttcattacatgaagagtcaagaccagtggttttgtggaatgcatgataatctgggttcttaaaaatcatttcttctt
    gattagatttcccattgtcttgaattgactcagtcagcctttcctcaccgctactccaggttcactaatg
    1829 2665536 C3orf48 YES gagaatggataggcttttaggtcttggaagaaaagaagtgtccagggttcaatggagtggctgctct
    1830 2833553 — NO ttttggggatgacattgtggaaagtttaccctca
    1831 3242698 — NO tgtaatacctcatcatagatatttggggtgcccttca
    1832 3911222 PMEPA1 NO gaagttctagccactcgagctcatgcatgtgaaacgtgtgctttacgaaggtggcagctgacagacgtgggctctgcatgccgccagcctagtagaaagttc
    tcgttcattggcaacagcagaacctgcctctccgtgaagtcgtcagcctaaaatttgtttctctcttgaagaggattctttgaaaaggtcctgcagagaaatcag
    tacaggttatcccgaaaggta
    1833 2676501 — NO attgaagaaccgctgctggagaact
    1834 2839345 — NO gcagccttattcagcaacgctggggatgacaacatg
    1835 3239038 — NO gaataagcagaaacggctgggcgtg
    1836 3475695 ZCCHC8 YES cctcggaatgctgctcgaataagtgaaaagagaaaagagtatatggatgcctgtggagaagcaaacaatcagaatttccagcagcgataccacgcagaag
    aagta
    1837 3563672 — NO gttctgaggcccagcaactctgaga
    1838 2333149 CDC20 YES acctgaaccttgtggattggagttctgggaatgtactggccgtggcactggacaacagtgtgtacctgtggagtgcaagctctggtgacatcctgcagctttt
    gcaaatggagcagcctggggaatatatatcctctgtggcctg
    1839 3740914 — NO ctggtgaggagccgcaactgggcatctcc
    1840 3949524 — NO ataaaacatctttgacgtgggagctgcagtactg
    1841 2598329 FN1 YES cattgtctccaccaacaaacttgcatctggag
    1842 2354732 — NO gggtgtcatggaatcttaggagccctgcattccaattgcccaggctt
    1843 2534399 — NO cagaatgatggagtttgcatggcacagt
    1844 2677654 C3orf63 NO cagtacctgcgcaatccttgatttaatgaaattaaattttttatttcaaaagataggcttctgtttatcaaaggcgttgaacaatttgatttttaaattagattttgcaaa
    atggaagtataatgggaatatatttttgaggtggtcttagtagtaattaccatttgttgaacacattaatgctatactagacagatacagtggagatagctttcaaa
    cccgtatctattcctaactactgcctctaatactaattactaacttgttactaatgctaacttttaaaaatgtttttgaaaattgcaatttctacaaataaatgtcatagtg
    caaataaatgtcaggatttagagaaggagcctaaactgaatttgtgttatttcagtaaaagttatggagttatgggtctagacgtgttaataagttagacagaact
    ttggcactttagaacaaatgcatgagtggtatttcagttcctaagttacataaaaagtgtgaaagaacactgtgaggtcccagcaacgccagactatattaagg
    taagtagaaagtgtttttatagggcttcaatacccaggtggtgacagagcagaagaaccggtttttttttttttttttttactactaagcttttacaaaagaagtatctg
    ttttattgtatagaacaagtacagcattttactacatagtatacaagtttttaatgagcatttaaaaaaataagtaaatctaggctatttgaaaaatacagttgagcca
    gtgagcacattttataatttggaagacacaaatcaaatgtgaaggatttgattttctacatttaaaatgaagaaccaaaactctcttcttgattttcagctaaaggca
    ggagactactttccaactccttttgcttctggagaaggccctgaaatcacattgatatatgtttgttagtaaaatgtgcacacctgacttgcaatgttgtgttaaact
    agaattatattcacttggaaaacatatcgcttaggataaaattttgtca
    1845 2495347 — NO agaaagtcttaatgggagagtgcccatggtatat
    1846 3436411 — NO caccatccttgaggggtcgagccaggactggaacctcagtccggccactacaacttcataaataccatcgccctgagatgctgaaatcccaggggccccc
    caccctcagaccaggtgccggtattg
    1847 3630941 — NO tccctggtatgtacacgcattcctgtgttttgtgaaaaaccgacaccatgctcctccctcactacatgtaaaacacttttattcattaaaaagaaaactgactggct
    tggacctacaaattagtttcattatttgttaatgtttgaaagccattaaaagatgaatattaaggtttctttatactcaatacttgtagttttgtttgggggaatgagag
    gatgcccttggtacctttgtgaggcctctccactgagggtcaatcatgacttctgttttaaaccagcccatcccatcttctccagctgctctccttatgtcttgcttct
    ctcccctccaaccttctcagcataaggactcaatcctaggctcctaccccagacgggtgccttccaacgttcctggtgc
    1848 3886257 — NO cacttgggttggaaactctggcttctttccccccatggcctgtttggctcacaggtgccaccagcctcaccttgatccactgtcacttgtgcttactcggtgttag
    ctgctttgcctcctttcagtccctcgaaccctgagctcttctcagagctcctagtgctcctctgtcggcctgcagtgcactcccgcttgtgcctattgtgta
    1849 4004292 — NO aggatgaattctcaccaaccatatattattttccgataacagtgtttggtagtgagggggatctattgctaggtaaaatacgatggattcaaggagcttactgtttg
    atgatagggcaagatgtgttcatggatactagattgaga
    1850 2960481 — NO ttggagccagtcaggcttttgtttagacattttaactttttcttgctttccttgcaaactcctcagccttcagactggttggaaagtaaatgtacaatcttacataaattt
    tcaggtaatagcatttcagctttttccccaagattttttgcttgggaggagacagattagactggattcggagtcttgattttgcaaaggtaacaaaagacatgttt
    ttttataagacttttcatcataagtttattttattcaacagaagcaaaatctaatataatggaaaaaataaagatctgtgataaatctgatctgtgtggataaacacaa
    ttagaaagacttaaagattaagtattgaaacaaactaccaaaatattttaatactgatttgtaaaaatttcagtacatttttctcttgcttaattctactgggtcctgttt
    1851 2977359 — NO tagtcattggtgaagcaggattccaa
    1852 3199214 — NO tcaggcttctgttgcaagccaatgtagggaacca
    1853 2743060 — NO ttcctgagttcaagatatagttaagtttaaataataggacttgtgtatgaattggatggtgtgggagggaaatcaaaagttctgggccgggcgcagtggctcac
    gcctgtaatcccagcactttgggagtctgaggcgggcagatcacaaggtcaggagattgagaccatcctggctaacacgctgaaaccccatctctactaaa
    gatacaacaaaatccgggcgtgg
    1854 2811122 — NO aggagttctccacatactctgcccaccctgatagcaactgaggtaggccagaaacactcatgcactggttacctcctgagccatccacagaaagggtca
    1855 3560070 — NO gtgtgatcaaaaaagtggtcagtgtgaa
    1856 2597541 — NO acattgaaattcaagatgcaggcagagaaagaggacatagaccagat
    1857 3747622 — NO gcgcgtgctcaacttggatgggacacacctagtctttcttcaagtccctggattcaaagagcttcaaccgttcttgcaccgtcaggc
    1858 2332216 — NO ttgattcatcctatccgtgagcgtgg
    1859 3029849 — NO gctggcaccccagaagaagctagctcagcatgtgcgggtc
    1860 3090304 ADAMDEC1 YES atacattgatctctatttggtgctgga
    1861 3441298 — NO actatctgaaaatgggcaggtggtgca
    1862 3584491 — NO tgcgatctccgctcaaaaagatacttttgaatccttttcaaaagtaatttgtgtttcattttttaattagtatgataagcacttcaagaccctttacaattctggctagat
    ttggttgccatatttaatagcattttataaataatggagaaaagggaaacattatgcatgcttgattacggtcatgagctgcattaacaattccgttcaacaacaga
    ctgcatatgtcagagcagtcccttaagattacaaa
    1863 2775809 SEC31A YES gtaaactttgaggatgattctcgtggaaaataccttgaacttctaggataca
    1864 3380586 SHANK2 YES tttcgatacaagaagcgggtgtataaacaagccagtctcgatgagaaacagttggccaagctccacacgaag
    1865 3410510 — NO tgtgtcccgcagctcaatcagacttctggatgccatcaaggaggtctgcatgacctaaggatcattgttctttgaaaggaaaacaagttcattaatcttactggc
    tgccagggttaggatgcaaagttaatcaattattagtgactaccgtctaccgaatgactacgtgcaagcagtcatgcatggaggaagaaaaggacaaagag
    aaaggaaaataagtaaaaaacaaacgtttaatgattttgataatataggctcagttacatcaccacaaaca
    1866 3266758 — NO gttctggaactcttcacacctgtgacctgcat
    1867 3878506 SEC23B YES gaaactggagcacccatcctaactgatgatgt
    1868 3189392 — NO tgcaagattcttggatcctcgtccggtacattttggctgcattttatgtgacgtttgtgagggggttagaaatactttaaaatttcagggaacttgaataacaatga
    aagatgtgcagctagtccaaacagatggacttcagtagcaattccaggggcgtttc
    1869 3737624 KIAA1330 YES ctccctgcagaagcgtcccgacggccacatcgtgagtgtgag
    1870 2587558 SP3 NO tagccgctctcgaaaacctacgctgccacggccgctcattgtctctccccttccacccgggggcaaacaggaagcgcgccgcctggcagaccgacggac
    aggcgcctggaccaatgagcacagccgacaaagagcacggcggcgaatga
    1871 2636399 BOC YES gccctacgtggtgtcgggctacagcggtcgcgtgtacgagaggcccgtggcaggtccttatatcaccttcacggatgcggtcaatgagaccaccatcatgc
    tcaagtgg
    1872 3383004 RSF1 YES aactgccagtcatagtgaagctagaaaaacctttgccagaaaatgaagaaaaaaagattatcaaagaagaaagtgattccttcaaggaaaatgtcaaaccca
    ttaaagttgaggtgaaggaatgtagagcagatcctaaagataccaaaagtagcatggagaagccagtggcacaggagcctgaaaggatcgaatttggtgg
    caatattaaatcttctcacgaaattactgagaaatctactgaagaaactgagaaacttaaaaatgaccagcaggccaagataccactaaaaaaacgagaaatt
    aaactgagtgatgattttgacagtccagtcaagggacctttgtgtaaatcagttactccaacaaaagagttttgaaagatgaaataaaacaagaggaagaga
    cttgtaaaaggatctctacaatcactgctttgggtcatgaagggaaa
    1873 3959450 — NO tgtttttatcacagggccgtcgttgaagcatgtatgactatgtgtgtgaaaatgttctgcaaaccaaaaagggctcaggtgctataatt
    1874 3984482 SRPX2 YES gatgagatgccacgcactaccattcatcactagtggcacttacacctgcacaaatggagtgcttcttgactctcgctgtgacta
    1875 2333884 — NO ttgtagagtatgaacactcctttactttcagcaacgtcggcatctccaaataa
    1876 3392870 — NO atgcatgagggcacgcctcctactttc
    1877 2395894 CLSTN1 NO gccgcgcggtttcccttcgcagatgtgtat
    1878 2701311 — NO attgagcctgcccatcatgcattgcaacaggaaggtggatttgaaaagggaaaagaattaaaacatcccatcacacgtgtaat
    1879 2976681 — NO cagatacgggtgtgtacttgaatcaaggagaggcagtagagcagccttatgttttgttccccaaagagtgagatgtgtacccaattcttgcacatagtgaaga
    agctgttctcttttttgttgtttgtcacatctgattattcatggagaaagttgcagcttggggctagtaaaatttttttttaacaccgttctcatattatttgctctcttctttt
    aataaaggacagataggccttgatgtggctgtaa
    1880 3398768 — NO gcaactttcagtggaggcgctgagagcaaattgcagcagagatgcgctcagggtgcagtaacaaggaaggacccgctctccgtgtcagtggcctgcagg
    ggaagtgagaaccgggctcatgctgggctcctctactttgcagggtttaaggccg
    1881 2376766 SRGAP2 YES actacagcatgaaggaattttccgggtgtcaggatccca
    1882 2648351 — NO ggagcagcttcaatcaaaaggcggggctt
    1883 2855376 FLJ32255 NO ccttttctgggggatcctaggcagaagcgatggcaggacaa
    1884 3715585 — NO aatcaccatgacaggcagagtgtgggca
    1885 2432021 — NO agtttagttctcttacgtgtggctagccaat
    1886 2527209 RPL37A NO tttttataatgtgtctaggctgggt
    1887 3753258 — NO ttgagctgcccaagccacctagagg
    1888 2607727 — NO gctgtgcgaatggactcagctgcccgaactcacagaatatcagtaacagcaccgaaacttcaca
    1889 2970557 HDAC2 YES gctgtcaattttccaatgagagatggtatagatgatgagtcatatgggcagatatttaagcct
    1890 3233715 LOC399715 NO ccttctgcaaatggggatgagtcctc
    1891 2555212 PUS10 YES catgctgcatggttgctggtaaaaca
    1892 2601671 DOCK10 YES tatcctggtggagcagctatacatgtgtgtggagtttctctggaagtctgagcgatatgaactcattgctgatgtcaacaagcccatcattgctgtctttgag
    1893 3630677 CALML4 NO tgggcctgaaaacttggagcaattaattttttttaaaaagtgttcttttcacttgggagagatggcaaacacagtggcaagacaacattacccaactatagaaga
    gaggctaactagcaacaataatagatgatttcagccatggtatgagtagatcttta
    1894 2677724 ARHGEF3 NO ggcgccatcagccacttttagaagccatcagccagtgtgttgggaaaagaggtttgtcaagtgttggcctatgggaaggtggtcaatgaatgttttga
    1895 2898386 — NO tggaggcatttaatggcgatgtgcaggtgcaag
    1896 3412766 ARID2 NO catccacctcgaaagctgggcattaacgatattgaaggacagcgggtacttcagattgcagtgattttgagaaatctttcctttgaggagggcaatgttaagct
    cttggcagctaatcgtacctgtc
    1897 3975856 — NO tggaatgtacctggaatagggaagtggacagtgagggc
    1898 2466297 — NO ccaggtcgcacatcagctgcaggcacagccagttcatgggtagacagccacatcctgccccaggaggagggcagccagcatgggcgatgcaagctcc
    cctcgtctggaaccagcacaacctcaggcactcgagccttggcccctcacaagcaacgtcctcaatgggtggcgttcgttcat
    1899 3240817 — NO tccatcgattgactgcgaggggctagggttcacagcaagcagaacgtcctgggtttctcttcaataccacctcctcctctcctgttcagatgctgagaaacatc
    tggcgcagtagagatgctgcctctgacatttctatgacaaaacgcgtgcctgtgctagggtttgcacaggcacaagttatcacaacctcgggatggggctg
    1900 3454311 LASS5 YES catcacttggtcaccattgggcttatctccttctcctacatcaacaatatggttcgagtgggaactctgatcatgtgtctaca
    1901 2437092 DPM3 NO gggagtgggtctcaaatatagagggggtagcaaggtggaaggggcccttccaccttttgtgggcactcaagttcggacctctgggatcggcgattccc
    1902 2683293 — NO catctgtgcttgacgcagaggcctccggggtcgcgagcttcggaggtggaggtgccccgtcttcgggttcccacgccgccctggcgacctggggctcca
    gccccaccgcggactccggtgggacgtgggtggcgcaagcacaccttgcccctgtgactcagcttgagggggcccaagctgtcccactgagcacgcgc
    ccagcaggccgtcgcgctgcgggtcctggtcctcctgtcatttactggggtgcggaggcctccgaggagtctgagggtgggacagtcccacttccggag
    gagctagggcagggaacacaaagtcccgagtgccggggca
    1903 3701415 — NO ccataaaattcgcatggtgaaatgcacgtaacataaaatttaccatcttaaccatttaaatgcacagttcagtggtatcagatacattaata
    1904 2590322 — NO ctagaattaagatatgctgatgagttgcttctgcagttcat
    1905 2973489 — NO tttggcgtttgctacagaatggtgaatttatgtatttctcttccactttgacatggacattgcctcattcttcagtagtgtgcatattcaccttaatttattcaaaagctat
    tttacctttttcaataacaccacatcaattaccttaacttattcacttacatcagtcttccc
    1906 3020769 — NO ggatgcaggactgagtcatgccact
    1907 2807755 — NO gagtagatgtaactaagaggtttgagaaaggaatttcagcagagttattgaaggagaagtcaaggagaggagaaggagaggagcagtgaatgttgtcgtg
    aagaggtgttgtcttgaaatactg
    1908 2918704 PRDM13 YES ctctggagtggatagggttaatccgggcagccagaaactcccag
    1909 3024096 — NO taacaatatgtgcaggcaggaccgaaaa
    1910 3270274 — NO gggcgctttcccactgttctagacgtaggagagaaagcacttctcagatggtgagcttttatcttccaatcttgtcaaccgaggagacctggaagttccctttca
    acctggaatgtgagccctgcttgctgggcacgagataaggaccaaggattgacccaggacaatttcagagagcacaggggtggcatatcctcatgtcagg
    gcgtggagctaatattcaga
    1911 3356025 — NO atggcccagaatgggttgtcagtgctccag
    1912 3913713 YTHDF1 NO ggaccgttgagctcactaccacctggagtttgagttgaagcatgaaaatggtgcccatgcctgacgctccagcgcctggatctgcacgtgcccttgtagagg
    atccttaccgtcctagagagcagacgctactgaaaactacttgctccaaaagaccctctgagttaacgatcagctgtatcattagacttgtatttagagcgtgtc
    acttcctctgaactgtta
    1913 3506761 — NO tgtagtgttgctgtatcttccatcgtacagtggaatggcatcttacagaaggggtttcggtcctatggttagcttaatgttgaagtcagggaaagtcaaaatcacc
    attggaactcccttcaactgtctataaaatacactatgcacagtaccttggtttacgtatatttgcataaatacatactttgtatagtcacatgttgtatgacaacttac
    tgagttgttcgatgaacaactctatgtgctaataataattttgatgtattaaaatgggaaagcatttgcttaactgagtggagaggcacaggttgctgagtcagac
    gtatctcctgttgcacacgtaccttcaggatgg
    1914 3888725 PTPN1 YES gcagatcgacaagtccgggagctggg
    1915 3357756 — NO tctgtccagagtgcaaggccgaaccagaggacacacatgatcatttctattttagaaacacgcctggggcagagaggacagcaggtgaaagagactgag
    agagaacagtcagaggctagtactggccaagacaggagagtgagggagcaaccgtaatgaggatggatgaataatttgagagagatttaggggtaacga
    accagactcactc
    1916 2371244 — NO atgagctcaccttgcctgcaactgtctct
    1917 2660674 — NO tgcccatttttctacggcttgttgatttcttgggagttccttgtaagctttatagtctctgtaattaatgagttccaaacatttttcctagtttgtcttttgtcttttgtttttgg
    tgtggtgtgtcaaacagaactgtttttttgttgttgttcttacatagtttaatttttaatgcttctgtattctaaatcatagccaaaaatgacgttcccatgcaaaggaat
    gtctcatgttttctttggatacttgctgtggtttcattacttttccgtggaaagctctgatccttgtgcagttgatcctgatataa
    1918 3199144 — NO tagaatgtttgtatattgctgcctggc
    1919 2411720 — NO agatccaattagagccagggtcagg
    1920 2682075 — NO tgataatagggacgttgtcagacccttaactaagccacacactgctgggagcctccggaataactttaatgtagttgtagggaagggagtcgaggcaggga
    tgaggatccctgcttgactgctctctttcctgacgaggaagaaaaggacagtgatcaagcacagggtctcaaaggaggtctta
    1921 2709855 — NO ggacagcattacggtggacagtgaa
    1922 3016026 MUC3B NO ctgcaaaacgggtacagcattcctgtatgatagctcacgccgtcgttgtgaaaaccacatagacttggtcaattctcggtcctactctgccctcccgtctcagc
    /// cctcgtgttgccattgc
    MUC3A
    1923 3550736 LOC730217 NO accactacttcatgcagggcagtgtgcc
    1924 3059100 — NO ggaagctaccaaggagactattaaagaaattcaggatggtgaagacagcttaaagggaaacagttctgcaaatagaggcgatgggagatataggaaaga
    gggactatgtgtaggtcttgttgcgtcgctgaag
    1925 3379723 MRPL21 YES tggttggggcagacaacttcacgctgcttggcaagccact
    1926 3432355 — NO cgtcgtggatggatcagttttgctcgatagagggacatgtttttctgtggcaacaggagggcaaaaggagaaggtggccacagatgccggtagatgagctg
    agagtgattgtattccctatcctctcggaagcttgaggcaaggccatcaacagacaatcagagggaataagaagagatagaatatatgaagaaagggaga
    aaagatgaaatcgtaattgtgtagcagggcaagaagtccagaaatttctgtgctgtgccaagttcccagttgaggcggtga
    1927 3511352 — NO ctgacggtttaagatgctgcattttaagtaatgctgagttgtatttttatttcagtcattcatttctacttattttgagcacccattatatgttaggttccatgctaggcac
    tgtaaagataaagatgagaaagactcagcccttacctaaaggagtatagagcctagttggggagacaggaggcagatagttacagcatggagagcaaatt
    ctctgagggaggaatgaagtgagataagagcacagaagaaagacccggggatcagagcagacttcctggaggaggcaatcattgacttg
    1928 2627501 — NO tcctgcttgtgaacagattcctatttccgtgaggaggtgacctcgaagaagagcagcttctattctgctgggaggtgtactgccttctggtatcaggcttctgca
    tcccgggaaagctcgggataacctgaggcacc
    1929 3608077 — NO agaccacaatgagggacatggcaagttcct
    1930 2393810 — NO ttgaggaaaattgctctgtccctat
    1931 2506539 — NO tccatttaaatgagagggtggagctgtccttgcaaaccaatgatgcagctgatgccatgcagtggatcttccttccccctaaa
    1932 3068053 — NO tttcccagagctctaccttgttgtcagcactccctgcaatag
    1933 3762439 — NO ctaagagagttactgaccctaactcccctaaaacctaactatcaaaagcctaccactgactggaagccttacaataacactaacagttgg
    1934 3896232 — NO tcagtctgcgatgaaggtgaacccatcttataaagcagagcttacttacattctgcaggattttggtgtggatgcatagaaggcttacctggttagtaagcctcc
    attcctccgacctacagaaggcaacccttctgcagctccaagcagggatttctagaaaagaccaggtgtacaaaacatctaagctgtgcctcccaccacag
    gtggggaagtcccctgatttggtcagacacagatgaatgtctgtgtctgactgagcccagaaacagttcaattgatgggggctggaaccaccaagaaaaca
    ctcctgacctgggcaacactgtcttccagattat
    1935 3916144 C21orf74 NO tgtgtgtacctgagataagatgatgtcttgtccaatgctggtttccaccttgtgccctgagctgttgggagaggctcctgcgacctgtgac
    1936 2389578 — NO ggcttacgcagcagatgcacgttcagcattgagaacccggtccgacaggaaagacacaccatttttccgccagaaactccagtgttcaaaatacaaactgc
    caacttttcaggcaataatcatgagcttccattagaaaaagccatcagctcaccagacgacgaaatatgctctcgggattaagaactttctcatcctccctgag
    ccctttcctttcaggggaagtgcaagtttg
    1937 3290995 ANK3 YES agcgggctaacaccactgcatgtagctgcacattacgataatcagaaagtggcccttctgcttttggaccaaggagcctcacctcacgcagccgcaaa
    1938 3403153 EMG1 NO tgtcacatcctttgaccctggtctgagctgactgctggaagatgatctttctgcactgagactgtggagtttggggaagccaaggctgtacatttgctatttgttta
    tcctatgaatactgttcttgcaaacctggttgttttggggttcctaaagtatccagtggtgtaaaactgtttgttccccgggacttcagggacagataggaggtta
    cagagtttgcagtttggttccatgctttgaaggcaggctttagctcccagattcccatgtgctaaaggagagaaccctgatgatggagaagaactgtgaaaga
    gagcagtcaggaatgctagtggtgaaaaactgaacaaacagaagtgattttatctaatacagttccaaggtagaaaaagtggagcaggcagggccttgcac
    ccctctccacccccccatggggggggtggtggtagcggcacatacacaatc
    1939 3439875 — NO acctggctttggttattgatgagaagagtaattaatagaacattccctttgctgtgataccctacccaaaatagctcggttgttggttcactttcttcagatacctcc
    ttgtctcatggaccgcctacttact
    1940 3568358 — NO tcatgggtttccaaatatgggatgcaatttcaagttcttaacaccaaatataaccctacttgttttagtttcctggcattcatcctatcatccccagtttactgcacctc
    aggttatcaaggatgtgggagggattctacaagggtatgttcccccagagctttttggtaccctgcaatcccagaagttgttgatgctaggatgtctggagagc
    actggccatttattactga
    1941 3701322 CDYL2 YES tgacgtgaatcacgctacactggcggagaacgggctc
    1942 2975832 — NO gccatgatcgtagcactatactctagcc
    1943 3072788 — NO gtctaattcagaacccggtgggctctccatgcattattggcagcacttttatccaggggcacagacagggaatagggttactggaaacagggagtgtagctc
    aaggaattgttctctctctggagtggataagttgtttgacctactgactcatttcataggaattaggaaaacaacctagtgtggtttttattgttagtcctggaggat
    tccaaaatctgtgtgcctgcaaataagatgagctggggaaagggagcaccagcatttggtgtttctacttgcctcttttcctgatggaatccaatcctctgcttc
    1944 3380982 — NO gctgtttcagtccacaccttgttcacagtaagatattcaattcaattcagcaaacatttgttgagtgcttgctgctctgtgcctgaccagaagaaatgaagccaag
    atacaaataatagaaccctgtcatgagcacagaaagacctgctgagtttctattgattgtggtaaaccagcctgcatccagttccaagtaacagctgcccactt
    agtgaatactctctcatgtttcaacactcagttctagtgtagcctcttctataaagcctttcttttccagataaaattggttaatgtgtcctgtgttaggctgattgatttt
    gatgatccctattcatggtctcccctgtatccatctctttttgcctataacattgtagtcccatctcactctgatgctgggaccagacatgtgacttgttttagccaat
    gagatgtcgataaacatgaagcaaacagaagctttaaaggaggcctgccctcttgctctttgccagtgccatgagaacatggctgatcagctggagggttat
    gagatgtgtaggtgagagacatgcaaaagagccagagataccagctgaagccatcctagactagcccacagtcagcctacccccagtcaagatcaggag
    agtcacccaacccacagatgactgccgacacatgagtaagcc
    1945 3902033 — NO attccacgcgtcaaattgtgggcagtga
    1946 3952107 — NO acaggcacaggggagtcaagcttag
    1947 2678585 — NO agcacccagtctctgttctcagagg
    1948 3463862 PPFIA2 YES tctcaggggatcacgagtggaatagaactcaacagattggagtactaagcagccacccttttgaaagtgacactgaaatgtctgatattgatgatgatgacag
    agaaacaatttttagctcaatggatcttctctccaagtggtcattccgatgcccagacgcta
    1949 3727958 — NO caccatcttctcggatggatggcaaag
    1950 3974043 — NO agcaagccagtgcagtccttggtcacagtcactcacag
    1951 3982214 — NO ccaaaaccaatgtgtctaaggtgcggcatcttg
    1952 2685843 — NO gcggtggtccaatcatagttcactat
    1953 2686522 ABI3BP NO ccagacatgccaccaactaaatccg
    1954 4014220 POF1B NO cttcctctgtagctgccagacctgc
    1955 2838069 TTC1 YES aatggccatcaatgactgcagcaaag
    1956 3701416 — NO cgcatctggcctataccagtgtatgttttctttaggaaaaaataaggcagaaaccagaaaactaacacttcacataaatgtaggtgcagaatattggtacgatat
    tggataacttaaattgctgaactgtatgaaacttaatttttctaaggcaaaaattgatatcattggaaggatcttggagtcagtggcaggcaaacaaaatttaaac
    ttggctgcattttcttttttcgtttcaaatgaatacttaactaggtgcaatggctttatttgtggtcttc
    1957 3756107 — NO tgaattcacagtgttgtatcccatgtagggaaaaataagactaattttccccccacactctaacacactgtaattttgcacttggaactttgctaatctactgtccaa
    cctccttctcaacaaagtcaaatcaaaggagaattaacctagaagaggggacaataaaataagaggtcctcagggagagggagaaccaaggaaatagaa
    tctacttaaatctggccagatagcacctcgtggatt
    1958 2382147 CAPN2 YES atgacaggctgcccaccaaggacggggagctgctctttgtgcattcagccgaagggagcgagttct
    1959 2590022 ZNF385B NO agagaaacacatcactagattgacgagggcttttagagactgctcctataattgaggaatcagcagcataggctttatctccctacttc
    1960 3831701 — NO gtattggcgactgcctgtgcatacac
    1961 2792492 — NO ctgactgtgaattagagtttgcgctattggaaggtggaacccactgtgctcattgtata
    1962 3289301 — NO gcatttactagtgctgtgtgcctcgttgcttttctgggtagtgtttggtgatgggcatagtgtggagtggtggtagagtacacagtgtgattctgtctggtaagga
    agctgtatgttgatgttcactgatgtgaataggttcatacagtcccttaggcatttggctggaggataaagaacagccattgaccagcagagtactttttttgaag
    tttatgcaagacagcgtgctaggtactactgccagcttga
    1963 3686344 XPO6 YES gtcctttctccagcccgacatccacctttttaaacaaaatctcttctacttggagactctcaacaccaagcaga
    1964 2596800 — NO tgactaaaattttgggtctgggctgttatatcactttgtgttaagttatttgtagtagctaatgtgctaacttatatatgtgttctttctgattttttggattttaccttttgatttt
    ggcataacttatctatatttttgtttacattattttaaaaatatcagtaactgtaataatataaaattgaagttgtattgagttgacaatacctctagtttttaaggtcatctgt
    cacataatttaagtgcaccagttcctaatgtataaag
    1965 2614940 — NO ctgctccattggagacttcctgagggcaacagacaaactatttgatagctgaat
    1966 3988991 NDUFA1 YES tcattttgggtatcactggagtctgatggaaagagataggcgcatctctggagttgatcgttactatgtgtcaaag
    1967 3068834 — NO tcatataatagacagtgcggttgcaccttgtgttcatgtactgatagctgttaagggtgcagtgatgaaccaacagagctc
    1968 3116499 — NO gcctctctgttctcatgggctacatg
    1969 3227229 FNBP1 YES ccaacctgaacgaaatgaatgattacgcagggcagcatgaagttatctccgagaacatggcatcacagatcattgtggacttggcacgctatgttcaggaa
    1970 3777767 — NO tgtgtttggggtgattagagcttcttgcaagcttagaagtaggaagctaatg
    1971 3950135 — NO cactggcacaggacgaccctgaagg
    1972 3425446 — NO gcatgtcttgctactacttcatagatgtcataagacccgtttatggattagagttggtgtagaaagccattgccttgagttgaaaaatgaatactgtaaaagctca
    atacaaatcctccaaagcacatgcactt
    1973 2359042 — NO ccaagttctcatcttcagcatcgcagtttcgttctccacc
    1974 2437704 GON4L NO ttccattctattactcttaggtttgtatctcatggaattcactttaacctctgcctcgtgttatttgctttagctgtacattatgctctta
    1975 2778373 — NO cccaaaacatagatccgaacaccagctttgccc
    1976 2954503 — NO atttcctacactgttgatggtggcaatgacaaaatcaattgcagtg
    1977 2441001 — NO ctggagaaatggctatgggtgactg
    1978 3162378 — NO gaattagttcctcagcccagtgtaagactggattaaaaatcgtgcatggatgtgcaggg
    1979 3199012 MPDZ YES cacccagtcagtcagagtcagagccagagaaggctccattgtgcag
    1980 3449682 — NO aagggtgtggcacattgctggtgttttcagggaagaaagcagaacgtctgtgggcaagcagtgg
    1981 3687337 — NO ggagatccttgtgtagcggcagaaagtttagcaacactgtctcctgcattagtgtggagggtaggaaatatacctaaggaacggatggtctagctaaggagc
    tttccagacagaatgttgaaggtgccacctggcttcttgctgcttatagtaaaactgaagaggagagagtaagttaaagaaaaaaaacacttaaatgaaaaag
    agcctgaaattgttgggtttgaaaattcccagcctttccagataacaagtgatgttaaaattaacaaatggcttccgtgcaaagattaaatacaaggcattaaata
    cagggaaatgtggtctaaaggtcaagctgaggatgtgatgaaaaagtcctttgttaagacctcagaaataccaacaagatgcctcagaggggacttccagtc
    gaatgaaataataatcacgcttctgagaaggttaaaggtgttgtctttcagcgtctcagcacaagcccaaagtagagaagggcttaccttgcagagattttc
    1982 2333554 ST3GAL3 YES cctacccttggcagtgtggcagtga
    1983 2570354 — NO gtgttacttccaccatggtgccacacacttaatatccattcc
    1984 2873144 — NO ggggcttctctatgcccggaaactgcctcatcaactgaaacaaatcctgaatcatcaaagggccaaacccactgccacctttagacggagcaggagagtta
    ccctggctctgtcactgccactaagtcta
    1985 3409485 — NO tgaataggcagctagtacatgaacctggcattaggggtttggggctggcatacttaaacatgtggctagatgtgatcaccttcagagtaaatgtaaatagtatc
    atccctccttatctgtatc
    1986 3476542 — NO gtgtgttccaggcgatggcaggaggga
    1987 3620299 — NO atgacagtttttctctaggctaataactcaatgagcagaaaggaaagtcctcccttttaaatgtatatgaatgtatatgtagttcacacttacactctgacacagat
    ctcattgtgtccaatgatgtgtgtgtgtgtgtgtgtgtgtgtgtctccaagactgagacacatgtactaaagagtgatactggccacatctactctgggcttggag
    ggtaacttcagcaa
    1988 3626913 — NO tgcaacctcgacctgcttggcttaagcaa
    1989 2699759 — NO ccatcatgagctgaccaacaatttctaaattcctactcagaaacacagcaaggggaatgcagtcaagcacaaagggcttaaatgaccagataaggctgggc
    tggatgaataaagaggaatatcctatgaatgtgactgtgtagttttagagtatcccgattcaactgttatatttgacttgtggccttgtagacagtgtgtta
    1990 2737582 — NO tagccaagtgcagagggtgtctccgggtgtgtgcgtggcccacaagagggcaagaagagagaaggcggggataggagggaagagggtgggggtga
    gaggcagccctgagagggcggaggaaggaagaggctgggagctcggcgcccgcggcgcagctgccgtcgctgccgcagctgtccagggaggatcg
    ccaaaacggcgacgaataaacaacttaccttgcggagaagagctacgactgcgatgc
    1991 2964449 MDN1 YES cccgatggaatatgcaggctctggacatgattagaaatttgatggactttgacccacaaacggaccagcctga
    1992 3695220 DYNC1LI2 YES ggagctgccttgatttacacatcag
    1993 2939888 LYRM4 YES taaagaatatctcctccaggtgtggt
    1994 3632627 — NO atggagatctacactgacaccctcagtcctagaggcagagaagaggttcagatctggcctg
    1995 3695228 DYNC1LI2 YES cacgcgctgcaacgtgtggattctggatggagacttgtaccacaaaggcctgctgaaatttgcagtttctgctgaatccttgccagagaccctcgtcatttttgt
    tgcag
    1996 3854016 — NO tagatctcgtcgctggtatgcttggttccgctcctcgtttcttagttgcttattctacccgttattcactgatgtta
    1997 3980369 FAM155B NO tccatcacagacagcagagccgggcagctttcttatgccattttctacactgtgcttcatgagtaggactttcttgcactagttcctatgactgagtctccaaact
    ggtttcctagtagtcccccatcccttcctcccttacccagctatgattcagttgtctctgccctccctcttaccctgcctctgtgtttcggtgagagtc
    1998 3799919 — NO tgtattacacagagactaccgcacaaaacacggacccaatgccaggcaagcacgcgcccagcctgaacctccaagaactgtctt
    1999 3032425 — NO cacacctgtaagctgaggtgaaggagtt
    2000 2475245 PPP1CB YES aaagaaagctaaataccagtatggtggactgaattctggacgtcctgtcactccacctcgaacagctaatccgccgaagaaaa
    2001 3487169 DGKH YES tctggggataccgaaagtgggtcatgtgaagcgaattctccag
    2002 3955155 — NO aatgacatcccttttgagctgtggatggtg
    2003 2827160 PHAX YES cacggcaactgcatgtgcaccagtatcacattatcgagctgttgaaagtgtggattcaagtgaagaaagtttttctgattcagatgatgatagctgtctttggaa
    acgcaaacgacagaaatgttttaaccctcctcccaaaccagagccttttcagtttggccagagcagtcagaaaccacctgttgctggaggaaagaagattaa
    caacatatggggtgctgtgctgcaggaacagaatcaagatgcagtggccactgaacttggtatcttgggaatggagggcactattgacagaagcagacaat
    ccgagacctacaatta
    2004 3186892 — NO atagataacgtttgtgtggcactccccaagactcaggcattgtgataactaacactttccatgaataatgtcatagaattctcacaaacatcctgtgagatagac
    actattattttcaaccccatgtacatatgagaatactgagagttggagagactgagtaacatgccctagatgactcagctagcaaggaatgaaaagcacattct
    aactccacccacatatatagttccaggatcccatctctctacctcacattaattagttctataccagctttatgtttcctactagaatgtgcatgttttaaaggctgag
    ctttc
    2005 3195536 — NO tggccttctggacagtaggtaggcatgtgatcactgttgtcactaaacctgggaaatgattcctgggtcagggttcattaattgc
    2006 3238305 — NO gtattgaaattcctcgagccgctgcttttctcactccataattctggccagaatttggtacttaaaatattttgtctaaaatattacaatagctacttaagtcatctccc
    tgactccactctgttgtctttcagggcgtcgtccacactgtagccaaagtgatcttataaaaacataattctaatcatggcactcttctgcttaaaaatgttttaatg
    gctttccgttaggttaaaatttaaaagtcctttgtagcctgtgaga
    2007 3744218 VAMP2 NO acttgctggaaaacggggatgcttgcccctctccaggactattgagcccagagagagctgtcctctcattgggtgaactgattgaggaagggtctattgtcttt
    ttaaatggcacaattttaagggtttgagggtacagtcccttaacctgccacgggagggggcccccaaactttcttccccccacacttctggttttctgtgtggag
    ggggagcagggatatctaagctgtggtgtgaaagggtaggagagatgctggaggtgggggtgctgtgttttagaccccccatattatcccagtgtcccctg
    cccccctcttcccccaccccatgcccccaattctgtggcgcatccagattgtgaaaatgta
    2008 3810033 — NO gtgaatatatctaggtccagcagggtctcagaagcagatgccaacctgaggggaatatttaccagatga
    2009 3943786 — NO cagcagctgctatccatcgtcatcaccagtgtcatcatcgccatccccatcatcaccaccaacaccgccacccccccagcgacacactagctgtggacaca
    tcctttacgcccttgaacctgagtttctacagctatgaagcaagtcccatggaatttacagaccaaacgctaagtgtagggctccctgggagctggtcttatgg
    agcacactggca
    2010 2321472 — NO cagtccatgaggtccacttgtctaaatatgtcacttgaagtgcaaggtaccaattgctcagtggctcaaaatgattttctggttctgttgtcatttcaagagcttctc
    ttgagggttgagagagtctgttttcctaagaatctggttctctccatcagtctctgtttccaccttatcttcctgggaaggtgtgctttctttgaggtgagatgtgaa
    gcctgcccacgtgcagttttatgtcgaattccaagtcagatcttaacttggtactcccggagcctgttggaagtctta
    2011 2361272 — NO gtgcaacatcactttgacttgattattcttgggtctgttttatttcccgcttttattttgcttttgaaatctttttccttggtggatttgtacgtgtcttcactagatgcctca
    aattaagtctgaccacaatcctactctactt
    2012 2447714 — NO tgccaacttctcttcaccacacaatctgcagaagc
    2013 3175671 VPS13A YES tatgatgatgcctatagatttgggggaaaagacaatatatttagtttcattctttgaaggtttacaacgcattattttattcactgaagatccaagggtatttaaagta
    acatatgaaagtgagaaagcagagttagcagagcaagaaattgcagtggcattacaagatgttggaatttctcttgtcaacaattacacgaagcaagaagta
    gcctatata
    2014 3517776 — NO tataaggacttcacagatagctgccgtggatgctg
    2015 3626941 — NO taatttcacaatgggtgtgggaggttggtgagtagatggactagattcaaaagtagatacctcgctctcacctatagcctagcagttt
    2016 2467805 TTC15 NO ctccaacacactacgtcagaaggacccgg
    2017 3701421 — NO ttgctttgtcttgtgatcgcagctcacggcagccttggactcgtgggcacgag
    2018 3717066 NF1 YES cagaaagtgctgcaattgcctgtgtca
    2019 2476534 — NO agatggtacaaaggtcgtgatagggctg
    2020 2750682 — NO ccaagattaggccactgccctgtaac
    2021 2412205 — NO gggttaagctgggaaccatgtctcctggggcaaaattttaattcttctagccacttgttatgtgatctcaagcaaggtacatacgtctctgggtctttttttctttatct
    aaaatatgaagagattaagtgttttcttaattttctttcagctctgatattatgtgattctgtgattaaatgacctggatgttgataatacatgcc
    2022 3019902 — NO ctttggagttttcgcccagatcagaattttattgccttttgccgtagactgctgcaagatttccagagcaaagagaaggtatagtgttccttaatgtgagttatgaa
    gatcaaaatacagcaaagagaagatttcagagatttaaaagtgataatttttactgaaatttggaaatatgtctccatattttaactttattttataaaaaagaattact
    ctgttttttgaaatggccaagcattaagtaatatatgaccgtgaatttcttgagggtgggaaatgtgactggattttatatttcgattgtatcacatgcagcctc
    2023 3750928 KIAA0100 YES acactatgtggcattgtgctttggagaagtgcgtatcagaacggacctacagaaagtttctgacctgtctgccccattc
    2024 2511032 — NO atgactgagtcttatagcggtgttgggcatagca
    2025 2568632 — NO atcctttgtcccgattgggtcccagatacacaaaa
    2026 3039827 — NO gagtccttcctggatagcagcaccaaag
    2027 2437284 C1orf2 YES cagctgccaccggttggagggctgg
    2028 3076362 — NO gcatacaagtctgcccagtcccaggaagaaagaggagagaccctgaattctgaccttttgatggtcaggcatgatggaaagaaactgctgctacagcttgg
    gagatttgctatggaaagtctgccagtcaactttgcccttctaaccaccagatcaatttgtggctgatcatctgatggggcagtttcaatcaccaagcatcgttct
    ctttcctgttctggaattttgttttggagctctttcccctagtgaccaccagttagtttctgagggatggaacaaaaatgcagcttgccctttctatgtggtgcgtgtt
    caggccttgacagattttatcaaaaggaaactattttatttaaatggaggctgagtggtgagtagatgtgtcttggtatggaggaaaagggcatgctgcatcttc
    ttcctgacctccggggtctctggccttttgtttccttgctcactgaggggtctgtctaaccaagcaggcta
    2029 3527927 FLJ10357 NO tgagtcagcatccccaatttctaccacatccagcactcctaccatcttgcatgtaccttccttcctgtccccggctacttgggagtcagcttcttccctctcccaac
    tcatctccctcttct
    2030 3889598 — NO caggtcttagcggtcatcaggatgaaggcggtgggaagtggagcaacagagatccaaatatggaaagagcacgtgctgataccagaggcactggaaata
    atagcaatatccgaaagtctgctcaccctgcgtcattccttcagacagtagtcgggctctattc
    2031 3735624 MFSD11 NO ttaaaatctgcaatactggccaatattcttttatcaaacaggagaccgcagctttaaagggggaaaatgcagacgttggataaaaacagcaagaaatagtcat
    tttcattaataggtctcaaacagtttacgaaacagccattattatc
    2032 2739508 — NO ggcatgtgtgggtaattagttctcactatggttagactcctgaagtgagtggtccaagttgttagcgtgcttctgctctgtgaggccaggccagtatcctgtctg
    2033 3819517 RAB11B YES gacatcgccaagcacctgacctatgagaacgtggagcgctggctgaaggagctgcgggaccacgcagacagcaacatc
    2034 3330082 PTPRJ NO ggggtcagctatgcagcccatcacgtgtgtttttcatctgggatgaaaaagcctggttctcttttgaaatgcttgattgtacttattgagctaaacaagtcttggtg
    actgttgttgatttgcctcaaaagttttaagtcctgggttttcagactactgtgta
    2035 3378442 SPTBN2 NO ggccacattctcctaatagcatgaaacagtcagctcactttctgcctcctcctcttacacttccctgctgtccactgcggccaactcagcacagtgtccttgaag
    ctgattgagggtc
    2036 2473789 — NO gcgcgggctttcgagcacatacaaacctgattacaaaagtcagatttctttatttcgtcttgggcacgtcattttaaccccgctcagcctctcttttgtgtatgaaa
    ctgaaagtaatagcttctgctgtgcaaaatgattagaggaatttgtgaagcgcttggcaacatactaggaccc
    2037 3115627 — NO ttgagatttatgtgtgtgccagacacacacacacacacatatgtacacaagcaatttttgtgtgtgtggctcaagccaggcagagaaagacaaatactaaatg
    atctcactcatatgtgaaatctaaaaaagttgatctcaaagaagtagaaaggagcctggtggttatcagagtctggggagggggttggggagatattggcca
    aaggatatacaatttcagttaggtaggaggaataagttcaagaagtcgattttgactatagttaataatgtgttgtattcatgaacaaggctaagagagtggatgt
    aaagtgttcttaccacaaaaaggataactacatgaggtaatgcacatgttaattagctagatttagtaattccataatgtatccactg
    2038 2745189 — NO tccatttctttttactgcgtccgtccctgacaatacctgctgtttactcagcccttaacgttg
    2039 3450260 — NO aaagtgatacatttgtgagggaggagg
    2040 2656876 — NO cagaccttatctcatagggtgattatgagcattagatgaaatcgtgggtgaaaggctcagtacagtgccaggtatacaagaagcattcagttaagtaatagct
    gttattgttataactgaggttttcacaagccgcacact
    2041 2952697 — NO gctagtttcaaagactgcgaccctgttttgaattggcttgtttatgttgcgacggtggctggaagccaggccaacccagggtcagctttcccaaatcagtcgcc
    aaggcccacgagaacagtagtttcagaactcccagaaataggttcaaagatgcctgtcctgtaccagtcctgcccagcctcgtttttccttaccaccctgactg
    cagtcttaactcctgcaaactaatttgatcgctctaagtttaaccgcgcccagaatttcacttttgcttgcttggcctttgctgtgggtcacaacagcccttcttgc
    2042 3579549 WARS YES cctggcctctgtaagcctgtgtatgttatcaatactgtttcttcctgtgagttccattatttctatctcttatgggcaaagcattgtgggtaattggtgctggctaacat
    tgcatggtcggatagagaagtccagctgtgagtctctccccaaagcagccccacagtggagcctttggctggaagtccatgggccaccctgttcttgtccat
    ggaggactccgagggttccaagtatactcttaagacccactctgtttaaaaatatatattctatgtatgcgtatatggaattgaaatgtcattattgtaacctagaa
    agtgctttgaaatattgatgtggggaggtttattgagcacaagatgtatttcagcccatgccccctcccaaaaagaaattgataagtaaaagcttcgttatacatt
    tgactaagaaatcacccagctttaaagctgcttttaacaatgaagattgaacagagttcagcaattttgattaaattaagacttgggggtgaaactttccagtttac
    tgaactccagaccatgcatgtagtccactccagaaatcatgctcgcttcccttggcacaccagtgttctcctgccaaatgaccctagaccctctgtcctgcaga
    gtcagggtggcttttcccctgactgtgtccgatgccaaggagtcctggcctccgcagatgcttcattttgacccttggctgcagtggaagtcagcacagagca
    gtgccctggctgtgtccctggacgggtggacttagctagggagaaagtcgaggcagcagccctcgaggccctcacagatgtctaggcaggcctca
    2043 3703035 — NO cgatggacactgatgcccacacaggtg
    2044 2444562 RC3H1 NO tccagatggatcgttggcctaaattttcacacttctccctgttcatcctttttcctcttccctgcttcctgggaataaaaggaacttttttaaaaaaattaattagtcc
    acaggtctcattatctttctttatgattaatctatgactttttggtacaagaacaatggaaaaagtgaattaaggtaatgaacaaaacctttcacccacttaaacattt
    tccagttttgagattcctcttcgtgtttgtggtgtcttccccttgttaccccttctgccctttttctctgactatggtaatttggtctttaggctcatatcagtctccccga
    gacattctgcagtcattatcacctttttgggtggattttattttgttttattttgttttttttaaaaaaataactttttaacattggtgcatatttgcttgggatagagcttgtg
    taatttaccaatcgtattgattgtaagtgattgtgccctgcagaggtatatttaacaagacaaaaataatcttggttaataaaggagcccatgagatttgagtcag
    gttgtaagtgaaatcacttacacttttggatagaatttatactcctgctcttataaatcagtggtagacttaccattttttaaagttttcttgcatttttttgtttttttattgc
    cacagctccctattctttcttgcctgcctccacccccctgttcaggaaaaaaaaaaattgagccttaaagtgacagctgattttttaattgctgaattttgtgaaattt
    tactttttccaagtgtttccaactttaaaaagagaagtgaagacaaataggttggaatggtgaagacaaatggattggaatttcacaggctgtgaataattcctta
    ggatctggcaaaccgtgaagtcttatttgaagaccttatctcctgagagttcttttggagtaggaaaaagaaccctatttgaaatagaccgtttttctcttgtttttaa
    tctgtttaatatttctgatttttaagcagcttt
    2045 3816284 DOT1L YES ccaggtcgtgctccaggttgctgctgccaccaactgcaaacatcactatggcgtcgagaaagcagacatcccggccaagtatgcgga
    2046 3231694 — NO atccaccaagcagtgcgtccaggtg
    2047 3760111 — NO gaatgaacgcagagagtgtcagtgctgaca
    2048 3960937 — NO caggcacaccgccttgaggtgggcagtgccc
    2049 2519659 COL3A1 NO gaaagattcattggcatgccacaggggattctcctcc
    2050 3380965 — NO tctaacccttgagacactgccaacatccctcctagtacaagacttttcttggtgcttgctgtttttagaggagttttggcccttcagtgtttgtaaagctctcggatc
    ctcagaaaaaaattctttagtgattaattttgaaattggagctgtttgattattttgattaagaagctgattttcggcctggcacg
    2051 3690096 DNAJA2 YES agatgggaatgatttgcacatgacatataaaataggacttgttgaagctctatgtggatttcagttcacatttaagcaccttgatggacgtcagattgtggtgaaa
    taccc
    2052 3777917 — YES aggatcctgccgaaaggtgctcagtggcct
    2053 3811929 — NO atgtatcattctccatacacctgtgcctt
    2054 2436400 — NO ccagccacgcgtccagcaggtcagggatt
    2055 3868616 SHANK1 YES tacatcattaaggagaagacagtcttgctgcagaagaaggacagtgaggggtttgg
    2056 2833315 — NO atcttttgattgctagcccagctgctttccttgttatcactttgtggagcaggctggacattgacaatgagttctgagactgagtggaatgggagacccctccca
    gctggtggtcgagctgcctagagcatggtccatctgtttgggactagggttgagctcc
    2057 2886091 — NO tgacgaatttcgtctttcttccctacggtggagtcagtgttaaacatacaacaaggagttctggggcacaggc
    2058 3146585 RNF19A YES atgtccacgatgtgctgcttatataataaagatgaatgatgggagctgcaatcacatgacatgtgc
    2059 3271059 — NO gtgagatacttgacatggggacctttac
    2060 3589673 — NO ttcaagaagttctggggacagaggg
    2061 3971336 MBTPS2 YES tccttggaaaaacgctgatgcagactttggcacaaatgatggctgactctccctcttcttattcttcctcctcttcttcctcttcctcctcttcttcctcttcctcttcttc
    atcttcttcctcttcctcgcttcacaatgaacaggtgttacaagttgtg
    2062 3304025 — NO gtatgtgataagtatttggatttgagagtagacctttcatagtgaggcttatcaggttgaggggaggtgatgactggaaatatatttatttattttaaatcccactttg
    gctttagtaaaatctgaatatgtgtgcatttctagtttcttacaccaaatgtaggttccgtaagttcatgcaagtacagtgggtc
    2063 3350758 PAFAH1B2 YES agacaaagagcctgatgtactgttcgtgggagactccatggtgcagttaatgcagcaat
    2064 3921733 — NO cagtgtcgctacaggggatctctcaggctcacaacgggccactcctctagggaagttctggtctcatcatgatccttgtttggtctcactccccatgtccttctct
    gtccctcctccaactgccatttatttatttaactgaaaaagtaccaatcacccacataggcatga
    2065 2361637 — NO acaggagccaatgcccaatcatagc
    2066 2625412 — NO accacctgggtattgaagccctataaaaacactttctacttaccttaatatagtctggcgttgctgggacctcacagtgttctttcacactttttatgtaacttagga
    actgaaataccactcatgcatttgttctaaag
    2067 2737704 — NO gattgctatggaagtactgagtccctgaaggagagacaaggtgcaggaagccccaatcgccaggccatcgatgaaattgtggagggcatcgcagagcgt
    tatcatccaggcaatcgtccctatt
    2068 2795252 — NO gttcggatgatttcacgggagcagc
    2069 3203541 AQP7 YES gctgtgacctttgctaactgtgcgctgggccgcg
    2070 3510917 — NO aagaccagggtaatcatagaactgccaagcagaaagaaatgtagaatgtagcagtggtgtggagacccgtggctgacaggtggtggtcttcatataggct
    gagggacaggctagatgcatgtcaagtggc
    2071 3670551 — NO gagctccagggatatctcttctgcacattcttccagagcagtgcatctctcttctggttgtttgtacacccttcttttactctccttattatcctctcccatgttcattca
    gtacatacttagtgagtgttcaccagatgcttagcacctggggtatac
    2072 3729159 DHX40 NO gcctatggcaggattctttcttgaattaatattaatccttaaattgatttttctgggattatacaaattcctttttatataaaagtatattgtttaaaacagtagctatagc
    cattaaccaaaggacagatgatatatatatatatgatatatatatatatataagttcttttttagctgtacctacgtacttatatcagcaccatgtatgtaggtgtgata
    gtactttcaaacagcgcctccacctggcctactctgttatttccacctgtttgggtagggccatttaacttccattatgccaaacttgggatgggattttcgaagca
    gacaacactatttcatcgtgtttcaaattggaaccttgaggctagttagtatcacact
    2073 2969482 CDC2L6 YES tgtatttgccggctgccagattccataccccaaacgagaattccttaatgaagat
    2074 3040116 SNX13 YES tggcaaccttattttactacacgcattgtagatgactttggcacacacttacgagtattcagaaaggctcaaca
    2075 3819122 LOC100129391 YES gaggtggctagaaaacggcaagaac
    2076 2359763 — NO acctgcgtcacaccctggctagtgacccagtcagacgtgctggggaccctggctgaccacctgtaccaggggcaaggaaggaaggagaggggagcatt
    gtgaagcagggcaggatgactcttgaaggtggagacaggccctggacagctctgggacccttaatggtggcagc
    2077 2969302 WASF1 YES ggtttgatagaaaatcgccctcagtcaccagctacaggcagaacacctgtgtttgt
    2078 2330410 C1orf113 NO gaagctggtcccacggaaagtggtatctcgggaatcag
    2079 3265461 FAM160B1 NO tctaggtggggaactgactgataacccttggcagcaatcaaagtgccagtggctcctcgatgtttacatttttttctattttgttcagtcttttgttttaaatgattcta
    aagagattaaagaaaacagagttttaaatgtcctatttacatgttaaaggatttggggaaattgggtatgtatgtgaatgggtgtacatgtaggaacctgtagttc
    agcaaagctgcgctgggcacagcatgcttgtacttgattgacaaaatcgtgtttgccagtccactttctatttttcctttaagtgatgctgatcactcaaataatgct
    tttaagctattgtttgtttttatttgacatgttaagccgcagcactttcttcttcatctttccatttactgatatttgggggaacaggctatcaaaggttccggcttgaag
    ggaactgtcactac
    2080 3735093 LOC643008 NO gccaccgacttcgtgcaggagatgcgc
    2081 2402500 PAFAH2 YES ggcaacattgacatgagccgtgtggctgtgatgggacattcatttggaggggccacagctatt
    2082 3552152 MEG3 YES tcttcaacccactgcttcctgactcgctctactccgtggaagcacgctcaca
    2083 2736402 — NO attataaggtatgatatggcttcccaattgtcaaagaattaaaatgctcattaggagaggagtgactgcttctccctttagtagaaaaacaattcaaactcaggtt
    accaattacaatacacaaactaaaacagttatgttgagccgggaaaccgtcttcttgtaggctatcttctagcaccaaataatgcccacatgatttctggctgaa
    ggcca
    2084 2751960 — NO gcttccttcgtgaattctaaccgtaccgttactgtgtttgaggatcactggcagccgagctctgagtggggaactgagataagaaaggtgttgtcatgataaca
    cctggacagctgcatcccacagactatgggagtgccaggaaactggctacctcacagcagagtagagaaaatggaaataaacacaaatataagcttttcag
    tgagctgtgggtcagagaaggccacaagtggtctggcagatcatggtgcagctctttgtttcatgagctacgtgcagcagtagtttttatgagctctttttgtag
    ctttccagccctaggattcagccatggtaa
    2085 3024231 — NO tgcccagaaacgaccattttggacaatctcatccagttttacgcttgttttattcagaaagagaatcacctatcctcttcacatc
    2086 2928814 — NO taaggaaattgggttgtcaccactggctttgagtaattcgttttgtctatgcaagctgtcttcatacgaaaaaggttttcatactatatccagtccc
    2087 3166955 NFX1 YES gttgaagtcgaaacatcccactggacat
    2088 3829651 KIAA0355 YES cctgactgtggtgcaagtccatttccagtttttgactcatgcgttacagaaggtccagccggtggctcactcttgctttgctgaggtcatcgtgcc
    2089 3709186 JMJD3 YES gtcaggcagctgtaagcggcgacagaag
    2090 2947628 — NO ctgttgacttcagagtcgagtgtgag
    2091 3820638 SLC44A2 NO cccagtgatggccacgtcttgtttctagaatcccttcctttgcacaagccatattctgaactcttaattccttcccttaacttcaatccctatgtctcctgtcctacctc
    atggttttcctggccccacacctgatgctcagagcccactgtgaacccctggtgcctcttttggactcggttc
    2092 3823661 AP1M1 NO cagcctcagactttttcccactgagggtccagagagcggggccacgtgtcacccacgtctgcgcttggtcacccgtcctccccaccctgtgtgtgtttatgtc
    atagttacattaa
    2093 4038647 — NO aggtctccgctttcctggaaatccagaccc
    2094 2543897 — NO agctctgggtgagacttgtcttccgggggctg
    2095 2353902 — NO ctctgattaggtcttgtgcccattgttgaaccaaatgctgtgcttaggaggatgggacatgttctttttgttttgcttagttagggcctggctctggagccaggaga
    ggggaggaggaaatgttgctggatgtaagttagcactgatactaattattctaacaatgattaatagttagaatggctgggtgcagtggcacatagtcccagct
    ccgcaggaggttgagatgggaggatcgcctggggccaggagtccaaggctatggggcaccatgatcatga
    2096 3190953 PPP2R4 YES cactttgtggatgagaaggccgtgaatgagaaccacaaggact
    2097 3922999 PKNOX1 YES gcgcccggccgagaatgacatcttaa
    2098 3701615 — NO atggacagcttcaaagggcagtttgggggtttctgtttattttcctgtatgttctggtcacctcaatcatctaaccagaagaactggcccaaaattaggcacaag
    aaaaaaggaaaaagtctagccctgccacataactcctggaactggttgcagaaactgaac
    2099 2528729 — NO gggaagacacgaagggagggcgctg
    2100 3188305 — NO ggatagcttctattgtggacgtggaatcc
    2101 3578798 — NO agatctactcctggatgcgggtacaggacagcatccccagactgtttgtaaagtctcatgtgatacatggagggcaggcct
    2102 3810041 — NO agcagaagcaaacgggggtgtctcaggagggggccccgtttccttcttgtaaagctgctcccacccacagccacactccattcagtcaggtttatgtgctgtt
    cttccttgtcccttatgaggtagaaccatcaccttgcgtgcaaagcagctta
    2103 2520084 MGC13057 NO ggtgtctgtcggtctttgcttgtcagctgt
    2104 2615285 — NO gtgtttgtgctcaatgtaagagcaaggaaggtgcgggaagatgagggggatgaggcgcaggagtacagggctgttattca
    2105 2676383 NEK4 YES tggtagagtggtttgtacagatcgccatggctttgcag
    2106 3337536 — NO aggcttcttgcacaggcagaaggggct
    2107 3670582 — NO tacgtgcccaagaatcaatccaatccaactgataacattttctctgaagatagctgcctcttcaaatactggtacagagattcaagaagctgtaccacagacca
    tcagtt
    2108 2359853 — NO cccatttttcattaggtccaggtgtatccaaatgttgcca
    2109 3349998 — NO tgatgtggccccgattgcagaattgagttggaggctgaagcatgtgagctctgatccttgcc
    2110 3431977 — NO cttccctctggaagactaacatgtactgctgaagtcttgttcagtgtccttctagccccagactttgcagcctaccaacatggactgagacagggaaagcgtg
    ggcaagtgagttccatactctaattttcctacagaagcatcctaagtggtgtgtgggttctcagatcaagtcacaaacacattcacagcccatgatatcgtacaa
    cactactttttagttcaaattaattatgagtaacaacagactatctgccaaaatagggagctgca
    2111 2482372 ACYP2 YES agctaggaaaataggagtggttggctg
    2112 2619332 SS18L2 YES cattgcagatgccagtccaaccagcac
    2113 3810037 — NO cccgtggctctaaaagtattatccgaaatcaaccagtcacccctttcaccttctctcagtttaaaaatggatccagtgcatacccaatag
    2114 2944959 — NO gtaggaatcaaacatagcgccatctatctgctttttatattatcctacactattttaaaaactgctcaacagtcttatacagaaatctttaaaagatagacaggataa
    catgctatattaaccccaccattgaaataatccaacaccatcacgattccgattaagagaagaaaaaaatcttttttttttctttttttttctttttttctttttttttttccga
    aaccactcgccctccactgactgcccctgtaccacatcaaacagtctcctctcctccacgcctccggggtctgggaagtctcacctcactgatttc
  • TABLE 4
    Differentially expressed RNA transcripts used to plot hierarchical
    clustering and expression matrix (‘heat map’) in FIG. 1B. The 526
    RNA transcripts represent a subset of the differentially expressed
    transcripts (Table 3) between patients in the three clinical status
    groups (i.e., ‘SYS’, ‘PSA’ and ‘NED’) disease using linear
    regression and a p-value cut-off of p < 0.01. Weighting factors were
    from the regression coeffecient values; positive and negative values
    indicated transcripts correlated to increased expression in ‘SYS’
    and ‘NED’ disease, respectively with intermediate expression
    values in the ‘PSA’ disease group. Weighting factors were used
    to derive 526-metagene values in FIG. 2.
    SEQ
    ID
    No Weights
    1 −6.08
    2 −5.71
    3 −5.68
    4 −5.39
    5 −5.26
    6 −4.84
    7 −4.7
    8 −4.68
    9 −4.66
    10 −4.55
    11 −4.53
    12 −4.47
    13 −4.4
    14 −4.37
    15 −4.32
    16 −4.27
    17 −4.23
    18 −4.2
    19 −4.18
    20 −4.1
    21 −4.09
    22 −4.06
    23 −4.03
    24 −4.02
    25 −4.01
    26 −4
    27 −3.96
    28 −3.95
    29 −3.95
    30 −3.95
    31 −3.95
    32 −3.92
    33 −3.91
    34 −3.88
    35 −3.86
    36 −3.85
    37 −3.8
    38 −3.8
    39 −3.79
    40 −3.74
    41 −3.73
    42 −3.73
    43 −3.71
    44 −3.7
    45 −3.7
    46 −3.7
    47 −3.68
    48 −3.67
    49 −3.66
    50 −3.66
    51 −3.65
    52 −3.65
    53 −3.64
    54 −3.64
    55 −3.63
    56 −3.62
    57 −3.6
    58 −3.6
    59 −3.59
    60 −3.58
    61 −3.58
    62 −3.58
    63 −3.58
    64 −3.58
    65 −3.57
    66 −3.57
    67 −3.57
    68 −3.55
    69 −3.52
    70 −3.51
    71 −3.5
    72 −3.5
    73 −3.49
    74 −3.48
    75 −3.48
    76 −3.47
    77 −3.47
    78 −3.47
    79 −3.47
    80 −3.46
    81 −3.45
    82 −3.45
    83 −3.44
    84 −3.43
    85 −3.43
    86 −3.43
    87 −3.43
    88 −3.42
    89 −3.41
    90 −3.41
    91 −3.4
    92 −3.4
    93 −3.39
    94 −3.38
    95 −3.36
    96 −3.36
    97 −3.36
    98 −3.36
    99 −3.35
    100 −3.35
    101 −3.35
    102 −3.34
    103 −3.34
    104 −3.34
    105 −3.33
    106 −3.33
    107 −3.32
    108 −3.32
    109 −3.31
    110 −3.31
    111 −3.3
    112 −3.3
    113 −3.3
    114 −3.3
    115 −3.27
    116 −3.27
    117 −3.26
    118 −3.26
    119 −3.26
    120 −3.25
    121 −3.25
    122 −3.24
    123 −3.24
    124 −3.23
    125 −3.23
    126 −3.22
    127 −3.22
    128 −3.22
    129 −3.22
    130 −3.22
    131 −3.21
    132 −3.21
    133 −3.21
    134 −3.2
    135 −3.19
    136 −3.19
    137 −3.19
    138 −3.19
    139 −3.18
    140 −3.17
    141 −3.17
    142 −3.16
    143 −3.16
    144 −3.15
    145 −3.14
    146 −3.14
    147 −3.13
    148 −3.13
    149 −3.12
    150 −3.12
    151 −3.11
    152 −3.11
    153 −3.11
    154 −3.11
    155 −3.1
    156 −3.1
    157 −3.09
    158 −3.09
    159 −3.09
    160 −3.08
    161 −3.08
    162 −3.08
    163 −3.07
    164 −3.07
    165 −3.07
    166 −3.07
    167 −3.07
    168 −3.07
    169 −3.06
    170 −3.06
    171 −3.06
    172 −3.05
    173 −3.05
    174 −3.05
    175 −3.05
    176 −3.04
    177 −3.03
    178 −3.03
    179 −3.03
    180 −3.02
    181 −3.02
    182 −3.02
    183 −3.01
    184 −3.01
    185 −3
    186 −3
    187 −2.96
    188 −2.96
    189 −2.96
    190 −2.95
    191 −2.95
    192 −2.95
    193 −2.94
    194 −2.94
    195 −2.94
    196 −2.93
    197 −2.92
    198 −2.92
    199 −2.92
    200 −2.92
    201 −2.91
    202 −2.91
    203 −2.9
    204 −2.89
    205 −2.89
    206 −2.88
    207 −2.88
    208 −2.87
    209 −2.87
    210 −2.87
    211 −2.86
    212 −2.85
    213 −2.85
    914 5.32
    915 5.27
    916 4.82
    917 4.64
    918 4.59
    919 4.54
    920 4.49
    921 4.45
    922 4.43
    923 4.38
    924 4.38
    925 4.36
    926 4.36
    927 4.33
    928 4.27
    929 4.27
    930 4.18
    931 4.17
    932 4.13
    933 4.12
    934 4.08
    935 4.08
    936 4.07
    937 4.07
    938 4.04
    939 4.03
    940 4.03
    941 4.02
    942 4.02
    943 4.01
    944 3.97
    945 3.95
    946 3.95
    947 3.95
    948 3.95
    949 3.92
    950 3.92
    951 3.9
    952 3.89
    953 3.88
    954 3.84
    955 3.84
    956 3.83
    957 3.8
    958 3.8
    959 3.8
    960 3.79
    961 3.77
    962 3.76
    963 3.75
    964 3.74
    965 3.72
    966 3.71
    967 3.71
    968 3.71
    969 3.7
    970 3.7
    971 3.69
    972 3.69
    973 3.68
    974 3.67
    975 3.66
    976 3.65
    977 3.64
    978 3.63
    979 3.62
    980 3.62
    981 3.61
    982 3.61
    983 3.6
    984 3.6
    985 3.59
    986 3.59
    987 3.58
    988 3.58
    989 3.57
    990 3.57
    991 3.56
    992 3.56
    993 3.55
    994 3.55
    995 3.55
    996 3.55
    997 3.54
    998 3.54
    999 3.54
    1000 3.54
    1001 3.54
    1002 3.53
    1003 3.53
    1004 3.53
    1005 3.53
    1006 3.53
    1007 3.53
    1008 3.52
    1009 3.52
    1010 3.51
    1011 3.51
    1012 3.5
    1013 3.49
    1014 3.49
    1015 3.48
    1016 3.48
    1017 3.48
    1018 3.48
    1019 3.47
    1020 3.46
    1021 3.45
    1022 3.45
    1023 3.44
    1024 3.44
    1025 3.44
    1026 3.43
    1027 3.43
    1028 3.42
    1029 3.41
    1030 3.41
    1031 3.41
    1032 3.41
    1033 3.4
    1034 3.4
    1035 3.4
    1036 3.39
    1037 3.39
    1038 3.39
    1039 3.39
    1040 3.38
    1041 3.38
    1042 3.38
    1043 3.38
    1044 3.37
    1045 3.37
    1046 3.37
    1047 3.36
    1048 3.35
    1049 3.35
    1050 3.35
    1051 3.34
    1052 3.34
    1053 3.33
    1054 3.33
    1055 3.33
    1056 3.32
    1057 3.31
    1058 3.31
    1059 3.31
    1060 3.31
    1061 3.3
    1062 3.3
    1063 3.3
    1064 3.29
    1065 3.29
    1066 3.29
    1067 3.28
    1068 3.27
    1069 3.27
    1070 3.27
    1071 3.27
    1072 3.26
    1073 3.26
    1074 3.25
    1075 3.24
    1076 3.24
    1077 3.24
    1078 3.22
    1079 3.22
    1080 3.22
    1081 3.21
    1082 3.21
    1083 3.2
    1084 3.2
    1085 3.2
    1086 3.2
    1087 3.2
    1088 3.19
    1089 3.19
    1090 3.19
    1091 3.19
    1092 3.19
    1093 3.18
    1094 3.18
    1095 3.18
    1096 3.18
    1097 3.18
    1098 3.17
    1099 3.17
    1100 3.17
    1101 3.16
    1102 3.16
    1103 3.16
    1104 3.16
    1105 3.15
    1106 3.15
    1107 3.15
    1108 3.15
    1109 3.14
    1110 3.14
    1111 3.14
    1112 3.14
    1113 3.13
    1114 3.13
    1115 3.12
    1116 3.12
    1117 3.12
    1118 3.11
    1119 3.11
    1120 3.11
    1121 3.11
    1122 3.1
    1123 3.1
    1124 3.1
    1125 3.09
    1126 3.09
    1127 3.09
    1128 3.09
    1129 3.09
    1130 3.08
    1131 3.08
    1132 3.08
    1133 3.08
    1134 3.08
    1135 3.07
    1136 3.07
    1137 3.07
    1138 3.06
    1139 3.06
    1140 3.06
    1141 3.06
    1142 3.05
    1143 3.05
    1144 3.05
    1145 3.05
    1146 3.05
    1147 3.04
    1148 3.04
    1149 3.04
    1150 3.04
    1151 3.04
    1152 3.03
    1153 3.03
    1154 3.03
    1155 3.03
    1156 3.02
    1157 3.02
    1158 3.02
    1159 3.01
    1160 3.01
    1161 3.01
    1162 3.01
    1163 3.01
    1164 3.01
    1165 3
    1166 3
    1167 3
    1168 3
    1169 3
    1170 2.99
    1171 2.99
    1172 2.99
    1173 2.99
    1174 2.99
    1175 2.99
    1176 2.99
    1177 2.98
    1178 2.98
    1179 2.97
    1180 2.97
    1181 2.97
    1182 2.97
    1183 2.96
    1184 2.96
    1185 2.96
    1186 2.96
    1187 2.96
    1188 2.96
    1189 2.95
    1190 2.94
    1191 2.94
    1192 2.94
    1193 2.94
    1194 2.93
    1195 2.93
    1196 2.93
    1197 2.93
    1198 2.93
    1199 2.92
    1200 2.92
    1201 2.91
    1202 2.91
    1203 2.91
    1204 2.91
    1205 2.9
    1206 2.89
    1207 2.89
    1208 2.89
    1209 2.89
    1210 2.88
    1211 2.88
    1212 2.88
    1213 2.87
    1214 2.86
    1215 2.86
    1216 2.86
    1217 2.86
    1218 2.86
    1219 2.85
    1220 2.85
    1221 2.85
    1222 2.85
    1223 2.85
    1224 2.85
    1225 2.85
    1226 2.85
  • TABLE 5
    Differentially expressed RNA transcripts used to plot
    hierarchical clustering and expression matrix (‘heat map’)
    in FIG. 1C. The 148 RNA transcripts represent a subset of the
    most differentially expressed transcripts between patients with
    clinically significant ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’
    (i.e., ‘PSA’ and ‘NED’) disease. Weighting factors were
    from the test statistic values; positive and negative values
    indicated transcripts correlated to increased expression in
    recurrent and non-recurrent disease, respectively. Weighting
    factors were used to derive 148-metagene values, which were
    converted by scaling and normalizing into ‘POP’ scores
    depicted in FIG. 7.
    SEQ ID No Weights
    1 −4.1
    2 −4.21
    3 −5.48
    4 −3.04
    6 −3.73
    8 −3.88
    14 −3.78
    20 −3.14
    32 −3.87
    33 −3.75
    36 −4.93
    42 −3.46
    45 −3.1
    46 −4.14
    60 −5.72
    63 −4.79
    65 −3.82
    66 −4.02
    67 −3.37
    69 −3.25
    79 −3.1
    86 −3.57
    88 −4.54
    96 −3.68
    100 −3.63
    104 −2.93
    115 −3.29
    129 −3.91
    130 −3.32
    181 −3.27
    182 −3.37
    187 −3.56
    189 −3.44
    194 −2.09
    217 −4
    225 −4.01
    241 −4.16
    265 −3.86
    280 −4.02
    293 −3.36
    295 −3.57
    334 −3.36
    355 −3.44
    387 −3.73
    400 −3.17
    437 −4.02
    445 −3.14
    460 −3.36
    468 −3
    536 −3.65
    592 −2.7
    596 −2.79
    684 −2.75
    915 3.78
    920 4.36
    923 3.23
    925 3.04
    926 4.61
    927 3.79
    933 3.24
    934 3.65
    935 3.64
    939 4.2
    941 4.14
    944 3.72
    945 4.03
    947 4.44
    949 3.77
    954 4.34
    960 3.54
    968 3.84
    970 3.5
    971 4.68
    974 3.63
    978 5.27
    986 2.59
    999 4.74
    1004 4.5
    1005 3.62
    1014 4.86
    1022 6.29
    1023 4.08
    1031 3.75
    1032 3.49
    1039 3.44
    1045 3.41
    1052 3.28
    1060 4.48
    1062 4.1
    1080 3.97
    1093 4.02
    1095 3.77
    1101 3.55
    1108 3.39
    1117 3.97
    1123 4.03
    1124 3.45
    1126 3.25
    1132 3.51
    1146 3.78
    1147 3.37
    1153 3.71
    1164 3.54
    1167 3.6
    1194 3.2
    1208 3.35
    1218 3.56
    1219 2.96
    1233 3.44
    1234 3.86
    1248 3.56
    1261 3.19
    1291 2.99
    1299 3.74
    1300 3.33
    1304 3.14
    1311 3.66
    1314 3.95
    1318 3.9
    1320 3.45
    1324 3.31
    1330 3.02
    1335 4.35
    1341 3.7
    1344 2.93
    1346 3.51
    1357 3.82
    1367 3.35
    1369 3.75
    1372 3.07
    1375 3.17
    1383 3.67
    1390 3.49
    1395 3.19
    1402 3.45
    1416 3.29
    1425 3.73
    1443 2.97
    1453 3.01
    1469 3.02
    1474 3.52
    1489 3.66
    1503 3.19
    1527 3.25
    1551 3.41
    1598 3.26
    1624 2.91
    1689 2.82
  • TABLE 6
    Genes identified in a literature search as being correlated to
    clinical outcome or prognosis in prostate cancer patients.
    Indicated are the gene name and HNGC gene symbol.
    Gene Name Symbol
    Aminoadipate-semialdehyde dehydrogenase AASDH
    ATP-binding cassette, sub-family A (ABC1), member 5 ABCA5
    ATP-binding cassette, sub-family B (MDR/TAP), member 1 ABCB1
    ATP-binding cassette, sub-family C (CFTR/MRP), member 2 ABCC2
    ATP-binding cassette, sub-family C (CFTR/MRP), member 4 ABCC4
    ATP-binding cassette, sub-family C (CFTR/MRP), member 5 ABCC5
    ATP-binding cassette, sub-family G (WHITE), member 2 ABCG2
    V-abl Abelson murine leukemia viral oncogene homolog 1 ABL1
    Acetyl-Coenzyme A carboxylase alpha ACACA
    Acyl-Coenzyme A oxidase 1, palmitoyl ACOX1
    Acid phosphatase 2, lysosomal ACP2
    Acid phosphatase, prostate ACPP
    Actin, gamma 2, smooth muscle, enteric ACTG2
    Aspartoacylase (aminocyclase) 3 ACY3
    AF4/FMR2 family, member 3 AFF3
    AF4/FMR2 family, member 4 AFF4
    Aryl hydrocarbon receptor AHR
    Absent in melanoma 2 AIM2
    V-akt murine thymoma viral oncogene homolog 2 AKT2
    Aminolevulinate, delta-, synthase 1 ALAS1
    Activated leukocyte cell adhesion molecule ALCAM
    Aldehyde dehydrogenase 1 family, member A2 ALDH1A2
    Anaplastic lymphoma kinase (Ki-1) ALK
    Arachidonate 12-lipoxygenase ALOX12
    Arachidonate 15-lipoxygenase, type B ALOX15B
    Alpha-methylacyl-CoA racemase AMACR
    Alanyl (membrane) aminopeptidase (aminopeptidase N, ANPEP
    aminopeptidase M, microsomal aminopeptidase, CD13,
    p150)
    Anthrax toxin receptor 2 ANTXR2
    Annexin A2 ANXA2
    APEX nuclease (multifunctional DNA repair enzyme) 1 APEX1
    Androgen receptor (dihydrotestosterone receptor; testicular AR
    feminization; spinal and bulbar muscular atrophy; Kennedy
    disease)
    V-raf murine sarcoma 3611 viral oncogene homolog ARAF
    Amphiregulin (schwannoma-derived growth factor) AREG
    AT rich interactive domain 4A (RBP1-like) ARID4A
    Armadillo repeat containing 5 ARMC5
    Aryl hydrocarbon receptor nuclear translocator ARNT
    N-acylsphingosine amidohydrolase (acid ceramidase)-like ASAHL
    ATPase family, AAA domain containing 2 ATAD2
    Activating transcription factor 1 ATF1
    Ataxia telangiectasia mutated ATM
    Atrophin 1 ATN1
    ATP synthase, H+ transporting, mitochondrial F1 complex, ATP5D
    delta subunit
    ATP synthase, H+ transporting, mitochondrial F0 complex, ATP5J
    subunit F6
    Aurora kinase A AURKA
    Aurora kinase B AURKB
    AXL receptor tyrosine kinase AXL
    Beta-2-microglobulin B2M
    BCL2-antagonist of cell death BAD
    BAI1-associated protein 2-like 2 BAIAP2L2
    BCL2-antagonist/killer 1 BAK1
    BRCA1 associated protein-1 (ubiquitin carboxy-terminal BAP1
    hydrolase)
    BRCA1 associated RING domain 1 BARD1
    B-cell CLL/lymphoma 2 BCL2
    BCL2-like 1 BCL2L1
    B-cell CLL/lymphoma 3 BCL3
    Breakpoint cluster region BCR
    BCS1-like (yeast) BCS1L
    Biglycan BGN
    Baculoviral IAP repeat-containing 2 BIRC2
    Baculoviral IAP repeat-containing 3 BIRC3
    Baculoviral IAP repeat-containing 5 (survivin) BIRC5
    Baculoviral IAP repeat-containing 7 (livin) BIRC7
    Bloom syndrome BLM
    BMI1 polycomb ring finger oncogene BMI1
    Bone morphogenetic protein 4 BMP4
    BolA homolog 2 (E. coli) BOLA2
    V-raf murine sarcoma viral oncogene homolog B1 BRAF
    Breast cancer 1, early onset BRCA1
    Breast cancer
    2, early onset BRCA2
    BTB (POZ) domain containing 14B BTBD14B
    Bruton agammaglobulinemia tyrosine kinase BTK
    BUB1 budding uninhibited by benzimidazoles 1 homolog BUB1
    (yeast)
    Chromosome 15 open reading frame 33 C15orf33
    Chromosome 17 open reading frame 56 C17orf56
    Chromosome 17 open reading frame 57 C17orf57
    Chromosome 1 open reading frame 115 C1orf115
    Chromosome 1 open reading frame 77 C1orf77
    Chromosome 2 open reading frame 33 C2orf33
    Chromosome
    2 open reading frame 37 C2orf37
    Chromosome 3 open reading frame 14 C3orf14
    Chromosome
    8 open reading frame 32 C8orf32
    Chromosome
    8 open reading frame 53 C8orf53
    Chromosome
    8 open reading frame 76 C8orf76
    Calcium channel, voltage-dependent, beta 4 subunit CACNB4
    Calmodulin binding transcription activator 1 CAMTA1
    Caspase 2, apoptosis-related cysteine peptidase (neural CASP2
    precursor cell expressed, developmentally down-regulated
    2)
    Caspase 3, apoptosis-related cysteine peptidase CASP3
    Caspase
    8, apoptosis-related cysteine peptidase CASP8
    Caveolin 1, caveolae protein, 22 kDa CAV1
    Cas-Br-M (murine) ecotropic retroviral transforming CBL
    sequence
    Cholecystokinin CCK
    Cyclin A2 CCNA2
    Cyclin B1 CCNB1
    Cyclin C CCNC
    Cyclin D1 CCND1
    Cyclin E1 CCNE1
    Cyclin H CCNH
    CD34 molecule CD34
    CD38 molecule CD38
    CD40 molecule, TNF receptor superfamily member 5 CD40
    CD44 molecule (Indian blood group) CD44
    CD59 molecule, complement regulatory protein CD59
    CD69 molecule CD69
    CD9 molecule CD9
    Cell division cycle 2, G1 to S and G2 to M CDC2
    Cell division cycle 25 homolog A (S. pombe) CDC25A
    Cell division cycle 25 homolog B (S. pombe) CDC25B
    Cell division cycle 25 homolog C (S. pombe) CDC25C
    CDC42 effector protein (Rho GTPase binding) 5 CDC42EP5
    Cadherin 1, type 1, E-cadherin (epithelial) CDH1
    Cadherin 11, type 2, OB-cadherin (osteoblast) CDH11
    Cadherin 13, H-cadherin (heart) CDH13
    Cyclin-dependent kinase 10 CDK10
    Cyclin-dependent kinase 2 CDK2
    Cyclin-dependent kinase 4 CDK4
    Cyclin-dependent kinase 6 CDK6
    Cyclin-dependent kinase 7 CDK7
    Cyclin-dependent kinase 9 CDK9
    Cyclin-dependent kinase inhibitor 1A (p21, Cip1) CDKN1A
    Cyclin-dependent kinase inhibitor 1B (p27, Kip1) CDKN1B
    CDKN2A interacting protein N-terminal like CDKN2AIPNL
    Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) CDKN2C
    Cyclin-dependent kinase inhibitor 3 (CDK2-associated dual CDKN3
    specificity phosphatase)
    CCAAT/enhancer binding protein (C/EBP), alpha CEBPA
    Centrosomal protein 135 kDa CEP135
    Centrosomal protein 70 kDa CEP70
    Chromatin assembly factor 1, subunit A (p150) CHAF1A
    CHK1 checkpoint homolog (S. pombe) CHEK1
    Chromogranin A (parathyroid secretory protein 1) CHGA
    Chromatin accessibility complex 1 CHRAC1
    Ceroid-lipofuscinosis, neuronal 5 CLN5
    Clusterin CLU
    Calponin 1, basic, smooth muscle CNN1
    Cannabinoid receptor 1 (brain) CNR1
    Collagen, type XVIII, alpha 1 COL18A1
    Collagen, type I, alpha 1 COL1A1
    Collagen, type IV, alpha 3 (Goodpasture antigen) COL4A3
    COMM domain containing 5 COMMD5
    Catechol-O-methyltransferase COMT
    Coatomer protein complex, subunit beta 2 (beta prime) COPB2
    COP9 constitutive photomorphogenic homolog subunit 5 COPS5
    (Arabidopsis)
    Cytoplasmic polyadenylation element binding protein 3 CPEB3
    Cysteine-rich secretory protein 3 CRISP3
    V-crk sarcoma virus CT10 oncogene homolog (avian) CRK
    V-crk sarcoma virus CT10 oncogene homolog (avian)-like CRKL
    Colony stimulating factor 1 receptor, formerly McDonough CSF1R
    feline sarcoma viral (v-fms) oncogene homolog
    Colony stimulating factor 2 (granulocyte-macrophage) CSF2
    Colony stimulating factor 3 receptor (granulocyte) CSF3R
    C-src tyrosine kinase CSK
    Cystatin B (stefin B) CSTB
    Connective tissue growth factor CTGF
    Collagen triple helix repeat containing 1 CTHRC1
    Catenin (cadherin-associated protein), alpha 1, 102 kDa CTNNA1
    Catenin (cadherin-associated protein), beta 1, 88 kDa CTNNB1
    Cathepsin B CTSB
    Cathepsin L1 CTSL1
    Cortactin CTTN
    Cullin 2 CUL2
    Chemokine (C—X—C motif) ligand 14 CXCL14
    Chemokine (C—X—C motif) ligand 9 CXCL9
    Chromosome X open reading frame 41 CXorf41
    Cytochrome b5 type A (microsomal) CYB5A
    Cytoplasmic FMR1 interacting protein 1 CYFIP1
    Cytochrome P450, family 27, subfamily A, polypeptide 1 CYP27A1
    Cytochrome P450, family 2, subfamily C, polypeptide 9 CYP2C9
    Cytochrome P450, family 3, subfamily A, polypeptide 5 CYP3A5
    Disabled homolog 2, mitogen-responsive phosphoprotein DAB2
    (Drosophila)
    Death associated protein 3 DAP3
    Death-associated protein kinase 1 DAPK1
    Deleted in colorectal carcinoma DCC
    Dodecenoyl-Coenzyme A delta isomerase (3,2 trans-enoyl- DCI
    Coenzyme A isomerase)
    Decorin DCN
    Dynactin 2 (p50) DCTN2
    Damage-specific DNA binding protein 2, 48 kDa DDB2
    Dopa decarboxylase (aromatic L-amino acid decarboxylase) DDC
    Development and differentiation enhancing factor 1 DDEF1
    DNA-damage-inducible transcript 3 DDIT3
    DEAD (Asp-Glu-Ala-Asp) box polypeptide 6 DDX6
    2,4-dienoyl CoA reductase 2, peroxisomal DECR2
    DEK oncogene (DNA binding) DEK
    DENN/MADD domain containing 3 DENND3
    DEP domain containing 1B DEPDC1B
    DEP domain containing 6 DEPDC6
    Diacylglycerol kinase, alpha 80 kDa DGKA
    DEAH (Asp-Glu-Ala-His) box polypeptide 9 DHX9
    Deiodinase, iodothyronine, type II DIO2
    DIRAS family, GTP-binding RAS-like 3 DIRAS3
    Dyskeratosis congenita 1, dyskerin DKC1
    DKEZP564O0823 protein DKEZP564O0823
    Discs, large homolog 3 (neuroendocrine-dlg, Drosophila) DLG3
    Discs, large (Drosophila) homolog-associated protein 1 DLGAP1
    Deleted in malignant brain tumors 1 DMBT1
    Dedicator of cytokinesis 5 DOCK5
    Desmoplakin DSP
    E2F transcription factor 1 E2F1
    E2F transcription factor 2 E2F2
    E2F transcription factor 3 E2F3
    E2F transcription factor 4, p107/p130-binding E2F4
    Endothelial differentiation, lysophosphatidic acid G-protein- EDG7
    coupled receptor, 7
    Endothelin receptor type B EDNRB
    Eukaryotic translation elongation factor 1 alpha 1 EEF1A1
    Embryonal Fyn-associated substrate EFS
    Epidermal growth factor (beta-urogastrone) EGF
    Epidermal growth factor receptor (erythroblastic leukemia EGFR
    viral (v-erb-b) oncogene homolog, avian)
    Early growth response 2 (Krox-20 homolog, Drosophila) EGR2
    Early growth response 3 EGR3
    Euchromatic histone-lysine N-methyltransferase 1 EHMT1
    Euchromatic histone-lysine N-methyltransferase 2 EHMT2
    Eukaryotic translation initiation factor 2-alpha kinase 2 EIF2AK2
    Eukaryotic translation initiation factor 3, subunit H EIF3H
    ELK1, member of ETS oncogene family ELK1
    ELK3, ETS-domain protein (SRF accessory protein 2) ELK3
    Elongation factor RNA polymerase II ELL
    Elongation factor RNA polymerase II-like 3 ELL3
    Epithelial membrane protein 2 EMP2
    Ectonucleotide pyrophosphatase/phosphodiesterase 2 ENPP2
    (autotaxin)
    Enhancer of yellow 2 homolog (Drosophila) ENY2
    EPH receptor A1 EPHA1
    EPH receptor B4 EPHB4
    Epsin 1 EPN1
    Erythropoietin EPO
    Epidermal growth factor receptor pathway substrate 15 EPS15
    Epidermal growth factor receptor pathway substrate 8 EPS8
    V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, ERBB2
    neuro/glioblastoma derived oncogene homolog (avian)
    V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 ERBB3
    (avian)
    V-erb-a erythroblastic leukemia viral oncogene homolog 4 ERBB4
    (avian)
    Excision repair cross-complementing rodent repair ERCC1
    deficiency, complementation group 1 (includes overlapping
    antisense sequence)
    Excision repair cross-complementing rodent repair ERCC2
    deficiency, complementation group 2 (xeroderma
    pigmentosum D)
    Excision repair cross-complementing rodent repair ERCC3
    deficiency, complementation group 3 (xeroderma
    pigmentosum group B complementing)
    Excision repair cross-complementing rodent repair ERCC4
    deficiency, complementation group 4
    Excision repair cross-complementing rodent repair ERCC5
    deficiency, complementation group 5 (xeroderma
    pigmentosum, complementation group G (Cockayne
    syndrome))
    Excision repair cross-complementing rodent repair ERCC6
    deficiency, complementation group 6
    V-ets erythroblastosis virus E26 oncogene homolog (avian) ERG
    Endoplasmic reticulum to nucleus signaling 2 ERN2
    Estrogen receptor 1 ESR1
    Estrogen receptor 2 (ER beta) ESR2
    V-ets erythroblastosis virus E26 oncogene homolog 1 ETS1
    (avian)
    V-ets erythroblastosis virus E26 oncogene homolog 2 ETS2
    (avian)
    Ets variant gene 1 ETV1
    Ets variant gene 4 (E1A enhancer binding protein, E1AF) ETV4
    Ets variant gene 6 (TEL oncogene) ETV6
    Even-skipped homeobox 1 EVX1
    Exocyst complex component 2 EXOC2
    Exostoses (multiple) 1 EXT1
    Exostoses (multiple) 2 EXT2
    Enhancer of zeste homolog 2 (Drosophila) EZH2
    Ezrin EZR
    Coagulation factor II (thrombin) receptor F2R
    Coagulation factor V (proaccelerin, labile factor) F5
    Family with sequence similarity 114, member A1 FAM114A1
    Family with sequence similarity 13, member C1 FAM13C1
    Family with sequence similarity 49, member B FAM49B
    Family with sequence similarity 84, member B FAM84B
    Family with sequence similarity 8, member A1 FAM8A1
    Fanconi anemia, complementation group A FANCA
    Fanconi anemia, complementation group G FANCG
    Fas (TNF receptor superfamily, member 6) FAS
    Fas ligand (TNF superfamily, member 6) FASLG
    Fatty acid synthase FASN
    Fibulin 1 FBLN1
    F-box protein 32 FBXO32
    F-box and WD repeat domain containing 11 FBXW11
    Farnesyl diphosphate synthase (farnesyl pyrophosphate FDPS
    synthetase, dimethylallyltranstransferase,
    geranyltranstransferase)
    Fer (fps/fes related) tyrosine kinase (phosphoprotein FER
    NCP94)
    Feline sarcoma oncogene FES
    FEV (ETS oncogene family) FEV
    Fibroblast growth factor 12 FGF12
    Fibroblast growth factor 3 (murine mammary tumor virus FGF3
    integration site (v-int-2) oncogene homolog)
    Fibroblast growth factor 5 FGF5
    Fibroblast growth factor 8 (androgen-induced) FGF8
    Fibroblast growth factor 9 (glia-activating factor) FGF9
    Fibroblast growth factor receptor 1 (fms-related tyrosine FGFR1
    kinase 2, Pfeiffer syndrome)
    Fibroblast growth factor receptor 2 (bacteria-expressed FGFR2
    kinase, keratinocyte growth factor receptor, craniofacial
    dysostosis 1, Crouzon syndrome, Pfeiffer syndrome,
    Jackson-Weiss syndrome)
    Fibroblast growth factor receptor 4 FGFR4
    Fragile histidine triad gene FHIT
    Folliculin FLCN
    Friend leukemia virus integration 1 FLI1
    Hypothetical protein FLJ90709 FLJ90709
    Fms-related tyrosine kinase 1 (vascular endothelial growth FLT1
    factor/vascular permeability factor receptor)
    Fms-related tyrosine kinase 4 FLT4
    Flavin containing monooxygenase 5 FMO5
    Fibromodulin FMOD
    Folate hydrolase (prostate-specific membrane antigen) 1 FOLH1
    Folate receptor 1 (adult) FOLR1
    V-fos FBJ murine osteosarcoma viral oncogene homolog FOS
    FK506 binding protein 12-rapamycin associated protein 1 FRAP1
    Frizzled-related protein FRZB
    FYN oncogene related to SRC, FGR, YES FYN
    Frizzled homolog 7 (Drosophila) FZD7
    Gamma-aminobutyric acid (GABA) A receptor, gamma 2 GABRG2
    Growth arrest and DNA-damage-inducible, alpha GADD45A
    G protein beta subunit-like GBL
    Gastrulation brain homeobox 2 GBX2
    Ganglioside-induced differentiation-associated protein 1 GDAP1
    Growth differentiation factor 15 GDF15
    Glioma-associated oncogene homolog 1 (zinc finger protein) GLI1
    Glutaredoxin 2 GLRX2
    GPI anchored molecule like protein GML
    Geminin, DNA replication inhibitor GMNN
    Guanine nucleotide binding protein (G protein), alpha 15 GNA15
    GNAS complex locus GNAS
    Guanine nucleotide binding protein (G protein), beta GNB1
    polypeptide 1
    Glucosamine (UDP-N-acetyl)-2-epimerase/N- GNE
    acetylmannosamine kinase
    N-acetylglucosamine-1-phosphate transferase, alpha and GNPTAB
    beta subunits
    Golgi membrane protein 1 GOLM1
    Golgi-localized protein GOLSYN
    G protein-coupled receptor 137B GPR137B
    Growth factor receptor-bound protein 2 GRB2
    Growth factor receptor-bound protein 7 GRB7
    Gremlin 2, cysteine knot superfamily, homolog (Xenopus GREM2
    laevis)
    Gastrin-releasing peptide receptor GRPR
    Glycogen synthase kinase 3 alpha GSK3A
    Glutathione S-transferase pi GSTP1
    Glucuronidase, beta GUSB
    H1 histone family, member X H1FX
    Heparin-binding EGF-like growth factor HBEGF
    HCCA2 protein HCCA2
    Host cell factor C1 (VP16-accessory protein) HCFC1
    Hemopoietic cell kinase HCK
    Histone deacetylase 1 HDAC1
    Histone deacetylase 7A HDAC7A
    Hepatoma-derived growth factor (high-mobility group HDGF
    protein 1-like)
    HECT, C2 and WW domain containing E3 ubiquitin protein HECW2
    ligase
    2
    Hypoxia-inducible factor 1, alpha subunit (basic helix-loop- HIF1A
    helix transcription factor)
    Hydroxymethylbilane synthase HMBS
    3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGCR
    Hyaluronan-mediated motility receptor (RHAMM) HMMR
    Hook homolog 1 (Drosophila) HOOK1
    Homeobox A9 HOXA9
    Homeobox C4 HOXC4
    Hepsin (transmembrane protease, serine 1) HPN
    Hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan HPRT1
    syndrome)
    V-Ha-ras Harvey rat sarcoma viral oncogene homolog HRAS
    Hydroxysteroid (17-beta) dehydrogenase 4 HSD17B4
    Hydroxysteroid (17-beta) dehydrogenase 6 homolog HSD17B6
    (mouse)
    Heat shock transcription factor 4 HSF4
    Heat shock 27 kDa protein 1 HSPB1
    Intercellular adhesion molecule 1 (CD54), human rhinovirus ICAM1
    receptor
    Immediate early response 3 IER3
    Interferon, gamma IFNG
    Interferon gamma receptor 1 IFNGR1
    Insulin-like growth factor 1 (somatomedin C) IGF1
    Insulin-like growth factor 1 receptor IGF1R
    Insulin-like growth factor 2 receptor IGF2R
    Insulin-like growth factor binding protein 1 IGFBP1
    Insulin-like growth factor binding protein 2, 36 kDa IGFBP2
    Insulin-like growth factor binding protein 3 IGFBP3
    Insulin-like growth factor binding protein 6 IGFBP6
    IKAROS family zinc finger 1 (Ikaros) IKZF1
    Interleukin 11 IL11
    Interleukin 12A (natural killer cell stimulatory factor 1, IL12A
    cytotoxic lymphocyte maturation factor 1, p35)
    Interleukin 12B (natural killer cell stimulatory factor 2, IL12B
    cytotoxic lymphocyte maturation factor 2, p40)
    Interleukin 13 IL13
    Interleukin 1, beta IL1B
    Interleukin 2 IL2
    Interleukin 3 (colony-stimulating factor, multiple) IL3
    Interleukin 4 IL4
    Interleukin 6 (interferon, beta 2) IL6
    Interleukin 6 receptor IL6R
    Interleukin 8 IL8
    Integrin-linked kinase ILK
    Inner membrane protein, mitochondrial (mitofilin) IMMT
    Inhibin, alpha INHA
    Inhibin, beta A INHBA
    Interferon regulatory factor 1 IRF1
    Insulin receptor substrate 2 IRS2
    ISL LIM homeobox 1 ISL1
    Integrin, alpha V (vitronectin receptor, alpha polypeptide, ITGAV
    antigen CD51)
    Integrin, beta 1 (fibronectin receptor, beta polypeptide, ITGB1
    antigen CD29 includes MDF2, MSK12)
    Integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) ITGB3
    Integrin, beta 4 ITGB4
    Inositol 1,4,5-trisphosphate 3-kinase A ITPKA
    Inositol 1,4,5-triphosphate receptor, type 1 ITPR1
    Isovaleryl Coenzyme A dehydrogenase IVD
    Janus kinase 2 (a protein tyrosine kinase) JAK2
    Jumonji, AT rich interactive domain 1A JARID1A
    Jumonji domain containing 2B JMJD2B
    Jun oncogene JUN
    Jun B proto-oncogene JUNB
    Jun D proto-oncogene JUND
    Potassium channel regulator KCNRG
    Kinase insert domain receptor (a type III receptor tyrosine KDR
    kinase)
    KH domain containing, RNA binding, signal transduction KHDRBS3
    associated 3
    KIAA0196 KIAA0196
    KIAA0922 KIAA0922
    KIAA1324 KIAA1324
    Kinesin family member C2 KIFC2
    V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene KIT
    homolog
    Kruppel-like factor 6 KLF6
    Ketch domain containing 4 KLHDC4
    Kallikrein-related peptidase 2 KLK2
    Kallikrein-related peptidase 3 KLK3
    Kallikrein-related peptidase 4 KLK4
    Karyopherin (importin) beta 1 KPNB1
    Keratin 15 KRT15
    Keratin 5 (epidermolysis bullosa simplex, Dowling- KRT5
    Meara/Kobner/Weber-Cockayne types)
    L1 cell adhesion molecule L1CAM
    Lymphocyte-specific protein tyrosine kinase LCK
    Lipocalin 2 LCN2
    Leprecan-like 1 LEPREL1
    Leucine-rich repeat-containing G protein-coupled receptor 4 LGR4
    Ligase I, DNA, ATP-dependent LIG1
    Ligase III, DNA, ATP-dependent LIG3
    LIM domain only 1 (rhombotin 1) LMO1
    LIM domain only 2 (rhombotin-like 1) LMO2
    Poly (ADP-ribose) polymerase family, member 1 LOC649459
    Lactotransferrin LOC728320
    Hypothetical protein BC008326 LOC89944
    Lysyl oxidase LOX
    Leucine rich repeat containing 2 LRRC2
    Limbic system-associated membrane protein LSAMP
    Latent transforming growth factor beta binding protein 2 LTBP2
    Mal, T-cell differentiation protein-like MALL
    Mucosa associated lymphoid tissue lymphoma translocation MALT1
    gene 1
    Monoamine oxidase B MAOB
    Mitogen-activated protein kinase kinase 6 MAP2K6
    Mitogen-activated protein kinase kinase kinase 8 MAP3K8
    Mitogen-activated protein kinase 1 MAPK1
    Mitogen-activated protein kinase 10 MAPK10
    Mitogen-activated protein kinase 14 MAPK14
    MARCKS-like 1 MARCKSL1
    MARVEL domain containing 3 MARVELD3
    MAS1 oncogene MAS1
    Megakaryocyte-associated tyrosine kinase MATK
    Methyl-CpG binding domain protein 2 MBD2
    Melanoma cell adhesion molecule MCAM
    Mutated in colorectal cancers MCC
    MCF.2 cell line derived transforming sequence MCF2
    Myeloid cell leukemia sequence 1 (BCL2-related) MCL1
    Minichromosome maintenance complex component 7 MCM7
    Microcephalin 1 MCPH1
    Mdm4, transformed 3T3 cell double minute 4, p53 binding MDM4
    protein (mouse)
    Mediator complex subunit 30 MED30
    Myocyte enhancer factor 2C MEF2C
    Meis homeobox 2 MEIS2
    Multiple endocrine neoplasia I MEN1
    Met proto-oncogene (hepatocyte growth factor receptor) MET
    Methyltransferase
    10 domain containing METT10D
    Hypothetical protein MGC15523 MGC15523
    Antigen identified by monoclonal antibody Ki-67 MKI67
    Myeloid leukemia factor 1 MLF1
    Myeloid leukemia factor 2 MLF2
    MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) MLH1
    Myeloid/lymphoid or mixed-lineage leukemia (trithorax MLLT3
    homolog, Drosophila); translocated to, 3
    Myeloid/lymphoid or mixed-lineage leukemia (trithorax MLLT4
    homolog, Drosophila); translocated to, 4
    Myeloid/lymphoid or mixed-lineage leukemia (trithorax MLLT6
    homolog, Drosophila); translocated to, 6
    Matrix metallopeptidase 1 (interstitial collagenase) MMP1
    Matrix metallopeptidase 10 (stromelysin 2) MMP10
    Matrix metallopeptidase 14 (membrane-inserted) MMP14
    Matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, MMP2
    72 kDa type IV collagenase)
    Matrix metallopeptidase 3 (stromelysin 1, progelatinase) MMP3
    Matrix metallopeptidase 7 (matrilysin, uterine) MMP7
    Matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, MMP9
    92 kDa type IV collagenase)
    V-mos Moloney murine sarcoma viral oncogene homolog MOS
    Membrane protein, palmitoylated 7 (MAGUK p55 MPP7
    subfamily member 7)
    Mitochondrial ribosomal protein L13 MRPL13
    MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) MSH2
    MutS homolog 3 (E. coli) MSH3
    MutS homolog 6 (E. coli) MSH6
    Microseminoprotein, beta- MSMB
    Macrophage scavenger receptor 1 MSR1
    Macrophage stimulating 1 receptor (c-met-related tyrosine MST1R
    kinase)
    Metastasis associated 1 MTA1
    5,10-methylenetetrahydrofolate reductase (NADPH) MTHFR
    Myotrophin MTPN
    5-methyltetrahydrofolate-homocysteine methyltransferase MTR
    Metastasis suppressor 1 MTSS1
    Mucin 1, cell surface associated MUC1
    MAX dimerization protein 1 MXD1
    MAX interactor 1 MXI1
    V-myb myeloblastosis viral oncogene homolog (avian) MYB
    V-myb myeloblastosis viral oncogene homolog (avian)-like 2 MYBL2
    Myosin binding protein C, slow type MYBPC1
    V-myc myelocytomatosis viral oncogene homolog (avian) MYC
    V-myc myelocytomatosis viral related oncogene, MYCN
    neuroblastoma derived (avian)
    Myosin, heavy chain 11, smooth muscle MYH11
    Myosin, light chain 9, regulatory MYL9
    Myosin, light chain kinase MYLK
    N-acetyltransferase 2 (arylamine N-acetyltransferase) NAT2
    Neuroblastoma, suppression of tumorigenicity 1 NBL1
    Nibrin NBN
    Non-SMC condensin II complex, subunit D3 NCAPD3
    N-myc downstream regulated gene 1 NDRG1
    NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9, NDUFB9
    22 kDa
    Neurofilament, heavy polypeptide 200 kDa NEFH
    Neogenin homolog 1 (chicken) NEO1
    Neuropilin (NRP) and tolloid (TLL)-like 2 NETO2
    Neurofibromin 1 (neurofibromatosis, von Recklinghausen NF1
    disease, Watson disease)
    Nuclear factor of kappa light polypeptide gene enhancer in NFKB1
    B-cells 1 (p105)
    Nuclear factor of kappa light polypeptide gene enhancer in NFKB2
    B-cells 2 (p49/p100)
    Nuclear factor of kappa light polypeptide gene enhancer in NFKBIA
    B-cells inhibitor, alpha
    Nitric oxide synthase 3 (endothelial cell) NOS3
    Notch homolog 1, translocation-associated (Drosophila) NOTCH1
    Notch homolog 2 (Drosophila) NOTCH2
    Notch homolog 4 (Drosophila) NOTCH4
    Nephroblastoma overexpressed gene NOV
    NADPH oxidase 4 NOX4
    Aminopeptidase-like 1 NPEPL1
    NAD(P)H dehydrogenase, quinone 1 NQO1
    Nuclear receptor subfamily 4, group A, member 1 NR4A1
    Neuroblastoma RAS viral (v-ras) oncogene homolog NRAS
    Neuropilin 1 NRP1
    Neurotrophic tyrosine kinase, receptor, type 1 NTRK1
    Neurotrophic tyrosine kinase, receptor, type 2 NTRK2
    Neurotrophic tyrosine kinase, receptor, type 3 NTRK3
    Nuclear mitotic apparatus protein 1 NUMA1
    Nucleoporin 98 kDa NUP98
    Ornithine decarboxylase antizyme 2 OAZ2
    Oxysterol binding protein-like 9 OSBPL9
    P antigen family, member 4 (prostate associated) PAGE4
    PAP associated domain containing 1 PAPD1
    Par-3 partitioning defective 3 homolog (C. elegans) PARD3
    PAS domain containing serine/threonine kinase PASK
    Pre-B-cell leukemia homeobox 1 PBX1
    Proliferating cell nuclear antigen PCNA
    PCTAIRE protein kinase 1 PCTK1
    Platelet-derived growth factor alpha polypeptide PDGFA
    Platelet-derived growth factor receptor, alpha polypeptide PDGFRA
    Platelet-derived growth factor receptor, beta polypeptide PDGFRB
    Protein disulfide isomerase family A, member 5 PDIA5
    PDZ and LIM domain 5 PDLIM5
    Phosphatidylethanolamine-binding protein 4 PEBP4
    Phosphatidylethanolamine N-methyltransferase PEMT
    Placental growth factor, vascular endothelial growth factor- PGF
    related protein
    Phosphoglycerate kinase 1 PGK1
    Progesterone receptor PGR
    Phosphatase and actin regulator 2 PHACTR2
    PHD finger protein 20-like 1 PHF20L1
    PHD finger protein 8 PHF8
    Phytanoyl-CoA 2-hydroxylase interacting protein-like PHYHIPL
    Protein inhibitor of activated STAT, 2 PIAS2
    Phosphoinositide-3-kinase, catalytic, alpha polypeptide PIK3CA
    Phosphoinositide-3-kinase, catalytic, delta polypeptide PIK3CD
    Polycystic kidney and hepatic disease 1 (autosomal PKHD1L1
    recessive)-like 1
    Phospholipase A2, group IIA (platelets, synovial fluid) PLA2G2A
    Phospholipase A2, group VII (platelet-activating factor PLA2G7
    acetylhydrolase, plasma)
    Pleiomorphic adenoma gene 1 PLAG1
    Plasminogen activator, tissue PLAT
    Plasminogen activator, urokinase receptor PLAUR
    Plasminogen PLG
    Plexin domain containing 1 PLXDC1
    Promyelocytic leukemia PML
    PMS1 postmeiotic segregation increased 1 (S. cerevisiae) PMS1
    Polymerase (RNA) I polypeptide C, 30 kDa POLR1C
    Periostin, osteoblast specific factor POSTN
    POU class 2 homeobox 1 POU2F1
    Peroxisome proliferator-activated receptor delta PPARD
    Peroxisome proliferator-activated receptor gamma PPARG
    Protein phosphatase 2 (formerly 2A), regulatory subunit A, PPP2R1B
    beta isoform
    Papillary renal cell carcinoma (translocation-associated) PRCC
    Peroxisomal proliferator-activated receptor A interacting PRIC285
    complex 285
    Protein kinase, cAMP-dependent, regulatory, type I, alpha PRKAR1A
    (tissue specific extinguisher 1)
    Protease, serine, 8 PRSS8
    Prostate stem cell antigen PSCA
    Proteasome (prosome, macropain) 26S subunit, non- PSMD1
    ATPase, 1
    Patched homolog 1 (Drosophila) PTCH1
    Patched homolog 2 (Drosophila) PTCH2
    Prostaglandin E receptor 3 (subtype EP3) PTGER3
    Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H PTGS1
    synthase and cyclooxygenase)
    Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H PTGS2
    synthase and cyclooxygenase)
    Parathyroid hormone-like hormone PTHLH
    PTK2 protein tyrosine kinase 2 PTK2
    PTK7 protein tyrosine kinase 7 PTK7
    Pleiotrophin (heparin binding growth factor 8, neurite PTN
    growth-promoting factor 1)
    Protein tyrosine phosphatase type IVA, member 3 PTP4A3
    Protein tyrosine phosphatase-like (proline instead of PTPLB
    catalytic arginine), member b
    Protein tyrosine phosphatase, receptor type, F PTPRF
    Protein tyrosine phosphatase, receptor type, G PTPRG
    Protein tyrosine phosphatase, receptor type, H PTPRH
    Protein tyrosine phosphatase, receptor type, N polypeptide 2 PTPRN2
    Poly-U binding splicing factor 60 KDa PUF60
    Purine-rich element binding protein A PURA
    Paxillin PXN
    Pyrroline-5-carboxylate reductase 1 PYCR1
    Pyrroline-5-carboxylate reductase-like PYCRL
    Glutaminyl-tRNA synthetase QARS
    RAB32, member RAS oncogene family RAB32
    RAB8A, member RAS oncogene family RAB8A
    Rabaptin, RAB GTPase binding effector protein 2 RABEP2
    RAD21 homolog (S. pombe) RAD21
    RAD23 homolog A (S. cerevisiae) RAD23A
    RAD50 homolog (S. cerevisiae) RAD50
    RAD54 homolog B (S. cerevisiae) RAD54B
    V-raf-1 murine leukemia viral oncogene homolog 1 RAF1
    V-ral simian leukemia viral oncogene homolog B (ras RALB
    related; GTP binding protein)
    RAP1, GTP-GDP dissociation stimulator 1 RAP1GDS1
    RAP2A, member of RAS oncogene family RAP2A
    Retinoic acid receptor, alpha RARA
    RAS p21 protein activator (GTPase activating protein) 1 RASA1
    Retinoblastoma 1 (including osteosarcoma) RB1
    Retinoblastoma binding protein 6 RBBP6
    Retinoblastoma-like 2 (p130) RBL2
    Retinol dehydrogenase 11 (all-trans/9-cis/11-cis) RDH11
    RecQ protein-like (DNA helicase Q1-like) RECQL
    RecQ protein-like 4 RECQL4
    V-rel reticuloendotheliosis viral oncogene homolog (avian) REL
    V-rel reticuloendotheliosis viral oncogene homolog A, RELA
    nuclear factor of kappa light polypeptide gene enhancer in
    B-cells 3, p65 (avian)
    Ret proto-oncogene RET
    Ras homolog gene family, member A RHOA
    Ras homolog gene family, member H RHOH
    Receptor (TNFRSF)-interacting serine-threonine kinase 1 RIPK1
    Relaxin 1 RLN1
    Ring finger protein 139 RNF139
    Ring finger protein 185 RNF185
    V-ros UR2 sarcoma virus oncogene homolog 1 (avian) ROS1
    Replication protein A1, 70 kDa RPA1
    Ras-related GTP binding C RRAGC
    Related RAS viral (r-ras) oncogene homolog RRAS
    Rhabdoid tumor deletion region gene 1 RTDR1
    S100 calcium binding protein A4 S100A4
    Sterile alpha motif domain containing 12 SAMD12
    Stearoyl-CoA desaturase 5 SCD5
    Sodium channel and clathrin linker 1 SCLT1
    Sodium channel, nonvoltage-gated 1 alpha SCNN1A
    Scribbled homolog (Drosophila) SCRIB
    Syndecan 2 SDC2
    Succinate dehydrogenase complex, subunit B, iron sulfur SDHB
    (Ip)
    Succinate dehydrogenase complex, subunit C, integral SDHC
    membrane protein, 15 kDa
    SEC14-like 1 (S. cerevisiae) SEC14L1
    Sema domain, immunoglobulin domain (Ig), short basic SEMA3F
    domain, secreted, (semaphorin) 3F
    Serpin peptidase inhibitor, clade B (ovalbumin), member 5 SERPINB5
    Serpin peptidase inhibitor, clade I (neuroserpin), member 1 SERPINI1
    Splicing factor 1 SF1
    Secreted frizzled-related protein 4 SFRP4
    SH3-domain binding protein 2 SH3BP2
    SH3 domain containing ring finger 2 SH3RF2
    Sonic hedgehog homolog (Drosophila) SHH
    Seven in absentia homolog 1 (Drosophila) SIAH1
    V-ski sarcoma viral oncogene homolog (avian) SKI
    SKI-like oncogene SKIL
    Solute carrier family 14 (urea transporter), member 1 (Kidd SLC14A1
    blood group)
    Solute carrier family 20 (phosphate transporter), member 1 SLC20A1
    Solute carrier family 22 (extraneuronal monoamine SLC22A3
    transporter), member 3
    Solute carrier family 25, member 42 SLC25A42
    Solute carrier family 44, member 1 SLC44A1
    Solute carrier family 45, member 3 SLC45A3
    SMAD family member 4 SMAD4
    SWI/SNF related, matrix associated, actin dependent SMARCB1
    regulator of chromatin, subfamily b, member 1
    SWI/SNF related, matrix associated, actin dependent SMARCC1
    regulator of chromatin, subfamily c, member 1
    Sphingomyelin phosphodiesterase, acid-like 3B SMPDL3B
    Small nuclear ribonucleoprotein polypeptide E SNRPE
    Syntrophin, beta 1 (dystrophin-associated protein A1, SNTB1
    59 kDa, basic component 1)
    Syntrophin, beta 2 (dystrophin-associated protein A1, SNTB2
    59 kDa, basic component 2)
    Syntrophin, gamma 1 SNTG1
    Suppressor of cytokine signaling 7 SOCS7
    Superoxide dismutase 1, soluble (amyotrophic lateral SOD1
    sclerosis 1 (adult))
    Secreted protein, acidic, cysteine-rich (osteonectin) SPARC
    SAM pointed domain containing ets transcription factor SPDEF
    Spleen focus forming virus (SFFV) proviral integration SPI1
    oncogene spi1
    Secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, SPP1
    early T-lymphocyte activation 1)
    Squalene epoxidase SQLE
    Sulfide quinone reductase-like (yeast) SQRDL
    V-src sarcoma (Schmidt-Ruppin A-2) viral oncogene SRC
    homolog (avian)
    Steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 SRD5A2
    alpha-steroid delta 4-dehydrogenase alpha 2)
    ST3 beta-galactoside alpha-2,3-sialyltransferase 1 ST3GAL1
    ST3 beta-galactoside alpha-2,3-sialyltransferase 5 ST3GAL5
    ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 ST6GAL1
    Suppression of tumorigenicity 7 ST7
    Signal transducer and activator of transcription 1, 91 kDa STAT1
    Signal transducer and activator of transcription 3 (acute- STAT3
    phase response factor)
    Signal transducer and activator of transcription 5B STAT5B
    Six transmembrane epithelial antigen of the prostate 2 STEAP2
    Stress-induced-phosphoprotein 1 (Hsp70/Hsp90-organizing STIP1
    protein)
    Serine/threonine kinase 11 STK11
    Spleen tyrosine kinase SYK
    Synapsin I SYN1
    Synapsin III SYN3
    Tumor-associated calcium signal transducer 1 TACSTD1
    TATA box binding protein (TBP)-associated factor, RNA TAF1C
    polymerase I, C, 110 kDa
    TAF2 RNA polymerase II, TATA box binding protein TAF2
    (TBP)-associated factor, 150 kDa
    T-cell acute lymphocytic leukemia 1 TAL1
    Tax1 (human T-cell leukemia virus type I) binding protein 1 TAX1BP1
    TATA box binding protein TBP
    Transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2
    TEK tyrosine kinase, endothelial (venous malformations, TEK
    multiple cutaneous and mucosal)
    Telomerase reverse transcriptase TERT
    Transcription factor AP-2 gamma (activating enhancer TFAP2C
    binding protein
    2 gamma)
    Transcription factor Dp-1 TFDP1
    Transcription factor binding to IGHM enhancer 3 TFE3
    Trefoil factor 1 TFF1
    TRK-fused gene TFG
    Transferrin receptor (p90, CD71) TFRC
    Transforming growth factor, alpha TGFA
    Transforming growth factor, beta 1 TGFB1
    Transforming growth factor, beta 2 TGFB2
    Transforming growth factor, beta 3 TGFB3
    Transforming growth factor, beta-induced, 68 kDa TGFBI
    Transforming growth factor, beta receptor I (activin A TGFBR1
    receptor type II-like kinase, 53 kDa)
    Transforming growth factor, beta receptor II (70/80 kDa) TGFBR2
    Transforming growth factor, beta receptor III TGFBR3
    Transglutaminase 2 (C polypeptide, protein-glutamine- TGM2
    gamma-glutamyltransferase)
    Thrombospondin 1 THBS1
    Thrombospondin 2 THBS2
    Thrombopoietin (myeloproliferative leukemia virus THPO
    oncogene ligand, megakaryocyte growth and development
    factor)
    T-cell lymphoma invasion and metastasis 1 TIAM1
    TIMP metallopeptidase inhibitor 2 TIMP2
    Thymidine kinase 1, soluble TK1
    Transmembrane protein with EGF-like and two follistatin- TMEFF2
    like domains 2
    Transmembrane protein 134 TMEM134
    Transmembrane protein 45B TMEM45B
    Transmembrane protein 65 TMEM65
    Transmembrane protein 71 TMEM71
    Transmembrane protease, serine 2 TMPRSS2
    Tumor necrosis factor receptor superfamily, member 10a TNFRSF10A
    Tumor necrosis factor receptor superfamily, member 10b TNFRSF10B
    Tumor necrosis factor receptor superfamily, member 11a, TNFRSF11A
    NFKB activator
    Tumor necrosis factor receptor superfamily, member 11b TNFRSF11B
    (osteoprotegerin)
    Tumor necrosis factor receptor superfamily, member 1A TNFRSF1A
    Tumor necrosis factor (ligand) superfamily, member 10 TNFSF10
    Tumor necrosis factor (ligand) superfamily, member 8 TNFSF8
    Topoisomerase (DNA) I TOP1
    Topoisomerase (DNA) II alpha 170 kDa TOP2A
    Tumor protein p53 (Li-Fraumeni syndrome) TP53
    Tumor protein p53 inducible protein 11 TP53I11
    Tumor protein p73 TP73
    Translocated promoter region (to activated MET oncogene) TPR
    TPX2, microtubule-associated, homolog (Xenopus laevis) TPX2
    Tripartite motif-containing 38 TRIM38
    TRNA methyltransferase 12 homolog (S. cerevisiae) TRMT12
    Transient receptor potential cation channel, subfamily M, TRPM8
    member 8
    Trichorhinophalangeal syndrome I TRPS1
    Tuberous sclerosis 1 TSC1
    Tuberous sclerosis 2 TSC2
    Tetraspanin 13 TSPAN13
    Tetraspanin 14 TSPAN14
    Tissue specific transplantation antigen P35B TSTA3
    Tetratricopeptide repeat domain 29 TTC29
    Thymidylate synthetase TYMS
    TYRO3 protein tyrosine kinase TYRO3
    Ubiquitin-conjugating enzyme E2, J2 (UBC6 homolog, UBE2J2
    yeast)
    UBX domain containing 3 UBXD3
    Vesicle-associated membrane protein 2 (synaptobrevin 2) VAMP2
    Vav 1 guanine nucleotide exchange factor VAV1
    Vav
    2 guanine nucleotide exchange factor VAV2
    Versican VCAN
    Vascular endothelial growth factor A VEGFA
    Vestigial like 3 (Drosophila) VGLL3
    Wiskott-Aldrich syndrome (eczema-thrombocytopenia) WAS
    WD repeat domain 67 WDR67
    WEE1 homolog (S. pombe) WEE1
    WNT1 inducible signaling pathway protein 1 WISP1
    Wingless-type MMTV integration site family, member 10B WNT10B
    Wingless-type MMTV integration site family member 2 WNT2
    Wingless-type MMTV integration site family, member 2B WNT2B
    Wingless-type MMTV integration site family, member 5A WNT5A
    Wingless-type MMTV integration site family, member 8B WNT8B
    Werner syndrome WRN
    Wilms tumor 1 WT1
    Xanthine dehydrogenase XDH
    Xeroderma pigmentosum, complementation group A XPA
    Xeroderma pigmentosum, complementation group C XPC
    X-ray repair complementing defective repair in Chinese XRCC1
    hamster cells 1
    X-ray repair complementing defective repair in Chinese XRCC4
    hamster cells 4
    X-ray repair complementing defective repair in Chinese XRCC5
    hamster cells 5 (double-strand-break rejoining; Ku
    autoantigen, 80 kDa)
    X-ray repair complementing defective repair in Chinese XRCC6
    hamster cells 6 (Ku autoantigen, 70 kDa)
    V-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 YES1
    Yip1 domain family, member 1 YIPF1
    Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase YWHAB
    activation protein, beta polypeptide
    Zinc finger protein 36, C3H type, homolog (mouse) ZFP36
    Zinc finger protein 313 ZNF313
    Zinc finger protein 34 ZNF34
    Zinc finger protein 511 ZNF511
    Zinc finger protein 7 ZNF7
  • TABLE 7
    RNA transcripts used to derive metagene values for 18-RNA
    metagene depicted in FIG. 3. The 6-RNA metagene is a subset
    of the sequences listed in Table 7, also depicted in FIG. 3.
    18-RNA metagene scores were scaled and normalized to
    generate ‘POP’ scores depicted in FIG. 4. Weighting
    factors were from the linear regression coefficient values;
    positive and negative values indicated transcripts correlated
    to increased expression in ‘SYS’ and ‘NED’ disease,
    respectively with intermediate expression values in the
    ‘PSA’ disease group.
    SEQ ID No Weights
    1 −6.08
    2 −5.71
    3 −5.68
    4 −5.39
    5 −5.26
    6 −4.84
    7 −4.7
    8 −4.68
    9 −4.66
    10 −4.55
    11 −4.53
    914 5.32
    915 5.27
    916 4.82
    917 4.64
    918 4.59
    919 4.54
    920 4.49
  • TABLE 8
    RNA transcripts used to derive metagene values for 20-RNA
    metagene depicted in FIG. 3. Weighting factors were from the
    linear regression coefficient values; positive and negative values
    indicated transcripts correlated to increased expression in
    ‘SYS’ and ‘NED’ disease, respectively with intermediate
    expression values in the ‘PSA’ disease group.
    SEQ ID No Weights
    1 −6.08
    4 −5.39
    6 −4.84
    9 −4.66
    14 −4.37
    15 −4.32
    16 −4.27
    18 −4.2
    19 −4.18
    20 −4.1
    21 −4.09
    915 5.27
    916 4.82
    917 4.64
    920 4.49
    922 4.43
    928 4.27
    929 4.27
    931 4.17
    935 4.08
    936 4.07
  • TABLE 9
    RNA transcripts used to derive 10-RNA metagene values, which
    were converted by scaling and normalizing into ‘POP’ scores
    depicted in FIG. 5. RNA transcripts were identified using Nearest
    Shrunken Centroids algorithm with leave-1-out cross-validation
    to distinguish ‘recurren’ (i.e., ‘SYS’) and ‘non-recurrent’
    (i.e., ‘PSA’ and ‘NED’) disease from Table 3 RNA transcripts.
    Weighting factors were from the test statistic values; positive and
    negative values indicated transcripts correlated to increased
    expression in ‘recurrent’ and ‘non-recurrent’ disease,
    respectively.
    Seq ID Weights
    3 −5.48
    36 −4.93
    60 −5.72
    63 −4.79
    926 4.61
    971 4.68
    978 5.27
    999 4.74
    1014 4.86
    1022 6.29
  • TABLE 10
    RNA transcripts used to derive 41-RNA metagene values, which
    were converted by scaling and normalizing into ‘POP’ scores
    depicted in FIG. 6. RNA transcripts were identified using Nearest
    Shrunken Centroids algorithm with leave-1-out cross-validation to
    distinguish ‘recurrent’ (i.e., ‘SYS’) and ‘non-recurrent’
    (i.e., ‘PSA’ and ‘NED’) disease from Table 3 RNA transcripts.
    Weighting factors were from the test statistic values; positive and
    negative values indicated transcripts correlated to increased
    expression in ‘recurrent’ and ‘non-recurrent’ disease,
    respectively.
    Seq ID Weights
    1 −4.1
    2 −4.21
    3 −5.48
    32 −3.87
    33 −3.75
    36 −4.93
    46 −4.14
    60 −5.72
    63 −4.79
    66 −4.02
    69 −3.25
    88 −4.54
    100 −3.63
    241 −4.16
    265 −3.86
    334 −3.36
    437 −4.02
    920 4.36
    925 3.04
    934 3.65
    945 4.03
    947 4.44
    954 4.34
    971 4.68
    978 5.27
    999 4.74
    1004 4.5
    1014 4.86
    1022 6.29
    1023 4.08
    1032 3.49
    1080 3.97
    1093 4.02
    1101 3.55
    1164 3.54
    1248 3.56
    1304 3.14
    1311 3.66
    1330 3.02
    1402 3.45
    1425 3.73
  • Although the invention has been described with reference to certain specific embodiments, various modifications thereof will be apparent to those skilled in the art without departing from the spirit and scope of the invention. All such modifications as would be apparent to one skilled in the art are intended to be included within the scope of the following claims.

Claims (42)

1. A system for expression-based assessment of prostate cancer recurrence risk, said system comprising one or more polynucleotides, each of said polynucleotides capable of specifically hybridizing to a RNA transcript of a gene selected from the group of genes set forth in Table 3 and/or Table 6.
2. The system of claim 1, wherein said one or more polynucleotides comprise one or more polynucleotide probes for the detection of the respective transcript.
3. The system of claim 1, wherein said one or more polynucleotides comprise one or more primer pairs, each of said primer pairs capable of amplifying a portion of a sequence corresponding to the respective transcript.
4. The system of any one of claims 1, 2 and 3, wherein said transcript comprises a sequence corresponding to one or more of the sequences set forth in SEQ ID NOs: 1-2114.
5. The system of any one of claims 1, 2 and 3, wherein said transcript comprises a sequence corresponding to one or more of the sequences set forth in a SEQ ID NOs: 914-2114.
6. The system according to any one of claims 1 to 5, wherein said system comprises at least 5 polynucleotides.
7. The system according to any one of claims 1 to 5, wherein said system comprises at least 10 polynucleotides.
8. The system according to any one of claims 1 to 5, wherein said system comprises at least 100 polynucleotides.
9. The system of claim 1, wherein each of said one or more polynucleotides comprises a sequence corresponding to, or complementary to, one or more of the sequences set forth in Table 4 or a fragment thereof.
10. The system of claim 1, wherein each of said one or more polynucleotides comprises a sequence corresponding to one or more nucleic acid molecules selected from the group consisting of:
(a) a nucleic acid depicted in any one of SEQ ID NOs: 1-2114;
(b) an RNA form of any one of the nucleic acids depicted in SEQ ID NOs: 1-2114;
(c) a peptide nucleic acid form of any one of the nucleic acids depicted in SEQ ID NOs: 1-2114;
(d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c);
(e) a nucleic acid comprising at least 25 consecutive bases having at least 90% sequence identity to any of (a-c); and
(f) a complement to any of (a-e).
11. The system of claim 1, wherein said transcript comprises one or more of the sequences as set forth in SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21 915-917, 920, 922, 928, 929, 931, 935 and 936.
12. The system of claim 1, wherein said transcript comprises one or more of the sequences as set forth in SEQ ID NOs: 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022.
13. The system of claim 1, wherein said transcript comprises one or more of the sequences as set forth in SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402, 1425.
14. Use of the system according to any one of claims 1, 2 and 4 to 11 for the preparation of a nucleic acid array
15. A nucleic acid array for expression-based assessment of prostate cancer recurrence risk, said array comprising at least ten probes immobilized on a solid support, each of said probes being between about 15 and about 500 nucleotides in length, each of said probes being derived from a sequence corresponding to, or complementary to, a transcript of a gene selected from the group of genes set forth in Table 3, or a portion of said transcript.
16. The nucleic acid array according to claim 15, wherein each of said probes comprises a sequence as set forth in any one of SEQ ID NOs: 1-2114 or complement thereof.
17. A method for expression-based assessment of prostate cancer recurrence risk, said method comprising: (a) determining the expression level of one or more transcripts of one or more genes in a test sample obtained from said subject to provide an expression pattern profile, said one or more genes selected from the group of genes set forth in Table 3, and (c) comparing said expression pattern profile with a reference expression pattern profile.
18. The method of claim 17, wherein an increased relative level of expression of one or more transcripts, a decreased relative level of expression of one or more transcripts, or a combination thereof is used to classify a prostate cancer as recurrent.
19. The method of claim 17, wherein an increased relative level of expression of one or more transcripts, a decreased relative level of expression of one or more transcripts, or a combination thereof is used to classify a prostate cancer as non-recurrent.
20. The method of claim 17; wherein said transcripts comprise a sequence as set forth in any one of SEQ ID NOs: 1-2114 or complement thereof.
21. The method of claim 17, wherein said one or more transcripts comprise one or more sequences as set forth in any one of SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21 915-917, 920, 922, 928, 929, 931, 935 and 936.
22. The method of claim 17, wherein said transcript comprises one or more of the sequences as set forth in SEQ ID NOs: 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022.
23. The method of claim 17, wherein said transcript comprises one or more of the sequences as set forth in SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402, 1425.
24. The method of claim 17, wherein the expression level of the one or more target sequences is determined by a method selected from the group consisting of RT-PCR, Northern blotting, ligase chain reaction, array hybridization, and a combination thereof.
25. The method of any one of claims 17 to 24, further comprising measuring the expression level of at least one control nucleic acid in the sample.
26. The method of any one of claims 17 to 25, wherein the sample is a fine needle aspirate biopsy [FNAB], cytology smear, cytology pellet, or a bulk tissue preparation.
27. The method of any one of claims 17 to 26, wherein the sample is fresh-frozen or fixed.
28. The method of any one of claims 17 to 27, wherein measuring the expression level utilizes a pattern recognition method.
29. The method of claim 28, wherein the pattern recognition method comprises a linear combination of expression levels of the target sequences.
30. The method of claim 28 or 29, wherein the pattern recognition method comprises a nonlinear combination of expression levels of the target sequences.
31. A kit for characterizing the expression of one or more nucleic acid sequences depicted in SEQ ID NOs: 1-2114 comprising one or more nucleic acids selected from:
(a) a nucleic acid depicted in any of SEQ ID NOs: 1-2114;
(b) an RNA form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114;
(c) a peptide nucleic acid form of any of the nucleic acids depicted in SEQ ID NOs: 1-2114;
(d) a nucleic acid comprising at least 20 consecutive bases of any of (a-c);
(e) a nucleic acid comprising at least 25 consecutive bases having at least 90% sequence identity to any of (a-c); or
(f) a complement to any of (a-e); and
optionally instructions for correlating the expression level of said one or more nucleic acid sequences with the disease state of prostate cancer tissue.
32. The kit of claim 31, wherein said one or more nucleic acids comprises one or more sequences as set forth in any one of SEQ ID NOs: 1, 4, 6, 9, 14-16, 18-21 915-917, 920, 922, 928, 929, 931, 935 and 936.
33. The kit of claim 31, wherein said one or more nucleic acids comprises one or more of the sequences as set forth in SEQ ID NOs: 3, 36, 60, 63, 926, 971, 978, 999, 1014 and 1022.
34. The kit of claim 31, wherein said one or more nucleic acids comprises one or more of the sequences as set forth in SEQ ID NOs 1-3, 32, 33, 36, 46, 60, 63, 66, 69, 88, 100, 241, 265, 334, 437, 920, 925, 934, 945, 947, 954, 971, 978, 999, 1004, 1014, 1022, 1023, 1032, 1080, 1093, 1101, 1164, 1248, 1304, 1311, 1330, 1402, 1425.
35. The kit of any one of claims 31 to 34, wherein said one or more nucleic acids comprises labeled nucleic acids.
36. The kit of any one of claims 31 to 35, wherein the kit comprises one or more primers or primer pairs that specifically amplify at least a portion of said nucleic acids.
37. The kit of any of claims 31 to 36, wherein the kit further comprises one or more control samples comprising expressed RNA, an amplification product produced therefrom or a surrogate therefore, said control one or more control samples selected from:
a sample from non-recurrent prostate cancer; and
a sample from recurrent prostate cancer.
38. An array of probe nucleic acids certified for use in expression-based assessment of prostate cancer recurrence risk, wherein said array comprises at least two different probe nucleic acids that specifically hybridize to corresponding different target nucleic acids depicted in one of SEQ ID NOs: 1-2114, an RNA form thereof, or a complement to either thereof.
39. The array of claim 38, further comprising one or more probe nucleic acids that specifically hybridize to house keeping genes.
40. A device for classifying a biological sample from a prostate cancer as recurrent or non-recurrent, the device comprising:
means for measuring the expression level of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6;
means for correlating the expression level with a classification of prostate cancer status; and
means for outputting the prostate cancer status.
41. The device of claim 40, wherein the machine utilizes an algorithm to characterize said expression level.
42. A computer-readable medium comprising one or more digitally-encoded expression pattern profiles representative of the level of expression of one or more transcripts of one or more genes selected from the group of genes set forth in Table 3 and/or 6, each of said one or more expression pattern profiles being associated with a value wherein each of said values is correlated with the presence of recurrent or non-recurrent prostate cancer.
US12/994,408 2008-05-28 2009-05-28 Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer Abandoned US20110136683A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/994,408 US20110136683A1 (en) 2008-05-28 2009-05-28 Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5682708P 2008-05-28 2008-05-28
US12/994,408 US20110136683A1 (en) 2008-05-28 2009-05-28 Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer
PCT/CA2009/000694 WO2009143603A1 (en) 2008-05-28 2009-05-28 Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2009/000694 A-371-Of-International WO2009143603A1 (en) 2008-05-28 2009-05-28 Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/092,468 Continuation US10865452B2 (en) 2008-05-28 2016-04-06 Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer

Publications (1)

Publication Number Publication Date
US20110136683A1 true US20110136683A1 (en) 2011-06-09

Family

ID=41376502

Family Applications (2)

Application Number Title Priority Date Filing Date
US12/994,408 Abandoned US20110136683A1 (en) 2008-05-28 2009-05-28 Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer
US15/092,468 Active US10865452B2 (en) 2008-05-28 2016-04-06 Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer

Family Applications After (1)

Application Number Title Priority Date Filing Date
US15/092,468 Active US10865452B2 (en) 2008-05-28 2016-04-06 Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer

Country Status (5)

Country Link
US (2) US20110136683A1 (en)
EP (2) EP2806054A1 (en)
AU (1) AU2009253675A1 (en)
CA (1) CA2725978A1 (en)
WO (1) WO2009143603A1 (en)

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013041731A1 (en) * 2011-09-23 2013-03-28 Katholieke Universiteit Leuven Marker gene based diagnosis, staging and prognosis of prostate cancer
WO2014025810A1 (en) 2012-08-07 2014-02-13 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Prostate cancer gene expression profiles
WO2014028907A1 (en) * 2012-08-16 2014-02-20 The Trustees Of Columbia University In The City Of New York Diagnostic markers of indolent prostate cancer
WO2014028884A3 (en) * 2012-08-16 2014-05-08 Genomedx Biosciences, Inc. Cancer diagnostics using biomarkers
WO2014152129A1 (en) * 2013-03-14 2014-09-25 Rutgers, The State University Of New Jersey A mathematical musical orchestral method for predicting classes of patients for medical treatment
WO2014205555A1 (en) * 2013-06-28 2014-12-31 British Columbia Cancer Agency Branch Methods and uses for diagnosis and treatment of prostate cancer
US20150191792A1 (en) * 2012-08-17 2015-07-09 Memorial Sloan-Kettering Cancer Center Gene expression profile associated with prostate cancer
JP2015528295A (en) * 2012-08-31 2015-09-28 ザ リージェンツ オブ ザ ユニヴァーシティ オブ コロラド，ア ボディ コーポレイト Cancer diagnosis and treatment methods
WO2015103287A3 (en) * 2013-12-30 2015-11-12 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Genomic rearrangements associated with prostate cancer and methods of using the same
WO2017007739A3 (en) * 2015-07-05 2017-02-23 Cytotest Inc. Nucleic acid probes
US10196697B2 (en) 2013-12-12 2019-02-05 Almac Diagnostics Limited Prostate cancer classification
CN109593835A (en) * 2017-09-29 2019-04-09 深圳华大基因股份有限公司 Method, kit and application for micro FFPE RNA Samples Estimates
US10260104B2 (en) 2010-07-27 2019-04-16 Genomic Health, Inc. Method for using gene expression to determine prognosis of prostate cancer
CN109709331A (en) * 2019-01-29 2019-05-03 广州瑞博奥生物科技有限公司 Purposes of the GDF15 in the kit that preparation is used for quantitative detection liver cancer marker
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
CN110456065A (en) * 2019-07-31 2019-11-15 四川大学华西医院 CCDC130 autoantibody detection reagent is preparing the purposes in screening lung cancer kit
US10494677B2 (en) 2006-11-02 2019-12-03 Mayo Foundation For Medical Education And Research Predicting cancer outcome
US10513737B2 (en) 2011-12-13 2019-12-24 Decipher Biosciences, Inc. Cancer diagnostics using non-coding transcripts
US10865452B2 (en) 2008-05-28 2020-12-15 Decipher Biosciences, Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
EP3739595A3 (en) * 2012-01-31 2021-01-27 Genomic Health, Inc. Gene expression profile algorithm and test for determining prognosis of prostate cancer
US11078542B2 (en) 2017-05-12 2021-08-03 Decipher Biosciences, Inc. Genetic signatures to predict prostate cancer metastasis and identify tumor aggressiveness
US11208697B2 (en) 2017-01-20 2021-12-28 Decipher Biosciences, Inc. Molecular subtyping, prognosis, and treatment of bladder cancer
US11414708B2 (en) 2016-08-24 2022-08-16 Decipher Biosciences, Inc. Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy
US11873532B2 (en) 2017-03-09 2024-01-16 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
JP7463357B2 (en) 2018-10-11 2024-04-08 コーニンクレッカ フィリップス エヌ ヴェ Preoperative risk stratification based on PDE4D7 and DHX9 expression

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10236078B2 (en) 2008-11-17 2019-03-19 Veracyte, Inc. Methods for processing or analyzing a sample of thyroid tissue
US9495515B1 (en) 2009-12-09 2016-11-15 Veracyte, Inc. Algorithms for disease diagnostics
US9074258B2 (en) 2009-03-04 2015-07-07 Genomedx Biosciences Inc. Compositions and methods for classifying thyroid nodule disease
WO2010124372A1 (en) 2009-04-29 2010-11-04 Genomedx Biosciences, Inc. Systems and methods for expression-based classification of thyroid tissue
WO2010129934A2 (en) 2009-05-07 2010-11-11 Veracyte, Inc. Methods and compositions for diagnosis of thyroid conditions
US10446272B2 (en) 2009-12-09 2019-10-15 Veracyte, Inc. Methods and compositions for classification of samples
AU2011235082B2 (en) 2010-04-02 2016-02-11 Veridex, Llc Gene-based prediction of PSA recurrence for clinically localized prostate cancer patients
US20120172244A1 (en) * 2010-12-20 2012-07-05 Steven Buechler Biomarkers and uses thereof in prognosis and treatment strategies for right-side colon cancer disease and left-side colon cancer disease
US20140113297A1 (en) * 2011-03-26 2014-04-24 Oregon Health & Science University Gene expression predictors of cancer prognosis
SE536352C2 (en) * 2011-10-24 2013-09-03 Chundsell Medicals Ab Cursor genes for classification of prostate cancer
WO2013190081A1 (en) * 2012-06-22 2013-12-27 Proyecto De Biomedicina Cima, S.L. Methods and reagents for the prognosis of cancer
US9889180B2 (en) 2012-11-19 2018-02-13 Agency For Science, Technology And Research Method of treating cancer
CN114606309A (en) 2014-11-05 2022-06-10 威拉赛特公司 Diagnostic system and method using machine learning and high-dimensional transcription data
US11217329B1 (en) 2017-06-23 2022-01-04 Veracyte, Inc. Methods and systems for determining biological sample integrity
CN109988836B (en) * 2019-03-18 2022-06-07 厦门艾德生物技术研究中心有限公司 FISH probe set for detecting NTRK fusion and application thereof
CN117511954A (en) * 2023-12-29 2024-02-06 湖南家辉生物技术有限公司 HCFC1 gene mutant, mutant protein, reagent, kit and application

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020168638A1 (en) * 2000-01-24 2002-11-14 Robert Schlegel Compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20030152980A1 (en) * 2001-12-21 2003-08-14 Whitehead Institute For Biomedical Research Prostate cancer diagnosis and outcome prediction by expression analysis
US20030224399A1 (en) * 2002-02-12 2003-12-04 Reed John C. Methods for determining the prognosis for patients with a prostate neoplastic condition
US20040009481A1 (en) * 2001-06-11 2004-01-15 Millennium Pharmaceuticals, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20040259086A1 (en) * 2000-02-17 2004-12-23 Millennium Pharmaceuticals, Inc. Novel genes, compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20050064455A1 (en) * 2003-05-28 2005-03-24 Baker Joffre B. Gene expression markers for predicting response to chemotherapy
US20050227917A1 (en) * 1997-12-23 2005-10-13 Williams Lewis T Gene products differentially expressed in cancerous cells and their methods of use II
US20050260646A1 (en) * 2004-04-09 2005-11-24 Genomic Health Inc. Gene expression markers for predicting response to chemotherapy
US20060046253A1 (en) * 2004-09-02 2006-03-02 Suntory Limited Method for analyzing genes of industrial yeasts
US20060204989A1 (en) * 1998-09-22 2006-09-14 Kopreski Michael S Comparative analysis of extracellular RNA species
US20070048738A1 (en) * 2003-07-14 2007-03-01 Mayo Foundation For Medical Education And Research Methods and compositions for diagnosis, staging and prognosis of prostate cancer
US20070083334A1 (en) * 2001-09-14 2007-04-12 Compugen Ltd. Methods and systems for annotating biomolecular sequences
US20070259352A1 (en) * 2004-10-04 2007-11-08 Itzhak Bentwich Prostate cancer-related nucleic acids
US20080009001A1 (en) * 2004-10-06 2008-01-10 Saverio Bettuzzi Method for Identification of Neoplastic Transformation with Particular Reference to Prostate Cancer
US20110045462A1 (en) * 2006-11-14 2011-02-24 The Regents Of The University Of California Digital analysis of gene expression

Family Cites Families (276)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT277936B (en) 1968-02-27 1970-01-12 Guenter Dipl Ing Knapp Method for the quantitative determination of iodine and thyroid hormones and device for carrying out the method
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4323546A (en) 1978-05-22 1982-04-06 Nuc Med Inc. Method and composition for cancer detection in humans
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
ATE88761T1 (en) 1986-01-10 1993-05-15 Amoco Corp COMPETITIVE HOMOGENEOUS TEST.
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US5283174A (en) 1987-09-21 1994-02-01 Gen-Probe, Incorporated Homogenous protection assay
US5130238A (en) 1988-06-24 1992-07-14 Cangene Corporation Enhanced nucleic acid amplification process
US5225326A (en) 1988-08-31 1993-07-06 Research Development Foundation One step in situ hybridization assay
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
AU650622B2 (en) 1989-07-11 1994-06-30 Gen-Probe Incorporated Nucleic acid sequence amplification methods utilizing a transcription complex
CA2020958C (en) 1989-07-11 2005-01-11 Daniel L. Kacian Nucleic acid sequence amplification methods
US5494810A (en) 1990-05-03 1996-02-27 Cornell Research Foundation, Inc. Thermostable ligase-mediated DNA amplifications system for the detection of genetic disease
US5798257A (en) 1990-07-09 1998-08-25 Research Corporation Technologies, Inc. Nucleic acid encoding human MTS-1 protein
ES2155822T3 (en) 1990-12-06 2001-06-01 Affymetrix Inc COMPOUNDS AND ITS USE IN A BINARY SYNTHESIS STRATEGY.
US5455166A (en) 1991-01-31 1995-10-03 Becton, Dickinson And Company Strand displacement amplification
US5994069A (en) 1996-01-24 1999-11-30 Third Wave Technologies, Inc. Detection of nucleic acids by multiple sequential invasive cleavages
US5846717A (en) 1996-01-24 1998-12-08 Third Wave Technologies, Inc. Detection of nucleic acid sequences by invader-directed cleavage
US5270184A (en) 1991-11-19 1993-12-14 Becton, Dickinson And Company Nucleic acid target generation
US5384261A (en) 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
AU675054B2 (en) 1991-11-22 1997-01-23 Affymetrix, Inc. Combinatorial strategies for polymer synthesis
US5545524A (en) 1991-12-04 1996-08-13 The Regents Of The University Of Michigan Compositions and methods for chromosome region-specific probes
US6204370B1 (en) 1992-03-11 2001-03-20 Institute Of Virology, Slovak Academy Of Sciences MN gene and protein
US6027887A (en) 1992-03-11 2000-02-22 Institute Of Virology, Solvak Academy Of Sciences MN gene and protein
US5541061A (en) 1992-04-29 1996-07-30 Affymax Technologies N.V. Methods for screening factorial chemical libraries
US5288514A (en) 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US5925517A (en) 1993-11-12 1999-07-20 The Public Health Research Institute Of The City Of New York, Inc. Detectably labeled dual conformation oligonucleotide probes, assays and kits
US5538848A (en) 1994-11-16 1996-07-23 Applied Biosystems Division, Perkin-Elmer Corp. Method for detecting nucleic acid amplification using self-quenching fluorescence probe
US5989815A (en) 1994-03-18 1999-11-23 University Of Utah Research Foundation Methods for detecting predisposition to cancer at the MTS gene
US5648211A (en) 1994-04-18 1997-07-15 Becton, Dickinson And Company Strand displacement amplification using thermophilic enzymes
US7625697B2 (en) 1994-06-17 2009-12-01 The Board Of Trustees Of The Leland Stanford Junior University Methods for constructing subarrays and subarrays made thereby
US5830753A (en) 1994-09-30 1998-11-03 Ludwig Institute For Cancer Research Isolated nucleic acid molecules coding for tumor rejection antigen precursor dage and uses thereof.
JP3189000B2 (en) 1994-12-01 2001-07-16 東ソー株式会社 Specific nucleic acid sequence detection method
US5710029A (en) 1995-06-07 1998-01-20 Gen-Probe Incorporated Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
US5705365A (en) 1995-06-07 1998-01-06 Gen-Probe Incorporated Kits for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
US5854206A (en) 1995-08-25 1998-12-29 Corixa Corporation Compounds and methods for treatment and diagnosis of prostate cancer
US5854033A (en) 1995-11-21 1998-12-29 Yale University Rolling circle replication reporter systems
US5985557A (en) 1996-01-24 1999-11-16 Third Wave Technologies, Inc. Invasive cleavage of nucleic acids
US6121489A (en) 1996-03-05 2000-09-19 Trega Biosciences, Inc. Selectively N-alkylated peptidomimetic combinatorial libraries and compounds therein
AU728186B2 (en) 1996-03-15 2001-01-04 Corixa Corporation Compounds and methods for immunotherapy and immunodiagnosis of prostate cancer
CA2252048C (en) 1996-04-12 2008-03-11 The Public Health Research Institute Of The City Of New York, Inc. Detection probes, kits and assays
US6225051B1 (en) 1996-04-16 2001-05-01 Haruo Sugiyama Method of detecting solid cancer cells and tissue atypia and method of testing tissues for use in bone marrow transplantation and peripheral blood stem cell transplantation
US6136182A (en) 1996-06-07 2000-10-24 Immunivest Corporation Magnetic devices and sample chambers for examination and manipulation of cells
US5711029A (en) 1996-06-21 1998-01-27 Visco; Raymond D. Protective apparatus for dispersing pressure applied at a joint
US20030185830A1 (en) 1997-02-25 2003-10-02 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
EP1005546A2 (en) 1997-02-25 2000-06-07 Corixa Corporation Compounds for immunotherapy of prostate cancer and methods for their use
AU6545898A (en) 1997-03-07 1998-09-22 Reprogen, Inc. Method for identifying hormonally modulated genes
US6198107B1 (en) 1997-03-07 2001-03-06 Clare Chemical Research, Inc. Fluorometric detection using visible light
US7008765B1 (en) 1997-04-10 2006-03-07 The Johns Hopkins University PCA3, PCA3 genes, and methods of use
GB9711040D0 (en) 1997-05-29 1997-07-23 Duff Gordon W Prediction of inflammatory disease
US20020076735A1 (en) 1998-09-25 2002-06-20 Williams Lewis T. Diagnostic and therapeutic methods using molecules differentially expressed in cancer cells
KR100501550B1 (en) 1998-06-08 2005-07-18 후소 야쿠힝 고교 가부시끼가이샤 Antibody against LAR phosphatase subunit
WO2000001850A2 (en) 1998-07-02 2000-01-13 Gen-Probe Incorporated Molecular torches
US6406921B1 (en) 1998-07-14 2002-06-18 Zyomyx, Incorporated Protein arrays for high-throughput screening
US6573043B1 (en) 1998-10-07 2003-06-03 Genentech, Inc. Tissue analysis and kits therefor
US6468476B1 (en) 1998-10-27 2002-10-22 Rosetta Inpharmatics, Inc. Methods for using-co-regulated genesets to enhance detection and classification of gene expression patterns
EP2287338B1 (en) 1998-11-09 2012-09-05 Eiken Kagaku Kabushiki Kaisha Process for synthesizing nucleic acid
US6828429B1 (en) 1999-03-26 2004-12-07 Henry M. Jackson Foundation For The Advancement Of Military Medicine Prostate-specific gene, PCGEM1, and the methods of using PCGEM1 to detect, treat, and prevent prostate cancer
US6303305B1 (en) 1999-03-30 2001-10-16 Roche Diagnostics, Gmbh Method for quantification of an analyte
US6436642B1 (en) 1999-04-20 2002-08-20 Curagen Corporation Method of classifying a thyroid carcinoma using differential gene expression
EP1055734B1 (en) 1999-05-24 2004-10-13 Tosoh Corporation Method for assaying ribonucleic acid
CA2384838C (en) 1999-09-13 2006-07-18 Nugen Technologies, Inc. Methods and compositions for linear isothermal amplification of polynucleotide sequences
US7211390B2 (en) 1999-09-16 2007-05-01 454 Life Sciences Corporation Method of sequencing a nucleic acid
US7244559B2 (en) 1999-09-16 2007-07-17 454 Life Sciences Corporation Method of sequencing a nucleic acid
WO2001052789A2 (en) 2000-01-20 2001-07-26 The Brigham And Women's Hospital, Inc. PAX8-PPARη NUCLEIC ACID MOLECULES AND POLYPEPTIDES AND USES THEREOF
US7700341B2 (en) 2000-02-03 2010-04-20 Dendreon Corporation Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon
US7361488B2 (en) 2000-02-07 2008-04-22 Illumina, Inc. Nucleic acid detection methods using universal priming
WO2001066753A2 (en) 2000-03-09 2001-09-13 Chiron Corporation Human genes and gene expression products
US7700359B2 (en) * 2000-06-02 2010-04-20 Novartis Vaccines And Diagnostics, Inc. Gene products differentially expressed in cancerous cells
FR2810677B1 (en) 2000-06-27 2004-10-01 Urogene PROCESS FOR IN VITRO DIAGNOSIS OF PROSTATE CANCER AND IMPLEMENTATION KIT
US6673545B2 (en) 2000-07-28 2004-01-06 Incyte Corporation Prostate cancer markers
US20070037165A1 (en) 2000-09-08 2007-02-15 Applera Corporation Polymorphisms in known genes associated with human disease, methods of detection and uses thereof
US7892730B2 (en) 2000-12-22 2011-02-22 Sagres Discovery, Inc. Compositions and methods for cancer
US6988040B2 (en) 2001-01-11 2006-01-17 Affymetrix, Inc. System, method, and computer software for genotyping analysis and identification of allelic imbalance
US20040029114A1 (en) 2001-01-24 2004-02-12 Eos Technology, Inc. Methods of diagnosis of breast cancer, compositions and methods of screening for modulators of breast cancer
WO2002064781A2 (en) 2001-02-09 2002-08-22 Active Pass Pharmaceuticals, Inc. Regulation of amyloid precursor protein expression by modification of abc transporter expression or activity
US7026163B1 (en) 2001-02-23 2006-04-11 Mayo Foundation For Medical Education And Research Sulfotransferase sequence variants
EP1392861A1 (en) 2001-02-27 2004-03-03 EOS Biotechnology, Inc. Novel methods of diagnosis of metastatic colorectal cancer, compositions and methods of screening for modulators of metastatic colorectal cancer
US20030190602A1 (en) 2001-03-12 2003-10-09 Monogen, Inc. Cell-based detection and differentiation of disease states
WO2002083921A2 (en) 2001-04-10 2002-10-24 Agensys, Inc. Nuleic acids and corresponding proteins useful in the detection and treatment of various cancers
US7229774B2 (en) 2001-08-02 2007-06-12 Regents Of The University Of Michigan Expression profile of prostate cancer
JP4291143B2 (en) 2001-08-31 2009-07-08 ジェン−プロウブ インコーポレイテッド Affinity-shifted probe for quantification of analyte polynucleotide
ES2253533T3 (en) 2001-09-06 2006-06-01 Adnagen Ag PROCEDURE FOR QUALITATIVE AND / OR QUANTITATIVE DETECTION OF CELLS.
US20050202442A1 (en) 2003-12-15 2005-09-15 Morris David W. Novel therapeutic targets in cancer
DE60235413D1 (en) 2001-12-07 2010-04-01 Novartis Vaccines & Diagnostic IN PROSTATE CANCER HIGHLY REGULATED ENDOGENIC RETROVIRUS
US20030186248A1 (en) 2002-03-29 2003-10-02 Erlander Mark G. Interpreting cytological specimens via molecular histological signatures
US20030194734A1 (en) 2002-03-29 2003-10-16 Tim Jatkoe Selection of markers
US20050143933A1 (en) 2002-04-23 2005-06-30 James Minor Analyzing and correcting biological assay data using a signal allocation model
US20050032065A1 (en) 2002-06-24 2005-02-10 Afar Daniel E. H. Methods of prognosis of prostate cancer
US20040018493A1 (en) 2002-07-12 2004-01-29 Anastasio Alison E. Haplotypes of the CD3E gene
EP2385139A1 (en) 2002-07-31 2011-11-09 University of Southern California Polymorphisms for predicting disease and treatment outcome
ATE414792T1 (en) 2002-09-20 2008-12-15 New England Biolabs Inc HELICASE-DEPENDENT AMPLIFICATION OF NUCLEIC ACIDS
US7300788B2 (en) 2002-10-08 2007-11-27 Affymetrix, Inc. Method for genotyping polymorphisms in humans
US20050266443A1 (en) 2002-10-11 2005-12-01 Thomas Jefferson University Novel tumor suppressor gene and compositions and methods for making and using the same
US20060127907A1 (en) 2002-11-07 2006-06-15 Daiichi Pure Chemicals Co., Ltd. Method of detecting gene mutation
AU2004254552B2 (en) 2003-01-29 2008-04-24 454 Life Sciences Corporation Methods of amplifying and sequencing nucleic acids
DK1597391T3 (en) 2003-02-20 2009-01-12 Genomic Health Inc Use of intron RNA to measure gene expression
US7378233B2 (en) 2003-04-12 2008-05-27 The Johns Hopkins University BRAF mutation T1796A in thyroid cancers
US20070275915A1 (en) 2003-04-15 2007-11-29 Cell Genesys, Inc. Tmprss2 Regulatory Sequences and Uses Thereof
JP2006525027A (en) 2003-05-01 2006-11-09 ジェン−プロウブ インコーポレイテッド Oligonucleotides containing molecular switches
WO2005001132A2 (en) 2003-05-30 2005-01-06 The Board Of Trustees Of The University Of Illinois Gene expression profiles that identify genetically elite ungulate mammals
JP2007516693A (en) 2003-06-09 2007-06-28 ザ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・ミシガン Compositions and methods for the treatment and diagnosis of cancer
EP1644858B1 (en) 2003-07-10 2017-12-06 Genomic Health, Inc. Expression profile algorithm and test for cancer prognosis
US20050118625A1 (en) 2003-10-02 2005-06-02 Mounts William M. Nucleic acid arrays for detecting gene expression associated with human osteoarthritis and human proteases
AU2004284434A1 (en) 2003-10-16 2005-05-06 Genomic Health, Inc. qRT-PCR assay system for gene expression profiling
US20050130177A1 (en) 2003-12-12 2005-06-16 3M Innovative Properties Company Variable valve apparatus and methods
US20070065827A1 (en) 2003-12-12 2007-03-22 Bayer Pharmaceuticals Corporation Gene expression profiles and methods of use
US20050250125A1 (en) 2003-12-19 2005-11-10 Novakoff James L Method for conducting pharmacogenomics-based studies
US20090020433A1 (en) 2003-12-31 2009-01-22 Microfabrica Inc. Electrochemical Fabrication Methods for Producing Multilayer Structures Including the use of Diamond Machining in the Planarization of Deposits of Material
US7407755B2 (en) 2004-01-15 2008-08-05 Lubinski Jan Determining a predisposition to cancer
WO2005078139A2 (en) 2004-02-09 2005-08-25 Thomas Jefferson University DIAGNOSIS AND TREATMENT OF CANCERS WITH MicroRNA LOCATED IN OR NEAR CANCER-ASSOCIATED CHROMOSOMAL FEATURES
WO2005085471A2 (en) 2004-03-03 2005-09-15 Universität Leipzig Method and means for differential diagnosis of thyroid tumours
US8426126B2 (en) 2004-03-18 2013-04-23 Applied Biosystems, Llc Modified surfaces as solid supports for nucleic acid purification
WO2005095654A1 (en) 2004-03-25 2005-10-13 Biohelix Corporation Helicase-dependent amplification of circular nucleic acids
US7319011B2 (en) 2004-04-08 2008-01-15 Duke University Method for distinguishing follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC)
WO2005100608A2 (en) 2004-04-09 2005-10-27 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, National Institutes Of Health Diagnostic tool for diagnosing benign versus malignant thyroid lesions
US20050240357A1 (en) 2004-04-26 2005-10-27 Minor James M Methods and systems for differential clustering
US7306916B2 (en) * 2004-05-04 2007-12-11 Dako Denmark A/S Methods for detecting chromosome aberrations
EP2471921A1 (en) 2004-05-28 2012-07-04 Asuragen, Inc. Methods and compositions involving microRNA
CA2569698A1 (en) 2004-06-04 2006-01-12 Mark G. Erlander The importance of the gene hoxb13 for cancer
US20060019615A1 (en) 2004-07-24 2006-01-26 Ditmer Larry R Wireless keying for a continuous wave (CW) amateur radio transmitter
WO2006014013A1 (en) 2004-08-04 2006-02-09 Riken Bone/joint disease sensitivity gene and use thereof
CA2576912A1 (en) 2004-08-11 2006-02-23 The Cleveland Clinic Foundation Method of detecting thyroid cancer
EP2071031B1 (en) 2004-08-27 2013-10-09 Gen-Probe Incorporated Single-primer nucleic acid amplification methods
MX2007004176A (en) 2004-10-06 2007-06-15 Mayo Foundation B7-h1 and methods of diagnosis, prognosis, and treatment of cancer.
US7629325B2 (en) 2004-10-11 2009-12-08 Technion Research & Development Foundation Ltd. Human Sef isoforms and methods of using same for cancer diagnosis and gene therapy
US7485468B2 (en) 2004-10-15 2009-02-03 Galapagos Bv Molecular targets and compounds, and methods to identify the same, useful in the treatment of joint degenerative and inflammatory diseases
WO2006047482A2 (en) 2004-10-22 2006-05-04 Redpath Integrated Pathology, Inc. Method for determining the diagnosis, malignant potential, and biologic behavior of pancreatic cysts using cyst aspirate
EP1815021A2 (en) 2004-11-03 2007-08-08 Almac Diagnostics Limited Transcriptome microarray technology and methods of using the same
US7666595B2 (en) 2005-02-25 2010-02-23 The Brigham And Women's Hospital, Inc. Biomarkers for predicting prostate cancer progression
US20120122718A1 (en) 2005-03-01 2012-05-17 Reisman David N BRM Expression and Related Diagnostics
JP2008536488A (en) * 2005-03-16 2008-09-11 シドニー キンメル キャンサー センター Methods and compositions for predicting cancer death and prostate cancer survival using gene expression signatures
US20070020657A1 (en) 2005-05-20 2007-01-25 Grebe Stefan K Methods for detecting circulating tumor cells
US20070037186A1 (en) 2005-05-20 2007-02-15 Yuqiu Jiang Thyroid fine needle aspiration molecular assay
WO2006135596A2 (en) 2005-06-06 2006-12-21 The Regents Of The University Of Michigan Prognostic meta signatures and uses thereof
EP1907858A4 (en) 2005-06-13 2009-04-08 Univ Michigan Compositions and methods for treating and diagnosing cancer
US20070099209A1 (en) 2005-06-13 2007-05-03 The Regents Of The University Of Michigan Compositions and methods for treating and diagnosing cancer
IL177006A0 (en) 2005-08-02 2006-12-10 Veridex Llc Predicting bone relapse of breast cancer
JP2009504183A (en) 2005-08-15 2009-02-05 ジェネンテック・インコーポレーテッド Gene disruption and related compositions and methods
AU2006291054B2 (en) 2005-09-12 2011-10-13 The Brigham And Women's Hospital, Inc. Recurrent gene fusions in prostate cancer
US9957569B2 (en) 2005-09-12 2018-05-01 The Regents Of The University Of Michigan Recurrent gene fusions in prostate cancer
CN101313306B (en) 2005-09-22 2011-11-16 中国合成橡胶股份有限公司 Gene expression profiling for identification of prognostic subclasses in nasopharyngeal carcinomas
WO2007038792A2 (en) 2005-09-28 2007-04-05 H. Lee Moffitt Cancer Center Individualized cancer treatments
US7962291B2 (en) 2005-09-30 2011-06-14 Affymetrix, Inc. Methods and computer software for detecting splice variants
WO2007039290A2 (en) 2005-10-03 2007-04-12 Epigenomics Ag Methods and nucleic acids for the analysis of gene expression associated with the prognosis of cell proliferative disorders
US7598052B2 (en) 2005-10-11 2009-10-06 The Regents Of The University Of Michigan Expression profile of thyroid cancer
US20070220621A1 (en) 2005-10-31 2007-09-20 Clarke Michael F Genetic characterization and prognostic significance of cancer stem cells in cancer
EP1945817A4 (en) 2005-11-02 2008-12-10 Univ Michigan Technology Man W Molecular profiling of cancer
WO2007070621A2 (en) 2005-12-13 2007-06-21 Children's Medical Center Corporation Prognosis indicators for solid human tumors
AU2007205234B2 (en) 2006-01-05 2012-07-12 The Ohio State University Research Foundation MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer
CN103642900B (en) 2006-01-05 2016-04-13 俄亥俄州立大学研究基金会 For the diagnosis and treatment of the method and composition based on Microrna of solid carcinoma
US20070172841A1 (en) 2006-01-25 2007-07-26 Hui Wang Probe/target stabilization with add-in oligo
FR2896881B1 (en) 2006-01-31 2008-04-18 Biomerieux Sa METHOD FOR DETERMINING PRONGF FOR IN VITRO DIAGNOSIS OF BREAST CANCER AND USE OF PRONGF IN THERAPY
US7670775B2 (en) 2006-02-15 2010-03-02 The Ohio State University Research Foundation Method for differentiating malignant from benign thyroid tissue
JP4867018B2 (en) 2006-03-22 2012-02-01 富士フイルム株式会社 Cancer detection method and suppression method
US7914988B1 (en) 2006-03-31 2011-03-29 Illumina, Inc. Gene expression profiles to predict relapse of prostate cancer
US20100279327A1 (en) 2006-06-12 2010-11-04 Bipar Sciences, Inc. Method of treating diseases with parp inhibitors
US20080076674A1 (en) 2006-07-06 2008-03-27 Thomas Litman Novel oligonucleotide compositions and probe sequences useful for detection and analysis of non coding RNAs associated with cancer
US20080028302A1 (en) 2006-07-31 2008-01-31 Steffen Meschkat Method and apparatus for incrementally updating a web page
FI20060751A0 (en) 2006-08-23 2006-08-23 Valtion Teknillinen Method of treating prostate cancer and screening of patients who benefit from said method
US8273539B2 (en) 2006-09-25 2012-09-25 Mayo Foundation For Medical Education And Research Extracellular and membrane-associated prostate cancer markers
AU2007324128B2 (en) 2006-10-10 2013-10-10 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Prostate cancer-specific alterations in ERG gene expression and detection and treatment methods based on those alterations
EP2090665A2 (en) 2006-10-20 2009-08-19 Exiqon A/S Novel human microRNAs associated with cancer
US8338109B2 (en) 2006-11-02 2012-12-25 Mayo Foundation For Medical Education And Research Predicting cancer outcome
US8470534B2 (en) 2006-12-01 2013-06-25 Erik S. Knudsen Methods of predicting resistance or sensitivity to therapies for cancer
WO2008086478A2 (en) 2007-01-10 2008-07-17 Henry Ford Health System Methods and compositions for identification of prostate cancer markers
WO2008112283A2 (en) 2007-03-12 2008-09-18 Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Microrna profiling of androgen responsiveness for predicting the appropriate prostate cancer treatment
US9096906B2 (en) 2007-03-27 2015-08-04 Rosetta Genomics Ltd. Gene expression signature for classification of tissue of origin of tumor samples
WO2010073248A2 (en) 2008-12-24 2010-07-01 Rosetta Genomics Ltd. Gene expression signature for classification of tissue of origin of tumor samples
WO2008117278A2 (en) 2007-03-27 2008-10-02 Rosetta Genomics Ltd. Gene expression signature for classification of cancers
US20100273172A1 (en) 2007-03-27 2010-10-28 Rosetta Genomics Ltd. Micrornas expression signature for determination of tumors origin
US8802599B2 (en) 2007-03-27 2014-08-12 Rosetta Genomics, Ltd. Gene expression signature for classification of tissue of origin of tumor samples
EP1975252A1 (en) 2007-03-29 2008-10-01 INSERM (Institut National de la Santé et de la Recherche Medicale) Methods for the prognosis or for the diagnosis of a thyroid disease
US20090062144A1 (en) 2007-04-03 2009-03-05 Nancy Lan Guo Gene signature for prognosis and diagnosis of lung cancer
US7901888B2 (en) 2007-05-09 2011-03-08 The Regents Of The University Of California Multigene diagnostic assay for malignant thyroid neoplasm
CA2692441C (en) 2007-07-06 2020-01-21 The Regents Of The University Of Michigan Solute carrier family 45 member 3 (slc45a3) and ets family gene fusions in prostate cancer
WO2009020521A2 (en) 2007-08-03 2009-02-12 The Brigham And Women's Hospital, Inc. Identification and treatment of estrogen responsive prostate tumors
EP2657353B1 (en) 2007-08-03 2017-04-12 The Ohio State University Research Foundation Ultraconserved regions encoding ncRNAs
US9234244B2 (en) 2007-08-27 2016-01-12 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Diagnostic tool for diagnosing benign versus malignant thyroid lesions
AT505726A2 (en) 2007-08-30 2009-03-15 Arc Austrian Res Centers Gmbh SET OF TUMOR MARKERS
NZ562237A (en) 2007-10-05 2011-02-25 Pacific Edge Biotechnology Ltd Proliferation signature and prognosis for gastrointestinal cancer
WO2009074968A2 (en) 2007-12-12 2009-06-18 Ecole Polytechnique Federale De Lausanne (Epfl) Method for predicting the efficacy of cancer therapy
US20090191535A1 (en) 2007-12-22 2009-07-30 Mark Carle Connelly Method of assessing metastatic carcinomas from circulating endothelial cells and disseminated tumor cells
WO2009087139A1 (en) 2008-01-04 2009-07-16 Centre National De La Recherche Scientifique Molecular in vitro diagnosis of breast cancer
US20100021538A1 (en) 2008-02-29 2010-01-28 Youngro Byun Pharmaceutical compositions containing heparin derivatives
US8293880B2 (en) 2008-03-25 2012-10-23 University Of Southern California Prognostic panel for urinary bladder cancer
CA2724312A1 (en) 2008-05-14 2009-11-19 Dnar, Inc. Biomarkers for the identification, monitoring, and treatment of head and neck cancer
WO2009143603A1 (en) 2008-05-28 2009-12-03 Genomedx Biosciences, Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
US20090298082A1 (en) 2008-05-30 2009-12-03 Klee George G Biomarker panels for predicting prostate cancer outcomes
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
US20110077168A1 (en) 2008-06-17 2011-03-31 Nitzan Rosenfeld Methods for distinguishing between specific types of lung cancers
WO2010004589A2 (en) 2008-07-07 2010-01-14 Decode Genetics Ehf Genetic variants predictive of cancer risk in humans
US20110212855A1 (en) 2008-08-15 2011-09-01 Decode Genetics Ehf. Genetic Variants Predictive of Cancer Risk
WO2010030365A2 (en) 2008-09-12 2010-03-18 Cornell Research Foundation, Inc. Wmc Thyroid tumors identified
AU2009299862B2 (en) 2008-10-01 2016-02-04 Noviogendix Research B.V. Molecular markers in prostate cancer
CN106153918A (en) 2008-10-14 2016-11-23 卡里斯Mpi公司 Describe tumor type biological marker pattern and the gene target of feature set and the protein targets of gene expression
CA2742489A1 (en) 2008-11-14 2010-05-20 Intelligent Oncotherapeutics, Inc. Methods for identification of tumor phenotype and treatment
WO2010056351A2 (en) 2008-11-14 2010-05-20 Stc.Unm Gene expression classifiers for relapse free survival and minimal residual disease improve risk classification and out come prediction in pedeatric b-precursor acute lymphoblastic leukemia
US10236078B2 (en) 2008-11-17 2019-03-19 Veracyte, Inc. Methods for processing or analyzing a sample of thyroid tissue
EP3029158A1 (en) 2008-11-17 2016-06-08 Veracyte, Inc. Methods and compositions of molecular profiling for disease diagnostics
US9495515B1 (en) 2009-12-09 2016-11-15 Veracyte, Inc. Algorithms for disease diagnostics
WO2010058572A1 (en) 2008-11-20 2010-05-27 Oncotherapy Science, Inc. Methods for diagnosing or treating prostate cancer
WO2010061407A1 (en) 2008-11-26 2010-06-03 Decode Genetics Ehf Genetic variants useful for risk assessment of thyroid cancer
US9090943B2 (en) 2008-11-30 2015-07-28 Rosetta Genomics Ltd. Methods for detecting an increased susceptibility to cancer
EP2370813A4 (en) 2008-12-04 2012-05-23 Univ California Materials and methods for determining diagnosis and prognosis of prostate cancer
US20120041274A1 (en) 2010-01-07 2012-02-16 Myriad Genetics, Incorporated Cancer biomarkers
CN102639709A (en) 2009-01-09 2012-08-15 密歇根大学董事会 Recurrent gene fusions in cancer
US9040286B2 (en) 2009-02-03 2015-05-26 Children's Medical Center Corporation Diagnosis and treatment of cancer
US9074258B2 (en) 2009-03-04 2015-07-07 Genomedx Biosciences Inc. Compositions and methods for classifying thyroid nodule disease
US8697275B2 (en) 2009-03-04 2014-04-15 Samsung Sdi Co., Ltd. Rechargeable battery having an extendable case region
WO2010123625A1 (en) 2009-04-24 2010-10-28 University Of Southern California Cd133 polymorphisms predict clinical outcome in patients with cancer
WO2010124372A1 (en) 2009-04-29 2010-11-04 Genomedx Biosciences, Inc. Systems and methods for expression-based classification of thyroid tissue
WO2010129934A2 (en) 2009-05-07 2010-11-11 Veracyte, Inc. Methods and compositions for diagnosis of thyroid conditions
AU2010288810A1 (en) 2009-08-31 2012-03-01 University Of Bremen MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of tumor involving chromosomal rearrangements
US9110065B2 (en) 2009-09-21 2015-08-18 Paul Walfish Methods and compositions for the diagnosis and treatment of thyroid cancer
EP2483813A1 (en) 2009-10-01 2012-08-08 Chipdx LLC System and method for classification of patients
US8975019B2 (en) 2009-10-19 2015-03-10 University Of Massachusetts Deducing exon connectivity by RNA-templated DNA ligation/sequencing
US10446272B2 (en) 2009-12-09 2019-10-15 Veracyte, Inc. Methods and compositions for classification of samples
GB0922085D0 (en) 2009-12-17 2010-02-03 Cambridge Entpr Ltd Cancer diagnosis and treatment
US9642821B2 (en) 2010-01-14 2017-05-09 Dana-Farber Cancer Institute, Inc. MiR-182 in the diagnosis and treatment of cancer
EP2366800A1 (en) 2010-03-01 2011-09-21 Centrum Onkologii-Instytut im M. Sklodowskiej-Curie Oddzial w Gliwicach Kit, method and use for the diagnosis of papillary thyroid cancer using a gene expression profile
WO2011116380A2 (en) 2010-03-19 2011-09-22 H. Lee Moffitt Cancer Center And Research Institute, Inc. Hybrid model for the classification of carcinoma subtypes
US9157123B2 (en) 2010-04-20 2015-10-13 The Johns Hopkins University Genetic amplification of IQGAP1 in cancer
US20110312520A1 (en) 2010-05-11 2011-12-22 Veracyte, Inc. Methods and compositions for diagnosing conditions
WO2011150453A1 (en) 2010-06-01 2011-12-08 The University Of Queensland Diagnostic, prognostic and therapeutic use of a long non-coding rna
US20130302808A1 (en) 2010-07-22 2013-11-14 Mayo Foundation For Medical Education And Research Predicting cancer outcome
WO2012031008A2 (en) 2010-08-31 2012-03-08 The General Hospital Corporation Cancer-related biological materials in microvesicles
ES2629890T3 (en) 2010-11-17 2017-08-16 Interpace Diagnostics, Llc miRNA as biomarkers to distinguish between benign and malignant thyroid neoplasms
US20130267443A1 (en) 2010-11-19 2013-10-10 The Regents Of The University Of Michigan ncRNA AND USES THEREOF
US20150284802A1 (en) 2010-11-19 2015-10-08 The Regents Of The University Of Michigan ncRNA AND USES THEREOF
US20130273543A1 (en) 2010-12-21 2013-10-17 Decode Genetics Ehf. Genetic variants useful for risk assessment of thyroid cancer
EP2663672A1 (en) 2011-01-11 2013-11-20 University Health Network Prognostic signature for oral squamous cell carcinoma
EP2686443A4 (en) 2011-03-17 2014-12-17 Decode Genetics Ehf Genetic variants useful for risk assessment of thyroid cancer
US8945829B2 (en) 2011-03-22 2015-02-03 Cornell University Distinguishing benign and malignant indeterminate thyroid lesions
US20140113297A1 (en) 2011-03-26 2014-04-24 Oregon Health & Science University Gene expression predictors of cancer prognosis
EP2505664B1 (en) 2011-03-30 2014-12-03 Universität Leipzig Method and means for distinguishing malignant from benign tumor samples, in particular in routine air dried fine needle aspiration biopsy (FNAB)
US20140302042A1 (en) 2011-07-01 2014-10-09 Dana-Farber Cancer Institute, Inc. Methods of predicting prognosis in cancer
US9435812B2 (en) 2011-08-31 2016-09-06 Ventana Medical Systems, Inc. Expression of ETS related gene (ERG) and phosphatase and tensin homolog (PTEN) correlates with prostate cancer capsular penetration
US20140243240A1 (en) 2011-10-26 2014-08-28 Georgetown University microRNA EXPRESSION PROFILING OF THYROID CANCER
US20130142728A1 (en) 2011-10-27 2013-06-06 Asuragen, Inc. Mirnas as diagnostic biomarkers to distinguish benign from malignant thyroid tumors
WO2013086429A2 (en) 2011-12-09 2013-06-13 Veracyte, Inc. Methods and compositions for classification of samples
WO2013086524A1 (en) 2011-12-09 2013-06-13 The Johns Hopkins University Compositions and methods for characterizing thyroid neoplasia
WO2013086522A1 (en) 2011-12-10 2013-06-13 Veracyte, Inc. Methods and compositions for sample identification
AU2012352153B2 (en) 2011-12-13 2018-07-26 Veracyte, Inc. Cancer diagnostics using non-coding transcripts
WO2013088457A1 (en) 2011-12-13 2013-06-20 Decode Genetics Ehf Genetic variants useful for risk assessment of thyroid cancer
US20130184999A1 (en) 2012-01-05 2013-07-18 Yan Ding Systems and methods for cancer-specific drug targets and biomarkers discovery
WO2013116742A1 (en) 2012-02-01 2013-08-08 Mayo Foundation For Medical Education And Research Predicting responses to androgen deprivation therapy and methods for treating prostate cancer
US20150038376A1 (en) 2012-03-15 2015-02-05 Qiagen Sciences Llc Thyroid cancer biomarker
US20150141470A1 (en) 2012-05-08 2015-05-21 The Broad Institute, Inc. Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy
EP2885640B1 (en) 2012-08-16 2018-07-18 Genomedx Biosciences, Inc. Prostate cancer prognostics using biomarkers
US9994907B2 (en) 2012-09-20 2018-06-12 Genomedx Biosciences, Inc. Thyroid cancer diagnostics
EP2906712A1 (en) 2012-10-10 2015-08-19 Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis Methods and means for predicting resistance to anti-cancer treatment
US20140121126A1 (en) 2012-10-25 2014-05-01 Memorial Sloan-Kettering Cancer Center Methods of detecting axl and gas6 in cancer patients
US20140143188A1 (en) 2012-11-16 2014-05-22 Genformatic, Llc Method of machine learning, employing bayesian latent class inference: combining multiple genomic feature detection algorithms to produce an integrated genomic feature set with specificity, sensitivity and accuracy
JP6309019B2 (en) 2012-11-27 2018-04-11 ポンティフィシア・ウニベルシダッド・カトリカ・デ・チレＰｏｎｔｉｆｉｃｉａ Ｕｎｉｖｅｒｓｉｄａｄ Ｃａｔｏｌｉｃａ ｄｅ Ｃｈｉｌｅ Compositions and methods for diagnosing thyroid tumors
WO2014085666A1 (en) 2012-11-27 2014-06-05 Board Of Regents, The University Of Texas System Methods of characterizing and treating molecular subset of muscle-invasive bladder cancer
CA2893745A1 (en) 2012-12-04 2014-06-12 Caris Mpi, Inc. Molecular profiling for cancer
WO2014164480A1 (en) 2013-03-12 2014-10-09 Cepheid Methods of detecting cancer
US20160032395A1 (en) 2013-03-14 2016-02-04 Elai Davicioni Cancer biomarkers and classifiers and uses thereof
BR112015022490A2 (en) 2013-03-15 2017-07-18 Veracyte Inc methods and compositions for sample classification
WO2014160645A2 (en) 2013-03-15 2014-10-02 Biotheranostics, Inc. Neuroendocrine tumors
US20160032400A1 (en) 2013-03-15 2016-02-04 Fundació Institut De Recerca Biomèdica (Irb Barcelona) Method for the prognosis and treatment of cancer metastasis
CN105378110A (en) 2013-04-17 2016-03-02 生命技术公司 Gene fusions and gene variants associated with cancer
CA2912052C (en) 2013-05-10 2021-12-14 Memorial Sloan Kettering Cancer Center Lipid scavenging in ras cancers
PL406033A1 (en) 2013-11-14 2015-05-25 Warszawski Uniwersytet Medyczny Method for diagnosing of thyroid papillous carcinoma, application of microRNA marker for diagnosing of the thyroid carcinoma, assessment of the disease progress and evaluation of patient and/or disease susceptibility to the proposed treatment and diagnostic set containing such markers
WO2015073949A1 (en) 2013-11-15 2015-05-21 The University Of North Carolina At Chapel Hill Method of subtyping high-grade bladder cancer and uses thereof
US9708667B2 (en) 2014-05-13 2017-07-18 Rosetta Genomics, Ltd. MiRNA expression signature in the classification of thyroid tumors
JP2016031772A (en) 2014-07-30 2016-03-07 株式会社日立ハイテクファインシステムズ Inspection method and apparatus of heat-assisted magnetic head element
JP2018514187A (en) 2015-03-04 2018-06-07 ベラサイト インコーポレイテッド Method for assessing risk of disease onset or recurrence using expression level and sequence variant information
US11174518B2 (en) 2015-10-05 2021-11-16 Cedars-Sinai Medical Center Method of classifying and diagnosing cancer
AU2016334893B2 (en) 2015-10-08 2022-11-17 Veracyte, Inc. Use of a genetic signature diagnostically to evaluate treatment strategies for prostate cancer
EP3593140A4 (en) 2017-03-09 2021-01-06 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
WO2019023517A2 (en) 2017-07-27 2019-01-31 Veracyte, Inc. Genomic sequencing classifier

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050227917A1 (en) * 1997-12-23 2005-10-13 Williams Lewis T Gene products differentially expressed in cancerous cells and their methods of use II
US20060204989A1 (en) * 1998-09-22 2006-09-14 Kopreski Michael S Comparative analysis of extracellular RNA species
US20020168638A1 (en) * 2000-01-24 2002-11-14 Robert Schlegel Compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20040259086A1 (en) * 2000-02-17 2004-12-23 Millennium Pharmaceuticals, Inc. Novel genes, compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20040009481A1 (en) * 2001-06-11 2004-01-15 Millennium Pharmaceuticals, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US20070083334A1 (en) * 2001-09-14 2007-04-12 Compugen Ltd. Methods and systems for annotating biomolecular sequences
US20030152980A1 (en) * 2001-12-21 2003-08-14 Whitehead Institute For Biomedical Research Prostate cancer diagnosis and outcome prediction by expression analysis
US20030224399A1 (en) * 2002-02-12 2003-12-04 Reed John C. Methods for determining the prognosis for patients with a prostate neoplastic condition
US20050064455A1 (en) * 2003-05-28 2005-03-24 Baker Joffre B. Gene expression markers for predicting response to chemotherapy
US20070048738A1 (en) * 2003-07-14 2007-03-01 Mayo Foundation For Medical Education And Research Methods and compositions for diagnosis, staging and prognosis of prostate cancer
US20050260646A1 (en) * 2004-04-09 2005-11-24 Genomic Health Inc. Gene expression markers for predicting response to chemotherapy
US20060046253A1 (en) * 2004-09-02 2006-03-02 Suntory Limited Method for analyzing genes of industrial yeasts
US20070259352A1 (en) * 2004-10-04 2007-11-08 Itzhak Bentwich Prostate cancer-related nucleic acids
US20080009001A1 (en) * 2004-10-06 2008-01-10 Saverio Bettuzzi Method for Identification of Neoplastic Transformation with Particular Reference to Prostate Cancer
US20110045462A1 (en) * 2006-11-14 2011-02-24 The Regents Of The University Of California Digital analysis of gene expression

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Sequence Alignment Search for SEQ ID NO: 1904. January 28, 2014. 1 page. *
Sequence Alignment Search for SEQ ID NO: 457. January 28, 2014. 2 pages. *

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10494677B2 (en) 2006-11-02 2019-12-03 Mayo Foundation For Medical Education And Research Predicting cancer outcome
US10865452B2 (en) 2008-05-28 2020-12-15 Decipher Biosciences, Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
US10260104B2 (en) 2010-07-27 2019-04-16 Genomic Health, Inc. Method for using gene expression to determine prognosis of prostate cancer
WO2013041731A1 (en) * 2011-09-23 2013-03-28 Katholieke Universiteit Leuven Marker gene based diagnosis, staging and prognosis of prostate cancer
US10513737B2 (en) 2011-12-13 2019-12-24 Decipher Biosciences, Inc. Cancer diagnostics using non-coding transcripts
EP3739595A3 (en) * 2012-01-31 2021-01-27 Genomic Health, Inc. Gene expression profile algorithm and test for determining prognosis of prostate cancer
US10081842B2 (en) 2012-08-07 2018-09-25 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Prostate cancer gene expression profiles
WO2014025810A1 (en) 2012-08-07 2014-02-13 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Prostate cancer gene expression profiles
US20150309036A1 (en) * 2012-08-16 2015-10-29 The Trustees Of Columbia University In The City Of New York Diagnostic Markers of Indolent Prostate Cancer
US11035005B2 (en) 2012-08-16 2021-06-15 Decipher Biosciences, Inc. Cancer diagnostics using biomarkers
WO2014028907A1 (en) * 2012-08-16 2014-02-20 The Trustees Of Columbia University In The City Of New York Diagnostic markers of indolent prostate cancer
AU2013302365B2 (en) * 2012-08-16 2019-03-21 Mayo Foundation For Medical Education And Research Cancer diagnostics using biomarkers
WO2014028884A3 (en) * 2012-08-16 2014-05-08 Genomedx Biosciences, Inc. Cancer diagnostics using biomarkers
AU2018217315B2 (en) * 2012-08-17 2021-04-22 Memorial Sloan-Kettering Cancer Center Gene expression profile associated with prostate cancer
AU2013302406B2 (en) * 2012-08-17 2018-05-17 Memorial Sloan-Kettering Cancer Center Gene expression profile associated with prostate cancer
US10030271B2 (en) * 2012-08-17 2018-07-24 Memorial Sloan-Kettering Cancer Center Gene expression profile associated with prostate cancer
US20150191792A1 (en) * 2012-08-17 2015-07-09 Memorial Sloan-Kettering Cancer Center Gene expression profile associated with prostate cancer
EP2890815A4 (en) * 2012-08-31 2016-05-11 Univ Colorado Methods for diagnosis and treatment of cancer
JP2015528295A (en) * 2012-08-31 2015-09-28 ザ リージェンツ オブ ザ ユニヴァーシティ オブ コロラド，ア ボディ コーポレイト Cancer diagnosis and treatment methods
WO2014152129A1 (en) * 2013-03-14 2014-09-25 Rutgers, The State University Of New Jersey A mathematical musical orchestral method for predicting classes of patients for medical treatment
WO2014205555A1 (en) * 2013-06-28 2014-12-31 British Columbia Cancer Agency Branch Methods and uses for diagnosis and treatment of prostate cancer
US10196697B2 (en) 2013-12-12 2019-02-05 Almac Diagnostics Limited Prostate cancer classification
US10711311B2 (en) 2013-12-30 2020-07-14 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Genomic rearrangements associated with prostate cancer and methods of using the same
WO2015103287A3 (en) * 2013-12-30 2015-11-12 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Genomic rearrangements associated with prostate cancer and methods of using the same
JP2017506910A (en) * 2013-12-30 2017-03-16 ザ ヘンリー エム． ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド Genomic rearrangement associated with prostate cancer and methods of using the genomic rearrangement
WO2017007739A3 (en) * 2015-07-05 2017-02-23 Cytotest Inc. Nucleic acid probes
US11414708B2 (en) 2016-08-24 2022-08-16 Decipher Biosciences, Inc. Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy
US11208697B2 (en) 2017-01-20 2021-12-28 Decipher Biosciences, Inc. Molecular subtyping, prognosis, and treatment of bladder cancer
US11873532B2 (en) 2017-03-09 2024-01-16 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
US11078542B2 (en) 2017-05-12 2021-08-03 Decipher Biosciences, Inc. Genetic signatures to predict prostate cancer metastasis and identify tumor aggressiveness
CN109593835A (en) * 2017-09-29 2019-04-09 深圳华大基因股份有限公司 Method, kit and application for micro FFPE RNA Samples Estimates
JP7463357B2 (en) 2018-10-11 2024-04-08 コーニンクレッカ フィリップス エヌ ヴェ Preoperative risk stratification based on PDE4D7 and DHX9 expression
CN109709331A (en) * 2019-01-29 2019-05-03 广州瑞博奥生物科技有限公司 Purposes of the GDF15 in the kit that preparation is used for quantitative detection liver cancer marker
CN110456065A (en) * 2019-07-31 2019-11-15 四川大学华西医院 CCDC130 autoantibody detection reagent is preparing the purposes in screening lung cancer kit

Also Published As

Publication number Publication date
US20170191133A1 (en) 2017-07-06
WO2009143603A1 (en) 2009-12-03
US10865452B2 (en) 2020-12-15
EP2291553A1 (en) 2011-03-09
AU2009253675A2 (en) 2011-01-27
EP2291553A4 (en) 2011-12-14
EP2806054A1 (en) 2014-11-26
CA2725978A1 (en) 2009-12-03
AU2009253675A1 (en) 2009-12-03

Similar Documents

Publication Publication Date Title
US20110136683A1 (en) Systems and Methods for Expression-Based Discrimination of Distinct Clinical Disease States in Prostate Cancer
US10422009B2 (en) Compositions and methods for classifying thyroid nodule disease
US9617604B2 (en) Systems and methods for expression-based classification of thyroid tissue
EP2885640B1 (en) Prostate cancer prognostics using biomarkers
CA2754049C (en) Compositions and methods for classifying thyroid nodule disease
US10533225B2 (en) Methods and systems for monitoring, diagnosing, and treating chronic obstructive pulmonary disease
EP2402464A1 (en) Gene expression profiling for identification, monitoring, and treatment of colorectal cancer
US20100216137A1 (en) Gene Expression Profiling for Identification, Monitoring and Treatment of Ovarian Cancer
EP3077531B1 (en) Novel rna-biomarkers for diagnosis of prostate cancer
WO2012152811A1 (en) Molecular markers in prostate cancer
US11814687B2 (en) Methods for characterizing bladder cancer
EP4332240A1 (en) Rna-biomarkers for diagnosis of prostate cancer
AU2014274499A1 (en) Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
MX2008003933A (en) Methods for diagnosing pancreatic cancer

Legal Events

Date Code Title Description
AS Assignment

Owner name: GENOMEDX BIOSCIENCES, INC., CANADA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DAVICIONI, ELAI;REEL/FRAME:025827/0624

Effective date: 20110210

AS Assignment

Owner name: CRG PARTNERS III - PARALLEL FUND "A" L.P., TEXAS

Free format text: SECURITY INTEREST;ASSIGNOR:GENOMEDX BIOSCIENCES INC.;REEL/FRAME:036639/0071

Effective date: 20150923

Owner name: CRG PARTNERS III (CAYMAN) L.P., TEXAS

Free format text: SECURITY INTEREST;ASSIGNOR:GENOMEDX BIOSCIENCES INC.;REEL/FRAME:036639/0071

Effective date: 20150923

Owner name: CRG PARTNERS III L.P., TEXAS

Free format text: SECURITY INTEREST;ASSIGNOR:GENOMEDX BIOSCIENCES INC.;REEL/FRAME:036639/0071

Effective date: 20150923

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: GENOMEDX INC., CALIFORNIA

Free format text: CHANGE OF NAME;ASSIGNOR:GENOMEDX BIOSCIENCES INC.;REEL/FRAME:055573/0354

Effective date: 20180711

Owner name: DECIPHER BIOSCIENCES, INC., CALIFORNIA

Free format text: CHANGE OF NAME;ASSIGNOR:GENOMEDX INC.;REEL/FRAME:055573/0437

Effective date: 20190124

AS Assignment

Owner name: DECIPHER BIOSCIENCES, INC., CALIFORNIA

Free format text: RELEASE BY SECURED PARTY;ASSIGNORS:CRG PARTNERS III L.P.;CRG PARTNERS III - PARALLEL FUND "A" L.P.;CRG PARTNERS III (CAYMAN) L.P.;REEL/FRAME:055595/0511

Effective date: 20210312

AS Assignment

Owner name: VERACYTE, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:VERACYTE SD, INC.;REEL/FRAME:065651/0354

Effective date: 20230801