Detecting Cancer Cell Of Origin

Abstract

Methods and compositions are provided for determining a pan-cancer clustering of cluster assignment (COCA) subtype of a cancer in an individual by detecting the expression level of at least one classifier biomarker selected from a group of classifier biomarkers for COCA subtypes. Also provided herein are methods and compositions for determining the response of an individual with a COCA subtype to a therapy such as immunotherapy.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 62/743,256 filed Oct. 9, 2018 and U.S. Provisional Application No. 62/819,893 filed Mar. 18, 2019, each of which is incorporated by reference herein in its entirety for all purposes.

FIELD

[0002] The present invention relates to methods for determining an integrated, pan-cancer subtype and for predicting the prognosis of a patient inflicted with said integrated subtype of cancer.

STATEMENT REGARDING SEQUENCE LISTING

[0003] The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is GNCN_016_01WO_SeqList_ST25.txt. The text file is .apprxeq.433 KB, was created on Oct. 8, 2019, and is being submitted electronically via EFS-Web.

BACKGROUND

[0004] Cancers are typically classified using pathologic criteria that rely heavily on the tissue site of origin. Recently, large-scale genomics projects spearheaded by The Cancer Genome Atlas (TCGA) have been undertaken in order to provide a detailed molecular characterization of thousands of tumors, thereby making a systematic molecular-based taxonomy of cancer possible (see, for example, The_Cancer_Genome_Atlas_Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008; 455:1061-1068; The_Cancer_Genome_Atlas_Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474:609-615; The_Cancer_Genome_Atlas_Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012a;489:519-525; The_Cancer_Genome_Atlas_Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012b; 487:330-337; The_Cancer_Genome_Atlas_Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012c; 490:61-70; The_Cancer_Genome_Atlas_Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013a; 499:43-49; The_Cancer_Genome_Atlas_Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. The New England journal of medicine. 2013b; 368:2059-2074; The_Cancer_Genome_Atlas_Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014; 507:315-322; each of which is herein incorporated by reference). These large-scale genomics projects have shown that each single-tissue cancer type can be further divided into three to four molecular subtypes and meaningful differences in clinical behavior can often be correlated with the single-tissue tumor types. In fact, in a few cases, single-tissue subtype identification has led to therapies that target the driving subtype-specific molecular alteration(s). EGFR-mutant lung adenocarcinomas and ERBB2-amplified breast cancer are two well-established examples.

[0005] Building off these projects, more recent studies have undertaken multi-platform integrative analysis of thousands of cancers from numerous tumor types in The Cancer Genome Atlas (TCGA) project in order to determine whether tissue-of-origin categories split into sub-types based upon multi-platform genomic analyses, what molecular alterations are shared across cancers arising from different tissues and if previously recognized disease subtypes in fact span multiple tissues of origin (see Hoadley et al., Cell. 2014 Aug. 14; 158(4):929-944 and Hoadley et al., Cell. 2018 Apr. 5; 173(2):291-304, each of which is herein incorporated by reference). While these studies have helped to elucidate a molecular taxonomy of cancer with newly defined integrated subtypes that can provide a significant increase in the accuracy for the prediction of clinical outcomes, they have relied on performing a second-level cluster analysis (i.e., clustering of cluster assignments (COCA)) using as input data from five `omic` platforms. The `omic` platforms used in the studies for the COCA analysis included whole-exome DNA sequence (Illumina HiSeq and GAII), DNA methylation (Illumina 450,000-feature microarrays), genome-wide mRNA levels (Illumina mRNA-seq), microRNA levels (Illumina microRNA-seq), and protein levels and/or phosphorylated proteins (Reverse Phase Protein Arrays; RPPA).

[0006] While the benefits of such a pan-cancer analysis from a clinical standpoint are clear, the resources necessary to perform said analysis can be laborious, time-consuming and expensive. Accordingly, there is need in the art for methods and resources for molecularly characterizing tumor samples in a rapid, efficient and reliable manner regardless of tissue of origin.

[0007] The present disclosure addresses the limitations of the current methods and other needs in the field for an efficient method for pan-cancer tumor classification that may inform prognosis and patient management based on underlying genomic and biologic tumor characteristics shared across tumor samples from multiple tissues of origin.

SUMMARY

[0008] The methods disclosed herein include determination of a cell of origin subtype, treatment of cancer based on a cell of origin subtype, prediction of overall survival of patients based on a cell of origin subtype, and application of an algorithm to gene expression data for one or a plurality of classifier biomarkers for categorization of tumor sample into one of 21 a clustering of cluster assignments (COCA) subtypes C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) such that the COCA subtype is indicative of the cell of origin of the tumor sample regardless of the anatomical location of said tumor sample. The algorithm can be a classification to the nearest centroid (CLaNC algorithm). The C1 COCA subtype can indicate that a tumor sample is substantially similar to or is adenocortical carcinoma. The C2 COCA subtype can indicate that a tumor sample is substantially similar to or is glioblastoma. The C3 COCA subtype can indicate that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer). The C4 COCA subtype can indicate that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder. The C6 COCA subtype can indicate that a tumor sample is substantially similar to or is lung adenocarcinoma. The C8 COCA subtype can indicate that a tumor sample is substantially similar to or is pancreatic adenocarcinoma. The C9 COCA subtype can indicate that a tumor sample is substantially similar to or is uterine carcinosarcoma. The C10 COCA subtype can indicate that a tumor sample is substantially similar to or is the basal subtype of breast cancer. The C12 COCA subtype can indicate that a tumor sample is substantially similar to or is uterine corpus endometrial cancer. The C14 COCA subtype can indicate that a tumor sample is substantially similar to or is prostate cancer. The C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer. The C16 COCA subtype can indicate that a tumor sample is substantially similar to or is a bladder urothelial carcinoma. The C17 COCA subtype can indicate that a tumor sample is substantially similar to or is a testicular germ cell tumor. The C19 COCA subtype can indicate that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma. The C20 COCA subtype can indicate that a tumor sample is substantially similar to or is a sarcoma. The C21 COCA subtype can indicate that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma. The C22 COCA subtype can indicate that a tumor sample is substantially similar to or is liver hepatocellular carcinoma. The C24 COCA subtype can indicate that a tumor sample is substantially similar to or is the luminal subtype of breast cancer. The C25 COCA subtype can indicate that a tumor sample is substantially similar to or is thymoma. The C26 COCA subtype can indicate that a tumor sample is substantially similar to or is melanoma. The C28 COCA subtype can indicate that a tumor sample is substantially similar to or is thyroid cancer.

[0009] In one aspect, provided herein is a method for determining a clustering of cluster assignments (COCA) subtype of a tumor cancer sample obtained from a patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1, wherein the detection of the expression level of the classifier biomarker specifically identifies a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype. In some cases, the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step. In some cases, the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm. In some cases, the expression level of the classifier biomarker is detected at the nucleic acid level. In some cases, the nucleic acid level is RNA or cDNA. In some cases, the detecting an expression level comprises performing a quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarray analysis, gene chips, an nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques. In some cases, the expression level is detected by performing RNAseq. In some cases, the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1. In some cases, the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, a fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient. In some cases, the bodily fluid is blood or fractions thereof (i.e., serum or plasma), urine, saliva, or sputum. In some cases, the at least one classifier biomarker comprises a plurality of classifier biomarkers. In some cases, the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 4 classifier biomarkers, at least 6 classifier biomarkers, at least 8 classifier biomarkers, at least 10 classifier biomarkers, at least 12 classifier biomarkers, at least 14 classifier biomarkers, at least 16 classifier biomarkers, at least 18 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1. In some cases, the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.

[0010] In another aspect, provided herein is a method of detecting a biomarker in a tumor sample obtained from a patient, the method comprising measuring the expression level of a plurality of classifier biomarker nucleic acids selected from Table 1 using an amplification, hybridization and/or sequencing assay. In some cases, the patient is suffering from or is suspected of suffering from kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); or Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC). In some cases, the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction(s) (qRT-PCR), RNAseq, microarray analysis, gene chips, nCounter Gene Expression Assay(s), Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques. In some cases, the expression level is detected by performing RNAseq. In some cases, the detection of the expression level comprises using at least one pair of oligonucleotide primers per each of the plurality of biomarker nucleic acids selected from Table 1. In some cases, the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient. In some cases, the bodily fluid is blood or fractions thereof, urine, saliva, or sputum. In some cases, the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1. In some cases, the plurality of biomarker nucleic acids comprises, consists essentially of or consists of all the classifier biomarker nucleic acids of Table 1.

[0011] In yet another aspect, provided herein is a method of treating cancer in a subject, the method comprising: measuring the expression level of at least one biomarker nucleic acid in a tumor sample obtained from the subject, wherein the at least one biomarker nucleic acid is selected from a set of biomarkers listed in Table 1, wherein the presence, absence and/or level of the at least one biomarker indicates a COCA subtype of the cancer; and administering a therapeutic agent based on the COCA subtype of the cancer. In some cases, the at least one biomarker nucleic acid selected from the set of biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1. In some cases, the method further comprises measuring the expression of at least one biomarker from an additional set of biomarkers. In some cases, the additional set of biomarkers comprises at least an immune cell signature, a cell proliferation signature, or drug target genes. In some cases, the measuring the expression level is conducted using an amplification, hybridization and/or sequencing assay. In some cases, the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction(s) (qRT-PCR), RNAseq, microarray analysis, gene chips, nCounter Gene Expression Assay(s), Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques. In some cases, the expression level is detected by performing RNAseq. In some cases, the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient. In some cases, the bodily fluid is blood or fractions thereof, urine, saliva, or sputum. In some cases, the subject's COCA subtype is selected from C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28.

[0012] In still another aspect, provided herein is a method of predicting overall survival in a cancer patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1 in a tumor sample obtained from a patient, wherein the detection of the expression level of the at least one classifier biomarker specifically identifies a COCA subtype, and wherein identification of the COCA subtype is predictive of the overall survival in the patient. In some cases, the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step. In some cases, the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm. In some cases, the expression level of the classifier biomarker is detected at the nucleic acid level. In some cases, the nucleic acid level is RNA or cDNA. In some cases, the detecting an expression level comprises performing quantitative real time reverse transcriptase polymerase chain reaction(s) (qRT-PCR), RNAseq, microarray analysis, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques. In some cases, the expression level is detected by performing RNAseq. In some cases, the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1. In some cases, the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient. In some cases, the bodily fluid is blood or fractions thereof, urine, saliva, or sputum. In some cases, the at least one classifier biomarker comprises a plurality of classifier biomarkers. In some cases, the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1. In some cases, the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 shows a cross-tabulation of the TCGA tumor type and COCA subtype from Hoadley et al., Cell. 2018 Apr. 5; 173(2):291-304 for samples with qualifying expression data as described in Example 1. FIG. 1 also provides the integrated tumor subtypes provided herein.

[0014] FIG. 2 illustrates how the TCGA samples were divided into a training set (2/3 of the data set; n=5696) and test set (1/3 of the data set), balancing for uniform tumor type of origin distributions for development of the 84-gene subtyper described herein (see the Table in FIG. 2). As illustrated in the graph on FIG. 2, using the training set, genes with low variance and/or low mean were filtered out, while genes with mean variance and mean expression values greater than 4 were kept resulting in gene expression data for 2190 genes.

[0015] FIG. 3 illustrates five-fold cross validation curves using classification to the nearest centroid (ClaNC) on the TCGA-2018 training dataset (n=408) to guide the selection of the number of genes per subtype to include in the signature for COCA subtyping provided herein.

[0016] FIG. 4 illustrates agreement and disagreement between the GS subtype (rows) and the subtype based on the 84-gene subtyper (columns) (left panel) for the test set described in Example 1. The right panel shows agreement for each COCA subtype listed. Overall agreement was 90%. Overall agreement with COCA on the training set was 91%.

[0017] FIG. 5 shows the proportion of COCA subtypes in the test set that were called correctly by the 84-gene typer developed in Example 1.

[0018] FIG. 6 shows results of within cancer-type survival analysis for bladder cancer (BLCA) via testing for association of COCA subtypes from BLCA sample with overall survival. p=0.0204 for COCA subtype C4 as determined using the 84 gene COCA subtyper provided herein.

[0019] FIG. 7 shows results of within cancer-type survival analysis for breast cancer (BRCA) via testing for association of COCA subtypes from BRCA sample with overall survival. p=0.00013 for COCA subtype C24 as determined using the 84 gene COCA subtyper provided herein.

[0020] FIG. 8 shows results of within cancer-type survival analysis for stomach adenocarcinoma (STAD) via testing for association of COCA subtypes from STAD sample with overall survival. p=0.00689 for COCA subtype C8 as determined using the 84 gene COCA subtyper provided herein.

DETAILED DESCRIPTION

Definitions

[0021] While the following terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter.

[0022] As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Additionally, the use of "or" is intended to include "and/or" unless the context clearly indicates otherwise. Furthermore, to the extent that the terms "including", "includes", "having", "has", "with", or variants thereof are used in either the detailed description and/or the claims, such terms are intended to be inclusive in a manner similar to the term "comprising". The term "about" as used herein can refer to a range that is 15%, 10%, 8%, 6%, 4%, or 2% plus or minus from a stated numerical value.

[0023] Unless the context requires otherwise, throughout the present specification and claims, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense that is as "including, but not limited to". The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms "about" and "consisting essentially of" mean+/-20% of the indicated range, value, or structure, unless otherwise indicated.

[0024] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment may be included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification may not necessarily all be referring to the same embodiment. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

[0025] Throughout this disclosure, various aspects of the methods and compositions provided herein can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0026] Unless otherwise indicated, the methods and compositions provided herein can utilize conventional techniques and descriptions of organic chemistry, polymer technology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology, which are within the skill of the art. Such conventional techniques include polymer array synthesis, hybridization, ligation, and detection of hybridization using a label. Specific illustrations of suitable techniques can be had by reference to the example herein below. However, other equivalent conventional procedures can, of course, also be used. Such conventional techniques and descriptions can be found in standard laboratory manuals such as Genome Analysis: A Laboratory Manual Series (Vols. I-IV), Using Antibodies: A Laboratory Manual, Cells: A Laboratory Manual, PCR Primer: A Laboratory Manual, and Molecular Cloning: A Laboratory Manual (all from Cold Spring Harbor Laboratory Press), Gait, "Oligonucleotide Synthesis: A Practical Approach" 1984, IRL Press, London, Nelson and Cox (2000), Lehninger et al., (2008) Principles of Biochemistry 5th Ed., W.H. Freeman Pub., New York, N.Y. and Berg et al. (2006) Biochemistry, 6.sup.th Ed., W.H. Freeman Pub., New York, N.Y., all of which are herein incorporated in their entirety by reference for all purposes.

[0027] Conventional software and systems may also be used in the methods and compositions provided herein. Computer software products for use herein typically include computer readable medium having computer-executable instructions for performing the logic steps of any of the methods provided herein. Suitable computer readable medium include floppy disk, CD-ROM/DVD/DVD-ROM, hard-disk drive, flash memory, ROM/RAM, magnetic tapes, etc. The computer-executable instructions may be written in a suitable computer language or combination of several languages. Basic computational biology methods are described in, for example, Setubal and Meidanis et al., Introduction to Computational Biology Methods (PWS Publishing Company, Boston, 1997); Salzberg, Searles, Kasif, (Ed.), Computational Methods in Molecular Biology, (Elsevier, Amsterdam, 1998); Rashidi and Buehler, Bioinformatics Basics: Application in Biological Science and Medicine (CRC Press, London, 2000) and Ouelette and Bzevanis Bioinformatics: A Practical Guide for Analysis of Gene and Proteins (Wiley & Sons, Inc., 2.sup.nd ed., 2001). See U.S. Pat. No. 6,420,108.

[0028] The methods and compositions provided herein may also make use of various computer program products and software for a variety of purposes, such as probe design, management of data, analysis, and instrument operation. See, U.S. Pat. Nos. 5,593,839, 5,795,716, 5,733,729, 5,974,164, 6,066,454, 6,090,555, 6,185,561, 6,188,783, 6,223,127, 6,229,911 and 6,308,170. Computer methods related to genotyping using high density microarray analysis may also be used in the present methods, see, for example, US Patent Pub. Nos. 20050250151, 20050244883, 20050108197, 20050079536 and 20050042654.

[0029] Additionally, the present disclosure may have preferred embodiments that include methods for providing genetic information over networks such as the Internet as shown in U.S. Patent Pub. Nos. 20030097222, 20020183936, 20030100995, 20030120432, 20040002818, 20040126840, and 20040049354.

[0030] As used herein, the terms "individual," "patient," and "subject" can refer to any single animal, more preferably a mammal (including such non-human animals as, for example, dogs, cats, horses, rabbits, zoo animals, cows, pigs, sheep, and non-human primates) for which treatment is desired. In particular embodiments, the individual or patient herein is a human.

[0031] It will be appreciated that the term "healthy" as used herein, is relative to cancer status, as the term "healthy" cannot be defined to correspond to any absolute evaluation or status. Thus, an individual defined as healthy with reference to any specified disease or disease criterion, can in fact be diagnosed with any other one or more diseases, or exhibit any other one or more disease criterion, including one or more other cancers.

[0032] The term "tumor," as used herein, can refer to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. The terms "cancer," "cancerous," and "tumor" are not mutually exclusive and can be used interchangeably.

[0033] The term "detection" can include any means of detecting, including direct and indirect detection.

[0034] The terms "substantially" or "substantial" as used herein can mean substantially similar in function or capability or otherwise competitive to the products, items (e.g., type of cancer, nucleic acid complement), services or methods recited herein. Substantially similar products, items (e.g., type of cancer, nucleic acid complement), services or methods are at least 80%, 81%, 82%, 83%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5% similar or the same as a product, item (e.g., type of cancer, nucleic acid complement), service or method recited herein.

Overview

[0035] Provided herein are kits, compositions and methods for identifying, determining, detecting or diagnosing integrated, pan-cancer clustering of cluster assignment (COCA) subtypes. That is, the methods can be useful for molecularly defining subsets of cancer regardless of tissue of origin. The methods provide a pan-cancer classification of a tumor sample obtained from subject that can be prognostic and predictive for therapeutic response. The therapeutic response can include chemotherapy, immunotherapy, angiogenesis inhibitor therapy, surgical intervention and/or radiotherapy. The methods can be also provide a prognosis of overall survival for cancer patients according to their pan-cancer, integrated COCA subtype. The kits, compositions and methods provided herein can be used to classify a tumor sample as being any type of COCA subtype known in the art. In one embodiment, the COCA subtype determined or diagnosed by the methods and compositions provided herein are selected from C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA).

[0036] The COCA subtype determined using the kits, compositions or methods provided herein can indicate or disclose the cell or tissue of origin of a tumor sample obtained from a subject. For example, the C1 COCA subtype can indicate that a tumor sample is substantially similar to or is adenocortical carcinoma; the C2 COCA subtype can indicate that a tumor sample is substantially similar to or is glioblastoma; the C3 COCA subtype can indicate that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer); the C4 COCA subtype can indicate that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder; the C6 COCA subtype can indicate that a tumor sample is substantially similar to or is lung adenocarcinoma; the C8 COCA subtype can indicate that a tumor sample is substantially similar to or is pancreatic adenocarcinoma; the C9 COCA subtype can indicate that a tumor sample is substantially similar to or is uterine carcinosarcoma; the C10 COCA subtype can indicate that a tumor sample is substantially similar to or is the basal subtype of breast cancer; the C12 COCA subtype can indicate that a tumor sample is substantially similar to or is uterine corpus endometrial cancer; the C14 COCA subtype can indicate that a tumor sample is substantially similar to or is prostate cancer; the C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer; the C16 COCA subtype can indicate that a tumor sample is substantially similar to or is a bladder urothelial carcinoma; the C17 COCA subtype can indicate that a tumor sample is substantially similar to or is a testicular germ cell tumor; the C19 COCA subtype can indicate that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma; the C20 COCA subtype can indicate that a tumor sample is substantially similar to or is a sarcoma; the C21 COCA subtype can indicate that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma; the C22 COCA subtype can indicate that a tumor sample is substantially similar to or is liver hepatocellular carcinoma; the C24 COCA subtype can indicate that a tumor sample is substantially similar to or is the luminal subtype of breast cancer; the C25 COCA subtype can indicate that a tumor sample is substantially similar to or is thymoma; the C26 COCA subtype can indicate that a tumor sample is substantially similar to or is melanoma; or the C28 COCA subtype can indicate that a tumor sample is substantially similar to or is thyroid cancer.

[0037] "Determining a COCA subtype" can include, for example, diagnosing or detecting the presence, sub-type and cell-of-origin of a cancer, monitoring the progression of the disease, and identifying or detecting cells or samples that are indicative of said pan-cancer subtypes.

[0038] In one embodiment, the COCA subtype is assessed or determined through the evaluation of expression patterns, or profiles, of one or a plurality of classifier biomarkers or biomarkers in one or more subject samples. The term subject, or subject sample, may refer to an individual regardless of health and/or disease status. A subject can be a subject, a study participant, a test subject, a control subject, a screening subject, or any other class of individual from whom a sample is obtained and assessed in the context of the methods and compositions provided herein. Accordingly, a subject can be previously diagnosed with one type of a myriad of cancers, can present with one or more symptoms of said type of cancer, or a predisposing factor, such as a family (genetic) or medical history (medical) factor for said type of cancer, can be undergoing treatment or therapy for said cancer, or the like. Alternatively, a subject can be healthy as de fin e d herein with respect to any of the aforementioned factors or criteria.

[0039] The myriad of cancers from which a subject may be suffering from or suspected of suffering from can be any cancer known in the art. The classifier biomarkers provided herein (e.g., the classifier biomarkers of Table 1) and methods of using said classifier biomarkers can be used to determine an integrated, pan-cancer COCA subtype of the cancer that said subject may be or is suspected of suffering from. Further to any of the embodiments provided herein, the cancer can include, but is not limited to, carcinoma, lymphoma, blastoma (including medulloblastoma and retinoblastoma), sarcoma (including liposarcoma and synovial cell sarcoma), neuroendocrine tumors (including carcinoid tumors, gastrinoma, and islet cell cancer), mesothelioma, schwannoma (including acoustic neuroma), meningioma, adenocarcinoma, melanoma, and leukemia or lymphoid malignancies. Examples of a cancer can also include, but are not limited to, a lung cancer (e.g., a non-small cell lung cancer (NSCLC) or small cell lung cancer), a kidney cancer (e.g., a kidney urothelial carcinoma or RCC), a bladder cancer (e.g., a bladder urothelial (transitional cell) carcinoma (e.g., locally advanced or metastatic urothelial cancer, including 1L or 2L+locally advanced or metastatic urothelial carcinoma)), a breast cancer, a colorectal cancer (e.g., a colon adenocarcinoma), an ovarian cancer, a pancreatic cancer, a gastric carcinoma, an esophageal cancer, a mesothelioma, a melanoma (e.g., a skin melanoma), a head and neck cancer (e.g., a head and neck squamous cell carcinoma (HNSCC)), a thyroid cancer, a sarcoma (e.g., a soft-tissue sarcoma, a fibrosarcoma, a myxosarcoma, a liposarcoma, an osteogenic sarcoma, an osteosarcoma, a chondrosarcoma, an angiosarcoma, an endotheliosarcoma, a lymphangiosarcoma, a lymphangioendotheliosarcoma, a leiomyosarcoma, or a rhabdomyosarcoma), a prostate cancer, a glioblastoma, a cervical cancer, a thymic carcinoma, a leukemia (e.g., an acute lymphocytic leukemia (ALL), an acute myelocytic leukemia (AML), a chronic myelocytic leukemia (CML), a chronic eosinophilic leukemia, or a chronic lymphocytic leukemia (CLL)), a lymphoma (e.g., a Hodgkin lymphoma or a non-Hodgkin lymphoma (NHL)), a myeloma (e.g., a multiple myeloma (MM)), a mycosis fungoides, a Merkel cell cancer, a hematologic malignancy, a cancer of hematological tissues, a B cell cancer, a bronchus cancer, a stomach cancer, a brain or central nervous system cancer, a peripheral nervous system cancer, a uterine or endometrial cancer, a cancer of the oral cavity or pharynx, a liver cancer, a testicular cancer, a biliary tract cancer, a small bowel or appendix cancer, a salivary gland cancer, an adrenal gland cancer, an adenocarcinoma, an inflammatory myofibroblastic tumor, a gastrointestinal stromal tumor (GIST), a colon cancer, a myelodysplastic syndrome (MDS), a myeloproliferative disorder (MPD), a polycythemia Vera, a chordoma, a synovioma, a Ewing's tumor, a squamous cell carcinoma, a basal cell carcinoma, a sweat gland carcinoma, a sebaceous gland carcinoma, a papillary carcinoma, a papillary adenocarcinoma, a medullary carcinoma, a bronchogenic carcinoma, a renal cell carcinoma, a hepatoma, a bile duct carcinoma, a choriocarcinoma, a seminoma, an embryonal carcinoma, a Wilms' tumor, a bladder carcinoma, an epithelial carcinoma, a glioma, an astrocytoma, a medulloblastoma, a craniopharyngioma, an ependymoma, a pinealoma, a hemangioblastoma, an acoustic neuroma, an oligodendroglioma, a meningioma, a neuroblastoma, a retinoblastoma, a follicular lymphoma, a diffuse large B-cell lymphoma, a mantle cell lymphoma, a hepatocellular carcinoma, a thyroid cancer, a small cell cancer, an essential thrombocythemia, an agnogenic myeloid metaplasia, a hypereosinophilic syndrome, a systemic mastocytosis, a familiar hypereosinophilia, a neuroendocrine cancer, or a carcinoid tumor.

[0040] In one embodiment, the cancer is selected from kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC); and Acute Myeloid Leukemia [LAML] mother embodiment, the cancer is selected from kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); and Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC).

[0041] As used herein, an "expression profile" or an "expression pattern" or a "biomarker profile" or a "gene signature" can comprise one or more values corresponding to a measurement of the relative abundance, level, presence, or absence of expression of a discriminative or classifier biomarker or biomarker. An expression profile can be derived from a subject prior to or subsequent to a diagnosis of a type of cancer, can be derived from a biological sample collected from a subject at one or more time points prior to or following treatment or therapy, can be derived from a biological sample collected from a subject at one or more time points during which there is no treatment or therapy (e.g., to monitor progression of disease or to assess development of disease in a subject diagnosed with or at risk for a type of cancer), or can be collected from a healthy subject. The term subject can be used interchangeably with patient. The patient can be a human patient. The one or a plurality of classifier biomarkers that can make up an expression profile as provided herein can be selected from one or more biomarkers of Table 1 and/or any additional set of biomarker classifiers disclosed herein.

[0042] As used herein, the term "determining an expression level" or "determining an expression profile" or "detecting an expression level" or "detecting an expression profile" as used in reference to a biomarker or classifier can mean the application of a biomarker specific reagent such as a probe, primer or antibody and/or a method applied to a sample, for example a sample of the subject or patient and/or a control sample, for ascertaining or measuring quantitatively, semi-quantitatively or qualitatively the amount of a biomarker or biomarkers, for example the amount of biomarker polypeptide or mRNA (or cDNA derived therefrom). The level of a biomarker as provided herein can be determined by any number of methods known in the art and/or provided herein. The methods can include for example immunoassays including for example immunohistochemistry, ELISA, Western blot, immunoprecipitation and the like, where a biomarker detection agent such as an antibody for example, a labeled antibody, specifically binds the biomarker and permits for example relative or absolute ascertaining of the amount of polypeptide biomarker, hybridization and PCR protocols where a probe or primer or primer set are used to ascertain the amount of nucleic acid biomarker, including for example probe based and amplification based methods including for example microarray analysis, RT-PCR such as quantitative RT-PCR (qRT-PCR), serial analysis of gene expression (SAGE), Northern Blot, digital molecular barcoding technology, for example Nanostring Counter Analysis, and TaqMan quantitative PCR assays. Other methods of mRNA detection and quantification can be applied, such as mRNA in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples or cells. This technology is currently offered by the QuantiGene ViewRNA (Affymetrix), which uses probe sets for each mRNA that bind specifically to an amplification system to amplify the hybridization signals; these amplified signals can be visualized using a standard fluorescence microscope or imaging system. This system for example can detect and measure transcript levels in heterogeneous samples; for example, if a sample has normal and tumor cells present in the same tissue section. As mentioned, TaqMan probe-based gene expression analysis (PCR-based) can also be used for measuring gene expression levels in tissue samples, and this technology has been shown to be useful for measuring mRNA levels in FFPE samples. In brief, TaqMan probe-based assays utilize a probe that hybridizes specifically to the mRNA target. This probe contains a quencher dye and a reporter dye (fluorescent molecule) attached to each end, and fluorescence is emitted only when specific hybridization to the mRNA target occurs. During the amplification step, the exonuclease activity of the polymerase enzyme causes the quencher and the reporter dyes to be detached from the probe, and fluorescence emission can occur. This fluorescence emission is recorded and signals are measured by a detection system; these signal intensities are used to calculate the abundance of a given transcript (gene expression) in a sample.

[0043] In one embodiment, the "expression profile" or a "biomarker profile" or "gene signature" associated with the classifier biomarkers described herein (e.g., Table 1 and/or any additional set of biomarker classifiers as disclosed herein) can be useful for distinguishing between normal and tumor samples. In another embodiment, the tumor samples are one type of cancer as determined based on tissue of origin. The one type of cancer can be any type of cancer known in the art and/or provided herein. In another embodiment, the cancer can be further classified as a specific clustering of cluster assignment (COCA) subtype based upon an expression profile of one or more classifier biomarkers (e.g., Table 1) determined using the methods provided herein. The specific COCA subtype can be any COCA subtype as described in Hoadley, Katherine A., Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304. In one embodiment, the specific COCA subtype can be selected from C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA. Expression profiles using the classifier biomarkers disclosed herein (e.g., Table 1, Table 2 and any additional set of biomarker classifiers as disclosed herein) can provide valuable molecular tools for specifically identifying COCA subtypes, and for treating a cancer based on its COCA subtype. Accordingly, provided herein are methods for screening and classifying a subject for pan-cancer COCA subtypes.

[0044] In some instances, a single classifier biomarker or a plurality of classifier biomarkers provided herein (e.g., from Table 1) is capable of identifying COCA subtypes of cancer with a predictive success of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at 1 east about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, inclusive of all ranges and subranges therebetween.

[0045] In some instances, a single classifier biomarker or a plurality of classifier biomarkers as provided herein (e.g., from Table 1) is capable of determining COCA subtypes of cancer with a sensitivity or specificity of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at 1 east about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, inclusive of all ranges and subranges therebetween.

[0046] Also encompassed herein is a system capable of distinguishing various COCA subtypes of cancer not detectable using current methods. This system can b e capable of processing a large number of subjects and subject variables such as expression profiles and other diagnostic criteria. In one embodiment, the methods for determining a COCA subtype as provided herein using one or a plurality of classifier biomarkers as provided herein (e.g., Table 1) can be part of system capable of distinguishing various COCA subtypes that also utilizes data accumulated from other diagnostic methods. The other diagnostic methods can include additional genome-wide molecular assays or platforms, histochemical, immunohistochemical, cytologic, immunocytologic, visual diagnostic methods including histologic or morphometric evaluation of cancer or tumor tissue or any combination thereof. The additional genome-wide molecular assays or platforms can be selected from whole-exome DNA sequencing assays (e.g., Illumina HiSeq and GAID, DNA copy-number variation assays (e.g., Affymetrix 6.0 microarrays), DNA methylation assays (e.g., Illumina 450,000-feature microarrays), genome-wide mRNA level assays (e.g., Illumina mRNA-seq), microRNA level assays (e.g., Illumina microRNA-seq), and protein level assays for proteins and/or phosphorylated proteins (e.g., Reverse Phase Protein Arrays; RPPA).

[0047] In various embodiments, the expression profile derived from a subject (e.g., from a sample obtained from said subject) is compared to a reference expression profile. A "reference expression profile" or "control expression profile" can be a profile derived from the subject prior to treatment or therapy; can be a profile produced from the subject sample at a particular time point (usually prior to or following treatment or therapy, but can also include a particular time point prior to or following diagnosis of a type of cancer); or can be derived from a healthy individual or a pooled reference from healthy individuals. A reference expression profile can be specific to different C O C A subtypes of cancer. The COCA reference expression profile can be from any tissues from which a specific COCA has been found. As provided herein, in one embodiment, the specific COCA subtype can be any COCA subtype as described in Hoadley, Katherine A., Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304. In one embodiment, the specific COCA subtype can be selected from a C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM or C28 THCA COCA subtype.

[0048] The reference expression profile can be compared to a test expression profile or vice versa. A "test expression profile" can be derived from the same subject as the reference expression profile except at a subsequent time point (e.g., one or more days, weeks or months following collection of the reference expression profile) or can be derived from a different subject. In summary, any test expression profile of a subject can be compared to a previously collected profile from a subject that has a specific COCA subtype. The specific COCA subtype can be any COCA subtype as described in Hoadley, Katherine A., Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304. In one embodiment, the specific COCA subtype can be selected from a C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM or C28 THCA COCA subtype.

[0049] The classifier biomarkers provided herein (e.g., Table 1) for use in the methods, compositions or kits provided herein can include nucleic acids (RNA, cDNA, and DNA) and proteins, and variants and fragments thereof. Such biomarkers can include DNA comprising the entire or partial sequence of the nucleic acid sequence encoding the biomarker, or the complement of such a sequence. The biomarkers described herein can include RNA comprising the entire or partial sequence of any of the nucleic acid sequences of interest, or their non-natural cDNA products, obtained synthetically in vitro in a reverse transcription reaction. The biomarker nucleic acids can also include any expression product or portion thereof of the nucleic acid sequences of interest. A biomarker protein can be a protein encoded by or corresponding to a DNA biomarker provided herein. A biomarker protein can comprise the entire or partial amino acid sequence of any of the biomarker proteins or polypeptides. The biomarker nucleic acid can be extracted from a bodily fluid (e.g., blood or fractions thereof, urine, saliva, CSF, etc.), a cell or can be cell free or extracted from an extracellular vesicular entity such as an exosome.

[0050] A "classifier biomarker" or "biomarker" or "classifier gene" can be any nucleic acid (DNA, RNA or cDNA) or protein whose level of expression in a tissue or cell is altered compared to that of a normal or healthy cell or tissue or any other reference or control as provided herein. For example, a "classifier biomarker" or "biomarker" or "classifier gene" can be any nucleic acid (DNA, RNA or cDNA) or protein whose level of expression in a tissue or cell is altered in a specific COCA subtype. The detection of the biomarkers provided herein can permit the determination of the specific COCA subtype. The "classifier biomarker" or "biomarker" or "classifier gene" may be one that is up-regulated (e.g. expression is increased) or down-regulated (e.g. expression is decreased) relative to a reference or control as provided herein. The reference or control can be any reference or control as provided herein. In some embodiments, the expression values of nucleic acids (DNA, RNA or cDNA) that are up-regulated or down-regulated in a particular C O C A subtype of cancer can be pooled into one gene signature. The overall expression level in each gene signature is referred to herein as the "`expression profile" and is used to classify a test sample (i.e., a sample obtained from a subject suffering from or suspected of suffering from cancer) according to the COCA subtype of cancer. However, it is understood that independent evaluation of expression for each of the genes disclosed herein can be used to classify tumor subtypes without the need to group up-regulated and down-regulated genes into one or more gene signatures. In some cases, as shown in Tables 1 and 2, a total of 84 biomarkers can be used for COCA subtype determination. For a specific COCA subtype, for example, expression of 4 of the 84 biomarkers of Table 1 can have altered expression that is correlated therewith. Further, the correlation of the 4 of the 84 biomarkers of Table 1 with the specific COCA subtype can be positive, negative or a combination thereof.

[0051] The classifier biomarkers for use in the methods provided herein can include any nucleic acid (DNA, RNA or cDNA) or protein that is selectively expressed in COCA subtypes of cancer, as defined herein above. Sample biomarker genes are listed in Table 1 below.

[0052] In one embodiment, the 84-gene gene signature for COCA subtyping is found in Table 1. The relative gene expression levels as represented by nearest centroid coefficients of the classifier biomarkers for the 84-gene pan-cancer subtyper of Table 1 are shown in Table 2.

TABLE-US-00001 TABLE 1 84 Gene Classifier Biomarker Signature for Pan-Cancer COCA subtyping. GenBank SEQ Gene Accession ID NO. Symbol Gene Name Number* 1 A1BG Alpha-1-B NM_130786.3 Glycoprotein 2 ACPP Acid Phosphatase, NM_001099.5 Prostate 3 APC2 APC2, WNT Signaling NM_001351273.1 Pathway Regulator 4 AQP5 Aquaporin 5 NM_001651.4 5 ASGR1 asialoglycoprotein NM_001671.5 receptor 1 6 BCAN brevican NM_021948.5 7 BCL2L15 BCL2 like 15 NM_001010922.3 8 C1orf172 keratinocyte NM_152365.3 differentiation factor 1 9 CAPS calcyphosine NM_004058.5 10 CBLC Cbl proto- NM_012116.4 oncogene C 11 CDH1 cadherin 1 NM_004360.5 12 CEACAM5 carcinoembryonic NM_004363.5 antigen related cell adhesion molecule 5 13 CEACAM6 carcinoembryonic NM_002483.7 antigen related cell adhesion molecule 6 14 CHMP4C multivesicular NM_152284.4 body protein 4C 15 CLCA2 chloride channel NM_006536.7 accessory 2 16 CLDN4 claudin 4 NM_001305.4 17 COL11A2 collagen type NM_080680.2 XI alpha 2 chain 18 CRB3 crumbs cell NM_139161.5 polarity complex component 3 19 CTSE cathepsin E NM_001910.4 20 CUBN cubilin NM_001081.3 21 CYP2B7P1 cytochrome P450 NR_001278.1 family 2 subfamily B member 7, pseudogene 22 DLX5 distal-less homeobox 5 NM_005221.6 23 DMGDH dimethylglycine NM_013391.3 dehydrogenase 24 ELF3 E74 like ETS NM_004433.5 transcription factor 3 25 EMX2 empty spiracles NM_004098.4 homeobox 2 26 EMX2OS EMX2 opposite NR_002791.2 strand/antisense RNA 27 EPCAM epithelial cell NM_002354.2 adhesion molecule 28 ERBB3 erb-b2 receptor NM_001982.3 tyrosine kinase 3 29 ESR1 estrogen receptor 1 NM_000125.3 30 FAM171A2 family with sequence NM_198475.2 similarity 171 member A2 31 FOLH1 folate hydrolase 1 NM_004476.3 32 GABRP gamma-aminobutyric NM_014211.3 acid type A receptor pi subunit 33 GATA3 GATA binding protein 3 NM_001002295.2 34 GCNT3 glucosaminyl (N-acetyl) NM_004751.3 transferase 3, mucin type 35 GPC2 glypican 2 NM_152742.3 36 GPR35 G protein-coupled NM_001195381.1 receptor 35 37 GPRC5A G protein-coupled NM_003979.3 receptor class C group 5 member A 38 GRHL2 grainyhead like NM_024915.3 transcription factor 2 39 HNF1A HNF1 homeobox A NM_000545.6 40 HPX hemopexin NM_000613.3 41 IYD iodotyrosine NM_203395.2 deiodinase 42 KRT18 keratin 18 NM_000224.3 43 KRT6A keratin 6A NM_005554.4 44 KRT6B keratin 6B NM_005555.4 45 KRT81 keratin 81 NM_002281.3 46 KRT8 keratin 8 NM_002273.3 47 LAD1 ladinin 1 NM_005558.3 48 LCK LCK proto-oncogene, NM_005356.5 Src family tyrosine kinase 49 LGALS4 galectin 4 NM_006149.4 50 LYPD1 LY6/PLAUR domain NM_144586.6 containing 1 51 MARVELD3 MARVEL domain NM_052858.5 containing 3 52 MEG3 maternally NR_046473.1 expressed 3 53 MUC13 mucin 13, cell NM_033049.4 surface associated 54 MUC16 mucin 16, cell NM_024690.2 surface associated 55 MUC4 mucin 4, cell NM_018406.7 surface associated 56 MYCN MYCN proto-oncogene, NM_005378.6 bHLH transcription factor 57 NAPSA napsin A aspartic NM_004851.3 peptidase 58 NKX3-1 NK3 homeobox 1 NM_006167.4 59 NPR1 natriuretic NM_000906.4 peptide receptor 1 60 PAX8 paired box 8 NM_003466.4 61 PRAME preferentially NM_206956.3 expressed antigen in melanoma 62 PSCA prostate stem NM_005672.5 cell antigen 63 PVRL4 nectin cell NM_030916.3 adhesion molecule 4 64 S100P calcium binding NM_005980.3 protein P 65 SALL4 spalt like NM_020436.5 transcription factor 4 66 SFTPD surfactant protein D NM_003019.5 67 SILV premelanosome NM_006928.4 protein 68 SIT1 signaling threshold NM_014450.3 regulating transmem- brane adaptor 1 69 SLC26A4 solute carrier NM_000441.1 family 26 member 4 70 SLC3A1 solute carrier NM_000341.3 family 3 member 1 71 SLC45A3 solute carrier NM_033102.3 family 45 member 3 72 SOX17 SRY-box 17 NM_022454.4 73 SPDEF SAM pointed domain NM_012391.3 containing ETS transcription factor 74 SPINT2 serine peptidase NM_021102.4 inhibitor, Kunitz type 2 75 TCEAL5 transcription NM_001012979.3 elongation factor A like 5 76 TG thyroglobulin NM_003235.5 77 TMEM27 collectrin, amino NM_020665.6 acid transport regulator 78 TP63 tumor protein p63 NM_003722.5 79 TRPS1 transcriptional NM_001330599.1 repressor GATA binding 1 80 TSPAN8 tetraspanin 8 NM_004616.3 81 UPK3B uroplakin 3B NM_001347684.1 82 VTN vitronectin NM_000638.4 83 ZNF578 zinc finger NM_001099694.2 protein 578 84 ZNF695 zinc finger NM_020394.5 protein 695 *Each GenBank Accession Number is a representative or exemplary GenBank Accession Number for the listed gene and is herein incorporated by reference in its entirety for all purposes. Further, each listed representative or exemplary accession number should not be construed to limit the claims to the specific accession number.

TABLE-US-00002 TABLE 2 Nearest centroid classifier coefficients of 84 Gene Classifier Biomarker Signature for Pan-Cancer COCA subtyping. C4 C6 C8 Gene C1 C2 C3 (Squamous- (LUAD (PAAD/some C9 # Symbol (ACC/PCPG) (GBM/LGG) (OV) like) enriched) STAD) (UCS) 1 A1BG 1.591560699 0.190424 0.486501004 -0.428197254 0.412635759 -0.184279 2.001627705 2 ACPP -3.165733781 -3.12929 1.422642856 1.55810748 1.220541761 0.3613543 -0.523609534 3 APC2 5.927921166 9.535164 -0.596869926 0.426709368 -0.235550248 0.211678867 0.296218394 4 AQP5 0.913265915 -1.5756 6.077199618 0.038435948 3.968116521 5.439757901 4.689537595 5 ASGR1 0.200382941 2.23723 -0.270715575 -0.385421722 0.9311113 0.377002269 1.767020071 6 BCAN 3.407338299 11.97624 -1.053982755 -0.662093738 -0.729179033 0.649031299 0.667042943 7 BCL2L15 -0.658510708 0.077946 0.865164587 -0.382856173 4.273114175 5.648586443 -0.38038599 8 C1orf172 -7.367511726 -8.11012 0.639328401 0.482516142 0.16674242 -0.401651641 -2.035170988 9 CAPS -0.328076695 -0.34918 2.841784698 -1.13544035 1.075257629 0.923666447 0.259472216 10 CBLC -8.155167351 -8.15517 0.559363299 1.283503926 0.054904876 0.803955968 -1.909451133 11 CDH1 -11.31993378 -6.63507 -0.611897157 0.320830787 0.259254437 0.32354087 -2.417624306 12 CEACAM5 -4.263447619 -4.26345 -2.162761329 5.453807243 8.01040042 8.25154716 -1.643025427 13 CEACAM6 -6.692665202 -6.69267 -1.411084364 3.660636032 8.117243572 7.181029674 -2.853743681 14 CHMP4C -4.851564145 -6.7881 0.477705202 0.092903499 0.246039693 0.425978288 -1.619930594 15 CLCA2 -1.916026013 -0.55212 -2.135469493 10.56468928 0.196047759 -0.982688048 0.230995571 16 CLDN4 -7.769800248 -8.52437 1.293661429 -0.21590352 0.923225733 0.698989001 -2.196157068 17 COL11A2 0.994719726 3.794411 0.981227344 -0.355884432 -0.290171902 -0.134024256 5.747006193 18 CRB3 -6.855921321 -6.69387 0.314038459 -0.051924366 0.42596628 0.230134355 -2.12978152 19 CTSE -2.769179309 -2.76918 0.690060563 -0.068850571 8.211338748 10.27849106 -1.795164025 20 CUBN 1.417595067 1.109969 -1.06751464 -1.098119051 0.200954954 0.214406457 1.001364945 21 CYP2B7P1 -0.494004573 0.493388 -0.20904464 -0.38882331 7.020240242 1.642138931 0.554846851 22 DLX5 0.646764837 -0.46515 -0.543489219 3.043312263 -1.037762982 -0.615048606 3.664621768 23 DMGDH 1.35983288 1.246526 -0.621678415 -1.957477961 0.403167757 0.050041264 -0.042151268 24 ELF3 -9.499613685 -8.35834 1.621031579 0.270463158 1.261978364 1.664172061 -1.774337463 25 EMX2 -1.445515678 4.196057 7.930390253 -0.743521137 -3.08024833 -1.20337606 5.823681705 26 EMX2OS -1.40599953 4.680959 6.731039756 -1.182024547 -3.142205278 -1.044827924 5.399413819 27 EPCAM -4.140528206 -8.15621 1.301641135 -0.969949548 1.349981921 1.210777667 -0.808127169 28 ERBB3 -6.795539466 -2.20761 -0.171425783 -0.850309305 0.543205553 0.488891046 -1.571378197 29 ESR1 -1.563757872 -2.7205 4.824366357 -0.395784527 0.80814913 -0.646508959 -0.041535695 30 FAM171A2 2.31912146 3.133851 2.782191887 -0.20635555 0.23640564 -0.553185081 4.13232199 31 FOLH1 0.35530613 1.32629 0.070865602 -0.437336881 -0.404293953 -0.516227658 0.984459412 32 GABRP -3.114382282 -3.80051 2.138616034 2.054140007 -0.13455569 5.495459292 0.876924899 33 GATA3 3.645314335 -4.46319 1.041365419 0.137891422 -0.30939716 0.245236202 -0.485018337 34 GCNT3 -3.715677872 -4.43208 -0.425219053 1.24405515 3.332011974 6.140028092 -2.627063776 35 GPC2 0.327681714 3.748559 0.567306982 0.383564177 0.020301437 -0.493055636 4.27187925 36 GPR35 -1.123275158 0.288748 0.479762937 -0.401845781 0.612377482 3.964562506 1.02539215 37 GPRC5A -5.029113731 -6.47264 -1.03988769 0.471927094 2.504432044 2.440959491 -1.902607145 38 GRHL2 -9.186320721 -9.01009 0.20905294 0.759772508 0.222957527 -0.501711577 -2.025188838 39 HNF1A -0.226398309 0.326606 -0.566429337 -0.634513541 -0.056397283 3.532952512 0.664824374 40 HPX 0.285105569 -0.08725 -0.761181725 -0.99545754 0.077064824 0.031571949 0.655698572 41 IYD -3.48501457 -3.48501 -2.700731814 -1.942508868 2.764256302 4.516203307 -2.338163874 42 KRT18 -6.139551755 -9.93225 0.824379787 -1.150398992 0.366193169 0.669054426 -1.559549225 43 KRT6A -3.978012535 -3.97801 3.985705153 13.04837042 1.834983617 2.826759232 0.495449701 44 KRT6B -3.679513879 -3.67951 -0.284781052 10.86983161 -0.095874456 4.031758881 -0.319655407 45 KRT81 -1.52156723 -2.24431 1.219674513 0.808360415 0.685287495 0.157557306 1.332452992 46 KRT8 -9.333378281 -12.0127 0.923200159 -0.888982445 0.25864778 1.104030262 -1.049517897 47 LAD1 -9.54391772 -9.93659 0.152727678 2.525900274 1.096406409 2.02745431 -1.338565911 48 LCK -2.653249024 -4.15782 -0.449932121 0.595456972 1.114873169 1.294851611 -0.905250193 49 LGALS4 -1.069860082 -0.88856 -0.804776299 -0.636711502 0.902648195 9.957840161 0.300844381 50 LYPD1 0.161356715 4.620573 6.06218977 0.619464566 0.866852785 1.287462226 2.488687449 51 MARVELD3 -6.499693064 -1.92762 -0.006137317 0.236649367 0.110533207 0.419749056 -1.459194862 52 MEG3 6.987769361 4.00401 0.481443128 -0.367973396 0.187829444 2.037867641 5.549924389 53 MUC13 -1.096164161 -1.549 -0.857929123 -0.216081121 3.60927036 9.342999034 -0.087884353 54 MUC16 -2.940429889 -2.94043 8.971152269 3.553030115 5.922759027 2.391002348 2.159619147 55 MUC4 -2.659938287 -1.76141 1.013937899 4.360400601 6.293886393 4.455995593 0.8936279 56 MYCN 2.635001351 3.722476 3.48370589 -0.476428956 -0.4996297 -0.139261692 4.259965299 57 NAPSA -1.134449647 -0.6277 -0.350262749 0.121656227 11.53466505 -0.206023725 -0.551300842 58 NKX3-1 0.643122217 -0.8988 -1.012928267 0.87446207 0.131533121 0.091873999 -0.013147747 59 NPR1 1.562673445 -1.70035 4.826134025 -0.898468302 0.426172792 0.791217063 0.909336394 60 PAX8 -1.207977403 -2.70163 6.131772035 -0.109570392 -0.507568017 0.425575927 0.567460764 61 PRAME -2.720513358 -3.0116 7.417738065 4.107800576 1.634537806 -0.732218434 8.835740874 62 PSCA -2.62692522 -1.51466 1.088832807 2.403172672 0.853737331 6.468730165 -0.867506614 63 PVRL4 -7.123332103 -7.84158 0.298515276 2.072952358 1.11395964 0.537458726 -2.175556637 64 S100P -4.176354266 -4.39339 -2.039708839 2.60206496 3.54339421 5.588006332 -0.835327459 65 SALL4 -0.350139755 -1.98283 0.992610931 0.242440795 0.631851425 1.50741502 2.172219002 66 SFTPD 1.229072592 0.156327 1.095837733 0.844728495 6.616682345 -0.138899031 -0.528759079 67 SILV -1.601355906 -3.16131 0.436716938 -0.17041022 0.318281992 0.27070394 0.049533868 68 SIT1 -2.339171989 -3.35217 -0.160872017 0.621892503 1.468402409 0.74432008 -1.226672618 69 SLC26A4 -0.01413008 0.420072 -1.783069972 -0.415510022 0.74827946 -0.100896769 -0.464161483 70 SLC3A1 1.225854746 0.996711 -0.32436489 -1.197295399 -0.603148658 5.542018189 0.717943528 71 SLC45A3 -2.005759994 -0.41185 -0.428424528 -0.241045139 0.557739049 1.726290953 0.128310421 72 SOX17 0.824116164 -0.22888 6.125476978 -1.080390132 -0.166935984 0.604218197 1.286142427 73 SPDEF -2.615781968 -2.0345 3.94966981 -0.755535616 4.925193925 4.243866593 0.699764031 74 SPINT2 -2.997432839 -4.83916 1.007795827 0.294659358 0.15758716 0.166037725 -0.979250422 75 TCEAL5 4.349410995 5.379822 1.642558611 -0.898540151 -0.528496105 0.788010053 4.759050684 76 TG 2.696748103 -0.10465 -1.217878931 0.390892921 -0.793389805 -0.297668711 1.286415669 77 TMEM27 -0.42619294 -0.29365 -0.1091435 -0.496636878 0.747255703 0.386605101 -0.460703305 78 TP63 -2.443322255 -2.69429 -1.072539715 8.079773017 1.080093521 -0.122917429 0.715521461 79 TRPS1 -0.827302587 0.82757 1.115573024 0.379838983 -0.553191739 -0.163032265 1.067422295 80 TSPAN8 -1.517176876 -1.38543 1.264805902 -0.971215985 4.123187886 8.120119283 1.88608684 81 UPK3B -1.800031107 -1.79259 6.496391778 2.591465189 1.916362767 1.31370249 1.253864936 82 VTN 4.532732542 0.962046 -0.35391519 -0.827839727 0.374371855 3.646375202 0.21090879 83 ZNF578 1.940365745 2.606116 1.274215935 -2.128937852 -0.532541888 -0.12176826 1.417239081 84 ZNF695 -2.395893789 -0.97465 2.29727236 1.015039672 -0.170693901 -0.682198412 2.909908974 Gene C10 C12 C14 C15 C16 C17 C19 # Symbol (BRCA/Basal) (UCEC) (PAAD) (CESC) (BLCA) (TGCT) (COAD/READ) 1 A1BG 0.142304769 -0.093163359 -1.141696682 -1.152290675 -1.29740042 0.256130124 -1.788698924 2 ACPP -1.398401725 -0.082101813 10.45064724 1.42121 0.266257162 0.477828173 0.992457174 3 APC2 -0.572616388 -0.977273763 0.32549264 0.054659498 0.405219188 1.45040744 0.15536217 4 AQP5 3.702869943 6.247684679 -1.136288477 8.250686508 -2.413179516 2.019598373 -0.061400955 5 ASGR1 -0.374333329 -0.307671908 -1.422479203 -0.69544287 -0.284590427 0.811900301 0.284656903 6 BCAN -0.843138597 -0.389425497 -2.101665722 0.113052513 -0.411742591 2.451102537 1.398031108 7 BCL2L15 -0.509343675 2.21556825 -0.416331352 5.642847062 -0.076320616 -0.539990486 5.956925607 8 C1orf172 0.377167732 0.541078744 0.28000935 0.529249282 0.78721152 -0.331669012 0.205165485 9 CAPS 1.236614303 3.401999923 1.140742546 3.129590389 3.356392461 -1.598575877 -1.041036365 10 CBLC 0.528896861 0.860866464 0.983689368 1.366858965 2.004650922 -1.590854285 1.462118274 11 CDH1 0.147729378 0.016506631 0.816575199 0.187211685 0.578678097 -1.440668807 0.796827631 12 CEACAM5 -0.578531195 -0.226926702 0.223892364 8.216176042 2.697562315 -3.025546808 11.26786682 13 CEACAM6 0.378171192 -0.861664584 -1.150176451 5.321201782 1.780316958 0.990910873 7.545948521 14 CHMP4C 0.932335566 0.332852097 0.654936052 -0.061505461 0.701272543 -2.076344669 0.955706036 15 CLCA2 1.252518338 -0.870513832 0.834994065 0.083375317 5.899414972 0.277783481 -1.434642506 16 CLDN4 0.596506064 0.783384706 0.695706592 0.872264084 1.666131843 -4.130304775 1.506307594 17 COL11A2 1.152615114 1.094477267 -0.512589565 0.34882784 -0.277012497 0.921823497 -0.972050734 18 CRB3 -0.252190917 0.447730499 0.314262173 0.485822293 0.422819651 -1.015012817 0.63102577 19 CTSE -1.579272399 -0.27402142 -0.123593233 4.329326574 3.964690014 0.131319517 6.509851516 20 CUBN -0.042341755 0.692484506 -0.083311834 -1.016397158 -1.291707376 -0.060942034 -1.2605976 21 CYP2B7P1 -0.793782659 -1.135804901 -0.048029795 2.920741779 -1.769335752 -1.106667891 0.57204011 22 DLX5 1.065680224 6.63897818 1.203219318 0.244733336 2.095413211 -0.874548488 -2.278703058 23 DMGDH -1.016515828 -0.716060074 0.747670367 -1.492260644 -2.335607422 -0.511890494 -1.983626926 24 ELF3 0.867636291 1.089943222 -0.33693125 2.161246514 1.979945601 -2.024525261 1.906780054 25 EMX2 0.398485049 7.622270699 -1.139800617 3.497783132 2.434679878 -0.070065196 -2.337175682 26 EMX2OS 0.35047227 6.672513444 -0.771169469 2.651126602 1.918119816 0.003917034 -2.749389229 27 EPCAM 1.070959088 1.65345969 0.656584363 1.491420181 -0.23366156 0.118017267 2.502744305 28 ERBB3 0.156681689 -0.354419176 0.85480606 0.70559009 0.245664699 -1.125976575 1.142628311 29 ESR1 -0.114307986 4.969542469 1.603982283 2.334162784 -0.866991852 -1.616321139 -2.643912362 30 FAM171A2 1.110078033 2.742226868 -0.598712372 1.23539718 0.196442464 2.52966238 -2.299101465 31 FOLH1 1.342626401 1.95199662 7.506581427 -1.68931756 -1.160417237 -1.194199537 -0.990382338 32 GABRP 8.062957771 3.497605248 3.292130436 7.257298478 -1.104614063 -2.409859347 1.866998203 33 GATA3 2.883744656 -1.322536343 0.362300268 0.172939031 5.863126341 0.347938903 -1.305257494 34 GCNT3 -2.229182519 1.453042898 -1.612817806 4.45653155 -2.101854264 -1.198296139 5.978745374

35 GPC2 1.844529239 1.87662419 -0.31412767 -0.281008532 1.248099969 3.603718475 -0.446098297 36 GPR35 -0.201147094 1.145430196 -0.633581001 3.403228537 -0.074926063 0.037914492 4.997511501 37 GPRC5A 0.136594075 -0.047037042 -1.729389157 1.713890286 0.947387044 1.099444707 2.341085357 38 GRHL2 0.887932851 0.608466746 1.846078681 0.587744821 0.927526179 -4.112841993 0.296403053 39 HNF1A -0.757149534 0.998266857 -0.224121716 3.083804118 -0.876897763 -0.071449343 4.816960704 40 HPX 0.083502266 0.467027224 1.898436273 -0.011129604 -0.443467655 1.739428473 -0.713289667 41 IYD -1.986600368 -1.163865741 1.126629676 1.43730223 0.098371764 -3.48501457 5.821174506 42 KRT18 -0.774406938 0.534341861 0.455271746 1.038944818 0.900515088 -0.471025112 1.117607068 43 KRT6A 3.285148104 2.483810663 -0.073242302 4.424176683 4.698929835 -3.375318162 0.482454829 44 KRT6B 6.929849448 -0.029392703 -0.881504967 3.541676869 2.041513217 -3.679513879 2.619439855 45 KRT81 3.704809399 1.125852117 -1.180411884 1.855047045 -0.224822743 -1.682654755 -1.136304837 46 KRT8 0.117987473 0.541422454 -0.071910723 1.371770589 1.338626534 -0.317434922 1.536661174 47 LAD1 1.117718225 0.900829355 -0.184554726 1.845819432 2.28378527 -1.0294741 2.021237694 48 LCK 0.323828061 -0.2698455 -0.135093489 0.809447978 -0.427656591 1.876095595 0.766125516 49 LGALS4 -1.049805056 -0.658445291 0.33823429 2.270150332 1.671819995 1.025358005 10.63263886 50 LYPD1 0.318704537 2.561660067 -1.46291243 0.106783622 -0.846380974 0.579452651 -1.457927861 51 MARVELD3 0.594064846 0.59864298 0.746088507 0.673220178 0.379141989 -1.349340309 0.960362538 52 MEG3 -0.760697048 -0.559506246 0.124435896 -0.790286218 0.176547542 7.212428882 -0.102624496 53 MUC13 -0.415482063 2.373448458 3.347855433 9.337472272 -1.260341969 -1.137285921 11.16914163 54 MUC16 5.749271478 7.257302838 -0.380117549 9.47128499 -0.667829704 2.503910209 -1.68279375 55 MUC4 -0.533649289 1.580638241 1.704056599 7.6185769 1.358543899 3.416007758 4.848907641 56 MYCN 1.167011131 1.749261819 -3.028046397 0.244478213 0.693171089 6.57493164 0.586544197 57 NAPSA -0.568068159 0.272590794 -0.267650347 0.491103798 -0.068387887 0.784909839 -0.516593433 58 NKX3-1 0.636142588 -0.165152927 8.791444726 1.213527947 0.111824365 0.401176282 -1.098810432 59 NPR1 -0.108559874 -0.014674711 -0.783482295 -1.047763786 -1.086165265 -0.51156436 -1.013472417 60 PAX8 -1.679043287 6.175626455 -1.300676688 3.829761838 -0.264941996 0.019241642 0.199759138 61 PRAME 5.753805128 8.637405593 -1.641025038 2.240303364 -1.86413095 6.249324024 0.732324816 62 PSCA 2.380934424 0.822962284 5.024448953 5.074590237 9.409030075 -1.378514517 0.823284273 63 PVRL4 1.983169736 0.54330796 0.274629626 1.209370824 2.956273849 -1.709650966 -0.443057331 64 S100P 3.387292842 0.722588023 0.264728445 6.102225171 7.587401555 -0.745010036 6.222215668 65 SALL4 -0.212011363 -0.183118884 -0.428196415 1.736697609 1.763666611 6.22003894 1.160887388 66 SFTPD -0.864741869 0.18743199 0.85637944 -0.169964303 -1.953003098 0.810342471 -3.059355397 67 SILV -0.445152541 0.023561013 -0.906600385 1.276911935 0.671250555 -0.419750375 0.364343543 68 SIT1 0.404484797 -0.245179126 -0.698370063 -0.228329389 -0.700949754 1.862224753 0.160038551 69 SLC26A4 -0.242562803 -0.736362299 4.542023228 0.049925703 -1.244893781 -1.393279547 -0.773795962 70 SLC3A1 -0.811991759 1.503175223 0.81337641 0.685335393 -0.830561409 0.02998455 4.234950007 71 SLC45A3 0.50351858 -0.257430773 7.798304016 0.259038112 0.761165507 1.057588337 1.253011444 72 SOX17 -0.436621464 6.590489885 0.258734252 0.190327448 -0.537074063 4.1051736 -0.639722737 73 SPDEF 2.428928058 4.878948809 9.396200085 5.896810841 0.785079512 -1.183433789 3.426972043 74 SPINT2 0.199553149 0.669655069 0.202002754 0.813009857 0.747461864 -0.67968284 0.224352664 75 TCEAL5 -0.580215651 0.283236555 1.291973501 -0.314854034 -0.207630749 1.239038231 -1.642797685 76 TG -1.043977276 -1.109552249 1.299196722 -1.24118987 -0.588195791 -0.92548737 0.175292614 77 TMEM27 0.248102359 0.030206129 0.611157159 -0.754191803 -0.750158332 1.251273614 -1.235570332 78 TP63 1.282401189 -1.071684619 3.203409462 -1.13139572 6.245170227 -0.345850774 -2.304303836 79 TRPS1 3.153356243 1.248382334 0.226726961 0.003939999 -2.35803211 -1.170459499 -1.794640325 80 TSPAN8 -1.77985797 0.74692949 6.457395474 4.704465483 -0.385074926 -0.435573001 8.97062099 81 UPK3B 0.43781618 1.273683944 -0.408516441 2.151943812 7.898733759 -0.735658973 -0.139912799 82 VTN -1.022686104 -1.195484585 -0.273276881 -1.471670906 0.728314508 3.181634913 -0.582351194 83 ZNF578 -0.128482728 -0.291752675 0.60523606 -2.466912276 -1.115858745 5.469695435 -1.515460348 84 ZNF695 2.994868611 2.77909196 -1.075168344 2.286781576 1.644923103 3.609635955 1.952089723 C21 Gene C20 (KIRK/ C22 C24 C25 C26 C28 # Symbol (SARC/MESO) KICH/KIRP) (Liver) (BRCA/Luminal) (THYM) (SKCM/UVM) (THCA) 1 A1BG 0.070192984 -0.940840591 8.703413543 0.936369381 -1.706237879 1.914831468 0.703529067 2 ACPP -2.032541038 -2.305500467 -4.40459131 -1.024439493 -2.066553063 -3.741468299 0.699426376 3 APC2 0.552360013 -0.679752407 -0.062564922 -0.527174725 -0.177801985 1.332087657 -1.406046015 4 AQP5 -1.419094969 -2.627502329 -2.379706191 -0.280015058 0.67166607 -1.438430189 3.948999547 5 ASGR1 0.462676231 -0.369411855 9.174063668 -1.440166184 -0.048667321 -1.316415138 1.003468362 6 BCAN -0.209671799 0.222422862 0.598814814 -0.685014857 -2.971866954 7.441867064 -2.689173959 7 BCL2L15 -0.946597411 0.308006633 -0.847993525 -0.339415371 0.44529515 -1.396188006 -1.219332417 8 C1orf172 -7.714313141 -2.053892696 -1.961055619 0.097896284 -1.121520119 -5.883858505 0.420348593 9 CAPS -0.499052174 -1.362494555 -0.691670099 0.575620059 0.228128949 -0.326249828 1.883752499 10 CBLC -8.155167351 -3.648064102 0.283666077 0.197383744 -8.155167351 -8.155167351 -4.683902455 11 CDH1 -7.229104847 -1.902809546 -0.803408059 0.453092886 -1.794492653 -0.380697254 1.07759058 12 CEACAM5 -4.263447619 -4.263447619 -4.263447619 3.43408992 -4.263447619 -3.826859325 -3.766911393 13 CEACAM6 -6.003097658 -6.22642964 -6.020466183 2.793954656 -5.749231419 -6.088214272 -1.029763418 14 CHMP4C -6.433893852 -0.448980057 -0.477565154 0.166274869 -3.416609246 -6.4170014 0.423295456 15 CLCA2 1.090083657 -1.916425099 -2.448293094 2.423949605 0.511588318 -0.16703996 -0.923829634 16 CLDN4 -6.877306455 -0.800472122 -4.850938463 -0.062787487 -6.750496629 -8.258170243 1.193098579 17 COL11A2 0.407171494 -0.522028403 -1.162577547 -1.391989324 2.822133446 4.012255459 0.998530701 18 CRB3 -6.899881762 0.409378715 0.082599609 -0.202979549 -3.405323461 -5.927493049 0.442041688 19 CTSE -2.104241431 0.366273475 -1.243260786 -2.250040026 -2.122740123 -1.826195711 5.586773138 20 CUBN 0.713604848 7.281399905 -1.384529654 -0.145536797 1.410829201 3.566340978 3.20938295 21 CYP2B7P1 -0.654635147 -1.447176918 5.139802834 6.622628205 -1.379336644 -1.212199304 -0.964049728 22 DLX5 0.462490967 0.017699215 -3.265329736 -0.745686562 -2.117303943 -0.829299281 -0.068606829 23 DMGDH 0.028856242 6.060504719 6.702437958 -0.060898439 -0.46134749 -1.489004211 2.38214753 24 ELF3 -7.606527581 -0.555341599 -0.334664939 0.302735788 -5.416983065 -8.778305188 -1.61788093 25 EMX2 2.802771238 7.074822861 -3.08024833 1.035384246 -1.557188268 -0.213597469 -1.488833995 26 EMX2OS 2.520378612 7.353718721 -3.593640608 1.294980889 -1.893334068 -0.333268626 -1.117234841 27 EPCAM -8.94327619 -1.582907817 -6.179887918 0.150227096 -3.89203662 -9.927578427 1.469515171 28 ERBB3 -7.397006842 0.362674201 0.676372657 1.354976731 -7.751611174 1.393383686 -0.864197462 29 ESR1 -0.204263771 0.353961842 -0.001186471 7.045755877 -0.917732083 -0.567345455 1.658056187 30 FAM171A2 0.843521911 -1.147803639 -1.94488491 -0.67709113 -0.913518602 -0.123166538 2.177241264 31 FOLH1 -0.285087483 2.107020634 2.114399746 -0.44262496 -3.693628465 -1.90866141 -0.126630866 32 GABRP -2.303619388 -1.113604356 -2.60527593 2.880519078 -2.969804846 -0.477412964 -2.451544871 33 GATA3 -0.479072713 -0.694342037 -2.42000097 7.039537351 2.449239776 -2.642455615 1.305924613 34 GCNT3 -3.369932214 3.012084991 0.745283917 -3.199989256 0.677330491 -4.065793513 -0.452261295 35 GPC2 -0.655639972 -1.345174813 -2.097850016 -0.520643983 2.326152106 -0.721335705 -2.085120953 36 GPR35 -0.15384199 0.320806564 -0.470378252 -0.642499168 1.115849375 -1.434965852 -1.068214302 37 GPRC5A -1.978637673 -3.708321529 -7.617162596 1.869297678 -7.799087331 -2.526958538 1.836642695 38 GRHL2 -8.760984555 -8.300732853 -8.41380076 0.977699908 -2.733003314 -9.346544321 -0.260490678 39 HNF1A -0.460004648 5.003097445 5.740038488 -0.419983585 -0.254057708 -0.06916107 -1.339783101 40 HPX 0.428825996 -0.644318213 12.34302566 4.13452407 -0.715914255 -1.121106629 -0.927626931 41 IYD -3.48501457 1.83359512 5.111462206 0.63980155 -3.48501457 -3.48501457 9.864317761 42 KRT18 -5.393634178 -0.214336662 0.659378292 0.645722621 -3.361767124 -6.292360598 0.141599862 43 KRT6A -2.750394666 -3.593741642 -3.978012535 -1.007177282 1.775950277 -1.756754105 -1.199299426 44 KRT6B -2.809563532 -3.679513879 -3.007677051 3.038039173 1.074967474 -0.771604139 -2.767720312 45 KRT81 -0.708340478 -0.549017438 -1.474487037 1.719278698 0.293233459 -2.832035518 1.29934714 46 KRT8 -6.585518291 -0.445328958 0.292357177 0.583940663 -1.211875599 -7.214684995 0.11941998 47 LAD1 -6.366889981 -3.487703983 -0.03314457 -0.937855879 -2.032988069 -4.586601984 -0.415235244 48 LCK -0.077998068 0.355214635 -0.747932263 -0.312039768 5.221543649 -1.853755715 -0.526016141 49 LGALS4 -0.883963009 1.366073433 9.773901918 -1.137042557 0.240641913 -1.598817352 -0.203473823 50 LYPD1 0.387124296 -0.528951531 0.547288234 -0.876913408 0.13379984 0.661428164 -0.897772519 51 MARVELD3 -5.995262907 -0.510050567 -0.675659361 0.322410532 -2.735366823 -6.383666653 -0.153513769 52 MEG3 2.478280919 -2.166933932 -0.320863598 0.160100014 2.853324939 -2.730675804 -3.166451005 53 MUC13 -0.981854002 1.997077234 6.771194467 -1.618112428 -1.772933448 -2.419188288 -1.948580943 54 MUC16 -1.427646768 -1.678538069 -2.940429889 1.60919 -1.668765178 -2.940429889 1.33450999 55 MUC4 -3.199831606 -0.551376679 -2.460727016 -2.202007274 -1.442945771 -4.022799483 -1.386650033 56 MYCN -1.115153774 -1.072643704 -0.572987836 -0.563222061 2.256763699 -1.121103788 0.383429385 57 NAPSA -0.441224683 5.357444831 -0.330311961 -0.680826272 1.54889432 -1.10948967 3.230552348 58 NKX3-1 0.34424304 -0.695607881 -0.636037275 1.380598103 -0.358807355 -1.225980043 -1.347772078 59 NPR1 3.611141372 2.936608674 0.739290647 -0.02018339 -0.04911732 -1.692369146 0.560520251 60 PAX8 -0.438408776 5.138704009 -0.439224734 -1.115572722 -0.742610195 -1.098989328 7.330352514 61 PRAME -2.28601297 3.648546027 -1.904681098 -1.204180981 3.601719603 9.250663624 -3.172944285 62 PSCA -1.664873567 -2.372135296 -2.32137749 1.204841172 -1.580925941 0.391748243 -3.189626014 63 PVRL4 -4.983285402 -6.308620694 -6.330798801 1.140190077 -3.872718208 -6.359272034 0.126583059 64 S100P -4.27172475 -4.04897439 0.499095434 2.122747189 -4.765549062 -4.663901764 -4.574712189 65 SALL4 -0.701854731 -2.670674063 -1.068969101 0.308484856 -1.113633609 2.219699773 0.019104844 66 SFTPD -2.015504097 -0.059979562 -1.883528068 -0.664564777 -1.784683096 -1.174451747 2.77077955 67 SILV -0.404015329 0.403352323 1.696442392 0.346443524 -1.809580739 12.3265592 -0.064184971 68 SIT1 0.560522874 0.56641542 -0.448541127 0.083905789 6.077538122 -1.010014644 -0.588029822 69 SLC26A4 0.245073029 0.600404783 -1.143209401 0.077251179 0.024544315 0.276126125 7.424523266 70 SLC3A1 -0.360884127 10.50265557 1.764194349 -0.750224836 -0.620498156 -0.303626634 -0.228977476 71 SLC45A3 -1.119761006 0.021163292 0.733358084 -0.480014382 -2.00381626 -1.453023157 -2.254242818 72 SOX17 0.817442439 0.837037779 0.345260582 0.26054328 -0.203888143 -1.596069152 0.733884158 73 SPDEF 2.697057213 -2.838870874 -2.854924213 7.609282727 -3.084262875

-2.745456716 -2.779572185 74 SPINT2 -3.920290094 -0.542550342 -5.841694183 0.163004523 -0.712680222 -5.966064445 0.738611694 75 TCEAL5 0.881390897 -0.79947069 -2.066499307 0.638825329 0.319737925 -0.114766242 0.788194285 76 TG 0.984073587 0.60666684 -1.221557274 -1.111088643 1.124956459 -0.727984197 15.10003804 77 TMEM27 -1.803900196 6.875082323 0.633259141 -0.517663186 -0.292695792 -0.470425257 1.189669219 78 TP63 -0.665339268 -2.068568045 -1.9563835 1.974020464 5.386578658 -2.022259539 -0.159043543 79 TRPS1 0.01584306 -0.129451899 -2.232072347 4.425365059 -1.181551745 -1.947966145 -0.277029596 80 TSPAN8 -1.889160765 -1.739590705 5.986779156 -2.397233332 -1.9296585 -4.08731649 -2.677540765 81 UPK3B -0.660628051 -0.514196839 -0.477166533 -0.755620892 -0.069584588 -1.061067781 -0.712380093 82 VTN 2.923525274 -0.52452731 14.37513361 -0.702306293 -0.029929938 1.884788007 -0.627880077 83 ZNF578 1.22614863 0.540308545 -1.87596215 -0.083197077 0.429479376 -0.209295458 2.232739055 84 ZNF695 -0.449132017 -2.051634999 -3.038221841 0.76346101 0.74872153 -0.970490477 -1.99162398

[0053] In one embodiment, a subset of one or more of the 84 genes of Table 1 can be used to classify or determine the COCA subtype of a tumor sample. In one embodiment, all 84 genes of Table 1 can be used to classify or determine the COCA subtype of a tumor sample. In some embodiments, the up-regulation of a classifier biomarker (e.g. expression is increased) can refer to an expression value that is positive (i.e., higher than zero) relative to a reference or control as provided herein. In some embodiments, the down-regulation of a classifier biomarker (e.g. expression is decreased) can refer to an expression value that is negative (i.e., lower than zero) relative to a reference or control as provided herein. In some embodiments, a classifier biomarker may have no specific effects on a certain COCA subtype when the expression level equals to zero.

[0054] In some embodiments, determining integrated, pan-cancer COCA subtypes can further include measuring the expression of at least one biomarker from an additional set of biomarker classifiers. In one embodiment, an additional set of biomarker classifiers can include measuring gene signatures related to cell proliferation. The gene signatures related to cell proliferation for use in the methods provided herein can include the 11 gene signature comprising BIRC5, CCNB1, CDCl20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS, and UBE2C found in Martin M. et al., Breast Cancer Res Treat, 138: 457-466 (2013), the 18 gene signature found in US 20160115551 and/or the 26 gene signature found in 62/789,668 filed Jan. 8, 2019, each of which is herein incorporated by reference. In one embodiment, an additional set of biomarker classifiers can include a 5 gene signature comprising tumor driver genes such as TP53 and RB1, and receptor tyrosine kinases including FGFR2, FGFR3, and ERBB2. In one embodiment, the 5 gene signature is related to the signature of tumor driver genes. In one embodiment, the biomarker classifiers can also include immune cell signatures that are known in the art (Bindea G. et al., Immunity, 39(4): 782-95 (2013); Faruki H. et al., JTO, 12(6): 943-953 (2017); Charoentong P. et al., Cell reports, 18, 248-262 (2017); Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T. H. O., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A. and Ziv, E., 2018, The immune landscape of cancer. Immunity, 48(4), pp. 812-830; and/or WO2017/201165, and WO2017/201164), each of which is herein incorporated by reference). In one embodiment, an additional set of biomarker classifiers can include assessing tumor purity ABSOLUTE derived from the TCGA supplementary data. In one embodiment, the additional set of biomarker can be gene signatures known in the art for specific types of cancer. In one embodiment, the cancer is lung cancer and the gene signature is selected from the gene signatures found in WO2017/201165, WO2017/201164, US20170114416 or U.S. Pat. No. 8,822,153, each of which is herein incorporated by reference in their entirety. In one embodiment, the cancer is head and neck squamous cell carcinoma (HNSCC) and the gene signature is selected from the gene signatures found in PCT/US18/45522 or PCT/US18/48862, each of which is herein incorporated by reference in their entirety. In one embodiment, the cancer is breast cancer and the gene signature is the PAM50 sub-typer found in Parker J S et al., (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160-1167, which is herein incorporated by reference in its entirety. In one embodiment, the cancer is bladder cancer and the gene signature can include the bladder cancer biomarker signature described in Gene Expression Omnibus (GEO) dataset: GSE87304, Seiler R. et al., Eur Urol, 72(4):544-554 (2017); Gene Expression Omnibus (GEO) dataset: GSE32894, Sjodahl G. et al., Clin Cancer Res, 18(12):3377-86 (2012), each of which is herein incorporated by reference). In one embodiment, the cancer is bladder cancer (e.g., MIBC) and the gene signature can include the bladder cancer biomarker signatures described in 62/629,975 filed Feb. 13, 2018, which is herein incorporated by reference. In one embodiment, the cancer is bladder cancer (e.g., MIBC) and the gene signature can include the bladder cancer biomarker signature described in The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature volume 507, pages 315-322 (2014), or Robertson, A G, et al., Cell, 171(3): 540-556 (2017), each of which is herein incorporated by reference.

[0055] In some embodiments, determining integrated, pan-cancer COCA subtypes can further include assessing tumor mutation burden (TMB) and/or TMB rate. In one embodiment, the TMB value and/or rate can be calculated from RNA (e.g., via transcriptome profiling or RNA sequencing)) as provided in U.S. 62/771,702 filed Nov. 27, 2018 and U.S. 62/743,257 filed Oct. 9, 2018, which is herein incorporated by reference herein.

[0056] As provided herein, the expression levels of the at least one of the classifier biomarkers (such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein) determined, measured or detected from the sample obtained from the subject can then be compared to reference expression levels of the at least one of the classifier biomarkers (such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein) from at least one sample training set. The at least one sample training set can comprise, (i) expression levels of the at least one biomarker from a sample that overexpresses the at least one biomarker or (ii) expression levels from a reference sample for a specific COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) and classifying the sample obtained from the subject sample as a specific COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) based on the results of the comparing step. In one embodiment, the comparing step can comprise applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample obtained from the subject and the expression data from the at least one training set(s); and classifying the sample obtained from the subject as a specific COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) based on the results of the statistical algorithm. The statistical algorithm can be any statistical algorithm found in the art and/or provided herein.

[0057] In one embodiment, the statistical algorithm for the comparing step can be an algorithm that comprises determining a correlation between the expression data obtained from the tumor sample obtained from the subject (i.e., test sample) and centroids constructed from the expression levels or profiles measured or detected for the at least one classifier biomarkers (such as the classifier biomarkers of Table 1 or subsets thereof or any additional set of biomarker classifiers or subsets thereof as disclosed herein) from the at least one training set. The COCA subtype for the tumor sample (i.e., test sample) can then be assigned by finding the centroid to which it is nearest from the centroids constructed from the expression data from the at least one training set, using any distance measure e.g. Euclidean distance or correlation. The centroids can be constructed using any method known in the art for generating centroids such as, for example, those found in Mullins et al. (2007) Clin Chem. 53(7):1273-9 or Dabney (2005) Bioinformatics 21(22):4148-4154 The COCA subtype can then be assigned to the tumor sample obtained from subject based on the use of a classification to the nearest centroid (CLaNC) algorithm as applied to the expression data generated or measured from the tumor sample and the centroid(s) constructed for the at least one training sets. The CLaNC algorithm for use in the methods, compositions and kits provided herein can be the CLaNC algorithm implemented by the CLaNC software found in Dabney A R. ClaNC: Point-and-click software for classifying microarrays to nearest centroids. Bioinformatics. 2006; 22: 122-123 or equivalents or derivatives thereof.

Sample Types/Methods of Detection

[0058] The methods and compositions provided herein allow for the differentiation or diagnosis of a sample obtained from a subject as being a specific COCA subtype. The COCA subtype can be one of 21 integrated, pan-cancer COCA subtypes of cancer selected from C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA). The differentiation, detection or diagnosis of the sample obtained from the subject as being a COCA subtype as provided herein can be accomplished by measuring or detecting the presence and/or level of one or more classifier biomarkers from a publically available pan-cancer dataset and/or a pan-cancer dataset provided herein (e.g., Table 1). The measuring can be at the nucleic acid or protein level.

[0059] A sample for use in any of the methods and compositions provided herein can be a tumor sample obtained from a subject or patient suffering from or suspected of suffering from a type of cancer. The type of cancer can be any type of cancer provided herein and/or known in the art. The tumor sample used for the detection or differentiation methods described herein can be a sample previously determined or diagnosed as a type of cancer sample using traditional tissue-of-origin methods. The previous diagnosis can be based on a histological analysis. The histological analysis can be performed by one or more pathologists.

[0060] The sample (e.g., tumor sample) can be any sample (e.g., tumor) isolated from the subject or patient. In one embodiment, the subject or patient is a human subject or patient. For example, in one embodiment, the analysis is performed on biopsies that are embedded in paraffin wax. In one embodiment, the sample can be a fresh frozen tissue sample. In another embodiment, the sample can be a bodily fluid obtained from the patient. The bodily fluid can be blood or fractions thereof (i.e., serum, plasma), urine, saliva, sputum or cerebrospinal fluid (CSF). The sample can contain cellular as well as extracellular sources of nucleic acid or protein for use in the methods provided herein. The extracellular sources can be cell-free DNA and/or exosomes. In one embodiment, the sample can be a cell pellet or a wash. This aspect of the methods provided herein provides a means to improve current diagnostics by accurately identifying the major histological types, even from small biopsies. The methods provided herein, including the RT-PCR methods, are sensitive, precise and have multi-analyte capability for use with paraffin-embedded samples. See, for example, Cronin et al. (2004) Am. J Pathol. 164(1):35-42, herein incorporated by reference.

[0061] Formalin fixation and tissue embedding in paraffin wax is a universal approach for tissue processing prior to light microscopic evaluation. A major advantage afforded by formalin-fixed paraffin-embedded (FFPE) specimens is the preservation of cellular and architectural morphologic detail in tissue sections. (Fox et al. (1985) J Histochem Cytochem 33:845-853). The standard buffered formalin fixative in which biopsy specimens are processed is typically an aqueous solution containing 37% formaldehyde and 10-15% methyl alcohol. Formaldehyde is a highly reactive dipolar compound that results in the formation of protein-nucleic acid and protein-protein crosslinks in vitro (Clark et al. (1986) J Histochem Cytochem 34:1509-1512; McGhee and von Hippel (1975) Biochemistry 14:1281-1296, each incorporated by reference herein).

[0062] In one embodiment, the sample used herein is obtained from an individual, and comprises formalin-fixed paraffin-embedded (FFPE) tissue. However, other tissue and sample types are amenable for use herein. In one embodiment, the other tissue and sample types can be fresh frozen tissue, wash fluids, cell pellets, or the like. In one embodiment, the sample can be a bodily fluid obtained from the individual. The bodily fluid can be blood or fractions thereof (e.g., serum, plasma), urine, sputum, saliva or cerebrospinal fluid (CSF). A biomarker nucleic acid as provided herein can be extracted from a cell, can be cell free or extracted from an extracellular vesicular entity such as an exosome.

[0063] Methods are known in the art for the isolation of nucleic acid (e.g., RNA) from FFPE tissue. In one embodiment, total RNA can be isolated from FFPE tissues as described by Bibikova et al. (2004) American Journal of Pathology 165:1799-1807, herein incorporated by reference. Likewise, the High Pure RNA Paraffin Kit (Roche) can be used. Paraffin is removed by xylene extraction followed by ethanol wash. RNA can be isolated from sectioned tissue blocks using the MasterPure Purification kit (Epicenter, Madison, Wis.); a DNase I treatment step is included. RNA can be extracted from frozen samples using Trizol reagent according to the supplier's instructions (Invitrogen Life Technologies, Carlsbad, Calif.). Samples with measurable residual genomic DNA can be resubjected to DNasel treatment and assayed for DNA contamination. All purification, DNase treatment, and other steps can be performed according to the manufacturer's protocol. After total RNA isolation, samples can be stored at -80.degree. C. until use.

[0064] General methods for mRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al., ed., Current Protocols in Molecular Biology, John Wiley & Sons, New York 1987-1999. Methods for RNA extraction from paraffin embedded tissues are disclosed, for example, in Rupp and Locker (Lab Invest. 56:A67, 1987) and De Andres et al. (Biotechniques 18:42-44, 1995). In particular, RNA isolation can be performed using a purification kit, a buffer set and protease from commercial manufacturers, such as Qiagen (Valencia, Calif.), according to the manufacturer's instructions. For example, total RNA from cells in culture can be isolated using Qiagen RNeasy mini-columns. Other commercially available RNA isolation kits include MasterPure.TM.. Complete DNA and RNA Purification Kit (Epicentre, Madison, Wis.) and Paraffin Block RNA Isolation Kit (Ambion, Austin, Tex.). Total RNA from tissue samples can be isolated, for example, using RNA Stat-60 (Tel-Test, Friendswood, Tex.). RNA prepared from a tumor can be isolated, for example, by cesium chloride density gradient centrifugation. Additionally, large numbers of tissue samples can readily be processed using techniques well known to those of skill in the art, such as, for example, the single-step RNA isolation process of Chomczynski (U.S. Pat. No. 4,843,155, incorporated by reference in its entirety for all purposes).

[0065] In one embodiment, a sample comprises cells harvested from a tumor sample. Cells can be harvested from a biological sample using standard techniques known in the art. For example, in one embodiment, cells are harvested by centrifuging a cell sample and resuspending the pelleted cells. The cells can be resuspended in a buffered solution such as phosphate-buffered saline (PBS). After centrifuging the cell suspension to obtain a cell pellet, the cells can be lysed to extract nucleic acid, e.g, messenger RNA. All samples obtained from a subject, including those subjected to any sort of further processing, are considered to be obtained from the subject.

[0066] The sample, in one embodiment, is further processed before the detection of the biomarker levels of the combination of biomarkers set forth herein. For example, mRNA in a cell or tissue sample can be separated from other components of the sample. The sample can be concentrated and/or purified to isolate mRNA in its non-natural state, as the mRNA is not in its natural environment. For example, studies have indicated that the higher order structure of mRNA in vivo differs from the in vitro structure of the same sequence (see, e.g., Rouskin et al. (2014). Nature 505, pp. 701-705, incorporated herein in its entirety for all purposes).

[0067] mRNA from the sample in one embodiment, is hybridized to a synthetic DNA probe, which in some embodiments, includes a detection moiety (e.g., detectable label, capture sequence, barcode reporting sequence). Accordingly, in these embodiments, a non-natural mRNA-cDNA complex is ultimately made and used for detection of the biomarker. In another embodiment, mRNA from the sample is directly labeled with a detectable label, e.g., a fluorophore. In a further embodiment, the non-natural labeled-mRNA molecule is hybridized to a cDNA probe and the complex is detected.

[0068] In one embodiment, once the mRNA is obtained from a sample, it is converted to complementary DNA (cDNA) prior to the hybridization reaction or is used in a hybridization reaction together with one or more cDNA probes. cDNA does not exist in vivo and therefore is a non-natural molecule. Furthermore, cDNA-mRNA hybrids are synthetic and do not exist in vivo. Besides cDNA not existing in vivo, cDNA is necessarily different than mRNA, as it includes deoxyribonucleic acid and not ribonucleic acid. The cDNA is then amplified, for example, by the polymerase chain reaction (PCR) or other amplification method known to those of ordinary skill in the art. For example, other amplification methods that may be employed include the ligase chain reaction (LCR) (Wu and Wallace, Genomics, 4:560 (1989), Landegren et al., Science, 241:1077 (1988), incorporated by reference in its entirety for all purposes, transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA, 86:1173 (1989), incorporated by reference in its entirety for all purposes), self-sustained sequence replication (Guatelli et al., Proc. Nat. Acad. Sci. USA, 87:1874 (1990), incorporated by reference in its entirety for all purposes), incorporated by reference in its entirety for all purposes, and nucleic acid based sequence amplification (NASBA). Guidelines for selecting primers for PCR amplification are known to those of ordinary skill in the art. See, e.g., McPherson et al., PCR Basics: From Background to Bench, Springer-Verlag, 2000, incorporated by reference in its entirety for all purposes. The product of this amplification reaction, i.e., amplified cDNA is also necessarily a non-natural product. First, as mentioned above, cDNA is a non-natural molecule. Second, in the case of PCR, the amplification process serves to create hundreds of millions of cDNA copies for every individual cDNA molecule of starting material. The numbers of copies generated are far removed from the number of copies of mRNA that are present in vivo.

[0069] In one embodiment, cDNA is amplified with primers that introduce an additional DNA sequence (e.g., adapter, reporter, capture sequence or moiety, barcode) onto the fragments (e.g., with the use of adapter-specific primers), or mRNA or cDNA biomarker sequences are hybridized directly to a cDNA probe comprising the additional sequence (e.g., adapter, reporter, capture sequence or moiety, barcode). Amplification and/or hybridization of mRNA to a cDNA probe therefore serves to create non-natural double stranded molecules from the non-natural single stranded cDNA, or the mRNA, by introducing additional sequences and forming non-natural hybrids. Further, as known to those of ordinary skill in the art, amplification procedures have error rates associated with them. Therefore, amplification introduces further modifications into the cDNA molecules. In one embodiment, during amplification with the adapter-specific primers, a detectable label, e.g., a fluorophore, is added to single strand cDNA molecules. Amplification therefore also serves to create DNA complexes that do not occur in nature, at least because (i) cDNA does not exist in vivo, (i) adapter sequences are added to the ends of cDNA molecules to make DNA sequences that do not exist in vivo, (ii) the error rate associated with amplification further creates DNA sequences that do not exist in vivo, (iii) the disparate structure of the cDNA molecules as compared to what exists in nature, and (iv) the chemical addition of a detectable label to the cDNA molecules.

[0070] In some embodiments, the expression of a biomarker of interest is detected at the nucleic acid level via detection of non-natural cDNA molecules.

[0071] The biomarkers described herein can include RNA comprising the entire or partial sequence of any of the nucleic acid sequences of interest, or their non-natural cDNA product, obtained synthetically in vitro in a reverse transcription reaction. The term "fragment" is intended to refer to a portion of the polynucleotide that generally comprise at least 10, 15, 20, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 800, 900, 1,000, 1,200, or 1,500 contiguous nucleotides, or up to the number of nucleotides present in a full-length biomarker polynucleotide disclosed herein. A fragment of a biomarker polynucleotide will generally encode at least 15, 25, 30, 50, 100, 150, 200, or 250 contiguous amino acids, or up to the total number of amino acids present in a full-length biomarker protein as provided herein.

[0072] Isolated mRNA can be used in hybridization or amplification assays that include, but are not limited to, Southern or Northern analyses, PCR analyses and probe arrays, NanoString Assays. One method for the detection of mRNA levels involves contacting the isolated mRNA or synthesized cDNA with a nucleic acid molecule (probe) that can hybridize to the mRNA encoded by the gene being detected. The nucleic acid probe can be, for example, a cDNA, or a portion thereof, such as an oligonucleotide of at least 7, 15, 30, 50, 100, 250, or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to the non-natural cDNA or mRNA biomarker provided herein.

[0073] In one embodiment, the measuring or detecting step in any method provided herein is at the nucleic acid level by performing RNA-seq, a reverse transcriptase polymerase chain reaction (RT-PCR) or a hybridization assay with oligonucleotides that are substantially complementary to portions of cDNA molecules of the at least one classifier biomarker (such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein) under conditions suitable for RNA-seq, RT-PCR or hybridization and obtaining expression levels of the at least one classifier biomarkers based on the detecting step.

[0074] In some embodiments, the method for COCA subtyping includes not only detecting expression levels of a classifier biomarker set in a sample obtained from a subject, but can further comprise detecting expression levels of said classifier biomarker set in one or more control or reference samples. The one or more control or reference samples can be selected from a normal or cancer-free sample, a cancer sample of a specific COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) or any combination thereof. In some embodiments, the detecting includes all of the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein at the nucleic acid level or protein level. In some embodiments, the detecting includes all of the classifier biomarkers of Table 1 at the nucleic acid level or protein level. In another embodiment, a single or a subset or a plurality of the classifier biomarkers of Table 1 are detected, for example, from about 1 to about 4, from about 4 to about 8, from about 8 to about 12, from about 12 to about 16, from about 16 to about 20, from about 20 to about 24, from about 24 to about 28, from about 28 to about 32, from about 32 to about 36, from about 36 to about 40, from about 40 to about 44, from about 44 to about 48, from about 48 to about 52, from about 52 to about 56, from about 56 to about 60, from about 60 to about 64, from about 64 to about 68, from about 68 to about 72, from about 72 to about 76, from about 76 to about 80 of the biomarkers in Table 1 are detected in a method to determine the COCA subtype. In another embodiment, each of the biomarkers from Table 1 is detected in a method to determine the COCA subtype. In another embodiment, any of 84 of the biomarkers from Table 1 are selected as the gene signatures for a specific COCA subtype. The detecting can be performed by any suitable technique including, but not limited to, RNA-seq, a reverse transcriptase polymerase chain reaction (RT-PCR), a microarray hybridization assay, or another hybridization assay, e.g., a NanoString assay for example, with primers and/or probes specific to the classifier biomarkers, and/or the like. In some cases, the primers useful for the amplification methods (e.g., RT-PCR or qRT-PCR) are any forward and reverse primers suitable for binding to a classifier biomarker provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein.

[0075] As explained above, in one embodiment, once the mRNA is obtained from a sample (e.g., form a subject suffering from or suspected of suffering from cancer or a control subject), it is converted to complementary DNA (cDNA) in a hybridization reaction. Conversion of the mRNA to cDNA can be performed with oligonucleotides or primers comprising sequence that is complementary to a portion of a specific mRNA. Conversion of the mRNA to cDNA can be performed with oligonucleotides or primers comprising random sequence. Conversion of the mRNA to cDNA can be performed with oligonucleotides or primers comprising sequence that is complementary to the poly(A) tail of an mRNA. cDNA does not exist in vivo and therefore is a non-natural molecule. In a further embodiment, the cDNA is then amplified, for example, by the polymerase chain reaction (PCR) or other amplification method known to those of ordinary skill in the art. PCR can be performed with the forward and/or reverse primers comprising sequence complementary to at least a portion of a classifier biomarker provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein. The product of this amplification reaction, i.e., amplified cDNA is necessarily a non-natural product. As mentioned above, cDNA is a non-natural molecule. Second, in the case of PCR, the amplification process serves to create hundreds of millions of cDNA copies for every individual cDNA molecule of starting material. The number of copies generated is far removed from the number of copies of mRNA that are present in vivo.

[0076] In one embodiment, cDNA is amplified with primers that introduce an additional DNA sequence (adapter sequence) onto the fragments (with the use of adapter-specific primers). The adaptor sequence can be a tail, wherein the tail sequence is not complementary to the cDNA. For example, the forward and/or reverse primers comprising sequence complementary to at least a portion of a classifier biomarker provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers as disclosed herein can comprise tail sequence. Amplification therefore serves to create non-natural double stranded molecules from the non-natural single stranded cDNA, by introducing barcode, adapter and/or reporter sequences onto the already non-natural cDNA. In one embodiment, during amplification with the adapter-specific primers, a detectable label, e.g., a fluorophore, is added to single strand cDNA molecules. Amplification therefore also serves to create DNA complexes that do not occur in nature, at least because (i) cDNA does not exist in vivo, (ii) adapter sequences are added to the ends of cDNA molecules to make DNA sequences that do not exist in vivo, (iii) the error rate associated with amplification further creates DNA sequences that do not exist in vivo, (iv) the disparate structure of the cDNA molecules as compared to what exists in nature, and (v) the chemical addition of a detectable label to the cDNA molecules.

[0077] In one embodiment, the synthesized cDNA (for example, amplified cDNA) is immobilized on a solid surface via hybridization with a probe, e.g., via a microarray. In another embodiment, cDNA products are detected via real-time polymerase chain reaction (PCR) via the introduction of fluorescent probes that hybridize with the cDNA products. For example, in one embodiment, biomarker detection is assessed by quantitative fluorogenic RT-PCR (e.g., with TaqMan.RTM. probes). For PCR analysis, well known methods are available in the art for the determination of primer sequences for use in the analysis.

[0078] In one embodiment, the measuring or detecting step in any method provided herein is performed via a hybridization assay that comprises probing the levels of at least one of the classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein, at the nucleic acid level, in a tumor sample obtained from the patient. The probing step, in one embodiment, comprises mixing the sample with one or more oligonucleotides that are substantially complementary to portions of cDNA molecules of the at least one classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein under conditions suitable for hybridization of the one or more oligonucleotides to their complements or substantial complements; detecting whether hybridization occurs between the one or more oligonucleotides to their complements or substantial complements; and obtaining hybridization values of the at least one classifier biomarkers based on the detecting step. The hybridization values of the at least one classifier biomarkers are then compared to reference hybridization value(s) from at least one sample training set. The tumor sample is classified, for example, as a COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) based on the results of the comparing step. In one embodiment, the hybridization values of the tumor sample can be compared to centroid(s) constructed from the hybridization values of the training set.

[0079] In one embodiment, the hybridization reaction utilized in methods provided herein employs a capture probe and/or a reporter probe. For example, the hybridization probe is a probe derivatized to a solid surface such as a bead, glass or silicon substrate. In another embodiment, the capture probe is present in solution and mixed with the patient's sample, followed by attachment of the hybridization product to a surface, e.g., via a biotin-avidin interaction (e.g., where biotin is a part of the capture probe and avidin is on the surface). The hybridization assay, in one embodiment, employs both a capture probe and a reporter probe. The reporter probe can hybridize to either the capture probe or the biomarker nucleic acid. Reporter probes e.g., are then counted and detected to determine the level of biomarker(s) in the sample. The capture and/or reporter probe, in one embodiment contain a detectable label, and/or a group that allows functionalization to a surface.

[0080] For example, the nCounter gene analysis system (see, e.g., Geiss et al. (2008) Nat. Biotechnol. 26, pp. 317-325, incorporated by reference in its entirety for all purposes, is amenable for use with the methods provided herein.

[0081] Hybridization assays described in U.S. Pat. Nos. 7,473,767 and 8,492,094, the disclosures of which are incorporated by reference in their entireties for all purposes, are amenable for use with the methods provided herein, i.e., to detect the biomarkers and biomarker combinations described herein.

[0082] Biomarker levels may be monitored using a membrane blot (such as used in hybridization analysis such as Northern, Southern, dot, and the like), or microwells, sample tubes, gels, beads, or fibers (or any solid support comprising bound nucleic acids). See, for example, U.S. Pat. Nos. 5,770,722, 5,874,219, 5,744,305, 5,677,195 and 5,445,934, each incorporated by reference in their entireties.

[0083] In one embodiment, microarrays are used to detect biomarker levels. Microarrays are particularly well suited for this purpose because of the reproducibility between different experiments. DNA microarrays provide one method for the simultaneous measurement of the expression levels of large numbers of genes. Each array consists of a reproducible pattern of capture probes attached to a solid support. Labeled RNA or DNA is hybridized to complementary probes on the array and then detected by laser scanning hybridization intensities for each probe on the array are determined and converted to a quantitative value representing relative gene expression levels. See, for example, U.S. Pat. Nos. 6,040,138, 5,800,992 and 6,020,135, 6,033,860, and 6,344,316, each incorporated by reference in their entireties. High-density oligonucleotide arrays are particularly useful for determining the gene expression profile for a large number of RNAs in a sample.

[0084] Techniques for the synthesis of these arrays using mechanical synthesis methods are described in, for example, U.S. Pat. No. 5,384,261. Although a planar array surface is generally used, the array can be fabricated on a surface of virtually any shape or even a multiplicity of surfaces. Arrays can be nucleic acids (or peptides) on beads, gels, polymeric surfaces, fibers (such as fiber optics), glass, or any other appropriate substrate. See, for example, U.S. Pat. Nos. 5,770,358, 5,789,162, 5,708,153, 6,040,193 and 5,800,992, each incorporated by reference in their entireties. Arrays can be packaged in such a manner as to allow for diagnostics or other manipulation of an all-inclusive device. See, for example, U.S. Pat. Nos. 5,856,174 and 5,922,591, each incorporated by reference in their entireties.

[0085] Serial analysis of gene expression (SAGE) in one embodiment is employed in the methods described herein. SAGE is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. See, Velculescu et al. Science 270:484-87, 1995; Cell 88:243-51, 1997, incorporated by reference in its entirety.

[0086] In another embodiment, the measuring or detecting step in any method provided herein is performed via an amplification assay. The amplification assay can be coupled with a sequencing method. In one embodiment, a method of biomarker level analysis at the nucleic acid level as provided herein utilizes an amplification reaction coupled with a sequencing method such as, for example, RNAseq, next generation sequencing, and massively parallel signature sequencing (MPSS) as described by Brenner et al. (Nat. Biotech. 18:630-34, 2000, incorporated by reference in its entirety). MPSS is a sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 .mu.m diameter microbeads. First, a microbead library of DNA templates is constructed by in vitro cloning. This is followed by the assembly of a planar array of the template-containing microbeads in a flow cell at a high density (typically greater than 3.0.times.10.sup.6 microbeads/cm.sup.2). The free ends of the cloned templates on each microbead are analyzed simultaneously, using a fluorescence-based signature sequencing method that does not require DNA fragment separation. This method has been shown to simultaneously and accurately provide, in a single operation, hundreds of thousands of gene signature sequences from a yeast cDNA library.

[0087] The expression level values of the at least one classifier biomarkers obtained from the amplification and/or sequencing assay are then compared to reference expression level value(s) from at least one sample training set. The tumor sample is classified, for example, as a COCA subtype (e.g., C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)) based on the results of the comparing step. In one embodiment, the expression level values of the tumor sample can be compared to centroid(s) constructed from the expression level values obtained from the training set.

[0088] Another method of biomarker level analysis at the nucleic acid level for use in any method provided herein is the use of an amplification method such as, for example, RT-PCR or quantitative RT-PCR (qRT-PCR). Methods for determining the level of biomarker mRNA in a sample may involve the process of nucleic acid amplification, e.g., by RT-PCR (the experimental embodiment set forth in Mullis, 1987, U.S. Pat. No. 4,683,202), ligase chain reaction (Barany (1991) Proc. Natl. Acad. Sci. USA 88:189-193), self-sustained sequence replication (Guatelli et al. (1990) Proc. Natl. Acad. Sci. USA 87:1874-1878), transcriptional amplification system (Kwoh et al. (1989) Proc. Natl. Acad. Sci. USA 86:1173-1177), Q-Beta Replicase (Lizardi et al. (1988) Bio/Technology 6:1197), rolling circle replication (Lizardi et al., U.S. Pat. No. 5,854,033) or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. Numerous different PCR or qRT-PCR protocols are known in the art and can be directly applied or adapted for use using the presently described compositions for the detection and/or quantification of expression of discriminative genes in a sample. See, for example, Fan et al. (2004) Genome Res. 14:878-885, herein incorporated by reference. Generally, in PCR, a target polynucleotide sequence is amplified by reaction with at least one oligonucleotide primer or pair of oligonucleotide primers. The primer(s) hybridize to a complementary region of the target nucleic acid and a DNA polymerase extends the primer(s) to amplify the target sequence. Under conditions sufficient to provide polymerase-based nucleic acid amplification products, a nucleic acid fragment of one size dominates the reaction products (the target polynucleotide sequence which is the amplification product). The amplification cycle is repeated to increase the concentration of the single target polynucleotide sequence. The reaction can be performed in any thermocycler commonly used for PCR.

[0089] Quantitative RT-PCR (qRT-PCR) (also referred as real-time RT-PCR) is preferred under some circumstances because it provides not only a quantitative measurement, but also reduced time and contamination. As used herein, "quantitative PCR" (or "real time qRT-PCR") refers to the direct monitoring of the progress of a PCR amplification as it is occurring without the need for repeated sampling of the reaction products. In quantitative PCR, the reaction products may be monitored via a signaling mechanism (e.g., fluorescence) as they are generated and are tracked after the signal rises above a background level but before the reaction reaches a plateau. The number of cycles required to achieve a detectable or "threshold" level of fluorescence varies directly with the concentration of amplifiable targets at the beginning of the PCR process, enabling a measure of signal intensity to provide a measure of the amount of target nucleic acid in a sample in real time. A DNA binding dye (e.g., SYBR green) or a labeled probe can be used to detect the extension product generated by PCR amplification. Any probe format utilizing a labeled probe comprising the sequences provided herein may be used.

[0090] Immunohistochemistry methods are also suitable for detecting the levels of the biomarkers provided herein. Samples can be frozen for later preparation or immediately placed in a fixative solution. Tissue samples can be fixed by treatment with a reagent, such as formalin, glutaraldehyde, methanol, or the like and embedded in paraffin. Methods for preparing slides for immunohistochemical analysis from formalin-fixed, paraffin-embedded tissue samples are well known in the art.

[0091] In one embodiment, COCA subtypes can be evaluated using levels of protein expression of one or more of the classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein. The level of protein expression can be measured using an immunological detection method. Immunological detection methods which can be used herein include, but are not limited to, competitive and non-competitive assay systems using techniques such as Western blots, radioimmunoassays, ELISA (enzyme linked immunosorbent assay), "sandwich" immunoassays, immunoprecipitation assays, precipitin reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, protein A immunoassays, and the like. Such assays are routine and well known in the art (see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. I, John Wiley & Sons, Inc., New York, which is incorporated by reference herein in its entirety).

[0092] In one embodiment, antibodies specific for biomarker proteins are utilized to detect the expression of a biomarker protein in a sample (e.g., tumor sample). The method comprises obtaining a sample from a patient or a subject, contacting the sample with at least one antibody directed to a biomarker that is selectively expressed in cancer cells, and detecting antibody binding to determine if the biomarker is expressed in the patient sample. Also provided herein is an immunocytochemistry technique for diagnosing COCA subtypes. One of skill in the art will recognize that the immunocytochemistry method described herein below may be performed manually or in an automated fashion.

[0093] In some embodiments, the expression level of a classifier biomarker(s) (e.g., from Table 1) as determined using any methods or compositions provided herein or its expression product, is determined by normalization to the level of reference nucleic acid(s) (e.g., RNA transcripts) or their expression products (e.g., proteins), which can be all measured nucleic acids (e.g., transcripts (or their products)) in the sample or a particular reference set of nucleic acids (e.g., RNA transcripts (or their non-natural cDNA products)). Normalization is performed to correct for or normalize away both differences in the amount of nucleic acid (e.g., RNA or cDNA) assayed and variability in the quality of the nucleic acid (e.g., RNA or cDNA) used. Therefore, an assay typically measures and incorporates the expression of certain normalizing genes, including well known housekeeping genes, such as, for example, GAPDH and/or .beta.-Actin. Alternatively, normalization can be based on the mean or median signal of all of the assayed biomarkers or a large subset thereof (global normalization approach).

[0094] In one embodiment, the levels of the biomarkers provided herein, such as the classifier biomarkers of Table 1 (or subsets thereof, for example, 1 to 4, 4 to 8, 8 to 12, 12 to 16, 16 to 20, 20 to 24, 24 to 28, 28 to 32, 32 to 36, 36 to 40, 40 to 44, 44 to 48, 48 to 52, 52 to 56, 56 to 60, 60 to 64, 64 to 68, 68 to 72, 72 to 76, 76 to 80, 80 to 84 of the classifier biomarkers) are normalized against the expression levels of all RNA transcripts or their non-natural cDNA expression products, or protein products in the sample, or of a reference set of RNA transcripts or a reference set of their non-natural cDNA expression products, or a reference set of their protein products in the sample. In one embodiment, the levels of the biomarkers provided herein, such as any of the additional set of classifier biomarkers disclosed herein are normalized against the expression levels of all RNA transcripts or their non-natural cDNA expression products, or protein products in the sample, or of a reference set of RNA transcripts or a reference set of their non-natural cDNA expression products, or a reference set of their protein products in the sample.

Statistical Methods

[0095] As provided throughout, the methods set forth herein provide a method for determining the COCA subtype of a patient. Once the biomarker levels (e.g., Table 1 or any other gene signature provided herein) are determined, for example by measuring non-natural cDNA biomarker levels or non-natural mRNA-cDNA biomarker complexes, the biomarker levels are compared to reference values or a reference sample as provided herein, for example with the use of statistical methods or direct comparison of detected levels, to make a determination of the COCA subtype. Based on the comparison, the patient's tumor sample is classified, e.g., as a specific COCA subtype (e.g., C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA).

[0096] In one embodiment, expression level values of the at least one classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 are compared to reference expression level value(s) from at least one sample training set, wherein the at least one sample training set comprises expression level values from a reference sample(s). In a further embodiment, the at least one sample training set comprises expression level values of the at least one classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein from a specific COCA subtype (e.g., C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA) or a combination thereof.

[0097] In a separate embodiment, for methods provided herein employing a hybridization assay, hybridization values of the at least one classifier biomarkers provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein are compared to reference hybridization value(s) from at least one sample training set, wherein the at least one sample training set comprises hybridization values from a reference sample(s). In a further embodiment, the at least one sample training set comprises hybridization values of the at least one classifier biomarker provided herein, such as the classifier biomarkers of Table 1 or any additional set of biomarker classifiers disclosed herein from a specific COCA subtype (e.g., C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA) or a combination thereof. Methods for comparing detected levels of biomarkers to reference values and/or reference samples are provided herein. Based on this comparison, in one embodiment a correlation between the biomarker levels obtained from the subject's sample and the reference values is obtained. An assessment of the COCA subtype is then made.

[0098] Various statistical methods can be used to aid in the comparison of the biomarker levels obtained from the patient and reference biomarker levels, for example, from at least one sample training set.

[0099] In one embodiment, a supervised pattern recognition method is employed. Examples of supervised pattern recognition methods can include, but are not limited to, the nearest centroid methods (Dabney (2005) Bioinformatics 21(22):4148-4154 and Tibshirani et al. (2002) Proc. Natl. Acad. Sci. USA 99(10):6576-6572); soft independent modeling of class analysis (SIMCA) (see, for example, Wold, 1976); partial least squares analysis (PLS) (see, for example, Wold, 1966; Joreskog, 1982; Frank, 1984; Bro, R., 1997); linear discriminant analysis (LDA) (see, for example, Nillson, 1965); K-nearest neighbor analysis (KNN) (sec, for example, Brown et al., 1996); artificial neural networks (ANN) (see, for example, Wasserman, 1989; Anker et al., 1992; Hare, 1994); probabilistic neural networks (PNNs) (see, for example, Parzen, 1962; Bishop, 1995; Speckt, 1990; Broomhead et al., 1988; Patterson, 1996); rule induction (RI) (see, for example, Quinlan, 1986); and, Bayesian methods (see, for example, Bretthorst, 1990a, 1990b, 1988). In one embodiment, the classifier for identifying COCA subtypes based on gene expression data is used in a centroid based method as described in Mullins et al. (2007) Clin Chem. 53(7):1273-9, which is incorporated herein by reference in its entirety. In another embodiment, the classifier for identifying tumor subtypes based on gene expression data is used in a nearest centroid based method as described in Dabney (2005) Bioinformatics 21(22):4148-4154, which is incorporated herein by reference in its entirety. The nearest centroid based method can be performed using CLaNC software as described in Dabney A R. ClaNC: Point-and-click software for classifying microarrays to nearest centroids. Bioinformatics. 2006; 22: 122-123 or equivalents or derivatives thereof.

[0100] In other embodiments, an unsupervised training approach is employed, and therefore, no training set is used.

[0101] Referring to sample training sets for supervised learning approaches again, in some embodiments, a sample training set(s) can include expression data of a plurality or all of the classifier biomarkers (e.g., all the classifier biomarkers of Table 1) from a specific COCA subtype sample. The plurality of classifier biomarkers can comprise at least 4 classifier biomarkers, at least 8 classifier biomarkers, at least 12 classifier biomarkers, at least 16 classifier biomarkers at least 20 classifier biomarkers, at least 24 classifier biomarkers, at least 28 classifier biomarkers, at least 32 classifier biomarkers, at least 36 classifier biomarkers, at least 40 classifier biomarkers, at least 44 classifier biomarkers, at least 48 classifier biomarkers, at least 52 classifier biomarkers, at least 56 classifier biomarkers, at least 60 classifier biomarkers, at least 64 classifier biomarkers, at least 68 classifier biomarkers, at least 72 classifier biomarkers, at least 76 classifier biomarkers or at least 80 classifier biomarkers of Table 1. In some embodiments, the plurality of classifier biomarkers comprises all 84 biomarkers of Table 1. In some embodiments, the sample training set(s) are normalized to remove sample-to-sample variation.

[0102] In some embodiments, comparing can include applying a statistical algorithm, such as, for example, any suitable multivariate statistical analysis model, which can be parametric or non-parametric. In some embodiments, applying the statistical algorithm can include determining a correlation between the expression data obtained from the tumor sample obtained from the subject suffering from or suspected of suffering from cancer (i.e., the test subject) and the expression data from the COCA subtyping training set(s). In some embodiments, cross-validation is performed, such as (for example), leave-one-out cross-validation (LOOCV). In some embodiments, integrative correlation is performed. In some embodiments, a Spearman correlation is performed. In some embodiments, a centroid based method based on gene expression data is employed for the statistical algorithm. The centroids can be constructed using any method known in the art for generating centroids such as, for example, those found in Mullins et al. (2007) Clin Chem. 53(7):1273-9 or the nearest centroid method found in Dabney (2005) Bioinformatics 21(22):4148-4154, which is herein incorporated by reference in its entirety. In one embodiment, a correlation analysis is performed on the expression data obtained from the tumor sample and the centroid(s) constructed from the expression data from the COCA training set(s). The correlation analysis can be a Spearman correlation or a Pearson correlation. In one embodiment, a distance measure analysis (e.g., Euclidean distance) is performed on the expression data obtained from the tumor sample and the centroid(s) constructed on the expression data from the COCA training set(s).

[0103] Results of the gene expression analysis performed on a sample from a subject (test sample) may be compared to a biological sample(s) or data derived from a biological sample(s) (e.g., expression data or levels from at least one classifier biomarker provided herein, e.g., Table 1) that is known or suspected to be normal ("reference sample" or "normal sample", e.g., non-cancer sample). In some embodiments, a reference sample or reference gene expression data (e.g., expression data or levels from at least one classifier biomarker provided herein, e.g., Table 1) is obtained or derived from an individual known to have a particular COCA subtype of cancer, e.g., C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA. In one embodiment, the gene expression levels or profile measured for the at least one classifier biomarkers from Table 1 measured or detected in the test sample (i.e., tumor sample obtained from the subject) may be compared to centroids constructed from the gene expression performed on the reference or normal sample or training set and classification can be based on determining which is the nearest centroid based on distance measure such as, for example, a Euclidean distance or a correlation. The centroids can be constructed using any of the methods provided herein such as, for example, using the ClaNC software described in Dabney A R. ClaNC: Point-and-click software for classifying microarrays to nearest centroids. Bioinformatics. 2006; 22: 122-123 or equivalents or derivatives related thereto. Classification or determination of the subtype of the test sample can then be ascertained by determining the nearest centroid from the reference or normal sample to which the expression levels or profile from said test sample is nearest based on a distance measure or correlation. The distance measure can be a Euclidean distance.

[0104] The reference sample may be assayed at the same time, or at a different time from the sample obtained from the test subject (i.e., test sample). Alternatively, the biomarker level information from a reference sample may be stored in a database or other means for access at a later date.

[0105] The biomarker level results of an assay on the test sample may be compared to the results of the same assay on a reference sample. In some cases, the results of the assay on the reference sample are from a database, or a reference value(s). In some cases, the results of the assay on the reference sample are a known or generally accepted value or range of values by those skilled in the art. In some cases, the comparison is qualitative. In other cases, the comparison is quantitative. In some cases, qualitative or quantitative comparisons may involve but are not limited to one or more of the following: comparing expression levels of a test sample to gene centroids constructed from expression level data from a reference sample (e.g., constructed from expression level data for one or a plurality of genes from Table 1), fluorescence values, spot intensities, absorbance values, chemiluminescent signals, histograms, critical threshold values, statistical significance values, expression levels of the genes described herein, mRNA copy numbers.

[0106] In one embodiment, an odds ratio (OR) is calculated for each biomarker level panel measurement. Here, the OR is a measure of association between the measured biomarker values for the patient and an outcome, e.g., COCA subtype. For example, see, J. Can. Acad. Child Adolesc. Psychiatry 2010; 19(3): 227-229, which is incorporated by reference in its entirety for all purposes.

[0107] In one embodiment, a specified statistical confidence level may be determined in order to provide a confidence level regarding the COCA subtype. For example, it may be determined that a confidence level of greater than 90% may be a useful predictor of the COCA subtype. In other embodiments, more or less stringent confidence levels may be chosen. For example, a confidence level of about or at least about 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, 99.5%, or 99.9% may be chosen. The confidence level provided may in some cases be related to the quality of the sample, the quality of the data, the quality of the analysis, the specific methods used, and/or the number of gene expression values (i.e., the number of genes) analyzed. The specified confidence level for providing the likelihood of response may be chosen on the basis of the expected number of false positives or false negatives. Methods for choosing parameters for achieving a specified confidence level or for identifying markers with diagnostic power include but are not limited to Receiver Operating Characteristic (ROC) curve analysis, binomial ROC, principal component analysis, odds ratio analysis, partial least squares analysis, singular value decomposition, least absolute shrinkage and selection operator analysis, least angle regression, and the threshold gradient directed regularization method.

[0108] Determining the COCA subtype in some cases can be improved through the application of algorithms designed to normalize and or improve the reliability of the gene expression data. In some embodiments, the data analysis utilizes a computer or other device, machine or apparatus for application of the various algorithms described herein due to the large number of individual data points that are processed. A "machine learning algorithm" refers to a computational-based prediction methodology, also known to persons skilled in the art as a "classifier," employed for characterizing a gene expression profile or profiles, e.g., to determine the COCA subtype. The biomarker levels, determined by, e.g., microarray-based hybridization assays, sequencing assays, NanoString assays, etc., are in one embodiment subjected to the algorithm in order to classify the profile. Supervised learning generally involves "training" a classifier to recognize the distinctions among COCA subtypes such as, for example, C1 ACC/PCPG positive, C2 GBM/LGG positive, C3 OV positive, C4 Squamous-like positive, C6 LUAD-Enriched positive, C8 PAAD/some STAD positive, C9 UCS positive, C10 BRCA/Basal positive, C12 UCEC positive, C14 PRAD positive, C15 CESC (subset of cervical) positive, C16 BLCA positive, C17 TGCT positive, C19 COAD/READ positive, C20 SARC/MESO positive, C21 KIRK/KICH/KIRP positive, C22 Liver positive, C24 BRCA/Luminal positive, C25 THYM positive, C26 SKCM/UVM positive and C28 THCA positive, and then "testing" the accuracy of the classifier on an independent test set. Therefore, for new, unknown samples the classifier can be used to predict, for example, the class (e.g., C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA) in which the samples belong. The machine learning algorithm can be a CLaNC algorithm as provided herein.

[0109] In some embodiments, a robust multi-array average (RMA) method may be used to normalize raw data. The RMA method begins by computing background-corrected intensities for each matched cell on a number of microarrays. In one embodiment, the background corrected values are restricted to positive values as described by Irizarry et al. (2003). Biostatistics April 4 (2): 249-64, incorporated by reference in its entirety for all purposes. After background correction, the base-2 logarithm of each background corrected matched-cell intensity is then obtained. The background corrected, log-transformed, matched intensity on each microarray is then normalized using the quantile normalization method in which for each input array and each probe value, the array percentile probe value is replaced with the average of all array percentile points, this method is more completely described by Bolstad et al. Bioinformatics 2003, incorporated by reference in its entirety. Following quantile normalization, the normalized data may then be fit to a linear model to obtain an intensity measure for each probe on each microarray. Tukey's median polish algorithm (Tukey, J. W., Exploratory Data Analysis. 1977, incorporated by reference in its entirety for all purposes) may then be used to determine the log-scale intensity level for the normalized probe set data.

[0110] Various other software programs may be implemented. In certain methods, feature selection and model estimation may be performed by logistic regression with lasso penalty using glmnet (Friedman et al. (2010). Journal of statistical software 33(1): 1-22, incorporated by reference in its entirety). Raw reads may be aligned using TopHat (Trapnell et al. (2009). Bioinformatics 25(9): 1105-11, incorporated by reference in its entirety). In methods, top features (N ranging from 10 to 200) are used to train a linear support vector machine (SVM) (Suykens J A K, Vandewalle J. Least Squares Support Vector Machine Classifiers. Neural Processing Letters 1999; 9(3): 293-300, incorporated by reference in its entirety) using the e1071 library (Meyer D. Support vector machines: the interface to libsvm in package e1071. 2014, incorporated by reference in its entirety). Confidence intervals, in one embodiment, are computed using the pROC package (Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC bioinformatics 2011; 12: 77, incorporated by reference in its entirety).

[0111] In addition, data may be filtered to remove data that may be considered suspect. In one embodiment, data derived from microarray probes that have fewer than about 4, 5, 6, 7 or 8 guanosine+cytosine nucleotides may be considered to be unreliable due to their aberrant hybridization propensity or secondary structure issues. Similarly, data deriving from microarray probes that have more than about 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 guanosine+cytosine nucleotides may in one embodiment be considered unreliable due to their aberrant hybridization propensity or secondary structure issues.

[0112] In some embodiments, data from probe-sets may be excluded from analysis if they are not identified at a detectable level (above background).

[0113] In some embodiments, probe-sets that exhibit no, or low variance may be excluded from further analysis. Low-variance probe-sets are excluded from the analysis via a Chi-Square test. In one embodiment, a probe-set is considered to be low-variance if its transformed variance is to the left of the 99 percent confidence interval of the Chi-Squared distribution with (N-1) degrees of freedom. (N-1)*Probe-set Variance/(Gene Probe-set Variance). Chi-Sq(N-1) where N is the number of input CEL files, (N-1) is the degrees of freedom for the Chi-Squared distribution, and the "probe-set variance for the gene" is the average of probe-set variances across the gene. In some embodiments, probe-sets for a given mRNA or group of mRNAs may be excluded from further analysis if they contain less than a minimum number of probes that pass through the previously described filter steps for GC content, reliability, variance and the like. For example in some embodiments, probe-sets for a given gene or transcript cluster may be excluded from further analysis if they contain less than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or less than about 20 probes.

[0114] Methods of biomarker level data analysis in one embodiment, further include the use of a feature selection algorithm as provided herein. In some embodiments, feature selection is provided by use of the LIMMA software package (Smyth, G. K. (2005). Limma: linear models for microarray data. In: Bioinformatics and Computational Biology Solutions using R and Bioconductor, R. Gentleman, V. Carey, S. Dudoit, R. Irizarry, W. Huber (eds.), Springer, New York, pages 397-420, incorporated by reference in its entirety for all purposes).

[0115] Methods of biomarker level data analysis, in one embodiment, include the use of a pre-classifier algorithm. For example, an algorithm may use a specific molecular fingerprint to pre-classify the samples according to their composition and then apply a correction/normalization factor. This data/information may then be fed in to a final classification algorithm which would incorporate that information to aid in the final diagnosis.

[0116] Methods of biomarker level data analysis, in one embodiment, further include the use of a classifier algorithm as provided herein. In one embodiment, a diagonal linear discriminant analysis, k-nearest neighbor algorithm, support vector machine (SVM) algorithm, linear support vector machine, random forest algorithm, or a probabilistic model-based method or a combination thereof is provided for classification of microarray data. In some embodiments, identified markers that distinguish samples (e.g., of varying biomarker level profiles, and/or varying COCA subtypes of cancer are selected based on statistical significance of the difference in biomarker levels between classes of interest. In some cases, the statistical significance is adjusted by applying a Benjamin Hochberg or another correction for false discovery rate (FDR).

[0117] In some cases, the classifier algorithm may be supplemented with a meta-analysis approach such as that described by Fishel and Kaufman et al. 2007 Bioinformatics 23(13): 1599-606, incorporated by reference in its entirety for all purposes. In some cases, the classifier algorithm may be supplemented with a meta-analysis approach such as a repeatability analysis.

[0118] Methods for deriving and applying posterior probabilities to the analysis of biomarker level data are known in the art and have been described for example in Smyth, G. K. 2004 Stat. Appl. Genet. Mol. Biol. 3: Article 3, incorporated by reference in its entirety for all purposes. In some cases, the posterior probabilities may be used in the methods provided herein to rank the markers provided by the classifier algorithm.

[0119] A statistical evaluation of the results of the biomarker level profiling may provide a quantitative value or values indicative of one or more of the following: COCA subtype of cancer; the likelihood of the success of a particular therapeutic intervention, e.g., angiogenesis inhibitor therapy, chemotherapy, or immunotherapy. In one embodiment, the data is presented directly to the physician in its most useful form to guide patient care, or is used to define patient populations in clinical trials or a patient population for a given medication. The results of the molecular profiling can be statistically evaluated using a number of methods known to the art including, but not limited to: the students T test, the two sided T test, Pearson rank sum analysis, hidden Markov model analysis, analysis of q-q plots, principal component analysis, one way ANOVA, two way ANOVA, LIMMA and the like.

[0120] In some cases, accuracy may be determined by tracking the subject over time to determine the accuracy of the original diagnosis. In other cases, accuracy may be established in a deterministic manner or using statistical methods. For example, receiver operator characteristic (ROC) analysis may be used to determine the optimal assay parameters to achieve a specific level of accuracy, specificity, positive predictive value, negative predictive value, and/or false discovery rate.

[0121] In some cases, the results of the biomarker level profiling assays, are entered into a database for access by representatives or agents of a molecular profiling business, the individual, a medical provider, or insurance provider. In some cases, assay results include sample classification, identification, or diagnosis by a representative, agent or consultant of the business, such as a medical professional. In other cases, a computer or algorithmic analysis of the data is provided automatically. In some cases, the molecular profiling business may bill the individual, insurance provider, medical provider, researcher, or government entity for one or more of the following: molecular profiling assays performed, consulting services, data analysis, reporting of results, or database access.

[0122] In some embodiments, the results of the biomarker level profiling assays are presented as a report on a computer screen or as a paper record. In some embodiments, the report may include, but is not limited to, such information as one or more of the following: the levels of biomarkers (e.g., as reported by copy number or fluorescence intensity, etc.) as compared to the reference sample or reference value(s); the likelihood the subject will respond to a particular therapy, based on the biomarker level values and the COCA subtype and proposed therapies.

[0123] In one embodiment, the results of the gene expression profiling may be classified into one or more of the following: C1 ACC/PCPG positive, C2 GBM/LGG positive, C3 OV positive, C4 Squamous-like positive, C6 LUAD-Enriched positive, C8 PAAD/some STAD positive, C9 UCS positive, C10 BRCA/Basal positive, C12 UCEC positive, C14 PRAD positive, C15 CESC (subset of cervical) positive, C16 BLCA positive, C17 TGCT positive, C19 COAD/READ positive, C20 SARC/MESO positive, C21 KIRK/KICH/KIRP positive, C22 Liver positive, C24 BRCA/Luminal positive, C25 THYM positive, C26 SKCM/UVM positive or C28 THCA positive, C1 ACC/PCPG negative, C2 GBM/LGG negative, C3 OV negative, C4 Squamous-like negative, C6 LUAD-Enriched negative, C8 PAAD/some STAD negative, C9 UCS negative, C10 BRCA/Basal negative, C12 UCEC negative, C14 PRAD negative, C15 CESC (subset of cervical) negative, C16 BLCA negative, C17 TGCT negative, C19 COAD/READ negative, C20 SARC/MESO negative, C21 KIRK/KICH/KIRP negative, C22 Liver negative, C24 BRCA/Luminal negative, C25 THYM negative, C26 SKCM/UVM negative or C28 THCA negative or a combination thereof.

[0124] In some embodiments, results are classified using a trained algorithm. Trained algorithms provided herein include algorithms that have been developed using a reference set of known gene expression values and/or normal samples, for example, samples from individuals diagnosed with a particular molecular COCA subtype of cancer. In some cases, a reference set of known gene expression values are obtained from individuals who have been diagnosed with a particular COCA subtype of cancer. In some cases, a reference set of known gene expression values are obtained from individuals who have been diagnosed with a particular COCA subtype of cancer, and are also known to possess certain immune cell signature. In some cases, a reference set of known gene expression values are obtained from individuals who have been diagnosed with a particular COCA subtype of cancer, and are also known to have certain expression of tumor driver genes.

[0125] Algorithms suitable for categorization of samples include but are not limited to k-nearest neighbor algorithms, support vector machines, linear discriminant analysis, centroid algorithms (e.g., CLaNC), diagonal linear discriminant analysis, updown, naive Bayesian algorithms, neural network algorithms, hidden Markov model algorithms, genetic algorithms, or any combination thereof.

[0126] When a binary classifier is compared with actual true values (e.g., values from a biological sample), there are typically four possible outcomes. If the outcome from a prediction is p (where "p" is a positive classifier output, such as the presence of a deletion or duplication syndrome) and the actual value is also p, then it is called a true positive (TP); however if the actual value is n then it is said to be a false positive (FP). Conversely, a true negative has occurred when both the prediction outcome and the actual value are n (where "n" is a negative classifier output, such as no deletion or duplication syndrome), and false negative is when the prediction outcome is n while the actual value is p. In one embodiment, consider a test that seeks to determine whether a person is likely or unlikely to respond to angiogenesis inhibitor therapy. A false positive in this case occurs when the person tests positive, but actually does respond. A false negative, on the other hand, occurs when the person tests negative, suggesting they are unlikely to respond, when they actually are likely to respond. The same holds true for classifying a COCA subtype.

[0127] The positive predictive value (PPV), or precision rate, or post-test probability of disease, is the proportion of subjects with positive test results who are correctly diagnosed as likely or unlikely to respond, or diagnosed with the correct COCA subtype, or a combination thereof. It reflects the probability that a positive test reflects the underlying condition being tested for. Its value does however depend on the prevalence of the disease, which may vary. In one example, the following characteristics are provided: FP (false positive); TN (true negative); TP (true positive); FN (false negative). False positive rate (.alpha.)=FP/(FP+TN)-specificity; False negative rate (.beta.)=FN/(TP+FN)-sensitivity; Power=sensitivity=1-.beta.; Likelihood-ratio positive=sensitivity/(1-specificity); Likelihood-ratio negative=(1-sensitivity)/specificity. The negative predictive value (NPV) is the proportion of subjects with negative test results who are correctly diagnosed.

[0128] In some embodiments, the results of the biomarker level analysis of the subject methods provide a statistical confidence level that a given diagnosis is correct. In some embodiments, such statistical confidence level is at least about, or more than about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 99.5%, or more.

[0129] In some embodiments, the method further includes classifying the tumor tissue sample as a particular COCA subtype based on the comparison of biomarker levels in the sample and reference biomarker levels, for example present in at least one training set. In some embodiments, the tumor tissue sample is classified as a particular subtype if the results of the comparison meet one or more criterion such as, for example, a minimum percent agreement, a value of a statistic calculated based on the percentage agreement such as (for example) a kappa statistic, a minimum correlation (e.g., Pearson's correlation) and/or the like.

[0130] It is intended that the methods described herein can be performed by software (stored in memory and/or executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, a general-purpose processor, a field programmable gate array (FPGA), and/or an application specific integrated circuit (ASIC). Software modules (executed on hardware) can be expressed in a variety of software languages (e.g., computer code), including Unix utilities, C, C++, Java.TM., Ruby, SQL, SAS.RTM., the R programming language/software environment, Visual Basic.TM., and other object-oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, micro-code or micro-instructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0131] Some embodiments described herein relate to devices with a non-transitory computer-readable medium (also can be referred to as a non-transitory processor-readable medium or memory) having instructions or computer code thereon for performing various computer-implemented operations and/or methods disclosed herein. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The media and computer code (also can be referred to as code) may be those designed and constructed for the specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to: magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as Compact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read Only Memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices that are specially configured to store and execute program code, such as Application-Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read-Only Memory (ROM) and Random-Access Memory (RAM) devices. Other embodiments described herein relate to a computer program product, which can include, for example, the instructions and/or computer code discussed herein.

[0132] In some embodiments, a single biomarker, or from about 1 to about 4, from about 4 to about 8, from about 8 to about 12, from about 12 to about 16, from about 16 to about 20, from about 20 to about 24, from about 24 to about 30, from about 34 to about 38, from about 38 to about 42, from about 42 to about 46, from about 46 to about 50, from about 50 to about 54, from about 54 to about 58, from about 58 to about 62, from about 62 to about 66, from about 66 to about 72, from about 72 to about 76, from about 76 to about 80, from about 80 to about 84 (e.g., as disclosed in Table 1) is capable of classifying COCA subtypes of cancer with a predictive success of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at 1 east about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, and all values in between. In some embodiments, any combination of biomarkers disclosed herein (e.g., in Table 1) can be used to obtain a predictive success of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, and all values in between.

[0133] In some embodiments, a single biomarker, or from about 1 to about 4, from about 4 to about 8, from about 8 to about 12, from about 12 to about 16, from about 16 to about 20, from about 20 to about 24, from about 24 to about 30, from about 34 to about 38, from about 38 to about 42, from about 42 to about 46, from about 46 to about 50, from about 50 to about 54, from about 54 to about 58, from about 58 to about 62, from about 62 to about 66, from about 66 to about 72, from about 72 to about 76, from about 76 to about 80, from about 80 to about 84 (e.g., as disclosed in Table 1) is capable of classifying COCA subtypes of cancer with a sensitivity or specificity of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, and all values in between. In some embodiments, any combination of biomarkers disclosed herein can be used to obtain a sensitivity or specificity of at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, up to 100%, and all values in between.

Classifier Biomarker Selection

[0134] In one embodiment, the methods and compositions provided herein are useful for determining the clustering of cluster assignments (COCA) subtype of a sample (e.g., tumor sample) from a patient by analyzing the expression of a set of biomarkers, whereby use of the set of biomarkers in detecting a COCA subtype comprises use of a fewer number of biomarkers from a single genome-wide platform as compared to methods known in the art for molecularly classifying a cell of origin cancer subtype (e.g., Hoadley et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304, and Hoadley et al. "Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin." Cell 158, no. 4 (2014): 929-944, both of which are herein incorporated by reference). In some cases, the set of biomarkers is less than 300, 290, 280, 270, 260, 250, 240, 230, 220, 210, 200, 150, 100 or 90 biomarkers. In some cases, the set of biomarkers is between 4 and 84 biomarkers. In some cases, the set of biomarkers is the set of 84 biomarkers listed in Table 1. In some cases, the set of biomarkers is a sub-set of biomarkers listed Table 1 such as, for example 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80 or 82 of the biomarkers listed in Table 1. The biomarkers or classifier biomarkers useful in the methods and compositions provided herein can be selected from one or more cancer datasets from one or more databases. The cancers can be any cancer known in the art. The cancers can include hematologic and lymphatic malignancies, solid tumor types, cancers of the central nervous system, cancers from neural-crest-derived tissues, and melanocytic cancers of the skin. The cancers for use in the methods herein can be the cancers studied in The Cancer Genome Atlas (TCGA) or a subset thereof. The cancers for use in the method provided herein can be those cancers listed herein. The databases can be public databases.

[0135] In one embodiment, classifier biomarkers (e.g., one or more genes listed in Table 1) useful in the methods and compositions provided herein for detecting or diagnosing subtypes were selected from a large data set of potential classifier biomarkers. In one embodiment, classifier biomarkers useful for the methods and compositions provided herein such as those in Table 1 are selected by subjecting a large set of classifier biomarkers to an in silico based process in order to determine the minimum number of genes whose expression profile can be used to determine a pan-cancer COCA subtype of a subject from a sample obtained from said subject. In some cases, the large set of classifier biomarkers can be a pan-cancer dataset such as, for example, the mRNA expression data (i.e., RNA-seq data) from TCGA found at gdc.cancer.gov/about-data/publications/pancanatlas. In some cases, the large set of classifier biomarkers can be the genes derived from the mRNA expression profile data derived from more than 10,000 tumors across more than 30 tumor types as described in Hoadley et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell 173, no. 2 (2018): 291-304, which comprised one of several genome-wide molecular platforms that together can serve to define the gold standard (GS) COCA subtyper. The in silico process for selecting a gene signature as provided herein (e.g., Table 1 and 2) for determining a COCA subtype of a sample from a patient can comprise applying or using a Classification to Nearest Centroid (CLaNC) algorithm on the pan-cancer mRNA expression data (i.e., RNA-seq data) from TCGA to choose a minimum number of correlated genes for each subtype. For determination of the optimal number of genes (e.g., 84 genes as shown in Table 1) to include in the signature, the process can further comprise performing a 5-fold cross validation using the TCGA pan-cancer dataset following application of the CLaNC algorithm as provided herein to produce cross-validation curves to test different numbers of correlated genes as shown in FIG. 3 in order to determine the minimum number of correlated genes needed per subtype. To get the final list of gene classifiers, the method can further comprise applying the CLaNC algorithm to the entire TCGA mRNA expression pan-cancer dataset. The CLaNC software used in the methods provided herein can be as found in or derived from Alan R. Dabney; ClaNC: point-and-click software for classifying microarrays to nearest centroids, Bioinformatics, Volume 22, Issue 1, 1 Jan. 2006, Pages 122-123).

[0136] In one embodiment, the method further comprises validating the gene classifiers. Validation can comprise testing the expression of the classifiers in a test set of samples and comparing the COCA subtype determined using the signature of Table 1 with the COCA subtype determined using the gold standard COCA subtyper method described in Hoadley et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304. The test set of samples can be any sample type provided herein such as, for example, fresh frozen or archived formalin-fixed paraffin-embedded (FFPE) cancer samples. In one embodiment, validation can comprise testing the expression of the classifiers in several fresh frozen publicly available array and/or RNAseq datasets and calling the subtype based on said expression levels and subsequently comparing the COCA subtype determined using the signature of Table 1 with the COCA subtype determined using the gold standard COCA subtyper method described in Hoadley et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell 173, no. 2 (2018): 291-304. In other words, validation can comprise calling the subtypes of the several fresh frozen publicly available array and RNAseq test datasets using their expression levels and the CLaNC algorithm as described herein and comparing the subtype calls with the gold standard subtype calls as defined in Hoadley et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell 173, no. 2 (2018): 291-304. Final validation of the gene signature (e.g., Table 1) can then be performed in a newly collected dataset of archived formalin-fixed paraffin-embedded (FFPE) cancer samples to assure comparable performance in the FFPE samples. In one embodiment, the classifier biomarkers of Table 1 were selected based on the in silico CLaNC process described herein. The gene symbols and official gene names are listed in Table 1. Further to the above embodiments, the in silico CLaNC process can entail use of the CLaNC process described in Dabney (2005) Bioinformatics 21(22):4148-4154. In one embodiment, the in silico CLaNC process can entail use of CLaNC software described in Dabney A R. ClaNC: Point-and-click software for classifying microarrays to nearest centroids. Bioinformatics. 2006; 22: 122-123 or equivalents or derivatives related thereto.

[0137] In one embodiment, the methods provided herein require the detection of the expression level of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 18, at least 20, at least 22, at least 24, at least 26, at least 28, at least 30, at least 32, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83 or up to 84 classifier biomarkers (e.g., from Table 1) in a cancer sample obtained from a patient whose expression is altered in order to identify a COCA cancer subtype. The same applies for other classifier biomarker expression datasets as provided herein.

[0138] In another embodiment, the methods provided herein require the detection of the expression level of a total of at least 2, at least 4, at least 6, at least 8, at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 22, at least 24, at least 26, at least 28, at least 30, at least 32, at least 34, at least 36, at least 38, at least 40, at least 42, at least 44, at least 46, at least 48, at least 50, at least 52, at least 54, at least 56, at least 58, at least 60, at least 62, at least 64, at least 66, at least 68, at least 70, at least 72, at least 74, at least 76, at least 78, at least 80, at least 82 or up to 84 classifier biomarkers out of the 84 gene biomarkers of Table 1 in a cancer cell sample obtained from a patient in order to identify a COCA cancer subtype. In another embodiment, the methods provided herein require the detection of the expression level of a total of at least 4, at least 8, at least 12, at least 16, at least 20, at least 24, at least 28, at least 32, at least 36, at least 40, at least 44, at least 48, at least 52, at least 56, at least 60, at least 64, at least 68, at least 72, at least 76, at least 80 or up to 84 classifier biomarkers out of the 84 gene biomarkers of Table 1 in a cancer cell sample obtained from a patient in order to identify a COCA cancer subtype. The same applies for other classifier biomarker expression datasets as provided herein.

[0139] In one embodiment, the expression level of one or more classifier biomarkers of Table 1 can be altered in a specific COCA subtype as detected in a sample obtained from a subject as described in any of the methods provided herein. The alteration of the expression level can be an "up-regulation" or "down-regulation" of the one or more classifier biomarkers of Table 1. In one embodiment, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 18, at least 20, at least 22, at least 24, at least 26, at least 28, at least 30, at least 32, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83 or up to 84 classifier biomarkers out of the 84 gene biomarkers of Table 1 are "up-regulated" in a specific COCA subtype of cancer. In another embodiment, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 18, at least 20, at least 22, at least 24, at least 26, at least 28, at least 30, at least 32, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83 or up to 84 classifier biomarkers out of the 84 gene biomarkers of Table 1 are "down-regulated" in a specific COCA subtype of cancer. In a still further embodiment, in methods provided herein utilizing more than one classifier biomarker (e.g., more than one classifier biomarker from Table 1) to determine a COCA subtype, the alteration in expression levels of the more than one classifier biomarkers can either be an up-regulation, a down-regulation or any combination thereof. Further to any of the above embodiments, the alteration of the expression level can be relative to or compared to a sample isolated from a healthy subject as defined herein. The sample obtained from the healthy subject can be form the same anatomical area of the body. The same applies for other classifier biomarker expression datasets as provided herein.

[0140] In one embodiment, the expression level of an "up-regulated" biomarker as provided herein is increased by about 0.2-fold, about 0.5-fold, about 1-fold, about 1.5-fold, about 2-fold, about 2.5-fold, about 3-fold, about 3.5-fold, about 4-fold, about 4.5-fold, about 5-fold, and any values in between. In another embodiment, the expression level of a "down-regulated" biomarker as provided herein is decreased by about 0.2-fold, about 0.5-fold, about 1-fold, about 1.5-fold, about 2-fold, about 2.5-fold, about 3-fold, about 3.5-fold, about 4-fold, about 4.5-fold, about 5-fold, and any values in between.

[0141] It is recognized that additional genes or proteins or molecular platforms can be used in the practice of the methods provided herein. In general, genes useful in classifying the COCA subtypes of cancer include those that are independently capable of distinguishing between normal versus tumor, or between different classes or grades of cancer. A gene is considered to be capable of reliably distinguishing between COCA subtypes if the area under the receiver operator characteristic (ROC) curve is approximately 1. Further, in general, molecular platforms that generate data that can be useful in classifying the COCA subtypes of cancer can include genome-wide platforms such as, for example, whole-exome DNA sequencing assays (e.g., Illumina HiSeq and GAII), DNA copy-number variation assays (e.g., Affymetrix 6.0 microarrays), DNA methylation assays (e.g., Illumina 450,000-feature microarrays), genome-wide mRNA level assays (e.g., Illumina mRNA-seq), microRNA level assays (e.g., Illumina microRNA-seq), and protein level assays for proteins and/or phosphorylated proteins (e.g., Reverse Phase Protein Arrays; RPPA).

Clinical/Therapeutic Uses

[0142] In one embodiment, a method is provided herein for determining a disease outcome or prognosis for a patient suffering from cancer. In some cases, the cancer can be any cancer known in the art and/or provided herein. The disease outcome or prognosis can be measured by examining the overall survival for a period of time or intervals (e.g., 0 to 36 months or 0 to 60 months). In one embodiment, survival is analyzed as a function of COCA subtype. In one embodiment, survival is analyzed as a function of COCA subtype across tissue of origin tumor types. In one embodiment, survival is analyzed as a function of COCA subtype within a tissue of origin tumor type (see, for example, FIGS. 6-8). The COCA subtype can be determined using the methods provided herein such as, for example, determining the expression of all or subsets of the genes in Table 1. Relapse-free and overall survival can be assessed using standard Kaplan-Meier plots as well as Cox proportional hazards modeling.

[0143] In one embodiment, the methods and compositions as provided herein for determining a COCA subtype of a patient suffering or suspected of suffering from cancer is used to determine whether or not said patient is a candidate for treatment with a specific type or types of cancer therapy. The sample can be any type of sample obtained from the patient as provided herein. The cancer can be any type of cancer known in the art and/or provided herein. In one embodiment, determining the COCA subtype is one of a number of methods that can be employed to characterize the sample obtained from the patient such that the determining the COCA subtype alone or in combination with one or more of the number of methods can be used to determine whether or not said patient is a candidate for treatment with a specific type or types of cancer therapy. In addition to assessing or determining a COCA subtype, the number of methods for characterizing the sample can entail determining a proliferation score, the tumor mutation burden (TMB), the tissue of origin subtype, the level of immune activation or any combination thereof. In one embodiment, one or all of the methods for characterizing the sample can be performed on RNA sequencing data obtained from the sample.

[0144] In one embodiment, in addition to assessing the COCA subtype as provided herein, the characterization entails determining proliferation or proliferation score. In one embodiment, proliferation or the proliferation score is determined using any method known in the art such as, for example, as provided in U.S. 62/789,668 filed Jan. 8, 2019, which is herein incorporated by reference herein.

[0145] In one embodiment, in addition to determining the COCA subtype as provided herein, the characterization entails calculating a TMB value and/or rate. The TMB value and/or rate can be calculated using any method known in the art. In one embodiment, the TMB value and/or rate can be calculated from RNA (e.g., via transcriptome profiling or RNA sequencing)) as provided in U.S. 62/771,702 filed Nov. 27, 2018 and U.S. 62/743,257 filed Oct. 9, 2018, which is herein incorporated by reference herein.

[0146] The determination of whether or not said patient is a candidate for treatment with a specific type or types of cancer therapy can be based on the COCA subtype alone or in combination with other methods known in the art for characterizing a sample obtained from a patient suffering from or suspected of suffering from cancer. The other methods for characterizing said sample can be histologically based methods, gene expression based methods or a combination thereof. The histologically based methods can include histological cancer subtyping by one or more trained pathologists as well as the histological based methods of assessing proliferation such as, for example, determining the mitotic activity index. The gene expression based methods can include subtyping, assessment of TMB, assessment of tissue of origin subtype, immune subtyping or any combination thereof. The gene expression based methods can be assessed from DNA, RNA or a combination thereof. In one embodiment, the characterization of the sample obtained from the patient suffering from or suspected of suffering from cancer is performed on RNA obtained or isolated from the sample.

[0147] The gene expression based tissue of origin cancer subtyping can be determined using gene signatures known in the art for specific types of cancer. In one embodiment, the tissue of origin of the cancer is the lung and the gene signature is selected from the gene signatures found in WO2017/201165, WO2017/201164, US20170114416 or U.S. Pat. No. 8,822,153, each of which is herein incorporated by reference in their entirety. In one embodiment, the tissue of origin cancer is head and neck squamous cell carcinoma (HNSCC) and the gene signature is selected from the gene signatures found in PCT/US18/45522 or PCT/US18/48862, each of which is herein incorporated by reference in their entirety. In one embodiment, the tissue of origin cancer is breast cancer and the gene signature is the PAM50 subtyper found in Parker J S et al., (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160-1167, which is herein incorporated by reference in its entirety. In one embodiment, the tissue of origin cancer is bladder cancer (e.g., MIBC) and the gene signature is selected from the gene signatures found in 62/629,975 filed Feb. 13, 2018, which is herein incorporated by reference in their entirety. In one embodiment, the tissue of origin cancer is bladder cancer (e.g., MIBC) and the gene signature is selected from the gene signature found in The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature volume 507, pages 315-322 (2014), or Robertson, A G, et al., Cell, 171(3): 540-556 (2017), each of which is herein incorporated by reference, which is herein incorporated by reference in their entirety.

[0148] The gene expression based immune subtyping or immune cell activation can be determined using immune expression signatures known in the art such as, for example, the gene signatures found in Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T. H. O., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A. and Ziv, E., 2018, The immune landscape of cancer. Immunity, 48(4), pp. 812-830, which is herein incorporated by reference in its entirety. In one embodiment, immune cell activation is determined by monitoring the immune cell signatures of Bindea et al (Immunity 2013; 39(4); 782-795), the contents of which are herein incorporated by reference in its entirety. In one embodiment, the method further comprises measuring single gene immune biomarkers, such as, for example, CTLA4, PDCD1 and CD274 (PD-LI), PDCDLG2(PD-L2) and/or IFN gene signatures. In one embodiment, the level of immune cell activation is determined by measuring gene expression signatures of immunomarkers. The immunomarkers can be measured in the same and/or different sample used to determine the COCA subtype as described herein. The immunomarkers can be those found in WO2017/201165, and WO2017/201164, each of which is herein incorporated by reference in their entirety.

[0149] The gene expression based method for calculating a TMB value and/or rate can be any method known in the art. In one embodiment, the TMB value and/or rate can be calculated from RNA (e.g., via transcriptome profiling or RNA sequencing)) as provided in U.S. 62/771,702 filed Nov. 27, 2018 and U.S. 62/743,257 filed Oct. 9, 2018, which is herein incorporated by reference herein.

[0150] In one embodiment, upon determining a patient's COCA subtype (e.g., by measuring the expression of all or subsets of the genes in Table 1), the patient is selected for suitable therapy, for example, radiotherapy (radiation therapy), surgical intervention, target therapy, chemotherapy or drug therapy with an angiogenesis inhibitor or immunotherapy or combinations thereof. In some embodiments, the suitable treatment can be any treatment or therapeutic method that can be used for a cancer patient. In one embodiment, upon determining a patient's COCA subtype, the patient is administered a suitable therapeutic agent, for example chemotherapeutic agent(s) or an angiogenesis inhibitor or immunotherapeutic agent(s). In one embodiment, the therapy is immunotherapy, and the immunotherapeutic agent is a checkpoint inhibitor, monoclonal antibody, biological response modifier, therapeutic vaccine or cellular immunotherapy. In some embodiments, the determination of a suitable treatment can identify treatment responders. In some embodiments, the determination of a suitable treatment can identify treatment non-responders. In some embodiments, upon determining a patient's COCA subtype, the cancer patient can be selected for any combination of suitable therapies. For example, chemotherapy or drug therapy with a radiotherapy, a tumor dissection with an immunotherapy or a chemotherapeutic agent with a radiotherapy. In some embodiments, immunotherapy, or immunotherapeutic agent can be a checkpoint inhibitor, monoclonal antibody, biological response modifier, therapeutic vaccine or cellular immunotherapy.

[0151] The methods provided herein are also useful for evaluating clinical response to therapy, as well as for endpoints in clinical trials for efficacy of new therapies. The extent to which sequential diagnostic expression profiles move towards normal can be used as one measure of the efficacy of the candidate therapy.

[0152] In one embodiment, the methods provided herein also find use in predicting response to different lines of therapies based on the COCA subtype of cancer alone or in combination with other characterization methods as described herein (e.g., tissue of origin cancer subtype, immune subtype, proliferation and/or TMB status). For example, chemotherapeutic response can be improved by more accurately assigning tumor cell of origin subtypes. Likewise, treatment regimens can be formulated based on the COCA subtype alone or in combination with other characterization methods as described herein (e.g., tissue of origin cancer subtype, immune subtype, proliferation and/or TMB status).

[0153] Immunotherapy

[0154] In one embodiment, provided herein is a method for determining whether a cancer patient is likely to respond to immunotherapy by determining the COCA subtype of cancer of a sample obtained from the patient and, based on the COCA subtype, assessing whether the patient is likely to respond to immunotherapy. In another embodiment, provided herein is a method of selecting a patient suffering from cancer for immunotherapy by determining a COCA subtype of a sample from the patient and, based on the COCA subtype, selecting the patient for immunotherapy. The determination of the COCA subtype of the sample obtained from the patient can be performed using any method for COCA subtyping known in the art. The determination of the COCA subtype of the sample obtained from the patient can be performed using any method for COCA subtyping provided herein. In one embodiment, the sample obtained from the patient has been previously diagnosed as being a particular type of cancer, and the methods provided herein are used to determine the COCA subtype of the sample. The previous diagnosis can be based on a histological analysis. The histological analysis can be performed by one or more pathologists. In one embodiment, the COCA subtyping is performed via gene expression analysis of a set or panel of biomarkers or subsets thereof in order to generate an expression profile. The gene expression analysis can be performed on a tumor sample obtained from a patient in order to determine the presence, absence or level of expression of one or more biomarkers selected from a publically available pan-cancer database described herein and/or Table 1 provided herein. The COCA subtype can be selected from the group consisting of C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA). The immunotherapy can be any immunotherapy provided herein. In one embodiment, the immunotherapy comprises administering one or more checkpoint inhibitors. The checkpoint inhibitors can be any checkpoint inhibitor provided herein such as, for example, a checkpoint inhibitor that targets PD-1, PD-LI or CTLA4.

[0155] As disclosed herein, the biomarkers panels, or subsets thereof, can be those disclosed in any publically available pan-cancer gene expression dataset or datasets. In one embodiment, the biomarker panel or subset thereof is, for example, the cancer genome atlas pan-cancer mRNA expression dataset. In one embodiment, the biomarker panel or subset thereof is, for example, the pan-cancer mRNA expression dataset disclosed in Hoadley, Katherine A., Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304, the contents of which are herein incorporated by reference in its entirety. In one embodiment, the biomarker panel or subset thereof is, for example, the gene expression signature disclosed in Table 1 in combination with one or more biomarkers from a publically available pan-cancer expression dataset.

[0156] In one embodiment, from about 1 to about 4, about 4 to about 8, from about 4 to about 12, from about 4 to about 16, from about 4 to about 20, from about 4 to about 24, from about 4 to about 28, from about 4 to about 32, from about 4 to about 36, from about 4 to about 40, from about 4 to about 44, from about 4 to about 48, from about 4 to about 52, from about 4 to about 56, from about 4 to about 60, from about 4 to about 64, from about 4 to about 68, from about 4 to about 72, from about 4 to about 76, from about 4 to about 80 or from about 4 to about 84 of the biomarkers in any of the pan-cancer gene expression datasets provided herein, including, for example, Table 1 for a tumor sample are detected in a method to determine the COCA subtype as provided herein. In another embodiment, each of the biomarkers from any one of the pan-cancer gene expression datasets provided herein, including, for example, Table 1 for a tumor sample are detected in a method to determine the COCA subtype as provided herein.

[0157] In one embodiment, the methods provided herein further comprise determining the presence, absence or level of immune activation in a COCA subtype. The presence or level of immune cell activation can be determined by creating an expression profile or detecting the expression of one or more biomarkers associated with innate immune cells and/or adaptive immune cells associated with each COCA subtype in a sample obtained from a patient. In one embodiment, immune cell activation associated with a COCA subtype of cancer is determined by monitoring the immune cell signatures of Thorsson, V. et al., 2018, The immune landscape of cancer. Immunity, 48(4), pp. 812-830, Bindea et al (Immunity 2013; 39(4); 782-795) Faruki H. et al., JTO, 12(6): 943-953 (2017), Charoentong P. et al., Cell reports, 18, 248-262 (2017) and/or WO2017/201165 and WO2017/201164, the contents of each of which are herein incorporated by reference in its entirety. In one embodiment, the method further comprises measuring single gene immune biomarkers, such as, for example, CTLA4, PDCD1 and CD274 (PD-LI), PDCDLG2(PD-L2) and/or IFN gene signatures. The presence or a detectable level of immune activation (Innate and/or Adaptive) associated with a COCA subtype can indicate or predict that a patient with said COCA subtype may be amendable to immunotherapy. The immunotherapy can be treatment with a checkpoint inhibitor as provided herein. In one embodiment, a method is provided herein for detecting the expression of at least one classifier biomarker provided herein in a sample (e.g., tumor sample) obtained from a patient further comprises administering an immunotherapeutic agent following detection of immune activation as provided herein in said sample.

[0158] In one embodiment, the method comprises determining a COCA subtype of a tumor sample and subsequently determining a level of immune cell activation of said sub-type. In one embodiment, the subtype is determined by determining the expression levels of one or more classifier biomarkers at the nucleic acid level using sequencing (e.g., RNASeq), amplification (e.g., qRT-PCR) or hybridization assays (e.g., microarray analysis) as described herein. The one or more biomarkers can be selected from a publically available database (e.g., TCGA pan-cancer mRNA expression datasets or any other publically available pan-cancer gene expression datasets provided herein). In some embodiments, the biomarkers of Table 1 can be used to specifically determine the COCA subtype of a tumor sample obtained from a patient. In one embodiment, the level of immune cell activation is determined by measuring gene expression signatures of immunomarkers. The immunomarkers can be measured in the same and/or different sample used to subtype the tumor sample as described herein. The immunomarkers that can be measured can comprise, consist of, or consistently essentially of innate immune cell (IIC) and/or adaptive immune cell (AIC) gene signatures, interferon (IFN) gene signatures, individual immunomarkers, major histocompatability complex class II (MHC class II) genes or a combination thereof. The gene expression signatures for IICs, AICs, IFN and MHC class II can be any known gene signatures for said cell types or genes known in the art. For example, the immune gene signatures can be those from Bindea et al. (Immunity 2013; 39(4); 782-795), Faruki H. et al., JTO, 12(6): 943-953 (2017), Charoentong P. et al., Cell reports, 18, 248-262 (2017) and/or WO2017/201165 and WO2017/201164. The individual immunomarkers can be CTLA4, PDCD1 and CD274 (PD-L1). In one embodiment, immune subtyping or immune cell activation can be determined using the gene signatures found in Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T. H. O., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A. and Ziv, E., 2018, The immune landscape of cancer. Immunity, 48(4), pp. 812-830.

[0159] In one embodiment, upon determining a patient's COCA cancer subtype using any of the methods and classifier biomarkers panels or subsets thereof as provided herein, the patient is selected for treatment with or administered an immunotherapeutic agent. The immunotherapeutic agent can be a checkpoint inhibitor, monoclonal antibody, biological response modifiers, therapeutic vaccine or cellular immunotherapy.

[0160] In another embodiment, the immunotherapeutic agent is a checkpoint inhibitor. In some cases, a method for determining the likelihood of response to one or more checkpoint inhibitors is provided. In one embodiment, the checkpoint inhibitor is a PD-1/PD-LI checkpoint inhibitor. The PD-1/PD-LI checkpoint inhibitor can be nivolumab, pembrolizumab, atezolizumab, durvalumab, lambrolizumab, or avelumab. In one embodiment, the checkpoint inhibitor is a CTLA-4 checkpoint inhibitor. The CTLA-4 checkpoint inhibitor can be ipilimumab or tremelimumab. In one embodiment, the checkpoint inhibitor is a combination of checkpoint inhibitors such as, for example, a combination of one or more PD-1/PD-LI checkpoint inhibitors used in combination with one or more CTLA-4 checkpoint inhibitors.

[0161] In one embodiment, the immunotherapeutic agent is a monoclonal antibody. In some cases, a method for determining the likelihood of response to one or more monoclonal antibodies is provided. The monoclonal antibody can be directed against tumor cells or directed against tumor products. The monoclonal antibody can be panitumumab, matuzumab, necitumunab, trastuzumab, amatuximab, bevacizumab, ramucirumab, bavituximab, patritumab, rilotumumab, cetuximab, immu-132, or demcizumab.

[0162] In yet another embodiment, the immunotherapeutic agent is a therapeutic vaccine. In some cases, a method for determining the likelihood of response to one or more therapeutic vaccines is provided. The therapeutic vaccine can be a peptide or tumor cell vaccine. The vaccine can target MAGE-3 antigens, NY-ESO-1 antigens, p53 antigens, survivin antigens, or MUC1 antigens. The therapeutic cancer vaccine can be GVAX (GM-CSF gene-transfected tumor cell vaccine), belagenpumatucel-L (allogeneic tumor cell vaccine made with four irradiated NSCLC cell lines modified with TGF-beta2 antisense plasmid), MAGE-A3 vaccine (composed of MAGE-A3 protein and adjuvant AS15), (1)-BLP-25 anti-MUC-1 (targets MUC-1 expressed on tumor cells), CimaVax EGF (vaccine composed of human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein), WT1 peptide vaccine (composed of four Wilms' tumor suppressor gene analogue peptides), CRS-207 (live-attenuated Listeria monocytogenes vector encoding human mesothelin), Bec2/BCG (induces anti-GD3 antibodies), GV1001 (targets the human telomerase reverse transcriptase), TG4010 (targets the MUC1 antigen), racotumomab (anti-idiotypic antibody which mimicks the NGcGM3 ganglioside that is expressed on multiple human cancers), tecemotide (liposomal BLP25; liposome-based vaccine made from tandem repeat region of MUC1) or DRibbles (a vaccine made from nine cancer antigens plus TLR adjuvants).

[0163] In one embodiment, the immunotherapeutic agent is a biological response modifier. In some cases, a method for determining the likelihood of response to one or more biological response modifiers is provided. The biological response modifier can trigger inflammation such as, for example, PF-3512676 (CpG 7909) (a toll-like receptor 9 agonist), CpG-ODN 2006 (downregulates Tregs), Bacillus Calmette-Guerin (BCG), mycobacterium vaccae (SRL172) (nonspecific immune stimulants now often tested as adjuvants). The biological response modifier can be cytokine therapy such as, for example, IL-2+tumor necrosis factor alpha (TNF-alpha) or interferon alpha (induces T-cell proliferation), interferon gamma (induces tumor cell apoptosis), or Mda-7 (IL-24) (Mda-7/IL-24 induces tumor cell apoptosis and inhibits tumor angiogenesis). The biological response modifier can be a colony-stimulating factor such as, for example granulocyte colony-stimulating factor. The biological response modifier can be a multi-modal effector such as, for example, multi-target VEGFR: thalidomide and analogues such as lenalidomide and pomalidomide, cyclophosphamide, cyclosporine, denileukin diftitox, talactoferrin, trabecetedin or all-trans-retinoic acid.

[0164] In one embodiment, the immunotherapy is cellular immunotherapy. In some cases, a method for determining the likelihood of response to one or more cellular therapeutic agents. The cellular immunotherapeutic agent can be dendritic cells (DCs) (ex vivo generated DC-vaccines loaded with tumor antigens), T-cells (ex vivo generated lymphokine-activated killer cells; cytokine-induce killer cells; activated T-cells; gamma delta T-cells), or natural killer cells.

[0165] In some cases, specific COCA subtypes of cancer have different levels of immune activation (e.g., innate immunity and/or adaptive immunity) such that COCA subtypes with elevated or detectable immune activation (e.g., innate immunity and/or adaptive immunity) are selected for treatment with one or more immunotherapeutic agents described herein. In some cases, specific COCA subtypes of cancer have high or elevated levels of immune activation. In some cases, the C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and/or C28 (THCA) subtype has elevated levels of immune activation (e.g., innate immunity and/or adaptive immunity) as compared to other blaCOCA subtypes. In some cases, the C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and/or C28 (THCA) subtype has reduced levels of immune activation (e.g., innate immunity and/or adaptive immunity) as compared to other COCA subtypes. In one embodiment, COCA subtypes with low levels of or no immune activation (e.g., innate immunity and/or adaptive immunity) are not selected for treatment with one or more immunotherapeutic agents described herein.

Angiogenesis Inhibitors

[0166] In one embodiment, upon determining a patient's or subject's COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.), the patient is selected for drug therapy with an angiogenesis inhibitor.

[0167] In one embodiment, the angiogenesis inhibitor is a vascular endothelial growth factor (VEGF) inhibitor, a VEGF receptor inhibitor, a platelet derived growth factor (PDGF) inhibitor or a PDGF receptor inhibitor.

[0168] In general, methods of determining whether a patient is likely to respond to angiogenesis inhibitor therapy, or methods of selecting a patient for angiogenesis inhibitor therapy are provided herein. In one embodiment, the method comprises determining a COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) and probing a sample from the patient for the levels of at least five hypoxia biomarkers selected from the group consisting of RRAGD, FABP5, UCHL1, GAL, PLOD, DDIT4, VEGF, ADM, ANGPTL4, NDRG1, NP, SLC16A3, and C14ORF58 (see Table A) at the nucleic acid level. In a further embodiment, the probing step comprises mixing the sample with five or more oligonucleotides that are substantially complementary to portions of nucleic acid molecules of the at least five biomarkers under conditions suitable for hybridization of the five or more oligonucleotides to their complements or substantial complements, detecting whether hybridization occurs between the five or more oligonucleotides to their complements or substantial complements; and obtaining hybridization values of the sample based on the detecting steps. The hybridization values of the sample are then compared to reference hybridization value(s) from at least one sample training set, wherein the at least one sample training set comprises (i) hybridization value(s) of the at least five biomarkers from a sample that overexpresses the at least five biomarkers, or overexpresses a subset of the at least five biomarkers, (ii) hybridization values of the at least five biomarkers from a reference cancer of COCA subtype specific sample, or (iii) hybridization values of the at least five biomarkers from a control or healthy sample. A determination of whether the patient is likely to respond to angiogenesis inhibitor therapy, or a selection of the patient for angiogenesis inhibitor is then made based upon (i) the patient's COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) and (ii) the results of comparison.

TABLE-US-00003 TABLE A Biomarkers for hypoxia profile GenBank Name Abbreviation Accession No. RRAGD Ras-related GTP BC003088 binding D FABP5 fatty acid binding M94856 protein 5 UCHL1 ubiquitin carboxyl- NM_004181 terminal esterase L1 GAL Galanin BC030241 PLOD procollagen-lysine, M98252 2-oxoglutarate 5- dioxygenase lysine hydroxylase DDIT4 DNA-damage-inducible NM_019058 transcript 4 VEGF vascular endothelial M32977 growth factor ADM Adrenomedullin NM_001124 ANGPTL4 angiopoietin-like 4 AF202636 NDRG1 N-myc downstream NM_006096 regulated gene 1 NP nucleoside phosphorylase NM 000270 SLC16A3 solute carrier family NM_004207 16 monocarboxylic acid transporters, member 3 C14ORF58 chromosome 14 open AK000378 reading frame 58

[0169] The aforementioned set of thirteen biomarkers, or a subset thereof, is also referred to herein as a "hypoxia profile".

[0170] In one embodiment, the method provided herein includes determining the levels of at least five biomarkers, at least six biomarkers, at least seven biomarkers, at least eight biomarkers, at least nine biomarkers, or at least ten biomarkers, or five to thirteen, six to thirteen, seven to thirteen, eight to thirteen, nine to thirteen or ten to thirteen biomarkers selected from RRAGD, FABP5, UCHL1, GAL, PLOD, DDIT4, VEGF, ADM, ANGPTL4, NDRG1, NP, SLC16A3, and C14ORF58 in a sample obtained from a subject. Biomarker expression in some instances may be normalized against the expression levels of all RNA transcripts or their expression products in the sample, or against a reference set of RNA transcripts or their expression products. The reference set as explained throughout, may be an actual sample that is tested in parallel with the sample, or may be a reference set of values from a database or stored dataset. Levels of expression, in one embodiment, are reported in number of copies, relative fluorescence value or detected fluorescence value. The level of expression of the biomarkers of the hypoxia profile together with the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) as determined using the methods provided herein can be used in the methods described herein to determine whether a patient is likely to respond to angiogenesis inhibitor therapy.

[0171] In one embodiment, the levels of expression of the thirteen biomarkers (or subsets thereof, as described above, e.g., five or more, from about five to about 13), are normalized against the expression levels of all RNA transcripts or their non-natural cDNA expression products, or protein products in the sample, or of a reference set of RNA transcripts or a reference set of their non-natural cDNA expression products, or a reference set of their protein products in the sample.

[0172] In one embodiment, angiogenesis inhibitor treatments include, but are not limited to an integrin antagonist, a selectin antagonist, an adhesion molecule antagonist, an antagonist of intercellular adhesion molecule (ICAM)-1, ICAM-2, ICAM-3, platelet endothelial adhesion molecule (PCAM), vascular cell adhesion molecule (VCAM)), lymphocyte function-associated antigen 1 (LFA-1), a basic fibroblast growth factor antagonist, a vascular endothelial growth factor (VEGF) modulator, a platelet derived growth factor (PDGF) modulator (e.g., a PDGF antagonist).

[0173] In one embodiment of determining whether a subject is likely to respond to an integrin antagonist, the integrin antagonist is a small molecule integrin antagonist, for example, an antagonist described by Paolillo et al. (Mini Rev Med Chem, 2009, volume 12, pp. 1439-1446, incorporated by reference in its entirety), or a leukocyte adhesion-inducing cytokine or growth factor antagonist (e.g., tumor necrosis factor-.alpha. (TNF-.alpha.), interleukin-1.beta. (IL-1.beta.), monocyte chemotactic protein-1 (MCP-1) and a vascular endothelial growth factor (VEGF)), as described in U.S. Pat. No. 6,524,581, incorporated by reference in its entirety herein.

[0174] The methods provided herein are also useful for determining whether a subject is likely to respond to one or more of the following angiogenesis inhibitors: interferon gamma 1.beta., interferon gamma 1.beta. (Actimmune.RTM.) with pirfenidone, ACUHTR028, .alpha.V.beta.5, aminobenzoate potassium, amyloid P, ANG1122, ANG1170, ANG3062, ANG3281, ANG3298, ANG4011, anti-CTGF RNAi, Aplidin, Astragalus membranaceus extract with salvia and Schisandra chinensis, atherosclerotic plaque blocker, Azol, AZX100, BB3, connective tissue growth factor antibody, CT140, danazol, Esbriet, EXC001, EXC002, EXC003, EXC004, EXC005, F647, FG3019, Fibrocorin, Follistatin, FT011, a galectin-3 inhibitor, GKT137831, GMCT01, GMCT02, GRMD01, GRMD02, GRN510, Heberon Alfa R, interferon .alpha.-2.beta., ITMN520, JKB119, JKB121, JKB122, KRX168, LPA1 receptor antagonist, MGN4220, MIA2, microRNA 29a oligonucleotide, MMI0100, noscapine, PBI4050, PBI4419, PDGFR inhibitor, PF-06473871, PGN0052, Pirespa, Pirfenex, pirfenidone, plitidepsin, PRM151, Px102, PYN17, PYN22 with PYN17, Relivergen, rhPTX2 fusion protein, RXI109, secretin, STX100, TGF-.beta. Inhibitor, transforming growth factor, .beta.-receptor 2 oligonucleotide, VA999260, XV615 or a combination thereof.

[0175] In another embodiment, a method is provided for determining whether a subject is likely to respond to one or more endogenous angiogenesis inhibitors. In a further embodiment, the endogenous angiogenesis inhibitor is endostatin, a 20 kDa C-terminal fragment derived from type XVIII collagen, angiostatin (a 38 kDa fragment of plasmin), a member of the thrombospondin (TSP) family of proteins. In a further embodiment, the angiogenesis inhibitor is a TSP-1, TSP-2, TSP-3, TSP-4 and TSP-5. Methods for determining the likelihood of response to one or more of the following angiogenesis inhibitors are also provided a soluble VEGF receptor, e.g., soluble VEGFR-1 and neuropilin 1 (NPR1), angiopoietin-1, angiopoietin-2, vasostatin, calreticulin, platelet factor-4, a tissue inhibitor of metalloproteinase (TIMP) (e.g., TIMP1, TIMP2, TIMP3, TIMP4), cartilage-derived angiogenesis inhibitor (e.g., peptide troponin I and chrondomodulin I), a disintegrin and metalloproteinase with thrombospondin motif 1, an interferon (IFN), (e.g., IFN-.alpha., IFN-.beta., IFN-.gamma.), a chemokine, e.g., a chemokine having the C--X--C motif (e.g., CXCL10, also known as interferon gamma-induced protein 10 or small inducible cytokine B10), an interleukin cytokine (e.g., IL-4, IL-12, IL-18), prothrombin, antithrombin III fragment, prolactin, the protein encoded by the TNFSF15 gene, osteopontin, maspin, canstatin, proliferin-related protein.

[0176] In one embodiment, a method for determining the likelihood of response to one or more of the following angiogenesis inhibitors is provided is angiopoietin-1, angiopoietin-2, angiostatin, endostatin, vasostatin, thrombospondin, calreticulin, platelet factor-4, TIMP, CDAI, interferon .alpha., interferon .beta., vascular endothelial growth factor inhibitor (VEGI) meth-1, meth-2, prolactin, VEGI, SPARC, osteopontin, maspin, canstatin, proliferin-related protein (PRP), restin, TSP-1, TSP-2, interferon gamma 1.beta., ACUHTR028, .alpha.V.beta.5, aminobenzoate potassium, amyloid P, ANG1122, ANG1170, ANG3062, ANG3281, ANG3298, ANG4011, anti-CTGF RNAi, Aplidin, Astragalus membranaceus extract with salvia and Schisandra chinensis, atherosclerotic plaque blocker, Azol, AZX100, BB3, connective tissue growth factor antibody, CT140, danazol, Esbriet, EXC001, EXC002, EXC003, EXC004, EXC005, F647, FG3019, Fibrocorin, Follistatin, FT011, a galectin-3 inhibitor, GKT137831, GMCT01, GMCT02, GRMD01, GRMD02, GRN510, Heberon Alfa R, interferon .alpha.-213, ITMN520, JKB119, JKB121, JKB122, KRX168, LPA1 receptor antagonist, MGN4220, MIA2, microRNA 29a oligonucleotide, MMI0100, noscapine, PBI4050, PBI4419, PDGFR inhibitor, PF-06473871, PGN0052, Pirespa, Pirfenex, pirfenidone, plitidepsin, PRM151, Px102, PYN17, PYN22 with PYN17, Relivergen, rhPTX2 fusion protein, RXI109, secretin, STX100, TGF-.beta. Inhibitor, transforming growth factor, .beta.-receptor 2 oligonucleotide, VA999260, XV615 or a combination thereof.

[0177] In yet another embodiment, the angiogenesis inhibitor can include pazopanib (Votrient), sunitinib (Sutent), sorafenib (Nexavar), axitinib (Inlyta), ponatinib (Iclusig), vandetanib (Caprelsa), cabozantinib (Cometrig), ramucirumab (Cyramza), regorafenib (Stivarga), ziv-aflibercept (Zaltrap), motesanib, or a combination thereof. In another embodiment, the angiogenesis inhibitor is a VEGF inhibitor. In a further embodiment, the VEGF inhibitor is axitinib, cabozantinib, aflibercept, brivanib, tivozanib, ramucirumab or motesanib. In yet a further embodiment, the angiogenesis inhibitor is motesanib.

[0178] In one embodiment, the methods provided herein relate to determining a subject's likelihood of response to an antagonist of a member of the platelet derived growth factor (PDGF) family, for example, a drug that inhibits, reduces or modulates the signaling and/or activity of PDGF-receptors (PDGFR). For example, the PDGF antagonist, in one embodiment, is an anti-PDGF aptamer, an anti-PDGF antibody or fragment thereof, an anti-PDGFR antibody or fragment thereof, or a small molecule antagonist. In one embodiment, the PDGF antagonist is an antagonist of the PDGFR-.alpha. or PDGFR-.beta.. In one embodiment, the PDGF antagonist is the anti-PDGF-.beta. aptamer E10030, sunitinib, axitinib, sorefenib, imatinib, imatinib mesylate, nintedanib, pazopanib HCl, ponatinib, MK-2461, dovitinib, pazopanib, crenolanib, PP-121, telatinib, imatinib, KRN 633, CP 673451, TSU-68, Ki8751, amuvatinib, tivozanib, masitinib, motesanib diphosphate, dovitinib dilactic acid, linifanib (ABT-869).

[0179] Upon making a determination of whether a patient is likely to respond to angiogenesis inhibitor therapy, or selecting a patient for angiogenesis inhibitor therapy, in one embodiment, the patient is administered the angiogenesis inhibitor. The angiogenesis in inhibitor can be any of the angiogenesis inhibitors described herein.

Radiotherapy

[0180] In one embodiment, provided herein is a method for determining whether a patient is likely to respond to radiotherapy by determining the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) of a sample obtained from the patient and, based on the COCA subtype alone or in combination with other characterization methods as described herein (e.g., tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.), assessing whether the patient is likely to respond to or benefit from radiotherapy. In another embodiment, provided herein is a method of selecting a patient suffering from cancer for radiotherapy by determining a COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) of a sample from the patient and, based on the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.), selecting the patient for radiotherapy.

[0181] In some embodiments, the radiotherapy can include but are not limited to proton therapy and external-beam radiation therapy. In some embodiments, the radiotherapy can include any types or forms of treatment that is suitable for patients with specific types of cancer.

[0182] In some embodiments, a patient with a specific type of cancer can have or display resistance to radiotherapy. Radiotherapy resistance in any cancer or subtype thereof can be determined by measuring or detecting the expression levels of one or more genes known in the art and/or provided herein associated with or related to the presence of radiotherapy resistance. Genes associated with radiotherapy resistance can include NFE2L2, KEAP1 and CUL3. In some embodiments, radiotherapy resistance can be associated with the alterations of KEAP1 (Kelch-like ECH-associated protein 1)/NRF2 (nuclear factor E2-related factor 2) pathway. Association of a particular gene to radiotherapy resistance can be determined by examining expression of said gene in one or more patients known to be radiotherapy non-responders and comparing expression of said gene in one or more patients known to be radiotherapy responders.

Surgical Intervention

[0183] In one embodiment, provided herein is a method for determining whether a cancer patient is likely to respond to surgical intervention by determining the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) of a sample obtained from the patient and, based on the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.), assessing whether the patient is likely to respond to or benefit from surgery. In another embodiment, provided herein is a method of selecting a patient suffering from cancer for surgery by determining a COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.) of a sample from the patient and, based on the COCA subtype alone or in combination with other characterization methods as described herein (e.g., determining tissue of origin cancer subtype, proliferation signature or score, immune subtype and/or TMB status, etc.), selecting the patient for surgery. In some embodiments, the surgery can include laser technology, excision, dissection, and reconstructive surgery.

Prediction of Overall Survival Rate and Metastasis for Cancer Patients

[0184] The present disclosure provides methods for predicting overall survival rate for a cancer patient. In some embodiments, the prediction of overall survival rate can involve obtaining a tumor sample for a cancer patient. In some embodiments, the cancer patients can have various stages of cancers. In some embodiments, the overall survival rate can be determined by detecting the expression level of at least one subtype classifier of a publically available pan-cancer database or dataset. In some embodiments, an overall survival rate can be determined by detecting the expression level (e.g., protein and/or nucleic acid) of any subtype classifiers that are relevant across many types of cancer, for example, subtype classifiers relevant to cell of origin. In one embodiment, the subtype classifiers can be all or a subset of classifiers from Table 1. In some embodiments, the identification of the cell of origin (COCA) subtype is indicative of the overall survival in the patient. In some embodiments, the COCA subtype is selected from C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM and C28 THCA.

[0185] The present disclosure provides methods for predicting nodal metastasis for a cancer patient. In some embodiments, the prediction of nodal metastasis can involve obtaining a tumor sample for a patient. In some embodiments, the patients can have various stages of cancers. In some embodiments, the nodal metastasis can be determined by detecting the expression level of at least one subtype classifier from a pan-cancer gene set. The pan-cancer gene set can be a publically available pan-cancer database or a gene set provided herein (e.g. Table 1) or a combination thereof. The publically available pan-cancer gene set can be a TCGA pan-cancer gene set. In one embodiment, nodal metastasis of cancer can be determined by detecting the expression level of all the subtype classifiers or subsets thereof of the classifiers found in Table 1.

[0186] In some embodiments, the C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM or C28 THCA COCA subtype can be more likely to be associated with nodal metastasis compared with other subtypes. In some embodiments, the C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM or C28 THCA COCA subtype can be most likely associated with positive lymph node metastasis compared with other subtypes. In some embodiments, the C1 ACC/PCPG, C2 GBM/LGG, C3 OV, C4 Squamous-like, C6 LUAD-Enriched, C8 PAAD/some STAD, C9 UCS, C10 BRCA/Basal, C12 UCEC, C14 PRAD, C15 CESC (subset of cervical), C16 BLCA, C17 TGCT, C19 COAD/READ, C20 SARC/MESO, C21 KIRK/KICH/KIRP, C22 Liver, C24 BRCA/Luminal, C25 THYM, C26 SKCM/UVM or C28 THCA COCA subtype can be at least about 0.1 times, at least about 0.2 times, at least about 0.3 times, at least about 0.4 times, at least about 0.5 times, at least about 0.6 times, at least about 0.7 times, at least about 0.8 times, at least about 0.9 times, at least about 1 time, at least about 1.2 times, at least about 1.5 times, at least about 1.7 times, at least about 2.0 times, at least about 2.2 times, at least about 2.5 times, at least about 2.7 times, at least about 3.0 times, at least about 3.2 times, at least about 3.5 times, at least about 3.7 times, at least about 4.0 times, at least about 4.2 times, at least about 4.5 times, at least about 4.7 times, at least about 5.0 times, inclusive of all ranges and subranges therebetween, more likely to have occult nodal metastasis compared to other COCA subtypes.

Detection Methods

[0187] In one embodiment, the methods and compositions provided herein allow for the detection of at least one biomarker in a tumor sample obtained from a subject. The at least one biomarker can be a classifier biomarker provided herein. The detection can be at the nucleic acid level or protein level. In one embodiment, the detection is at the nucleic acid level and the detection can be by using any amplification, hybridization and/or sequencing assay disclosed herein. In one embodiment, the at least one biomarker detected using the methods and compositions provided herein is selected from Table 1. Further to the above embodiment, the detection of the at least one biomarker selected from Table 1 is at the nucleic acid level. In one embodiment, the methods of detecting the biomarker(s) (e.g., classifier biomarkers) in the tumor sample obtained from the subject comprises, consists essentially of, or consists of measuring the expression level of at least one or a plurality of biomarkers using any of the methods provided herein. The biomarkers can be selected from Table 1. In one embodiment, the plurality of biomarker nucleic acids comprises, consists essentially of or consists of at least 4 biomarkers, at least 8 biomarkers, at least 12 biomarkers, at least 16 biomarkers, at least 20 biomarkers, at least 24 biomarkers, at least 28 biomarkers, at least 32 biomarkers, at least 36 biomarkers, at least 40 biomarkers, at least 44 biomarkers, at least 48 biomarkers, at least 52 biomarkers, at least 56 biomarkers, at least 60 biomarkers, at least 64 biomarkers, at least 68 biomarkers, at least 72 biomarkers, at least 76 biomarkers, at least 80 biomarkers or all 84 biomarkers of Table 1. In another embodiment, the plurality of biomarkers comprises, consists essentially of or consists of at least 8 biomarkers, at least 16 biomarkers, at least 24 biomarkers, at least 32 biomarkers, at least 40 biomarkers, at least 48 biomarkers, at least 56 biomarkers, at least 64 biomarkers, at least 72 biomarkers, at least 80 biomarkers or all 84 biomarkers of Table 1.

[0188] In another embodiment, the methods and compositions provided herein allow for the detection of at least one or a plurality of biomarkers selected from the biomarkers listed in Table 1 in combination with the detection of at least one or a plurality of biomarkers from one or more additional sets of biomarkers in a tumor sample obtained from a subject. The tumor sample can be any type of sample provided herein. The subject can be suffering from or suspected of suffering from cancer. The cancer can be any type of cancer provided herein. The detection can be at the nucleic acid level or protein level. In one embodiment, the detection is at the nucleic acid level and the detection can be by using any amplification, hybridization and/or sequencing assay disclosed herein. The one or more additional sets of biomarkers can be selected from a set of biomarkers whose presence, absence and/or level of expression is indicative of immune activation, proliferation, a tissue of origin cancer subtype, or any combination thereof. The additional set of biomarkers for indicating immune activation can be gene expression signatures of and/or Adaptive Immune Cells (AIC) and/or Innate immune Cells (IIC), individual immune biomarkers, interferon genes, major histocompatibility complex, class II (MHC II) genes or a combination thereof. The gene expression signatures of both IIC and AIC can be any gene signatures known in the art such as, for example, the gene signatures listed in Thorsson, V. et al., 2018, The immune landscape of cancer. Immunity, 48(4), pp. 812-830, Bindea et al. (Immunity 2013; 39(4); 782-795), Faruki H. et al., JTO, 12(6): 943-953 (2017), Charoentong P. et al., Cell reports, 18, 248-262 (2017) or WO2017/201165 and WO2017/201164, each of which is herein incorporated by reference in their entirety. The additional set of biomarkers for indicating proliferation can be gene expression signatures that include the 11 gene signature comprising BIRC5, CCNB1, CDC20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS, and UBE2C found in Martin M. et al., Breast Cancer Res Treat, 138: 457-466 (2013), the 18 gene signature found in US 20160115551 and/or the 26 gene signature found in 62/789,668 filed Jan. 8, 2019. The additional set of biomarkers for determining tissue of origin cancer subtypes can be any gene signature found in the art for subtyping specific tissue of origin cancers. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is the adenocarcinoma lung cancer subtyping gene expression signatures found in WO2017/201165, US20170114416 or U.S. Pat. No. 8,822,153. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is the squamous cell carcinoma lung cancer subtyping gene expression signatures found in WO2017/201164, US20170114416 or U.S. Pat. No. 8,822,153. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is the breast cancer subtyping gene expression signatures found in Parker J S et al., (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160-1167, which is herein incorporated by reference in its entirety. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is the bladder cancer subtyping gene expression signatures found in 62/629,975 filed Feb. 13, 2018. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is the bladder cancer subtyping gene expression signatures found in The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature volume 507, pages 315-322 (2014), or Robertson, A G, et al., Cell, 171(3): 540-556 (2017), each of which is herein incorporated by reference. In one embodiment, the additional set of biomarkers for determining tissue of origin cancer subtypes is a head and neck squamous cell carcinoma (HNSCC) subtyping gene expression signatures selected from PCT/US18/45522 or PCT/US18/48862. Further to any of the above embodiments, the methods and compositions provided herein further comprise determining tumor mutation burden (TMB) and/or TMB rate of the tumor sample. The TMB and/or TMB rate can be determined or calculated using any method known in the art. In one embodiment, the TMB and/or TMB rate is determined from RNA as described in 62/743,257 filed on Oct. 9, 2018 and 62/771,702 filed on Nov. 27, 2018.

Kits

[0189] Kits for practicing the methods provided herein can be further provided. By "kit" can encompass any manufacture (e.g., a package or a container) comprising at least one reagent, e.g., an antibody, a nucleic acid probe or primer, etc., for specifically detecting the expression of a biomarker provided herein. The kit may be promoted, distributed, or sold as a unit for performing the methods provided herein. Additionally, the kits may contain a package insert describing the kit and methods for its use.

[0190] In one embodiment, kits for practicing the methods provided herein are provided. Such kits are compatible with both manual and automated immunocytochemistry techniques (e.g., cell staining). These kits comprise at least one antibody directed to a biomarker of interest, chemicals for the detection of antibody binding to the biomarker, a counterstain, and, optionally, a bluing agent to facilitate identification of positive staining cells. Any chemicals that detect antigen-antibody binding may be used in the practice of the methods provided herein. The kits may comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, or more antibodies for use in the methods provided herein.

[0191] In one embodiment, the kits for practicing the methods provided herein comprise at least one primer pair directed to a biomarker of interest, chemicals for the detection of amplification of the biomarker of interest, and, optionally, any agent necessary for quantifying the detection level of the biomarker of interest. Any chemicals that detect amplification products may be used in the practice of the methods provided herein. The kits may comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, or more primer pairs for use in the methods provided herein.

[0192] In one embodiment, the kits for practicing the methods provided herein comprise at least one probe directed to a biomarker of interest, chemicals for the detection of hybridization of the probe to the biomarker of interest, and, optionally, any agent necessary for quantifying the level of the biomarker of interest. Any chemicals that detect hybridization products may be used in the practice of the methods provided herein. The kits may comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, or more probes for use in the methods provided herein.

EXAMPLES

[0193] The present invention is further illustrated by reference to the following Examples. However, it should be noted that these Examples, like the embodiments described above, are illustrative and are not to be construed as restricting the scope of the invention in any way.

Example 1--Development and Validation of the 84-Gene Pan Cancer Subtyping Signature

Background

[0194] Recent genomic analyses of pathologically-defined tumor types has identified disease subtypes within a tissue. The extent to which genomic signatures are shared across tumorous tissues remains unclear.

[0195] Provided within this example is the development and validation of an 84-gene gene signature that can be used in a method for classifying a tumor sample obtained from a patient as one of 21 possible integrated, pan-cancer cluster of cluster assignment (COCA) subtypes, thereby providing valuable insight into tumor biology and potential therapeutic response. The 21 COCA subtypes that can be determined using the gene signature developed herein alone are listed in FIG. 1 and are designated as C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA)).

Objective

[0196] This example was initiated to address the need for an efficient method for improved tumor classification based on cell-of-origin that could inform prognosis, drug response and patient management based on underlying genomic and biologic tumor characteristics. Using the data associated with the 2018 TCGA Pan-cancer publications (https://gdc.cancer.gov/about-data/publications/pancanatlas) and comparing to the multi-platform cluster of cluster assignment (COCA) analysis performed in Hoadley et al, Cell. 2018 Apr. 5; 173(2):291-304 (hereinafter referred to as the "Gold Standard" for COCA subtyping) a pan-cancer COCA subtyping signature was developed. The gene signature developed in this example can be used in diagnostic methods that include evaluation of gene expression subtypes and application of an algorithm for categorization of a tumor sample obtained from a subject into one of 21 COCA subtypes C1 (ACC/PCPG), C2 (GBM/LGG), C3 (OV), C4 (Squamous-like), C6 (LUAD-Enriched), C8 (PAAD/some STAD), C9 (UCS), C10 (BRCA/Basal), C12 (UCEC), C14 (PRAD), C15 (CESC (subset of cervical)), C16 (BLCA), C17 (TGCT), C19 (COAD/READ), C20 (SARC/MESO), C21 (KIRK/KICH/KIRP), C22 (Liver), C24 (BRCA/Luminal), C25 (THYM), C26 (SKCM/UVM) and C28 (THCA))).

Methods/Results

[0197] To develop the aforementioned pan-cancer, COCA subtyper, data associated with the 2018 TCGA Pan-cancer publications (https://gdc.cancer.gov/about-data/publications/pancanatlas) was downloaded. In particular, the expression data from primary solid tumor samples (n=8545; primary solid tumor per TCGA barcode) that had expression data from the "EBPlusPlusAdjustPANCAN_IlluminaHiSeq_RNASeqV2" platform (i.e., EBPlusPlusAdjustPANCAN_IlluminaHiSeq_RNASeqV@-v2.geneExp.tsv) from the TCGA dataset was used, as were the merged sample quality annotations (i.e., merged_sample_quality_annotations.tsv). Data from "do_not_use=False" specified in the sample quality file (merged_sample_quality_annotations.tsv) as well as data from samples from the pilot study (designated tumor type="FFFP") were excluded. The 8545 samples were from 32 tumor types. The 32 tumor types were kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); and Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC).

[0198] The COCA subtypes (i.e., COCA_Sample_Assignment_n9759.csv) from Hoadley et al, (Cell. 2018 Apr. 5; 173(2):291-304) were then assigned to the 8545 samples from the TCGA data described above, excluding COCA subtypes with 30 or fewer samples. FIG. 1 shows the cross-tabulation of the TCGA tumor type and COCA subtype from the Hoadley et al, 2018 paper for samples with qualifying expression data as described herein. FIG. 1 also provides the integrated COCA subtypes and their designations as provided herein.

[0199] To develop the reduced and clinically applicable pan cancer COCA subtyper, the 8545 samples from the TCGA dataset described above (and the RNA-seq expression data associated therewith) were divided into a training set (2/3 of the data set; n=5696) and a test set (1/3 of the data set; n=2849), balancing for uniform tumor type of origin distributions (see the Table in FIG. 2). Gene expression values were log 2 transformed and genes with low variance and/or low mean were filtered out, while genes with mean variance and mean expression values greater than 4 were kept resulting in gene expression data for 2190 genes (see graph in FIG. 2). It should be noted that samples that were found to have a COCA subtype 5 (C5; n=41) using the gold standard COCA subtyper described in Hoadley et al, 2018 were excluded from the training set due to the presence of a small number of samples that were not well differentiated by gene expression. As a result, the training set subsequently used to generate the COCA subtyper via cross-validation and classification to the nearest centroid (ClaNC (Dabney, 2006)) had an n of 5655 samples.

[0200] As mentioned, a Classification to Nearest Centroid (CLaNC) algorithm (see Alan R. Dabney; ClaNC: point-and-click software for classifying microarrays to nearest centroids, Bioinformatics, Volume 22, Issue 1, 1 Jan. 2006, Pages 122-123) was applied to the gene expression data from the training set (n=5655) in order to choose different numbers of genes per subtype (see. FIG. 3) that were subsequently tested using 5-fold cross-validation (CV) to find the minimum number of genes that would be required to provide differentiation of the aforementioned COCA subtypes with sufficient agreement with the previously developed gold standard (i.e., COCA analysis on multiplatform `omic` data as described in Hoadley et al, 2018). As shown in FIG. 3, said 5-fold cross validation suggested that 4 genes per subtype for a total of 84 genes (i.e., for the 21 COCA subtypes described herein) would achieve sufficient agreement between the classifier prediction and COCA subtype as determined using the gold standard method from Hoadley et al. 2018.

[0201] Regarding selection of the final 84 genes (i.e., 4 genes/COCA subtype) to be included in the 21 class COCA subtyper, the ClaNC software package (see Dabney, 2006) used on the entire training set calculated t-statistics and 84 genes were selected based on the ranks of the strongest t-statistics (i.e., both negatively and positively correlated genes for each COCA subtype can be and were selected) (see Table 1). Then an ordinary nearest centroid classifier was fit using the 21 COCA classes and 84 genes.

[0202] Validation of the reduced gene signature was performed by applying the 84-gene nearest centroid classifier of Table 1 to the test set (n=2849) and comparing the COCA subtypes as determined by the gold standard vs. the 84-gene classifier or signature (i.e., Table 1). As shown in FIG. 4, the test set showed an overall agreement of 90%, which was similar to the agreement with COCA GS subtyping of 91% for the training set. FIG. 5 showed that the 84 gene nearest centroid classifier called a vast majority of the COCA subtypes in the test set correctly.

Conclusion

[0203] Development and validation of an 84-gene signature for COCA subtyping was described. The resulting 84 gene signature maintains high concordance rates with the gold standard COCA subtyper as described in the art.

[0204] Subtypes provide potential biomarkers for targeted and immunotherapy response. The data demonstrate that differences in prognosis that may be meaningful to therapeutic management.

Example 2--Examination Use of COCA Subtype Signature as a Prognostic Indicator

Objective

[0205] This example describes the examination of the 84 gene COCA subtyper developed in Example 1 and found in Table 1 as a prognostic indicator for overall survival. Overall, the goal of the studies in this example was to determine if the 84-gene COCA signature has prognostic value across a myriad of tumor types.

Methods and Results

[0206] In order to determine if the 84 gene signature of Table 1 has prognostic utility, associations between overall survival and the 84 gene COCA signature were examined within specific tumor types (i.e., BLCA, BRCA and STAD). Associations between overall survival and the 84 gene signature were examined separately within tumor type by fitting cox models adjusted for age at diagnosis and stage with overall survival the outcome and classifier subtype as the predictor, reporting hazard ratios for classifier subtype, and testing (Wald's test) whether the coefficient for classifier subtype was different from zero. It should be noted that the association tests used only subtype categories having many samples. For example, BLCA tumors were classified into 8 predicted subtype categories (C10, C15, C16, C20, C25, C4, C8, C9; see FIG. 6) but 92% (345/375) were in two of them (C16 and C4), and only these categories were analyzed.

[0207] As shown in FIGS. 6-8, specific COCA subtypes can be associated with overall survival. For example, as shown in FIG. 6, the C4 COCA subtype was significantly associated with worse overall survival in BLCA (association test p-value for C4 subtype as determined using Table 1 gene signature was 0.0204, while the Hazard ratio was 1.53 (i.e., second column); FIG. 6), while the C8 COCA subtype in STAD (association test p-value for C8 subtype as determined using Table 1 gene signature was 0.00689, while the Hazard ratio was 1.67; FIG. 8) samples was also associated with worse overall survival. In contrast, the C24 COCA subtype in the BRCA sample had better overall survival (association test p-value was 0.00013, while the Hazard ratio was 0.37; FIG. 7).

INCORPORATION BY REFERENCE

[0208] The following references are incorporated by reference in their entireties for all purposes. [0209] Hoadley, Katherine A., Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen et al. "Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer." Cell173, no. 2 (2018): 291-304. [0210] Hoadley, Katherine A., Christina Yau, Denise M. Wolf, Andrew D. Cherniack, David Tamborero, Sam Ng, Max D M Leiserson et al. "Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin." Cell 158, no. 4 (2014): 929-944. [0211] Alan R. Dabney; ClaNC: point-and-click software for classifying microarrays to nearest centroids, Bioinformatics, Volume 22, Issue 1, 1 Jan. 2006, Pages 122-123.. [0212] Alan R. Dabney; Classification of microarrays to nearest centroids, Bioinformatics, Volume 21, Issue 22, 15 Nov. 2005, Pages 4148-4154.

Further Numbered Embodiments of the Disclosure

[0213] Other subject matter contemplated by the present disclosure is set out in the following numbered embodiments:

[0214] 1. A method for determining a clustering of cluster assignments (COCA) subtype of a tumor cancer sample obtained from a patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1, wherein the detection of the expression level of the classifier biomarker specifically identifies a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype.

[0215] 2. The method of embodiment 1, wherein the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step.

[0216] 3. The method of embodiment 2, wherein the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm.

[0217] 4. The method of any one of embodiments 1-3, wherein the C1 COCA subtype indicates that a tumor sample is substantially similar to or is adenocortical carcinoma; the C2 COCA subtype indicates that a tumor sample is substantially similar to or is glioblastoma; the C3 COCA subtype indicates that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer); the C4 COCA subtype indicates that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder; the C6 COCA subtype indicates that a tumor sample is substantially similar to or is lung adenocarcinoma; the C8 COCA subtype indicates that a tumor sample is substantially similar to or is pancreatic adenocarcinoma; the C9 COCA subtype indicates that a tumor sample is substantially similar to or is uterine carcinosarcoma; the C10 COCA subtype indicates that a tumor sample is substantially similar to or is the basal subtype of breast cancer; the C12 COCA subtype indicates that a tumor sample is substantially similar to or is uterine corpus endometrial cancer; the C14 COCA subtype indicates that a tumor sample is substantially similar to or is prostate cancer; the C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer; the C16 COCA subtype indicates that a tumor sample is substantially similar to or is a bladder urothelial carcinoma; the C17 COCA subtype indicates that a tumor sample is substantially similar to or is a testicular germ cell tumor; the C19 COCA subtype indicates that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma; the C20 COCA subtype indicates that a tumor sample is substantially similar to or is a sarcoma; the C21 COCA subtype indicates that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma; the C22 COCA subtype indicates that a tumor sample is substantially similar to or is liver hepatocellular carcinoma; the C24 COCA subtype indicates that a tumor sample is substantially similar to or is the luminal subtype of breast cancer; the C25 COCA subtype indicates that a tumor sample is substantially similar to or is thymoma; the C26 COCA subtype indicates that a tumor sample is substantially similar to or is melanoma; or the C28 COCA subtype indicates that a tumor sample is substantially similar to or is thyroid cancer.

[0218] 5. The method of any one of embodiments 1-4, wherein the expression level of the classifier biomarker is detected at the nucleic acid level.

[0219] 6. The method of embodiment 5, wherein the nucleic acid level is RNA or cDNA.

[0220] 7. The method embodiment 5 or 6, wherein the detecting an expression level comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

[0221] 8. The method of embodiment 7, wherein the expression level is detected by performing RNAseq.

[0222] 9. The method of embodiment 8, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1.

[0223] 10. The method of any one of embodiments 1-9, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, a fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

[0224] 11. The method of embodiment 10, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

[0225] 12. The method of any one embodiments 1-11, wherein the at least one classifier biomarker comprises a plurality of classifier biomarkers.

[0226] 13. The method of embodiment 12, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 4 classifier biomarkers, at least 6 classifier biomarkers, at least 8 classifier biomarkers, at least 10 classifier biomarkers, at least 12 classifier biomarkers, at least 14 classifier biomarkers, at least 16 classifier biomarkers, at least 18 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

[0227] 14. The method of any one of embodiments 1-13, wherein the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.

[0228] 15. A method of detecting a biomarker in a tumor sample obtained from a patient, the method comprising measuring the expression level of a plurality of classifier biomarker nucleic acids selected from Table 1 using an amplification, hybridization and/or sequencing assay.

[0229] 16. The method of embodiment 15, wherein the patient is suffering from or is suspected of suffering from kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); or Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC).

[0230] 17. The method of embodiment 15 or 16, wherein the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

[0231] 18. The method of embodiment 17, wherein the expression level is detected by performing RNAseq.

[0232] 19. The method of embodiment 18, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers per each of the plurality of biomarker nucleic acids selected from Table 1.

[0233] 20. The method of any one of embodiments 15-19, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

[0234] 21. The method of embodiment 20, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

[0235] 22. The method of any one of embodiments 15-21, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

[0236] 23. The method of any one of embodiments 15-22, wherein the plurality of biomarker nucleic acids comprises, consists essentially of or consists of all the classifier biomarker nucleic acids of Table 1.

[0237] 24. A method of treating cancer in a subject, the method comprising:

measuring the expression level of at least one biomarker nucleic acid in a tumor sample obtained from the subject, wherein the at least one biomarker nucleic acid is selected from a set of biomarkers listed in Table 1, wherein the presence, absence and/or level of the at least one biomarker indicates a COCA subtype of the cancer; and administering a therapeutic agent based on the COCA subtype of the cancer.

[0238] 25. The method of embodiment 24, wherein the at least one biomarker nucleic acid selected from the set of biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

[0239] 26. The method of embodiment 24 or 25, further comprising measuring the expression of at least one biomarker from an additional set of biomarkers.

[0240] 27. The method of embodiment 26, wherein the additional set of biomarkers comprises at least an immune cell signature, a cell proliferation signature, or drug target genes.

[0241] 28. The method of any one of embodiments 24-27, wherein the measuring the expression level is conducted using an amplification, hybridization and/or sequencing assay.

[0242] 29. The method of embodiment 28, wherein the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

[0243] 30. The method of embodiment 29, wherein the expression level is detected by performing RNAseq.

[0244] 31. The method of any one of embodiments 24-30, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

[0245] 32. The method of embodiment 31, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

[0246] 33. The method of any one of embodiments 24-32, wherein the subject's COCA subtype is selected from C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28.

[0247] 34. The method of embodiment 33, wherein the C1 COCA subtype indicates that a tumor sample is substantially similar to or is adenocortical carcinoma; the C2 COCA subtype indicates that a tumor sample is substantially similar to or is glioblastoma; the C3 COCA subtype indicates that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer); the C4 COCA subtype indicates that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder; the C6 COCA subtype indicates that a tumor sample is substantially similar to or is lung adenocarcinoma; the C8 COCA subtype indicates that a tumor sample is substantially similar to or is pancreatic adenocarcinoma; the C9 COCA subtype indicates that a tumor sample is substantially similar to or is uterine carcinosarcoma; the C10 COCA subtype indicates that a tumor sample is substantially similar to or is the basal subtype of breast cancer; the C12 COCA subtype indicates that a tumor sample is substantially similar to or is uterine corpus endometrial cancer; the C14 COCA subtype indicates that a tumor sample is substantially similar to or is prostate cancer; the C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer; the C16 COCA subtype indicates that a tumor sample is substantially similar to or is a bladder urothelial carcinoma; the C17 COCA subtype indicates that a tumor sample is substantially similar to or is a testicular germ cell tumor; the C19 COCA subtype indicates that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma; the C20 COCA subtype indicates that a tumor sample is substantially similar to or is a sarcoma; the C21 COCA subtype indicates that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma; the C22 COCA subtype indicates that a tumor sample is substantially similar to or is liver hepatocellular carcinoma; the C24 COCA subtype indicates that a tumor sample is substantially similar to or is the luminal subtype of breast cancer; the C25 COCA subtype indicates that a tumor sample is substantially similar to or is thymoma; the C26 COCA subtype indicates that a tumor sample is substantially similar to or is melanoma; or the C28 COCA subtype indicates that a tumor sample is substantially similar to or is thyroid cancer.

[0248] 35. A method of predicting overall survival in a cancer patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1 in a tumor sample obtained from a patient, wherein the detection of the expression level of the at least one classifier biomarker specifically identifies a COCA subtype, and wherein identification of the COCA subtype is predictive of the overall survival in the patient.

[0249] 36. The method of embodiment 35, wherein the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step.

[0250] 37. The method of embodiment 36, wherein the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm.

[0251] 38. The method of any one of the embodiments 35-37, wherein the expression level of the classifier biomarker is detected at the nucleic acid level.

[0252] 39. The method of embodiment 38, wherein the nucleic acid level is RNA or cDNA.

[0253] 40. The method of any one of embodiments 35-39, wherein the detecting an expression level comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

[0254] 41. The method of embodiment 40, wherein the expression level is detected by performing RNAseq.

[0255] 42. The method of embodiment 35, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1.

[0256] 43. The method of any one of embodiments 35-42, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

[0257] 44. The method of embodiment 43, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

[0258] 45. The method of any one of embodiments 35-44, wherein the at least one classifier biomarker comprises a plurality of classifier biomarkers.

[0259] 46. The method of embodiment 45, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

[0260] 47. The method of any one of embodiments 35-46, wherein the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.

[0261] The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent application, foreign patents, foreign patent application and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, application and publications to provide yet further embodiments.

[0262] These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Sequence CWU 1

1

8411766DNAHomo sapiens 1gggcctcatt gctgcagacg ctcaccccag acactcactg caccggagtg agcgcgacca 60tcatgtccat gctcgtggtc tttctcttgc tgtggggtgt cacctggggc ccagtgacag 120aagcagccat attttatgag acgcagccca gcctgtgggc agagtccgaa tcactgctga 180aacccttggc caatgtgacg ctgacgtgcc aggcccacct ggagactcca gacttccagc 240tgttcaagaa tggggtggcc caggagcctg tgcaccttga ctcacctgcc atcaagcacc 300agttcctgct gacgggtgac acccagggcc gctaccgctg ccgctcgggc ttgtccacag 360gatggaccca gctgagcaag ctcctggagc tgacagggcc aaagtccttg cctgctccct 420ggctctcgat ggcgccagtg tcctggatca cccccggcct gaaaacaaca gcagtgtgcc 480gaggtgtgct gcggggtgtg acttttctgc tgaggcggga gggcgaccat gagtttctgg 540aggtgcctga ggcccaggag gatgtggagg ccacctttcc agtccatcag cctggcaact 600acagctgcag ctaccggacc gatggggaag gcgccctctc tgagcccagc gctactgtga 660ccattgagga gctcgctgca ccaccaccgc ctgtgctgat gcaccatgga gagtcctccc 720aggtcctgca ccctggcaac aaggtgaccc tcacctgcgt ggctcccctg agtggagtgg 780acttccagct acggcgcggg gagaaagagc tgctggtacc caggagcagc accagcccag 840atcgcatctt ctttcacctg aacgcggtgg ccctggggga tggaggtcac tacacctgcc 900gctaccggct gcatgacaac caaaacggct ggtccgggga cagcgcgccg gtcgagctga 960ttctgagcga tgagacgctg cccgcgccgg agttctcccc ggagccggag tccggcaggg 1020ccttgcggct gcggtgcctg gcgcccctgg agggcgcgcg cttcgccctg gtgcgcgagg 1080acaggggcgg gcgccgcgtg caccgtttcc agagccccgc tgggaccgag gcgctcttcg 1140agctgcacaa catttccgtg gctgactccg ccaactacag ctgcgtctac gtggacctga 1200agccgccttt cgggggctcc gcgcccagcg agcgcttgga gctgcacgtg gacggacccc 1260ctcccaggcc tcagctccgg gcgacgtgga gtggggcggt cctggcgggc cgagatgccg 1320tcctgcgctg cgagggaccc atccccgacg tcaccttcga gctgctgcgc gagggcgaga 1380cgaaggccgt gaagacggtc cgcacccccg gggccgcggc gaacctcgag ctgatcttcg 1440tggggcccca gcacgccggc aactacaggt gccgctaccg ctcctgggtg ccccacacct 1500tcgaatcgga gctcagcgac cctgtggagc tcctggtggc agaaagctga tgcagccgcg 1560ggcccagggt gctgttggtg tcctcagaag tgccggggat tctggactgg ctccctcccc 1620tcctgttgca gcacaaggcc ggggtctctg gggggctgga gaagcctccc tcattcctcc 1680caggaattaa taaatgtgaa gagaggctct gtttaaaatg tctttggact cccagggctg 1740agtgggctgg gatctcgtgt cctcaa 176623174DNAHomo sapiens 2gaagtggtag cagttcctcc taactcctgc cagaaacagc tctcctcaac atgagagctg 60cacccctcct cctggccagg gcagcaagcc ttagccttgg cttcttgttt ctgctttttt 120tctggctaga ccgaagtgta ctagccaagg agttgaagtt tgtgactttg gtgtttcggc 180atggagaccg aagtcccatt gacacctttc ccactgaccc cataaaggaa tcctcatggc 240cacaaggatt tggccaactc acccagctgg gcatggagca gcattatgaa cttggagagt 300atataagaaa gagatataga aaattcttga atgagtccta taaacatgaa caggtttata 360ttcgaagcac agacgttgac cggactttga tgagtgctat gacaaacctg gcagccctgt 420ttcccccaga aggtgtcagc atctggaatc ctatcctact ctggcagccc atcccggtgc 480acacagttcc tctttctgaa gatcagttgc tatacctgcc tttcaggaac tgccctcgtt 540ttcaagaact tgagagtgag actttgaaat cagaggaatt ccagaagagg ctgcaccctt 600ataaggattt tatagctacc ttgggaaaac tttcaggatt acatggccag gacctttttg 660gaatttggag taaagtctac gaccctttat attgtgagag tgttcacaat ttcactttac 720cctcctgggc cactgaggac accatgacta agttgagaga attgtcagaa ttgtccctcc 780tgtccctcta tggaattcac aagcagaaag agaaatctag gctccaaggg ggtgtcctgg 840tcaatgaaat cctcaatcac atgaagagag caactcagat accaagctac aaaaaactca 900tcatgtattc tgcgcatgac actactgtga gtggcctaca gatggcgcta gatgtttaca 960acggactcct tcctccctat gcttcttgcc acttgacgga attgtacttt gagaaggggg 1020agtactttgt ggagatgtac tatcggaatg agacgcagca cgagccgtat cccctcatgc 1080tacctggctg cagccccagc tgtcctctgg agaggtttgc tgagctggtt ggccctgtga 1140tccctcaaga ctggtccacg gagtgtatga ccacaaacag ccatcaaggt actgaagaca 1200gtacagatta gtgtgcacag agatctctgt agaaggagta gctgcccttt ctcagggcag 1260atgatgcttt gagaacatac tttggccatt acccccagct ttgaggaaaa tgggctttgg 1320atgattattt tatgttttag ggacccccaa cctcaggcaa ttcctacctc ttcacctgac 1380cctgccccca cttgccataa aacttagcta agttttgttt tgtttttcag cgttaatgta 1440aaggggcagc agtgccaaaa tataatcaga gataaagctt aggtcaaagt tcatagagtt 1500cccatgaact atatgactgg ccacacagga tcttttgtat ttaaggattc tgagattttg 1560cttgagcagg attagataag gctgttcttt aaatgtctga aatggaacag atttcaaaaa 1620aaaaccccac aatctaggat gggaacaagg aaggaaagat gtgaataggc tgatgggcaa 1680aaaaccaatt tacccatcag ttccagcctt ctctcaagga gaggcaaaga aaggagatac 1740agtggagaca tctggaaagt tttctccact ggaaaactgc tactatctgt ttttatattt 1800ctgttaaaat atatgaggct acagaactaa aaattaaaac ctctttgtgt cccttggtcc 1860tggaacattt atgttccttt taaagaaaca aaaatcaaac tttacagaaa gatttgatgt 1920atgtaataca tatagcagct cttgaagtat atatatcata gcaaataagt catctgatga 1980gaacaagcta tttgggcaca acacatcagg aaagagagca ccacgtgatg gagtttctct 2040agaagctcca gtgataagag atgttgactc taaagttgat ttaaggccag gcatggtggt 2100ttacgcctat aatcccagca ttttgggagt ccgaggtggg cagatcactt gagctcagga 2160ggtcaagatc agcctgggca acatggtgaa acctggtctc tacataaaat acaaaaactt 2220agatgggcat ggtggtgtgt gcctatagtc ccactacttg tggggctaag gcaggaggat 2280cacttgagcc ccggaggtcg aggctacagt gagccaagag tgcactactg tactccagcc 2340agggcaagag agcgagaccc tgtctcaata aataaataaa taaataaata aataaataaa 2400taaataaata aaaacaaagt tgattaagaa aggaagtata ggccaggcac agtggctcac 2460acctgtaatc cttgcatttt ggaaggctga ggcaggagga tcactttagg cctggtgtgt 2520tcaagaccag cctggtcaac atagtgagac actgtctcta ccaaaaaaag gaaggaaggg 2580acacatatca aactgaaaca aaattagaaa tgtaattatg ttctaagtgc ctccaagttc 2640aaaacttatt ggaatgttga gagtgtggtt acgaaatacg ttaggaggac aaaaggaatg 2700tgtaagtctt taatgccgat atcttcagaa aacctaagca aacttacagg tcctgctgaa 2760actgcccact ctgcaagaag aaatcatgat atagctttgc catgtggcag atctacatgt 2820ctagagaaca ctgtgctcta ttaccattat ggataaagat gagatggttt ctagagatgg 2880tttctactgg ctgccagaat ctagagcaaa gccatccccg ctcctggttg gtcacagaat 2940gactgacaaa gacatcgatt gatatgcttc tttgtgttat ttccctccca agtaaatgtt 3000tgtccttggg tccattttct atgcttgtaa ctgtcttcta gcagtgagcc aaatgtaaaa 3060tagtgaataa agtcattatt aggaagttca aaagcattgc ttttataatg aacttagaaa 3120aacgtatgtg tgtgtgttta attagaataa aattcctcta ggcagatttc agga 317439958DNAHomo sapiens 3acgctgcagg agctgaagat ggcgagctcc gtggcgccct acgagcagct ggtgaggcag 60gtggaggcct tgaaggctga gaacagccac ctgaggcagg agctaaggga caactccagc 120cacctgtcca agctggagac agagacgtcg ggcatgaagg aggtcctgaa gcacctacag 180ggaaaactgg agcaggaggc ccgagtgctg gtgtcctcgg ggcagacgga ggtgctggag 240cagctgaagg ccctacagat ggacatcacc agcctgtaca acctcaagtt ccagccgccc 300accctgggcc cggagcctgc cgcccggacc cccgagggca gcccagtaca cggctccggg 360ccctccaagg acagctttgg ggagctgagc cgggccacca tccggctgct ggaggaactg 420gaccgggaac ggtgtttcct gctgaatgag attgagaagg aggagaagga gaagctctgg 480tactactctc agctgcaggg cctgtccaag cgcctggacg agctgccgca cgtggagacg 540ttctcgatgc agatggacct gatccggcag cagcttgagt tcgaggccca gcacatccgc 600tcgctgatgg aggagcgctt cggcacctcg gacgagatgg tgcagcgggc acagatccgc 660gcctcgcgcc tggagcagat tgacaaggag ctgctggagg cgcaggaccg agtgcagcag 720acggagcccc aggccttgct ggcggtgaag tcggtgccgg tggacgagga ccccgagaca 780gaggtcccca cacaccctga ggatggcacc cctcagccgg gcaacagcaa ggtggaggtg 840gtcttctggc tgttgtccat gttggcgacg cgcgaccagg aggatacagc gcgcacgctg 900ctggccatgt ccagctcgcc cgagagctgc gtggccatgc gccgctcggg ctgtctgcct 960ctgctgctgc aaatcctcca cggcaccgag gccgcggccg ggggtcgcgc cggggcccca 1020ggggcaccgg gcgccaagga cgcacgcatg cgcgccaacg cggcgctgca caacatcgtc 1080ttctcgcagc cggaccaggg cctggcgcgc aaggagatgc gcgtcctgca cgtgctggag 1140cagatccggg cctactgcga gacctgctgg gactggctgc aggcccgaga cggcgggccc 1200gagggaggtg gcgccggcag cgccccgatc cccatcgagc cgcagatctg ccaggccacc 1260tgtgctgtta tgaagctgtc ctttgatgag gagtaccgcc gtgccatgaa cgagctaggt 1320gggctgcagg ccgtggcaga gctgctgcag gttgactatg agatgcacaa gatgacccgg 1380gacccgctga acctggcgct gcgccgctac gcgggcatga ccctcaccaa cctcaccttt 1440ggggacgttg ccaacaaggc caccctgtgt gcgcgccgcg gctgcatgga ggccatcgtg 1500gcccagctgg cctccgacag tgaggagctc caccaggtgg tgtccagcat ccttcggaac 1560ttgtcctgga gggccgacat caacagcaag aaggtgctga gggaggcggg cagcgtgact 1620gccctggtgc agtgtgtcct gcgggccacc aaggagtcca ccctgaagag cgtgctgagc 1680gccctgtgga atctgtctgc acacagcaca gagaacaagg cggccatctg ccaggtggat 1740ggcgccctgg gcttcctggt gagcaccctg acctacaagt gtcagagcaa ctcgctggcc 1800atcatcgaga gcggcggcgg catcctccgc aatgtgtcca gcctcgtcgc cacccgtgag 1860gactacaggc aggtgctccg ggatcacaac tgtctgcaga cgctgctgca gcatctgact 1920tcgcacagcc tgaccatcgt gagcaacgcg tgcggcacgc tctggaacct gtcggcccgc 1980agcgcccgtg accaggagct gctgtgggac ctgggcgccg tgggcatgct gcgtaatctg 2040gtgcactcca agcacaagat gatcgccatg ggcagcgccg ccgccctgcg caacctgctg 2100gcccatcggc ccgccaagca ccaggcggcc gccaccgccg tgtccccagg cagctgcgtg 2160cccagcctgt acgtgcgcaa gcagcgggcg ctggaggccg agctggacgc acggcacctc 2220gcgcaggcgc tggagcacct ggagaagcag ggcccgccgg cagccgaggc cgccactaag 2280aagccgctgc cgcccctgcg acacctggac ggcctggccc aagactatgc ttccgattcg 2340ggctgctttg acgacgacga tgcaccgtca tccctggctg cggccgcggc caccggggag 2400ccagccagcc ctgccgcgct gtccctcttc ctgggcagcc ccttcctgca ggggcaggcg 2460ctggctcgca ccccgcccac ccgccgaggc ggcaaggagg cagagaagga caccagtggg 2520gaggcagccg tggcggccaa ggccaaggcc aagctggcgc ttgcagtggc gcgcatcgac 2580cagctggtgg aggacatctc cgccctgcac acctcgtccg acgatagctt cagcctcagc 2640tctggagacc cgggacagga ggcgccacgg gagggccgcg cccagtcctg ctcgccatgc 2700cgcggcccgg agggcgggcg gcgagaggca ggaagccggg cgcacccgct gctgcggctc 2760aaggcggccc acgccagcct ctccaacgac agcctcaaca gcggcagtgc cagcgacggg 2820tactgcccac gcgaacatat gctgccctgc ccgctggccg cactggcttc gcgccgcgag 2880gaccccaggt gtgggcagcc tcggcccagc cggcttgacc ttgacctgcc cggctgccag 2940gccgagcccc cggcccgcga ggccacctcc gccgacgccc gcgtgcgcac catcaagctg 3000tcgcctacct atcagcacgt gccactgctt gagggtgcct caagggcggg tgcagagccc 3060ctcgcggggc ctggaatctc tccaggggcc cggaagcagg cctggctgcc ggcagaccac 3120ctgagcaagg ttcccgagaa gctggcggct gccccgctgt ctgtggccag caaggcactg 3180cagaaactgg cggcgcaaga ggggccactc tcgctgtccc gatgcagctc cctttcctcg 3240ctgtcctcgg ccggccgccc aggccccagc gagggtggtg acctggatga cagtgactcc 3300tccctggagg ggctggagga ggccggcccc agcgaggctg agctggacag cacgtggcgg 3360gcgcccgggg ccacctcgct gcccgtagcc attccggctc cccggcgtaa ccgaggccgg 3420ggcctggggg tggaagacgc cacgccgtcc agctcgtcgg agaactacgt gcaggagaca 3480ccgcttgtgc tgagccgctg cagctctgtg agctcgctgg gcagcttcga gagcccgtcc 3540atcgccagct ccatccccag tgaaccttgc agcgggcagg gcagcggcac catcagccct 3600agcgagctgc ccgacagccc cggacagacc atgcctccca gccggagcaa gacgccaccg 3660ctggcgcccg cgccacaggg tccccccgag gccacccagt tcagcctgca gtgggagagc 3720tacgtgaagc gcttcctgga catcgccgac tgccgggagc gctgccggct gccatctgag 3780ctggacgcag gcagcgtgcg ctttaccgtg gagaagccag acgagaactt ctcgtgcgcc 3840tccagcctca gcgcgctggc cttgcacgag cactacgtgc agcaggacgt ggagctgcgg 3900ctgctgccct cggcctgccc cgagcgcggc gggggcgccg ggggcgccgg cctccacttt 3960gcagggcacc ggcggcggga ggaggggccg gcgcccacgg gttctcgccc tcgcggcgcc 4020gcggaccagg agctggaact gctgcgggag tgcctgggag ccgccgtgcc tgcccggctg 4080cgcaaggtgg cctccgcgct ggtgccaggt cgccgcgcac tccccgtgcc cgtctacatg 4140ttggtgcccg ccccggcccc ggcccaggag gacgactcct gcactgactc cgcggagggc 4200acgccggtca acttctctag cgccgcctcg ctcagcgacg agacgctgca gggacccccc 4260agggaccagc ccgggggacc agcgggcagg caaagaccca ccggccgccc cacctctgcc 4320agacaggcca tggggcaccg gcacaaggcg ggaggcgccg gccgcagcgc ggagcagtct 4380cggggcgcgg gcaagaacag agcagggctg gagctgcccc tgggccggcc cccgagcgcc 4440cccgcagaca aggacggctc aaagcccggc cggacccgcg gggacggggc gctccagtcg 4500ctgtgcctca cgacgcccac tgaggaggcc gtgtactgct tctacggcaa cgactcggac 4560gaggagcccc cggcggccgc gcccacgcca acccaccggc gcacatcggc catccctcgc 4620gcttttacgc gggagcgtcc gcagggccgg aaggaggccc ctgccccgtc caaggctgca 4680ccagctgccc cgccgcccgc ccggacccag cccagcctca ttgctgacga gaccccgccc 4740tgctactccc tgagctcctc cgccagctcc ctcagcgagc ccgagccctc ggagccgccg 4800gccgtccatc cacgaggccg ggagcccgcg gtcaccaagg acccgggccc aggaggcgga 4860cgcgacagct cgcccagccc gcgggccgcg gaggagcttc tgcagcggtg catcagctcg 4920gccctgccca ggcgccggcc ccccgtgtct ggcctgcggc gccgcaagcc ccgagccacc 4980cggctggatg agcggcccgc agaggggtcc cgggaacgcg gcgaggaggc agcgggctcg 5040gaccgggcct ccgacctgga tagcgtggag tggcgcgcca tccaggaggg cgccaattca 5100attgtcacgt ggctgcacca ggcagcagct gccacgcggg aggcctcgtc cgagtccgac 5160tccatcctgt ccttcgtatc cgggctgtca gtgggatcca ccctacagcc ccccaagcac 5220aggaagggac gacaggcgga gggagaaatg ggcagtgccc ggcggccaga gaaaaggggc 5280gcagcctcag tcaagaccag cgggagcccc cgttcccctg caggccccga gaagccacgt 5340ggcacacaga agaccacgcc cggggtgcca gctgtgctcc ggggacgaac agtgatctac 5400gtccccagcc cggcaccccg tgcccagccc aaagggaccc ccggcccccg cgccacaccg 5460cggaaggtgg cgcccccttg cctggcacag cccgcggctc cagccaaagt cccgagcccc 5520gggcagcagc ggtcgcggag cctacaccgg cctgccaaga cctcggagct ggcgacgctg 5580agccagcccc ccagaagcgc cacaccgccc gcccgcctcg ccaagacccc ctcctccagc 5640tcctcccaga cctcgcccgc ctcccagccc ctgcccagaa agcgcccccc ggtcacccag 5700gctgctgggg ccctgcccgg ccccggagcc tccccggtgc ccaaaacgcc ggcgcgcacc 5760cttctggcga agcagcacaa gacgcagaga tcgcccgtgc ggatcccgtt catgcagagg 5820ccggcccggc gtgggccgcc accgctggct cgggcagtcc cggagccggg ccccaggggc 5880cgggcgggga ccgaggcggg cccgggggcg cgcgggggcc gcctgggcct ggtgcgtgtg 5940gcctcagccc tctccagcgg cagcgagtcc tccgaccgct cgggcttccg gcgacagcta 6000accttcatca aggagtcgcc gggcttgcgg cgccgccgct ccgagctgtc ctcggccgag 6060tccgcggcct ctgcccccca gggcgcctcg ccccgccgcg gccggcccgc gctgcccgcc 6120gtcttcctct gctcctcgcg ctgcgaagag ctccgagcgg caccccggca gggcccggcc 6180ccggcccggc agcggccccc cgcggcccga cccagccctg gcgagcgccc tgcccggcgc 6240accacctccg agagcccgtc ccgcctgcct gtgcgcgcgc ccgccgcccg gccggagact 6300gtcaagcgct acgcgtcgct gccgcacatc agcgtggccc gcaggcccga cggcgccgtc 6360cccgcggccc ctgcctcagc cgacgccgcg cgccgcagca gcgacgggga gccccggccg 6420ctccccaggg tggccgcgcc gggcacgacc tggcggcgca tccgagatga ggacgtgccc 6480cacatcctgc gcagcacgct tcccgccacg gccctgccac tgcggggctc cacgcccgag 6540gacgccccgg ccgggccccc gccgcgcaag accagcgacg ccgtggtcca gaccgaggag 6600gtcgccgccc ccaagaccaa ctccagcacg tccccgagcc tggagaccag ggagcccccc 6660ggggcccccg ccggcggcca gctctccctc ctcggcagcg acgtggacgg tcccagcctc 6720gccaaggctc ccatctccgc acccttcgtg cacgagggcc tgggggtcgc cgtggggggc 6780ttccccgcca gccggcacgg ctcccccagc cgctcggccc gagtaccccc cttcaactat 6840gtgcccagcc ccatggtggt cgcagccacc accgactcgg ccgcggagaa agccccggcc 6900actgcctccg ccaccctcct ggaatagtgg cctaggccgg ccttctggaa cgttctctcc 6960cggccctgcg gcgcggtctg gctgccccat gggcctgcgc tgtagacgtc ccccataggt 7020cgccccaggg cctctgccca cccgagcccc accactctca gaacccccgc ccagcgcacg 7080gcgacctcgc gcctcaccgg aagaccttgc ctctgtgccg cggaggtcca ggaggaaacg 7140gggcggccgc taggcctcaa gtcccgaccg tggagcgctg gcaagggcgt cctggcccag 7200ccctgagcgc gcggcccttc ccctgtcgga agccgttgct tgaccccggg cgagggaggc 7260ggtagcctcc gggtccgggt ctgggtctgg gtccgctgct tcgcagggac agcgctgggg 7320aggtgacggc gcccgccgca ggtggggcga ggctggggga gggcggcgcc gcggcgggcc 7380tgccagctgg gggcctttgc ggcgcgcagg ggcgaagcct gtaatcactg cagccgccgg 7440taattcgcta atgagggctt tgcagggatt gttttcattc tcagccccag ctgtgggagt 7500gcgggtgggg gtgtggccga gccccggcag gaagccccgc ccagacggtg ttcagggaac 7560ccggagccca agcgctccgg cggagcccaa aagggtgggg gtgggagggg cagaggccaa 7620cggatccccc tgcctgtcgc accccttggc gggagacggg aaggcagcgg gctgcgtacg 7680atgggaccct ggtgcagacg ccgggccggc tgacatttgg accccatccc agaggagatg 7740ctggctacca gctggggcga ccccaagggt cgctggagtc agtatcggcc cggcgcagcc 7800gcggcgggcg aggccaatgg aaaggagact gaggggagtc ccggcagtga gcccgaggcc 7860ctgggacctg gagcccgcgc tggcctctcc ccagcggagc ctgcacgtta cggagaccat 7920cacatgtggg cgtggtcagt gcccaggacc gcaccgctgc tcatcttgtc ccttttcaat 7980tcccttctgg ttcatgatgc ataaagcgct aggccctaga actccagaaa cagcacagct 8040ggggcgggga cccagccttg ccctccaccc gaggctctgg gacaaggcgg gaggttcggg 8100ggccttccgg caggtgaacg cagggctgga gagtatttgg tgccagatga ggtgaaagct 8160tatagaaggg cctgaggggc tcggctgcct catcccctgg cgggggaggc tgggagctgg 8220gcctcctgcg tggggtggga ctcgcagggg ccgggtctcc gtgactgggg caacgcctcg 8280tcctgcagag ggagccgacg acctcttttc tgcagaaaag ctccagcagg cgctgccttc 8340acccacggat ctgcccaggc tgaaggcaca cgctcaatgc cccacgtgcc ttctccagga 8400ggaacgaagc agggtttgag ggttgggtgg atggagctca gaaggaaacc ccagccccac 8460cacggatgac accatccctc ccgtcccatc cccagcatgg gcaaggccag cctttctggc 8520agaaggagct gtcctcaact cagggccgct gtgagcaaag ctgaccccag cccccacccc 8580cagttaacac tgctgcttct ctgaatgcat gtcacgctgc accccatgct ccgggcccac 8640accctgcagg acaaggagct ccagacagga cgtccataag tcaccgaggt gtgccaccca 8700gcaggtgctg gaggtgccca atgctccctc ctaggacctc gcagccaggc aaggctgtca 8760ggttgttttg ggggaagagg gggtcatgga tggctgagca gagagcgggg aaaatgcagg 8820ctgagtgggg cgacctcctg cctgccagga gccccctttc aggacacagc gggggtctca 8880cacttgctgt ccccatccat ggcccgaggg ggaacctggt ggtctcttct gagcttttgg 8940acttggggat gccaaacacg tgctcaccct cacactcgcc ccggcccgct gcgcccctaa 9000ttgccaaagg gtagggaaat ggcgaagcca gccaccaggt cgctggtgac agggccaggg 9060ttatgcagga aggtggtgcg gcattgcctt ccacatatgt aagtctctgg gcggcgccct 9120cccagctccc tgcctctgtt tccccatgtg ggccgtgggg aactcccaga gctacctctt 9180gggggagcgt ggtggcagcg atgatgggga gacgcctgga agctcacaga acttgggtct 9240ggctggctcc tgcccgtgac gccttgccca gcagcaaggt gcgcaacatg gctgccagcc 9300ccgcctccca cccccacccc gagtcctgag ctcactttcg ccttctccat cccctgccgt 9360gggggccaca gccacacctc accgcccagt ccagctgtct ccagaagggg acaggcagtc 9420cgcggtctct ggacaatcaa ctcaaggtac gcccactgca aggcctccct cccaccgcgg 9480cccctgcctg gccacctggc ctctctgcac cagggtgaca aggggtcctc gtctgccccc 9540caatgctcca gggccagtcc taaggagctg agggtctgag gacgcaggga gggtggaggt 9600gtcctgaggc tgatggacag tgaccgccac tggcccccaa catgaccaca cgtgggtgct 9660gaactcgggg cgccgtgccc accggcatgg tcctcccgag ctccgacagc attacctcac 9720ccggccccat ctgttgcccc ggtccagccc tgatggcgcg cgcctggtct gtctgattcc 9780cctagccgcc accccacgtt tctgtaccgg gtctctgcag tgttaaacgg acgtgtaaat 9840agtggtaaat agtgaaagcc tgtccttccc taaatgtaaa gccatctgtc cggcgtaagg 9900acgacaccgt cagctgtccg actcgcacac atttaataaa ctgagctctt gcattgcc 995841449DNAHomo sapiens 4aggccgccag cctcggagtg ggcgcgggac agtgcgcggc

gccccgcagc caggcccccg 60cccccgccgc atccacctcc tccgccgcct gcgacccaac gggcgccccc cgccgcggca 120gctgccgccg ggcccccgcg gccaccatga agaaggaggt gtgctccgtg gccttcctca 180aggccgtgtt cgcagagttc ttggccaccc tcatcttcgt cttctttggc ctgggctcgg 240ccctcaagtg gccgtcggcg ctgcctacca tcctgcagat cgcgctggcg tttggcctgg 300ccataggcac gctggcccag gccctgggac ccgtgagcgg cggccacatc aaccccgcca 360tcaccctggc cctcttggtg ggcaaccaga tctcgctgct ccgggctttc ttctacgtgg 420cggcccagct ggtgggcgcc attgccgggg ctggcatcct ctacggtgtg gcaccgctca 480atgcccgggg caatctggcc gtcaacgcgc tcaacaacaa cacaacgcag ggccaggcca 540tggtggtgga gctgattctg accttccagc tggcactctg catcttcgcc tccactgact 600cccgccgcac cagccctgtg ggctccccag ccctgtccat tggcctgtct gtcaccctgg 660gccaccttgt cggaatctac ttcactggct gctccatgaa cccagcccgc tcttttggcc 720ctgcggtggt catgaatcgg ttcagccccg ctcactgggt tttctgggta gggcccatcg 780tgggggcggt cctggctgcc atcctttact tctacctgct cttccccaac tccctgagcc 840tgagtgagcg tgtggccatc atcaaaggca cgtatgagcc tgacgaggac tgggaggagc 900agcgggaaga gcggaagaag accatggagc tgaccacccg ctgaccagtg tcaggcaggg 960gccagcccct cagcccctga gccaaggggg aaaagaagaa aaagtaccta acacaagctt 1020cctttttgca caaccggtcc tcttggctga ggaggaggag ctggtcaccc tggctgcaca 1080gttagagagg ggagaaggaa cccatgatgg gactcctggg gtaggggcca ggggctgggg 1140tctgctgggg acaggtctct ctgggacaga cctcagagat tgtgaatgca gtgccaagct 1200cacaggctgc aagggccagg ccagaaaagg gcgggcctgc agcctgcacc ccccaccttc 1260cccaaccctt cctcaagagc tgaagggatc ccagccccta ggtgggcaga ggcagaccct 1320ccccagagct ccttaggaag aagacagact ggttcattga atgccgcctt atttatttct 1380ggtgaggatg catgcgtggg gctgctggtg tttagagtgg gggctaccca ataaatcact 1440gatactcac 144951310DNAHomo sapiens 5acacagacac gcagacacag agacaccggg gcccagggcc ctcctatgga ccctgcccgc 60tcccctccca ttgtccacgg ctgtccgccc acccccattc tccaagcttc agccccctcc 120ttagttcggc atctgcacag cactgaagaa cctgggaatc agaccctgag accctgagca 180atcccaggtc cagcgccagc cctatcatga ccaaggagta tcaagacctt cagcatctgg 240acaatgagga gagtgaccac catcagctca gaaaagggcc acctcctccc cagcccctcc 300tgcagcgtct ctgctccgga cctcgcctcc tcctgctctc cctgggcctc agcctcctgc 360tgcttgtggt tgtctgtgtg atcggatccc aaaactccca gctgcaggag gagctgcggg 420gcctgagaga gacgttcagc aacttcacag cgagcacgga ggcccaggtc aagggcttga 480gcacccaggg aggcaatgtg ggaagaaaga tgaagtcgct agagtcccag ctggagaaac 540agcagaagga cctgagtgaa gatcactcca gcctgctgct ccacgtgaag cagttcgtgt 600ctgacctgcg gagcctgagc tgtcagatgg cggcgctcca gggcaatggc tcagaaagga 660cctgctgccc ggtcaactgg gtggagcacg agcgcagctg ctactggttc tctcgctccg 720ggaaggcctg ggctgacgcc gacaactact gccggctgga ggacgcgcac ctggtggtgg 780tcacgtcctg ggaggagcag aaatttgtcc agcaccacat aggccctgtg aacacctgga 840tgggcctcca cgaccaaaac gggccctgga agtgggtgga cgggacggac tacgagacgg 900gcttcaagaa ctggaggccg gagcagccgg acgactggta cggccacggg ctcggaggag 960gcgaggactg tgcccacttc accgacgacg gccgctggaa cgacgacgtc tgccagaggc 1020cctaccgctg ggtctgcgag acagagctgg acaaggccag ccaggagcca cctctccttt 1080aatttatttc ttcaatgcct cgacctgccg caggggtccg ggattgggaa tccgcccatc 1140tgggggcctc ttctgctttc tcgggaattt tcatctagga ttttaaggga aggggaagga 1200tagggtgatg ttccgaaggt gaggagcttg aaacccgtgg cgctttctgc agtttgcagg 1260ttatcattgt gaactttttt tttttaagag taaaaagaaa tatacctaaa 131063297DNAHomo sapiens 6ctcttccgaa tgtcctgcgg ccccagcctc tcctcacgct cgcgcagtct ccgccgcagt 60ctcagctgca gctgcaggac tgagccgtgc acccggagga gacccccgga ggaggcgaca 120aacttcgcag tgccgcgacc caaccccagc cctgggtagc ctgcagcatg gcccagctgt 180tcctgcccct gctggcagcc ctggtcctgg cccaggctcc tgcagcttta gcagatgttc 240tggaaggaga cagctcagag gaccgcgctt ttcgcgtgcg catcgcgggc gacgcgccac 300tgcagggcgt gctcggcggc gccctcacca tcccttgcca cgtccactac ctgcggccac 360cgccgagccg ccgggctgtg ctgggctctc cgcgggtcaa gtggactttc ctgtcccggg 420gccgggaggc agaggtgctg gtggcgcggg gagtgcgcgt caaggtgaac gaggcctacc 480ggttccgcgt ggcactgcct gcgtacccag cgtcgctcac cgacgtctcc ctggcgctga 540gcgagctgcg ccccaacgac tcaggtatct atcgctgtga ggtccagcac ggcatcgatg 600acagcagcga cgctgtggag gtcaaggtca aaggggtcgt ctttctctac cgagagggct 660ctgcccgcta tgctttctcc ttttctgggg cccaggaggc ctgtgcccgc attggagccc 720acatcgccac cccggagcag ctctatgccg cctaccttgg gggctatgag caatgtgatg 780ctggctggct gtcggatcag accgtgaggt atcccatcca gaccccacga gaggcctgtt 840acggagacat ggatggcttc cccggggtcc ggaactatgg tgtggtggac ccggatgacc 900tctatgatgt gtactgttat gctgaagacc taaatggaga actgttcctg ggtgaccctc 960cagagaagct gacattggag gaagcacggg cgtactgcca ggagcggggt gcagagattg 1020ccaccacggg ccaactgtat gcagcctggg atggtggcct ggaccactgc agcccagggt 1080ggctagctga tggcagtgtg cgctacccca tcgtcacacc cagccagcgc tgtggtgggg 1140gcttgcctgg tgtcaagact ctcttcctct tccccaacca gactggcttc cccaataagc 1200acagccgctt caacgtctac tgcttccgag actcggccca gccttctgcc atccctgagg 1260cctccaaccc agcctccaac ccagcctctg atggactaga ggctatcgtc acagtgacag 1320agaccctgga ggaactgcag ctgcctcagg aagccacaga gagtgaatcc cgtggggcca 1380tctactccat ccccatcatg gaggacggag gaggtggaag ctccactcca gaagacccag 1440cagaggcccc taggacgctc ctagaatttg aaacacaatc catggtaccg cccacggggt 1500tctcagaaga ggaaggtaag gcattggagg aagaagagaa atatgaagat gaagaagaga 1560aagaggagga agaagaagag gaggaggtgg aggatgaggc tctgtgggca tggcccagcg 1620agctcagcag cccgggccct gaggcctctc tccccactga gccagcagcc caggaggagt 1680cactctccca ggcgccagca agggcagtcc tgcagcctgg tgcatcacca cttcctgatg 1740gagagtcaga agcttccagg cctccaaggg tccatggacc acctactgag actctgccca 1800ctcccaggga gaggaaccta gcatccccat caccttccac tctggttgag gcaagagagg 1860tgggggaggc aactggtggt cctgagctat ctggggtccc tcgaggagag agcgaggaga 1920caggaagctc cgagggtgcc ccttccctgc ttccagccac acgggcccct gagggtacca 1980gggagctgga ggccccctct gaagataatt ctggaagaac tgccccagca gggacctcag 2040tgcaggccca gccagtgctg cccactgaca gcgccagccg aggtggagtg gccgtggtcc 2100ccgcatcagg tgactgtgtc cccagcccct gccacaatgg tgggacatgc ttggaggagg 2160aggaaggggt ccgctgccta tgtctgcctg gctatggggg ggacctgtgc gatgttggcc 2220tccgcttctg caaccccggc tgggacgcct tccagggcgc ctgctacaag cacttttcca 2280cacgaaggag ctgggaggag gcagagaccc agtgccggat gtacggcgcg catctggcca 2340gcatcagcac acccgaggaa caggacttca tcaacaaccg gtaccgggag taccagtgga 2400tcggactcaa cgacaggacc atcgaaggcg acttcttgtg gtcggatggc gtccccctgc 2460tctatgagaa ctggaaccct gggcagcctg acagctactt cctgtctgga gagaactgcg 2520tggtcatggt gtggcatgat cagggacaat ggagtgacgt gccctgcaac taccacctgt 2580cctacacctg caagatgggg ctggtgtcct gtgggccgcc accggagctg cccctggctc 2640aagtgttcgg ccgcccacgg ctgcgctatg aggtggacac tgtgcttcgc taccggtgcc 2700gggaaggact ggcccagcgc aatctgccgc tgatccgatg ccaagagaac ggtcgttggg 2760aggcccccca gatctcctgt gtgcccagaa gacctgcccg agctctgcac ccagaggagg 2820acccagaagg acgtcagggg aggctactgg gacgctggaa ggcgctgttg atcccccctt 2880ccagccccat gccaggtccc tagggggcaa ggccttgaac actgccggcc acagcactgc 2940cctgtcaccc aaattttccc tcacaccctg cgctcccgcc accacaggaa gtgacaacat 3000gacgaggggt ggtactggag tccaggtgac agttcctgaa ggggcttctg ggaaatacct 3060aggaggctcc agcccagccc aggccctctc cccctaccct gggcaccaga tcttccatca 3120gggccggagt aaatccctaa gtgcctcaac tgccctctcc ctggcagcca tcttgtcccc 3180tctattcctc tagggagcac tgtgcccact ctttctgggt tttccaaggg aatgggcttg 3240caggatggag tgtctgtaaa atcaacagga aataaaactg tgtatgagcc caggcaa 329775005DNAHomo sapiens 7agttccaagt aggtaatcct tctgagaagt cccacctttc tgagcagctg tgtttgaaga 60aagctagtgg gaaaagttcc aggattacat gtcaggaaac tacaagaggt agaaacattt 120gttgatttac cagtgttttt aacttcctgc tgggctgaaa actgcttgtt tcgtggaaaa 180gcaaaacttg acagcaaaca tctaaaatga agagctccca aacttttgag gaacaaacgg 240aatgcattgt gaacactcta ctcatggact tcttgagccc aacattgcag gttgccagcc 300ggaacctatg ctgtgtagat gaagtagatt caggagagcc ttgttctttt gatgtggcta 360tcattgctgg tcgccttcgg atgttgggtg accagttcaa cggagaattg gaagcttctg 420ccaaaaacgt cattgcagaa accattaagg gacagacagg agctatactc caggacactg 480tggaatctct cagcaagacc tggtgtgctc aggattccag cttagcttat gagagagctt 540ttctggcagt gtcagtgaaa cttcttgagt acatggctca cattgctcct gaagtagtgg 600gacaggtggc tatccccatg acgggtatga tcaatgggaa ccaagccatc cgggagttca 660tccagggcca gggaggttgg gaaaatctgg agagctgaag agttggagct attcacgaga 720ctgaacatca cttccttgtt gactgattgg gtgattgatt cctgggaatt caaacaaaca 780aataaaaaag cacttttttc attttatcag aactgaactt agctgaataa gttatttttt 840actgattgtt aaagttggga gcagctgcca gaggcctgca gagttggttt ttgttttgtt 900ttgttttgtc aacttaatgc aaaccacaga gattttctac tttctgtttt cacatgagtt 960ttaatgaggt tctgttgaag caaagacccc tagacacaaa gtaatgactt gttagtagtg 1020gaattataag caacagggca ggcctttgct ggaggtattt tgagagaaag ggagaacaat 1080ggaaactatt tcttcagatg tagccctgtc ttttggtaag aattgtgcct actaattttg 1140caatttaaag gatttcagga agctttttgg ttgaaaaatc ttgttttttt ttttttagac 1200gtagtctcac tctgtcaccc aggctggagt gcagtggtgc gatctcagct cactgcaagc 1260tccacctccc ggtttcactc cattctcctg cctcagcctc ctgagtagct gggactacag 1320gagcccgcca tcacgcccgg ctaatttttt gtatttttag tagagatgag gtttcgccgt 1380gttagccagg atggtctgga tctcctgacc tcgtgattcg cccgccttgg cctcccaaag 1440tgctgggatt acaggcgtga gccaccacgc ccggcctaaa atcttgttat tttaagttga 1500gcattttcat tcaaaatcat ccctaaactt catgttaatt tcacctgaga aggactattt 1560tatgcatttt agaggttgga agcaaaaaac aaacaaacaa acaaaaacag ttgtttctac 1620taggaaggtc aaagaaaata aaagttactc catttttact gccacaggat gcaggaagtg 1680ctggcccaca tctaggacag caaggccacc ccagcttaga tgaagctagc tgcataacac 1740aaagctttaa aagtgtggtt cacacaccac ttgtggacct tattgaattg ctgattcgca 1800ttcctagaga ttctgattct gtaggggtag gctggagcct aggaacctac cttttaaact 1860agttccatag gtgattctga tgtacatata gagtgtgaca gccatcacta tagagaatag 1920attgataaat tacaacccac gcgtcaaatc tggcttgctg tcttattttg taaataaagt 1980tttattggaa tagagcaaca ttcacttgtt tacatattgt ccatggccgc ttttgtgcta 2040caatggcaga gttgaatgat tatagaagac catatggctg gttaagtcca aaatatttac 2100tagctggccc tttacagaaa aagttggctg accccttctc taaatcaaca tttctccttg 2160gtaactgaaa ctctattaca gtcctgacaa ttccagcaaa cacagctgta gatagggttt 2220aaactcaaag atatttaact cttctttggg aacttagtct ccatatgttt gttagttctt 2280gcataatcca cagtttctct gggtcttcag ccaatcagag agctctgtag ctcctgagta 2340gtccatttct ctggccctac aagtgagagt gattggaagc aaagcttatg atttgtatga 2400tcttgtatct caaaatagtc cttaatgatc taatagatta gtaggcagtc atcaggtaga 2460gactccaaaa accagactac tttcctaaat atcaagaaga aaggcattgc tacagtgatt 2520catgaaaagc agcattaata actttggcta aagtttaaca aagctaacca cttcccctct 2580atcagccagc catctatgta tctcctctaa atgcagagaa gtaaatatgt agtgctgtta 2640atacattttt gctttttaaa gttatgcttt gtcctggcgc agtggctcat gcctgtaatc 2700ccagcacttt gggaggccaa ggcgggtgga tcacctgagg ttaggagttt gagaccagcc 2760tggccaacat ggtgaaaccc tgtctctgct aaaaatacaa aaaattagcc aggcttggtg 2820gcacgtgcct gtaatgccag ctactcagga ggctgaggca ggagaatcac ttgaacctgg 2880gaggcggagg ttgctgtgag ctgagttcgc gccattgcac tccagcctgg gctacaaaag 2940cgaaactgtc taaaaaaaaa aaaagaaaat aaataaagtt atgctttttc ctctattcct 3000agttaaatca caacaagtta gtaatccata aatgatgtgt cctgtttctc tttagtagaa 3060attatatttt tggctaccag ttaagaaact tgtactcctt tgtcccttat gttactataa 3120actcaagatg atgagttttg tggtatttga cttcataggc aaaatcaaaa tttttacttt 3180gttgctattc tgttttatga aataaacttc tgtctatgca tttgaactaa gtttcagcaa 3240attcaatcta aattgaataa ttccagctcc cagttttatc ctatgttgct cataaaacag 3300ttccaagtat actgcattat cttgagattt gaagatatgg tgcccacggg gattatacta 3360ggcaaatgcg ttaagcagct ctggcctagg tgttgtgtat tttaagagac tctatcttag 3420gagagcttaa gtgattgggc tgcaggaaga agacattgta acccaggaat taaaaatgga 3480ttcagattgc ctgattttaa cactttagtt tcaccatagg ctaattatgt gacattgggc 3540aagagacata attcttctgt accttagttt ctacatttgt aaaatagaga tgatttggta 3600acttattaat aagatttttg tgagagataa ataaaacaaa tacattttgt aaagggtgag 3660tacttggaat attttaaaca ctgtgccatt agcaatttgg aattctgtgt tatgcagttc 3720ataaggttct agcttgactt ttttctctct ccattaaccc tgtctctcac agatgcaaac 3780cactcttaat ggctttactt tcacatcaat gtgagtgatt cctaaatatg atttatttcc 3840cttctcaatt ccatacccac agatgcttat tatttattta tgtgtacctt tcttatcccc 3900atactctccc tgtttgcgat acaactagct caaaacctca gtcattttta ccttgtctct 3960ctctctccag tccaactcac ccaactagtt tttctcattt gttacttcat ttttgtcctg 4020gttcttctac cagatttatt agcaactgcc tggactatta ataaagcctc ctacttaggc 4080tttcaataga ttgttctgtt cctgctccat tccagtctgt cctatatact gccatcagat 4140tgatcaaagc tgtggtttct ttgtctatta ttttgattca tttttagata tggtatcatt 4200catttttaaa tttaacatac caatgaagat tacaagactt aaacatctta tcagaagggg 4260gcatttattt tttaaatcaa gaaataactt tccaaaagca ttgctttgaa tgccattctc 4320ttaaagtcct tcagtggaac ttttgagtgt gattagacat gttcattatc ttgattgtag 4380tgattttatg ggtgatgatt tcacaccaac ttatcaaact gcatactttg aaatgtgtag 4440tttattgtac atcagcacta ccttaataag gttgtttttt ttaaaaaaaa aaaaaaaacc 4500ttcagctgct ccctactgtt catcaaataa cagtctgata ttcaaattcc cccagtatct 4560ggccctaact gccctatata gccttaatca atcatgattc tcctctacaa tcccaatgct 4620ctagtataac cgagccagtc actaaagctg ccctcctcct actgttccct atgtttcata 4680ttcctttttc tgaggctcta cctgtagaca tcttcaagac ccaacccaac tgtcatgaag 4740ccttctccat gaaggctatc catataacca gaataagaag tggtctttgc ctccttgaac 4800ttttgtttgt accactttta tgtttcttat ccaaaaaatg gccttaagtt gtaattatct 4860gtatagtcat cttccccact aggataaagg attgctgaat gatacaattt gttgtatact 4920tctgtaacac ccctcctctt cattatctgg catgtacatc gatattaaaa atattcatta 4980aatgaatgaa tagctgattg actca 500581855DNAHomo sapiens 8aagtgtgtcc ctagcggcgg cccgtgcagc gctcccgcga gacgctcacc tgcgccccag 60gtgagcggcg agggggcggg ggaggggctg agccggaggc ggctcacctg gcgggacagg 120tgcctggctg ctacaaacca tgcaatgagc catgccccgc cctggacacc cccgcccagc 180atctgggcct ccacgcttgg gaccgtggga gcggccaaca gagctatgtc tggagacata 240tgataaacca cctcagcccc caccaagccg ccgcacccgt agaccagacc ccaaggaccc 300tggccaccat gggccagaga gcattacctt catctctggc tctgctgagc cggcccttga 360gtcccccacc tgctgcctgc tctggcgacc ctgggtgtgg gagtggtgcc gggctgcctt 420ctgcttccgc cgctgccggg attgcctcca gcgctgtgga gcctgtgtgc ggggatgcag 480cccctgcctg tctactgagg actccactga ggggactgct gaagccaact gggccaagga 540gcacaatgga gtgcccccca gccctgatcg tgcacccccc agccggcggg atggccagcg 600gctcaagtca accatgggca gcagcttcag ctaccccgat gttaagctca aaggcatccc 660tgtgtatccc tacccgaggg ccacctcccc agcccctgat gcggactcct gctgcaagga 720gccactggcc gatcccccac ccatgcgaca cagcctgccc agcacctttg ccagtagtcc 780tcgtggctcc gaggagtact attctttcca tgagtcggac ctggacctgc cggagatggg 840cagtggctcc atgtcgagcc gagaaattga tgtgctcatc ttcaagaagc tgacagagct 900gttcagcgta caccagatcg atgagctggc caagtgcaca tcagacactg tgttcctgga 960gaagaccagt aagatctcgg accttatcag cagcatcacg caggactacc acctggatga 1020gcaggatgct gagggccgcc tggtacgcgg catcattcgc attagtaccc gaaagagccg 1080tgctcgccca cagacctcgg agggtcgttc aactcgggct gctgccccaa ccgctgctgc 1140ccctgacagt ggccatgaga ccatggtggg ctcaggtctc agccaggatg agctgacagt 1200gcagatctcc caggagacga ctgcagatgc catcgcccgg aagctgaggc cttatggagc 1260tccagggtac ccagcaagcc atgactcatc cttccagggc accgacacag actcgtcggg 1320ggcacccttg ctccaggtgt actgctaacc cctgccaggc ccagctgcca caccctttct 1380gggagaagca tggcctacag aatgaagagg gggaccagga acccctgtgg gagaggctta 1440gacctgaagc agtgcccact ctggctcctc ctgccttggc tgactgggtt cctggaccat 1500gtgcatttca ctgggccatg ggatctacat ctccttgcat ccccagctgg tctgatccct 1560gccagggccc cttccttcct gctcatggtc ttcaggtggc ctgatcatgg aaagtaagga 1620gttaggcatt accttctggg agtgaaccct gactccatcc ccctattgcc accctaacca 1680atcatgcaaa cttctccctc cctggggtaa ttcaacagtt aaaagaagct tatcttaaat 1740gtattgtatt ggggggtggg cagggcccac tctatgttat gttaaggagt tggttctggt 1800tcttggctga tgttctgtat cttaacatga ccacagtttg taagtacaaa ggtaa 185591537DNAHomo sapiens 9acaacacagc taacacaagg ccccgcaggc aggactctgg gacagacgca ggccagctgc 60ccagagccca gaccaagcat ggacgccgtg gatgccacca tggagaaact ccgggcacag 120tgcctgtccc gcggggcctc gggcatccag ggcctggcca ggtttttccg ccaactagac 180cgggacggga gcagatccct ggacgctgat gagttccggc agggtctggc caaactcggg 240ctggtgctgg accaggcgga ggcagagggt gtgtgcagga agtgggaccg caatggcagc 300gggacgctgg atctggagga gttccttcgg gcgctgcggc cccccatgtc ccaggcccgg 360gaggctgtca tcgcagctgc atttgccaag ctggaccgca gtggggacgg cgtcgtgacg 420gtggacgacc tccgcggggt gtacagtggc cgtgcccacc ccaaggtgcg cagtggggag 480tggaccgagg acgaggtgct gcgccgcttc ctggacaact tcgactcctc tgagaaggac 540gggcaggtca cactggcgga attccaggac tactacagcg gcgtgagtgc ctccatgaac 600acggatgagg agttcgtggc catgatgacc agtgcctggc agctgtgagc agctccggct 660cagccctgct gccctggcct gtcactcccc acccctgccg gagacctccc ttccctgggc 720cccttctctc ctgggcagcc acaccacaga gcggggaggg gcaggtgggg gaatggaggc 780tgcaggactg gctagaccag gtccctgccg gtccaccagg cggaggtggg acaaaggtcc 840taacaggagt cactggctca ggaccccagg gagaaacgct ctccccaccc acgccatgct 900gaccagagat cttgcagccc ctgtggatgc ccccgccgag gtcccccgat ccccgcaccc 960ggactgctgc tccctgcccc tcccttgcgg gtcccccagg aagccaggtg accccaggtg 1020ggaggctgtg tgtggaggcc atcctggaag gaagtttaga cctgcccagg tgtggagcga 1080ggggcacagg ggcatcctaa cctcagaaac tgaaataaag cctttgaaaa aaaaatctgt 1140aaaacatcaa cccccaatca gaagatggca aatggggaat aaaaatagca ggtaacatgt 1200ccagcgggcc cagtatctac attctggtga gcggcccgag gctgggagct ctgggcgggg 1260gcagaccggc ggggccttgc agcaggggtg ggggtaaagt gcgggtggtg gtggagagaa 1320cagggctgtg gctggacccc agcactggtg acacgctggg tgggagcatg aggccccagg 1380ctgctggagg tcctcgcccg gggaggtgga ggccgttcct ggtcaggggc ttcctgaggc 1440ccctggggca tgcagaggcc agggttttag ttaaaagttt aatgtagttc ccaaatacat 1500ttcatatgac aatcttacat aaatgttcca aaacaca 1537101576DNAHomo sapiens 10atcccagccg caccggtcct tcccggcaca cgcgaggctc ccatggctct ggcggtggcc 60ccgtgggggc gacagtggga agaggcccgc gccctgggcc gggcagtcag gatgctgcag 120cgcctagaag agcaatgcgt cgacccccgg ctgtccgtga gtcccccttc gctgcgggac 180ctgctgcccc gcacagcgca gctgcttcga gaggtggccc attctcggcg ggcggccggc 240ggaggcggcc ccgggggtcc cggcggctct ggggactttc tactcatcta cctggccaat 300ctggaggcca agagcaggca ggtggccgcg ctgctgcctc cccggggccg aaggagtgcc 360aacgacgagc tcttccgggc gggctccaga ctcaggcgac

agctggccaa gctggccatc 420atcttcagcc acatgcacgc agagctgcac gcactcttcc ccgggggaaa gtactgtgga 480cacatgtacc agctcaccaa ggcccccgcc cacaccttct ggagggaaag ttgcggagcc 540cggtgtgtgc tgccctgggc tgagtttgag tccctcctgg gcacctgcca ccctgtggaa 600ccaggctgca cagccctggc cttgcgcacc accattgacc tcacctgcag cgggcacgtg 660tccatcttcg agttcgacgt cttcaccagg ctctttcagc catggccaac actcctcaag 720aactggcagc tcctggcagt caaccaccca ggctacatgg ccttcctcac ctatgatgag 780gtccaagagc gtctgcaggc ctgcagggac aagccaggca gttacatctt ccggcccagc 840tgtactcgcc tggggcagtg ggccatcggc tatgtgagct cagatggcag catcctgcag 900accatccctg ccaacaaacc cctgtcccag gtgctcctgg agggacagaa ggacggcttc 960tacctctacc cagatggaaa gacccacaac ccagacctga ctgagctcgg ccaggcagaa 1020ccccagcagc gcatccacgt gtcagaggag cagctgcagc tctactgggc catggactcc 1080acatttgagc tctgcaagat ctgtgctgag agcaacaagg atgtgaagat tgagccgtgc 1140gggcacctgc tctgcagctg ctgcctggct gcctggcagc actcggacag ccagacctgc 1200cccttctgcc gctgcgagat caagggctgg gaggccgtga gtatctacca gttccacggt 1260caggctactg ctgaggactc agggaacagc agtgaccagg aaggcaggga gttggagctg 1320gggcaggtgc ccctttcggc tcctccattg cccccacggc cagatctgcc ccccaggaag 1380cccagaaatg cccagccgaa agtgagactc ctaaagggga actcccctcc agctgcgctg 1440ggaccccagg accctgcccc ggcctgaagg ccagggcacc cagatgtgct gctcaaggga 1500gccccaaggg ctggaagggg gttgtgaaac cgaaataaac tgccaagcct ggtctgtcct 1560ccagggtgca aaggaa 1576114811DNAHomo sapiens 11agtggcgtcg gaactgcaaa gcacctgtga gcttgcggaa gtcagttcag actccagccc 60gctccagccc ggcccgaccc gaccgcaccc ggcgcctgcc ctcgctcggc gtccccggcc 120agccatgggc ccttggagcc gcagcctctc ggcgctgctg ctgctgctgc aggtctcctc 180ttggctctgc caggagccgg agccctgcca ccctggcttt gacgccgaga gctacacgtt 240cacggtgccc cggcgccacc tggagagagg ccgcgtcctg ggcagagtga attttgaaga 300ttgcaccggt cgacaaagga cagcctattt ttccctcgac acccgattca aagtgggcac 360agatggtgtg attacagtca aaaggcctct acggtttcat aacccacaga tccatttctt 420ggtctacgcc tgggactcca cctacagaaa gttttccacc aaagtcacgc tgaatacagt 480ggggcaccac caccgccccc cgccccatca ggcctccgtt tctggaatcc aagcagaatt 540gctcacattt cccaactcct ctcctggcct cagaagacag aagagagact gggttattcc 600tcccatcagc tgcccagaaa atgaaaaagg cccatttcct aaaaacctgg ttcagatcaa 660atccaacaaa gacaaagaag gcaaggtttt ctacagcatc actggccaag gagctgacac 720accccctgtt ggtgtcttta ttattgaaag agaaacagga tggctgaagg tgacagagcc 780tctggataga gaacgcattg ccacatacac tctcttctct cacgctgtgt catccaacgg 840gaatgcagtt gaggatccaa tggagatttt gatcacggta accgatcaga atgacaacaa 900gcccgaattc acccaggagg tctttaaggg gtctgtcatg gaaggtgctc ttccaggaac 960ctctgtgatg gaggtcacag ccacagacgc ggacgatgat gtgaacacct acaatgccgc 1020catcgcttac accatcctca gccaagatcc tgagctccct gacaaaaata tgttcaccat 1080taacaggaac acaggagtca tcagtgtggt caccactggg ctggaccgag agagtttccc 1140tacgtatacc ctggtggttc aagctgctga ccttcaaggt gaggggttaa gcacaacagc 1200aacagctgtg atcacagtca ctgacaccaa cgataatcct ccgatcttca atcccaccac 1260gtacaagggt caggtgcctg agaacgaggc taacgtcgta atcaccacac tgaaagtgac 1320tgatgctgat gcccccaata ccccagcgtg ggaggctgta tacaccatat tgaatgatga 1380tggtggacaa tttgtcgtca ccacaaatcc agtgaacaac gatggcattt tgaaaacagc 1440aaagggcttg gattttgagg ccaagcagca gtacattcta cacgtagcag tgacgaatgt 1500ggtacctttt gaggtctctc tcaccacctc cacagccacc gtcaccgtgg atgtgctgga 1560tgtgaatgaa gcccccatct ttgtgcctcc tgaaaagaga gtggaagtgt ccgaggactt 1620tggcgtgggc caggaaatca catcctacac tgcccaggag ccagacacat ttatggaaca 1680gaaaataaca tatcggattt ggagagacac tgccaactgg ctggagatta atccggacac 1740tggtgccatt tccactcggg ctgagctgga cagggaggat tttgagcacg tgaagaacag 1800cacgtacaca gccctaatca tagctacaga caatggttct ccagttgcta ctggaacagg 1860gacacttctg ctgatcctgt ctgatgtgaa tgacaacgcc cccataccag aacctcgaac 1920tatattcttc tgtgagagga atccaaagcc tcaggtcata aacatcattg atgcagacct 1980tcctcccaat acatctccct tcacagcaga actaacacac ggggcgagtg ccaactggac 2040cattcagtac aacgacccaa cccaagaatc tatcattttg aagccaaaga tggccttaga 2100ggtgggtgac tacaaaatca atctcaagct catggataac cagaataaag accaagtgac 2160caccttagag gtcagcgtgt gtgactgtga aggggccgct ggcgtctgta ggaaggcaca 2220gcctgtcgaa gcaggattgc aaattcctgc cattctgggg attcttggag gaattcttgc 2280tttgctaatt ctgattctgc tgctcttgct gtttcttcgg aggagagcgg tggtcaaaga 2340gcccttactg cccccagagg atgacacccg ggacaacgtt tattactatg atgaagaagg 2400aggcggagaa gaggaccagg actttgactt gagccagctg cacaggggcc tggacgctcg 2460gcctgaagtg actcgtaacg acgttgcacc aaccctcatg agtgtccccc ggtatcttcc 2520ccgccctgcc aatcccgatg aaattggaaa ttttattgat gaaaatctga aagcggctga 2580tactgacccc acagccccgc cttatgattc tctgctcgtg tttgactatg aaggaagcgg 2640ttccgaagct gctagtctga gctccctgaa ctcctcagag tcagacaaag accaggacta 2700tgactacttg aacgaatggg gcaatcgctt caagaagctg gctgacatgt acggaggcgg 2760cgaggacgac taggggactc gagagaggcg ggccccagac ccatgtgctg ggaaatgcag 2820aaatcacgtt gctggtggtt tttcagctcc cttcccttga gatgagtttc tggggaaaaa 2880aaagagactg gttagtgatg cagttagtat agctttatac tctctccact ttatagctct 2940aataagtttg tgttagaaaa gtttcgactt atttcttaaa gctttttttt ttttcccatc 3000actctttaca tggtggtgat gtccaaaaga tacccaaatt ttaatattcc agaagaacaa 3060ctttagcatc agaaggttca cccagcacct tgcagatttt cttaaggaat tttgtctcac 3120ttttaaaaag aaggggagaa gtcagctact ctagttctgt tgttttgtgt atataatttt 3180ttaaaaaaaa tttgtgtgct tctgctcatt actacactgg tgtgtccctc tgcctttttt 3240ttttttttaa gacagggtct cattctatcg gccaggctgg agtgcagtgg tgcaatcaca 3300gctcactgca gccttgtcct cccaggctca agctatcctt gcacctcagc ctcccaagta 3360gctgggacca caggcatgca ccactacgca tgactaattt tttaaatatt tgagacgggg 3420tctccctgtg ttacccaggc tggtctcaaa ctcctgggct caagtgatcc tcccatcttg 3480gcctcccaga gtattgggat tacagacatg agccactgca cctgcccagc tccccaactc 3540cctgccattt tttaagagac agtttcgctc catcgcccag gcctgggatg cagtgatgtg 3600atcatagctc actgtaacct caaactctgg ggctcaagca gttctcccac cagcctcctt 3660tttatttttt tgtacagatg gggtcttgct atgttgccca agctggtctt aaactcctgg 3720cctcaagcaa tccttctgcc ttggcccccc aaagtgctgg gattgtgggc atgagctgct 3780gtgcccagcc tccatgtttt aatatcaact ctcactcctg aattcagttg ctttgcccaa 3840gataggagtt ctctgatgca gaaattattg ggctctttta gggtaagaag tttgtgtctt 3900tgtctggcca catcttgact aggtattgtc tactctgaag acctttaatg gcttccctct 3960ttcatctcct gagtatgtaa cttgcaatgg gcagctatcc agtgacttgt tctgagtaag 4020tgtgttcatt aatgtttatt tagctctgaa gcaagagtga tatactccag gacttagaat 4080agtgcctaaa gtgctgcagc caaagacaga gcggaactat gaaaagtggg cttggagatg 4140gcaggagagc ttgtcattga gcctggcaat ttagcaaact gatgctgagg atgattgagg 4200tgggtctacc tcatctctga aaattctgga aggaatggag gagtctcaac atgtgtttct 4260gacacaagat ccgtggtttg tactcaaagc ccagaatccc caagtgcctg cttttgatga 4320tgtctacaga aaatgctggc tgagctgaac acatttgccc aattccaggt gtgcacagaa 4380aaccgagaat attcaaaatt ccaaattttt ttcttaggag caagaagaaa atgtggccct 4440aaagggggtt agttgagggg tagggggtag tgaggatctt gatttggatc tctttttatt 4500taaatgtgaa tttcaacttt tgacaatcaa agaaaagact tttgttgaaa tagctttact 4560gtttctcaag tgttttggag aaaaaaatca accctgcaat cactttttgg aattgtcttg 4620atttttcggc agttcaagct atatcgaata tagttctgtg tagagaatgt cactgtagtt 4680ttgagtgtat acatgtgtgg gtgctgataa ttgtgtattt tctttggggg tggaaaagga 4740aaacaattca agctgagaaa agtattctca aagatgcatt tttataaatt ttattaaaca 4800attttgttaa a 4811123542DNAHomo sapiens 12gatgctgaga agtactcctg ccctaggaag agactcaggg cagagggagg aaggacagca 60gaccagacag tcacagcagc cttgacaaaa cgttcctgga actcaagctc ttctccacag 120aggaggacag agcagacagc agagaccatg gagtctccct cggcccctcc ccacagatgg 180tgcatcccct ggcagaggct cctgctcaca gcctcacttc taaccttctg gaacccgccc 240accactgcca agctcactat tgaatccacg ccgttcaatg tcgcagaggg gaaggaggtg 300cttctacttg tccacaatct gccccagcat ctttttggct acagctggta caaaggtgaa 360agagtggatg gcaaccgtca aattatagga tatgtaatag gaactcaaca agctacccca 420gggcccgcat acagtggtcg agagataata taccccaatg catccctgct gatccagaac 480atcatccaga atgacacagg attctacacc ctacacgtca taaagtcaga tcttgtgaat 540gaagaagcaa ctggccagtt ccgggtatac ccggagctgc ccaagccctc catctccagc 600aacaactcca aacccgtgga ggacaaggat gctgtggcct tcacctgtga acctgagact 660caggacgcaa cctacctgtg gtgggtaaac aatcagagcc tcccggtcag tcccaggctg 720cagctgtcca atggcaacag gaccctcact ctattcaatg tcacaagaaa tgacacagca 780agctacaaat gtgaaaccca gaacccagtg agtgccaggc gcagtgattc agtcatcctg 840aatgtcctct atggcccgga tgcccccacc atttcccctc taaacacatc ttacagatca 900ggggaaaatc tgaacctctc ctgccacgca gcctctaacc cacctgcaca gtactcttgg 960tttgtcaatg ggactttcca gcaatccacc caagagctct ttatccccaa catcactgtg 1020aataatagtg gatcctatac gtgccaagcc cataactcag acactggcct caataggacc 1080acagtcacga cgatcacagt ctatgcagag ccacccaaac ccttcatcac cagcaacaac 1140tccaaccccg tggaggatga ggatgctgta gccttaacct gtgaacctga gattcagaac 1200acaacctacc tgtggtgggt aaataatcag agcctcccgg tcagtcccag gctgcagctg 1260tccaatgaca acaggaccct cactctactc agtgtcacaa ggaatgatgt aggaccctat 1320gagtgtggaa tccagaacga attaagtgtt gaccacagcg acccagtcat cctgaatgtc 1380ctctatggcc cagacgaccc caccatttcc ccctcataca cctattaccg tccaggggtg 1440aacctcagcc tctcctgcca tgcagcctct aacccacctg cacagtattc ttggctgatt 1500gatgggaaca tccagcaaca cacacaagag ctctttatct ccaacatcac tgagaagaac 1560agcggactct atacctgcca ggccaataac tcagccagtg gccacagcag gactacagtc 1620aagacaatca cagtctctgc ggagctgccc aagccctcca tctccagcaa caactccaaa 1680cccgtggagg acaaggatgc tgtggccttc acctgtgaac ctgaggctca gaacacaacc 1740tacctgtggt gggtaaatgg tcagagcctc ccagtcagtc ccaggctgca gctgtccaat 1800ggcaacagga ccctcactct attcaatgtc acaagaaatg acgcaagagc ctatgtatgt 1860ggaatccaga actcagtgag tgcaaaccgc agtgacccag tcaccctgga tgtcctctat 1920gggccggaca cccccatcat ttccccccca gactcgtctt acctttcggg agcgaacctc 1980aacctctcct gccactcggc ctctaaccca tccccgcagt attcttggcg tatcaatggg 2040ataccgcagc aacacacaca agttctcttt atcgccaaaa tcacgccaaa taataacggg 2100acctatgcct gttttgtctc taacttggct actggccgca ataattccat agtcaagagc 2160atcacagtct ctgcatctgg aacttctcct ggtctctcag ctggggccac tgtcggcatc 2220atgattggag tgctggttgg ggttgctctg atatagcagc cctggtgtag tttcttcatt 2280tcaggaagac tgacagttgt tttgcttctt ccttaaagca tttgcaacag ctacagtcta 2340aaattgcttc tttaccaagg atatttacag aaaagactct gaccagagat cgagaccatc 2400ctagccaaca tcgtgaaacc ccatctctac taaaaataca aaaatgagct gggcttggtg 2460gcgcacacct gtagtcccag ttactcggga ggctgaggca ggagaatcgc ttgaacccgg 2520gaggtggaga ttgcagtgag cccagatcgc accactgcac tccagtctgg caacagagca 2580agactccatc tcaaaaagaa aagaaaagaa gactctgacc tgtactcttg aatacaagtt 2640tctgatacca ctgcactgtc tgagaatttc caaaacttta atgaactaac tgacagcttc 2700atgaaactgt ccaccaagat caagcagaga aaataattaa tttcatggga ctaaatgaac 2760taatgaggat aatattttca taatttttta tttgaaattt tgctgattct ttaaatgtct 2820tgtttcccag atttcaggaa actttttttc ttttaagcta tccacagctt acagcaattt 2880gataaaatat acttttgtga acaaaaattg agacatttac attttctccc tatgtggtcg 2940ctccagactt gggaaactat tcatgaatat ttatattgta tggtaatata gttattgcac 3000aagttcaata aaaatctgct ctttgtatga cagaatacat ttgaaaacat tggttatatt 3060accaagactt tgactagaat gtcgtatttg aggatataaa cccataggta ataaacccac 3120aggtactaca aacaaagtct gaagtcagcc ttggtttggc ttcctagtgt caattaaact 3180tctaaaagtt taatctgaga ttccttataa aaacttccag caaagcaact ttaaaaaagt 3240ctgtgtgggc cgggcgcggt ggctcacgcc tgtaatccca gcactttgat ccgccgaggc 3300gggcggatca cgaggtcagg agatccagac catcctggct aacacagtga aaccccgtct 3360ctactaaaaa tacaaaaaaa gttagccggg cgtggtggtg ggggcctgta gtcccagcta 3420ctcaggaggc tgaggcagga gaacggcatg aacccgggag gcagggcttg cagtgagcca 3480agatcatgcc gctgcactcc agcctgggag acaaagtgag actccgtcaa aaaaaaaaaa 3540aa 3542132594DNAHomo sapiens 13acagaaggag gaaggacagc agggccaaca gtcacagcag ccctgaccag agcattcctg 60gagctcaagc tcctctacaa agaggtggac agagaagaca gcagagacca tgggaccccc 120ctcagcccct ccctgcagat tgcatgtccc ctggaaggag gtcctgctca cagcctcact 180tctaaccttc tggaacccac ccaccactgc caagctcact attgaatcca cgccgttcaa 240tgtcgcagag gggaaggagg ttcttctact cgcccacaac ctgccccaga atcgtattgg 300ttacagctgg tacaaaggcg aaagagtgga tggcaacagt ctaattgtag gatatgtaat 360aggaactcaa caagctaccc cagggcccgc atacagtggt cgagagacaa tataccccaa 420tgcatccctg ctgatccaga acgtcaccca gaatgacaca ggattctata ccctacaagt 480cataaagtca gatcttgtga atgaagaagc aaccggacag ttccatgtat acccggagct 540gcccaagccc tccatctcca gcaacaactc caaccccgtg gaggacaagg atgctgtggc 600cttcacctgt gaacctgagg ttcagaacac aacctacctg tggtgggtaa atggtcagag 660cctcccggtc agtcccaggc tgcagctgtc caatggcaac atgaccctca ctctactcag 720cgtcaaaagg aacgatgcag gatcctatga atgtgaaata cagaacccag cgagtgccaa 780ccgcagtgac ccagtcaccc tgaatgtcct ctatggccca gatgtcccca ccatttcccc 840ctcaaaggcc aattaccgtc caggggaaaa tctgaacctc tcctgccacg cagcctctaa 900cccacctgca cagtactctt ggtttatcaa tgggacgttc cagcaatcca cacaagagct 960ctttatcccc aacatcactg tgaataatag cggatcctat atgtgccaag cccataactc 1020agccactggc ctcaatagga ccacagtcac gatgatcaca gtctctggaa gtgctcctgt 1080cctctcagct gtggccaccg tcggcatcac gattggagtg ctggccaggg tggctctgat 1140atagcagccc tggtgtattt tcgatatttc aggaagactg gcagattgga ccagaccctg 1200aattcttcta gctcctccaa tcccatttta tcccatggaa ccactaaaaa caaggtctgc 1260tctgctcctg aagccctata tgctggagat ggacaactca atgaaaattt aaagggaaaa 1320ccctcaggcc tgaggtgtgt gccactcaga gacttcacct aactagagac agtcaaactg 1380caaaccatgg tgagaaattg acgacttcac actatggaca gcttttccca agatgtcaaa 1440acaagactcc tcatcatgat aaggctctta ccccctttta atttgtcctt gcttatgcct 1500gcctctttcg cttggcagga tgatgctgtc attagtattt cacaagaagt agcttcagag 1560ggtaacttaa cagagtgtca gatctatctt gtcaatccca acgttttaca taaaataaga 1620gatcctttag tgcacccagt gactgacatt agcagcatct ttaacacagc cgtgtgttca 1680aatgtacagt ggtccttttc agagttggac ttctagactc acctgttctc actccctgtt 1740ttaattcaac ccagccatgc aatgccaaat aatagaattg ctccctacca gctgaacagg 1800gaggagtctg tgcagtttct gacacttgtt gttgaacatg gctaaataca atgggtatcg 1860ctgagactaa gttgtagaaa ttaacaaatg tgctgcttgg ttaaaatggc tacactcatc 1920tgactcattc tttattctat tttagttggt ttgtatcttg cctaaggtgc gtagtccaac 1980tcttggtatt accctcctaa tagtcatact agtagtcata ctccctggtg tagtgtattc 2040tctaaaagct ttaaatgtct gcatgcagcc agccatcaaa tagtgaatgg tctctctttg 2100gctggaatta caaaactcag agaaatgtgt catcaggaga acatcataac ccatgaagga 2160taaaagcccc aaatggtggt aactgataat agcactaatg ctttaagatt tggtcacact 2220ctcacctagg tgagcgcatt gagccagtgg tgctaaatgc tacatactcc aactgaaatg 2280ttaaggaaga agatagatcc aattaaaaaa aattaaaacc aatttaaaaa aaaaaagaac 2340acaggagatt ccagtctact tgagttagca taatacagaa gtcccctcta ctttaacttt 2400tacaaaaaag taacctgaac taatctgatg ttaaccaatg tatttatttc tgtggttctg 2460tttccttgtt ccaatttgac aaaacccact gttcttgtat tgtattgccc agggggagct 2520atcactgtac ttgtagagtg gtgctgcttt aattcataaa tcacaaataa aagccaatta 2580gctctataac taaa 2594141852DNAHomo sapiens 14agccaggaaa tgccctggag tgtgtgtcac ctgtccagga cgacttgttg attcccagga 60gggccgcctt tccggtctgg gtccccgaga ggactgcctt gctcacctgt cccctcggcg 120cggccccggg gagctcccga gaggcccccg ggatcgctgg ccctccgaac tccacagcaa 180tgagcaagtt gggcaagttc tttaaagggg gcggctcttc taagagccga gccgctccca 240gtccccagga ggccctggtc cgacttcggg agactgagga gatgctgggc aagaaacaag 300agtacctgga aaatcgaatc cagagagaaa tcgccctggc caagaagcac ggcacgcaga 360ataagcgagc tgcattacag gcactaaaga gaaagaagag gttcgagaaa cagctcactc 420agattgatgg cacactttct accattgagt tccagagaga agccctggag aactcacaca 480ccaacactga ggtgttgagg aacatgggct ttgcagcaaa agcgatgaaa tctgttcatg 540aaaacatgga tctgaacaaa atagatgatt tgatgcaaga gatcacagag caacaggata 600tcgcccaaga aatctcagaa gcattttctc aacgggttgg ctttggtgat gactttgatg 660aggatgagtt gatggcagaa cttgaagaat tggaacagga ggaattaaat aagaagatga 720caaatatccg ccttccaaat gtgccttcct cttctctccc agcacagcca aatagaaaac 780caggcatgtc gtccactgca cgtcgatccc gagcagcatc ttcccagagg gcagaagaag 840aggatgatga tatcaaacaa ttggcagctt gggctaccta aactaaaaca catttttgat 900acctaaatta atgagctata gataaaatat aaaaaatgtt tttaccaagt tcagaagtta 960acaaagactc tgctttataa ttatattgaa tgaataattg tgttttaagc ctcctaagta 1020aaagtaaaaa aggagtcatg tgcatacata gaatcagtga tggaggccag gcacggtatc 1080tcatgcctat aatcccagca ctttgggagg ctgaggcagt tgagaccagg agttcgagtc 1140cagcctgacc aacatgaaga aaccctgtct gtactaaaaa tacaaaaatt agccggacat 1200ggtggcaggc acctgtaatc ccagctactt gggaggctga gtcaggagaa tcgcttgagc 1260ccaggagatg gaggttgcag tgagccaaga tcatgccact gcactccaga ctgggcaaca 1320gagggagact ccgtctcaaa aactaaaaaa aaaaaataca tttagtatag cggggggtgg 1380gggggagaaa taatgttatt tcctatgcga atgacgtgta tccctgtacc catggtaaat 1440gtaaatatac tgtgtctctt ttgggagagc cttttagtag aggagtctta tatgagtctc 1500tacataagta gtttcacttg agttttgcag tttgaaatct taaaggagct ttaattgaca 1560tttattatac caattaagct tggaatgggg caatggatgc atttcccaaa acgtgtgaaa 1620gcactaacag cttatattgc tgaatgagaa tctcctgggt gtaatttagc cacttaggga 1680actgcgtgaa cactcccagg ccattatgat gctgttacag cttcagtgta taaatgcatg 1740agtattcttt ctgttctgtt ttgtgctctc ttgtacattt atttaccctt tacagaatat 1800ttcttgtaaa tacataaaaa tattggcaat taaaagtaca tcttgaataa aa 1852153935DNAHomo sapiens 15atctgcatcc atattgaaaa cctgacacaa tgtatgcagc aggctcagtg tgagtgaact 60ggaggcttct ctacaacatg acccaaagga gcattgcagg tcctatttgc aacctgaagt 120ttgtgactct cctggttgcc ttaagttcag aactcccatt cctgggagct ggagtacagc 180ttcaagacaa tgggtataat ggattgctca ttgcaattaa tcctcaggta cctgagaatc 240agaacctcat ctcaaacatt aaggaaatga taactgaagc ttcattttac ctatttaatg 300ctaccaagag aagagtattt ttcagaaata taaagatttt aatacctgcc acatggaaag 360ctaataataa cagcaaaata aaacaagaat catatgaaaa ggcaaatgtc atagtgactg 420actggtatgg ggcacatgga gatgatccat acaccctaca atacagaggg tgtggaaaag 480agggaaaata cattcatttc acacctaatt tcctactgaa tgataactta acagctggct 540acggatcacg aggccgagtg tttgtccatg aatgggccca cctccgttgg ggtgtgttcg 600atgagtataa caatgacaaa cctttctaca taaatgggca aaatcaaatt aaagtgacaa 660ggtgttcatc tgacatcaca ggcatttttg tgtgtgaaaa aggtccttgc ccccaagaaa 720actgtattat tagtaagctt tttaaagaag gatgcacctt tatctacaat agcacccaaa

780atgcaactgc atcaataatg ttcatgcaaa gtttatcttc tgtggttgaa ttttgtaatg 840caagtaccca caaccaagaa gcaccaaacc tacagaacca gatgtgcagc ctcagaagtg 900catgggatgt aatcacagac tctgctgact ttcaccacag ctttcccatg aatgggactg 960agcttccacc tcctcccaca ttctcgcttg tacaggctgg tgacaaagtg gtctgtttag 1020tgctggatgt gtccagcaag atggcagagg ctgacagact ccttcaacta caacaagccg 1080cagaatttta tttgatgcag attgttgaaa ttcatacctt cgtgggcatt gccagtttcg 1140acagcaaagg agagatcaga gcccagctac accaaattaa cagcaatgat gatcgaaagt 1200tgctggtttc atatctgccc accactgtat cagctaaaac agacatcagc atttgttcag 1260ggcttaagaa aggatttgag gtggttgaaa aactgaatgg aaaagcttat ggctctgtga 1320tgatattagt gaccagcgga gatgataagc ttcttggcaa ttgcttaccc actgtgctca 1380gcagtggttc aacaattcac tccattgccc tgggttcatc tgcagcccca aatctggagg 1440aattatcacg tcttacagga ggtttaaagt tctttgttcc agatatatca aactccaata 1500gcatgattga tgctttcagt agaatttcct ctggaactgg agacattttc cagcaacata 1560ttcagcttga aagtacaggt gaaaatgtca aacctcacca tcaattgaaa aacacagtga 1620ctgtggataa tactgtgggc aacgacacta tgtttctagt tacgtggcag gccagtggtc 1680ctcctgagat tatattattt gatcctgatg gacgaaaata ctacacaaat aattttatca 1740ccaatctaac ttttcggaca gctagtcttt ggattccagg aacagctaag cctgggcact 1800ggacttacac cctgaacaat acccatcatt ctctgcaagc cctgaaagtg acagtgacct 1860ctcgcgcctc caactcagct gtgcccccag ccactgtgga agcctttgtg gaaagagaca 1920gcctccattt tcctcatcct gtgatgattt atgccaatgt gaaacaggga ttttatccca 1980ttcttaatgc cactgtcact gccacagttg agccagagac tggagatcct gttacgctga 2040gactccttga tgatggagca ggtgctgatg ttataaaaaa tgatggaatt tactcgaggt 2100attttttctc ctttgctgca aatggtagat atagcttgaa agtgcatgtc aatcactctc 2160ccagcataag caccccagcc cactctattc cagggagtca tgctatgtat gtaccaggtt 2220acacagcaaa cggtaatatt cagatgaatg ctccaaggaa atcagtaggc agaaatgagg 2280aggagcgaaa gtggggcttt agccgagtca gctcaggagg ctccttttca gtgctgggag 2340ttccagctgg cccccaccct gatgtgtttc caccatgcaa aattattgac ctggaagctg 2400taaaagtaga agaggaattg accctatctt ggacagcacc tggagaagac tttgatcagg 2460gccaggctac aagctatgaa ataagaatga gtaaaagtct acagaatatc caagatgact 2520ttaacaatgc tattttagta aatacatcaa agcgaaatcc tcagcaagct ggcatcaggg 2580agatatttac gttctcaccc caaatttcca cgaatggacc tgaacatcag ccaaatggag 2640aaacacatga aagccacaga atttatgttg caatacgagc aatggatagg aactccttac 2700agtctgctgt atctaacatt gcccaggcgc ctctgtttat tccccccaat tctgatcctg 2760tacctgccag agattatctt atattgaaag gagttttaac agcaatgggt ttgataggaa 2820tcatttgcct tattatagtt gtgacacatc atactttaag caggaaaaag agagcagaca 2880agaaagagaa tggaacaaaa ttattataaa taaatatcca aagtgtcttc cttcttagat 2940ataagaccca tggccttcga ctacaaaaac atactaacaa agtcaaatta acatcaaaac 3000tgtattaaaa tgcattgagt ttttgtacaa tacagataag atttttacat ggtagatcaa 3060caaattcttt ttgggggtag attagaaaac ccttacactt tggctatgaa caaataataa 3120aaattattct ttaaagtaat gtctttaaag gcaaagggaa gggtaaagtc ggaccagtgt 3180caaggaaagt ttgttttatt gaggtggaaa aatagcccca agcagagaaa aggagggtag 3240gtctgcatta taactgtctg tgtgaagcaa tcatttagtt actttgatta atttttcttt 3300tctccttatc tgtgcagaac aggttgcttg tttacaactg aagatcatgc tatattttat 3360atatgaagcc cctaatgcaa agctctttac ctcttgctat tttgttatat atattacaga 3420tgaaatctca ctgctaatgc tcagagatct tttttcactg taagaggtaa cctttaacaa 3480tatgggtatt acctttgtct cttcataccg gttttatgac aaaggtctat tgaatttatt 3540tgtttgtaag tttctactcc catcaaagca gctttctaag ttattgcctt ggttattatg 3600gatgatagtt atagccctta taatgcctta actaaggaag aaaagatgtt attctgagtt 3660tgttttaata catatatgaa catatagttt tattcaatta aaccaaagaa gaggtcagca 3720gggagatact aacctttgga aatgattagc tggctctgtt ttttggttaa ataagagtct 3780ttaatccttt ctccatcaag agttacttac caagggcagg ggaaggggga tatagaggtc 3840acaaggaaat aaaaatcatc tttcatcttt aattttactc cttcctctta tttttttaaa 3900agattatcga acaataaaat catttgcctt tttaa 3935161859DNAHomo sapiens 16aaaagtgcct ttgttggcct gggctcagga atccagagaa actggtcagg aggaggcccc 60agtgacaaaa acccctccct ctgcccccgc ccctctgcca gagccatata actgctcaac 120ctgtccccga gagagagtgc cctggcagct gtcggctgga aggaactggt ctgctcacac 180ttgctggctt gcgcatcagg actggcttta tctcctgact cacggtgcaa aggtgcactc 240tgcgaacgtt aagtccgtcc ccagcgcttg gaatcctacg gcccccacag ccggatcccc 300tcagccttcc aggtcctcaa ctcccgtgga cgctgaacaa tggcctccat ggggctacag 360gtaatgggca tcgcgctggc cgtcctgggc tggctggccg tcatgctgtg ctgcgcgctg 420cccatgtggc gcgtgacggc cttcatcggc agcaacattg tcacctcgca gaccatctgg 480gagggcctat ggatgaactg cgtggtgcag agcaccggcc agatgcagtg caaggtgtac 540gactcgctgc tggcactgcc gcaggacctg caggcggccc gcgccctcgt catcatcagc 600atcatcgtgg ctgctctggg cgtgctgctg tccgtggtgg ggggcaagtg taccaactgc 660ctggaggatg aaagcgccaa ggccaagacc atgatcgtgg cgggcgtggt gttcctgttg 720gccggcctta tggtgatagt gccggtgtcc tggacggccc acaacatcat ccaagacttc 780tacaatccgc tggtggcctc cgggcagaag cgggagatgg gtgcctcgct ctacgtcggc 840tgggccgcct ccggcctgct gctccttggc ggggggctgc tttgctgcaa ctgtccaccc 900cgcacagaca agccttactc cgccaagtat tctgctgccc gctctgctgc tgccagcaac 960tacgtgtaag gtgccacggc tccactctgt tcctctctgc tttgttcttc cctggactga 1020gctcagcgca ggctgtgacc ccaggagggc cctgccacgg gccactggct gctggggact 1080ggggactggg cagagactga gccaggcagg aaggcagcag ccttcagcct ctctggccca 1140ctcggacaac ttcccaaggc cgcctcctgc tagcaagaac agagtccacc ctcctctgga 1200tattggggag ggacggaagt gacagggtgt ggtggtggag tggggagctg gcttctgctg 1260gccaggatag cttaaccctg actttgggat ctgcctgcat cggcgttggc cactgtcccc 1320atttacattt tccccactct gtctgcctgc atctcctctg ttccgggtag gccttgatat 1380cacctctggg actgtgcctt gctcaccgaa acccgcgccc aggagtatgg ctgaggcctt 1440gcccacccac ctgcctggga agtgcagagt ggatggacgg gtttagaggg gaggggcgaa 1500ggtgctgtaa acaggtttgg gcagtggtgg gggagggggc cagagaggcg gctcaggttg 1560cccagctctg tggcctcagg actctctgcc tcacccgctt cagcccaggg cccctggaga 1620ctgatcccct ctgagtcctc tgccccttcc aaggacacta atgagcctgg gagggtggca 1680gggaggaggg gacagcttca cccttggaag tcctggggtt tttcctcttc cttctttgtg 1740gtttctgttt tgtaatttaa gaagagctat tcatcactgt aattattatt attttctaca 1800ataaatggga cctgtgcaca ggaggaaatt taaaaaaaaa aaaaaaaaaa aaaaaaaaa 1859176425DNAHomo sapiens 17cacacagaag cggcagccac cgaggaggga gcagtgccgg gagccccgac ggcgccttgc 60tgcatggagc tgggccgctg acagctgtcg ctgcccgcag cctctgacct ccctgggacc 120ccggcgtctg aggctcatag tctgctccct gtcttctgtc agcctcaggg catccagcgt 180ctcaggccga cctgggtccc tgggacccgg cgtttcggct tctcagccat ggagcggtgc 240agccgctgcc atcgcctcct cctcctccta cctctggtgc tggggctgag cgcggcccca 300ggctgggcag gtgcaccccc tgtggatgtg ctccgggccc tgaggttccc ctccctccct 360gatggtgtcc ggagagcgaa aggcatctgt ccagctgatg tggcctaccg agtggcacga 420cctgcccagc tcagtgcacc cactcgccag cttttcccag gaggatttcc caaagatttc 480tctctgctga ctgttgtccg gacccgccct ggtctccaag ctcccctcct gactctctac 540agtgcccagg gtgtccgaca gctgggcctg gagctgggcc gacctgtccg cttcctgtat 600gaagaccaga ctgggcggcc tcaacctccc tctcagccag tcttccgagg cctcagccta 660gcagatggca agtggcaccg tgtggctgtg gctgtgaagg gccagtctgt caccctcatt 720gttgactgca agaagcgagt cacccggcct ctcccccgaa gtgctcgtcc agtattggac 780acccatggag tgatcatctt tggtgcccgt attctggatg aagaagtctt tgagggtgat 840gtccaggagc tggccattgt cccaggggtc caggcagcct atgaatcatg tgaacagaag 900gagctggaat gcgagggggg ccagagggaa agaccccaaa accaacagcc tcacagagcc 960cagagatctc cacagcagca accatcaaga cttcacaggc cacaaaatca ggaaccccag 1020agccagccca ctgagtctct ctactatgac tacgagcccc cctattatga tgtgatgact 1080acggggacaa cccctgatta tcaggacccc accccaggtg aagaggaaga aatcctggag 1140tcgagcctct tgccacccct tgaggaggag cagacagatc tccaggtccc ccccacagcc 1200gacaggttcc aggcagagga atatggggag ggtggcacag acccccctga agggccctac 1260gattacacct atggctatgg ggatgattat cgtgaggaga cagagcttgg ccctgccctc 1320tctgcggaga cagcccactc aggagccgct gcccatggac cccgagggct gaagggagag 1380aaaggagagc ctgcagtgtt ggaacctggt atgctcgtgg aggggccccc tggcccagaa 1440ggccctgcgg gattgattgg tccccctggc atccagggga acccaggccc agttggagac 1500cctggagaga ggggcccccc tggccgagca gggctccctg gatcagatgg ggctcctggt 1560cctcctggca catctctcat gctcccattc cggtttggca gtggtggggg tgacaagggc 1620cctgtggtgg cggcccagga ggctcaggcc caggcgatcc tgcagcaggc gaggctggcg 1680ctccgtggac cccctggccc catgggatac acagggcgcc ctggaccctt gggccaacct 1740gggagccctg gcctgaaagg agagtctgga gacttaggac ctcagggccc cagaggacct 1800cagggcctca caggccctcc tggcaaggct gggcgaaggg gccgggcagg tgctgatgga 1860gcccgaggga tgcctggaga tcctggagtg aagggtgacc gaggttttga tggactccca 1920gggctccctg gagagaaggg ccataggggt gatactggtg cccagggcct tcctggtccc 1980cctggtgagg atggagagag gggagatgac ggggagattg ggcctcgagg gctgcctgga 2040gagtcgggac ctcgaggtct ccttggcccc aaaggcccac ctggtattcc tggaccccct 2100ggcgtccgag gcatggatgg tccccagggc cccaaaggga gcttgggacc ccagggagag 2160ccaggacctc ctggacaaca gggcacccct gggacccagg gtcttcccgg gccccagggt 2220gccatcggcc ctcatggaga gaagggtcct caagggaagc cagggctccc cggcatgcct 2280ggctcagacg gacccccggg tcacccaggg aaggaaggtc cccctggaac caaaggaaac 2340cagggtccct ctggacctca gggacctcta ggatacccag gacctcgagg ggtcaagggt 2400gtggacggaa ttcggggtct gaagggtcat aagggtgaga agggtgagga tggctttcct 2460gggttcaaag gtgacatagg cgtgaaaggt gacaggggcg aagttggagt ccctggttcc 2520aggggagagg atggtcctga ggggccaaag ggacgcactg gaccgactgg agaccctggg 2580cccccagggc tcatgggcga gaagggcaag ctgggtgttc ctggtctgcc tggctatcct 2640ggacgtcagg gacccaaggg gtccctagga tttcctggct ttcctggtgc cagtggagag 2700aagggagccc ggggcctgtc ggggaagtca gggcctcggg gagaacgggg ccccacgggt 2760ccacggggtc agcggggacc ccgaggtgcc actgggaagt ctggagctaa gggaacatct 2820ggtggtgatg gcccccatgg gccccctgga gagaggggcc tccctggacc tcagggtccc 2880aacgggtttc ctggaccgaa aggacccccg ggcccccctg ggaaggatgg gctgccggga 2940cacccaggcc aaagaggaga agtgggtttc caagggaaga ccggcccccc tggtcctcca 3000ggagtggtgg gacctcaggg agcagcagga gaaaccggcc ctatggggga gagaggtcac 3060ccaggccccc cggggccccc tggagagcag ggactacctg ggacagctgg aaaagaagga 3120acaaagggtg accctggtcc ccctggggcc ccagggaagg atggtcctgc tggtctgagg 3180ggattcccag gagagagagg cctcccaggc actgctggtg gacctggttt gaaggggaat 3240gaaggtccgt ctggcccccc tggccctgca ggctcccctg gggaacgagg tgcagcagga 3300tcagggggac ccattggtcc gccagggcgc ccaggcccgc agggtccccc tggagcagca 3360ggagagaaag gtgtcccagg tgagaagggc cccattggcc cgactggccg agatggagtg 3420cagggtcctg tggggcttcc tggtcctgct gggcctccag gtgtggctgg agaggatgga 3480gacaagggtg aggtggggga ccccggacag aagggcacca aagggaacaa gggtgaacat 3540ggccctcctg gaccccctgg acccattggt cctgtggggc agcctggagc agcgggagca 3600gatggggagc ccggagctcg gggaccccag ggacactttg gagccaaagg tgatgaagga 3660acaagaggat tcaatgggcc cccaggaccc attggcctac agggtttgcc aggcccctct 3720ggggagaagg gagaaacagg agatgtgggt cctatgggac cacctggccc cccaggacct 3780cgaggtccag ctggacccaa tggcgctgat ggcccacaag gtcccccagg aggtgttggg 3840aacctgggtc cccctggaga gaagggggaa ccaggagagt caggatctcc agggatccag 3900ggcgagccag gtgtcaaggg tccacgcggg gaacgtggag agaaaggaga gtcggggcag 3960ccaggagagc cagggccacc agggcctaaa ggccccacag gcgatgatgg ccccaaaggg 4020aaccctggtc ctgttggttt tcctggtgac cctggccccc ctggagaagg tggccctcgg 4080ggccaggatg gtgctaaggg tgaccgaggc gaggatggtg agccaggaca gcctggatcc 4140cctggtccca ccggggagaa tggaccccca gggccacttg gaaagcgagg tcctgctggc 4200tcgcctggtt ccgaggggcg acaaggaggg aagggagcca agggagatcc tggcgctata 4260ggtgccccgg ggaagacagg cccggtgggt cctgcaggcc cagcagggaa acctggccct 4320gatggtctga gggggctccc aggctcagtg ggtcagcaag gccgacctgg agctacaggc 4380caggctgggc ccccaggtcc tgtgggaccc ccagggctgc ctggtctccg gggcgatgct 4440ggagccaagg gagagaaggg ccacccaggt ctcattggac tgattgggcc cccgggtgag 4500cagggagaga agggagatcg gggacttcct gggcctcagg gctcccctgg gcagaagggt 4560gagatgggta tcccaggagc atccggcccc attggtcctg gaggtccccc cggcctcccc 4620ggacctgctg gccccaaagg agccaaagga gccacaggcc caggcggacc caagggagag 4680aagggtgtgc agggccctcc aggacacccg ggtcccccag gcgaggtgat ccagccactg 4740cccattcaga tgcccaagaa gactcggcgc tcggtggatg gaagccgtct gatgcaggaa 4800gatgaggcca taccgaccgg gggagccccc ggcagtcctg gggggctgga ggagatcttt 4860ggctcactcg actccctgcg ggaggagatc gagcagatga ggcggccaac agggacccag 4920gacagccctg ctcgcacctg ccaggacctg aagctgtgcc acccagagct tcccgatgga 4980gagtactggg tcgaccccaa ccagggctgt gctcgggatg ccttccgagt tttctgcaac 5040ttcacagcag ggggtgagac ctgtgtgacg cctagggatg acgtcacgca gttctcttac 5100gtggactcag agggctcccc agtgggtgtg gtccagctca ccttcctgcg gctgctcagc 5160gtctcagccc accaggacgt ctcctacccc tgctctggag cagcccgtga cggtcccctg 5220agactccgtg gggccaatga ggatgagctg agcccggaga ctagccccta tgtcaaagaa 5280ttcagagatg gctgccagac acagcaaggc cggacggtgc tggaggtgcg aacgcctgtg 5340ctggagcagc tgccagtgct ggatgcctcc ttctcagacc tgggagcccc accgaggcgg 5400ggaggggtgc tgctggggcc tgtctgcttc atgggatagg accgtctctg tctgatcctg 5460tccattcgga accaggccca cctggaatcc cacaacatca gctctgtgcc acctcccaag 5520agggctcctc actatctagg gagccctggg ccagggcgtg gagagccctc agtcggggca 5580ggccagggga ggggtgaagt ggttgcctgg acaccccacg ggaggagtgg catctggggc 5640tcttggccct cccacctgga gcctgttacc cgttagagag ctgagaccct tatttaaaac 5700tcacctccca atcaccccaa acaaatggaa gagaagagaa aggacatggc gtattttgta 5760tttaaaagta attgtattaa ttatttaaag tgtggaaagc aaaataacaa aaaagagaaa 5820cgccaacaaa aatcagcaga tgttgaagac aggggtctcg ggggtgggct ccggcaccca 5880catcctggag tcaggacttt cctcagtgac tgtgtgtagg ggggtttcag ggctgaaccc 5940cacctccctc ccaccttcct cccacctcac ctgtcgcacc cactgtgaaa gttggaatat 6000gtggtctccc tggcctcagg gctctgactc tgccagggtg gggctctcta acccacaggt 6060gttggctgcc tggcccatgt gcccactgtc tcttccactt ggtctgggtt tggcaggcac 6120tgcctgctac ttgagggcca ggatgctccc ccagggaaga aacggaatag tgtggggtgt 6180gtgcagggct gcatcccgca gatggctgga atattaaaat tcttctatat tggctggtaa 6240attgccatgg ccctgagcca ctgagtatgt tcattgccac ccctgtccct cccctgggca 6300cccctcactt tccctgatcc tgcaattaaa gggttaatgt gtggcatatg gaagggactc 6360ccaggaccct gtgcccagct tccatgctga ctgatggtta aataatgtga ttgtctcctc 6420ccagg 6425181086DNAHomo sapiens 18acagaacgac cgacggaccg agggttcgag ggagggacac ggaccaggaa cctgagctag 60gtcaaagacg cccgggccag gtgccccgtc gcaggtgccc ctggccggag atgcggtagg 120aggggcgagc gcgagaagcc ccttcctcgg cgctgccaac ccgccaccca gcccatggcg 180aaccccgggc tggggctgct tctggcgctg ggcctgccgt tcctgctggc ccgctggggc 240cgagcctggg ggcaaataca gaccacttct gcaaatgaga atagcactgt tttgccttca 300tccaccagct ccagctccga tggcaacctg cgtccagaag ccatcactgc tatcatcgtg 360gtcttctccc tcttggctgc cttgctcctg gctgtggggc tggcactgtt ggtgcggaag 420cttcgggaga agcggcagac ggagggcacc taccggccca gtagcgagga gcaggtgggt 480gcccgcgtgc caccgacccc caacctcaag ttgccgccgg aagagcggct catctgaacg 540ctggggcctg ctgcagccac caacactgcc caggactgcg ggttgctggc ttgtacaccg 600cagctgccac cgagacacca gcctctgatg gctcaggagg acttgtgggg agaggctggg 660ggcacccatg tggtgggctc tgtgcagcat gttgcctctg cttggctgtg cctgcagctc 720agggtgctgg ggctcgggac ccacccccct gcttgcggaa ccaacttttc tctgtgtgtc 780cagcaggccc cacaaccccc tctcctttct ttcagttctc ccatgcagcc gaggcccggg 840cccctcagga ctccaaggag acggtgcagg gctgcctgcc catctaggtc ccctctcctg 900catctgtctc ccttcattgc tgtgtgacct tggggaaagg cagtgccctc tctgggcagt 960cagatccacc cagtgcttaa tagcagggaa gaaggtactt caaagactct gcccctgagg 1020tcaagagagg atggggctat tcacttttat atatttatat aaaattagta gtgagatgta 1080acaaaa 1086192214DNAHomo sapiens 19agactgggct gggcaggtct gagagttagg gaaagtccgt tcccactgcc ctcggggaga 60gaagaaagga gggggcaagg gagaagctgc tggtcggact cacaatgaaa acgctccttc 120ttttgctgct ggtgctcctg gagctgggag aggcccaagg atcccttcac agggtgcccc 180tcaggaggca tccgtccctc aagaagaagc tgcgggcacg gagccagctc tctgagttct 240ggaaatccca taatttggac atgatccagt tcaccgagtc ctgctcaatg gaccagagtg 300ccaaggaacc cctcatcaac tacttggata tggaatactt cggcactatc tccattggct 360ccccaccaca gaacttcact gtcatcttcg acactggctc ctccaacctc tgggtcccct 420ctgtgtactg cactagccca gcctgcaaga cgcacagcag gttccagcct tcccagtcca 480gcacatacag ccagccaggt caatctttct ccattcagta tggaaccggg agcttgtccg 540ggatcattgg agccgaccaa gtctctgtgg aaggactaac cgtggttggc cagcagtttg 600gagaaagtgt cacagagcca ggccagacct ttgtggatgc agagtttgat ggaattctgg 660gcctgggata cccctccttg gctgtgggag gagtgactcc agtatttgac aacatgatgg 720ctcagaacct ggtggacttg ccgatgtttt ctgtctacat gagcagtaac ccagaaggtg 780gtgcggggag cgagctgatt tttggaggct acgaccactc ccatttctct gggagcctga 840attgggtccc agtcaccaag caagcttact ggcagattgc actggataac atccaggtgg 900gaggcactgt tatgttctgc tccgagggct gccaggccat tgtggacaca gggacttccc 960tcatcactgg cccttccgac aagattaagc agctgcaaaa cgccattggg gcagcccccg 1020tggatggaga atatgctgtg gagtgtgcca accttaacgt catgccggat gtcaccttca 1080ccattaacgg agtcccctat accctcagcc caactgccta caccctactg gacttcgtgg 1140atggaatgca gttctgcagc agtggctttc aaggacttga catccaccct ccagctgggc 1200ccctctggat cctgggggat gtcttcattc gacagtttta ctcagtcttt gaccgtggga 1260ataaccgtgt gggactggcc ccagcagtcc cctaaggagg ggccttgtgt ctgtgcctgc 1320ctgtctgaca gaccttgaat atgttaggct ggggcattct ttacacctac aaaaagttat 1380tttccagaga atgtagctgt ttccagggtt gcaacttgaa ttaagaccaa acagaacatg 1440agaatacaca cacacacaca catatacaca cacacacact tcacacatac acaccactcc 1500caccaccgtc atgatggagg aattacgtta tacattcata ttttgtattg atttttgatt 1560atgaaaatca aaaattttca catttgatta tgaaaatctc caaacatatg cacaagcaga 1620gatcatggta taataaatcc ctttgcaact ccactcagcc ctgacaaccc atccacacac 1680ggccaggcct gtttatctac actgctgccc actcctctct ccagctccac atgctgtacc 1740tggatcattc tgaagcaaat tccgagcatt acatcatttt gtccataaat atttctaaca 1800tccttaaata tacaatcgga attcaagcat ctcccattgt cccacaaatg tttggctgtt 1860tttgtagttg gattgtttgt attaggattc aagcaaggcc catatattgc atttatttga 1920aatgtctgta agtctctttc catctacaga gtttagcaca tttgaacgtt gctggttgaa 1980atcccgaggt gtcatttgac atggttctct gaacttatct ttcctataaa atggtagtta 2040gatctggagg tctgattttg tggcaaaaat acttcctagg tggtgctggg tacttcttgt 2100tgcatcctgt caggaggcag ataatgctgg tgcctctcta ttggtaatgt taagactgct 2160gggtgggttt ggagttcttg gctttaatca ttcattacaa agttcagcat ttta 22142011933DNAHomo sapiens 20atgctcagtt ggttggagtg gcctcactct tacctgccaa cctgggaggt tgatgatgaa 60catgtcttta

ccttttcttt ggagtttgct taccttatta atatttgctg aagtaaatgg 120cgaagctgga gaacttgagc tgcagagaca aaaaagaagc atcaatctcc aacagcctcg 180aatggctaca gagagaggaa atttggtgtt tcttacgggg tctgctcaaa acattgagtt 240tagaaccgga tccctgggaa aaattaaatt aaatgatgaa gatctcagtg agtgtttaca 300tcagatccag aaaaacaaag aagatattat agagttaaaa gggagtgcaa ttggtctgcc 360tcaaaatata tctagtcaaa tctatcagct taattccaag ctggtggatc ttgagagaaa 420attccaaggc ttgcagcaga ctgttgacaa aaaggtttgc agcagcaatc cttgccagaa 480tggtggaacc tgcctcaatc tgcatgattc ctttttttgt atctgtcccc cacagtggaa 540gggtcctctc tgctcagctg atgttaacga atgtgagatt tactcaggaa cacccttgag 600ctgccagaat ggaggcacat gtgttaatac aatgggaagt tacagttgtc actgcccacc 660tgagacgtac ggaccccagt gtgcatccaa atatgacgac tgtgaagggg gttctgtggc 720acgctgtgtc catggcatct gtgaggattt aatgcgagag caagctggag agcccaagta 780cagctgcgtc tgtgatgctg ggtggatgtt ttcacccaac agccctgcct gcacgctgga 840cagagacgag tgcagcttcc agcccgggcc ttgctccaca cttgtgcagt gtttcaacac 900tcaaggctct ttctactgtg gggcctgtcc aacaggctgg caaggcaatg gatatatttg 960cgaagatatc aatgaatgtg agataaataa cggcggctgt tctgtggctc cacccgttga 1020gtgtgtgaat acacctgggt cttcccactg ccaggcctgt ccaccagggt accagggtga 1080cggaagagtg tgcacactca cagacatctg ctcagtcagt aatggaggct gccacccaga 1140tgcctcatgc tcctcaactc taggttcctt acctctctgc acgtgtctcc cgggttatac 1200tggaaatggt tatgggccaa atggatgtgt gcagctcagt aatatttgcc taagtcaccc 1260ctgtctaaat ggacaatgca tcgacactgt ctctggttat ttttgtaagt gtgactcagg 1320ttggacaggt gtcaactgta cagaaaacat caatgagtgt ttgagcaacc cctgtttgaa 1380tggaggaact tgtgttgatg gcgttgattc tttcagttgt gaatgcacac gtctctggac 1440tggagctctc tgtcaggttc ctcagcaagt ttgtggagag tccctctcag gaataaatgg 1500aagcttcagc tacaggagcc cggatgttgg ttatgttcat gatgttaact gcttctgggt 1560tatcaaaact gaaatgggaa aggtcctgcg tatcactttc acttttttcc ggttagaatc 1620catggacaac tgtccacacg agtttcttca ggtttatgat ggagattcct cttctgcttt 1680tcaacttgga agattttgtg gctccagcct ccctcatgaa ctcctcagca gtgacaatgc 1740tctctatttt catctctatt ctgaacattt aagaaatggg agaggcttta cagtaagatg 1800ggaaacacag caaccagagt gtggaggtat cctgactggt ccttacggtt ctattaagtc 1860tccggggtat cctggaaact atcccccagg aagagattgt gtctggattg ttgtaactag 1920tcctgacctc ctggtaacat ttacttttgg gaccttgagc ctcgagcacc atgatgactg 1980caacaaagat taccttgaga ttcgagatgg tcctttgtat caggaccccc ttcttgggaa 2040gttctgcacc actttctctg tcccaccgct ccagactact ggcccctttg ccagaattca 2100cttccattca gactcccaga ttagtgacca aggcttccat atcacctact taacatcacc 2160ttcggatctg cgttgtggtg ggaactacac ggacccagag ggtgaactct tcttgcctga 2220gttgtctggg cctttcactc acaccaggca atgcgtctat atgatgaagc agccccaggg 2280agaacaaata caaatcaact tcacccacgt ggagctgcaa tgccagagtg acagttctca 2340gaattacatt gaggttcgag atggtgaaac cttacttgga aaagtctgtg gcaacggaac 2400catctctcac attaaatcca ttactaatag tgtctggatc aggtttaaaa tagatgcttc 2460tgttgaaaaa gctagtttca gagctgttta tcaagtcgct tgcggggatg aattaactgg 2520agaaggggtc attcgctcgc ctttttttcc taacgtgtat cctggagaaa gaacctgtag 2580gtggaccatc caccagcccc aaagccaagt cattctcctc aacttcactg tctttgaaat 2640tggaagttct gcccactgtg aaacagatta tgttgagatt ggtagcagtt ccattttggg 2700ttctcctgaa aataaaaagt attgcggtac agacatacct tcatttataa catctgtgta 2760caattttctt tatgtcacat tcgtgaaaag ttcttctact gaaaaccatg gtttcatggc 2820taagttcagt gctgaggatt tggcatgtgg agaaattctt acagaatcaa cagggaccat 2880tcaaagtcct ggccatccaa atgtctaccc ccacggtatc aactgtactt ggcatatatt 2940agtccaacct aatcacctga ttcatttaat gttcgaaaca tttcatctgg agtttcatta 3000caattgcaca aacgactact tggaagttta tgacaccgac tctgagacat cccttggaag 3060atactgtgga aagtcgatcc cgccatctct cacaagcagt ggtaactcat tgatgctggt 3120gtttgtgact gactccgacc tcgcttatga aggcttctta ataaactatg aagcaatcag 3180tgcagcaaca gcatgtttgc aagactacac agatgatttg gggacattca cttctccaaa 3240cttccccaat aattatccca acaactggga atgcatttat cggatcacag tgagaactgg 3300ccaactgatt gcagtgcact tcacaaactt ctccttggag gaagccattg gaaactatta 3360tacagatttt ctggaaatca gagatggagg ctatgaaaaa tcaccattgc tgggaatatt 3420ctatggctca aatctacccc caacaatcat ctctcatagt aacaaactat ggttaaaatt 3480taagagtgac caaatagaca caaggtctgg attctcagct tactgggatg ggtcatcaac 3540aggttgcggg ggtaatctca ccacttcaag cggcacgttc atatctccca actacccgat 3600gccctattac cacagctctg aatgctactg gtggttgaaa tctagccacg gcagcgcatt 3660tgaactggaa ttcaaagact ttcacttgga gcatcatcca aactgcactt tagattacct 3720ggctgtatat gatggcccaa gtagcaactc tcatctgcta actcagcttt gtggggatga 3780gaaaccccct cttattcgtt ctagtggaga cagcatgttt ataaaactga ggacagatga 3840aggtcagcaa ggacgtggct tcaaggctga ataccggcag acatgtgaga atgtggtaat 3900agtcaatcaa acctatggca tcttagagag tatagggtat ccgaatcctt attctgaaaa 3960tcagcattgc aactggacca tccgggcaac aacaggcaac actgtgaact acacattttt 4020agcatttgac ttggaacatc acataaactg ctccacagat tatttagagc tctatgatgg 4080accacggcag atgggacgct actgtggagt agacctgccc cctccaggga gtactacaag 4140ctccaagctt caagtgctgc tccttacaga tggggttggc cgccgtgaga aaggatttca 4200gatgcagtgg tttgtttacg gttgtggtgg agagctgtct ggggccacag gctccttcag 4260cagccccggg ttccccaaca ggtatccacc aaacaaggag tgtatctggt acattaggac 4320ggaccccggg agtagcattc agctcaccat ccatgacttc gatgtggagt atcattcaag 4380gtgcaacttt gatgtcttgg agatctatgg aggccccgat ttccactctc ccagaatagc 4440ccaactgtgt acccagagat cacctgagaa ccccatgcag gtctccagca ctggaaatga 4500gctagcaatt cgattcaaga ccgacttgtc cataaatggg agaggcttca atgcgtcatg 4560gcaagcagtc actggaggtt gtggtgggat tttccaggct cccagtggag agattcattc 4620tccaaattac cccagtcctt ataggagcaa cacagactgt tcttgggtca ttcgggttga 4680cagaaatcat cgtgttctct tgaacttcac tgactttgat cttgaaccac aagactcttg 4740tattatggca tacgatggct taagctccac aatgtcccgc cttgccagga cgtgtggaag 4800ggagcagctg gctaacccca tcgtctcctc aggaaacagc ctcttcttga gatttcagtc 4860tggcccttcc agacagaaca gaggcttccg agctcaattc aggcaagcct gcggaggcca 4920catcctcacc agctcatttg atactgtttc ctctccacgg ttccctgcca attatccaaa 4980caatcagaac tgcagctgga tcattcaagc gcaacctcca ttaaatcata tcaccctctc 5040ttttacccac tttgaacttg aaagaagcac aacgtgtgca cgtgactttg tagaaatttt 5100ggatggcggc cacgaagacg cgcccctccg aggccgttac tgtggcaccg acatgcccca 5160tcctatcaca tccttcagca gcgccctgac gctgagattc gtctctgatt ctagcatcag 5220tgctgggggt ttccacacca cggtcaccgc atcagtgtcg gcttgtggtg gaacgttcta 5280catggctgaa ggcatcttca acagccctgg ctacccagac atttatcccc ctaatgtgga 5340atgtgtctgg aacatcgtca gttcccctgg caaccggctc cagctgtctt ttatatcttt 5400ccagttggaa gactctcagg actgcagcag agattttgtg gagatccgtg aaggaaatgc 5460cacgggtcac ttggtgggac gatactgtgg aaactccttc cctctcaatt attcttccat 5520cgttggacat accctgtggg tcagatttat ctcagatggt tctggcagcg gcacgggctt 5580ccaggccaca tttatgaaga tatttggcaa tgataatatt gtgggaactc atgggaaagt 5640cgcctctcct ttctggcctg aaaactaccc acataactcc aattaccaat ggacagtaaa 5700tgtgaatgca tctcacgttg tccatggtag aatcttggag atggacatag aagaaataca 5760aaactgctat tatgacaaat taaggatcta tgatgggcct agcattcacg cccgcctaat 5820tggagcttac tgtggtaccc agactgaatc tttcagctcc actggaaatt ctttgacatt 5880tcatttttac tccgactctt caatctcagg gaagggattc cttctggagt ggtttgcagt 5940ggatgcacct gatggtgttt tacctaccat tgctccaggt gcttgtggtg gcttcctgag 6000gacgggagat gcacccgtgt ttctcttctc cccgggctgg cctgacagtt acagtaatag 6060agtggactgt acgtggctca tccaggctcc cgactctacc gtggaactca acattctttc 6120cctggacatt gaatctcacc gaacgtgtgc ctatgatagc cttgtgatac gagatggaga 6180taataacttg gcccagcagc tagcagttct ctgtggcaga gagatccctg ggcccatccg 6240gtctactgga gagtacatgt tcatccgctt cacctcggac tccagtgtaa ccagggcagg 6300cttcaatgca tcctttcaca agagctgcgg tggatatttg catgcagaca gagggatcat 6360cacgtccccc aagtatccag agacttaccc atccaacctc aactgttctt ggcacgtcct 6420ggtccaaagt ggcctgacca ttgctgtcca ttttgaacag cctttccaga ttccaaatgg 6480agattcttct tgcaaccagg gggattactt ggtgctaaga aatggtcctg atatctgttc 6540tccacccttg ggaccccctg gaggaaatgg tcatttttgt ggcagtcatg cttcatcaac 6600tctgttcacc tcggataatc aaatgtttgt tcagtttatt tctgatcaca gtaatgaagg 6660gcaaggattt aaaatcaaat atgaggcaaa gagtttagcc tgtgggggca acgtctacat 6720ccatgatgct gattctgctg ggtatgtgac ctcccccaac caccctcata attatccccc 6780gcacgctgat tgcatttgga tcttagcggc tccaccggaa acacgcatac agctgcaatt 6840tgaagatcga ttcgatattg aagtaacacc caactgtact tccaactacc ttgagttgcg 6900ggatggagtg gattcggatg caccaatact ttccaaattt tgtgggacat ctttgcccag 6960cagtcagtgg tcctcaggag aggttatgta tttgagattt cgatctgaca acagccccac 7020acatgtggga ttcaaggcca agtattctat agctcagtgt gggggaagag taccagggca 7080aagtggtgtt gttgaaagca ttggacatcc aacacttcca tacagagaca acttattctg 7140tgagtggcat ctccaggggc tctctggaca ctatctcacc atctcttttg aagactttaa 7200ccttcagaat tcttctggct gtgaaaaaga cttcgtggag atctgggaca atcatacctc 7260tggaaacatc ttgggcagat actgtggaaa caccattcct gacagcatag acacttctag 7320caatactgct gtggtcaggt ttgtcacaga cggctctgtg actgcctcag gattcagact 7380gcgatttgaa tccagtatgg aagagtgtgg tggggatctt cagggctcta ttggaacatt 7440tacttctccc aactacccga acccaaatcc tcatggccgg atctgcgagt ggagaatcac 7500tgccccggag ggaaggcgga tcaccctaat gtttaacaac ctgaggctgg ccacgcatcc 7560gtcctgcaac aatgagcatg tgatagtatt caatggcatt agaagtaact caccccagct 7620agagaaactg tgtagtagtg tgaatgtaag caatgagatt aaatcttcag gaaacacaat 7680gaaagtcatt tttttcacgg atggatccag gccatatggc ggcttcactg cttcctatac 7740ctccagtgaa gatgcagtgt gtggtgggtc tcttccaaat actcctgaag gaaactttac 7800ttctcctggc tatgacggag tcaggaatta ctcaagaaac ctgaactgcg aatggactct 7860cagcaatcca aatcagggaa attcatccat ttccattcac tttgaagatt tttacctaga 7920aagtcaccaa gactgtcaat ttgatgtcct cgagtttcga gtgggtgatg ctgatgggcc 7980cctgatgtgg agactttgtg gtccttcaaa gcctacattg ccattggtta taccttattc 8040tcaggtatgg attcactttg tcaccaacga acgtgtagaa cacattggat tccatgcaaa 8100gtattccttt acagattgtg gcggaataca gataggtgac agtggagtga tcacaagccc 8160caactatcca aatgcttatg acagcctgac ccactgctct tcgctgttgg aggccccaca 8220agggcacacc atcactctca catttagtga ctttgatatt gaaccccata caacttgtgc 8280ttgggactct gtcactgtca ggaatggtgg gtcccctgaa tcacccatca taggacaata 8340ctgtggaaat tcaaacccca ggacaataca gtcaggttcc aatcagctgg tcgtgacttt 8400taactcagac cattcattgc aaggtggtgg attttatgct acgtggaaca cacaaacttt 8460aggttgtggt ggaatatttc attctgataa tggtacaatc agatcccctc actggcctca 8520gaattttccc gaaaacagca gatgttcctg gacggccatt actcacaaaa gtaaacactt 8580ggagatcagc tttgacaaca acttcctaat ccccagcggt gatggacaat gtcagaatag 8640cttcgtgaag gtgtgggcag gaactgagga ggtggacaaa gccctgctag ccactggctg 8700tgggaacgtg gctccgggtc ccgttatcac accaagtaac acattcactg ccgtcttcca 8760gtctcaggag gcaccagctc agggcttctc cgcgtccttt gttagccgat gtggaagtaa 8820tttcactggc ccttcaggtt acatcatttc tccaaattac ccaaaacaat atgacaacaa 8880catgaattgc acctatgtca tagaggctaa tcctctgtca gtggtcctct tgacttttgt 8940gtccttccac ttagaagctc gttccgctgt gacgggaagc tgtgtcaacg atggcgtgca 9000cattatcaga ggttacagcg tcatgtccac cccatttgct actgtgtgtg gggatgagat 9060gccagctccc ctcaccatcg ctgggccggt tctgcttaac ttctactcca acgagcaaat 9120cacagacttc ggattcaagt tttcctatag gataatctcc tgtggtggtg tgttcaattt 9180ctcttctgga atcatcacaa gtcctgccta ttcatacgca gactacccaa atgatatgca 9240ctgtctgtat accatcaccg ttagtgacga caaggtgatc gagctcaagt tcagtgattt 9300tgatgtggtt ccctccacct cctgctccca tgactacctg gcaatttacg atggtgccaa 9360taccagcgat ccccttcttg gcaaattctg cggttccaag cgcccaccaa atgtgaagag 9420cagcaataat agtatgctcc tggtgttcaa gacagattca tttcagacag caaaaggctg 9480gaagatgtct ttccggcaga cattggggcc tcagcaagga tgtggtggtt atctgacagg 9540ctcgaataat acctttgcct ctcctgattc tgattcgaat ggaatgtatg acaagaattt 9600aaactgtgta tggatcataa ttgcacctgt aaacaaagta attcacctca ccttcaatac 9660atttgctctg gaggcagcaa gtactaggca aagatgcctt tatgattatg taaagttata 9720tgatggggat agtgaaaatg cgaacttggc tggaacgttt tgtggttcca cagtacctgc 9780tccttttatc tcttctggta acttccttac ggttcaattc atcagtgact taacattaga 9840gagggaagga tttaatgcta catacaccat catggacatg ccttgtggtg gaacatacaa 9900tgcaacttgg accccacaaa atatttcatc acccaattca tcagacccag atgtcccatt 9960ttccatctgt acttgggtca ttgattcccc tccgcatcag caggtcaaga taactgtgtg 10020ggcattacag ctgacctcgc aagactgcac gcagaattac ttacagcttc aggactcacc 10080gcagggtcac ggaaattcaa gatttcagtt ctgtggcaga aatgcttcgg ctgtgccagt 10140gttttattct tctatgagta ctgcaatggt cattttcaaa tctggagttg taaacagaaa 10200ctctagaatg agtttcacct atcagattgc agattgcaac agagactatc acaaggcatt 10260tggcaacctg agaagccctg gatggccaga taactacgac aatgacaagg attgcaccgt 10320tactctcaca gccccccaga accacaccat ttccctcttt tttcattcac ttggcatcga 10380gaactcagtt gaatgcagaa acgatttctt ggaggtgaga aatggaagta acagcaattc 10440accattactg ggcaagtact gtggaactct gctgccaaac cctgtcttct ctcaaaataa 10500tgaactatac ctacgattta agagtgatag tgtaacttct gatcgtggat atgaaatcat 10560ctggacttca tcaccctctg gatgtggtgg aactctttat ggagacagag gctcattcac 10620cagccccggc tatccaggca catacccaaa caacacgtac tgcgagtggg tccttgttgc 10680tcctgctgga aggcttgtca ccatcaactt ctacttcatc agcattgacg atccaggaga 10740ctgtgtccag aactatctca cactctatga tgggcccaac gccagctctc catcctctgg 10800accatactgc ggaggcgaca ccagcatagc tcccttcgtg gcttcctcaa atcaggtctt 10860cataaaattt catgctgatt atgcacggcg tccatccgca ttccgattaa cttgggacag 10920ctaagtgggt aacaactcgt gttcactcag cactttccct ctgcagcacg ctggacagca 10980ctctgccatc ctgatacatg acccctgctg atgccacaga gaataagctg aacttgtatg 11040gtttttcacc aaaccatgga tagaatcaat atttgtaggc caggcgtggt ggctcacccc 11100cctgtattct cagcactttg ggaggccgag gcaggttgat cacctgaggt caggagtttg 11160agactagcct ggccagcatg gtgaaacctc atctctctaa caatataata attagccagg 11220cgtggtggtg ggtgcctgta attccagcca ctcgagaggc tgaggcagga gaattgcttg 11280aacccaggag gcagaggttg cagtgagcta agatcacacc actacactcc agcctgggcg 11340agacggcaag actccatctc aaaaaaaaaa gaaacaaaaa aaaccagaat caatatttgt 11400acattttctc gaacatagaa tatagcttct ttagtcttga gtgtgcattt cattctaata 11460ttttgagctg aaatttaaaa aaactttgaa agagttggaa atgattatgg catatgtgac 11520atacattttt aaaagttaat aataatagcc aggggcagtg gctcataccc ataatcccag 11580cacgctggga ggccatgatg ggaggattgc ttgaacctag gagtttgaga ccagcctggg 11640caacaaagtg agacctgatt tttacaaaaa atcaaaaaat tagccaggca tggtggcatg 11700cacccgtggt tccagctaca caggaggttg aagcaggagg atcacttgag cccagtaggt 11760taaggctgca gtgaaaccct gtgaattaac cactgtactc cagcctgggt gacagactga 11820gaccctatct caaaaatgac aacaagaaca acaaaagtta atgataatat agaagcataa 11880atttcctgtg aatgttcaat tacacataat aaacattatt gaattgtaca caa 11933213000DNAHomo sapiens 21ctggaaccat ggagctcagc gtcctcctct tccttgcact cctcacaggc ctcttgctac 60tcctggttca gcgtcaccct aactcccatg gcaccctccc accagggccc cgccctctgc 120cccttttggg gaaccttctg cagatggaca gaagaggcct actcaaatcc tttctgaggt 180tccgagagaa atatggggac gtcttcacgg tacacctggg accgaggccc gtggtcatgc 240tgtgtggagt agaggccata cgggaggccc tggtggacaa cgctgaggcc ttctctggcc 300ggggaaaaat cgtcatcatg gacccagtct accagggata tggcatgctc tttgccaatg 360gaaaccgctg gaaggtgctt cggcgattct ctgtgaccac catgagggac ttcgggatgg 420gaaagcggag tgtggaggag cggattcagg acgaggctca gtgtctgata gaggaacttc 480ggaaatccaa gggagccctc gtggacccca ccttcctctt ccattccatt accgccaaca 540tcatctgctc catcatcttt ggaaaacgct tccactacca agatcaagag ttcctgaaga 600cgctgaactt gttctgccag agtttcttac tcatcagctc tatatccagc cagctgtttg 660agctcttctc tggcttcttg aaatactttc ctggggcaca caggcaagtt tacaaaaacc 720tacaggaaat caatgcttac attggccaca gtgtggagaa gcaccgtgaa accctggacc 780ccagcgcccc cagggacctc atcgacacct acctgctcca catggaaaaa gagaaatcca 840acccacacag tgaattcagc caccagaacc tcatcatcaa cacgctctcg ctcttctttg 900ctggcactga gaccaccagc accactctcc gctacggctt cctgctcatg ctcaaatacc 960ctcatgtcgc agagagagtc tacaaggaga ttgaacaggt ggttggccca catcgccctc 1020cagcgcttga tgaccgagcc aaaatgccat acacagaggc agtcatccgt gagattcaga 1080gatttgctga ccttctcccc atgggtgtgc cccacattgt cacccaacac accagcttct 1140gagggtacac catccccaag gacacggaag tatttctcat cctgagcact gctctccgtg 1200acccacacta ctttgaaaaa ccagacgcct tcaatcctga ccactttctg gatgccaatg 1260gggcactgaa aaagaatgaa gcttttatcc ccttctcctt agggaagcgg atttgtcttg 1320gtgaaggcat tgcccgtgcg gaattgttcc tcttcttcac caccatcctc cagaacttct 1380ccgtggccag ccccgtggct cctgaagaca tcgatctgac accccaggag tgtggtgtgg 1440gcaaaatacc cccaacatac cagatctgct tcctgccccg ctgaaggggc tgagggaagg 1500gggtcaaagg attccagggt cattcagtgt ccccacctct gtagataatg gctctgactc 1560cctgcaactt cctgcctctg agagacctgc tgcaagccag cttccttccc ttccatggca 1620ccagttgtct gaggtcgcag tgcaaatgag tggaggagtg agattattga aaattataat 1680atacaaaatt atatatatat attttgagac agagtctcac tcagttgccc aggctggagt 1740gcagtggcgt gatctcggct cactgcaacc tccacccccg gggttcaaga aattctcctg 1800cctcagcctc cctagtagct gggattacag gtgtgtgcta ccatgcctgg ctaatttttg 1860tatttttagt agagatgggg tttcaccgtg ttggccaggc tgatctcaaa ctcctgaact 1920caagtgattc acccacctta gcctcccaaa gtgctgggat tacaggtgtg agtcaccatg 1980cccggccatg tatatatata attttaaaaa ttaagatgaa attcacataa aataaaatta 2040gccattttaa agtgtacaat ttagtggtgt gtggttcatt cacaaagctg tacaaccacc 2100accatctagt tccaaacatt ttcttttttt ctgagacgga gtctcactct gtcacccagg 2160ttcgagttca gtggtcttga actcctgatg tcaggtgatt ctcctagttc caaatgtttt 2220cattatctcc ccccaacaaa acccatacct atcaagctgt cactccccat accccattct 2280ctttttcatc tcagcccctg tcaatctggt ttttgtcctt atggacttac caattctgaa 2340tatttcctat aaacagaatc acacaatatt tgattttttt tttaaaacta agccttgctc 2400tgtctcccag gctggagtgc tgtggcgtga ttttggttca ctgcaacctc cgccttccaa 2460gttcaagaga ttctcctgcc tcagcttcca agtagctggg attacaggca tgtggtacca 2520cgcctggcta attttcttgt atttttagta gggacatgtt ggccaggctg gttgtgagct 2580cctggcctca ggtgatccac acgcctcagt gtcccagagt gctgatatta caggcgtaat 2640atgtgatctt ttgtgtctgg ttcctttcac gttgaacgct atttttgagg ttcgtgcctg 2700ttgtagacca cagtcacaca ctgctgtagt cttcccccat cctcattccc agctgcctcc 2760tcctactgtt tccctctatc aaaaagcctc cttggcgcag gttccctgag ctgtgggatt 2820ctgcactggt gctttggatt ccctgatatg ttccttcaaa tccactgaga attaaataaa 2880catcgctaaa gcatgacctc cccacgtcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2940aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3000221418DNAHomo sapiens 22agcagtcagc cggccggaga cagagacttc acgactccca gtctcctcct cgccgcggcc 60gccgcctcct ccttctctcc tcctcctctt cctcctcctc cctcgctccc acagccatgt 120ctgcttagac cagagcagcc

ccacagccaa ctagggcagc tgccgccgcc acaacagcaa 180ggacagccgc tgccgccgcc cgtgagcgat gacaggagtg tttgacagaa gggtccccag 240catccgatcc ggcgacttcc aagctccgtt ccagacgtcc gcagctatgc accatccgtc 300tcaggaatcg ccaactttgc ccgagtcttc agctaccgat tctgactact acagccctac 360ggggggagcc ccgcacggct actgctctcc tacctcggct tcctatggca aagctctcaa 420cccctaccag tatcagtatc acggcgtgaa cggctccgcc gggagctacc cagccaaagc 480ttatgccgac tatagctacg ctagctccta ccaccagtac ggcggcgcct acaaccgcgt 540cccaagcgcc accaaccagc cagagaaaga agtgaccgag cccgaggtga gaatggtgaa 600tggcaaacca aagaaagttc gtaaacccag gactatttat tccagctttc agctggccgc 660attacagaga aggtttcaga agactcagta cctcgccttg ccggaacgcg ccgagctggc 720cgcctcgctg ggattgacac aaacacaggt gaaaatctgg tttcagaaca aaagatccaa 780gatcaagaag atcatgaaaa acggggagat gcccccggag cacagtccca gctccagcga 840cccaatggcg tgtaactcgc cgcagtctcc agcggtgtgg gagccccagg gctcgtcccg 900ctcgctcagc caccaccctc atgcccaccc tccgacctcc aaccagtccc cagcgtccag 960ctacctggag aactctgcat cctggtacac aagtgcagcc agctcaatca attcccacct 1020gccgccgccg ggctccttac agcacccgct ggcgctggcc tccgggacac tctattagat 1080gggctgctct ctcttactct cttttttggg actactgtgt tttgctgttc tagaaaatca 1140taaagaaagg aattcatatg gggaagttcg gaaaactgaa aaagattcat gtgtaaagct 1200tttttttgca tgtaagttat tgcatttcaa aagacccccc ctttttttac agaggacttt 1260ttttgcgcaa ctgtggacac tttcaatggt gccttgaaat ctatgacctc aacttttcaa 1320aagacttttt tcaatgttat tttagccatg taaataagtg tagatagagg aattaaactg 1380tatattctgg ataaataaaa ttatttcgac catgaaaa 1418233173DNAHomo sapiens 23aggctgcccg ctggcctcgg agcaggcgcc tgcgccctcg gcctcggcct agtcatgctc 60cgtcccggcg cgcagctgct gcggggcctc ctgctgcgga gctgcccgct gcagggctcc 120cccgggcgcc cgcgctctgt ctgcggccgg gaaggagagg aaaaaccacc cttatctgca 180gaaacacaat ggaaagacag agcagaaaca gtgataattg gaggtggctg tgttggtgtg 240agtctggctt atcacctggc caaagcaggg atgaaagatg tggtcctgct ggagaaatca 300gagctcacgg ctggatctac ctggcacgca gcaggtttaa caacttactt tcatcctgga 360ataaacttga agaaaataca ttatgatagc atcaaacttt atgagaaact ggaagaagaa 420actggtcagg tggtgggatt ccatcagcca ggtagtatca gacttgctac cacccctgta 480agggtagatg aatttaaata tcaaatgact cggactggct ggcatgcaac agaacagtat 540ctcattgaac ctgaaaaaat tcaagagatg ttccctttac tcaacatgaa taaggtttta 600gctggattgt ataatcctgg agatggtcac attgatcctt attctctaac tatggcactg 660gctgctgggg ctaggaaatg tggtgccctt ttaaaatatc ctgcaccagt aacttctctg 720aaagccaggt cagatggaac atgggacgtt gaaacaccac aggggtctat gagagcaaat 780agaattgtga atgctgcagg attttgggct cgtgaagtag gtaaaatgat tggactagaa 840catcctctca ttccggttca acatcaatat gttgttacat cgactatatc tgaagtgaaa 900gctttgaaac gagaactgcc tgtgctccgt gacctggaag gatcatatta tctccgacag 960gaaagggatg ggcttttgtt tggtccatat gaaagtcaag agaaaatgaa agttcaggac 1020tcctgggtca ccaatggagt tcctccaggt tttggaaagg aactctttga gtctgatcta 1080gatcgaatca tggaacacat caaagctgcc atggaaatgg ttcctgtctt gaaaaaggct 1140gacatcatca atgttgtcaa tggtcctatc acgtattctc ctgacattct gcctatggtg 1200gggccccatc agggggtcag aaactactgg gtggctatag gctttggata tggcataatc 1260cacgctggtg gggtagggaa atatctcagt gactggatcc tgcatggaga acctcctttt 1320gatctgatag aattggatcc taatcgctat ggcaaatgga caacaaccca gtacactgag 1380gccaaagcaa gagaatcata tggattcaac aatattgttg gttatcctaa agaagaacgg 1440tttgctggga ggccgactca acgagtcagt gggctctatc aaaggctgga gtctaagtgt 1500tccatggggt tccatgctgg ctgggagcag ccgcactggt tctacaaacc aggccaggac 1560actcagtaca ggccaagttt tcgccgcaca aactggtttg agcctgtggg ctcggagtat 1620aaacaggtta tgcaaagagt agcggtaact gacctatcac catttggcaa gtttaacatc 1680aaaggccaag attccattag actactggac catctctttg caaatgtcat tccaaaggtg 1740ggttttacaa atataagtca catgttaaca cccaagggtc gagtgtatgc tgagctgact 1800gtttctcacc aatctcctgg ggagtttctt ttaattactg gctctggatc agaacttcat 1860gatcttagat ggattgaaga agaagcagtc aaaggtggat atgatgttga aattaaaaac 1920ataactgatg agcttggagt tcttggagtt gctgggccac aggcaagaaa ggtccttcag 1980aaactgacct ctgaagatct tagtgatgat gttttcaagt ttcttcaaac caagtcctta 2040aaggtttcca acattcctgt cactgctatt aggatatctt atactggtga gctgggttgg 2100gagctgtatc acagaagaga agattctgtg gcgctgtatg acgctatcat gaatgcaggc 2160caggaggagg gaatcgacaa ttttggaacc tatgccatga atgccttacg cctggagaaa 2220gccttcagag cctgggggtt agagatgaac tgtgatacaa atcctttgga agctggactg 2280gaatattttg tgaagttaaa taagccagca gacttcatag gaaagcaagc actgaaacag 2340attaaagcca aggggctgaa acgaagactg gtctgcctca ccttggcaac ggatgatgtt 2400gatccagagg gaaatgaaag catctggtac aatggcaagg tggttggcaa cacgacatct 2460ggaagctata gctacagcat ccagaagagt ctggctttcg catatgtccc tgtacaacta 2520agtgaagtgg gacagcaagt ggaagttgaa ctattaggca aaaattaccc agcagtcatc 2580atacaagaac ctttggtatt gaccgaacca accagaaacc ggcttcagaa aaaaggtgga 2640aaggacaaaa cttgaaaaaa gaccttcagc agtcaactga attagagttg ctaatgactg 2700tccttgaaat tattataact ggctcccagg ggaatagagg aaaccaggaa ttcatttcaa 2760aatcatcaaa gtctaaattt agaatcttaa tgaaaccttt ctgttaagtg ttttctaagc 2820aagacagaat aatagataaa tgatttacat tgttctttta aatgaagaaa tttgaaatga 2880atgttttttt atttacccca cattacccaa tcagtaaaac atttaggtgt ttgctaatat 2940acacaatcat tactataacc taattaaggg acattttata attttagtaa caaatgcatt 3000cggttcttga cagctgaaaa caaattaata aattatcttt tacataaaaa catgtacaat 3060attgtttatg gatttacttc tttgagaaat ctttccttag atgaataaat gaaagtttta 3120atttttcatg atatatctgt gatgaaaata gtaaaactta acattgacat ata 3173243104DNAHomo sapiens 24aggctctatt tagagccggg taggggagcg cagcggccag atacctcagc gctacctggc 60ggaactggat ttctctcccg cctgccggcc tgcctgccac agccggactc cgccactccg 120gtagcctcat ggctgcaacc tgtgagatta gcaacatttt tagcaactac ttcagtgcga 180tgtacagctc ggaggactcc accctggcct ctgttccccc tgctgccacc tttggggccg 240atgacttggt actgaccctg agcaaccccc agatgtcatt ggagggtaca gagaaggcca 300gctggttggg ggaacagccc cagttctggt cgaagacgca ggttctggac tggatcagct 360accaagtgga gaagaacaag tacgacgcaa gcgccattga cttctcacga tgtgacatgg 420atggcgccac cctctgcaat tgtgcccttg aggagctgcg tctggtcttt gggcctctgg 480gggaccaact ccatgcccag ctgcgagacc tcacttccag ctcttctgat gagctcagtt 540ggatcattga gctgctggag aaggatggca tggccttcca ggaggcccta gacccagggc 600cctttgacca gggcagcccc tttgcccagg agctgctgga cgacggtcag caagccagcc 660cctaccaccc cggcagctgt ggcgcaggag ccccctcccc tggcagctct gacgtctcca 720ccgcagggac tggtgcttct cggagctccc actcctcaga ctccggtgga agtgacgtgg 780acctggatcc cactgatggc aagctcttcc ccagcgatgg ttttcgtgac tgcaagaagg 840gggatcccaa gcacgggaag cggaaacgag gccggccccg aaagctgagc aaagagtact 900gggactgtct cgagggcaag aagagcaagc acgcgcccag aggcacccac ctgtgggagt 960tcatccggga catcctcatc cacccggagc tcaacgaggg cctcatgaag tgggagaatc 1020ggcatgaagg cgtcttcaag ttcctgcgct ccgaggctgt ggcccaacta tggggccaaa 1080agaaaaagaa cagcaacatg acctacgaga agctgagccg ggccatgagg tactactaca 1140aacgggagat cctggaacgg gtggatggcc ggcgactcgt ctacaagttt ggcaaaaact 1200caagcggctg gaaggaggaa gaggttctcc agagtcggaa ctgagggttg gaactatacc 1260cgggaccaaa ctcacggacc actcgaggcc tgcaaacctt cctgggagga caggcaggcc 1320agatggcccc tccactgggg aatgctccca gctgtgctgt ggagagaagc tgatgttttg 1380gtgtattgtc agccatcgtc ctgggactcg gagactatgg cctcgcctcc ccaccctcct 1440cttggaatta caagccctgg ggtttgaagc tgactttata gctgcaagtg tatctccttt 1500tatctggtgc ctcctcaaac ccagtctcag acactaaatg cagacaacac cttcctcctg 1560cagacacctg gactgagcca aggaggcctg gggaggccct aggggagcac cgtgatggag 1620aggacagagc aggggctcca gcaccttctt tctggactgg cgttcacctc cctgctcagt 1680gcttgggctc cacgggcagg ggtcagagca ctccctaatt tatgtgctat ataaatatgt 1740cagatgtaca tagagatcta ttttttctaa aacattcccc tccccactcc tctcccacag 1800agtgctggac tgttccaggc cctccagtgg gctgatgctg ggacccttag gatggggctc 1860ccagctcctt tctcctgtga atggaggcag agacctccaa taaagtgcct tctgggcttt 1920ttctaacctt tgtcttagct acctgtgtac tgaaatttgg gcctttggat cgaatatggt 1980caagaggttg gaggggagga aaatgaaggt ctaccaggct gagggtgagg gcaaaggctg 2040acgaagaggg gagttacaga tttcctgtag caggtgtggg cttacagaca catggactgg 2100gctgggaggc gagcaaagga agcagctgag actgttggag aacgcttaca agacttcatg 2160caagcaagga catgaactca gaacactgag gtcagaagca tcctgctgtc atgacaccgc 2220tcgagtgacc ttgaccttga ccaagtctgt cctgtttagg actgattttt cctattaggc 2280tagggtttgg acctgatgtt ctcaagatgt ctagaattgc atggctggcc ttgtggaata 2340gatggttttg cattccagcc aagtgtgctg taaactgtat atctgtaata tgaatcccag 2400cttttgagtc tgacaaaatc agagttagga tcttgtaaag gaaaaaaaaa aaaaaacaaa 2460acaaaatgga gatgagtact tgctgagaaa gaatgaggga aggagttggc atttgttgaa 2520agtgtagtct ttttctcttt tttttttaat tgcaactttt actttagatt taggaggtcg 2580tgcgcaggtt tgttacatgg gtatattgtg tgatgctgag cttgggatgc gaatgatcct 2640gtcacccagg tagtgagtat agcacccagt gaaactgtag tctcatgcca ggcactgtgc 2700tagcccactc tggctcattt aatcctctcc taagaagaga ggagacacag cgtccccatt 2760tgacagatgc agaaagaggt tccacaggtg tgccttgatt ctgtcctaaa accgtttccc 2820ggaagctttt cctggtgtgg gcgcttctaa cctaatcctc aatcgattcc agaactatta 2880ctctgtttcc acagtgatac tgtgtctagg ttttagggag gacagttcat tgatgttact 2940taagaatgct ttccaggtgg aaagttcctt aagtttgagg cttcaaattc catacagcac 3000attaaaatcc cattcatgag tttgaaatac tgctctgttg tcttggaaat accaatcaga 3060ttgttggctg aagtgatgtg gataaagaag ggatcttaga aaaa 3104252595DNAHomo sapiens 25gcacaacttg tgaagaagcg aacacttcca tggattgtcc ttggacttag ggcgccctgc 60ccgccttttg cagaggagaa aaaacttttt tttttttttg cctcccccga gaactttccc 120cccttctcct ccctgcctct aactccgatc cccccacgcc atctcgccaa aaaaaaaaaa 180aaaaaaaaaa aagaaaaaaa aagaaaaaaa aagaaaaaaa attaccccaa tccacgcctg 240caaattcttc tggaaggatt ttcccccctc tcttcaggtt gggcgcgttt ggtgcaagat 300tctcgggatc ctcggctttg cctctccctc tccctccccc ctcctttcct ttttcctttc 360ctttcctttc tttcttcctt tccttccccc cacccccacc cccaccccaa acaaacgagt 420ccccaattct cgtccgtcct cgccgcgggc agcgggcggc ggaggcagcg tgcggcggtc 480gccaggagct gggagcccag ggcgcccgct cctcggcgca gcatgttcca gccggcgccc 540aagcgctgct tcaccatcga gtcgctggtg gccaaggaca gtcccctgcc cgcctcgcgc 600tccgaggacc ccatccgtcc cgcggcactc agctacgcta actccagccc cataaatccg 660ttcctcaacg gcttccactc ggccgccgcc gccgccgccg gtaggggcgt ctactccaac 720ccggacttgg tgttcgccga ggcggtctcg cacccgccca accccgccgt gccagtgcac 780ccggtgccgc cgccgcacgc cctggccgcc caccccctac cctcctcgca ctcgccacac 840cccctattcg cctcgcagca gcgggatccg tccaccttct acccctggct catccaccgc 900taccgatatc tgggtcatcg cttccaaggg aacgacacta gccccgagag tttccttttg 960cacaacgcgc tggcccgaaa gcccaagcgg atccgaaccg ccttctcccc gtcccagctt 1020ctaaggctgg aacacgcctt tgagaagaat cactacgtgg tgggcgccga aaggaagcag 1080ctggcacaca gcctcagcct cacggaaact caggtaaaag tatggtttca gaaccgaaga 1140acaaagttca aaaggcagaa gctggaggaa gaaggctcag attcgcaaca aaagaaaaaa 1200gggacgcacc atattaaccg gtggagaatc gccaccaagc aggcgagtcc ggaggaaata 1260gacgtgacct cagatgatta aaaacataaa cctaacccca cagaaacgga caacatggag 1320caaaagagac agggagaggt ggagaaggaa aaaaccctac aaaacaaaaa caaaccgcat 1380acacgttcac cgagaaaggg agagggaatc ggagggagca gcggaatgcg gcgaagactc 1440tggacagcga gggcacaggg tcccaaaccg aggccgcgcc aagatggcag aggatggagg 1500ctccttcatc aacaagcgac cctcgtctaa agaggcagct gagtgagaga cacagagaga 1560aggagaaaga gggagggaga gagagaaaga gagagaaaga gagagagaga gagagagaga 1620gaaagctgaa cgtgcactct gacaagggga gctgtcaatc aaacaccaaa ccggggagac 1680aagatgattg gcaggtattc cgtttatcac agtccactta aaaaatgatg atgatgataa 1740aaaccacgac ccaaccaggc acaggacttt tttgtttttt gcacttcgct gtgtttcccc 1800cccatcttta aaaataatta gtaataaaaa acaaaaattc catatctagc cccatcccac 1860acctgtttca aatccttgaa atgcatgtag cagttgttgg gcgaatggtg tttaaagacc 1920gaaaatgaat tgtaattttc ttttcctttt aaagacaggt tctgtgtgct ttttattttg 1980attttttttc ccaagaaatg tgcagtctgt aaacactttt tgataccttc tgatgtcaaa 2040gtgattgtgc aagctaaatg aagtaggctc agcgatagtg gtcctcttac agagaaacgg 2100ggagcaggac gacggggggg ctgggggtgg cgggggaggg tgcccacaaa aagaatcagg 2160acttgtactg ggaaaaaaac ccctaaatta attatatttc ttggacattc cctttcctaa 2220catcctgagg cttaaaaccc tgatgcaaac ttctcctttc agtggttgga gaaattggcc 2280gagttcaacc attcactgca atgcctattc caaactttaa atctatctat tgcaaaacct 2340gaaggactgt agttagcggg gatgatgtta agtgtggcca agcgcacggc ggcaagtttt 2400caagcactga gtttctattc caagatcata gacttactaa agagagtgac aaatgcttcc 2460ttaatgtctt ctataccaga atgtaaatat ttttgtgttt tgtgttaatt tgttagaatt 2520ctaacacact atatacttcc aagaagtatg tcaatgtcaa tattttgtca ataaagattt 2580atcaatatgc cctca 2595267282DNAHomo sapiens 26gtgcttggct acagccgctg ctgcctctcg cgaactgggc tccggggctc ccggctcccg 60agaactagaa gagaaacgcg agcgaaggga tcgaaacccg gggggttacc gacttgcaga 120caccgccagg acagtctgta acgcaggaag atcccagcgg ctccgggtct ggtgagggga 180ccataagcat gactgatagc gaatgaggaa gggcagccct aaacttttca agcaaagcct 240cagagttttg ggttcactca ttagcatagg aaatcgattc accgaaaacc caaacaaaga 300aaaacaagcc gacagtccag gcaggatgca ggcaaatcca gttcgggatt aagggtaaaa 360ggctttttgg gttttttttc ctttggtttg attttttaaa atatggggag gggggtgaca 420tctacccgat tctaggctcc ggcaggaacg caatgggtta atgaatggac aagccgcgga 480gtattgatcg gctgccgccg gagaaagaaa gaaaaacaaa aaccagaccg aacctgcctt 540cccgctgtgg ctgctcggcg ccccaattaa gcagggtcat ctcaggctgg ctgcatgcct 600cagctgaaga tcccagctcc tgtcaatgcc acctctctgc ttgactgtct ccttccagat 660tcgagcaggt atgagctggg aagaatgaag gcagggcatg cccgtgtgcc agctctgcac 720agctggatag ctgaggaaag atgtggagga gaagccgggg attgtgtgga agtctaaggg 780tgttgtttgc cctttgggtt ccagaagatg catgccagga ccctgggtgg cactgccagg 840aagcaacaga gaggagataa aactcacagc agacagactt gccttaacaa caactccctt 900gaattaaaac acgcttttca agaaaacaaa ttatcagttc gatcagcaaa cagcagagaa 960gtttctctca taatggcaaa gaagggccgg gttgctgacc agtgaaagag cttcagaaaa 1020ggagagggga gatgagatgg ccagaaggag caagagcacc gtacatccct ggacaacctc 1080attctaatgg gtcaggggct gggacgtgca ttttggagtg caggagaagt ggcaactcac 1140aaatgctaga ttttcttcta gagatgacca agctgtagtt cttaaagcag tggcactagg 1200gcagaaaact ctcacacttt gatgtgcaca cacagcccct ggggatcttg ttgacatgta 1260gattctgatt ccgtaagtcg ggctgagatt ctgcatttcc aacaagctcc tagatgaggt 1320ccattttgct ggtccatgaa acacacttag aataagtagc aaggtatagg aggatactga 1380ctttgctcag tgatgcttgg gcttccgtcc aaactaaaat aaaacaaaag cagacataaa 1440tggcccaatt caacagcctg agaagtttgg tgataatgac ccaagccctg gcctggtgac 1500caagtggctg ctcagagagc tctatctcca aactccttcc cttcctgcct cccctccaag 1560agtgagtaat gtgccagagt tcattggggt ctgctgtccc cagggaaagg tggcccagtt 1620gccaagtgca agtgtataga acggcttacc tgtgcaaagc tatcagccct ggacctatgg 1680gcctagaaac attacttgcc actcactcac tcactatcat tcattcattt ctgcaacaaa 1740cacttcctga gcatatgcta tacaccaggc cctgagctca gctctgggga tacaggatga 1800atggcagatt gtgccatcag gaagccgact gcacagtcag cccgctggag cacatatgaa 1860aaacaatacg gatgttttga tttattatca tattgatcat tatgatggta gcgtatactt 1920ttggaaggct tgccatacat taggcattgt gctaagcaca ttatatggtt aatctcatca 1980atcttcacaa cctatgtggc aggtactatt attaaaccca cttcaaagag gagggaactg 2040aacctcagag agggtaagtg acttgcacaa ggacacaagc tagtgaggag aggaactgag 2100aggaatggcc agacaggcca tcagcctctg tccccacatg ctgggtctga gtgtctgacg 2160gtggacacat tcccttcctg gagggagagc tcctagggag ctgatggcag cactgagtct 2220ggaatgtgat gggagtgcat tagatgacgt gggtgatctg atgagtacag aggcgtcaca 2280ctgcaatgac ttcatgcaca tatctcccct tgaatgcaca gagattcagc agaggccagg 2340agctcaagtt tctggcccag tgtccccctc ttcccctggg gaaagccagg gacacactgc 2400ctggctttgc tacacctttc taggcaaagg cagtatgctc tccctctcct tggcctccct 2460ggctgtccac acatccacac ccactcacac acacatgcac atgatcatac acattacaca 2520agcccacatg cccacagaca tgctcacact cacactcaca tgcatacact gccatacaca 2580acacacatac atacattcac acacacttgc acacacacac acacacacag ttctgatggc 2640caatcttttg gggctatgtt gacactgtga agcaggtgaa acaaagtctt tgccactccc 2700tgctttgggc ctattatgtt tgttttatag tttaactctc aaaagacaac tttattttcc 2760aaaattattc aggttcccag ccaggtgcag tggctcacac ctgtaatccc agtactttgg 2820gaggccaagg cgggcagatc acctgaggtc aggagtttga gaccagcttg gccaacatgg 2880tgaaacccag tctctactaa aaatacaaaa attagccaga catggtggca cacacatgta 2940atcccagcta ttcgggaggc tgaggcagga gaatcgcttg aacccgggag gcggaggttg 3000cagtgggcca agatcgtgcc actgcactcc agcctgggca acagagcaag actccatctc 3060aaaaaacaaa aacaaaatca ttcaggttct gtaggggacc ctcactgtgt cctggattcc 3120attccacttt taaagtccca aacagcttgt atggccactt cccttgacac ccaaaccaga 3180taggagtctt aaatgacaca gagtattgat ggtttcttta aaaggaaatc cactctcaat 3240gggaagctgg ataacttcgc atccagattt catccatctt gggctttggt ggctgctgtt 3300tgtttttgtg caggagaatc tctcccagcc aacgtcgatt tcactaacac agtggttaac 3360ctttgctctc tactcctgca tcaatcttcc gcctaccgca tgttgagcca tgctgctttc 3420tggcattcct tttggatttt cagtttacta cccaactacc agtcctaata acatcagata 3480aaagggcttc cgctgtgctg cacttgtttt caaaaactat aaatgccatc gacccagagt 3540taagtccagc ctcagagaga cagaatataa atacccaagt ggccctgggc cactgagttc 3600ctcagacatt atgtgctatg ggagttccag aaagggggat tgcctggttt tgagtgcaga 3660aggcttcctg gaggaggcga gatttctgat gggcctctgt tatgagctaa attgagtcca 3720ccccaaaatt cagatgttca aatcctaacc tgtagtacct aagcatgtgg ccttatttgg 3780aagcagaagc ataacagagg taattcgtta agatgaggtc acagtggaag agggtggacc 3840ccaatctgat acaactcgtg tccttataaa aagcagaaat ttgaagacag acacacaaga 3900agatgaaggc agagacctgg ctgatgcggc tataagccaa ggaacgccaa agattgccag 3960caaagcacca gcagccaggg agaggcctcg aacaaattct ccctcccagc aaaaaggagg 4020aaggaaggaa cctccaaaag aagcaggcca ggcacagtgg ctcacgcctg taatcccagt 4080actttgggag gttaaggcag gcggatcacc tgagatcaag agttcaagac cagcctggcc 4140aacatggtga aacctcatct ctacagaaaa atacaaaaat tagtcaggtg tagtggcgtg 4200cacctgtagt cccagttact cgggaggctg aggcaagaga atcgcttgaa cctgggaggt 4260ggaggttgca gtgagccaag atcgtgccat tgcactccag cctgggtgac agagcgagac 4320tccatctcag aaaaacaaaa aagaacccta ctgacacctg gatttcagac ttccagcctc 4380cagaactgtg agatgttaca tttctgtcat ttaaacaccc agtttgtagt actttgttgc 4440aacagctcta gtgagctaat acagccttgt aggacaggta ggaatttgta atgcacagag 4500aaagccaact ggccacagtt gttgaaaata atagaatcga agcgccccta tcactaccac 4560cccaggccat cactttcaaa gctgttcaaa atgatgcagc cgcgtgagaa ggccggaagg 4620ccagggcggg agatgggctc caggtgggcc caggctgcct gcagaaccag cttgcctcac 4680tgcctggttg ccaaggagca cctgtggcta ggaggagatg cccaggaaga aaatttggcc

4740acatccctgc ctgcctccct ggcaatgggt gatgctctct gccagctggc ccagctcccc 4800caccacatac ctggctagga gtcagtagga aaacagtgtg tgtttgtagg gctctgcact 4860gaagggcatt agatccatgc aaaggctaat aaattagaga taagtgggat ttgtagattt 4920gctggaggtt agagctgcag ggtctggcat cagctctggg tcttttccat ggccccaggc 4980tggctcaggt gtgagctgaa gaggcaaaac tgtctgttta ggttgcattg ggttcccctg 5040aaagatctgt tgaagtccta acctcgggta cctctgtttg tgctatttgc aaacaggctc 5100tttgcagatg taatcaagga aagatgaggc aacgctgatt tagtcaggcc ttaatccagt 5160gactggtgtc ttcataagac aaggaaatct ggacacagac acacaaagag gaaaaagcca 5220aagacacaga gacacatgta cacagggaga actccatggg acaacgcagg cacagatcgg 5280agtgacgcgg ctgcaagcca aggagcgcca agattgccag caaccccctg gggctgcaag 5340aggtgagaag gagccttcgg agggaacatg cactgctgat tccttgattc cagatttctg 5400acctccagaa gcatgggaga acagatttcc cttgtttgaa ggcacccagt ctgtggtcct 5460tcatcatggc agccctcagg aatggataca ggcccttccc tgcctgcctg gtggagcagc 5520ctccaagggg agcctttgct agcaggaaga ggcatcgcat ggagctcaga cccgcctcag 5580aggaacttct ctcagcctcc tctctccgca cacccgacca aggtgtgaaa tccctcccct 5640ttacctctgc cacttgcagg tggcaggatg ctggagctgt ccctgcctct ttgtaaagtg 5700agggaagggc agccctctct gctctttttt tttttttttt tgagacagag tctcactctg 5760tctcccaggc tggagtgcaa tagcacgatc tcggctcact gcaacctccg cctcccaggt 5820tcaagcgatt ctcctgcctc aacctcctga gtagctggaa ttacaggtgc ctgccaccac 5880gcccagctaa ttttgtattg ttagtagagc cagggtttca ccatgtcggc caggctagtc 5940tcaaactcct gacctcaggt gatccacctg cctcggcctc ccaaagtgct gcgattacag 6000acatgagcca ccacgcccgg cctgctccac ttctaaggct tcttgtgaca atgtaagaga 6060aaggagatga cagagctttg caacgggagg agggctatgt gttctggtga ccaattcact 6120gtcttgtgtc gggacaggaa gaagcccttc atacgggcag caggctggga gccagggagg 6180aggaaagatc acgatccact ccctggtaca tggcccttct gcaccccgca gtctccttcc 6240aggtgccaca acgagaaggc acacatcctt ggcacagcac ttgaggcttt tcaccactgg 6300ctgcactcac ccctccagac tcactgcctt gcaccaaccc ttttccgccc accccactct 6360atgctgtcca cagcctccac cccagccacc tgattctgca ggccaatgtc acattcttcc 6420agtccaggtt ctattctggc atttcttgtc attattttgc tgagaatgtg tctctcttga 6480ctttgaactt attgagagca ggaatcatga ctcagccata tatcccagca cttggcccag 6540ggcctgtcgt ttccagggta ggtggtctag gctgattgaa ggaatggcat ttagtcttta 6600aaatgaaagc atgttgccta gcttggttat ttttgaactc tataatcaag gactacgttt 6660acctgaatag cctctgcaga acaccaattc cgtaaggtgc ttcacacaca cacaccaatt 6720ctatcattta atacattttg gaaaggctac atactactac agcctctttt acagattagc 6780aatgtccatg agcgcactaa aggttgagac attctgcagt gaagaagcct atttcatttt 6840gtttaaccaa gtatttctca aatttatttg atcatatgtg gcagaaaatg ctgtgtctgg 6900cattcttcat ttccctcttc ctcctttaac atggaacccc tgatgtcttt agcttggcac 6960atcgccaccc agaataaaaa ctacctttcc cagctcttcc tgcagctagg ggcagccctg 7020ggataaattc tggacaatga aatacaggca gaagtaaatc atatacgatt tccatgaagg 7080gaccttaaac agaagtgtgc ccttctcttc cccacacatt cctcctcctg tctgaaatgt 7140agatgcaact gctggcattt gagcagccat cttgggccat gtggtagctt cttatggatg 7200atctaggact aattcaaggg tctagattta cctccaaact ttgtttatct acaaaaaata 7260aaactctatc ttcttaaagc ta 7282271731DNAHomo sapiens 27aactgcagcg ccggggctgg gggaggggag cctactcact cccccaactc ccgggcggtg 60actcatcaac gagcaccagc ggccagaggt gagcagtccc gggaaggggc cgagaggcgg 120ggccgccagg tcgggcaggt gtgcgctccg ccccgccgcg cgcacagagc gctagtcctt 180cggcgagcga gcaccttcga cgcggtccgg ggaccccctc gtcgctgtcc tcccgacgcg 240gacccgcgtg ccccaggcct cgcgctgccc ggccggctcc tcgtgtccca ctcccggcgc 300acgccctccc gcgagtcccg ggcccctccc gcgcccctct tctcggcgcg cgcgcagcat 360ggcgcccccg caggtcctcg cgttcgggct tctgcttgcc gcggcgacgg cgacttttgc 420cgcagctcag gaagaatgtg tctgtgaaaa ctacaagctg gccgtaaact gctttgtgaa 480taataatcgt caatgccagt gtacttcagt tggtgcacaa aatactgtca tttgctcaaa 540gctggctgcc aaatgtttgg tgatgaaggc agaaatgaat ggctcaaaac ttgggagaag 600agcaaaacct gaaggggccc tccagaacaa tgatgggctt tatgatcctg actgcgatga 660gagcgggctc tttaaggcca agcagtgcaa cggcacctcc atgtgctggt gtgtgaacac 720tgctggggtc agaagaacag acaaggacac tgaaataacc tgctctgagc gagtgagaac 780ctactggatc atcattgaac taaaacacaa agcaagagaa aaaccttatg atagtaaaag 840tttgcggact gcacttcaga aggagatcac aacgcgttat caactggatc caaaatttat 900cacgagtatt ttgtatgaga ataatgttat cactattgat ctggttcaaa attcttctca 960aaaaactcag aatgatgtgg acatagctga tgtggcttat tattttgaaa aagatgttaa 1020aggtgaatcc ttgtttcatt ctaagaaaat ggacctgaca gtaaatgggg aacaactgga 1080tctggatcct ggtcaaactt taatttatta tgttgatgaa aaagcacctg aattctcaat 1140gcagggtcta aaagctggtg ttattgctgt tattgtggtt gtggtgatag cagttgttgc 1200tggaattgtt gtgctggtta tttccagaaa gaagagaatg gcaaagtatg agaaggctga 1260gataaaggag atgggtgaga tgcataggga actcaatgca taactatata atttgaagat 1320tatagaagaa gggaaatagc aaatggacac aaattacaaa tgtgtgtgcg tgggacgaag 1380acatctttga aggtcatgag tttgttagtt taacatcata tatttgtaat agtgaaacct 1440gtactcaaaa tataagcagc ttgaaactgg ctttaccaat cttgaaattt gaccacaagt 1500gtcttatata tgcagatcta atgtaaaatc cagaacttgg actccatcgt taaaattatt 1560tatgtgtaac attcaaatgt gtgcattaaa tatgcttcca cagtaaaatc tgaaaaactg 1620atttgtgatt gaaagctgcc tttctattta cttgagtctt gtacatacat acttttttat 1680gagctatgaa ataaaacatt ttaaactgaa tttcttaaaa aaaaaaaaaa a 1731285765DNAHomo sapiens 28actccagcct cgcgcgggag ggggcgcggc cgtgactcac ccccttccct ctgcgttcct 60ccctccctct ctctctctct ctcacacaca cacacccctc ccctgccatc cctccccgga 120ctccggctcc ggctccgatt gcaatttgca acctccgctg ccgtcgccgc agcagccacc 180aattcgccag cggttcaggt ggctcttgcc tcgatgtcct agcctagggg cccccgggcc 240ggacttggct gggctccctt caccctctgc ggagtcatga gggcgaacga cgctctgcag 300gtgctgggct tgcttttcag cctggcccgg ggctccgagg tgggcaactc tcaggcagtg 360tgtcctggga ctctgaatgg cctgagtgtg accggcgatg ctgagaacca ataccagaca 420ctgtacaagc tctacgagag gtgtgaggtg gtgatgggga accttgagat tgtgctcacg 480ggacacaatg ccgacctctc cttcctgcag tggattcgag aagtgacagg ctatgtcctc 540gtggccatga atgaattctc tactctacca ttgcccaacc tccgcgtggt gcgagggacc 600caggtctacg atgggaagtt tgccatcttc gtcatgttga actataacac caactccagc 660cacgctctgc gccagctccg cttgactcag ctcaccgaga ttctgtcagg gggtgtttat 720attgagaaga acgataagct ttgtcacatg gacacaattg actggaggga catcgtgagg 780gaccgagatg ctgagatagt ggtgaaggac aatggcagaa gctgtccccc ctgtcatgag 840gtttgcaagg ggcgatgctg gggtcctgga tcagaagact gccagacatt gaccaagacc 900atctgtgctc ctcagtgtaa tggtcactgc tttgggccca accccaacca gtgctgccat 960gatgagtgtg ccgggggctg ctcaggccct caggacacag actgctttgc ctgccggcac 1020ttcaatgaca gtggagcctg tgtacctcgc tgtccacagc ctcttgtcta caacaagcta 1080actttccagc tggaacccaa tccccacacc aagtatcagt atggaggagt ttgtgtagcc 1140agctgtcccc ataactttgt ggtggatcaa acatcctgtg tcagggcctg tcctcctgac 1200aagatggaag tagataaaaa tgggctcaag atgtgtgagc cttgtggggg actatgtccc 1260aaagcctgtg agggaacagg ctctgggagc cgcttccaga ctgtggactc gagcaacatt 1320gatggatttg tgaactgcac caagatcctg ggcaacctgg actttctgat caccggcctc 1380aatggagacc cctggcacaa gatccctgcc ctggacccag agaagctcaa tgtcttccgg 1440acagtacggg agatcacagg ttacctgaac atccagtcct ggccgcccca catgcacaac 1500ttcagtgttt tttccaattt gacaaccatt ggaggcagaa gcctctacaa ccggggcttc 1560tcattgttga tcatgaagaa cttgaatgtc acatctctgg gcttccgatc cctgaaggaa 1620attagtgctg ggcgtatcta tataagtgcc aataggcagc tctgctacca ccactctttg 1680aactggacca aggtgcttcg ggggcctacg gaagagcgac tagacatcaa gcataatcgg 1740ccgcgcagag actgcgtggc agagggcaaa gtgtgtgacc cactgtgctc ctctggggga 1800tgctggggcc caggccctgg tcagtgcttg tcctgtcgaa attatagccg aggaggtgtc 1860tgtgtgaccc actgcaactt tctgaatggg gagcctcgag aatttgccca tgaggccgaa 1920tgcttctcct gccacccgga atgccaaccc atggagggca ctgccacatg caatggctcg 1980ggctctgata cttgtgctca atgtgcccat tttcgagatg ggccccactg tgtgagcagc 2040tgcccccatg gagtcctagg tgccaagggc ccaatctaca agtacccaga tgttcagaat 2100gaatgtcggc cctgccatga gaactgcacc caggggtgta aaggaccaga gcttcaagac 2160tgtttaggac aaacactggt gctgatcggc aaaacccatc tgacaatggc tttgacagtg 2220atagcaggat tggtagtgat tttcatgatg ctgggcggca cttttctcta ctggcgtggg 2280cgccggattc agaataaaag ggctatgagg cgatacttgg aacggggtga gagcatagag 2340cctctggacc ccagtgagaa ggctaacaaa gtcttggcca gaatcttcaa agagacagag 2400ctaaggaagc ttaaagtgct tggctcgggt gtctttggaa ctgtgcacaa aggagtgtgg 2460atccctgagg gtgaatcaat caagattcca gtctgcatta aagtcattga ggacaagagt 2520ggacggcaga gttttcaagc tgtgacagat catatgctgg ccattggcag cctggaccat 2580gcccacattg taaggctgct gggactatgc ccagggtcat ctctgcagct tgtcactcaa 2640tatttgcctc tgggttctct gctggatcat gtgagacaac accggggggc actggggcca 2700cagctgctgc tcaactgggg agtacaaatt gccaagggaa tgtactacct tgaggaacat 2760ggtatggtgc atagaaacct ggctgcccga aacgtgctac tcaagtcacc cagtcaggtt 2820caggtggcag attttggtgt ggctgacctg ctgcctcctg atgataagca gctgctatac 2880agtgaggcca agactccaat taagtggatg gcccttgaga gtatccactt tgggaaatac 2940acacaccaga gtgatgtctg gagctatggt gtgacagttt gggagttgat gaccttcggg 3000gcagagccct atgcagggct acgattggct gaagtaccag acctgctaga gaagggggag 3060cggttggcac agccccagat ctgcacaatt gatgtctaca tggtgatggt caagtgttgg 3120atgattgatg agaacattcg cccaaccttt aaagaactag ccaatgagtt caccaggatg 3180gcccgagacc caccacggta tctggtcata aagagagaga gtgggcctgg aatagcccct 3240gggccagagc cccatggtct gacaaacaag aagctagagg aagtagagct ggagccagaa 3300ctagacctag acctagactt ggaagcagag gaggacaacc tggcaaccac cacactgggc 3360tccgccctca gcctaccagt tggaacactt aatcggccac gtgggagcca gagcctttta 3420agtccatcat ctggatacat gcccatgaac cagggtaatc ttggggagtc ttgccaggag 3480tctgcagttt ctgggagcag tgaacggtgc ccccgtccag tctctctaca cccaatgcca 3540cggggatgcc tggcatcaga gtcatcagag gggcatgtaa caggctctga ggctgagctc 3600caggagaaag tgtcaatgtg taggagccgg agcaggagcc ggagcccacg gccacgcgga 3660gatagcgcct accattccca gcgccacagt ctgctgactc ctgttacccc actctcccca 3720cccgggttag aggaagagga tgtcaacggt tatgtcatgc cagatacaca cctcaaaggt 3780actccctcct cccgggaagg caccctttct tcagtgggtc tcagttctgt cctgggtact 3840gaagaagaag atgaagatga ggagtatgaa tacatgaacc ggaggagaag gcacagtcca 3900cctcatcccc ctaggccaag ttcccttgag gagctgggtt atgagtacat ggatgtgggg 3960tcagacctca gtgcctctct gggcagcaca cagagttgcc cactccaccc tgtacccatc 4020atgcccactg caggcacaac tccagatgaa gactatgaat atatgaatcg gcaacgagat 4080ggaggtggtc ctgggggtga ttatgcagcc atgggggcct gcccagcatc tgagcaaggg 4140tatgaagaga tgagagcttt tcaggggcct ggacatcagg ccccccatgt ccattatgcc 4200cgcctaaaaa ctctacgtag cttagaggct acagactctg cctttgataa ccctgattac 4260tggcatagca ggcttttccc caaggctaat gcccagagaa cgtaactcct gctccctgtg 4320gcactcaggg agcatttaat ggcagctagt gcctttagag ggtaccgtct tctccctatt 4380ccctctctct cccaggtccc agcccctttt ccccagtccc agacaattcc attcaatctt 4440tggaggcttt taaacatttt gacacaaaat tcttatggta tgtagccagc tgtgcacttt 4500cttctctttc ccaaccccag gaaaggtttt ccttattttg tgtgctttcc cagtcccatt 4560cctcagcttc ttcacaggca ctcctggaga tatgaaggat tactctccat atcccttcct 4620ctcaggctct tgactacttg gaactaggct cttatgtgtg cctttgtttc ccatcagact 4680gtcaagaaga ggaaagggag gaaacctagc agaggaaagt gtaattttgg tttatgactc 4740ttaaccccct agaaagacag aagcttaaaa tctgtgaaga aagaggttag gagtagatat 4800tgattactat cataattcag cacttaacta tgagccaggc atcatactaa acttcaccta 4860cattatctca cttagtcctt tatcatcctt aaaacaattc tgtgacatac atattatctc 4920attttacaca aagggaagtc gggcatggtg gctcatgcct gtaatctcag cactttggga 4980ggctgaggca gaaggattac ctgaggcaag gagtttgaga ccagcttagc caacatagta 5040agacccccat ctctttaaaa aaaaaaaaaa aaaaaaaaaa aaaactttag aactgggtgc 5100agtggctcat gcctgtaatc ccagccagca ctttgggagg ctgagatggg aagatcactt 5160gagcccagaa ttagagataa gcctatggaa acatagcaag acactgtctc tacaggggaa 5220aaaaaaaaaa gaaactgagc cttaaagaga tgaaataaat taagcagtag atccaggatg 5280caaaatcctc ccaattcctg tgcatgtgct cttattgtaa ggtgccaaga aaaactgatt 5340taagttacag cccttgttta aggggcactg tttcttgttt ttgcactgaa tcaagtctaa 5400ccccaacagc cacatcctcc tatacctaga catctcatct caggaagtgg tggtgggggt 5460agtcagaagg aaaaataact ggacatcttt gtgtaaacca taatccacat gtgccgtaaa 5520tgatcttcac tccttatccg agggcaaatt cacaaggatc cccaagatcc acttttagaa 5580gccattctca tccagcagtg agaagcttcc aggtaggaca gaaaaaagat ccagcttcag 5640ctgcacacct ctgtcccctt ggatggggaa ctaagggaaa acgtctgttg tatcactgaa 5700gttttttgtt ttgtttttat acgtgtctga ataaaaatgc caaagttttt tttcagcaaa 5760aaaaa 5765296330DNAHomo sapiens 29aggagctggc ggagggcgtt cgtcctggga ctgcacttgc tcccgtcggg tcgcccggct 60tcaccggacc cgcaggctcc cggggcaggg ccggggccag agctcgcgtg tcggcgggac 120atgcgctgcg tcgcctctaa cctcgggctg tgctcttttt ccaggtggcc cgccggtttc 180tgagccttct gccctgcggg gacacggtct gcaccctgcc cgcggccacg gaccatgacc 240atgaccctcc acaccaaagc atctgggatg gccctactgc atcagatcca agggaacgag 300ctggagcccc tgaaccgtcc gcagctcaag atccccctgg agcggcccct gggcgaggtg 360tacctggaca gcagcaagcc cgccgtgtac aactaccccg agggcgccgc ctacgagttc 420aacgccgcgg ccgccgccaa cgcgcaggtc tacggtcaga ccggcctccc ctacggcccc 480gggtctgagg ctgcggcgtt cggctccaac ggcctggggg gtttcccccc actcaacagc 540gtgtctccga gcccgctgat gctactgcac ccgccgccgc agctgtcgcc tttcctgcag 600ccccacggcc agcaggtgcc ctactacctg gagaacgagc ccagcggcta cacggtgcgc 660gaggccggcc cgccggcatt ctacaggcca aattcagata atcgacgcca gggtggcaga 720gaaagattgg ccagtaccaa tgacaaggga agtatggcta tggaatctgc caaggagact 780cgctactgtg cagtgtgcaa tgactatgct tcaggctacc attatggagt ctggtcctgt 840gagggctgca aggccttctt caagagaagt attcaaggac ataacgacta tatgtgtcca 900gccaccaacc agtgcaccat tgataaaaac aggaggaaga gctgccaggc ctgccggctc 960cgcaaatgct acgaagtggg aatgatgaaa ggtgggatac gaaaagaccg aagaggaggg 1020agaatgttga aacacaagcg ccagagagat gatggggagg gcaggggtga agtggggtct 1080gctggagaca tgagagctgc caacctttgg ccaagcccgc tcatgatcaa acgctctaag 1140aagaacagcc tggccttgtc cctgacggcc gaccagatgg tcagtgcctt gttggatgct 1200gagcccccca tactctattc cgagtatgat cctaccagac ccttcagtga agcttcgatg 1260atgggcttac tgaccaacct ggcagacagg gagctggttc acatgatcaa ctgggcgaag 1320agggtgccag gctttgtgga tttgaccctc catgatcagg tccaccttct agaatgtgcc 1380tggctagaga tcctgatgat tggtctcgtc tggcgctcca tggagcaccc agggaagcta 1440ctgtttgctc ctaacttgct cttggacagg aaccagggaa aatgtgtaga gggcatggtg 1500gagatcttcg acatgctgct ggctacatca tctcggttcc gcatgatgaa tctgcaggga 1560gaggagtttg tgtgcctcaa atctattatt ttgcttaatt ctggagtgta cacatttctg 1620tccagcaccc tgaagtctct ggaagagaag gaccatatcc accgagtcct ggacaagatc 1680acagacactt tgatccacct gatggccaag gcaggcctga ccctgcagca gcagcaccag 1740cggctggccc agctcctcct catcctctcc cacatcaggc acatgagtaa caaaggcatg 1800gagcatctgt acagcatgaa gtgcaagaac gtggtgcccc tctatgacct gctgctggag 1860atgctggacg cccaccgcct acatgcgccc actagccgtg gaggggcatc cgtggaggag 1920acggaccaaa gccacttggc cactgcgggc tctacttcat cgcattcctt gcaaaagtat 1980tacatcacgg gggaggcaga gggtttccct gccacggtct gagagctccc tggctcccac 2040acggttcaga taatccctgc tgcattttac cctcatcatg caccacttta gccaaattct 2100gtctcctgca tacactccgg catgcatcca acaccaatgg ctttctagat gagtggccat 2160tcatttgctt gctcagttct tagtggcaca tcttctgtct tctgttggga acagccaaag 2220ggattccaag gctaaatctt tgtaacagct ctctttcccc cttgctatgt tactaagcgt 2280gaggattccc gtagctcttc acagctgaac tcagtctatg ggttggggct cagataactc 2340tgtgcattta agctacttgt agagacccag gcctggagag tagacatttt gcctctgata 2400agcacttttt aaatggctct aagaataagc cacagcaaag aatttaaagt ggctccttta 2460attggtgact tggagaaagc taggtcaagg gtttattata gcaccctctt gtattcctat 2520ggcaatgcat ccttttatga aagtggtaca ccttaaagct tttatatgac tgtagcagag 2580tatctggtga ttgtcaattc attcccccta taggaataca aggggcacac agggaaggca 2640gatcccctag ttggcaagac tattttaact tgatacactg cagattcaga tgtgctgaaa 2700gctctgcctc tggctttccg gtcatgggtt ccagttaatt catgcctccc atggacctat 2760ggagagcagc aagttgatct tagttaagtc tccctatatg agggataagt tcctgatttt 2820tgtttttatt tttgtgttac aaaagaaagc cctccctccc tgaacttgca gtaaggtcag 2880cttcaggacc tgttccagtg ggcactgtac ttggatcttc ccggcgtgtg tgtgccttac 2940acaggggtga actgttcact gtggtgatgc atgatgaggg taaatggtag ttgaaaggag 3000caggggccct ggtgttgcat ttagccctgg ggcatggagc tgaacagtac ttgtgcagga 3060ttgttgtggc tactagagaa caagagggaa agtagggcag aaactggata cagttctgag 3120gcacagccag acttgctcag ggtggccctg ccacaggctg cagctaccta ggaacattcc 3180ttgcagaccc cgcattgccc tttgggggtg ccctgggatc cctggggtag tccagctctt 3240cttcatttcc cagcgtggcc ctggttggaa gaagcagctg tcacagctgc tgtagacagc 3300tgtgttccta caattggccc agcaccctgg ggcacgggag aagggtgggg accgttgctg 3360tcactactca ggctgactgg ggcctggtca gattacgtat gcccttggtg gtttagagat 3420aatccaaaat cagggtttgg tttggggaag aaaatcctcc cccttcctcc cccgccccgt 3480tccctaccgc ctccactcct gccagctcat ttccttcaat ttcctttgac ctataggcta 3540aaaaagaaag gctcattcca gccacagggc agccttccct gggcctttgc ttctctagca 3600caattatggg ttacttcctt tttcttaaca aaaaagaatg tttgatttcc tctgggtgac 3660cttattgtct gtaattgaaa ccctattgag aggtgatgtc tgtgttagcc aatgacccag 3720gtgagctgct cgggcttctc ttggtatgtc ttgtttggaa aagtggattt cattcatttc 3780tgattgtcca gttaagtgat caccaaagga ctgagaatct gggagggcaa aaaaaaaaaa 3840aaagttttta tgtgcactta aatttgggga caattttatg tatctgtgtt aaggatatgt 3900ttaagaacat aattcttttg ttgctgtttg tttaagaagc accttagttt gtttaagaag 3960caccttatat agtataatat atattttttt gaaattacat tgcttgttta tcagacaatt 4020gaatgtagta attctgttct ggatttaatt tgactgggtt aacatgcaaa aaccaaggaa 4080aaatatttag tttttttttt tttttttgta tacttttcaa gctaccttgt catgtataca 4140gtcatttatg cctaaagcct ggtgattatt catttaaatg aagatcacat ttcatatcaa 4200cttttgtatc cacagtagac aaaatagcac taatccagat gcctattgtt ggatactgaa 4260tgacagacaa tcttatgtag caaagattat gcctgaaaag gaaaattatt cagggcagct 4320aattttgctt ttaccaaaat atcagtagta atatttttgg acagtagcta atgggtcagt 4380gggttctttt taatgtttat acttagattt tcttttaaaa aaattaaaat aaaacaaaaa 4440aaaatttcta ggactagacg atgtaatacc agctaaagcc aaacaattat acagtggaag 4500gttttacatt attcatccaa tgtgtttcta ttcatgttaa gatactacta catttgaagt 4560gggcagagaa catcagatga ttgaaatgtt cgcccagggg tctccagcaa ctttggaaat 4620ctctttgtat ttttacttga agtgccacta atggacagca gatattttct ggctgatgtt 4680ggtattgggt gtaggaacat gatttaaaaa aaaactcttg cctctgcttt cccccactct 4740gaggcaagtt aaaatgtaaa agatgtgatt tatctggggg gctcaggtat ggtggggaag 4800tggattcagg aatctgggga atggcaaata tattaagaag agtattgaaa gtatttggag

4860gaaaatggtt aattctgggt gtgcaccagg gttcagtaga gtccacttct gccctggaga 4920ccacaaatca actagctcca tttacagcca tttctaaaat ggcagcttca gttctagaga 4980agaaagaaca acatcagcag taaagtccat ggaatagcta gtggtctgtg tttcttttcg 5040ccattgccta gcttgccgta atgattctat aatgccatca tgcagcaatt atgagaggct 5100aggtcatcca aagagaagac cctatcaatg taggttgcaa aatctaaccc ctaaggaagt 5160gcagtctttg atttgatttc cctagtaacc ttgcagatat gtttaaccaa gccatagccc 5220atgccttttg agggctgaac aaataaggga cttactgata atttactttt gatcacatta 5280aggtgttctc accttgaaat cttatacact gaaatggcca ttgatttagg ccactggctt 5340agagtactcc ttcccctgca tgacactgat tacaaatact ttcctattca tactttccaa 5400ttatgagatg gactgtgggt actgggagtg atcactaaca ccatagtaat gtctaatatt 5460cacaggcaga tctgcttggg gaagctagtt atgtgaaagg caaatagagt catacagtag 5520ctcaaaaggc aaccataatt ctctttggtg caggtcttgg gagcgtgatc tagattacac 5580tgcaccattc ccaagttaat cccctgaaaa cttactctca actggagcaa atgaactttg 5640gtcccaaata tccatctttt cagtagcgtt aattatgctc tgtttccaac tgcatttcct 5700ttccaattga attaaagtgt ggcctcgttt ttagtcattt aaaattgttt tctaagtaat 5760tgctgcctct attatggcac ttcaattttg cactgtcttt tgagattcaa gaaaaatttc 5820tattcttttt tttgcatcca attgtgcctg aacttttaaa atatgtaaat gctgccatgt 5880tccaaaccca tcgtcagtgt gtgtgtttag agctgtgcac cctagaaaca acatattgtc 5940ccatgagcag gtgcctgaga cacagacccc tttgcattca cagagaggtc attggttata 6000gagacttgaa ttaataagtg acattatgcc agtttctgtt ctctcacagg tgataaacaa 6060tgctttttgt gcactacata ctcttcagtg tagagctctt gttttatggg aaaaggctca 6120aatgccaaat tgtgtttgat ggattaatat gcccttttgc cgatgcatac tattactgat 6180gtgactcggt tttgtcgcag ctttgctttg tttaatgaaa cacacttgta aacctctttt 6240gcactttgaa aaagaatcca gcgggatgct cgagcacctg taaacaattt tctcaaccta 6300tttgatgttc aaataaagaa ttaaactaaa 6330302634DNAHomo sapiens 30cggctccggt cggagacaat cgcgctgagc gggcgccgca gcgggagcgg gagccggagc 60tgcgaggcgc ggcgcagagc tggggctgcg cggggccggg cgagcgggac caggcgggag 120ccatggaccg ctagggcccg gcctagcccc gcgatgccgc cggcgagtgg ccccagcgtc 180ctcgcgcggc tgttgccgct gctggggctg ctgctcggca gcgcctcccg ggctcccggc 240aagtcgccgc cggagccccc cagcccgcag gagatcctga tcaaggtgca ggtgtatgtg 300agcggggagc tggtgcccct ggcccgggcc tcagtggatg tgtttgggaa ccggactctg 360ctggcagctg gcaccacaga ctcagagggt gtggccaccc tgcccctcag ttatcgcttg 420ggcacctggg tgctggtcac tgctgcccgc cctggcttcc tcaccaactc tgtgccctgg 480cgtgttgaca agctgccctt gtatgcgtct gtcagcctct acctgctccc tgagcggccg 540gccacgctca tcctctatga ggacctggtg cacattctcc taggctctcc cggtgcccgc 600tcccagccct tggtgcagtt ccagcgccgg gctgcccgcc tgcctgtcag ctccacctac 660agccagctct gggcgtcact tacgcctgcc agcacccagc aggaaatgcg ggctttccct 720gccttcctgg gcactgaggc ctccagctca ggcaatggct cctggctgga gctgatgccc 780ctgactgctg tgagcgtgca cctgctgaca ggtaatggga cagaggtgcc gctctcaggc 840cccattcacc tgtccctgcc cgtgccctcc gagactcgtg ccctcaccgt gggcaccagc 900attccagcct ggagatttga ccccaagagt gggctgtggg tgcgcaatgg cactggtgta 960atccggaagg aaggccggca gctctactgg accttcgtct ccccccagct ggggtactgg 1020gtggccgcca tggcctcccc cacggctggg ctggtcacca tcacgtcggg catccaggac 1080atcggcacct accacaccat cttcttgctc accatcctgg cagccctggc cctgctggtg 1140cttatcctgc tgtgtctgct catctactac tgccggaggc gctgcctgaa gccgaggcaa 1200cagcaccgca agctgcagct ctcggggccc tctgacggta acaaacgaga ccaggccacc 1260tcgatgtccc agctccacct catctgtggg ggacccctgg aacccgcccc gtcgggggac 1320cccgaggctc cgcctccagg ccccctccac tcggccttct ccagctcccg ggacttggcc 1380tcctcccggg atgacttctt ccgcaccaag ccgcgctctg ccagccgccc ggccgccgag 1440ccttcgggtg cccgcggggg cgagagcgcc gggctcaagg gcgctcgctc ggccgagggc 1500cccggcgggc tggagcccgg cctagaggag caccggcggg ggccctcggg ggctgcggcc 1560ttcctgcacg agccgccctc gccgccgccg cccttcgacc actacctggg ccacaagggg 1620gcggccgagg gcaagacccc cgacttcctg ctgtcgcagt cggtggacca gctggcgcgg 1680ccgccgtcgc tgggccaggc ggggcagctc atcttctgcg gctccatcga ccacctcaag 1740gacaacgtct accgcaacgt catgcccacc ctggtgatcc ccgcgcacta cgtgcgcctc 1800ggcggcgagg cgggcgccgc cggcgtgggc gacgagccgg ccccgccgga gggcacggca 1860cccggcccgg cgcgcgcttt tccccagccc gacccccagc gcccgcagat gccgggccac 1920tcgggcccgg ggggcgaggg cggcgggggc ggcggcgagg gctggggggc cgggcgcgcg 1980gcgcccgtca gtggctcagt caccatccct gtgctattca acgagtccac catggcgcag 2040ctcaacgggg agctgcaggc cctgaccgag aagaagctgc tggaactggg cgtgaagccg 2100cacccgcgcg cctggttcgt gtccctcgac gggcgctcca actcgcaagt gcgccactct 2160tacatcgacc tgcaggcggg cggcggggca cgcagcaccg acgccagcct ggactcgggc 2220gtagatgtcc acgaggcgcg gcccgcgcgc cgccggcccg cgagggagga gcgggagcgc 2280gccccgcctg ccgcgccgcc gccgccgccc gcgcccccgc gcctggcgct cagcgaggac 2340acggagccca gcagcagcga gagccgcacg ggcctctgct ctccggagga caactcgctg 2400acgccgctgc tggacgaggt ggcggcgccc gagggccggg cggccacggt accccggggg 2460cggggccgca gccgcgggga cagctcccgc agcagcgcca gcgagctgcg gcgcgactcg 2520ctcaccagcc cggaggacga gctgggggcg gaggtgggcg acgaggcggg agacaagaag 2580agcccgtggc agcggcggga ggagcggccg ctgatggtgt tcaacgtcaa gtag 2634314110DNAHomo sapiens 31agtgcactct agaaacactg ctgtggtgga gaaactggac cccaggtctg gagcgaattc 60cagcctgcag ggctgataag cgaggcatta gtgagattga gagagacttt accccgccgt 120ggtggttgga gggcgcgcag tagagcagca gcacaggcgc gggtcccggg aggccggctc 180tgctcgcgcc gagatgtgga atctccttca cgaaaccgac tcggctgtgg ccaccgcgcg 240ccgcccgcgc tggctgtgcg ctggggcgct ggtgctggcg ggtggcttct ttctcctcgg 300cttcctcttc gggtggttta taaaatcctc caatgaagct actaacatta ctccaaagca 360taatatgaaa gcatttttgg atgaattgaa agctgagaac atcaagaagt tcttatataa 420ttttacacag ataccacatt tagcaggaac agaacaaaac tttcagcttg caaagcaaat 480tcaatcccag tggaaagaat ttggcctgga ttctgttgag ctagcacatt atgatgtcct 540gttgtcctac ccaaataaga ctcatcccaa ctacatctca ataattaatg aagatggaaa 600tgagattttc aacacatcat tatttgaacc acctcctcca ggatatgaaa atgtttcgga 660tattgtacca cctttcagtg ctttctctcc tcaaggaatg ccagagggcg atctagtgta 720tgttaactat gcacgaactg aagacttctt taaattggaa cgggacatga aaatcaattg 780ctctgggaaa attgtaattg ccagatatgg gaaagttttc agaggaaata aggttaaaaa 840tgcccagctg gcaggggcca aaggagtcat tctctactcc gaccctgctg actactttgc 900tcctggggtg aagtcctatc cagatggttg gaatcttcct ggaggtggtg tccagcgtgg 960aaatatccta aatctgaatg gtgcaggaga ccctctcaca ccaggttacc cagcaaatga 1020atatgcttat aggcgtggaa ttgcagaggc tgttggtctt ccaagtattc ctgttcatcc 1080aattggatac tatgatgcac agaagctcct agaaaaaatg ggtggctcag caccaccaga 1140tagcagctgg agaggaagtc tcaaagtgcc ctacaatgtt ggacctggct ttactggaaa 1200cttttctaca caaaaagtca agatgcacat ccactctacc aatgaagtga caagaattta 1260caatgtgata ggtactctca gaggagcagt ggaaccagac agatatgtca ttctgggagg 1320tcaccgggac tcatgggtgt ttggtggtat tgaccctcag agtggagcag ctgttgttca 1380tgaaattgtg aggagctttg gaacactgaa aaaggaaggg tggagaccta gaagaacaat 1440tttgtttgca agctgggatg cagaagaatt tggtcttctt ggttctactg agtgggcaga 1500ggagaattca agactccttc aagagcgtgg cgtggcttat attaatgctg actcatctat 1560agaaggaaac tacactctga gagttgattg tacaccgctg atgtacagct tggtacacaa 1620cctaacaaaa gagctgaaaa gccctgatga aggctttgaa ggcaaatctc tttatgaaag 1680ttggactaaa aaaagtcctt ccccagagtt cagtggcatg cccaggataa gcaaattggg 1740atctggaaat gattttgagg tgttcttcca acgacttgga attgcttcag gcagagcacg 1800gtatactaaa aattgggaaa caaacaaatt cagcggctat ccactgtatc acagtgtcta 1860tgaaacatat gagttggtgg aaaagtttta tgatccaatg tttaaatatc acctcactgt 1920ggcccaggtt cgaggaggga tggtgtttga gctagccaat tccatagtgc tcccttttga 1980ttgtcgagat tatgctgtag ttttaagaaa gtatgctgac aaaatctaca gtatttctat 2040gaaacatcca caggaaatga agacatacag tgtatcattt gattcacttt tttctgcagt 2100aaagaatttt acagaaattg cttccaagtt cagtgagaga ctccaggact ttgacaaaag 2160caacccaata gtattaagaa tgatgaatga tcaactcatg tttctggaaa gagcatttat 2220tgatccatta gggttaccag acaggccttt ttataggcat gtcatctatg ctccaagcag 2280ccacaacaag tatgcagggg agtcattccc aggaatttat gatgctctgt ttgatattga 2340aagcaaagtg gacccttcca aggcctgggg agaagtgaag agacagattt atgttgcagc 2400cttcacagtg caggcagctg cagagacttt gagtgaagta gcctaagagg attctttaga 2460gaatccgtat tgaatttgtg tggtatgtca ctcagaaaga atcgtaatgg gtatattgat 2520aaattttaaa attggtatat ttgaaataaa gttgaatatt atatatagtt atgtgagtgt 2580ttatatatgt gtgtgtttat attgtttatc ttctccctat ggattaaaac tgaatttcat 2640aattataaga ggttattctg aagtggaaaa atttaactca gtattaaatc taaggagaat 2700ggcctaatat agtaaaactc tcatctggca ttatcaggga atcaagtcta atctattcat 2760gtcacttcac acagaagaaa acatcagtat gtcagagagc acactgggga atatgcacaa 2820gattatccca agccagaggc ctcacggcct acctggccag cctgggctga gaggatcact 2880atctcagcac actatttggg aaatggatca aatcacactt ttagtaaatg ttatcactct 2940atagcataag aaataattat tttttattta tataaaaggc tatagtataa aatatatgta 3000tagtaattaa atgaacactt gtgaacctaa tagccatatg aagaaaataa catttctaat 3060atctttggat gccccatgta ctaatgacag ttatgctttt gcattttctt gaattttatg 3120tttatttatc tttcctctgt cattatttat aattttatca cacatggctg tatcctttac 3180atgttttggc attatgtatt tttgaacttt ttgtaaagac aatcatacca tgtgtaattt 3240tcagggactt gatttttttc attgactttt aagggttcaa atatattatc actgtggctg 3300tagtttgcca tattttgctg atatagagca ttcattcaca tgagggtagg attcagggtc 3360catcaagaca gagaaaacat acagtaatgt gaatagggaa agttaatatg aagaattatt 3420aattgttaca gcattggaac aatgaaatat tgtctagtaa tatgtaaaga gaagtctcaa 3480gaatatgtga tgagcagatg taaggaattg ctcttgtctc catggtgaat ttggagcagc 3540caatgaagag tcccctcaca ttgtggcctc gctcaaagtt aagaagtcgc tgtagtgttg 3600cccttgaaga atctgcttca aattgacact tcagaactcc ccagaaactt gtcttctggg 3660ccaatgtgta aagctgttta tgaagaaatg tcaagccaga ggggctctac tacaaatttg 3720gcaaaggaca atttcaggag aagctcttgg ccgctgggtt ctcctggcca ccatgaactt 3780caggaagtgg gtgccatagc agcagcctga actacagaat ctgggcactg gtgtagctct 3840gtatgccctc cgtgtcagat gctggagatg tcatttgcat tgccagagtt tgccaagggt 3900gcacacagaa agcagattga aaagcaccct cttggaacat ctctccaatg ccttctactc 3960acaaagttta acatcattaa cacgtgacaa agaagaacta tttaatgggc ccagatctat 4020ttatgaagac aatcaagtgg gagtttggag tggataaccc aaatttggat aactggtgaa 4080taataaaatg tatttatttc tgctggtgta 4110323304DNAHomo sapiens 32actccatctg agggtggctg cgtgtccaca tacgagggga cagggctgag gatgaggaga 60accctgggga cccagaagac cgtgccttgc ctggaagtcc tgcctgtagg cctgaaggac 120ttgccctaac agagcctcaa caactacctg gtgattccta cttcagcccc ttggtgtgag 180cagcttctca acatgaacta cagcctccac ttggccttcg tgtgtctgag tctcttcact 240gagaggatgt gcatccaggg gagtcagttc aacgtcgagg tcggcagaag tgacaagctt 300tccctgcctg gctttgagaa cctcacagca ggatataaca aatttctcag gcccaatttt 360ggtggagaac ccgtacagat agcgctgact ctggacattg caagtatctc tagcatttca 420gagagtaaca tggactacac agccaccata tacctccgac agcgctggat ggaccagcgg 480ctggtgtttg aaggcaacaa gagcttcact ctggatgccc gcctcgtgga gttcctctgg 540gtgccagata cttacattgt ggagtccaag aagtccttcc tccatgaagt cactgtggga 600aacaggctca tccgcctctt ctccaatggc acggtcctgt atgccctcag aatcacgaca 660actgttgcat gtaacatgga tctgtctaaa taccccatgg acacacagac atgcaagttg 720cagctggaaa gctggggcta tgatggaaat gatgtggagt tcacctggct gagagggaac 780gactctgtgc gtggactgga acacctgcgg cttgctcagt acaccataga gcggtatttc 840accttagtca ccagatcgca gcaggagaca ggaaattaca ctagattggt cttacagttt 900gagcttcgga ggaatgttct gtatttcatt ttggaaacct acgttccttc cactttcctg 960gtggtgttgt cctgggtttc attttggatc tctctcgatt cagtccctgc aagaacctgc 1020attggagtga cgaccgtgtt atcaatgacc acactgatga tcgggtcccg cacttctctt 1080cccaacacca actgcttcat caaggccatc gatgtgtacc tggggatctg ctttagcttt 1140gtgtttgggg ccttgctaga atatgcagtt gctcactaca gttccttaca gcagatggca 1200gccaaagata gggggacaac aaaggaagta gaagaagtca gtattactaa tatcatcaac 1260agctccatct ccagctttaa acggaagatc agctttgcca gcattgaaat ttccagcgac 1320aacgttgact acagtgactt gacaatgaaa accagcgaca agttcaagtt tgtcttccga 1380gaaaagatgg gcaggattgt tgattatttc acaattcaaa accccagtaa tgttgatcac 1440tattccaaac tactgtttcc tttgattttt atgctagcca atgtatttta ctgggcatac 1500tacatgtatt tttgagtcaa tgttaaattt cttgcatgcc ataggtcttc aacaggacaa 1560gataatgatg taaatggtat tttaggccaa gtgtgcaccc acatccaatg gtgctacaag 1620tgactgaaat aatatttgag tctttctgct caaagaatga agctccaacc attgttctaa 1680gctgtgtaga agtcctagca ttataggatc ttgtaataga aacatcagtc cattcctctt 1740tcatcttaat caaggacatt cccatggagc ccaagattac aaatgtactc agggctgttt 1800attcggtggc tccctggttt gcatttacct catataaaga atgggaagga gaccattggg 1860taaccctcaa gtgtcagaag ttgtttctaa agtaactata catgtttttt actaaatctc 1920tgcagtgctt ataaaataca ttgttgccta tttagggagt aacattttct agtttttgtt 1980tctggttaaa atgaaatatg ggcttatgtc aattcattgg aagtcaatgc actaactcaa 2040taccaagatg agtttttaaa taatgaatat tatttaatac cacaacagaa ttatccccaa 2100tttccaataa gtcctatcat tgaaaattca aatataagtg aagaaaaaat tagtagatca 2160acaatctaaa caaatccctc ggttctaaga tacaatggat tccccatact ggaaggactc 2220tgaggcttta ttcccccact atgcatatct tatcatttta ttattataca cacatccatc 2280ctaaactata ctaaagccct tttcccatgc atggatggaa atggaagatt tttttttaac 2340ttgttctaga agtcttaata tgggctgttg ccatgaaggc ttgcagaatt gagtccattt 2400tctagctgcc tttattcaca tagtgatggg gtactaaaag tactgggttg actcagagag 2460tcgctgtcat tctgtcattg ctgctactct aacactgagc aacactctcc cagtggcaga 2520tcccctgtat cattccaaga ggagcattca tccctttgct ctaatgatca ggaatgatgc 2580ttattagaaa acaaactgct tgacccagga acaagtggct tagcttaagt aaacttggct 2640ttgctcagat ccctgatcct tccagctggt ctgctatgag tggcttatcc cgcatgagca 2700ggagcgtgct ggccctgagt actgaacttt ctgagtaaca atgagatacg ttacagaacc 2760tatgttcagg ttgcgggtga gctgccctct ccaaatccag ccagagatgc acattcctcg 2820gccagtctca gccaacagta ccaaaagtga tttttgagtg tgccagggta aaggcttcca 2880gttcagcctc agttatttta gacaatctcg ccatctttaa tttcttagct tcctgttcta 2940ataaatgcac ggctttacct ttcctgtcag aaataaacca aggctctaaa agatgatttc 3000ccttctgtaa ctccctagag ccacaggttc tcattccttt tcccattata cttctcacaa 3060ttcagtttct atgagtttga tcacctgatt tttttaacaa aatatttcta acgggaatgg 3120gtgggagtgc tggtgaaaag aggtgaaatg tggttgtatg agccaatcat atttgtgatt 3180ttttaaaaaa agtttaaaag gaaatatctg ttctgaaacc ccacttaagc attgttttta 3240tataaaaaca atgataaaga tgtgaaactg tgaaataaat ataccatatt agctacccac 3300caaa 3304333083DNAHomo sapiens 33gaacactgag ctgcctggcg ccgtcttgat actttcagaa agaatgcatt ccctgtaaaa 60aaaaaaaaaa aatactgaga gagggagaga gagagagaag aagagagaga gacggaggga 120gagcgagaca gagcgagcaa cgcaatctga ccgagcaggt cgtacgccgc cgcctcctcc 180tcctctctgc tcttcgctac ccaggtgacc cgaggaggga ctccgcctcc gagcggctga 240ggaccccggt gcagaggagc ctggctcgca gaattgcaga gtcgtcgccc ctttttacaa 300cctggtcccg ttttattctg ccgtacccag tttttggatt tttgtcttcc ccttcttctc 360tttgctaaac gacccctcca agataatttt taaaaaacct tctcctttgc tcacctttgc 420ttcccagcct tcccatcccc ccaccgaaag caaatcattc aacgaccccc gaccctccga 480cggcaggagc cccccgacct cccaggcgga ccgccctccc tccccgcgcg cgggttccgg 540gcccggcgag agggcgcgag cacagccgag gccatggagg tgacggcgga ccagccgcgc 600tgggtgagcc accaccaccc cgccgtgctc aacgggcagc acccggacac gcaccacccg 660ggcctcagcc actcctacat ggacgcggcg cagtacccgc tgccggagga ggtggatgtg 720ctttttaaca tcgacggtca aggcaaccac gtcccgccct actacggaaa ctcggtcagg 780gccacggtgc agaggtaccc tccgacccac cacgggagcc aggtgtgccg cccgcctctg 840cttcatggat ccctaccctg gctggacggc ggcaaagccc tgggcagcca ccacaccgcc 900tccccctgga atctcagccc cttctccaag acgtccatcc accacggctc cccggggccc 960ctctccgtct accccccggc ctcgtcctcc tccttgtcgg ggggccacgc cagcccgcac 1020ctcttcacct tcccgcccac cccgccgaag gacgtctccc cggacccatc gctgtccacc 1080ccaggctcgg ccggctcggc ccggcaggac gagaaagagt gcctcaagta ccaggtgccc 1140ctgcccgaca gcatgaagct ggagtcgtcc cactcccgtg gcagcatgac cgccctgggt 1200ggagcctcct cgtcgaccca ccaccccatc accacctacc cgccctacgt gcccgagtac 1260agctccggac tcttcccccc cagcagcctg ctgggcggct cccccaccgg cttcggatgc 1320aagtccaggc ccaaggcccg gtccagcaca gaaggcaggg agtgtgtgaa ctgtggggca 1380acctcgaccc cactgtggcg gcgagatggc acgggacact acctgtgcaa cgcctgcggg 1440ctctatcaca aaatgaacgg acagaaccgg cccctcatta agcccaagcg aaggctgtct 1500gcagccagga gagcagggac gtcctgtgcg aactgtcaga ccaccacaac cacactctgg 1560aggaggaatg ccaatgggga ccctgtctgc aatgcctgtg ggctctacta caagcttcac 1620aatattaaca gacccctgac tatgaagaag gaaggcatcc agaccagaaa ccgaaaaatg 1680tctagcaaat ccaaaaagtg caaaaaagtg catgactcac tggaggactt ccccaagaac 1740agctcgttta acccggccgc cctctccaga cacatgtcct ccctgagcca catctcgccc 1800ttcagccact ccagccacat gctgaccacg cccacgccga tgcacccgcc atccagcctg 1860tcctttggac cacaccaccc ctccagcatg gtcaccgcca tgggttagag ccctgctcga 1920tgctcacagg gcccccagcg agagtccctg cagtcccttt cgacttgcat ttttgcagga 1980gcagtatcat gaagcctaaa cgcgatggat atatgttttt gaaggcagaa agcaaaatta 2040tgtttgccac tttgcaaagg agctcactgt ggtgtctgtg ttccaaccac tgaatctgga 2100ccccatctgt gaataagcca ttctgactca tatcccctat ttaacagggt ctctagtgct 2160gtgaaaaaaa aaatgctgaa cattgcatat aacttatatt gtaagaaata ctgtacaatg 2220actttattgc atctgggtag ctgtaaggca tgaaggatgc caagaagttt aaggaatatg 2280ggagaaatag tgtggaaatt aagaagaaac taggtctgat attcaaatgg acaaactgcc 2340agttttgttt cctttcactg gccacagttg tttgatgcat taaaagaaaa taaaaaaaag 2400aaaaaagaga aaagaaaaaa aaagaaaaaa gttgtaggcg aatcatttgt tcaaagctgt 2460tggcctctgc aaaggaaata ccagttctgg gcaatcagtg ttaccgttca ccagttgccg 2520ttgagggttt cagagagcct ttttctaggc ctacatgctt tgtgaacaag tccctgtaat 2580tgttgtttgt atgtataatt caaagcacca aaataagaaa agatgtagat ttatttcatc 2640atattataca gaccgaactg ttgtataaat ttatttactg ctagtcttaa gaactgcttt 2700ctttcgtttg tttgtttcaa tattttcctt ctctctcaat ttttggttga ataaactaga 2760ttacattcag ttggcctaag gtggttgtgc tcggagggtt tcttgtttct tttccatttt 2820gtttttggat gatatttatt aaatagcttc taagagtccg gcggcatctg tcttgtccct 2880attcctgcag cctgtgctga gggtagcagt gtatgagcta ccagcgtgca tgtcagcgac 2940cctggcccga caggccacgt cctgcaatcg gcccggctgc ctcttcgccc tgtcgtgttc 3000tgtgttagtg atcactgcct ttaatacagt ctgttggaat aatattataa gcataataat 3060aaagtgaaaa tattttaaaa cta 3083344934DNAHomo sapiens 34gagtcagagc ctcttctctc taagtcacgg gaactgccct tgctacttgt gacctgccct 60ttactcagca gtttttgttc tgggaagccc tgggattctg ctaataccta tcactgtagg 120tgctgaaggg aaacagatga agaacatgac ctcaaggagc ttcctgtcaa tgagaagacc 180aagctgacgc ctggcaaaga

tattaaagag gagcctgaaa ctgttccttg gacatcttat 240gaatgtcaga aaataccttt tggagggtta gaagatcagg ggacatggtt gttcacattt 300gctgccacgg aacaccgcca gtcttcactt ggaaacagaa tcacgccttg tgaagagatc 360atccctaagc aggagagaag ctactaaagg attgtgtcct cctccacctt ccctgtgctc 420ggtctccacc tgtctcccat tctgtgacga tggttcaatg gaagagactc tgccagctgc 480attacttgtg ggctctgggc tgctatatgc tgctggccac tgtggctctg aaactttctt 540tcaggttgaa gtgtgactct gaccacttgg gtctggagtc cagggaatct caaagccagt 600actgtaggaa tatcttgtat aatttcctga aacttccagc aaagaggtct atcaactgtt 660caggggtcac ccgaggggac caagaggcag tgcttcaggc tattctgaat aacctggagg 720tcaagaagaa gcgagagcct ttcacagaca cccactacct ctccctcacc agagactgtg 780agcacttcaa ggctgaaagg aagttcatac agttcccact gagcaaagaa gaggtggagt 840tccctattgc atactctatg gtgattcatg agaagattga aaactttgaa aggctactgc 900gagctgtgta tgcccctcag aacatatact gtgtccatgt ggatgagaag tccccagaaa 960ctttcaaaga ggcggtcaaa gcaattattt cttgcttccc aaatgtcttc atagccagta 1020agctggttcg ggtggtttat gcctcctggt ccagggtgca agctgacctc aactgcatgg 1080aagacttgct ccagagctca gtgccgtgga aatacttcct gaatacatgt gggacggact 1140ttcctataaa gagcaatgca gagatggtcc aggctctcaa gatgttgaat gggaggaata 1200gcatggagtc agaggtacct cctaagcaca aagaaacccg ctggaaatat cactttgagg 1260tagtgagaga cacattacac ctaaccaaca agaagaagga tcctccccct tataatttaa 1320ctatgtttac agggaatgcg tacattgtgg cttcccgaga tttcgtccaa catgttttga 1380agaaccctaa atcccaacaa ctgattgaat gggtaaaaga cacttatagc ccagatgaac 1440acctctgggc cacccttcag cgtgcacggt ggatgcctgg ctctgttccc aaccacccca 1500agtacgacat ctcagacatg acttctattg ccaggctggt caagtggcag ggtcatgagg 1560gagacatcga taagggtgct ccttatgctc cctgctctgg aatccaccag cgggctatct 1620gcgtttatgg ggctggggac ttgaattgga tgcttcaaaa ccatcacctg ttggccaaca 1680agtttgaccc aaaggtagat gataatgctc ttcagtgctt agaagaatac ctacgttata 1740aggccatcta tgggactgaa ctttgagaca cactatgaga gcgttgctac ctgtggggca 1800agagcatgta caaacatgct cagaacttgc tgggacagtg tgggtgggag accagggctt 1860tgcaattcgt ggcatccttt aggataagag ggctgctatt agagtgtggg taagtagatc 1920ttttgccttg caaattgctg cctgggtgaa tgctgcttgt tctctcaccc ctaaccctag 1980tagttcctcc actaactttc tcactaagtg agaatgagaa ctgctgtgat agggagagtg 2040aaggagggat atgtggtaga gcacttgatt tcagttgaat gcctgctggt agcttttcca 2100ttctgtggag ctgccgttcc taataattcc aggtttggta gcgtggagga gaactttgat 2160ggaaagagaa ccttcccttc tgtactgtta acttaaaaat aaatagctcc tgattcaaag 2220tattacctct actttttgcc tagtatgcca gaaataatat aaatataaac agataaagtg 2280tgtgagactt tttctcataa ctattcatga catttaaaat ccctaggggc tggcaagaga 2340gttctcatta ttctgaaatg gtcctgacaa gctgcatgaa tagcaatttt ttttttgaga 2400cagagtcttg ctctgtcacc caggctggac tgcagtagtg caatctcagt tcactgcaac 2460ctccgcctcc caggttcaag cgatactccc acctcagcct cctgagtagc tgggactaca 2520ggcatgcagc accatgtctg gctaattttt gtatttttag tagaggccgg gtttcaccat 2580attcgccagg ctggtcttga actcctgacc ttgtgatctg cccgcctcgg ccttccgaaa 2640tgctgggatt acaggtggga actactgcgc ctggcctaca aatagcaaat tctaacgaag 2700acaggggaac agggatggtt cttccattgt taaaagccat cctcattttg tttatattgc 2760caggtttgtg atttttctgt aaaggaaaag gcagggtgat ttaaccagtt tgaccacctt 2820tcctgtactc ttacaggaaa atcgcagcac taattctaat tttgtccact ttacagccaa 2880agcttagcta atgttccata aaggagataa tagccaatca ggtaaggtaa tgtgtaattc 2940attattcaaa gtggaacatg tttttgtagg gggagagtct gcactattaa taattgtatt 3000gagaaataaa aataaactag gactattcag ttaaaccagg atgtcttatt attccatgtt 3060taggcctctt gagtcaaaac tctttttttt tttttttttt tttttttttt tggagacagg 3120ttctcactct gttgcccagg ctggagtgca gtggcatgat cttggctcac tgaagcctct 3180gcctcccagg ttcaagtgat tctcccccca aaccttgcaa gtagctggga ttacagatgt 3240gagccaccat gcccagctga tttttgtgta tttttagtaa agatggggtt tcaccatgtt 3300ggccaggttg gtctcaaact cctggcctca agtgatccac ctgccccagc ctcccaaagt 3360gctgggatta caggtgtgag ccaccatgcc tggtcccctc ttgagtcaaa actcttattt 3420cagaatgcga atggaaggat cgctattagt gattctgcag attacacatt tccttgcggg 3480gagacaataa ggtatgtgta aatacatata tgtgtgtgta tgtatacaca catacagcac 3540gctacctccc aagtgttacc tagtgaaaca gtttcctttc cgaagctcca gagatggttg 3600ttggctaagt tatactcttc tgtgatgggc aagggatact ataaaaacat aggcagtgcc 3660ctttgaatat agtacagctc atcttctgca tacgatatgc cctggaaagg tgatttatat 3720gcaagttaat tggtgtaatc tgaaggatgc tcccattaat acgtcatgat gtcattaata 3780tgtttcttcc tttctgattt ttgttttttt tttttttttt gagacagagt ctcactctgt 3840cacccaggtt ggagtgcaac gaatggcgca atcttggctc attacaacct ccgcctcctg 3900ggtccaagcg attctcctgc ctcagcctcc tgagtaactg ggattacagg tgtgtgccac 3960cttgcctggc taattttttt gtattttttt agtagaaaca gggtttcacc atgttggtca 4020ggctggtctg aactcctgac ctcaagtgat ccacttgcct tggcttccca aagtgctggg 4080attacaggcg tgagctaccg cacccagccc tttctgagtg ttgtcattca attcatcaag 4140ttttctgtca tgatcaactt tctctatgca aaccctgtaa ctctgacagt tatcactgtg 4200tctgacacag tgaatttttt atttataagg tagttacttt tggccaggtg tggtggctga 4260cgcctgtaat cccagcactt tgggaggcca aggtaggcag atcacttgag gtcaggagtt 4320caagatcagc ctggccaaca tggtgaatcc ccatctctac taaaaatata aaaattagcc 4380agacatggtg gtgggtacct gtaatcccag ctacttggga ggctgaggca ggagaatcgc 4440ttgaacatgg gaggcagagg ttgcagtgag ctgagatcgt accactgcac tccagcctgg 4500gcgatagagc cagactgagt ctcaaaaaaa aaaaaaaagt tacctttttt tggtaaggtt 4560gtacttctta gataatggtc attgtcacta ccaacttgcc tgcattgtaa tagagtccta 4620ttcactttgc tcccaacccc actacggaga tgactgatga ctagttgtat acacagtggg 4680tgtgccctga gaggtctgtt gccagcagtg gtgatcgatc acggcctccc cctgctggct 4740gatgtgatgg tccttggtcc tcctctgaag gaggtagaag gggcacacgg ccaccgtggg 4800aagtaggcag aaaagcctcc ctgggtgcag attctctgag aaaagaactt tggcctcata 4860gttaacttac tccaaaagct ttcatgtgaa ataatttata attttttata taaataaaaa 4920gattaaaatg tgaa 4934352546DNAHomo sapiens 35gctcccattg tctcggcaga tgccgcctgg tccagctatc gtgctcggta ttcagttttc 60cggagcagcg ctctttctct ggcccgcgga gcggtcccgc ggccgagtac cggattcccg 120agtttgggag gctctgcttt cctccttagg acccactttg ccgtcctggg gtggctgcag 180ttatgtccgc gctgcgacct ctcctgcttc tgctgctgcc tctgtgtccc ggtcctggtc 240ccggacccgg gagcgaggca aaggtcaccc ggagttgtgc agagacccgg caggtgctgg 300gggcccgggg atatagctta aacctaatcc ctcccgccct gatctcaggt gagcacctcc 360gggtctgtcc ccaggagtac acctgctgtt ccagtgagac agagcagagg ctgatcaggg 420agactgaggc caccttccga ggcctggtgg aggacagcgg ctcctttctg gttcacacac 480tggctgccag gcacagaaaa tttgatgagt tttttctgga gatgctctca gtagcccagc 540actctctgac ccagctcttc tcccactcct acggccgcct gtatgcccag cacgccctca 600tattcaatgg cctgttctct cggctgcgag acttctatgg ggaatctggt gaggggttgg 660atgacaccct ggcggatttc tgggcacagc tcctggagag agtgttcccg ctgctgcacc 720cacagtacag cttcccccct gactacctgc tctgcctctc acgcttggcc tcatctaccg 780atggctctct gcagcccttt ggggactcac cccgccgcct ccgcctgcag ataacccgga 840ccctggtggc tgcccgagcc tttgtgcagg gcctggagac tggaagaaat gtggtcagcg 900aagcgcttaa ggtgccggtg tctgaaggct gcagccaggc tctgatgcgt ctcatcggct 960gtcccctgtg ccggggggtc ccctcactta tgccctgcca gggcttctgc ctcaacgtgg 1020ttcgtggctg tctcagcagc aggggactgg agcctgactg gggcaactat ctggatggtc 1080tcctgatcct ggctgataag ctccagggcc ccttttcctt tgagctgacg gccgagtcca 1140ttggggtgaa gatctcggag ggtttgatgt acctgcagga aaacagtgcg aaggtgtccg 1200cccaggtgtt tcaggagtgc ggcccccccg acccggtgcc tgcccgcaac cgtcgagccc 1260cgccgccccg ggaagaggcg ggccggctgt ggtcgatggt gaccgaggag gagcggccca 1320cgacggccgc aggcaccaac ctgcaccggc tggtgtggga gctccgcgag cgtctggccc 1380ggatgcgggg cttctgggcc cggctgtccc tgacggtgtg cggagactct cgcatggcag 1440cggacgcctc gctggaggcg gcgccctgct ggaccggagc cgggcggggc cggtacttgc 1500cgccagtggt cgggggctcc ccggccgagc aggtcaacaa ccccgagctc aaggtggacg 1560cctcgggccc cgatgtcccg acacggcggc gtcggctaca gctccgggcg gccacggcca 1620gaatgaaaac ggccgcactg ggacacgacc tggacgggca ggacgcggat gaggatgcca 1680gcggctctgg agggggacag cagtatgcag atgactggat ggctggggct gtggctcccc 1740cagcccggcc tcctcggcct ccataccctc ctagaaggga tggttctggg ggcaaaggag 1800gaggtggcag tgcccgctac aaccagggcc ggagcaggag tgggggggca tctattggtt 1860ttcacaccca aaccatcctc attctctccc tctcagccct ggccctgctt ggacctcgat 1920aacgggggag gggtgcccta gcatcagaag ggttcatggc cctttcccct cctcccccct 1980cagctgggcc tggggaggag tcgaaggggg ctgcagagag ggtagagaag ggactttgca 2040ggtgaatggc tggggcccca aatccaggag attttcatca gaggtgggtg ggtgttcaca 2100atatttattt tttcatttgg taatgggagg ggggcctggg ggtatttatt taggagggag 2160tgtggtttcc ttagaaggta tagtctctag ccctctaagg ctggggctgg tgatcagccc 2220caacagagaa aatgaggagt ttagagttgc agctggggaa ggggtttgaa ggaagttgga 2280agtggggagg ggtgggggca tctggtctca gaaatggacc agctggatgc agggcagggg 2340actgagggtg cttgagtagg atgtgagact tcatgggcct gggttctgtt gagttttttc 2400agtatcaatt tcttaaacca aattttaaaa aaaacaaggt gggggggtgc tcatctcgtg 2460acctctgcca cccacatcct tcacaaactc catgtttcag tgtttgagtc catgtttatt 2520ctgcaaataa atggtaatgt attgga 2546362293DNAHomo sapiens 36acaccacctg cctgggttcc ttcctttagt cacttccagc tccaggcaca gcagttggtg 60actccttggt gggagccgtg tcccacccgg tcctgatact gccgtcttct ctttcacagt 120cctccaggct tgggccagcc ttgggggcag cagagcttct gggctgacat gggctcattg 180ctccttctcc aagccctctg aggacatcaa aagcgtggac gcatcacttt ccaccatctt 240gctgcccact gtccctccat cctgaggcct cctaagcaca tgtgtggggt ggcaggcaca 300ctgctgatag ctgtggatgc ggccgtgaca tccttcaccc ctgcccccat ggcatgcatg 360atccattagg gaggaccgtc tgcacaaagg tctcttgccc tgtgcagctt cctgcagact 420ggacttgcaa agtccagcct gtatggctgg agttcccatg cctgccaatc tcctgtcgac 480tgcgagtcag ctccgatact tcaccagatt cagccacctg ggggagctgg aagtgaatct 540cctcgtagct gagccttctg atgagactgc agccccggct gacacctgga ttgcagactc 600atgaaagacc tgaaactcta ccaacagcca cctgggggag ctggaagtga atctcctcgt 660agctgagcct tctgatgaga ctgcagcccc ggctgacacc tggattgcag actcatgaaa 720gaccctgagc agaggaccca gtttggcaga gcccgaattc ctgacccaca ggaactggga 780gataaaactc tgtggtttta atcttctcat tttagagtgc tcagtgtcct gtggtgtgaa 840cacgcttcat tcaacctggg cccttgggag agatgctgag tggttcccgg gctgtcccca 900ctccacaccg tggcagtgaa gagctgctga agtacatgct tcatagtcct tgcgtctctc 960tgaccatgaa tggcacctac aacacctgtg gctccagcga cctcacctgg cccccagcga 1020tcaagctggg cttctacgcc tacttgggcg tcctgctggt gctaggcctg ctgctcaaca 1080gcctggcgct ctgggtgttc tgctgccgca tgcagcagtg gacggagacc cgcatctaca 1140tgaccaacct ggcggtggcc gacctctgcc tgctgtgcac cttgcccttc gtgctgcact 1200ccctgcgaga cacctcagac acgccgctgt gccagctctc ccagggcatc tacctgacca 1260acaggtacat gagcatcagc ctggtcacgg ccatcgccgt ggaccgctat gtggccgtgc 1320ggcacccgct gcgtgcccgc gggctgcggt cccccaggca ggctgcggcc gtgtgcgcgg 1380tcctctgggt gctggtcatc ggctccctgg tggctcgctg gctcctgggg attcaggagg 1440gcggcttctg cttcaggagc acccggcaca atttcaactc catggcgttc ccgctgctgg 1500gattctacct gcccctggcc gtggtggtct tctgctccct gaaggtggtg actgccctgg 1560cccagaggcc acccaccgac gtggggcagg cagaggccac ccgcaaggct gcccgcatgg 1620tctgggccaa cctcctggtg ttcgtggtct gcttcctgcc cctgcacgtg gggctgacag 1680tgcgcctcgc agtgggctgg aacgcctgtg ccctcctgga gacgatccgt cgcgccctgt 1740acataaccag caagctctca gatgccaact gctgcctgga cgccatctgc tactactaca 1800tggccaagga gttccaggag gcgtctgcac tggccgtggc tcccagtgct aaggcccaca 1860aaagccagga ctctctgtgc gtgaccctcg cctaagaggc gtgctgtggg cgctgtgggc 1920caggtctcgg gggctccggg aggtgctgcc tgccagggga agctggaacc agtagcaagg 1980agcccgagat cagccctgaa ctcactgtgt attctcttgg agccttgggt gggcagggac 2040ggcccaggta cctgctctct tgggaagaga gagggacagg gacaagggca agaggactga 2100ggccagagca aggccaatgt cagagacccc cgggatgggg cctcacactt gccaccccca 2160gaaccagctc acctggccag agtgggttcc tgctggccag ggtgcagcct tgatgacacc 2220tgccgctgcc cctcggggct ggaataaaac tccccaccca gagtcagtcc taaaaaaaaa 2280aaaaaaaaaa aaa 2293372856DNAHomo sapiens 37gcttcccata cggcagtggc tgggggagag tgatggagag aaaggctaag ctaaggtcaa 60agaaagtgga ggaaggctgg cttgtcccgc tggacttgac ggcggagctg ctgcaatctc 120gcgggctggg cccttgcccc gggtggaccc gagtgcctgc ggggaggcgg gtgtggctcc 180cccgggaggt gacagctggc ggggcccgta aggagctggt ctgctccggc tcccctctcg 240tagccggcgc cctgggacca gcgcgtgagc acgtctcgga ggagtccgat gcgctgggca 300gggccgggtg gtcacccccg cccagcttcc aggggtgact gtgcctctga cgtcagacgg 360tttttgggtc attccctggc acggggactt tattttcata acagcatgaa gtgccgtgga 420actggaatag gcgtgtcctc tccctcgacc ctccccctcc ttgtccctct gctcacccct 480cgctcgttcc ctccctccgg cgagggccgc ctttataaca actgctcaga gtgcgagggc 540gggatagctg tccaaggtct cccccagcac tgaggagctc gcctgctgcc ctcttgcgcg 600cgggaagcag caccaagttc acggccaacg ccttggcact agggtccaga atggctacaa 660cagtccctga tggttgccgc aatggcctga aatccaagta ctacagactt tgtgataagg 720ctgaagcttg gggcatcgtc ctagaaacgg tggccacagc cggggttgtg acctcggtgg 780ccttcatgct cactctcccg atcctcgtct gcaaggtgca ggactccaac aggcgaaaaa 840tgctgcctac tcagtttctc ttcctcctgg gtgtgttggg catctttggc ctcaccttcg 900ccttcatcat cggactggac gggagcacag ggcccacacg cttcttcctc tttgggatcc 960tcttttccat ctgcttctcc tgcctgctgg ctcatgctgt cagtctgacc aagctcgtcc 1020gggggaggaa gcccctttcc ctgttggtga ttctgggtct ggccgtgggc ttcagcctag 1080tccaggatgt tatcgctatt gaatatattg tcctgaccat gaataggacc aacgtcaatg 1140tcttttctga gctttccgct cctcgtcgca atgaagactt tgtcctcctg ctcacctacg 1200tcctcttctt gatggcgctg accttcctca tgtcctcctt caccttctgt ggttccttca 1260cgggctggaa gagacatggg gcccacatct acctcacgat gctcctctcc attgccatct 1320gggtggcctg gatcaccctg ctcatgcttc ctgactttga ccgcaggtgg gatgacacca 1380tcctcagctc cgccttggct gccaatggct gggtgttcct gttggcttat gttagtcccg 1440agttttggct gctcacaaag caacgaaacc ccatggatta tcctgttgag gatgctttct 1500gtaaacctca actcgtgaag aagagctatg gtgtggagaa cagagcctac tctcaagagg 1560aaatcactca aggttttgaa gagacagggg acacgctcta tgccccctat tccacacatt 1620ttcagctgca gaaccagcct ccccaaaagg aattctccat cccacgggcc cacgcttggc 1680cgagccctta caaagactat gaagtaaaga aagagggcag ctaactctgt cctgaagagt 1740gggacaaatg cagccgggcg gcagatctag cgggagctca aagggatgtg ggcgaaatct 1800tgagtcttct gagaaaactg tacaagacac tacgggaaca gtttgcctcc ctcccagcct 1860caaccacaat tcttccatgc tggggctgat gtgggctagt aagactccag ttcttagagg 1920cgctgtagta tttttttttt tttgtctcat cctttggata cttcttttaa gtgggagtct 1980caggcaactc aagtttagac ccttactctt tttgtttgtt ttttgaaaca ggatcttgct 2040ctgtcaccca ggcttgagtg cagtggtgcg atcacagccc agtgcagcct cgaccacctg 2100tgctcaagca atcctcccat ctccatctcc caaagtgctg ggatgacagg cgtgagccac 2160agctcccagc ctaggccctt aatcttgctg ttattttcca tggactaaag gtctggtcat 2220ctgagctcac gctggctcac acagctctag gggcctgctc ctctaactca cagtgggttt 2280tgtgaggctc tgtggcccag agcagacctg catatctgag caaaaatagc aaaagcctct 2340ctcagcccac tggcctgaat ctacactgga agccaacttg ctggcacccc cgctccccaa 2400cccttcttgc ctgggtagga gaggctaaag atcaccctaa atttactcat ctctctagtg 2460ctgcctcaca ttgggcctca gcagctcccc agcaccaatt cacaggtcac ccctctcttc 2520ttgcactgtc cccaaacttg ctgtcaattc cgagatctaa tctcccccta cgctctgcca 2580ggaattcttt cagacctcac tagcacaagc ccggttgctc cttgtcagga gaatttgtag 2640atcattctca cttcaaattc ctggggctga tacttctctc atcttgcacc ccaacctctg 2700taaatagatt taccgcattt acggctgcat tctgtaagtg ggcatggtct cctaatggag 2760gagtgttcat tgtataataa gttattcacc tgagtatgca ataaagatgt ggtggccact 2820ctttcatggt ggtggcagca gttaccagta aaaaaa 2856385231DNAHomo sapiens 38agaaagttac ctgtggccgc ccaagtccgc cactttctgc tctgtgtctg cccattgcca 60cgatccagga ggactccgcg ccgcccggcc gcctccgagc tcgggcccca tgtgaggggc 120ccccccttat cccacctttc cggctaggtg agggcgcgag cgggcgagcg agcgagagtg 180gtgagggggg acggaaaagc agaattacct gtagctcttg ttctgccatc tcgggcgctc 240tcacacacct tcacctgcac agacttgaaa gtccagtttc accagaggct gaggctccag 300gaaaagcgga gcaagttcat tggatcaaac atgtcacaag agtcggacaa taataaaaga 360ctagtggcct tagtgcccat gcccagtgac cctccattca atacccgaag agcctacacc 420agtgaggatg aagcctggaa gtcatacttg gagaatcccc tgacagcagc caccaaggcc 480atgatgagca ttaatggtga tgaggacagt gctgctgccc tcggcctgct ctatgactac 540tacaaggttc ctcgagacaa gaggctgctg tctgtaagca aagcaagtga cagccaagaa 600gaccaggaga aaagaaactg ccttggcacc agtgaagccc agagtaattt gagtggagga 660gaaaaccgag tgcaagtcct aaagactgtt ccagtgaacc tttccctaaa tcaagatcac 720ctggagaatt ccaagcggga acagtacagc atcagcttcc ccgagagctc tgccatcatc 780ccggtgtcgg gaatcacggt ggtgaaagct gaagatttca caccagtttt catggcccca 840cctgtgcact atccccgggg agatggggaa gagcaacgag tggttatctt tgaacagact 900cagtatgacg tgccctcgct ggccacccac agcgcctatc tcaaagacga ccagcgcagc 960actccggaca gcacatacag cgagagcttc aaggacgcag ccacagagaa atttcggagt 1020gcttcagttg gggctgagga gtacatgtat gatcagacat caagtggcac atttcagtac 1080accctggaag ccaccaaatc tctccgtcag aagcaggggg agggccccat gacctacctc 1140aacaaaggac agttctatgc cataacactc agcgagaccg gagacaacaa atgcttccga 1200caccccatca gcaaagtcag gagtgtggtg atggtggtct tcagtgaaga caaaaacaga 1260gatgaacagc tcaaatactg gaaatactgg cactctcggc agcatacggc gaagcagagg 1320gtccttgaca ttgccgatta caaggagagc tttaatacga ttggaaacat tgaagagatt 1380gcatataatg ctgtttcctt tacctgggac gtgaatgaag aggcgaagat tttcatcacc 1440gtgaattgct tgagcacaga tttctcctcc caaaaagggg tgaaaggact tcctttgatg 1500attcagattg acacatacag ttataacaat cgtagcaata aacccattca tagagcttat 1560tgccagatca aggtcttctg tgacaaagga gcagaaagaa aaatccgaga tgaagagcgg 1620aagcagaaca ggaagaaagg gaaaggccag gcctcccaaa ctcaatgcaa cagctcctct 1680gatgggaagt tggctgccat acctttacag aagaagagtg acatcaccta cttcaaaacc 1740atgcctgatc tccactcaca gccagttctc ttcatacctg atgttcactt tgcaaacctg 1800cagaggaccg gacaggtgta ttacaacacg gatgatgaac gagaaggtgg cagtgtcctt 1860gttaaacgga tgttccggcc catggaagag gagtttggtc cagtgccttc aaagcagatg 1920aaagaagaag ggacaaagcg agtgctcttg tacgtgagga aggagactga cgatgtgttc 1980gatgcattga tgttgaagtc tcccacagtg aagggcctga tggaagcgat atctgagaaa 2040tatgggctgc ccgtggagaa gatagcaaag ctttacaaga aaagcaaaaa aggcatcttg 2100gtgaacatgg atgacaacat catcgagcac tactcgaacg aggacacctt catcctcaac 2160atggagagca tggtggaggg cttcaaggtc acgctcatgg aaatctagcc ctgggtttgg 2220catccgcttt ggctggagct ctcagtgcgt tcctccctga gagagacaga agccccagcc 2280ccagaacctg gagacccatc tcccccatct cacaactgct gttacaagac cgtgctgggg 2340agtggggcaa gggacaggcc ccactgtcgg tgtgcttggc ccatccactg gcacctacca

2400cggagctgaa gcctgagccc ctcaggaagg tgccttaggc ctgttggatt cctatttatt 2460gcccaccttt tcctggagcc caggtccagg cccgccagga ctctgcaggt cactgctagc 2520tccagatgag accgtccagc gttccccctt caagagaaac actcatcccg aacagcctaa 2580aaaattccca tcccttctct ctcacccctc catatctatc tcccgagtgg ctggacaaaa 2640tgagctacgt ctgggtgcag tagttatagg tggggcaaga ggtggatgcc cactttctgg 2700tcagacacct ttaggttgct ctggggaagg ctgtcttgct aaatacctcc agggttccca 2760gcaagtggcc accaggcctt gtacaggaag acattcagtc accgtgtaat tagtaacaca 2820gaaagtctgc ctgtctgcat tgtacatagt gtttataata ttgtaataat atattttacc 2880tgtggtatgt gggcatgttt actgccactg gcctagagga gacacagacc tggagaccgt 2940tttaatgggg gtttttgcct ctgtgcctgt tcaagagact tgcagggcta ggtagagggc 3000ctttgggatg ttaaggtgac tgcagctgat gccaagatgg actctgcaat gggcatacct 3060gggggctcgt tccctgtccc cagaggaagc cccctctcct tctccatggg catgactctc 3120cttcgaggcc accacgttta tctcacaatg atgtgttttg cttgactttc cctttgcgct 3180gtctcgtggg aaaggtcatt ctgtctgaga ccccagctcc ttctccagct ttggctgcgg 3240gcatggcctg agctttctgg agagcctctg cagggggttt gccatcaggg ccctgtggct 3300gggtctgctg cagagctcct tggctatcag gagaatcctg gacactgtac tgtgcctccc 3360agtttacaaa cacgcccttc atctcaagtg gccctttaaa aggcctgctg ccatgtgaga 3420gctgtgaaca gctcagctct gagtcggcag gctggggctt cctcctgggc caccagatgg 3480aaagggggta ttgtttgcct cactcctgga tgctgcgttt taaggaagtg agtgagaaag 3540aatgtgccaa gatacctggc tcctgtgaaa ccagcctcag gagggaaact gggagagaga 3600agctgtggtc tcctgctaca tgccctggga gctggaagag aaaaacactc ccctaaacaa 3660tcgcaaaatg atgaaccatc atgggccact gttctctttg aggggacagg tttaggggtt 3720tgcgttcgcc cttgtgggct gaagcactag ctttttggta gctagacaca tcctgcaccc 3780aaaggttctc tacaaaggcc cagatttgtt tgtaaagcac tttgactctt acctggaggc 3840ccgctctcta agggcttcct gcgctcccac ctcatctgtc cctgagatgc agagcaggat 3900ggagggtctg cttctagctc agctgtttct ccttgaggtt gcggaggaat tgaattgaat 3960gggacagagg gcaggtgctg tggccaagaa gatctccgag cagcagtgac ggggcacctt 4020gctgtgtgtc ctctgggcat gttaaccctt ctgtggggcc aaaggtttgc atcgtggatc 4080cagctgtgct ccagtctgtc ccctcctcct ccactctgac tgccacgccc cggaccagca 4140gcttggggac cctccagggt actaatgggg ctctgttctg agatggacaa attcagtgtt 4200ggaaatacat gttgtactat gcacttccca tgctcctagg gttaggaata gtttcaaaca 4260tgattggcag acataacaac ggcaaatact cggactgggg cataggactc cagagtagga 4320aaaagacaaa agatttggca gcctgacaca ggcaacctac ccctctctct ccagcctctt 4380tatgaaactg tttgtttgcc agtcctgccc taaggcagaa gatgaattga agatgctgtg 4440catgtttcct aagtccttga gcaatcatgg tggtgacaat tgccacaagg gatatgaggc 4500cagtgccacc agagggtggt gccaagtgcc acatcccttc cgatccattc ccctctgcat 4560cctcggagca ccccagtttg cctttgatgt gtccgctgtg tatgttagct gaactttgat 4620gagcaaaatt tcctgagcga aacactccaa agagatagga aaacttgccg cctcttcttt 4680tttgtccctt aatcaaactc aaataagctt aaaaaaaatc catggaagat catggacatg 4740tgaaatgagc atttttttct tttttttttt taacaaagtc tgaactgaac agaacaagac 4800tttttcctca tacatctcca aattgtttaa acttacttta tgagtgtttg tttagaagtt 4860cggaccaaca gaaaaatgca gtcagatgtc atcttggaat tggtttctaa aagagtaagg 4920catgtccctg cccagaaact taggaagcat gaaataaatc aaatgtttat tttccttctt 4980atttaaaatc atgcaaatgc aacagaaata gagggtttgt gccaaatgct atgaacggcc 5040ctttcttaaa gacaagcaag ggagattgat atatgtacaa tttgctctca tgttttaaaa 5100aaaaaaaggt aaatgtaact taatagtttt gtaaatggga gagggggaat ctataaacta 5160taaatacagt tattttattt tttgtacatt tttaaggaga aaaaataaat attcataaca 5220taagagtaaa a 5231393417DNAHomo sapiens 39ggggccctga ttcacgggcc gctggggcca gggttggggg ttgggggtgc ccacagggct 60tggctagtgg ggttttgggg gggcagtggg tgcaaggagt ttggtttgtg tctgccggcc 120ggcaggcaaa cgcaacccac gcggtggggg aggcggctag cgtggtggac ccgggccgcg 180tggccctgtg gcagccgagc catggtttct aaactgagcc agctgcagac ggagctcctg 240gcggccctgc tcgagtcagg gctgagcaaa gaggcactga tccaggcact gggtgagccg 300gggccctacc tcctggctgg agaaggcccc ctggacaagg gggagtcctg cggcggcggt 360cgaggggagc tggctgagct gcccaatggg ctgggggaga ctcggggctc cgaggacgag 420acggacgacg atggggaaga cttcacgcca cccatcctca aagagctgga gaacctcagc 480cctgaggagg cggcccacca gaaagccgtg gtggagaccc ttctgcagga ggacccgtgg 540cgtgtggcga agatggtcaa gtcctacctg cagcagcaca acatcccaca gcgggaggtg 600gtcgatacca ctggcctcaa ccagtcccac ctgtcccaac acctcaacaa gggcactccc 660atgaagacgc agaagcgggc cgccctgtac acctggtacg tccgcaagca gcgagaggtg 720gcgcagcagt tcacccatgc agggcaggga gggctgattg aagagcccac aggtgatgag 780ctaccaacca agaaggggcg gaggaaccgt ttcaagtggg gcccagcatc ccagcagatc 840ctgttccagg cctatgagag gcagaagaac cctagcaagg aggagcgaga gacgctagtg 900gaggagtgca atagggcgga atgcatccag agaggggtgt ccccatcaca ggcacagggg 960ctgggctcca acctcgtcac ggaggtgcgt gtctacaact ggtttgccaa ccggcgcaaa 1020gaagaagcct tccggcacaa gctggccatg gacacgtaca gcgggccccc cccagggcca 1080ggcccgggac ctgcgctgcc cgctcacagc tcccctggcc tgcctccacc tgccctctcc 1140cccagtaagg tccacggtgt gcgctatgga cagcctgcga ccagtgagac tgcagaagta 1200ccctcaagca gcggcggtcc cttagtgaca gtgtctacac ccctccacca agtgtccccc 1260acgggcctgg agcccagcca cagcctgctg agtacagaag ccaagctggt ctcagcagct 1320gggggccccc tcccccctgt cagcaccctg acagcactgc acagcttgga gcagacatcc 1380ccaggcctca accagcagcc ccagaacctc atcatggcct cacttcctgg ggtcatgacc 1440atcgggcctg gtgagcctgc ctccctgggt cctacgttca ccaacacagg tgcctccacc 1500ctggtcatcg gcctggcctc cacgcaggca cagagtgtgc cggtcatcaa cagcatgggc 1560agcagcctga ccaccctgca gcccgtccag ttctcccagc cgctgcaccc ctcctaccag 1620cagccgctca tgccacctgt gcagagccat gtgacccaga gccccttcat ggccaccatg 1680gctcagctgc agagccccca cgccctctac agccacaagc ccgaggtggc ccagtacacc 1740cacacgggcc tgctcccgca gactatgctc atcaccgaca ccaccaacct gagcgccctg 1800gccagcctca cgcccaccaa gcaggtcttc acctcagaca ctgaggcctc cagtgagtcc 1860gggcttcaca cgccggcatc tcaggccacc accctccacg tccccagcca ggaccctgcc 1920ggcatccagc acctgcagcc ggcccaccgg ctcagcgcca gccccacagt gtcctccagc 1980agcctggtgc tgtaccagag ctcagactcc agcaatggcc agagccacct gctgccatcc 2040aaccacagcg tcatcgagac cttcatctcc acccagatgg cctcttcctc ccagtaacca 2100cggcacctgg gccctggggc ctgtactgcc tgcttggggg gtgatgaggg cagcagccag 2160ccctgcctgg aggacctgag cctgccgagc aaccgtggcc cttcctggac agctgtgcct 2220cgctccccac tctgctctga tgcatcagaa agggagggct ctgaggcgcc ccaacccgtg 2280gaggctgctc ggggtgcaca ggagggggtc gtggagagct aggagcaaag cctgttcatg 2340gcagatgtag gagggactgt cgctgcttcg tgggatacag tcttcttact tggaactgaa 2400gggggcggcc tatgacttgg gcacccccag cctgggccta tggagagccc tgggaccgct 2460acaccactct ggcagccaca cttctcagga cacaggcctg tgtagctgtg acctgctgag 2520ctctgagagg ccctggatca gcgtggcctt gttctgtcac caatgtaccc accgggccac 2580tccttcctgc cccaactcct tccagctagt gacccacatg ccatttgtac tgaccccatc 2640acctactcac acaggcattt cctgggtggc tactctgtgc cagagcctgg ggctctaacg 2700cctgagccca gggaggccga agctaacagg gaaggcaggc agggctctcc tggcttccca 2760tccccagcga ttccctctcc caggccccat gacctccagc tttcctgtat ttgttcccaa 2820gagcatcatg cctctgaggc cagcctggcc tcctgcctct actgggaagg ctacttcggg 2880gctgggaagt cgtccttact cctgtgggag cctcgcaacc cgtgccaagt ccaggtcctg 2940gtggggcagc tcctctgtct cgagcgccct gcagaccctg cccttgtttg gggcaggagt 3000agctgagctc acaaggcagc aaggcccgag cagctgagca gggccgggga actggccaag 3060ctgaggtgcc caggagaaga aagaggtgac cccagggcac aggagctacc tgtgtggaca 3120ggactaacac tcagaagcct gggggcctgg ctggctgagg gcagttcgca gccaccctga 3180ggagtctgag gtcctgagca ctgccaggag ggacaaagga gcctgtgaac ccaggacaag 3240catggtccca catccctggg cctgctgctg agaacctggc cttcagtgta ccgcgtctac 3300cctgggattc aggaaaaggc ctggggtgac ccggcacccc ctgcagcttg tagccagccg 3360gggcgagtgg cacgtttatt taacttttag taaagtcaag gagaaatgcg gtggaaa 3417401575DNAHomo sapiens 40gtcctgtggc ctctgcagct cagcatggct agggtactgg gagcacccgt tgcactgggg 60ttgtggagcc tatgctggtc tctggccatt gccacccctc ttcctccgac tagtgcccat 120gggaatgttg ctgaaggcga gaccaagcca gacccagacg tgactgaacg ctgctcagat 180ggctggagct ttgatgctac caccctggat gacaatggaa ccatgctgtt ttttaaaggg 240gagtttgtgt ggaagagtca caaatgggac cgggagttaa tctcagagag atggaagaat 300ttccccagcc ctgtggatgc tgcattccgt caaggtcaca acagtgtctt tctgatcaag 360ggggacaaag tctgggtata ccctcctgaa aagaaggaga aaggataccc aaagttgctc 420caagatgaat ttcctggaat cccatcccca ctggatgcag ctgtggaatg tcaccgtgga 480gaatgtcaag ctgaaggcgt cctcttcttc caaggtgacc gcgagtggtt ctgggacttg 540gctacgggaa ccatgaagga gcgttcctgg ccagctgttg ggaactgctc ctctgccctg 600agatggctgg gccgctacta ctgcttccag ggtaaccaat tcctgcgctt cgaccctgtc 660aggggagagg tgcctcccag gtacccgcgg gatgtccgag actacttcat gccctgccct 720ggcagaggcc atggacacag gaatgggact ggccatggga acagtaccca ccatggccct 780gagtatatgc gctgtagccc acatctagtc ttgtctgcac tgacgtctga caaccatggt 840gccacctatg ccttcagtgg gacccactac tggcgtctgg acaccagccg ggatggctgg 900catagctggc ccattgctca tcagtggccc cagggtcctt cagcagtgga tgctgccttt 960tcctgggaag aaaaactcta tctggtccag ggcacccagg tatatgtctt cctgacaaag 1020ggaggctata ccctagtaag cggttatccg aagcggctgg agaaggaagt cgggacccct 1080catgggatta tcctggactc tgtggatgcg gcctttatct gccctgggtc ttctcggctc 1140catatcatgg caggacggcg gctgtggtgg ctggacctga agtcaggagc ccaagccacg 1200tggacagagc ttccttggcc ccatgagaag gtagacggag ccttgtgtat ggaaaagtcc 1260cttggcccta actcatgttc cgccaatggt cccggcttgt acctcatcca tggtcccaat 1320ttgtactgct acagtgatgt ggagaaactg aatgcagcca aggcccttcc gcaaccccag 1380aatgtgacca gtctcctggg ctgcactcac tgaggggcct tctgacatga gtctggcctg 1440gccccacctc ctagttcctc ataataaaga cagattgctt cttcgcttct cactgagggg 1500ccttctgaca tgagtctggc ctggccccac ctccccagtt tctcataata aagacagatt 1560gcttcttcac ttgaa 1575417419DNAHomo sapiens 41gaagagttct gcactttgtt ccttccctgg cacacctgtg tctgcattcc ttctatctcc 60cggcattctc cactcctgtc tctgtgtgtt taaaaaccgg tgtgggaagt gtgcacgcct 120gtgacgtcag actccagacc atgtatttcc tgactcccat cttggtagcc attctctgca 180ttttggttgt gtggatcttt aaaaatgccg acagaagcat ggagaaaaag aagggggagc 240ctagaaccag ggccgaagct cgcccctggg tggatgaaga cttaaaagac agcagtgacc 300tgcaccaagc agaagaagat gctgatgaat ggcaagaatc agaagaaaat gttgaacaca 360tccccttctc tcataaccac tatcctgaga aggaaatggt taagaggtct caggaatttt 420atgaacttct caataagaga cggtcagtca ggttcataag taatgagcaa gtcccaatgg 480aagtcattga taatgtcatc agaacggcag gaacagcccc gagtggggct cacacagagc 540cctggacctt cgtggttgtg aaggacccag acgtgaagca caagattcga aagatcattg 600aggaggaaga ggagatcaac tacatgaaaa ggatgggaca tcgctgggtc acagacctca 660agaaactgag aaccaactgg attaaagagt acttggatac tgcccctatt ttgattctca 720ttttcaaaca agtacatggt ttcgccgcaa atggcaagaa aaaagtccac tactacaatg 780agatcagtgt ttccatcgct tgtggcatcc tgctagctgc cctgcagaat gcaggtctgg 840tgactgtcac taccactcct ctcaactgtg gccctcgact gagggtgctc ctgggccgcc 900ccgcacatga aaagctgctg atgctgctcc ccgtggggta ccccagcaag gaggccacgg 960tgcctgacct caagcgcaaa cctctggacc agatcatggt gacagtgtag gcagggcccc 1020ccaagggagt ggcagggaga tggcgcccct gcttttccct gagcctctcg cctgctcctc 1080ttgggtctct tggctgctct ttctccaggt gtcaggtccc ctcattgctc ttctcaggtg 1140gccacactat gtcaagaagc ctctccacac tctgtggcac ttccagtccc ataaatcctg 1200tttcttatcc actttggaaa tgcatgaaca ctttacaaag aacatgcccg ggtttttaca 1260ttttaaaagt tattctagac aatcactatt ggcttttttc ttttattttt aaaaaactca 1320catagaggag acaatcagaa atttaccata gtcccaagaa ttcagctaca tgatgactcg 1380aatttaaatt tagattaatc aaatggtctc ctgttctctg atttctggtg gcttttagac 1440actaattttt gagaactact tttttttttt taccaaactt cagggacact ctgctagttt 1500tgaataagta accatcaaag ttactaaaac atggccaggc gcagtggctc atgcctgtaa 1560tcccagcact ttgggaggcc gaggtgggca gattgcctga gctcaagagt tcgagaccag 1620cctggccaac atggtgaaac cccatctcta ctaaaaatac aaaaaattag ctgggcatgc 1680acttgtaatt ccagctactc aggaggctga ggcaagagaa ctgcttgaat ccgggaggta 1740gagattgcag tgagtcaaga tgctgagatg ccaccactgc actccagcct gggcaacaga 1800gcgagaacct gtctcaaaaa aaacaaaaac aaagttacta aaatgtcacc ttcacagaac 1860aggacagggt acccttgggt cgcacgggcc tggctggcat gtaaacggtc agttgcactg 1920cctagtggtt tggtagatct gacttgtaag cagttcatag aagctgctca atactcaaga 1980atcttgcaag acagttatta aacattcata gcttgaaatt gcccatggtg ggagagttta 2040catcacaacc actacaaatc agcacttgct ttcttcttct taaagagagc tgcttaccat 2100acatagcacc cacagtgtct cccttctctt ctaccccaac ccctgaaaca cactgacccc 2160tattctccag atgacagcac agctgtttgg gactgatagg gtcacagttg ccaggttggg 2220aatgctagat gtagtcttca cccatcacct tctgtcgtcc tcccaggggt gtcatattta 2280cagaggcaaa ctcttacagc ttggatgatt tctcatcaag caactctact cacctctttt 2340tcccctttcc ctgtgcgttt cttcttcttg tcctcatttt ccttgagaaa actctctcta 2400taaaaaattt ccatagagta tgtggctgat aaacaacaga aatttgtttc tcacagttct 2460ggaggctgga agtccaaggt cggggtgccc tcatggtcag gtgctggtga ggaccctgat 2520ctgggttgca gactgctgac ttcttattgt gtcctcgtgg tagaaagagg gttagagcct 2580ctggcatgcc ttttataagg gtactaatcc catcatgagg ccccgtcctt atgacctcat 2640cacctcccaa aggaccccct cctaatacca tcacattggg ggttagggtt tcaacatatg 2700aattgcgggg gacacaaaca ttccgtccat ggcacctact tcatagggtt tggcatgctg 2760ctcggtacat ggttaacatt cataaatggt gggggccctt actgtggtag aaaccattgt 2820cactgcaagg cagccctgct tgggattcag gtgaacaaat gtaacgtggg tgggtgaggg 2880actccctcct cttcagagaa gccctcctgt ggctcagggg cagctgcagg gccagatgga 2940gttggcctgc agggagtcag ccttacccca tcagagacca acttgaaaga tttttttctc 3000tgtgtagttc gtgttatcaa tctgatctgc agccaggtta tttacttctg aagcattgga 3060gttatcgatt gccattgccc catggttctc actctttgca ggcactcttc aaatttttat 3120tttaaaaatt ataatgcaaa catctggcca tcaccttaac caagtgacaa agtcctagca 3180caccattaat ggtaggataa ctgacattaa gtgttcctgc tgggatgaat tatgaagtat 3240tccttccaaa gatgtcaatg gaaactaatc gagtcttaca cctaattttc agtttacagt 3300aaatacagag gataaagaag ttaatggcat ggtggaataa ccaaaatgtg tatcattcta 3360caaaaaaata ggcctggact atttaaggag tgagtgtcac tgtgggaaga ataagagggg 3420gactgtcttg tccttgctac tcaaagagtg gtcctgggcc tgtatcatca ttgggaccac 3480ctgggcgctt gttagaatca aagactctca ggcctcacct agacatccag aatcaaaatc 3540tgcattttaa caagatgccc aggtgatctg catgcctgtt aaagtctgag ctctgttgca 3600gataaccaga gacccaacaa ccaaaggcaa agcgtaagcc ttgattggat tttggtttag 3660gaaaaatctc ataggtataa aagacaactg ggaatgttga atgtggatct ggtggtaggt 3720gatattgtta gtgatgtgag tgatgcctgc tgaagtactg agagatgaag catcatattg 3780acaacttact ccaggaaaaa aggtgtgtgt ataggtgtgt gtttggagag tgtgagcgag 3840aactaacatg gtaaaatgtt aggtggagca tatacagttc tcattatact cttattttaa 3900atttatattt gaacacagtc aaatctgaat ggaaatacat ttaaataagc atttctttca 3960gtcatataag taatttgcct aaaaatgccc tctaagtcca tcattaggtt aagcgattta 4020ctgaaggtgc agatatcatg cttatttcat tgggttgttt tggaatgtcc cccacttgga 4080gagtttgagg aatggaaatg agaatcggag gagaaataag gccagaggct cacattgctt 4140gcagggaacc gactgagtaa tgaagaagag gaaggaagcc cttggaagga acgtaaaatc 4200catttcagcc tgccgcccct tggaatggag ggtcttctag ggaccagaaa caccagacac 4260ttcttctgcc ccaagcacac cccacactaa tttctgctgc agcatcacga tcagggcaaa 4320tcagcacagc cccccagcca tcagtggtgt ctagaaaagt aaggataatt ttcttccttc 4380tcactgcagc cccaagctct tattaacctt cttttatgtg ttcattaaat gcagtcatgt 4440gacaactgtg ttcaaagtta gaaatagtgg tcggggaggc ttatagatcc tcttgctgtt 4500ctgaggcctt aaaaccaaaa aaataatgga atgattgcat cactgcgagg aagtatactt 4560aattaagaaa gttgaaaatg gtttgtgtct tactaatagg actcacctga agactctact 4620ttgccaagag ggaattttta actcaaagtt gtgtcagcca gcacggggta gagccatggt 4680cctcatactt gctggcatcc ctcatctggt ggtctgttaa agcacagatt gctgggccgc 4740accctcaggg tgtgtgattg tgtgattcag tattgctggg tggtgcccaa atgctccagt 4800tctaatgtat tcccaggtgt tgctgatgct ggtgattggg taccacattt tgagaaccat 4860ggggcattgg caatcaacaa atgcaatgct tgtgacttga cgtgataaaa gttcatttat 4920tgggcaggca aagtcctctg caggcctgga aaccctccga gacaattact tgcatggggt 4980aacccagtaa tactgtggga tgcaacttct agggcatggc tgcctccttc ctagaggcag 5040cagggggaga aaacactgga agaggtcacc ccaacaattc catcgtacct tggcctagga 5100gtgacctcct cagtctcaca accctttggc tagaactagt catgtgacct cacaggaggt 5160ggagcagtgt cgtcaatgtt atcatccccc tgcacctgca aggaaggagg cccagatgtg 5220tgtaggtgct ggatgtctct tccccaaaac atataactct ggatttggaa aacaaaactg 5280gatataacag aaaagaaaag gaggggagaa ggaaagttga agaaattggt gaaatcagaa 5340taggacagtg aaaggcataa agattttctt ctgaaacgct aagatcggtt gatatttgtc 5400taatacagct ttaaatagag tatcactttg ggccaaagaa aattgatata aacatacata 5460aagtggaact aagattgact tcttcctaga catctctgcc tctgtccaca aaatggaaac 5520ttccatcaag gagtactgga ggacagttca gtatttcttc ttatttgctc ctccctatga 5580aaggaagagt gacttctctg ctgcatgata ttgggggtaa atagttattg cacatttgct 5640caaaccccag caaagtgcac cccattttaa gccaaattta caaacttaca aagatgatcc 5700accaatagtt ttctctattt actttattct tgctctgtca cccaggctag aatgcagtgg 5760tgtgattata gctcactgca gcctccaact tctggactca agtgatcctc ccaccttagc 5820ttcccaggta gctgggatac aggtgcacgc caccacaccc aggctagttt ttctaaatat 5880tggagttccc aaagagtatt caaactgatg tgatatttta aaagacattt tgtaagcatc 5940ttttaggaat atcagtaagt ggaagaaaaa cacatagtta tcagtggata ttatgccaga 6000gaggcatgag aaatataatt ttattttgct aggtatcagc agagtgccct cttataattt 6060gtgtgaaatg gaaacaaagg taacatcgtg ttttcaattc acacatatat acaagtaatg 6120agaggtccag aagaaatgtg gcttcagctc tgctgctact gtgcctccct tctcctgccc 6180cactcagccc acaaaatagg ctggacactc aaaaaacgtt gcgtttatct accttttaga 6240gagggtgaat agcagagaac tggaggtggg aatggtaagg aactcccagc agggtagtgg 6300agggaatggg ctgacgcatc taaggctgat gccaggtctg ctccctatct gggtggcctc 6360agcaaatgac gtccagcaca tccaggggca ggctcaaggg agaacagccc ccaaagctaa 6420gatcctgcca agctaaatac agtagttcta atgaaatgtg agaggctata atcccatttg 6480ggaaattcct aaaaagtcat gaggcagggg attggtttat gttattatca tgacctgaga 6540gtcatggctc agagccaaat gttcaggatt gaattcaaca gcatttaaat gtctttagag 6600caggatggaa atatgttagc aatgcctgca gagtgccaag taaacgcaaa agccaatgag 6660atcataaagg aagttgttag ctaacctagg tggagtcgcc aacttccttc tactctaata 6720attaaaaata aaaataatac ttgggaggta actggaataa aggttctaaa atcaaaaccc 6780tctgaagggt gaaaactggg agcctcctgt tcccatagta accacagcac tcagggcact 6840gtctcccagc gctggagtac tgtcttatga ccagagatcc taagcaacct ctgctcatct 6900gagttgtcca ccatattgtg ggcatgagtc cttgacaata gtaaatagca cctctgttcc 6960cttattgggt aaatgatttt ccaactctgg gaatgtgtag aattcattat ggaaataatg 7020caataattca aatccataat attgatactt tcatgttaag tttaggacta atcttgtgta

7080tgctccttaa gtgatttgaa tctttaaaaa gcttatgatt ccaatttgaa atgtgaaatt 7140gattttacgt ttgtgatttg aagttgaaag gtataagaat atttaactta gctcatgaaa 7200agtattagac tagatttact ataagtttaa tgtattagat ttacaagaga tgcttaaata 7260tatgagaatg ttttgtctta attggttata atcttgtcat atcaatgatt tgaagtgcta 7320aaatagaaaa ttaaatatga taaattacac aagaagttta gaatgtttaa aagattttaa 7380taaacaaagc ctataactaa gaaaaaaaaa aaaaaaaaa 7419421413DNAHomo sapiens 42gccgccaccg tcgtccgcaa agcctgagtc ctgtcctttc tctctccccg gacagcatga 60gcttcaccac tcgctccacc ttctccacca actaccggtc cctgggctct gtccaggcgc 120ccagctacgg cgcccggccg gtcagcagcg cggccagcgt ctatgcaggc gctgggggct 180ctggttcccg gatctccgtg tcccgctcca ccagcttcag gggcggcatg gggtccgggg 240gcctggccac cgggatagcc gggggtctgg caggaatggg aggcatccag aacgagaagg 300agaccatgca aagcctgaac gaccgcctgg cctcttacct ggacagagtg aggagcctgg 360agaccgagaa ccggaggctg gagagcaaaa tccgggagca cttggagaag aagggacccc 420aggtcagaga ctggagccat tacttcaaga tcatcgagga cctgagggct cagatcttcg 480caaatactgt ggacaatgcc cgcatcgttc tgcagattga caatgcccgt cttgctgctg 540atgactttag agtcaagtat gagacagagc tggccatgcg ccagtctgtg gagaacgaca 600tccatgggct ccgcaaggtc attgatgaca ccaatatcac acgactgcag ctggagacag 660agatcgaggc tctcaaggag gagctgctct tcatgaagaa gaaccacgaa gaggaagtaa 720aaggcctaca agcccagatt gccagctctg ggttgaccgt ggaggtagat gcccccaaat 780ctcaggacct cgccaagatc atggcagaca tccgggccca atatgacgag ctggctcgga 840agaaccgaga ggagctagac aagtactggt ctcagcagat tgaggagagc accacagtgg 900tcaccacaca gtctgctgag gttggagctg ctgagacgac gctcacagag ctgagacgta 960cagtccagtc cttggagatc gacctggact ccatgagaaa tctgaaggcc agcttggaga 1020acagcctgag ggaggtggag gcccgctacg ccctacagat ggagcagctc aacgggatcc 1080tgctgcacct tgagtcagag ctggcacaga cccgggcaga gggacagcgc caggcccagg 1140agtatgaggc cctgctgaac atcaaggtca agctggaggc tgagatcgcc acctaccgcc 1200gcctgctgga agatggcgag gactttaatc ttggtgatgc cttggacagc agcaactcca 1260tgcaaaccat ccaaaagacc accacccgcc ggatagtgga tggcaaagtg gtgtctgaga 1320ccaatgacac caaagttctg aggcattaag ccagcagaag cagggtaccc tttggggagc 1380aggaggccaa taaaaagttc agagttcatt gga 1413432308DNAHomo sapiens 43agtcctgctt ctcttccctc tctcctccag cctctcacac tctcctcagc tctctcatct 60cctggaacca tggccagcac atccaccacc atcaggagcc acagcagcag ccgccggggt 120ttcagtgcca actcagccag gctccctggg gtcagccgct ctggcttcag cagcgtctcc 180gtgtcccgct ccaggggcag tggtggcctg ggtggtgcat gtggaggagc tggctttggc 240agccgcagtc tgtatggcct ggggggctcc aagaggatct ccattggagg gggcagctgt 300gccatcagtg gcggctatgg cagcagagcc ggaggcagct atggctttgg tggcgccggg 360agtggatttg gtttcggtgg tggagccggc attggctttg gtctgggtgg tggagccggc 420cttgctggtg gctttggggg ccctggcttc cctgtgtgcc cccctggagg catccaagag 480gtcaccgtca accagagtct cctgactccc ctcaacctgc aaatcgatcc caccatccag 540cgggtgcggg ctgaggagcg tgaacagatc aagaccctca acaacaagtt tgcctccttc 600atcgacaagg tgcggttcct ggagcagcag aacaaggttc tggaaacaaa gtggaccctg 660ctgcaggagc agggcaccaa gactgtgagg cagaacctgg agccgttgtt cgagcagtac 720atcaacaacc tcaggaggca gctggacagc attgtcgggg aacggggccg cctggactca 780gagctcagag gcatgcagga cctggtggag gacttcaaga acaaatatga ggatgaaatc 840aacaagcgca cagcagcaga gaatgaattt gtgactctga agaaggatgt ggatgctgcc 900tacatgaaca aggttgaact gcaagccaag gcagacactc tcacagacga gatcaacttc 960ctgagagcct tgtatgatgc agagctgtcc cagatgcaga cccacatctc agacacatct 1020gtggtgctgt ccatggacaa caaccgcaac ctggacctgg acagcatcat cgctgaggtc 1080aaggcccaat atgaggagat tgctcagaga agccgggctg aggctgagtc ctggtaccag 1140accaagtacg aggagctgca ggtcacagca ggcagacatg gggacgacct gcgcaacacc 1200aagcaggaga ttgctgagat caaccgcatg atccagaggc tgagatctga gatcgaccac 1260gtcaagaagc agtgcgccaa cctgcaggcc gccattgctg atgctgagca gcgtggggag 1320atggccctca aggatgccaa gaacaagctg gaagggctgg aggatgccct gcagaaggcc 1380aagcaggacc tggcccggct gctgaaggag taccaggagc tgatgaatgt caagctggcc 1440ctggacgtgg agatcgccac ctaccgcaag ctgctggagg gtgaggagtg caggctgaat 1500ggcgaaggcg ttggacaagt caacatctct gtggtgcagt ccaccgtctc cagtggctat 1560ggcggtgcca gtggtgtcgg cagtggctta ggcctgggtg gaggaagcag ctactcctat 1620ggcagtggtc ttggcgttgg aggtggcttc agttccagca gtggcagagc cattgggggt 1680ggcctcagct ctgttggagg cggcagttcc accatcaagt acaccaccac ctcctcctcc 1740agcaggaaga gctataagca ctaaagtgcg tctgctagct ctcggtccca cagtcctcag 1800gcccctctct ggctgcagag ccctctcctc aggttgcctt tcctctcctg gcctccagtc 1860tcccctgctg tcccaggtag agctgggtat ggatgcttag tgccctcact tcttctctct 1920ctctctatac catctgagca cccattgctc accatcagat caacctctga ttttacatca 1980tgatgtaatc accactggag cttcactgtt actaaattat taatttcttg cctccagtgt 2040tctatctctg aggctgagca ttataagaaa atgacctctg ctccttttca ttgcagaaaa 2100ttgccagggg cttatttcag aacaacttcc acttactttc cactggctct caaactctct 2160aacttataag tgttgtgaac ccccacccag gcagtatcca tgaaagcaca agtgactagt 2220cctatgatgt acaaagcctg tatctctgtg atgatttctg tgctcttcgc tgtttgcaat 2280tgctaaataa agcagattta taatacaa 2308442302DNAHomo sapiens 44gtcctgcttc tcctccctct cgcctccagc ctctcacact ctcctaagcc ctctcatctc 60ctggaaccat ggccagcaca tccaccacca tcaggagcca cagcagcagc cgccggggtt 120tcagtgccaa ctcagccagg ctccctgggg tcagccgctc tggcttcagc agcatctccg 180tgtcccgctc caggggcagt ggtggcctgg gtggcgcatg tggaggagct ggctttggca 240gccgcagtct gtatggcctg gggggctcca agaggatctc cattggaggg ggcagctgtg 300ccatcagtgg cggctatggc agcagagccg gaggcagcta tggctttggt ggcgccggga 360gtggatttgg tttcggtggt ggagccggca ttggctttgg tctgggtggt ggagccggcc 420ttgctggtgg ctttgggggc cctggcttcc ctgtgtgccc ccctggaggc atccaagagg 480tcactgtcaa ccagagtctc ctgactcccc tcaacctgca aattgacccc gccatccagc 540gggtgcgggc cgaggagcgt gagcagatca agaccctcaa caacaagttt gcctccttca 600tcgacaaggt gcggttccta gagcagcaga acaaggttct ggacaccaag tggaccctgc 660tgcaggagca gggcaccaag actgtgaggc agaacctgga gccgttgttc gagcagtaca 720tcaacaacct caggaggcag ctggacaaca tcgtggggga acggggtcgt ctggactcgg 780agctgagaaa catgcaggac ctggtggagg acctcaagaa caaatatgag gatgaaatca 840acaagcgcac agcagcagag aatgaatttg tgactctgaa gaaggatgtg gatgctgcct 900acatgaacaa ggttgaactg caagccaagg cagacactct tacagatgag atcaacttcc 960tgagagcctt gtatgatgca gagctgtccc agatgcagac ccacatctca gacacatccg 1020tggtgctatc catggacaac aaccgcaacc tggacctgga cagcatcatc gctgaggtca 1080aggcccaata tgaggagatt gctcagagga gcagggctga ggctgagtcc tggtaccaga 1140caaagtacga ggagctgcag atcacagcag gcagacatgg ggacgacctg cgcaacacca 1200agcaggagat tgctgagatc aaccgcatga tccagaggct gagatctgag atcgaccacg 1260tcaagaagca gtgtgccaac ctacaggccg ccattgctga tgctgagcag cgtggggaga 1320tggccctcaa ggatgctaag aacaagctgg aagggctgga ggatgccctg cagaaggcca 1380agcaggacct ggcccggctg ctgaaggagt accaggagct gatgaacgtc aagctggccc 1440tggatgtgga gatcgccacc taccgcaagc tgctggaggg cgaggagtgc aggctgaatg 1500gcgaaggcgt tggacaagtc aacatctctg tagtgcagtc caccgtctcc agtggctatg 1560gcggtgccag cggtgtcggc agtggcttag gcctgggtgg aggaagcagc tactcctatg 1620gcagtggtct tggcgttgga ggcggcttta gttccagcag cggcagagcc actgggggtg 1680gcctcagctc tgttggaggc ggcagttcca ccatcaagta caccaccacc tcctcctcca 1740gcaggaagag ctacaagcac tgaagtgctg ccgccagctc tcagtcccac agctctcagg 1800cccctctctg gcagcagagc cctctcctca ggttgcttgt cctcccctgg cctccagtct 1860cccctgccct cccgggtaga gctgggatgc cctcactttt cttctcatca atacctgttc 1920cactgagctc ctgttgctta ccatcaagtc aacagttatc agcactcaga catgcgaatg 1980tcctttttag ttcccgtatt attacaggta tctgagtctg ccataattct gagaagaaaa 2040tgacctatat ccccataaga actgaaactc agtctaggtc cagctgcaga tgaggagtcc 2100tctctttaat tgctaaccat cctgcccatt atagctacac tcaggagttc tcatctgaca 2160agtcagttgt cctgatcttc tcttgcagtg tccctgaatg gcaagtgatg taccttctga 2220tgcagtctgc attcctgcac tgctttctct gctctctttg ccttcttttg ttctgttgaa 2280taaagcatat tgagaatgtg aa 2302451926DNAHomo sapiens 45actccaggtc ccctatcctg tcctctgcaa cccaaacgtc caggaggatc atgacctgcg 60gatcaggatt tggtgggcgc gccttcagct gcatctcggc ctgcgggccg cggcccggcc 120gctgctgcat caccgccgcc ccctaccgtg gcatctcctg ctaccgcggc ctcaccgggg 180gcttcggcag ccacagcgtg tgcggaggct ttcgggccgg ctcctgcgga cgcagcttcg 240gctaccgctc cgggggcgtg tgcgggccca gtcccccatg catcaccacc gtgtcggtca 300acgagagcct cctcacgccc ctcaacctgg agatcgaccc caacgcgcag tgcgtgaagc 360aggaggagaa ggagcagatc aagtccctca acagcaggtt cgcggccttc atcgacaagg 420tgcgcttcct ggagcagcag aacaaactgc tggagacaaa gctgcagttc taccagaacc 480gcgagtgttg ccagagcaac ctggagcccc tgtttgaggg ctacatcgag actctgcggc 540gggaggccga gtgcgtggag gccgacagcg ggaggctggc ctcagagctt aaccacgtgc 600aggaggtgct ggagggctac aagaagaagt atgaggagga ggtttctctg agagcaacag 660ctgagaacga gtttgtggct ctgaagaagg atgtggactg cgcctacctc cgcaagtcag 720acctggaggc caacgtggag gccctgatcc aggagatcga cttcctgagg cggctgtatg 780aggaggagat cctcattctc cagtcgcaca tctcagacac ctccgtggtt gtcaagctgg 840acaacagccg ggacctgaac atggactgca tcattgccga gattaaggca cagtatgacg 900acattgtcac ccgcagccgg gccgaggccg agtcctggta ccgcagcaag tgtgaggaga 960tgaaggccac ggtgatcagg cacggggaga ccctgcgccg caccaaggag gagatcaatg 1020agctgaaccg catgatccaa aggctgacgg ccgaggtgga gaatgccaag tgccagaact 1080ccaagctgga ggccgcggtg gcccagtctg agcagcaggg tgaggcggcc ctcagtgatg 1140cccgctgcaa gctggccgag ctggagggcg ccctgcagaa ggccaagcag gacatggcct 1200gcctgatcag ggagtaccag gaggtgatga actccaagct gggcctggac atcgagatcg 1260ccacctacag gcgcctgctg gagggcgagg agcagaggct atgtgaaggc attggggctg 1320tgaatgtctg tgtcagcagc tcccggggcg gggtcgtgtg cggggacctc tgcgtgtcag 1380gctcccggcc agtgactggc agtgtctgca gcgctccgtg caacgggaac gtggcggtga 1440gcaccggcct gtgtgcgccc tgcggccaat tgaacaccac ctgcggaggg ggttcctgcg 1500gcgtgggctc ctgtggtatc agctccctgg gtgtggggtc ttgcggcagc agctgccgga 1560aatgttaggc accccaactc aagtcccagg ccccaggcat ctttcctgcc ctgccttgct 1620tggcccatcc agtccaggcg cctggagcaa gtgctcagct acttctcctg cactttgaaa 1680gacccctccc actcctggcc tcacatttct ctgtgtgatc ccccacttct gggctctgcc 1740accccacagt gggaaaggcc accctagaaa gaagtccgct ggcacccata ggaaggggcc 1800tcaggagcag gaagggccag gaccagaacc ttgcccacgg caactgcctt cctgcctctc 1860cccttcctcc tctgctcttg atctgtgttt caataaatta atgtagccaa aaaaaaaaaa 1920aaaaaa 1926461802DNAHomo sapiens 46aaaaggccat tcctgagagc tctcctcacc aagaagcagc ttctccgctc cttctaggat 60ctccgcctgg ttcggcccgc ctgcctccac tcctgcctct accatgtcca tcagggtgac 120ccagaagtcc tacaaggtgt ccacctctgg cccccgggcc ttcagcagcc gctcctacac 180gagtgggccc ggttcccgca tcagctcctc gagcttctcc cgagtgggca gcagcaactt 240tcgcggtggc ctgggcggcg gctatggtgg ggccagcggc atgggaggca tcaccgcagt 300tacggtcaac cagagcctgc tgagccccct tgtcctggag gtggacccca acatccaggc 360cgtgcgcacc caggagaagg agcagatcaa gaccctcaac aacaagtttg cctccttcat 420agacaaggta cggttcctgg agcagcagaa caagatgctg gagaccaagt ggagcctcct 480gcagcagcag aagacggctc gaagcaacat ggacaacatg ttcgagagct acatcaacaa 540ccttaggcgg cagctggaga ctctgggcca ggagaagctg aagctggagg cggagcttgg 600caacatgcag gggctggtgg aggacttcaa gaacaagtat gaggatgaga tcaataagcg 660tacagagatg gagaacgaat ttgtcctcat caagaaggat gtggatgaag cttacatgaa 720caaggtagag ctggagtctc gcctggaagg gctgaccgac gagatcaact tcctcaggca 780gctatatgaa gaggagatcc gggagctgca gtcccagatc tcggacacat ctgtggtgct 840gtccatggac aacagccgct ccctggacat ggacagcatc attgctgagg tcaaggcaca 900gtacgaggat attgccaacc gcagccgggc tgaggctgag agcatgtacc agatcaagta 960tgaggagctg cagagcctgg ctgggaagca cggggatgac ctgcggcgca caaagactga 1020gatctctgag atgaaccgga acatcagccg gctccaggct gagattgagg gcctcaaagg 1080ccagagggct tccctggagg ccgccattgc agatgccgag cagcgtggag agctggccat 1140taaggatgcc aacgccaagt tgtccgagct ggaggccgcc ctgcagcggg ccaagcagga 1200catggcgcgg cagctgcgtg agtaccagga gctgatgaac gtcaagctgg ccctggacat 1260cgagatcgcc acctacagga agctgctgga gggcgaggag agccggctgg agtctgggat 1320gcagaacatg agtattcata cgaagaccac cagcggctat gcaggtggtc tgagctcggc 1380ctatgggggc ctcacaagcc ccggcctcag ctacagcctg ggctccagct ttggctctgg 1440cgcgggctcc agctccttca gccgcaccag ctcctccagg gccgtggttg tgaagaagat 1500cgagacacgt gatgggaagc tggtgtctga gtcctctgac gtcctgccca agtgaacagc 1560tgcggcagcc cctcccagcc tacccctcct gcgctgcccc agagcctggg aaggaggccg 1620ctatgcaggg tagcactggg aacaggagac ccacctgagg ctcagcccta gccctcagcc 1680cacctgggga gtttactacc tggggacccc ccttgcccat gcctccagct acaaaacaat 1740tcaattgctt tttttttttg gtccaaaata aaacctcagc tagctctgcc aatgtcaaaa 1800aa 1802472869DNAHomo sapiens 47ggtccaccca gtgcttgcgg cctcgcggcc gggccggcct gggctgcaat caatgcggct 60ttgtctggga cgcccacatc ccagaggcca ttcccgggtc ggcaaatcgg agcgcggccg 120gggcgcgcgg gggtgagata agcggccatg tgatcccacc tgggctggaa ggggaggggc 180gccaggtgag gcggcggccg gcggggcgcg ggcggccacg cggggctcct gcagcatggc 240tgtcagcagg aaggactggt ccgcgctgtc cagccttgcc cggcagagga ctctggagga 300tgaggaggaa caggagcgcg agcgcaggcg gcggcaccgc aacctgagct ccaccacgga 360cgatgaggct cccaggctca gccagaatgg agaccggcag gcctctgctt ctgagagact 420accgagcgtg gaagaagcag aggtgcccaa gccactgccc ccagcctcca aagatgagga 480cgaggacatc cagagcatcc tcagaacacg gcaggagcgg aggcagaggc ggcaggtggt 540ggaggctgca caggccccca tccaggagag gctggaggca gaggagggga ggaacagctt 600gagccctgtg caggccacac agaaacccct agtctccaag aaggaactgg aaatcccacc 660tcgccggaga ctgagtcggg aacagcgggg cccctgggcc ctggaggagg agagcttggt 720gggcagggag ccagaagaga ggaagaaagg ggttccagaa aagtccccag tcttggagaa 780gtcctccatg ccaaagaaga cggcacctga aaagagcctg gtctccgata aaacctccat 840ctctgagaag gtgctggcct cagagaagac atctctatca gagaagatag cagtgtcaga 900gaaaagaaac agctcagaga agaagtctgt tctagaaaaa accagtgtct ctgagaagtc 960gctggcccca gggatggcac tgggctcagg aaggaggctg gtgtctgaga aagcttccat 1020ctttgagaag gcactggcct cagagaagag cccaactgca gatgctaagc cggccccaaa 1080gagggccaca gcctcagagc agcccctggc gcaggagccg ccagcctctg ggggaagccc 1140agccaccacc aaggagcaga gaggaagggc cctccctggg aagaacctgc cctctttggc 1200aaagcagggg gcttcagacc ctccgactgt ggcctcccgc ctcccacccg tcacactcca 1260ggtgaaaatc cccagcaagg aggaagaggc agatatgtcc tcacccacac agcgaaccta 1320cagcagctcc ctcaaacgct ccagccccag gaccatctcc tttcggatga aacccaagaa 1380agaaaactcg gaaacaaccc taactcgcag tgccagcatg aagctcccag acaacacagt 1440gaagttggga gagaagctgg agagatacca cacggccata cggagatcag aatctgtcaa 1500gtctcggggt ctgccttgca ctgagttatt cgtggctcct gtgggtgtag ccagcaagcg 1560ccacctcttt gagaaggaac tggcgggcca gagccgagca gaaccagcct ccagccggaa 1620ggagaacttg aggctctcag gggttgtgac atcaaggctc aacctgtgga tcagcaggac 1680ccaggaatct ggagatcagg acccccagga ggcacagaaa gcatcatctg caaccgagag 1740gactcagtgg ggacagaaat ctgactcctc gctggacgct gaggtgtgac aagccccgcc 1800aagacagacc tgcaagtctt cgtctcaagg gacctccctc atgccaggcc cctgcctctc 1860acagcagcac cctttcctct cattgtccct gttccctttt tgcctgtgga tctgtttggc 1920cagggtccct ggggtcagga atatttgcaa gactcagcca gctccttccc agcccagcct 1980cttggggctg ggactttctc accctgcggc aggcacaaca gatgctggga cccagtctct 2040gcccaggtca cagcacaagt gcacatcagc actatggggc ctatgtcctg cccagagacc 2100tctgctcctt cctgctcaca tccacagtca gggcacggcg cccctcaaga actccagagt 2160cacctgtctc atcggctccc agcaagtgcc tctttgtcta tgatgtcccc cttctctgag 2220gcctggaccc acccatcttt gtccctgggg cctgctccca gccactgagg cccgctctgg 2280ccaggggaga aggagctgcc gtgcgtcttc cctgtgcccc gtctccctgc ttggttctcc 2340cctcccttcc ctggccggct gccatggcca ggagctaagt gcctttttgt gtgcaaccac 2400ttaccctttc tctgaaaaac ctgttctcag gaaggatctg ataaactcat ttactctcag 2460gtgtaagaga ctgatgagac cttagaagcg aattcctctc tggaggcctt gctttctagc 2520agaggtcacc tgaagtgtgt gaggaggatc atcattttcc tcatcccccc tcttctcaca 2580ttaaggtggt ggcttgccac tcagcagtcc tagcttggtg actgggaact gccacataca 2640gggccaggcc taccctcctt ccccacaagc cccctccaac ccccaccccc atgctctgga 2700cctcatggct cctatgagct tggagcatgg tgaaccatca gagaatctag aaccaaccaa 2760gctaggaaca tcagcctggt gccctgttaa ccccttaaag ctgtggttta caacttttca 2820aaaatttaaa tcattagaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2869482091DNAHomo sapiens 48gagacaggtg gtggctacga cggcgaaggg agctgagact gtccaggcag ccaggttagg 60ccaggaggac catgtgaatg gggccagagg gctcccgggc tgggcaggga ccatgggctg 120tggctgcagc tcacacccgg aagatgactg gatggaaaac atcgatgtgt gtgagaactg 180ccattatccc atagtcccac tggatggcaa gggcacgctg ctcatccgaa atggctctga 240ggtgcgggac ccactggtta cctacgaagg ctccaatccg ccggcttccc cactgcaaga 300caacctggtt atcgctctgc acagctatga gccctctcac gacggagatc tgggctttga 360gaagggggaa cagctccgca tcctggagca gagcggcgag tggtggaagg cgcagtccct 420gaccacgggc caggaaggct tcatcccctt caattttgtg gccaaagcga acagcctgga 480gcccgaaccc tggttcttca agaacctgag ccgcaaggac gcggagcggc agctcctggc 540gcccgggaac actcacggct ccttcctcat ccgggagagc gagagcaccg cgggatcgtt 600ttcactgtcg gtccgggact tcgaccagaa ccagggagag gtggtgaaac attacaagat 660ccgtaatctg gacaacggtg gcttctacat ctcccctcga atcacttttc ccggcctgca 720tgaactggtc cgccattaca ccaatgcttc agatgggctg tgcacacggt tgagccgccc 780ctgccagacc cagaagcccc agaagccgtg gtgggaggac gagtgggagg ttcccaggga 840gacgctgaag ctggtggagc ggctgggggc tggacagttc ggggaggtgt ggatggggta 900ctacaacggg cacacgaagg tggcggtgaa gagcctgaag cagggcagca tgtccccgga 960cgccttcctg gccgaggcca acctcatgaa gcagctgcaa caccagcggc tggttcggct 1020ctacgctgtg gtcacccagg agcccatcta catcatcact gaatacatgg agaatgggag 1080tctagtggat tttctcaaga ccccttcagg catcaagttg accatcaaca aactcctgga 1140catggcagcc caaattgcag aaggcatggc attcattgaa gagcggaatt atattcatcg 1200tgaccttcgg gctgccaaca ttctggtgtc tgacaccctg agctgcaaga ttgcagactt 1260tggcctagca cgcctcattg aggacaacga gtacacagcc agggaggggg ccaagtttcc 1320cattaagtgg acagcgccag aagccattaa ctacgggaca ttcaccatca agtcagatgt 1380gtggtctttt gggatcctgc tgacggaaat tgtcacccac ggccgcatcc cttacccagg 1440gatgaccaac ccggaggtga ttcagaacct ggagcgaggc taccgcatgg tgcgccctga 1500caactgtcca gaggagctgt accaactcat gaggctgtgc tggaaggagc gcccagagga 1560ccggcccacc tttgactacc tgcgcagtgt gctggaggac ttcttcacgg ccacagaggg 1620ccagtaccag cctcagcctt gagaggcctt gagaggccct ggggttctcc ccctttctct 1680ccagcctgac ttggggagat ggagttcttg tgccatagtc

acatggccta tgcacatatg 1740gactctgcac atgaatccca cccacatgtg acacatatgc accttgtgtc tgtacacgtg 1800tcctgtagtt gcgtggactc tgcacatgtc ttgtacatgt gtagcctgtg catgtatgtc 1860ttggacactg tacaaggtac ccctttctgg ctctcccatt tcctgagacc acagagagag 1920gggagaagcc tgggattgac agaagcttct gcccacctac ttttctttcc tcagatcatc 1980cagaagttcc tcaagggcca ggactttatc taatacctct gtgtgctcct ccttggtgcc 2040tggcctggca cacatcagga gttcaataaa tgtctgttga tgactgttgt a 2091491121DNAHomo sapiens 49accatctccc actcctgcag ctcttctcac aggaccagcc actagcgcag cctcgagcga 60tggcctatgt ccccgcaccg ggctaccagc ccacctacaa cccgacgctg ccttactacc 120agcccatccc gggcgggctc aacgtgggaa tgtctgttta catccaagga gtggccagcg 180agcacatgaa gcggttcttc gtgaactttg tggttgggca ggatccgggc tcagacgtcg 240ccttccactt caatccgcgg tttgacggct gggacaaggt ggtcttcaac acgttgcagg 300gcgggaagtg gggcagcgag gagaggaaga ggagcatgcc cttcaaaaag ggtgccgcct 360ttgagctggt cttcatagtc ctggctgagc actacaaggt ggtggtaaat ggaaatccct 420tctatgagta cgggcaccgg cttcccctac agatggtcac ccacctgcaa gtggatgggg 480atctgcaact tcaatcaatc aacttcatcg gaggccagcc cctccggccc cagggacccc 540cgatgatgcc accttaccct ggtcccggac attgccatca acagctgaac agcctgccca 600ccatggaagg acccccaacc ttcaacccgc ctgtgccata tttcgggagg ctgcaaggag 660ggctcacagc tcgaagaacc atcatcatca agggctatgt gcctcccaca ggcaagagct 720ttgctatcaa cttcaaggtg ggctcctcag gggacatagc tctgcacatt aatccccgca 780tgggcaacgg taccgtggtc cggaacagcc ttctgaatgg ctcgtgggga tccgaggaga 840agaagatcac ccacaaccca tttggtcccg gacagttctt tgatctgtcc attcgctgtg 900gcttggatcg cttcaaggtt tacgccaatg gccagcacct ctttgacttt gcccatcgcc 960tctcggcctt ccagagggtg gacacattgg aaatccaggg tgatgtcacc ttgtcctatg 1020tccagatcta atctattcct ggggccataa ctcatgggaa aacagaatta tcccctagga 1080ctcctttcta agcccctaat aaaatgtctg agggtgtctc a 1121503646DNAHomo sapiens 50gcgggagaag aggaagacag gaagggggtg gggatgtgaa gcgaccgtcc cagccttccc 60cgcccgccac ccccacccca actcggcagc cgtcacgtga tgcctggagt gggaggtggg 120gagaaaaggc gagacttttg tgggtgctcc cgatcgccag tagttccttc agtctcagcc 180gccaactccg gaggcgcggt gctcggcccg ggagcgcgag cgggaggagc agagacccgc 240agccgggagc ccgagcgcgg gcgatgcagg ctccgcgagc ggcacctgcg gctcctctaa 300gctacgaccg tcgtctccgc ggcagcagcg cgggccccag cagcctcggc agccacagcc 360gctgcagccg gggcagcctc cgctgctgtc gcctcctctg atgcgcttgc cctctcccgg 420ccccgggact ccgggagaat gtgggtccta ggcatcgcgg caactttttg cggattgttc 480ttgcttccag gctttgcgct gcaaatccag tgctaccagt gtgaagaatt ccagctgaac 540aacgactgct cctcccccga gttcattgtg aattgcacgg tgaacgttca agacatgtgt 600cagaaagaag tgatggagca aagtgccggg atcatgtacc gcaagtcctg tgcatcatca 660gcggcctgtc tcatcgcctc tgccgggtac cagtccttct gctccccagg gaaactgaac 720tcagtttgca tcagctgctg caacacccct ctttgtaacg ggccaaggcc caagaaaagg 780ggaagttctg cctcggccct caggccaggg ctccgcacca ccatcctgtt cctcaaatta 840gccctcttct cggcacactg ctgaagctga aggagatgcc accccctcct gcattgttct 900tccagccctc gcccccaacc ccccacctcc ctgagtgagt ttcttctggg tgtcctttta 960ttctgggtag ggagcgggag tccgtgttct cttttgttcc tgtgcaaata atgaaagagc 1020tcggtaaagc attctgaata aattcagcct gactgaattt tcagtatgta cttgaaggaa 1080ggaggtggag tgaaagttca cccccatgtc tgtgtaaccg gagtcaaggc caggctggca 1140gagtcagtcc ttagaagtca ctgaggtggg catctgcctt ttgtaaagcc tccagtgtcc 1200attccatccc tgatgggggc atagtttgag actgcagagt gagagtgacg ttttcttagg 1260gctggagggc cagttcccac tcaaggctcc ctcgcttgac attcaaactt catgctcctg 1320aaaaccattc tctgcagcag aattggctgg tttcgcgcct gagttgggct ctagtgactc 1380gagactcaat gactgggact tagactgggg ctcggcctcg ctctgaaaag tgcttaagaa 1440aatcttctca gttctccttg cagaggactg gcgccgggac gcgaagagca acgggcgctg 1500cacaaagcgg gcgctgtcgg tggtggagtg cgcatgtacg cgcaggcgct tctcgtggtt 1560ggcgtgctgc agcgacaggc ggcagcacag cacctgcacg aacacccgcc gaaactgctg 1620cgaggacacc gtgtacagga gcgggttgat gaccgagctg aggtagaaaa acgtctccga 1680gaaggggagg aggatcatgt acgcccggaa gtaggacctc gtccagtcgt gcttgggttt 1740ggccgcagcc atgatcctcc gaatctggtt gggcatccag catacggcca atgtcacaac 1800aatcagccct gggcagacac gagcaggagg gagagacaga gaaaagaaaa acacagcatg 1860agaacacagt aaatgaataa aaccataaaa tatttagccc ctctgttctg tgcttactgg 1920ccaggaaatg gtaccaattt ttcagtgttg gacttgacag cttcttttgc cacaagcaag 1980agagaattta acactgtttc aaacccgggg gagttggctg tgttaaagaa agaccattaa 2040atgctttaga cagtgtattt ataccagttg atgtctgtta attttaaaaa aatgttttca 2100ttggtgtttg tttgcgtatc cagaaagcag ttcatgttat ccataaatct ggttttgtct 2160ttttttgttt taaagaaaaa gatgtataca tacagtatag ctgcattaga taaagcagtg 2220tttgtatttt aaaggatgtc tgcacaaaga agacctagtg atatttttaa atcaaatgga 2280agaagtgtcc ctttggcaac aaagcagcat atttaatgac actggttttg cattcagttt 2340caggggaagc aaagtcagga atagcctgtc gccaagaatg ttttttggac atatacatac 2400taggtatgca cacctataat catgatgctc atatctgcaa cagcatatgt gtttcttttc 2460agacactttt agatccctca tgtggggaaa aagaattatt cagagatggc aaatataaaa 2520cttccttcta gttcagccag taacatgttc ccttcctttg cagcactgag ctgtgctgtc 2580aacagcccag aagcaatcag gccctagaga agagaccact caaaggccct tctgtagatc 2640aaatgtttac tgcatgtaca tttgtttgca tgcccacata tttgtattcc aacttaagta 2700accaccacca gttctgcaat tctgactgac agagataaag atgctacata gaccacaaac 2760aactgaaatc acaggtatca tgagagttta gttacagtga caaaagcaaa aaagaacaaa 2820ggaagatcag gggatctgtg aagcatttgc tctctctttt cgtaaggagc caagacaccc 2880acagtaaatt cccctgtaga gagctgctac cttaaagcag gatttgcatt ttcagaaatg 2940cttccttcct ctcctacatt tcaatcgtag taagaaacat ttactcacat tttcaatctt 3000ctgattttct agaaacccta gggaagtgac agttggcaat gaatgcttcc tgcctatgac 3060ccatggtaaa tattctatta ataaatgggg gccagacatg gtggcgcatg cctgatatct 3120caatactctg ggaggccaag gcagaaggat cacttaagcc tagaaatttg agacccacct 3180aggcaacata gcaagacccc atctctacaa aaaaagaaaa acttagccag gcatggtggt 3240acatacacac ctgtggtctc agatactttt tgggggctga ggcgggagga tcacttgagc 3300ccaggaggtg aaggctacag tgagacacga atgtgccact gcactccagc ctggctgaca 3360gagtgaaact gtctcaataa accaataaat aaatgctcca ggaaaaaaca gccacattca 3420cacatccaga attgagcctc ctgtatgcac tggcctgagt attccttgcc tgctgttgga 3480ggggacccta gctgtgttca aatcctccac aaatccatat gtgagcaagg aaggccttgg 3540aaactcttct cctttgttaa tttccacagg tttctcctgt caactcccag cctaaaactt 3600tgaaatataa gccaatttgt ttatttttta aaaaaaaaaa aaaaaa 3646512698DNAHomo sapiens 51gggcttggcc acctgcccaa gaaacttgtt ggttgttgcc ctcaggtcgc tcccgggcgc 60ggacacggaa cccggccatg gaagatccgt cgggggctcg cgagccccgg gcccggccga 120gagagcggga cccgggacgg cgcccccacc cagaccaagg ccgcacccac gatcgaccgc 180gggaccgacc cggggacccg cgcaggaagc gaagcagcga cgggaaccgg cgaagggacg 240gggaccggga cccggagaga gaccaggaga gggacgggaa ccgcgaccgg aaccgggacc 300gggagaggga gagagagagg gaaagagacc cggaccgagg cccccgccgg gacacacaca 360gggacgcggg ccctcgcgca ggtgaacacg gagtttggga aaaaccgcgc caaagccgga 420cgcgggacgg agcccgggga ctgacctggg acgcagccgc gcctcctggg cccgcgccct 480gggaagcccc ggagccgccg cagccgcaga ggaagggaga ccccgggcgc cgcagacccg 540aaagtgaacc cccttcggag agatatctgc cctcgacccc caggcctgga cgagaggagg 600tggaatatta ccagtcagag gcggaaggac tcctggaatg ccacaaatgc aaatacttgt 660gcactgggag agcctgctgc caaatgctgg aggttctcct gaacttgctg atcctggcct 720gcagctctgt gtcttacagt tccacagggg gctacacggg catcaccagc ttggggggca 780tttactacta tcagttcgga ggggcttaca gtggctttga tggtgctgac ggggagaagg 840cccagcaact ggatgtccag ttctaccagc taaagctgcc catggtcact gtggcaatgg 900cctgtagtgg agccctcaca gccctctgct gcctcttcgt tgccatgggt gtcctgcggg 960tcccgtggca ttgtccactg ttgctggtga ccgaaggctt gttggacatg ctcatcgcgg 1020gggggtacat cccggccttg tacttctact tccactacct ctctgctgcc tatggctctc 1080ctgtgtgtaa agagaggcag gcgctgtacc aaagcaaagg ctacagcggt ttcggctgca 1140gtttccacgg agcagatata ggagctggaa tctttgctgc cctgggcatt gtggtctttg 1200ccctgggggc tgtcctggcc ataaagggct accgaaaagt taggaagcta aaagagaagc 1260cagcagaaat gtttgaattt taagggtttc taaaacgctc tgacagatgc aagtggtggt 1320ggaaggtagt ctgagccact gcctttccca agaatccctt gttgtggaag tttccagtgc 1380tggaaaagca gcgagccagc gttggtgtgg tgggcggagc tcccagtcgc atggagcggt 1440gttcatggat gcaacagacc ctggcttctg gagtcctctg tgagtgaggg accaatcaaa 1500attatttttc aaaaagcaaa aaaatggccg gcctcggcgg ctcacacctg taaccccagc 1560actttgggag gctgaggtgg gtggatcact tgaggtcagg agctcgagac cagcttggcc 1620aacatggtga gcccccgtct ctactaaaat acaaaaaaat tagccaggcg tggtggcggg 1680cgcctgtaat cccagctact tgggaggctg aggcaggaga atcgcttgaa tctgggaggc 1740ggagattgca gtgagccgag atcccgccac tgcactccag cccaggtgac agagcgagac 1800tccatctcaa aaaaaaaaaa aagcaaaaaa actggacccc aagagccaca aggaaaaagc 1860atgtactaca acagagtgca cctcttcatt cagtaaaggg aggtcaccaa gagaatttga 1920tgaaccttac cttcaaagtt cctgggcaca gtggctcaca cctgtaatcc cagagctttg 1980ggaggctgag gtaggaggat tgcttgaacc caggagttca agtttgcagt gcgctatgat 2040tgtcccacta cactctagcc tgagcaacag accaagaccg tattgccaaa ataccaaaaa 2100aaaaaaaagt tcatggagag ccacatagac atgagaccac acttcagcct gaatttttct 2160aaaacacagt tgtctcaagc agattactcc acacgttttt ccacactgaa ctctccagtc 2220cttccacttc cttaattctg caaatggagg gggtggggac tcttgggaaa ctactcctgt 2280aaaattgaag ttggaggtag gcgtgggctg aggaaagagg aatcagatta attctctggg 2340ttgcaaagag gctattctgc aagcccctta cagtggccct gaaagctcaa taagtgtttt 2400gtacctcttg taaatgtgcc attgtgtgaa gcattaaacc caacatctag aattcaggat 2460tcatccagaa taaaaggatg taaaatcttt cccaacagaa gagtgttact tttggtcaga 2520caacttcatg ggttcttact gcacattaaa ttatgactta tggaacattg caatatattc 2580tcggtcctta agttatgact tatggaacat tacaatatat tctcggtcca agtgagtaag 2640ttctttgctt tatgtgaatc caataaaaaa tccaaagaat tttaaaaaaa aaaaaaaa 2698529701DNAHomo sapiens 52agcccctagc gcagacggcg gagagcagag agggagcgcg ccttggctcg ctggccttgg 60cggcggctcc tcaggagagc tggggcgccc acgagaggat ccctcacccg ggtctctcct 120cagggatgac atcatccgtc cacctccttg tcttcaagga ccacctcctc tccatgctga 180gctgctgcca aggggcctgc tgcccatcta cacctcacga gggcactagg agcacggttt 240cctggatccc accaacatac aaagcagcca ctcactgacc cccaggacca ggatggcaaa 300ggatgaagag gaccggaact gaccagccag ctgtccctct tacctaaaga cttaaaccaa 360tgccctagtg agggggcatt gggcattaag ccctgacctt tgctatgctc atactttgac 420tctatgagta ctttcctata agtctttgct tgtgttcacc tgctagcaaa ctggagtgtt 480tccctcccca agggggtgtc agtctttgtc gactgactct gtcatcaccc ttatgatgtc 540ctgaatggaa ggatcccttt gggaaattct caggaggggg acctgggcca agggcttggc 600cagcatcctg ctggcaactc caaggccctg ggtgggcttc tggaatgagc atgctactga 660atcaccaaag gcacgcccga cctctctgaa gatcttccta tccttttctg ggggaatggg 720gtcgatgaga gcaacctcct agggttgttg tgagaattaa atgagataaa agaggcctca 780ggcaggatct ggcatagagg aggtgatcag caaatgtttg ttgaaaaggt ttgacaggtc 840agtcccttcc cacccctctt gcttgtctta cttgtcttat ttattctcca acagcactcc 900aggcagccct tgtccacggg ctctccttgc atcagccaag cttcttgaaa ggcctgtcta 960cacttgctgt cttccttcct cacctccaat ttcctcttca acccactgct tcctgactcg 1020ctctactccg tggaagcacg ctcacaaagg cacgtgggcc gtggcccggc tgggtcggct 1080gaagaactgc ggatggaagc tgcggaagag gccctgatgg ggcccaccat cccggaccca 1140agtcttcttc ctggcgggcc tctcgtctcc ttcctggttt gggcggaagc catcacctgg 1200atgcctacgt gggaagggac ctcgaatgtg ggaccccagc ccctctccag ctcgaaatcg 1260gcagactagg atggaagtgc cctgtgagct ggggggccct tcaaagggcc aaggagaaaa 1320cgcaggccga gggaccagcc ttccaaatgg gcttcaagct ccaatgacct ccgctcgccc 1380cctcgaaatg tctggaaaac ataatgggca gattttctgt cttcaaagtt tccggctaaa 1440cctcttcaag ttctttattg tttgggactg agacactcag ccatgttaat gggtagtttc 1500ttttgtattt gccttgaaag gccaaaatat ttttatattg ccacagacaa agccacctat 1560ttaaaaatga actccatgtc cgtcgtttcc caccaggaga ctatgtacca tgtgtgtgtc 1620tctatgtatt ctggggtctt gaaacaggtt tctcatgggg atggtcattc accacggtcc 1680agaggggcag aacaggcggc gcttgccttg cccagggggc ctggggaacg tgggccctca 1740tctcagatct gcccccagta tgtttaggac gcgagcccca gaaggatctg ggagtaaact 1800taacattcac tgtgtctctg ctctgcatcc gccatttgtg tgtgtttctg gactgtgggc 1860tgtgtgtacc ttggttggtg actcagtgag aagaagcagg aatgccaaag atactgtgaa 1920tgttctgagt tttgttgctg ttgttgttga gaggttgttt cactggtatc tattgcattg 1980tataataaat gaccagatga atgaatgagt gaagcaagag agaatgaata aacaagtaaa 2040taggtaaaga agtaagcaag ccaggatgag agtgtgtgta cacaagacca tggttcatcc 2100gctttgatgg ctaggcaatc aatatataaa tagaaaaaaa ccagtgaatc actaagtaat 2160agggcaacac acaaagcgat atcaggtgat tatggactaa ggggtatgtg taactcaaat 2220atatgcctct gacatttgac aatgaaaaag aacctaaatg aaagaaagaa tggatgtatg 2280agtagtgaag tgcagaatga gacatagatt ttgaggcccg tcaaaatgaa aagatgcaag 2340ttagggaaca agtgatcaaa agggagaagg gaaaggtttt ttttaaaaaa ccaaaacaac 2400aaagaaaggt taaaaaaaaa aacagactag aggatgagta atgagtaact ctgtaaggag 2460gaccatgtca gactattgta agctaagcat taggactgat acaaataata tatgctcctg 2520gcatagaaaa ataaaccaca gagaacgagt tcaaagaata gcaaagaaag aaagaggacc 2580cagtgggcga aagatgagag tgtactttta ccaaaagtta tctaagcctg agcacttgaa 2640gtctgcacat aaataaataa atgacaaaag aaagaaaaaa aggccaaaaa gtctacattg 2700cgtgtgtgga tggatgaatg agcagtggga gtgcagcgcc aggtgacaag atgttgtgag 2760gggttttgag tcatccagtc ctgggcactg aggtctgtta gatgaaagga tatgagaaag 2820gtaatattgg taaataaaga aataggaaac aatgtaacaa atgttaagta cagaaataca 2880ttaatgggtg gtaaataaag atgtaaaaga aggcaatgcg atcgatggtg gcaaaagatc 2940atcacagatt aagggctatg gctggtccac ttctagaaaa ccacaggctg tccattaaat 3000aatgaacatc taagtgaaca agtcagtgag tacctaaata gacaaggatg aggtgaatga 3060gaagacatgg ccccatgggt cctcctgatg agggtgttgg ggtcccccct gggcacccca 3120gctgcatgaa aatgaaggac aggaggtatg gaaagctatg acagaagaga gaaaggaacg 3180gtaaaaagaa ataacaacca aatggataaa tgggtagatc cacgagaaga gttaggctag 3240gacttgtcat aagggcacct gactccacta atagaggaat aaatgcctaa taaaaagaga 3300gcaagcagga aggaaggatg ctatgaatgc aggaaggaag taatgagtga gacgtggaac 3360cgcacggcca aggatggacg tttgcgggtg gctttttgat gcgtacagcc aagccactcc 3420atggcaatga gctccgaaga caaagtgcaa gagagaatga gtgagagagt gagagagaga 3480gaaacaataa aaaatgggaa gaaatgtaaa aaggaagaaa ggaagagagg taatatatta 3540aggaataaat acatgcatgc agatttaaga cagagccatg ctagaacagg aatgaaaggc 3600tgtgtgaacc aagcagaccg cttaattggc accagtgctg ctggtatggt caatcaccta 3660ctcaactaag gaacggctca aagcatacac atgggaggga ggagtggggc cacagagaga 3720gggcccatta gttgcagatt acgatgtatc cagttaggtg cacctgcctt cgagaagtgt 3780aaaaataagt atttacatag aaagaaagac tgaatggatg cacggtgaat gcatgaatga 3840ttgaacgaca gaaaagattt gcattgaccg atgaggaggg cattgtagac agggatgagg 3900gtcattgatc ctgggtgcag atctccaaaa gaatgacaga aagaaagagg gagtggtgga 3960aagaaacaat aggatgggaa aaaatgaaaa tagaaaaaag gaagtgaaag agataataaa 4020taattagatc aaataagttg atgaaagggg actggtttag cacaagccat ccacattaat 4080tcaaacctgt ggctctgaag tttgtttttt aaatgaccac aagtgtaaga ctgaatgaaa 4140gaataaatgc gtgcattcca taggatgcaa gaaaaggagt gaggaatggg aaaattggaa 4200gaacgagaga gggagagatg taagaaaaga aaggaaaagt gaagtaggca tatgaaagaa 4260aaggcacttc ttggacaagc actgaaatat aatgagacag ttttacccat taaatataat 4320aaacagtaaa cgttgaggtt catcaataaa agcacagata cctgaataga ggagtgacct 4380gaatagaatt cgttcagccg aacgaatgag aatggatgat tttcactatc ctgtgcactc 4440aaggcccaaa agagaaagca agagaggaga gaatatggaa acgtatgaca ggatgtatat 4500aagcaataca aacatattga atgaataaat aaagacataa atatgtggga gagtggacca 4560cgcaaggaca aaaagaggag agaaggcagc aagaattatg actaattcaa aactgggttc 4620ctgagatagt taaataaatc ctgcaccaaa tccccagggg gagaaattaa caaacaaaag 4680acagccccac acggaccagt gtgcagaagg ctccaggaac cgcagattat ggttaatcca 4740attctgtgca cctgaggtcc ataaataaaa gaataagtat tgaaatgaaa gaatgacaga 4800aagaatgaat ggacacatga acgactgaat tagaaatgga aatgcctggc acagccagga 4860aggagctgcc catgggattg tcattcatct cactctgggc acctgaggtc cataagcgtg 4920aaaagaggca ggaagagaag tgtcagggag tcaaagatag agctaaggaa aggcaaaaat 4980gaaactaaat gaaagcgaaa gggaaaataa agaaaaacca ataaaaaaga gaacgaatac 5040gtgggtgtat ctgtaagagt aggatctgtt aggattagtc ataagactgt cagtaatcct 5100gaagatggat gagataatcc aggcccaggt tcccaggggg agggaaaatg gagaaaatat 5160aaaaagatgt gaaaaaggaa aaaggaaagg taataaacaa acaaccaaag tgataaatgg 5220atagttaagg gaggttgtct gaacagggat tataattagt ttacatacat actccttaaa 5280cagataaata cattacacct ttcaaagaat aaatgaaaaa tagagagaca tacctggctc 5340caaaacaagg ctgtatcttc tgccactgta ataaaataga tgcaattgag gttcataaat 5400aaaagaataa atacttaaac gtgaaaggtg actaaatgcg gggaagaaag attgcaaata 5460aatacatggg ccaaagatgt ttggtttgcc catggagttt taattaaaaa aattaataag 5520gaaaacaaat acccaaaata aggaagactg acaaatgagt gagtggatga gagagtgaat 5580ggtgcttgac gtaggagcag tagtgcttta gggaccagca tgaaggtggt gaccgggagc 5640cctgattcat gggattctgt ccacctgact ttataagaac caagaatggc tgggaatggt 5700ggctcacgcc tgtaatccca gcactttggg aggccgaggt gggcggatca tgaggtcagg 5760agtttgagac cagccagttt gagatcagcc tggccaacat ggtgaaattc catctctact 5820aaaaaaatac aaaaattatg ggcgtggtgg cacctgtctg taatcctagc tactcgggag 5880gctgagagag gagaattgct tgaacccggg aggtggaggt tgtagtgagc caagattgca 5940ccactgcact ccagcctggg ctacagagca agacactatc ttagatcaaa aaagaaaaaa 6000aaaaaaagaa ggagaaagaa ccagagaaac ataaggaaga gtgagaggaa gaaagaaaga 6060tgcaatttgg gaagaaatga aaaagaaatg aataaagaat aaaataatgt aacggtcaat 6120aaataggact tgtgaatgga ggcctttagg ccaaaggcta tgattaattt caagctatgt 6180tactgaagtc cataaacaaa ggactcagat ctaaatggat gaacgaatga ctggaagaaa 6240gggtggtagg aaggtaggaa gaaaggaagg agggaaaaag ggaagagagg aaggaacctt 6300ctttccagtc ctgtgttcta gacagtggaa tgaagtggtc cccagggagg gtggctgtag 6360gcatgtcatg tgcttgtcac atgcacttgc cctggcaggg aggagctggc tcaggaagac 6420cctggtcttg gggtgctgtt gccctatctt ggctgtgtgg gccatttcac tgcatctgtc 6480tcttcctcag tttccccatc tgtaaacctg gagtggcacc agctgcctac tagagttgat 6540cttatgtgtc tctgttgatg gtaccccatc tatggcctgg ataggcagga agggcttgga 6600ccctgagccc cgcagaaggt tgcatgaacg agtggtgtga agcctgttgg gtagcttggc 6660cactcccgcg gcatgggtca cctgcacagg aggttttgcc caccaggggg cagcagaggg 6720tcagggagca ataggccctg ggtggagcat gggccccgcc tgctgtgtgc caccctgggt 6780gtggcaccta ctcacatcca ggggttggtg cagggaaagg ccagaaggtg gccaggcgca 6840cctgagaagg gggacccaga agccccggga cccaggagcc ctgggcaagc caccagaaac 6900cttgttcttg caactctctg cagtgtgccc aggccaccct ctggcctggt cttccatggg 6960gcagggcgcc cacccttctc aactcaggtt tccctgggca gcaggtgcac ctcagcaccc 7020ctggggttgc agaagtggtc cggggaccct ggcttccttg acatgccatc cccagagcct 7080ggttcaaggc ctctctgtct

tctcggctgt ttcacgacgt gttttgtaac ttggcgggat 7140tgcgtttcgc tgtgtcgagg ttgtctcttc tctgactcgc cctccggggg actgccgggg 7200taaatctgga gagttgctcg tgctgacagt cctcccccag ggcctccccg gttctgttga 7260gtctcctttc tctgtagtgg aggaaatgtg tgtagttttg tgttgtgtgc ctgtgtttgt 7320ctgtaaaagc aaggaccaaa gtctcccttg ttgacctctc aattcctatt tgggacatat 7380aaaaacactg gattcttaac aagcgcccgg agcagtagga gcacagcttg gatggactca 7440ggacttgtgg cagggagcac gtgggaggca ggggagtggg gtggggccag gccatctgga 7500gtgggaggcg tcatgctcag agtgactctg tagacgctgg gtgggatggg gagtgcgggc 7560gcaggcatgg atggggctgt tagctagtgt gatgcttgag gtctgagctg atggcagcaa 7620agtggggtgc tcaggaatca aagctatggg gttatagaca ggatatgaag gagggaggga 7680ggcaagaaga agggggtggt tcccacgctt ctagctccgg ccgagtggat ggcaacagca 7740tttggaaggc ggaggacatg gaattcatgt gtcaggagcc accttccgag cctccagtac 7800cacgtgtcag ggccacatga gctgggcctc gtgggcctga tgtggtgctg gggcctcagg 7860ggtctgctct tcttctcttt cagaatctgg ggctccaggc tatgccttgg ctggactgag 7920gtctgggggt gcacttatta tccctgggga cacctgctga agcttctccc tgacaagctg 7980tgtcactgtt ggatgaggat ggggcgggag gggttcaggg cagaagaaga ccgggagggt 8040ctttcaaaag aactcatgta cggctgttaa aaaaagtcag cagaggctca ggaagactta 8100aagtgtgcag aaggcgggga agggagggcc cattgcatgc accaagagga aattggaagg 8160aacaagcgac gttggctgct aggagagcct gctcccaaca tctaggggct gtcctgacgg 8220gtcacagtgg gtcgaactga gccaatgaga gcagctctgg ggagacccac tggtgccctg 8280gaggctgggt gggtttgggt tggatgaatt ctgtgtgtcc ttttggaaat gtggaggcca 8340tgagggggga tcagggctct tagggttttg acccttaaga gttttgtatc tgtaattcaa 8400aggttcttta gttctgggat gctgagattc gggatagggt tcctaatggc acaaaagcca 8460gagataaaac atccttcacg tgctccctac ccggttcttt ctgtaccaga cccacaaggt 8520ccgagttggg atcctagtgc tcctgtctgg tcagggccta tctttatgtg ttcgttaaac 8580ttttaacaat gagaattaat tctgtctctt gacattgtca tttgcatgct ccccacacac 8640aaatcctttc ctggtgacac caggagctac aactctcctt ggcctcctct tgtgactccc 8700aactccctcc ttgggaagct tggcctcagg acctctggga tagacaggcc acgaatcctg 8760ctgtgtcccg ttgtgttcct aatataaatg gtgtggatgg cacttgacct agagcagtgg 8820gaaatgcatg caccactcaa cattctgaca tgtcacccat tttacattct tacaggcata 8880ctttttttaa aaaaagagtg tctattcttt aatgagcatc ccttctttaa aaaaacctaa 8940ttgccattat tcaccacata cacttttttt tttttgtatc ctgcctcttc tatttaattt 9000tctgtcatca acattttccc ttgttccatg aatcttcata acctcacttg ctgcgttgtg 9060ccttgttgag tggctatggc atcattcaca gaaccattct gttattctta tgtataacca 9120ccttttaaaa atattatgaa taatgccaca actaactgct taaaacaccc tttttttcat 9180tcttaagaat tatgttcttc cacccagaaa ttatcattgc ttcactacag atcagtttcc 9240cctgctagac tgtgagcccc ataagggcaa ggagcttatt gaattggcct ttgtatctct 9300gatgcccaac atgttgtaga ctataaataa atgatgaatg agtggatgga agaatggagg 9360aaggagcgag tgagtgagtg tttggctgat ggataagagg gtggaaggat aggcggaagg 9420atggattggt gaatgaatga atgaatttcc tttggttaag tctcttgaaa gaaaggctat 9480ggatctttgt atggatgttg aataatttca gtaagcttac agcattttac aatgttcagc 9540aatgtatgac cacttaatta agatatggct agtttgtctc tgttataaag tacttttgca 9600ttactttaac ttgcattgct ttaattacta atgatgggtg aacactttga cctatgtttg 9660ttaacaaatt gtattttatc ttctgtgaaa aaaaaaaaaa a 9701532879DNAHomo sapiens 53atcatttcct cctcagatta ccaagcaaga acagctaaaa tgaaagccat cattcatctt 60actcttcttg ctctcctttc tgtaaacaca gccaccaacc aaggcaactc agctgatgct 120gtaacaacca cagaaactgc gactagtggt cctacagtag ctgcagctga taccactgaa 180actaatttcc ctgaaactgc tagcaccaca gcaaatacac cttctttccc aacagctact 240tcacctgctc cccccataat tagtacacat agttcctcca caattcctac acctgctccc 300cccataatta gtacacatag ttcctccaca attcctatac ctactgctgc agacagtgag 360tcaaccacaa atgtaaattc attagctacc tctgacataa tcaccgcttc atctccaaat 420gatggattaa tcacaatggt tccttctgaa acacaaagta acaatgaaat gtcccccacc 480acagaagaca atcaatcatc agggcctccc actggcaccg ctttattgga gaccagcacc 540ctaaacagca caggtcccag caatccttgc caagatgatc cctgtgcaga taattcgtta 600tgtgttaagc tgcataatac aagtttttgc ctgtgtttag aagggtatta ctacaactct 660tctacatgta agaaaggaaa ggtattccct gggaagattt cagtgacagt atcagaaaca 720tttgacccag aagagaaaca ttccatggcc tatcaagact tgcatagtga aattactagc 780ttgtttaaag atgtatttgg cacatctgtt tatggacaga ctgtaattct tactgtaagc 840acatctctgt caccaagatc tgaaatgcgt gctgatgaca agtttgttaa tgtaacaata 900gtaacaattt tggcagaaac cacaagtgac aatgagaaga ctgtgactga gaaaattaat 960aaagcaatta gaagtagctc aagcaacttt ctaaactatg atttgaccct tcggtgtgat 1020tattatggct gtaaccagac tgcggatgac tgcctcaatg gtttagcatg cgattgcaaa 1080tctgacctgc aaaggcctaa cccacagagc cctttctgcg ttgcttccag tctcaagtgt 1140cctgatgcct gcaacgcaca gcacaagcaa tgcttaataa agaagagtgg tggggcccct 1200gagtgtgcgt gcgtgcccgg ctaccaggaa gatgctaatg ggaactgcca aaagtgtgca 1260tttggctaca gtggactcga ctgtaaggac aaatttcagc tgatcctcac tattgtgggc 1320accatcgctg gcattgtcat tctcagcatg ataattgcat tgattgtcac agcaagatca 1380aataacaaaa cgaagcatat tgaagaagag aacttgattg acgaagactt tcaaaatcta 1440aaactgcggt cgacaggctt caccaatctt ggagcagaag ggagcgtctt tcctaaggtc 1500aggataacgg cctccagaga cagccagatg caaaatccct attcaagaca cagcagcatg 1560ccccgccctg actattagaa tcataagaat gtggaacccg ccatggcccc caaccaatgt 1620acaagctatt atttagagtg tttagaaaga ctgatggaga agtgagcacc agtaaagatc 1680tggcctccgg ggtttttctt ccatctgaca tctgccagcc tctctgaatg gaagttgtga 1740atgtttgcaa cgaatccagc tcacttgcta aataagaatc tatgacatta aatgtagtag 1800atgctattag cgcttgtcag agaggtggtt ttcttcaatc agtacaaagt actgagacaa 1860tggttagggt tgttttctta attcttttcc tggtagggca acaagaacca tttccaatct 1920agaggaaagc tccccagcat tgcttgctcc tgggcaaaca ttgctcttga gttaagtgac 1980ctaattcccc tgggagacat acgcatcaac tgtggaggtc cgaggggatg agaagggata 2040cccaccatct ttcaagggtc acaagctcac tctctgacaa gtcagaatag ggacactgct 2100tctatccctc caatggagag attctggcaa cctttgaaca gcccagagct tgcaacctag 2160cctcacccaa gaagactgga aagagacata tctctcagct ttttcaggag gcgtgcctgg 2220gaatccagga actttttgat gctaattaga aggcctggac taaaaatgtc cactatgggg 2280tgcactctac agtttttgaa atgctaggag gcagaagggg cagagagtaa aaaacatgac 2340ctggtagaag gaagagaggc aaaggaaact gggtggggag gatcaattag agaggaggca 2400cctgggatcc accttcttcc ttaggtcccc tcctccatca gcaaaggagc acttctctaa 2460tcatgccctc ccgaagactg gctgggagaa ggtttaaaaa caaaaaatcc aggagtaaga 2520gccttaggtc agtttgaaat tggagacaaa ctgtctggca aagggtgcga gagggagctt 2580gtgctcagga gtccagccgt ccagcctcgg ggtgtaggtt tctgaggtgt gccattgggg 2640cctcagcctt ctctggtgac agaggctcag ctgtggccac caacacacaa ccacacacac 2700acaaccacac acacaaatgg gggcaaccac atccagtaca agcttttaca aatgttatta 2760gtgtcctttt ttatttctaa tgccttgtcc tcttaaaagt tattttattt gttattatta 2820tttgttcttg actgttaatt gtgaatggta atgcaataaa gtgcctttgt tagatggtg 28795443816DNAHomo sapiens 54aagcgttgca caattccccc aacctccata catacggcag ctcttctaga cacaggtttt 60cccaggtcaa atgcggggac cccagccata tctcccaccc tgagaaattt tggagtttca 120gggagctcag aagctctgca gaggccaccc tctctgaggg gattcttctt agacctccat 180ccagaggcaa atgttgacct gtccatgctg aaaccctcag gccttcctgg gtcatcttct 240cccacccgct ccttgatgac agggagcagg agcactaaag ccacaccaga aatggattca 300ggactgacag gagccacctt gtcacctaag acatctacag gtgcaatcgt ggtgacagaa 360catactctgc cctttacttc cccagataag accttggcca gtcctacatc ttcggttgtg 420ggaagaacca cccagtcttt gggggtgatg tcctctgctc tccctgagtc aacctctaga 480ggaatgacac actccgagca aagaaccagc ccatcgctga gtccccaggt caatggaact 540ccctctagga actaccctgc tacaagcatg gtttcaggat tgagttcccc aaggaccagg 600accagttcca cagaaggaaa ttttaccaaa gaagcatcta catacacact cactgtagag 660accacaagtg gcccagtcac tgagaagtac acagtcccca ctgagacctc aacaactgaa 720ggtgacagca cagagacccc ctgggacaca agatatattc ctgtaaaaat cacatctcca 780atgaaaacat ttgcagattc aactgcatcc aaggaaaatg ccccagtgtc tatgactcca 840gctgagacca cagttactga ctcacatact ccaggaagga caaacccatc atttgggaca 900ctttattctt ccttccttga cctatcacct aaagggaccc caaattccag aggtgaaaca 960agcctggaac tgattctatc aaccactgga tatcccttct cctctcctga acctggctct 1020gcaggacaca gcagaataag taccagtgcg cctttgtcat catctgcttc agttctcgat 1080aataaaatat cagagaccag catattctca ggccagagtc tcacctcccc tctgtctcct 1140ggggtgcccg aggccagagc cagcacaatg cccaactcag ctatcccttt ttccatgaca 1200ctaagcaatg cagaaacaag tgccgaaagg gtcagaagca caatttcctc tctggggact 1260ccatcaatat ccacaaagca gacagcagag actatcctta ccttccatgc cttcgctgag 1320accatggata tacccagcac ccacatagcc aagactttgg cttcagaatg gttgggaagt 1380ccaggtaccc ttggtggcac cagcacttca gcgctgacaa ccacatctcc atctaccact 1440ttagtctcag aggagaccaa cacccatcac tccacgagtg gaaaggaaac agaaggaact 1500ttgaatacat ctatgactcc acttgagacc tctgctcctg gagaagagtc cgaaatgact 1560gccaccttgg tccccactct aggttttaca actcttgaca gcaagatcag aagtccatct 1620caggtctctt catcccaccc aacaagagag ctcagaacca caggcagcac ctctgggagg 1680cagagttcca gcacagctgc ccacgggagc tctgacatcc tgagggcaac cacttccagc 1740acctcaaaag catcatcatg gaccagtgaa agcacagctc agcaatttag tgaaccccag 1800cacacacagt gggtggagac aagtcctagc atgaaaacag agagaccccc agcatcaacc 1860agtgtggcag cccctatcac cacttctgtt ccctcagtgg tctctggctt caccaccctg 1920aagaccagct ccacaaaagg gatttggctt gaagaaacat ctgcagacac actcatcgga 1980gaatccacag ctggcccaac cacccatcag tttgctgttc ccactgggat ttcaatgaca 2040ggaggcagca gcaccagggg aagccagggc acaacccacc tactcaccag agccacagca 2100tcatctgaga catccgcaga tttgactctg gccacgaacg gtgtcccagt ctccgtgtct 2160ccagcagtga gcaagacggc tgctggctca agtcctccag gagggacaaa gccatcatat 2220acaatggttt cttctgtcat ccctgagaca tcatctctac agtcctcagc tttcagggaa 2280ggaaccagcc tgggactgac tccattaaac actagacatc ccttctcttc ccctgaacca 2340gactctgcag gacacaccaa gataagcacc agcattcctc tgttgtcatc tgcttcagtt 2400cttgaggata aagtgtcagc gaccagcaca ttctcacacc acaaagccac ctcatctatt 2460accacaggga ctcctgaaat ctcaacaaag acaaagccca gctcagccgt tctttcctcc 2520atgaccctaa gcaatgcagc aacaagtcct gaaagagtca gaaatgcaac ttcccctctg 2580actcatccat ctccatcagg ggaagagaca gcagggagtg tcctcactct cagcacctct 2640gctgagacta cagactcacc taacatccac ccaactggga cactgacttc agaatcgtca 2700gagagtccta gcactctcag cctcccaagt gtctctggag tcaaaaccac attttcttca 2760tctactcctt ccactcatct atttactagt ggagaagaaa cagaggaaac ttcgaatcca 2820tctgtgtctc aacctgagac ttctgtttcc agagtaagga ccaccttggc cagcacctct 2880gtccctaccc cagtattccc caccatggac acctggccta cacgttcagc tcagttctct 2940tcatcccacc tagtgagtga gctcagagct acgagcagta cctcagttac aaactcaact 3000ggttcagctc ttcctaaaat atctcacctc actgggacgg caacaatgtc acagaccaat 3060agagacacgt ttaatgactc tgctgcaccc caaagcacaa cttggccaga gactagtccc 3120agattcaaga cagggttacc ttcagcaaca accactgttt caacctctgc cacttctctc 3180tctgctactg taatggtctc taaattcact tctccagcaa ctagttccat ggaagcaact 3240tctatcaggg aaccatcaac aaccatcctc acaacagaga ccacgaatgg cccaggctct 3300atggctgtgg cttctaccaa catcccaatt ggaaagggct acattactga aggaagattg 3360gacacaagcc atctgcccat tggaaccaca gcttcctctg agacatctat ggattttacc 3420atggccaaag aaagtgtctc aatgtcagta tctccatctc agtccatgga tgctgctggc 3480tcaagcactc caggaaggac aagccaattc gttgacacat tttctgatga tgtctatcat 3540ttaacatcca gagaaattac aatacctaga gatggaacaa gctcagctct gactccacaa 3600atgactgcaa ctcaccctcc atctcctgat cctggctctg ctagaagcac ctggcttggc 3660atcttgtcct catctccttc ttctcctact cccaaagtca caatgagctc cacattttca 3720actcagagag tcaccacaag catgataatg gacacagttg aaactagtcg gtggaacatg 3780cccaacttac cttccacgac ttccttgaca ccaagtaata ttccaacaag tggtgccata 3840ggaaaaagca ccctggttcc cttggacact ccatctccag ccacatcatt ggaggcatca 3900gaagggggac ttccaaccct cagcacctac cctgaatcaa caaacacacc cagcatccac 3960ctcggagcac acgctagttc agaaagtcca agcaccatca aacttaccat ggcttcagta 4020gtaaaacctg gctcttacac acctctcacc ttcccctcaa tagagaccca cattcatgta 4080tcaacagcca gaatggctta ctcttctggg tcttcacctg agatgacagc tcctggagag 4140actaacactg gtagtacctg ggaccccacc acctacatca ccactacgga tcctaaggat 4200acaagttcag ctcaggtctc tacaccccac tcagtgagga cactcagaac cacagaaaac 4260catccaaaga cagagtccgc caccccagct gcttactctg gaagtcctaa aatctcaagt 4320tcacccaatc tcaccagtcc ggccacaaaa gcatggacca tcacagacac aactgaacac 4380tccactcaat tacattacac aaaattggca gaaaaatcat ctggatttga gacacagtca 4440gctccaggac ctgtctctgt agtaatccct acctccccta ccattggaag cagcacattg 4500gaactaactt ctgatgtccc aggggaaccc ctggtccttg ctcccagtga gcagaccaca 4560atcactctcc ccatggcaac atggctgagt accagtttga cagaggaaat ggcttcaaca 4620gaccttgata tttcaagtcc aagttcaccc atgagtacat ttgctatttt tccacctatg 4680tccacacctt ctcatgaact ttcaaagtca gaggcagata ccagtgccat tagaaataca 4740gattcaacaa cgttggatca gcacctagga atcaggagtt tgggcagaac tggggactta 4800acaactgttc ctatcacccc actgacaacc acgtggacca gtgtgattga acactcaaca 4860caagcacagg acaccctttc tgcaacgatg agtcctactc acgtgacaca gtcactcaaa 4920gatcaaacat ctataccagc ctcagcatcc ccttcccatc ttactgaagt ctaccctgag 4980ctcgggacac aagggagaag ctcctctgag gcaaccactt tttggaaacc atctacagac 5040acactgtcca gagagattga gactggccca acaaacattc aatccactcc acccatggac 5100aacacaacaa cagggagcag tagtagtgga gtcaccctgg gcatagccca ccttcccata 5160ggaacatcct ccccagctga gacatccaca aacatggcac tggaaagaag aagttctaca 5220gccactgtct ctatggctgg gacaatggga ctccttgtta ctagtgctcc aggaagaagc 5280atcagccagt cattaggaag agtttcctct gtcctttctg agtcaactac tgaaggagtc 5340acagattcta gtaagggaag cagcccaagg ctgaacacac agggaaatac agctctctcc 5400tcctctcttg aacccagcta tgctgaagga agccagatga gcacaagcat ccctctaacc 5460tcatctccta caactcctga tgtggaattc atagggggca gcacattttg gaccaaggag 5520gtcaccacag ttatgacctc agacatctcc aagtcttcag caaggacaga gtccagctca 5580gctaccctta tgtccacagc tttgggaagc actgaaaata caggaaaaga aaaactcaga 5640actgcctcta tggatcttcc atctccaact ccatcaatgg aggtgacacc atggatttct 5700ctcactctca gtaatgcccc caataccaca gattcacttg acctcagcca tggggtgcac 5760accagctctg cagggacttt ggccactgac aggtcattga atactggtgt cactagagcc 5820tccagattgg aaaacggctc tgatacctct tctaagtccc tgtctatggg aaacagcact 5880cacacttcca tgacttacac agagaagagt gaagtgtctt cttcaatcca tccccgacct 5940gagacctcag ctcctggagc agagaccact ttgacttcca ctcctggaaa cagggccata 6000agcttaacat tgcctttttc atccattcca gtggaagaag tcatttctac aggcataacc 6060tcaggaccag acatcaactc agcacccatg acacattctc ccatcacccc accaacaatt 6120gtatggacca gtacaggcac aattgaacag tccactcaac cactacatgc agtttcttca 6180gaaaaagttt ctgtgcagac acagtcaact ccatatgtca actctgtggc agtgtctgct 6240tcccctaccc atgagaattc agtctcttct ggaagcagca catcctctcc atattcctca 6300gcctcacttg aatccttgga ttccacaatc agtaggagga atgcaatcac ttcctggcta 6360tgggacctca ctacatctct ccccactaca acttggccaa gtactagttt atctgaggca 6420ctgtcctcag gccattctgg ggtttcaaac ccaagttcaa ctacgactga atttccactc 6480ttttcagctg catccacatc tgctgctaag caaagaaatc cagaaacaga gacccatggt 6540ccccagaata cagccgcgag tactttgaac actgatgcat cctcggtcac aggtctttct 6600gagactcctg tgggggcaag tatcagctct gaagtccctc ttccaatggc cataacttct 6660agatcagatg tttctggcct tacatctgag agtactgcta acccgagttt aggcacagcc 6720tcttcagcag ggaccaaatt aactaggaca atatccctgc ccacttcaga gtctttggtt 6780tcctttagaa tgaacaagga tccatggaca gtgtcaatcc ctttggggtc ccatccaact 6840actaatacag aaacaagcat cccagtaaac agcgcaggtc cacctggctt gtccacagta 6900gcatcagatg taattgacac accttcagat ggggctgaga gtattcccac tgtctccttt 6960tccccctccc ctgatactga agtgacaact atctcacatt tcccagaaaa gacaactcat 7020tcatttagaa ccatttcatc tctcactcat gagttgactt caagagtgac acctattcct 7080ggggattgga tgagttcagc tatgtctaca aagcccacag gagccagtcc ctccattaca 7140ctgggagaga gaaggacaat cacctctgct gctccaacca cttcccccat agttctcact 7200gctagtttca cagagaccag cacagtttca ctggataatg aaactacagt aaaaacctca 7260gatatccttg acgcacggaa aacaaatgag ctcccctcag atagcagttc ttcttctgat 7320ctgatcaaca cctccatagc ttcttcaact atggatgtca ctaaaacagc ctccatcagt 7380cccactagca tctcaggaat gacagcaagt tcctccccat ctctcttctc ttcagataga 7440ccccaggttc ccacatctac aacagagaca aatacagcca cctctccatc tgtttccagt 7500aacacctatt ctcttgatgg gggctccaat gtgggtggca ctccatccac tttaccaccc 7560tttacaatca cccaccctgt cgagacaagc tcggccctat tagcctggtc tagaccagta 7620agaactttca gcaccatggt cagcactgac actgcctccg gagaaaatcc tacctctagc 7680aattctgtgg tgacttctgt tccagcacca ggtacatgga ccagtgtagg cagtactact 7740gacttacctg ccatgggctt tctcaagaca agtcctgcag gagaggcaca ctcacttcta 7800gcatcaacta ttgaaccagc cactgccttc actccccatc tctcagcagc agtggtcact 7860ggatccagtg ctacatcaga agccagtctt ctcactacga gtgaaagcaa agccattcat 7920tcttcaccac agaccccaac tacacccacc tctggagcaa actgggaaac ttcagctact 7980cctgagagcc ttttggtagt cactgagact tcagacacaa cacttacctc aaagattttg 8040gtcacagata ccatcttgtt ttcaactgtg tccacgccac cttctaaatt tccaagtacg 8100gggactctgt ctggagcttc cttccctact ttactcccgg acactccagc catccctctc 8160actgccactg agccaacaag ttcattagct acatcctttg attccacccc actggtgact 8220atagcttcgg atagtcttgg cacagtccca gagactaccc tgaccatgtc agagacctca 8280aatggtgatg cactggttct taagacagta agtaacccag ataggagcat ccctggaatc 8340actatccaag gagtaacaga aagtccactc catccttctt ccacttcccc ctctaagatt 8400gttgctccac ggaatacaac ctatgaaggt tcgatcacag tggcactttc tactttgcct 8460gcgggaacta ctggttccct tgtattcagt cagagttctg aaaactcaga gacaacggct 8520ttggtagact catcagctgg gcttgagagg gcatctgtga tgccactaac cacaggaagc 8580cagggtatgg ctagctctgg aggaatcaga agtgggtcca ctcactcaac tggaaccaaa 8640acattttctt ctctccctct gaccatgaac ccaggtgagg ttacagccat gtctgaaatc 8700accacgaaca gactgacagc tactcaatca acagcaccca aagggatacc tgtgaagccc 8760accagtgctg agtcaggcct cctaacacct gtctctgcct cctcaagccc atcaaaggcc 8820tttgcctcac tgactacagc tcccccaact tgggggatcc cacagtctac cttgacattt 8880gagttttctg aggtcccaag tttggatact aagtccgctt ctttaccaac tcctggacag 8940tccctgaaca ccattccaga ctcagatgca agcacagcat cttcctcact gtccaagtct 9000ccagaaaaaa acccaagggc aaggatgatg acttccacaa aggccataag tgcaagctca 9060tttcaatcaa caggttttac tgaaacccct gagggatctg cctccccttc tatggcaggg 9120catgaaccca gagtccccac ttcaggaaca ggggacccta gatatgcctc agagagcatg 9180tcttatccag acccaagcaa ggcatcatca gctatgacat cgacctctct tgcatcaaaa 9240ctcacaactc tcttcagcac aggtcaagca gcaaggtctg gttctagttc ctctcccata 9300agcctatcca ctgagaaaga aacaagcttc ctttccccca ctgcatccac ctccagaaag 9360acttcactat ttcttgggcc ttccatggca aggcagccca acatattggt gcatcttcag 9420acttcagctc tgacactttc tccaacatcc actctaaata tgtcccagga ggagcctcct 9480gagttaacct caagccagac cattgcagaa gaagagggaa

caacagctga aacacagacg 9540ttaaccttca caccatctga gaccccaaca tccttgttac ctgtctcttc tcccacagaa 9600cccacagcca gaagaaagag ttctccagaa acatgggcaa gctctatttc agttcctgcc 9660aagacctcct tggttgaaac aactgatgga acgctagtga ccaccataaa gatgtcaagc 9720caggcagcac aaggaaattc cacgtggcct gccccagcag aggagacggg gagcagtcca 9780gcaggcacat ccccaggaag cccagaaatg tctaccactc tcaaaatcat gagctccaag 9840gaacccagca tcagcccaga gatcaggtcc actgtgagaa attctccttg gaagactcca 9900gaaacaactg ttcccatgga gaccacagtg gaaccagtca cccttcagtc cacagcccta 9960ggaagtggca gcaccagcat ctctcacctg cccacaggaa ccacatcacc aaccaagtca 10020ccaacagaaa atatgttggc tacagaaagg gtctccctct ccccatcccc acctgaggct 10080tggaccaacc tttattctgg aactccagga gggaccaggc agtcactggc cacaatgtcc 10140tctgtctccc tagagtcacc aactgctaga agcatcacag ggactggtca gcaaagcagt 10200ccagaactgg tttcaaagac aactggaatg gaattctcta tgtggcatgg ctctactgga 10260gggaccacag gggacacaca tgtctctctg agcacatctt ccaatatcct tgaagaccct 10320gtaaccagcc caaactctgt gagctcattg acagataaat ccaaacataa aaccgagaca 10380tgggtaagca ccacagccat tccctccact gtcctgaata ataagataat ggcagctgaa 10440caacagacaa gtcgatctgt ggatgaggct tattcatcaa ctagttcttg gtcagatcag 10500acatctggga gtgacatcac ccttggtgca tctcctgatg tcacaaacac attatacatc 10560acctccacag cacaaaccac ctcactagtg tctctgccct ctggagacca aggcattaca 10620agcctcacca atccctcagg aggaaaaaca agctctgcgt catctgtcac atctccttca 10680atagggcttg agactctgag ggccaatgta agtgcagtga aaagtgacat tgcccctact 10740gctgggcatc tatctcagac ttcatctcct gcggaagtga gcatcctgga cgtaaccaca 10800gctcctactc caggtatctc caccaccatc accaccatgg gaaccaactc aatctcaact 10860accacaccca acccagaagt gggtatgagt accatggaca gcaccccggc cacagagagg 10920cgcacaactt ctacagaaca cccttccacc tggtcttcca cagctgcatc agattcctgg 10980actgtcacag acatgacttc aaacttgaaa gttgcaagat ctcctggaac aatttccaca 11040atgcatacaa cttcattctt agcctcaagc actgaattag actccatgtc tactccccat 11100ggccgtataa ctgtcattgg aaccagcctg gtcactccat cctctgatgc ttcagctgta 11160aagacagaga ccagtacaag tgaaagaaca ttgagtcctt cagacacaac tgcatctact 11220cccatctcaa ctttttctcg tgtccagagg atgagcatct cagttcctga cattttaagt 11280acaagttgga ctcccagtag tacagaagca gaagatgtgc ctgtttcaat ggtttctaca 11340gatcatgcta gtacaaagac tgacccaaat acgcccctgt ccacttttct gtttgattct 11400ctgtccactc ttgactggga cactgggaga tctctgtcat cagccacagc cactacctca 11460gctcctcagg gggccacaac tccccaggaa ctcactttgg aaaccatgat cagcccagct 11520acctcacagt tgcccttctc tatagggcac attacaagtg cagtcacacc agctgcaatg 11580gcaaggagct ctggagttac tttttcaaga ccagatccca caagcaaaaa ggcagagcag 11640acttccactc agcttcccac caccacttct gcacatccag ggcaggtgcc cagatcagca 11700gcaacaactc tggatgtgat cccacacaca gcaaaaactc cagatgcaac ttttcagaga 11760caagggcaga cagctcttac aacagaggca agagctacat ctgactcctg gaatgagaaa 11820gaaaaatcaa ccccaagtgc accttggatc actgagatga tgaattctgt ctcagaagat 11880accatcaagg aggttaccag ctcctccagt gtattaagga ccctgaatac gctggacata 11940aacttggaat ctgggacgac ttcatcccca agttggaaaa gcagcccata tgagagaatt 12000gccccttctg agtccaccac agacaaagag gcaattcacc cttctacaaa cacagtagag 12060accacaggct gggtcacaag ttccgaacat gcttctcatt ccactatccc agcccactca 12120gcgtcatcca aactcacatc tccagtggtt acaacctcca ccagggaaca agcaatagtt 12180tctatgtcaa caaccacatg gccagagtct acaagggcta gaacagagcc taattccttc 12240ttgactattg aactgaggga cgtcagccct tacatggaca ccagctcaac cacacaaaca 12300agtattatct cttccccagg ttccactgcg atcaccaagg ggcctagaac agaaattacc 12360tcctctaaga gaatatccag ctcattcctt gcccagtcta tgaggtcgtc agacagcccc 12420tcagaagcca tcaccaggct gtctaacttt cctgccatga cagaatctgg aggaatgatc 12480cttgctatgc aaacaagtcc acctggcgct acatcactaa gtgcacctac tttggataca 12540tcagccacag cctcctggac agggactcca ctggctacga ctcagagatt tacatactca 12600gagaagacca ctctctttag caaaggtcct gaggatacat cacagccaag ccctccctct 12660gtggaagaaa ccagctcttc ctcttccctg gtacctatcc atgctacaac ctcgccttcc 12720aatattttgt tgacatcaca agggcacagt ccctcctcta ctccacctgt gacctcagtt 12780ttcttgtctg agacctctgg cctggggaag accacagaca tgtcgaggat aagcttggaa 12840cctggcacaa gtttacctcc caatttgagc agtacagcag gtgaggcgtt atccacttat 12900gaagcctcca gagatacaaa ggcaattcat cattctgcag acacagcagt gacgaatatg 12960gaggcaacca gttctgaata ttctcctatc ccaggccata caaagccatc caaagccaca 13020tctccattgg ttacctccca catcatgggg gacatcactt cttccacatc agtatttggc 13080tcctccgaga ccacagagat tgagacagtg tcctctgtga accagggact tcaggagaga 13140agcacatccc aggtggccag ctctgctaca gagacaagca ctgtcattac ccatgtgtct 13200agtggtgatg ctactactca tgtcaccaag acacaagcca ctttctctag cggaacatcc 13260atctcaagcc ctcatcagtt tataacttct accaacacat ttacagatgt gagcaccaac 13320ccctccacct ctctgataat gacagaatct tcaggagtga ccatcaccac ccaaacaggt 13380cctactggag ctgcaacaca gggtccatat ctcttggaca catcaaccat gccttacttg 13440acagagactc cattagctgt gactccagat tttatgcaat cagagaagac cactctcata 13500agcaaaggtc ccaaggatgt gtcctggaca agccctccct ctgtggcaga aaccagctat 13560ccctcttccc tgacaccttt cttggtcaca accatacctc ctgccacttc cacgttacaa 13620gggcaacata catcctctcc tgtttctgcg acttcagttc ttacctctgg actggtgaag 13680accacagata tgttgaacac aagcatggaa cctgtgacca attcacctca aaatttgaac 13740aatccatcaa atgagatact ggccactttg gcagccacca cagatataga gactattcat 13800ccttccataa acaaagcagt gaccaatatg gggactgcca gttcagcaca tgtactgcat 13860tccactctcc cagtcagctc agaaccatct acagccacat ctccaatggt tcctgcctcc 13920agcatggggg acgctcttgc ttctatatca atacctggtt ctgagaccac agacattgag 13980ggagagccaa catcctccct gactgctgga cgaaaagaga acagcaccct ccaggagatg 14040aactcaacta cagagtcaaa catcatcctc tccaatgtgt ctgtgggggc tattactgaa 14100gccacaaaaa tggaagtccc ctcttttgat gcaacattca taccaactcc tgctcagtca 14160acaaagttcc cagatatttt ctcagtagcc agcagtagac tttcaaactc tcctcccatg 14220acaatatcta cccacatgac caccacccag acagggtctt ctggagctac atcaaagatt 14280ccacttgcct tagacacatc aaccttggaa acctcagcag ggactccatc agtggtgact 14340gaggggtttg cccactcaaa aataaccact gcaatgaaca atgatgtcaa ggacgtgtca 14400cagacaaacc ctccctttca ggatgaagcc agctctccct cttctcaagc acctgtcctt 14460gtcacaacct taccttcttc tgttgctttc acaccgcaat ggcacagtac ctcctctcct 14520gtttctatgt cctcagttct tacttcttca ctggtaaaga ccgcaggcaa ggtggataca 14580agcttagaaa cagtgaccag ttcacctcaa agtatgagca acactttgga tgacatatcg 14640gtcacttcag cagccaccac agatatagag acaacgcatc cttccataaa cacagtagtt 14700accaatgtgg ggaccaccgg ttcagcattt gaatcacatt ctactgtctc agcttaccca 14760gagccatcta aagtcacatc tccaaatgtt accacctcca ccatggaaga caccacaatt 14820tccagatcaa tacctaaatc ctctaagact acaagaactg agactgagac aacttcctcc 14880ctgactccta aactgaggga gaccagcatc tcccaggaga tcacctcgtc cacagagaca 14940agcactgttc cttacaaaga gctcactggt gccactaccg aggtatccag gacagatgtc 15000acttcctcta gcagtacatc cttccctggc cctgatcagt ccacagtgtc actagacatc 15060tccacagaaa ccaacaccag gctgtctacc tccccaataa tgacagaatc tgcagaaata 15120accatcacca cccaaacagg tcctcatggg gctacatcac aggatacttt taccatggac 15180ccatcaaata caacccccca ggcagggatc cactcagcta tgactcatgg attttcacaa 15240ttggatgtga ccactcttat gagcagaatt ccacaggatg tatcatggac aagtcctccc 15300tctgtggata aaaccagctc cccctcttcc tttctgtcct cacctgcaat gaccacacct 15360tccctgattt cttctacctt accagaggat aagctctcct ctcctatgac ttcacttctc 15420acctctggcc tagtgaagat tacagacata ttacgtacac gcttggaacc tgtgaccagc 15480tcacttccaa atttcagcag cacctcagat aagatactgg ccacttctaa agacagtaaa 15540gacacaaagg aaatttttcc ttctataaac acagaagaga ccaatgtgaa agccaacaac 15600tctggacatg aatcccattc ccctgcactg gctgactcag agacacccaa agccacaact 15660caaatggtta tcaccaccac tgtgggagat ccagctcctt ccacatcaat gccagtgcat 15720ggttcctctg agactacaaa cattaagaga gagccaacat atttcttgac tcctagactg 15780agagagacca gtacctctca ggagtccagc tttcccacgg acacaagttt tctactttcc 15840aaagtcccca ctggtactat tactgaggtc tccagtacag gggtcaactc ttctagcaaa 15900atttccaccc cagaccatga taagtccaca gtgccacctg acaccttcac aggagagatc 15960cccagggtct tcacctcctc tattaagaca aaatctgcag aaatgacgat caccacccaa 16020gcaagtcctc ctgagtctgc atcgcacagt acccttccct tggacacatc aaccacactt 16080tcccagggag ggactcattc aactgtgact cagggattcc catactcaga ggtgaccact 16140ctcatgggca tgggtcctgg gaatgtgtca tggatgacaa ctccccctgt ggaagaaacc 16200agctctgtgt cttccctgat gtcttcacct gccatgacat ccccttctcc tgtttcctcc 16260acatcaccac agagcatccc ctcctctcct cttcctgtga ctgcacttcc tacttctgtt 16320ctggtgacaa ccacagatgt gttgggcaca acaagcccag agtctgtaac cagttcacct 16380ccaaatttga gcagcatcac tcatgagaga ccggccactt acaaagacac tgcacacaca 16440gaagccgcca tgcatcattc cacaaacacc gcagtgacca atgtagggac ttccgggtct 16500ggacataaat cacaatcctc tgtcctagct gactcagaga catcgaaagc cacacctctg 16560atgagtacca cctccaccct gggggacaca agtgtttcca catcaactcc taatatctct 16620cagactaacc aaattcaaac agagccaaca gcatccctga gccctagact gagggagagc 16680agcacgtctg agaagaccag ctcaacaaca gagacaaata ctgccttttc ttatgtgccc 16740acaggtgcta ttactcaggc ctccagaaca gaaatctcct ctagcagaac atccatctca 16800gaccttgatc ggcccacaat agcacccgac atctccacag gaatgatcac caggctcttc 16860acctccccca tcatgacaaa atctgcagaa atgaccgtca ccactcaaac aactactcct 16920ggggctacat cacagggtat ccttccctgg gacacatcaa ccacactttt ccagggaggg 16980actcattcaa ccgtgtctca gggattccca cactcagaga taaccactct tcggagcaga 17040acccctggag atgtgtcatg gatgacaact ccccctgtgg aagaaaccag ctctgggttt 17100tccctgatgt caccttccat gacatcccct tctcctgttt cctccacatc accagagagc 17160atcccctcct ctcctctccc tgtgactgca cttcttactt ctgttctggt gacaaccaca 17220aatgtattgg gcacaacaag cccagagccc gtaacgagtt cacctccaaa tttaagcagc 17280cccacacagg agagactgac cacttacaaa gacactgcgc acacagaagc catgcatgct 17340tccatgcata caaacactgc agtggccaac gtggggacct ccatttctgg acatgaatca 17400caatcttctg tcccagctga ttcacacaca tccaaagcca catctccaat gggtatcacc 17460ttcgccatgg gggatacaag tgtttctaca tcaactcctg ccttctttga gactagaatt 17520cagactgaat caacatcctc tttgattcct ggattaaggg acaccaggac gtctgaggag 17580atcaacactg tgacagagac cagcactgtc ctttcagaag tgcccactac tactactact 17640gaggtctcca ggacagaagt tatcacttcc agcagaacaa ccatctcagg gcctgatcat 17700tccaaaatgt caccctacat ctccacagaa accatcacca ggctctccac ttttcctttt 17760gtaacaggat ccacagaaat ggccatcacc aaccaaacag gtcctatagg gactatctca 17820caggctaccc ttaccctgga cacatcaagc acagcttcct gggaagggac tcactcacct 17880gtgactcaga gatttccaca ctcagaggag accactacta tgagcagaag tactaagggc 17940gtgtcatggc aaagccctcc ctctgtggaa gaaaccagtt ctccttcttc cccagtgcct 18000ttacctgcaa taacctcaca ttcatctctt tattccgcag tatcaggaag tagccccact 18060tctgctctcc ctgtgacttc ccttctcacc tctggcagga ggaagaccat agacatgttg 18120gacacacact cagaacttgt gaccagctcc ttaccaagtg caagtagctt ctcaggtgag 18180atactcactt ctgaagcctc cacaaataca gagacaattc acttttcaga gaacacagca 18240gaaaccaata tggggaccac caattctatg cataaactac attcctctgt ctcaatccac 18300tcccagccat ccggacacac acctccaaag gttactggat ctatgatgga ggacgctatt 18360gtttccacat caacacctgg ttctcctgag actaaaaatg ttgacagaga ctcaacatcc 18420cctctgactc ctgaactgaa agaggacagc accgccctgg tgatgaactc aactacagag 18480tcaaacactg ttttctccag tgtgtccctg gatgctgcta ctgaggtctc cagggcagaa 18540gtcacctact atgatcctac attcatgcca gcttctgctc agtcaacaaa gtccccagac 18600atttcacctg aagccagcag cagtcattct aactctcctc ccttgacaat atctacacac 18660aagaccatcg ccacacaaac aggtccttct ggggtgacat ctcttggcca actgaccctg 18720gacacatcaa ccatagccac ctcagcagga actccatcag ccagaactca ggattttgta 18780gattcagaaa caaccagtgt catgaacaat gatctcaatg atgtgttgaa gacaagccct 18840ttctctgcag aagaagccaa ctctctctct tctcaggcac ctctccttgt gacaacctca 18900ccttctcctg taacttccac attgcaagag cacagtacct cctctcttgt ttctgtgacc 18960tcagtaccca cccctacact ggcgaagatc acagacatgg acacaaactt agaacctgtg 19020actcgttcac ctcaaaattt aaggaacacc ttggccactt cagaagccac cacagataca 19080cacacaatgc atccttctat aaacacagca gtggccaatg tggggaccac cagttcacca 19140aatgaattct attttactgt ctcacctgac tcagacccat ataaagccac atccgcagta 19200gttatcactt ccacctcggg ggactcaata gtttccacat caatgcctag atcctctgcg 19260atgaaaaaga ttgagtctga gacaactttc tccctgatat ttagactgag ggagactagc 19320acctcccaga aaattggctc atcctcagac acaagcacgg tctttgacaa agcattcact 19380gctgctacta ctgaggtctc cagaacagaa ctcacctcct ctagcagaac atccatccaa 19440ggcactgaaa agcccacaat gtcaccggac acctccacaa gatctgtcac catgctttct 19500acttttgctg gcctgacaaa atccgaagaa aggaccattg ccacccaaac aggtcctcat 19560agggcgacat cacagggtac ccttacctgg gacacatcaa tcacaacctc acaggcaggg 19620acccactcag ctatgactca tggattttca caattagatt tgtccactct tacgagtaga 19680gttcctgagt acatatcagg gacaagccca ccctctgtgg aaaaaaccag ctcttcctct 19740tcccttctgt ctttaccagc aataacctca ccgtcccctg tacctactac attaccagaa 19800agtaggccgt cttctcctgt tcatctgact tcactcccca cctctggcct agtgaagacc 19860acagatatgc tggcatctgt ggccagttta cctccaaact tgggcagcac ctcacataag 19920ataccgacta cttcagaaga cattaaagat acagagaaaa tgtatccttc cacaaacata 19980gcagtaacca atgtggggac caccacttct gaaaaggaat cttattcgtc tgtcccagcc 20040tactcagaac cacccaaagt cacctctcca atggttacct ctttcaacat aagggacacc 20100attgtttcca catccatgcc tggctcctct gagattacaa ggattgagat ggagtcaaca 20160ttctccctgg ctcatgggct gaagggaacc agcacctccc aggaccccat cgtatccaca 20220gagaaaagtg ctgtccttca caagttgacc actggtgcta ctgagacctc taggacagaa 20280gttgcctctt ctagaagaac atccattcca ggccctgatc attccacaga gtcaccagac 20340atctccactg aagtgatccc cagcctgcct atctcccttg gcattacaga atcttcaaat 20400atgaccatca tcactcgaac aggtcctcct cttggctcta catcacaggg cacatttacc 20460ttggacacac caactacatc ctccagggca ggaacacact cgatggcgac tcaggaattt 20520ccacactcag aaatgaccac tgtcatgaac aaggaccctg agattctatc atggacaatc 20580cctccttcta tagagaaaac cagcttctcc tcttccctga tgccttcacc agccatgact 20640tcacctcctg tttcctcaac attaccaaag accattcaca ccactccttc tcctatgacc 20700tcactgctca cccctagcct agtgatgacc acagacacat tgggcacaag cccagaacct 20760acaaccagtt cacctccaaa tttgagcagt acctcacatg agatactgac aacagatgaa 20820gacaccacag ctatagaagc catgcatcct tccacaagca cagcagcgac taatgtggaa 20880accaccagtt ctggacatgg gtcacaatcc tctgtcctag ctgactcaga aaaaaccaag 20940gccacagctc caatggatac cacctccacc atggggcata caactgtttc cacatcaatg 21000tctgtttcct ctgagactac aaaaattaag agagagtcaa catattcctt gactcctgga 21060ctgagagaga ccagcatttc ccaaaatgcc agcttttcca ctgacacaag tattgttctt 21120tcagaagtcc ccactggtac tactgctgag gtctccagga cagaagtcac ctcctctggt 21180agaacatcca tccctggccc ttctcagtcc acagttttgc cagaaatatc cacaagaaca 21240atgacaaggc tctttgcctc gcccaccatg acagaatcag cagaaatgac catccccact 21300caaacaggtc cttctgggtc tacctcacag gataccctta ccttggacac atccaccaca 21360aagtcccagg caaagactca ttcaactttg actcagagat ttccacactc agagatgacc 21420actctcatga gcagaggtcc tggagatatg tcatggcaaa gctctccctc tctggaaaat 21480cccagctctc tcccttccct gctgtcttta cctgccacaa cctcacctcc tcccatttcc 21540tccacattac cagtgactat ctcctcctct cctcttcctg tgacttcact tctcacctct 21600agcccggtaa cgaccacaga catgttacac acaagcccag aacttgtaac cagttcacct 21660ccaaagctga gccacacttc agatgagaga ctgaccactg gcaaggacac cacaaataca 21720gaagctgtgc atccttccac aaacacagca gcgtccaatg tggagattcc cagctctgga 21780catgaatccc cttcctctgc cttagctgac tcagagacat ccaaagccac atcaccaatg 21840tttattacct ccacccagga ggatacaact gttgccatat caacccctca cttcttggag 21900actagcagaa ttcagaaaga gtcaatttcc tccctgagcc ctaaattgag ggagacaggc 21960agttctgtgg agacaagctc agccatagag acaagtgctg tcctttctga agtgtccatt 22020ggtgctacta ctgagatctc caggacagaa gtcacctcct ctagcagaac atccatctct 22080ggttctgctg agtccacaat gttgccagaa atatccacca caagaaaaat cattaagttc 22140cctacttccc ccatcctggc agaatcatca gaaatgacca tcaagaccca aacaagtcct 22200cctgggtcta catcagagag tacctttaca ttagacacat caaccactcc ctccttggta 22260ataacccatt cgactatgac tcagagattg ccacactcag agataaccac tcttgtgagt 22320agaggtgctg gggatgtgcc acggcccagc tctctccctg tggaagaaac aagccctcca 22380tcttcccagc tgtctttatc tgccatgatc tcaccttctc ctgtttcttc cacattacca 22440gcaagtagcc actcctcttc tgcttctgtg acttcacttc tcacaccagg ccaagtgaag 22500actactgagg tgttggacgc aagtgcagaa cctgaaacca gttcacctcc aagtttgagc 22560agcacctcag ttgaaatact ggccacctct gaagtcacca cagatacgga gaaaattcat 22620cctttctcaa acacggcagt aaccaaagtt ggaacttcca gttctggaca tgaatcccct 22680tcctctgtcc tacctgactc agagacaacc aaagccacat cggcaatggg taccatctcc 22740attatggggg atacaagtgt ttctacatta actcctgcct tatctaacac taggaaaatt 22800cagtcagagc cagcttcctc actgaccacc agattgaggg agaccagcac ctctgaagag 22860accagcttag ccacagaagc aaacactgtt ctttctaaag tgtccactgg tgctactact 22920gaggtctcca ggacagaagc catctccttt agcagaacat ccatgtcagg ccctgagcag 22980tccacaatgt cacaagacat ctccatagga accatcccca ggatttctgc ctcctctgtc 23040ctgacagaat ctgcaaaaat gaccatcaca acccaaacag gtccttcgga gtctacacta 23100gaaagtaccc ttaatttgaa cacagcaacc acaccctctt gggtggaaac ccactctata 23160gtaattcagg gatttccaca cccagagatg accacttcca tgggcagagg tcctggaggt 23220gtgtcatggc ctagccctcc ctttgtgaaa gaaaccagcc ctccatcctc cccgctgtct 23280ttacctgccg tgacctcacc tcatcctgtt tccaccacat tcctagcaca tatccccccc 23340tctccccttc ctgtgacttc acttctcacc tctggcccgg cgacaaccac agatatcttg 23400ggtacaagca cagaacctgg aaccagttca tcttcaagtt tgagcaccac ctcccatgag 23460agactgacca cttacaaaga cactgcacat acagaagccg tgcatccttc cacaaacaca 23520ggagggacca atgtggcaac caccagctct ggatataaat cacagtcctc tgtcctagct 23580gactcatctc caatgtgtac cacctccacc atgggggata caagtgttct cacatcaact 23640cctgccttcc ttgagactag gaggattcag acagagctag cttcctccct gacccctgga 23700ttgagggagt ccagcggctc tgaagggacc agctcaggca ccaagatgag cactgtcctc 23760tctaaagtgc ccactggtgc tactactgag atctccaagg aagacgtcac ctccatccca 23820ggtcccgctc aatccacaat atcaccagac atctccacaa gaaccgtcag ctggttctct 23880acatcccctg tcatgacaga atcagcagaa ataaccatga acacccatac aagtccttta 23940ggggccacaa cacaaggcac cagtactttg gacacgtcaa gcacaacctc tttgacaatg 24000acacactcaa ctatatctca aggattttca cactcacaga tgagcactct tatgaggagg 24060ggtcctgagg atgtatcatg gatgagccct ccccttctgg aaaaaactag accttccttt 24120tctctgatgt cttcaccagc cacaacttca ccttctcctg tttcctccac attaccagag 24180agcatctctt cctctcctct tcctgtgact tcactcctca cgtctggctt ggcaaaaact 24240acagatatgt tgcacaaaag ctcagaacct gtaaccaact cacctgcaaa tttgagcagc 24300acctcagttg aaatactggc cacctctgaa gtcaccacag atacagagaa aactcatcct 24360tcttcaaaca gaacagtgac cgatgtgggg acctccagtt ctggacatga atccacttcc 24420tttgtcctag ctgactcaca gacatccaaa gtcacatctc caatggttat tacctccacc 24480atggaggata cgagtgtctc cacatcaact cctggctttt ttgagactag cagaattcag 24540acagaaccaa catcctccct gacccttgga ctgagaaaga

ccagcagctc tgaggggacc 24600agcttagcca cagagatgag cactgtcctt tctggagtgc ccactggtgc cactgctgaa 24660gtctccagga cagaagtcac ctcctctagc agaacatcca tctcaggctt tgctcagctc 24720acagtgtcac cagagacttc cacagaaacc atcaccagac tccctacctc cagcataatg 24780acagaatcag cagaaatgat gatcaagaca caaacagatc ctcctgggtc tacaccagag 24840agtactcata ctgtggacat atcaacaaca cccaactggg tagaaaccca ctcgactgtg 24900actcagagat tttcacactc agagatgacc actcttgtga gcagaagccc tggtgatatg 24960ttatggccta gtcaatcctc tgtggaagaa accagctctg cctcttccct gctgtctctg 25020cctgccacga cctcaccttc tcctgtttcc tctacattag tagaggattt cccttccgct 25080tctcttcctg tgacttctct tctcaaccct ggcctggtga taaccacaga caggatgggc 25140ataagcagag aacctggaac cagttccact tcaaatttga gcagcacctc ccatgagaga 25200ctgaccactt tggaagacac tgtagataca gaagacatgc agccttccac acacacagca 25260gtgaccaacg tgaggacctc catttctgga catgaatcac aatcttctgt cctatctgac 25320tcagagacac ccaaagccac atctccaatg ggtaccacct acaccatggg ggaaacgagt 25380gtttccatat ccacttctga cttctttgag accagcagaa ttcagataga accaacatcc 25440tccctgactt ctggattgag ggagaccagc agctctgaga ggatcagctc agccacagag 25500ggaagcactg tcctttctga agtgcccagt ggtgctacca ctgaggtctc caggacagaa 25560gtgatatcct ctaggggaac atccatgtca gggcctgatc agttcaccat atcaccagac 25620atctctactg aagcgatcac caggctttct acttccccca ttatgacaga atcagcagaa 25680agtgccatca ctattgagac aggttctcct ggggctacat cagagggtac cctcaccttg 25740gacacctcaa caacaacctt ttggtcaggg acccactcaa ctgcatctcc aggattttca 25800cactcagaga tgaccactct tatgagtaga actcctggag atgtgccatg gccgagcctt 25860ccctctgtgg aagaagccag ctctgtctct tcctcactgt cttcacctgc catgacctca 25920acttcttttt tctccacatt accagagagc atctcctcct ctcctcatcc tgtgactgca 25980cttctcaccc ttggcccagt gaagaccaca gacatgttgc gcacaagctc agaacctgaa 26040accagttcac ctccaaattt gagcagcacc tcagctgaaa tattagccac gtctgaagtc 26100accaaagata gagagaaaat tcatccctcc tcaaacacac ctgtagtcaa tgtagggact 26160gtgatttata aacatctatc cccttcctct gttttggctg acttagtgac aacaaaaccc 26220acatctccaa tggctaccac ctccactctg gggaatacaa gtgtttccac atcaactcct 26280gccttcccag aaactatgat gacacagcca acttcctccc tgacttctgg attaagggag 26340atcagtacct ctcaagagac cagctcagca acagagagaa gtgcttctct ttctggaatg 26400cccactggtg ctactactaa ggtctccaga acagaagccc tctccttagg cagaacatcc 26460accccaggtc ctgctcaatc cacaatatca ccagaaatct ccacggaaac catcactaga 26520atttctactc ccctcaccac gacaggatca gcagaaatga ccatcacccc caaaacaggt 26580cattctgggg catcctcaca aggtaccttt accttggaca catcaagcag agcctcctgg 26640ccaggaactc actcagctgc aactcacaga tctccacact cagggatgac cactcctatg 26700agcagaggtc ctgaggatgt gtcatggcca agccgcccat cagtggaaaa aactagccct 26760ccatcttccc tggtgtcttt atctgcagta acctcacctt cgccacttta ttccacacca 26820tctgagagta gccactcatc tcctctccgg gtgacttctc ttttcacccc tgtcatgatg 26880aagaccacag acatgttgga cacaagcttg gaacctgtga ccacttcacc tcccagtatg 26940aatatcacct cagatgagag tctggccact tctaaagcca ccatggagac agaggcaatt 27000cagctttcag aaaacacagc tgtgactcag atgggcacca tcagcgctag acaagaattc 27060tattcctctt atccaggcct cccagagcca tccaaagtga catctccagt ggtcacctct 27120tccaccataa aagacattgt ttctacaacc atacctgctt cctctgagat aacaagaatt 27180gagatggagt caacatccac cctgaccccc acaccaaggg agaccagcac ctcccaggag 27240atccactcag ccacaaagcc aagcactgtt ccttacaagg cactcactag tgccacgatt 27300gaggactcca tgacacaagt catgtcctct agcagaggac ctagccctga tcagtccaca 27360atgtcacaag acatatccac tgaagtgatc accaggctct ctacctcccc catcaagaca 27420gaatctacag aaatgaccat taccacccaa acaggttctc ctggggctac atcaaggggt 27480acccttacct tggacacttc aacaactttt atgtcaggga cccactcaac tgcatctcaa 27540ggattttcac actcacagat gaccgctctt atgagtagaa ctcctggaga tgtgccatgg 27600ctaagccatc cctctgtgga agaagccagc tctgcctctt tctcactgtc ttcacctgtc 27660atgacctcat cttctcccgt ttcttccaca ttaccagaca gcatccactc ttcttcgctt 27720cctgtgacat cacttctcac ctcagggctg gtgaagacca cagagctgtt gggcacaagc 27780tcagaacctg aaaccagttc acccccaaat ttgagcagca cctcagctga aatactggcc 27840atcactgaag tcactacaga tacagagaaa ctggagatga ccaatgtggt aacctcaggt 27900tatacacatg aatctccttc ctctgtccta gctgactcag tgacaacaaa ggccacatct 27960tcaatgggta tcacctaccc cacaggagat acaaatgttc tcacatcaac ccctgccttc 28020tctgacacca gtaggattca aacaaagtca aagctctcac tgactcctgg gttgatggag 28080accagcatct ctgaagagac cagctctgcc acagaaaaaa gcactgtcct ttctagtgtg 28140cccactggtg ctactactga ggtctccagg acagaagcca tctcttctag cagaacatcc 28200atcccaggcc ctgctcaatc cacaatgtca tcagacacct ccatggaaac catcactaga 28260atttctaccc ccctcacaag gaaagaatca acagacatgg ccatcacccc caaaacaggt 28320ccttctgggg ctacctcgca gggtaccttt accttggact catcaagcac agcctcctgg 28380ccaggaactc actcagctac aactcagaga tttccacagt cagtggtgac aactcctatg 28440agcagaggtc ctgaggatgt gtcatggcca agcccgctgt ctgtggaaaa aaacagccct 28500ccatcttccc tggtatcttc atcttcagta acctcacctt cgccacttta ttccacacca 28560tctgggagta gccactcctc tcctgtccct gtcacttctc ttttcacctc tatcatgatg 28620aaggccacag acatgttgga tgcaagtttg gaacctgaga ccacttcagc tcccaatatg 28680aatatcacct cagatgagag tctggccgct tctaaagcca ccacggagac agaggcaatt 28740cacgtttttg aaaatacagc agcgtcccat gtggaaacca ccagtgctac agaggaactc 28800tattcctctt ccccaggctt ctcagagcca acaaaagtga tatctccagt ggtcacctct 28860tcctctataa gagacaacat ggtttccaca acaatgcctg gctcctctgg cattacaagg 28920attgagatag agtcaatgtc atctctgacc cctggactga gggagaccag aacctcccag 28980gacatcacct catccacaga gacaagcact gtcctttaca agatgccctc tggtgccact 29040cctgaggtct ccaggacaga agttatgccc tctagcagaa catccattcc tggccctgct 29100cagtccacaa tgtcactaga catctccgat gaagttgtca ccaggctgtc tacctctccc 29160atcatgacag aatctgcaga aataaccatc accacccaaa caggttattc tctggctaca 29220tcccaggtta cccttccctt gggcacctca atgacctttt tgtcagggac ccactcaact 29280atgtctcaag gactttcaca ctcagagatg accaatctta tgagcagggg tcctgaaagt 29340ctgtcatgga cgagccctcg ctttgtggaa acaactagat cttcctcttc tctgacatca 29400ttacctctca cgacctcact ttctcctgtg tcctccacat tactagacag tagcccctcc 29460tctcctcttc ctgtgacttc acttatcctc ccaggcctgg tgaagactac agaagtgttg 29520gatacaagct cagagcctaa aaccagttca tctccaaatt tgagcagcac ctcagttgaa 29580ataccggcca cctctgaaat catgacagat acagagaaaa ttcatccttc ctcaaacaca 29640gcggtggcca aagtgaggac ctccagttct gttcatgaat ctcattcctc tgtcctagct 29700gactcagaaa caaccataac cataccttca atgggtatca cctccgctgt ggacgatacc 29760actgttttca catcaaatcc tgccttctct gagactagga ggattccgac agagccaaca 29820ttctcattga ctcctggatt cagggagact agcacctctg aagagaccac ctcaatcaca 29880gaaacaagtg cagtccttta tggagtgccc actagtgcta ctactgaagt ctccatgaca 29940gaaatcatgt cctctaatag aatacacatc cctgactctg atcagtccac gatgtctcca 30000gacatcatca ctgaagtgat caccaggctc tcttcctcat ccatgatgtc agaatcaaca 30060caaatgacca tcaccaccca aaaaagttct cctggggcta cagcacagag tactcttacc 30120ttggccacaa caacagcccc cttggcaagg acccactcaa ctgttcctcc tagattttta 30180cactcagaga tgacaactct tatgagtagg agtcctgaaa atccatcatg gaagagctct 30240ctctttgtgg aaaaaactag ctcttcatct tctctgttgt ccttacctgt cacgacctca 30300ccttctgttt cttccacatt accgcagagt atcccttcct cctctttttc tgtgacttca 30360ctcctcaccc caggcatggt gaagactaca gacacaagca cagaacctgg aaccagttta 30420tctccaaatc tgagtggcac ctcagttgaa atactggctg cctctgaagt caccacagat 30480acagagaaaa ttcatccttc ttcaagcatg gcagtgacca atgtgggaac caccagttct 30540ggacatgaac tatattcctc tgtttcaatc cactcggagc catccaaggc tacataccca 30600gtgggtactc cctcttccat ggctgaaacc tctatttcca catcaatgcc tgctaatttt 30660gagaccacag gatttgaggc tgagccattt tctcatttga cttctggatt taggaagaca 30720aacatgtccc tggacaccag ctcagtcaca ccaacaaata caccttcttc tcctgggtcc 30780actcaccttt tacagagttc caagactgat ttcacctctt ctgcaaaaac atcatcccca 30840gactggcctc cagcctcaca gtatactgaa attccagtgg acataatcac cccctttaat 30900gcttctccat ctattacgga gtccactggg ataacctcct tcccagaatc caggtttact 30960atgtctgtaa cagaaagtac tcatcatctg agtacagatt tgctgccttc agctgagact 31020atttccactg gcacagtgat gccttctcta tcagaggcca tgacttcatt tgccaccact 31080ggagttccac gagccatctc aggttcaggt agtccattct ctaggacaga gtcaggccct 31140ggggatgcta ctctgtccac cattgcagag agcctgcctt catccactcc tgtgccattc 31200tcctcttcaa ccttcactac cactgattct tcaaccatcc cagccctcca tgagataact 31260tcctcttcag ctaccccata tagagtggac accagtcttg ggacagagag cagcactact 31320gaaggacgct tggttatggt cagtactttg gacacttcaa gccaaccagg caggacatct 31380tcatcaccca ttttggatac cagaatgaca gagagcgttg agctgggaac agtgacaagt 31440gcttatcaag ttccttcact ctcaacacgg ttgacaagaa ctgatggcat tatggaacac 31500atcacaaaaa tacccaatga agcagcacac agaggtacca taagaccagt caaaggccct 31560cagacatcca cttcgcctgc cagtcctaaa ggactacaca caggagggac aaaaagaatg 31620gagaccacca ccacagctct gaagaccacc accacagctc tgaagaccac ttccagagcc 31680accttgacca ccagtgtcta tactcccact ttgggaacac tgactcccct caatgcatca 31740atgcaaatgg ccagcacaat ccccacagaa atgatgatca caaccccata tgttttccct 31800gatgttccag aaacgacatc ctcattggct accagcctgg gagcagaaac cagcacagct 31860cttcccagga caaccccatc tgttttcaat agagaatcag agaccacagc ctcactggtc 31920tctcgttctg gggcagagag aagtccggtt attcaaactc tagatgtttc ttctagtgag 31980ccagatacaa cagcttcatg ggttatccat cctgcagaga ccatcccaac tgtttccaag 32040acaaccccca attttttcca cagtgaatta gacactgtat cttccacagc caccagtcat 32100ggggcagacg tcagctcagc cattccaaca aatatctcac ctagtgaact agatgcactg 32160accccactgg tcactatttc ggggacagat actagtacaa cattcccaac actgactaag 32220tccccacatg aaacagagac aagaaccaca tggctcactc atcctgcaga gaccagctca 32280actattccca gaacaatccc caatttttct catcatgaat cagatgccac accttcaata 32340gccaccagtc ctggggcaga aaccagttca gctattccaa ttatgactgt ctcacctggt 32400gcagaagatc tggtgacctc acaggtcact agttctggga cagacagaaa tatgactatt 32460ccaactttga ctctttctcc tggtgaacca aagacgatag cctcattagt cacccatcct 32520gaagcacaga caagttcggc cattccaact tcaactatct cgcctgctgt atcacggttg 32580gtgacctcaa tggtcaccag tttggcggca aagacaagta caactaatcg agctctgaca 32640aactcccctg gtgaaccagc tacaacagtt tcattggtca cgcatcctgc acagaccagc 32700ccaacagttc cctggacaac ttccattttt ttccatagta aatcagacac cacaccttca 32760atgaccacca gtcatggggc agaatccagt tcagctgttc caactccaac tgtttcaact 32820gaggtaccag gagtagtgac ccctttggtc accagttcta gggcagtgat cagtacaact 32880attccaattc tgactctttc tcctggtgaa ccagagacca caccttcaat ggccaccagt 32940catggggaag aagccagttc tgctattcca actccaactg tttcacctgg ggtaccagga 33000gtggtgacct ctctggtcac tagttctagg gcagtgacta gtacaactat tccaattctg 33060actttttctc ttggtgaacc agagaccaca ccttcaatgg ccaccagtca tgggacagaa 33120gctggctcag ctgttccaac tgttttacct gaggtaccag gaatggtgac ctctctggtt 33180gctagttcta gggcagtaac cagtacaact cttccaactc tgactctttc tcctggtgaa 33240ccagagacca caccttcaat ggccaccagt catggggcag aagccagctc aactgttcca 33300actgtttcac ctgaggtacc aggagtggtg acctctctgg tcactagttc tagtggagta 33360aacagtacaa gtattccaac tctgattctt tctcctggtg aactagaaac cacaccttca 33420atggccacca gtcatggggc agaagccagc tcagctgttc caactccaac tgtttcacct 33480ggggtatcag gagtggtgac ccctctggtc actagttcca gggcagtgac cagtacaact 33540attccaattc taactctttc ttctagtgag ccagagacca caccttcaat ggccaccagt 33600catggggtag aagccagctc agctgttcta actgtttcac ctgaggtacc aggaatggtg 33660acctctctgg tcactagttc tagagcagta accagtacaa ctattccaac tctgactatt 33720tcttctgatg aaccagagac cacaacttca ttggtcaccc attctgaggc aaagatgatt 33780tcagccattc caactttagc tgtctcccct actgtacaag ggctggtgac ttcactggtc 33840actagttctg ggtcagagac cagtgcgttt tcaaatctaa ctgttgcctc aagtcaacca 33900gagaccatag actcatgggt cgctcatcct gggacagaag caagttctgt tgttccaact 33960ttgactgtct ccactggtga gccgtttaca aatatctcat tggtcaccca tcctgcagag 34020agtagctcaa ctcttcccag gacaacctca aggttttccc acagtgaatt agacactatg 34080ccttctacag tcaccagtcc tgaggcagaa tccagctcag ccatttcaac aactatttca 34140cctggtatac caggtgtgct gacatcactg gtcactagct ctgggagaga catcagtgca 34200acttttccaa cagtgcctga gtccccacat gaatcagagg caacagcctc atgggttact 34260catcctgcag tcaccagcac aacagttccc aggacaaccc ctaattattc tcatagtgaa 34320ccagacacca caccatcaat agccaccagt cctggggcag aagccacttc agattttcca 34380acaataactg tctcacctga tgtaccagat atggtaacct cacaggtcac tagttctggg 34440acagacacca gtataactat tccaactctg actctttctt ctggtgagcc agagaccaca 34500acctcattta tcacctattc tgagacacac acaagttcag ccattccaac tctccctgtc 34560tcccctggtg catcaaagat gctgacctca ctggtcatca gttctgggac agacagcact 34620acaactttcc caacactgac ggagacccca tatgaaccag agacaacagc catacagctc 34680attcatcctg cagagaccaa cacaatggtt cccaggacaa ctcccaagtt ttcccatagt 34740aagtcagaca ccacactccc agtagccatc accagtcctg ggccagaagc cagttcagct 34800gtttcaacga caactatctc acctgatatg tcagatctgg tgacctcact ggtccctagt 34860tctgggacag acaccagtac aaccttccca acattgagtg agaccccata tgaaccagag 34920actacagcca cgtggctcac tcatcctgca gaaaccagca caacggtttc tgggacaatt 34980cccaactttt cccatagggg atcagacact gcaccctcaa tggtcaccag tcctggagta 35040gacacgaggt caggtgttcc aactacaacc atcccaccca gtataccagg ggtagtgacc 35100tcacaggtca ctagttctgc aacagacact agtacagcta ttccaacttt gactccttct 35160cctggtgaac cagagaccac agcctcatca gctacccatc ctgggacaca gactggcttc 35220actgttccaa ttcggactgt tccctctagt gagccagata caatggcttc ctgggtcact 35280catcctccac agaccagcac acctgtttcc agaacaacct ccagtttttc ccatagtagt 35340ccagatgcca cacctgtaat ggccaccagt cctaggacag aagccagttc agctgtactg 35400acaacaatct cacctggtgc accagagatg gtgacttcac agatcactag ttctggggca 35460gcaaccagta caactgttcc aactttgact cattctcctg gtatgccaga gaccacagcc 35520ttattgagca cccatcccag aacagagaca agtaaaacat ttcctgcttc aactgtgttt 35580cctcaagtat cagagaccac agcctcactc accattagac ctggtgcaga gactagcaca 35640gctctcccaa ctcagacaac atcctctctc ttcaccctac ttgtaactgg aaccagcaga 35700gttgatctaa gtccaactgc ttcacctggt gtttctgcaa aaacagcccc actttccacc 35760catccaggga cagaaaccag cacaatgatt ccaacttcaa ctctttccct tggtttacta 35820gagactacag gcttactggc caccagctct tcagcagaga ccagcacgag tactctaact 35880ctgactgttt cccctgctgt ctctgggctt tccagtgcct ctataacaac tgataagccc 35940caaactgtga cctcctggaa cacagaaacc tcaccatctg taacttcagt tggaccccca 36000gaattttcca ggactgtcac aggcaccact atgaccttga taccatcaga gatgccaaca 36060ccacctaaaa ccagtcatgg agaaggagtg agtccaacca ctatcttgag aactacaatg 36120gttgaagcca ctaatttagc taccacaggt tccagtccca ctgtggccaa gacaacaacc 36180accttcaata cactggctgg aagcctcttt actcctctga ccacacctgg gatgtccacc 36240ttggcctctg agagtgtgac ctcaagaaca agttataacc atcggtcctg gatctccacc 36300accagcagtt ataaccgtcg gtactggacc cctgccacca gcactccagt gacttctaca 36360ttctccccag ggatttccac atcctccatc cccagctcca cagcagccac agtcccattc 36420atggtgccat tcaccctcaa cttcaccatc accaacctgc agtacgagga ggacatgcgg 36480caccctggtt ccaggaagtt caacgccaca gagagagaac tgcagggtct gctcaaaccc 36540ttgttcagga atagcagtct ggaatacctc tattcaggct gcagactagc ctcactcagg 36600ccagagaagg atagctcagc cacggcagtg gatgccatct gcacacatcg ccctgaccct 36660gaagacctcg gactggacag agagcgactg tactgggagc tgagcaatct gacaaatggc 36720atccaggagc tgggccccta caccctggac cggaacagtc tctatgtcaa tggtttcacc 36780catcgaagct ctatgcccac caccagcact cctgggacct ccacagtgga tgtgggaacc 36840tcagggactc catcctccag ccccagcccc acgactgctg gccctctcct gatgccgttc 36900accctcaact tcaccatcac caacctgcag tacgaggagg acatgcgtcg cactggctcc 36960aggaagttca acaccatgga gagtgtcctg cagggtctgc tcaagccctt gttcaagaac 37020accagtgttg gccctctgta ctctggctgc agattgacct tgctcaggcc cgagaaagat 37080ggggcagcca ctggagtgga tgccatctgc acccaccgcc ttgaccccaa aagccctgga 37140ctcaacaggg agcagctgta ctgggagcta agcaaactga ccaatgacat tgaagagctg 37200ggcccctaca ccctggacag gaacagtctc tatgtcaatg gtttcaccca tcagagctct 37260gtgtccacca ccagcactcc tgggacctcc acagtggatc tcagaacctc agggactcca 37320tcctccctct ccagccccac aattatggct gctggccctc tcctggtacc attcaccctc 37380aacttcacca tcaccaacct gcagtatggg gaggacatgg gtcaccctgg ctccaggaag 37440ttcaacacca cagagagggt cctgcagggt ctgcttggtc ccatattcaa gaacaccagt 37500gttggccctc tgtactctgg ctgcagactg acctctctca ggtctgagaa ggatggagca 37560gccactggag tggatgccat ctgcatccat catcttgacc ccaaaagccc tggactcaac 37620agagagcggc tgtactggga gctgagccaa ctgaccaatg gcatcaaaga gctgggcccc 37680tacaccctgg acaggaacag tctctatgtc aatggtttca cccatcggac ctctgtgccc 37740accagcagca ctcctgggac ctccacagtg gaccttggaa cctcagggac tccattctcc 37800ctcccaagcc ccgcaactgc tggccctctc ctggtgctgt tcaccctcaa cttcaccatc 37860accaacctga agtatgagga ggacatgcat cgccctggct ccaggaagtt caacaccact 37920gagagggtcc tgcagactct gcttggtcct atgttcaaga acaccagtgt tggccttctg 37980tactctggct gcagactgac cttgctcagg tccgagaagg atggagcagc cactggagtg 38040gatgccatct gcacccaccg tcttgacccc aaaagccctg gagtggacag ggagcagcta 38100tactgggagc tgagccagct gaccaatggc atcaaagagc tgggccccta caccctggac 38160aggaacagtc tctatgtcaa tggtttcacc cattggatcc ctgtgcccac cagcagcact 38220cctgggacct ccacagtgga ccttgggtca gggactccat cctccctccc cagccccaca 38280actgctggcc ctctcctggt gccgttcacc ctcaacttca ccatcaccaa cctgaagtac 38340gaggaggaca tgcattgccc tggctccagg aagttcaaca ccacagagag agtcctgcag 38400agtctgcttg gtcccatgtt caagaacacc agtgttggcc ctctgtactc tggctgcaga 38460ctgaccttgc tcaggtccga gaaggatgga gcagccactg gagtggatgc catctgcacc 38520caccgtcttg accccaaaag ccctggagtg gacagggagc agctatactg ggagctgagc 38580cagctgacca atggcatcaa agagctgggt ccctacaccc tggacagaaa cagtctctat 38640gtcaatggtt tcacccatca gacctctgcg cccaacacca gcactcctgg gacctccaca 38700gtggaccttg ggacctcagg gactccatcc tccctcccca gccctacatc tgctggccct 38760ctcctggtgc cattcaccct caacttcacc atcaccaacc tgcagtacga ggaggacatg 38820catcacccag gctccaggaa gttcaacacc acggagcggg tcctgcaggg tctgcttggt 38880cccatgttca agaacaccag tgtcggcctt ctgtactctg gctgcagact gaccttgctc 38940aggcctgaga agaatggggc agccactgga atggatgcca tctgcagcca ccgtcttgac 39000cccaaaagcc ctggactcaa cagagagcag ctgtactggg agctgagcca gctgacccat 39060ggcatcaaag agctgggccc ctacaccctg gacaggaaca gtctctatgt caatggtttc 39120acccatcgga gctctgtggc ccccaccagc actcctggga cctccacagt ggaccttggg 39180acctcaggga ctccatcctc cctccccagc cccacaacag ctgttcctct cctggtgccg 39240ttcaccctca actttaccat caccaatctg cagtatgggg aggacatgcg tcaccctggc 39300tccaggaagt tcaacaccac agagagggtc ctgcagggtc tgcttggtcc cttgttcaag 39360aactccagtg tcggccctct gtactctggc tgcagactga tctctctcag gtctgagaag 39420gatggggcag ccactggagt ggatgccatc tgcacccacc accttaaccc tcaaagccct 39480ggactggaca gggagcagct gtactggcag ctgagccaga tgaccaatgg catcaaagag 39540ctgggcccct acaccctgga ccggaacagt ctctacgtca atggtttcac ccatcggagc 39600tctgggctca ccaccagcac tccttggact tccacagttg

accttggaac ctcagggact 39660ccatcccccg tccccagccc cacaaccacc ggccctctcc tggtgccatt cacactcaac 39720ttcaccatca ctaacctaca gtatgaggag aacatgggtc accctggctc caggaagttc 39780aacatcacgg agagtgttct gcagggtctg ctcaagccct tgttcaagag caccagtgtt 39840ggccctctgt attctggctg cagactgacc ttgctcaggc ctgagaagga tggagtagcc 39900accagagtgg acgccatctg cacccaccgc cctgacccca aaatccctgg gctagacaga 39960cagcagctat actgggagct gagccagctg acccacagca tcactgagct gggaccctac 40020accctggata gggacagtct ctatgtcaat ggtttcaccc agcggagctc tgtgcccacc 40080accagcactc ctgggacttt cacagtacag ccggaaacct ctgagactcc atcatccctc 40140cctggcccca cagccactgg ccctgtcctg ctgccattca ccctcaattt taccatcact 40200aacctgcagt atgaggagga catgcgtcgc cctggctcca ggaagttcaa caccacggag 40260agggtccttc agggtctgct tatgcccttg ttcaagaaca ccagtgtcag ctctctgtac 40320tctggttgca gactgacctt gctcaggcct gagaaggatg gggcagccac cagagtggat 40380gctgtctgca cccatcgtcc tgaccccaaa agccctggac tggacagaga gcggctgtac 40440tggaagctga gccagctgac ccacggcatc actgagctgg gcccctacac cctggacagg 40500cacagtctct atgtcaatgg tttcacccat cagagctcta tgacgaccac cagaactcct 40560gatacctcca caatgcacct ggcaacctcg agaactccag cctccctgtc tggacccatg 40620accgccagcc ctctcctggt gctattcaca attaacttca ccatcactaa cctgcggtat 40680gaggagaaca tgcatcaccc tggctctaga aagtttaaca ccacggagag agtccttcag 40740ggtctgctca ggcctgtgtt caagaacacc agtgttggcc ctctgtactc tggctgcaga 40800ctgaccttgc tcaggcccaa gaaggatggg gcagccacca aagtggatgc catctgcacc 40860taccgccctg atcccaaaag ccctggactg gacagagagc agctatactg ggagctgagc 40920cagctgaccc acagcatcac tgagctgggc ccctacaccc tggacaggga cagtctctat 40980gtcaatggtt tcacacagcg gagctctgtg cccaccacta gcattcctgg gacccccaca 41040gtggacctgg gaacatctgg gactccagtt tctaaacctg gtccctcggc tgccagccct 41100ctcctggtgc tattcactct caacttcacc atcaccaacc tgcggtatga ggagaacatg 41160cagcaccctg gctccaggaa gttcaacacc acggagaggg tccttcaggg cctgctcagg 41220tccctgttca agagcaccag tgttggccct ctgtactctg gctgcagact gactttgctc 41280aggcctgaaa aggatgggac agccactgga gtggatgcca tctgcaccca ccaccctgac 41340cccaaaagcc ctaggctgga cagagagcag ctgtattggg agctgagcca gctgacccac 41400aatatcactg agctgggccc ctatgccctg gacaacgaca gcctctttgt caatggtttc 41460actcatcgga gctctgtgtc caccaccagc actcctggga cccccacagt gtatctggga 41520gcatctaaga ctccagcctc gatatttggc ccttcagctg ccagccatct cctgatacta 41580ttcaccctca acttcaccat cactaacctg cggtatgagg agaacatgtg gcctggctcc 41640aggaagttca acactacaga gagggtcctt cagggcctgc taaggccctt gttcaagaac 41700accagtgttg gccctctgta ctctggctgc aggctgacct tgctcaggcc agagaaagat 41760ggggaagcca ccggagtgga tgccatctgc acccaccgcc ctgaccccac aggccctggg 41820ctggacagag agcagctgta tttggagctg agccagctga cccacagcat cactgagctg 41880ggcccctaca cactggacag ggacagtctc tatgtcaatg gtttcaccca tcggagctct 41940gtacccacca ccagcaccgg ggtggtcagc gaggagccat tcacactgaa cttcaccatc 42000aacaacctgc gctacatggc ggacatgggc caacccggct ccctcaagtt caacatcaca 42060gacaacgtca tgcagcacct gctcagtcct ttgttccaga ggagcagcct gggtgcacgg 42120tacacaggct gcagggtcat cgcactaagg tctgtgaaga acggtgctga gacacgggtg 42180gacctcctct gcacctacct gcagcccctc agcggcccag gtctgcctat caagcaggtg 42240ttccatgagc tgagccagca gacccatggc atcacccggc tgggccccta ctctctggac 42300aaagacagcc tctaccttaa cggttacaat gaacctggtc cagatgagcc tcctacaact 42360cccaagccag ccaccacatt cctgcctcct ctgtcagaag ccacaacagc catggggtac 42420cacctgaaga ccctcacact caacttcacc atctccaatc tccagtattc accagatatg 42480ggcaagggct cagctacatt caactccacc gagggggtcc ttcagcacct gctcagaccc 42540ttgttccaga agagcagcat gggccccttc tacttgggtt gccaactgat ctccctcagg 42600cctgagaagg atggggcagc cactggtgtg gacaccacct gcacctacca ccctgaccct 42660gtgggccccg ggctggacat acagcagctt tactgggagc tgagtcagct gacccatggt 42720gtcacccaac tgggcttcta tgtcctggac agggatagcc tcttcatcaa tggctatgca 42780ccccagaatt tatcaatccg gggcgagtac cagataaatt tccacattgt caactggaac 42840ctcagtaatc cagaccccac atcctcagag tacatcaccc tgctgaggga catccaggac 42900aaggtcacca cactctacaa aggcagtcaa ctacatgaca cattccgctt ctgcctggtc 42960accaacttga cgatggactc cgtgttggtc actgtcaagg cattgttctc ctccaatttg 43020gaccccagcc tggtggagca agtctttcta gataagaccc tgaatgcctc attccattgg 43080ctgggctcca cctaccagtt ggtggacatc catgtgacag aaatggagtc atcagtttat 43140caaccaacaa gcagctccag cacccagcac ttctacctga atttcaccat caccaaccta 43200ccatattccc aggacaaagc ccagccaggc accaccaatt accagaggaa caaaaggaat 43260attgaggatg cgctcaacca actcttccga aacagcagca tcaagagtta tttttctgac 43320tgtcaagttt caacattcag gtctgtcccc aacaggcacc acaccggggt ggactccctg 43380tgtaacttct cgccactggc tcggagagta gacagagttg ccatctatga ggaatttctg 43440cggatgaccc ggaatggtac ccagctgcag aacttcaccc tggacaggag cagtgtcctt 43500gtggatgggt attctcccaa cagaaatgag cccttaactg ggaattctga ccttcccttc 43560tgggctgtca tcctcatcgg cttggcagga ctcctgggag tcatcacatg cctgatctgc 43620ggtgtcctgg tgaccacccg ccggcggaag aaggaaggag aatacaacgt ccagcaacag 43680tgcccaggct actaccagtc acacctagac ctggaggatc tgcaatgact ggaacttgcc 43740ggtgcctggg gtgcctttcc cccagccagg gtccaaagaa gcttggctgg ggcagaaata 43800aaccatattg gtcgga 438165516756DNAHomo sapiens 55gcacttggtt cgggccagcc gcctgagggg acgggctcac gtctgctcct cacactgcag 60ctgctgggcc gtggagcttc cccagggagc cagggggact tttgccgcag ccatgaaggg 120ggcacgctgg aggagggtcc cctgggtgtc cctgagctgc ctgtgtctct gcctccttcc 180gcatgtggtc ccaggaacca cagaggacac attaataact ggaagtaaaa ctgctgcccc 240agtcacctca acaggctcaa caacagcgac actagaggga caatcaactg cagcttcttc 300aaggacctct aatcaggaca tatcagcttc atctcagaac caccagacta agagcacgga 360gaccaccagc aaagctcaaa ccgacaccct cacgcagatg atgacatcaa ctcttttttc 420ttccccaagt gtacacaatg tgatggagac agctcctcca gatgaaatga ccacatcatt 480tccctccagt gtcaccaaca cactcatgat gacatcaaag actataacaa tgacaacctc 540cacagactcc actcttggaa acacagaaga gacatcaaca gcaggaactg aaagttctac 600cccagtgacc tcagcagtct caataacagc tggacaggaa ggacaatcac gaacaacttc 660ctggaggacc tctatccaag acacatcagc ttcttctcag aaccactgga ctcggagcac 720gcagaccacc agggaatctc aaaccagcac cctaacacac agaaccactt caactccttc 780tttctctcca agtgtacaca atgtgacagg gactgtttct cagaagacat ctccttcagg 840tgaaacagct acctcatccc tctgtagtgt cacaaacaca tccatgatga catcagagaa 900gataacagtg acaacctcca caggctccac tcttggaaac ccaggggaga catcatcagt 960acctgttact ggaagtctta tgccagtcac ctcagcagcc ttagtaacat ttgatccaga 1020aggacaatca ccagcaactt tctcaaggac ttctactcag gacacaacag ctttttctaa 1080gaaccaccag actcagagcg tggagaccac cagagtatct caaatcaaca ccctcaacac 1140cctcacaccg gttacaacat caactgtttt atcctcacca agtggattca acccaagtgg 1200aacagtttct caggagacat tcccttctgg tgaaacaacc acctcatccc cttccagtgt 1260cagcaataca ttcctggtaa catcaaaggt gttcagaatg ccaacctcca gagactctac 1320tcttggaaac acagaggaga catcactatc tgtaagtgga accatttctg caatcacttc 1380caaagtttca accatatggt ggtcagacac tctgtcaaca gcactctccc ccagttctct 1440acctccaaaa atatccacag ctttccacac ccagcagagt gaaggtgcag agaccacagg 1500acggcctcat gagaggagct cattctctcc aggtgtgtct caagaaatat ttactctaca 1560tgaaacaaca acatggcctt cctcattctc cagcaaaggc cacacaactt ggtcacaaac 1620agaactgccc tcaacatcaa caggtgctgc cactaggctt gtcacaggaa atccatctac 1680agggacagct ggcactattc caagggtccc ctctaaggtc tcagcaatag gggaaccagg 1740agagcccacc acatactcct cccacagcac aactctccca aaaacaacag gggcaggcgc 1800ccagacacaa tggacacaag aaacggggac cactggagag gctcttctca gcagcccaag 1860ctacagtgtg actcagatga taaaaacggc cacatcccca tcttcttcac ctatgctgga 1920tagacacaca tcccaacaaa ttacaacggc accatcaaca aatcattcaa caatacattc 1980cacaagcacc tctcctcagg aatcaccagc tgtttcccaa aggggtcaca ctcaagcccc 2040gcagaccaca caagaatcac aaaccacgag gtccgtctcc cccatgactg acaccaagac 2100agtcaccacc ccaggttctt ccttcacagc cagtgggcac tcgccctcag aaattgttcc 2160tcaggacgca cccaccataa gtgcagcaac aacctttgcc ccagctccca ccggggatgg 2220tcacacaacc caggccccga ccacagcact gcaggcagca cccagcagcc atgatgccac 2280cctggggccc tcaggaggca cgtcactttc caaaacaggt gcccttactc tggccaactc 2340tgtagtgtca acaccagggg gcccagaagg acaatggaca tcagcctctg ccagcacctc 2400acctgacaca gcagcagcca tgacccatac ccaccaggct gagagcacag aggcctctgg 2460acaaacacag accagcgaac cggcctcctc agggtcacga accacctcag cgggcacagc 2520taccccttcc tcatccgggg cgagtggcac aacaccttca ggaagcgaag gaatatccac 2580ctcaggagag acgacaaggt tttcatcaaa cccctccagg gacagtcaca caacccagtc 2640aacaaccgaa ttgctgtccg cctcagccag tcatggtgcc atcccagtaa gcacaggaat 2700ggcgtcttcg atcgtccccg gcacctttca tcccaccctc tctgaggcct ccactgcagg 2760gagaccgaca ggacagtcaa gcccaacttc tcccagtgcc tctcctcagg agacagccgc 2820catttcccgg atggcccaga ctcagaggac aagaaccagc agagggtctg acactatcag 2880cctggcgtcc caggcaaccg acaccttctc aacagtccca cccacacctc catcgatcac 2940atccactggg cttacatctc cacaaaccga gacccacact ctgtcacctt cagggtctgg 3000taaaaccttc accacggccc tcatcagcaa cgccacccct cttcctgtca cctacgcttc 3060ctcggcatcc acaggtcaca ccacccctct tcatgtcacc gatgcttcct cagtatccac 3120aggtcacgcc acccctcttc ctgtcaccag cccttcctca gtatccacag gtcacaccac 3180ccctcttcct gtcaccgaca cttcctcaga atccacaggt cacgtcaccc ctcttcctgt 3240caccagcttt tcctcagcat ccacaggtga cagcacccct cttcctgtca ctgacacttc 3300ctcagcatcc acaggtcacg tcacccctct tcctgtcacc agcctttcct cagcatccac 3360aggtgacacc acccctcttc ctgtcactga cacttcctca gcatccacag gtcacgccac 3420ctctcttcct gtcaccgaca cttcctcagt atccacaggt cacaccaccc ctcttcctgt 3480caccgacact tcctcagcat ccacaggtca cgccacctct cttcctgtca ccgacacttc 3540ctcagtatcc acaggtcaca ccacccctct tcatgtcact gatgcttcct cagcatccac 3600aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 3660gcctcttcct gtcactagcc cttcctcagc atccacaggt cacgccaccc ctcttcttgt 3720caccgacact tcctcagcat ccacaggaca cgccacccct cttcctgtca ccgacgcttc 3780ctcagtgtcc acagatcacg ccacctctct tcctgtaacc atcccttccg cagcatccac 3840aggtcacacc acccctcttc ctgtcaccga cacttcctca gcatccacag gtcaggccac 3900ctctcttctt gtcaccgaca cttcctcagt atccacaggt gacaccacgc ctcttcctgt 3960cactagcact tcctcagcat ccacaggtca cgtcactcct cttcatgtca ccagcccttc 4020ctcagcatcc acaggtcacg ccacccctct tcctgtcacc agcctttcct cagcatccac 4080aggtgacacc atgcctcttc ctgtcactag cccttcctca gcatccacag gtgacaccac 4140ccctcttcct gtcaccgacg cttcctcagt atccacaggt cacaccaccc ctcttcatgt 4200cactgatgct tcctcagcat ccacaggtca ggccacccct cttcctgtca ccagcctttc 4260ctcagtatcc acaggtgaca ccacgcctct tcctgtcact agcccttcct cagcatccac 4320aggtcacgcc acccctcttc ttgtcaccga cacttcctca gcatccacag gacacgccac 4380ccctcttcct gtcaccgacg cttcctcagt gtccacagat cacgccacct ctcttcctgt 4440aaccatccct tccgcagcat ccacaggtca caccacccct cttcctgtca ccgacacttc 4500ctcagcatcc acaggtcagg ccacctctct tcttgtcacc gacacttcct cagtatccac 4560aggtgacacc acgcctcttc ctgtcactag cacttcctca gcatccacag gtcacgtcac 4620tcctcttcat gtcaccagcc cttcctcagc atccacaggt cacgccaccc ctcttcctgt 4680caccagcctt tcctcagcat ccacaggtga caccatgcct cttcctgtca ctagcccttc 4740ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacgcttcct cagtatccac 4800aggtcacacc acccctcttc ctgtcaccag cccttcctca gcatctacag gtcacaccac 4860ccctcttcct gtcaccgaca cttcctcagc atccaaaggt gacaccaccc ctcttcctgt 4920caccagccct tcctcagcat ctacaggtca caccacccct cttcctgtca ccgacacttc 4980ctcagcatcc acaggtgaca ccacccctct tcctgtcacc aatgcttcct cattatccac 5040aggtcacgcc acccctcttc atgtcaccag cccttcctca gcatccacag gtcacgccac 5100ccctcttcct gtcaccagca cttcctcagc atccaccggt cacgccaccc ctcttcctgt 5160caccggcctt tcctcagcta ccacagatga caccacccgt cttcctgtca ccgacgtttc 5220ctcggcatcc acaggtcagg ccacccctct tcctgtcacc agcctttcct cagtatccac 5280aggtgacacc acgcctcttc ctgtcactag cccttcctca gcatccacag gtcacgccag 5340ccctcttctt gtcactgacg cttcctcagc atccacaggt caggccaccc ctcttcctgt 5400caccgacact tcctcagtat ccacagctca cgccacccca cttcctgtca ccggcctttc 5460ttcagcttcc acagatgaca ccacccgtct tcctgtcacc gacgtttcct cggcatccac 5520aggtcaggcc atccctcttc ctgtcaccag cccttcctca gcatccacag gtgacaccac 5580ccctcttcct gtcaccgacg cttcctcagc atccacaggt gacaccacct ctcttcctgt 5640caccatccct tcctcagcat cttcaggtca caccacctct cttcctgtca ccgacgcttc 5700ctcagtgtcc acaggtcacg ccacctctct tcttgtcacc gacgcttcct cagtatccac 5760aggtgacacc acccctcttc ctgtcaccga cactaactca gcatccacag gtgacaccac 5820ccctcttcat gtcaccgacg cttcctcagt atccacaggt cacgccacct ctcttcctgt 5880caccagcctt tcctcagcat ccacaggtga caccacgcct cttcctgtca ctagcccttc 5940ctcagcatcc tcaggtcaca ccacccctct tcctgtcacc gacgcttcct cagtacccac 6000aggtcacgcc acctctcttc ctgtcaccga cgcttcctca gtgtccacag gtcacgccac 6060ccctcttcct gtcaccgacg cttcctcagt gtccacaggt catgccaccc ctcttccggt 6120caccgacact tcctcagtat ctacaggaca ggccacccct cttcctgtca ccagcctttc 6180ctcagcatcc actggtgaca ccacgccgct tcctgtcacc gatacttcct cagcatccac 6240aggtcaggac acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 6300gcctcttcct gtcactaacc cttcctcagc atccacaggt cacgccaccc ctcttcttgt 6360caccgacgct tcctcaatat ccacaggtca cgccacctct cttcttgtca ccgacgcttc 6420ctcagtatcc acaggtcacg ccaccgctct tcatgacacc gatgcttcct cattatccac 6480aggggacacc acccctcttc ctgtcaccag cccttcctca acatccacag gtgacaccac 6540ccctcttcct gtcaccgaaa cttcctcagt atccacaggt cacgccacct ctcttcctgt 6600caccgacact tcctcagcat ccacaggtca cgccacctct cttcctgtca ccgacacttc 6660ctcagcatcc acaggtcacg ccacccctct tcctgtcacc gacacttcct cagcatccac 6720aggtcaggcc acccctcttc ctgtcaccag cccttcctca gcatccacag gtcacgccat 6780ccctcttctt gtcaccgaca cttcctcagc atccacagga caggccaccc ctcttcctgt 6840caccagcctt tcctcagcat ccacaggtga caccacccct cttcctgtca ccgacgcttc 6900ctcagtgtcc acaggtcacg ccacctctct tcctgtcacc agcctttcct cagtatccac 6960aggtgacacc actcctcttc ctgtcactag cccttcctca gcatccacag gtcacgccac 7020ccctcttcat gtcaccgacg cttcctcagc atccacaggt cacgccaccc ctcttcctgt 7080caccagcctt tcctcagcat ccacaggtga caccacgcct cttcctgtca ctagcccttc 7140ctcagcatcc acaggtcacg ccacccctct tcatgtcacc gacgcttcct cagtatccac 7200aggtgacacc acccctcttc ctgtcaccag ctcttcctca gcatcctcag gtcacaccac 7260ccctcttcct gtcaccgacg cttcctcagc atccacaggt gacaccaccc ctcttcctgt 7320caccgacact tcctcagcat ccacaggtca cgccacccat cttcctgtca ccggcctttc 7380ctcagcttcc acaggtgaca ccacccgtct tcctgtcacc aacgtttcct cggcatccac 7440aggtcatgcc acccctcttc ctgtcaccag cacttcctca gcatccacag gtgacaccac 7500ccctcttcct ggcaccgaca cttcctcagt atccacaggt cacaccaccc ctcttcttgt 7560caccgacgct tcgtcagtat ccacaggtga caccacccgt cttcctgtca ccagcccttc 7620ctcagcatct acaggtcaca ccacccctct acctgtcacc gacactccct cagcatccac 7680aggtgacacc acccctcttc ctgtcaccaa tgcttcctca ttatccacac gtcacgccac 7740ctctcttcat gtcaccagcc cttcctcagc atccacaggt cacgccacct ctcttcctgt 7800caccgacact tccgcagcat ccacaggtca cgccacccct cttcctgtca ccagcacttc 7860ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacacttact cagcatccac 7920aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 7980gcctcttcct gtcactagcc cttcctcagc atccacaggt cacgccactc ctcttcttgt 8040caccgacgct tcctcagcat ccacaggtca ggccacccct cttcctgtca ccagcctttc 8100ctcagtatcc acaggtgaca ccacgcctct tcctgtcact agcccttcct cagcatccac 8160cggtcatgcc acctctcttc ctgtcaccga cacttcctca gcatccacag gtgacaccac 8220ctctcttcct gtcaccgaca cttcctcagc atacacaggt gacaccacct ctcttcctgt 8280caccgacact tcctcatcat ccacaggtga caccacccct cttcttgtca ccgagacttc 8340ctcagtatcc acaggtgaca ccacccctct tcctgtcacc gacacttcct cagcatccac 8400aggtcacgcc acccctcttc ctgtcaccaa cacttcctca gtatccacag gtcacgccac 8460ccctcttcat gtcaccagcc cttcctcagc atccacaggt cacaccaccc ctcttcctgt 8520caccgacgct tcgtcagtgt ccacaggtca cgccacctct cttcctgtca ccgacgcttc 8580ctcagtgttc acaggtcatg ccacctctct tcctgtcacc atcccttcct cagcatcctc 8640aggtcacacc acccctcttc ctgtcaccga cgcttcctca gtgtccacag gtcacgccac 8700ctctcttcct gtcaccgacg cttcctcagt gtccacaggt catgccaccc ctcttcctgt 8760caccgacgct tcctcagtgt ccacaggtca cgctacccct cttcctctca ccagcctttc 8820ctcagtatcc acaggtgaca ccacgcctct tcctgtcacc gacacttcct cagcatccac 8880aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 8940ccctcttcct gtcaccgaca cttcctcagc atccacaggt cacgccacct ctcttcctgt 9000caccgacact tcctcagcat ccacaggtca cgccacccct cttcctgaca ccgacacttc 9060ctcagcatcc acaggtcacg ccacccttct tcctgtcacc gacacttcct cagcatccat 9120aggtcacgcc acctctcttc ctgtcaccga cacttcctca atatccacag gtcacgccac 9180ccctcttcat gtcaccagcc cttcctcagc atccaccggt cacgccaccc cgcttcctgt 9240caccgacact tcctcagcat ccacaggtca cgccaaccct cttcatgtca ccagcccttc 9300ctcagcatcc accggtcacg ccaccccgct tcctgtcacc gacacttcct cagcatccac 9360aggtcacgcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 9420gcctcttcct gtcactagcc cttcctcagc atccacaggt cacaccaccc ctcttcctgt 9480caccgacact tcctcagcat ccacaggtca ggccaccgct cttcctgtca ccagcacttc 9540ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacacttcct cagcatccac 9600aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 9660gcctcttcct gtcactagcc cttcctcagc atccacaggt cacgccactc ctcttcttgt 9720caccgacgct tcctcagcat ccacaggtca ggccacccct cttcctgtca ccagcctttc 9780ctcagtatcc acaggtgaca ccacgcctct tcctgtcact agcccttcct cagcatccac 9840cggtcatgcc acctctcttc ctgtcaccga cacttcctca gcatccacag gtgacaccac 9900ctctcttcct gtcaccgaca cttcctcagc atacacaggt gacaccacct ctcttcctgt 9960caccgacact tcctcatcat ccacaggtga caccacccct cttcttgtca ccgagacttc 10020ctcagtatcc acaggtcacg ccactcctct tcttgtcacc gacgcttcct cagcatccac 10080aggtcacgcc acccctcttc atgtcaccag cccttcctca gcatccacag gtgacaccac 10140ccctgtgcct gtcaccgaca cttcctcagt atccacaggt cacgccaccc ctcttcctgt 10200caccggcctt tcctcagctt ccacaggtga caccacccgt cttcctgtca ccgacatttc 10260ctcggcatcc acaggtcagg ccacccctct tcctgtcacc aacacttcct cagtatccac 10320aggtgacacc atgcctcttc ctgtcactag cccttcctca gcatccacag gtcacgccac 10380ccctcttcct gtcaccagca cttcctcagc atccaccggt cacgccaccc ctgttcctgt 10440caccagcact tcctcagcat ctacaggtca caccacccct cttcctgtca ccgacacttc 10500ctcagcatcc acaggtgaca ccacccctct tcctgtcacc agcccttcct cagcatctac 10560aggtcacacc acccctcttc atgtcaccat cccttcctca gcatccacag gtgacaccag 10620cactcttcct gtcaccggcg cttcctcagc atccaccggt cacgccaccc ctcttcctgt 10680caccgacact tcctcagtat ccaccggtca cgccacgcct cttcctgtca ccagcctttc 10740ctcagtatcc acaggtgaca ccacccctct tcctgtcacc gacgcttcct cggcatccac 10800aggtcaggcc acccctcttc

ctgtcaccag cctttcctca gtatccacag gtgacaccac 10860ccctcttctt gtcaccgacg cttcctcagt atccacaggt cacgccaccc ctcttcctgt 10920caccgacact tcctcagcat ccacaggtga caccacccgt cttcctgtca cggacacttc 10980ctcagcatcc acaggtcagg ccacccctct tcctgtcacc agcctttcct cagtatccac 11040aggtgacacc acccctcttc ttgtcaccga cgcttcctca gtatccacag gtcacgccac 11100ccctcttcct gtcaccgaca cttcctcagc atccacaggt gacaccaccc gtcttcctgt 11160cacggacact tcctcagcat ccacaggtca ggccacccct cttcctgtca ccatcccttc 11220ctcatcatcc tcaggtcaca ccacccctct tcctgtcacc agcacttcct cagtatctac 11280aggtcacgtc acccctcttc atgtcaccag cccttcctca gcatccacag gtcacgtcac 11340ccctcttcct gtcaccagca cttcctcagc atccacaggt cacgccaccc ctcttcttgt 11400caccgacgct tcctcagtgt ccacaggtca cgccacgcct cttcctgtca ccgacgcttc 11460ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacacttcct cagcatccac 11520aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 11580ccctcttcct gtcaccgacg cttcctcagc atccacaggt cacgccaccc ctcttcctgt 11640caccatccct tcctcagtat ccacaggtga caccatgcct cttcctgtca ctagcccttc 11700ctcagcatcc acaggtcacg ccacccctct tcctgttacc ggcctttcct cagcttccac 11760aggtgacacc acccctcttc ctgtcaccga cacttcctca gcatccacac gtcacgccac 11820ccctcttcct gtcaccgaca cttcctcagc ttccacagat gacaccaccc gtcttcctgt 11880caccgacgtt tcctcggcat ccacaggaca tgccacccct cttcctgtca ccagcacttc 11940ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacacttcct cagtatccac 12000aggtcacgcc acctctcttc ctgtcaccag ccgttcctca gcatccacag gtcacgccac 12060cccccttcct gtcaccgaca cttcctcagt atccacaggt cacgccaccc ctcttcctgt 12120caccagcact tcctcagtat ctacaggtca cgccacccct cttcctgtca ccagcccttc 12180ctcagcatcc acaggtcacg ccacccctgt tcctgtcacc agcacttcct cagcatccac 12240aggtgacacc acccctcttc ctgtcaccaa tgcttcctca ttatccacag gtcacgccac 12300ccctcttcat gtcaccagcc cttcctcagc atccagaggt gacaccagca ctcttcctgt 12360caccgatgct tcctcagcat ccaccggtca cgccacccct cttcctctca ccagcctttc 12420ctcagtatcc acaggtgaca ccacgcctct tcctgtcacc gacacttcct ctgcatccac 12480aggtcaggcc acccctcttc ctgtcaccag cctttcctca gtatccacag gtgacaccac 12540gcctcttcct gtcaccatcc cttcctcagc atcctcaggt cacaccacct ctcttcctgt 12600caccgacgct tcctcagtgt ccacaggtca cggcacccct cttcctgtca ccagcacttc 12660ctcagcatcc acaggtgaca ccacccctct tcctgtcacc gacacttcct cagcatccac 12720aggtcacgcc acccctcttc ctgtcaccga cacttcctca gcatccacag gtcacgccac 12780ccctcttcct gtcaccagcc tttcctcagt atccacaggt cacgccaccc ctcttgctgt 12840cagcagtgct acctcagctt ccacagtatc ctcggactcc cctctgaaga tggaaacacc 12900aggaatgaca acaccgtcac tgaagacaga cggtgggaga cgcacagcca catcaccacc 12960ccccacaacc tcccagacca tcatttccac cattcccagc actgccatgc acacccgctc 13020cacagctgcc cccatcccca tcctgcctga gagaggagtt tccctcttcc cctatggggc 13080aggcgccggg gacctggagt tcgtcaggag gaccgtggac ttcacctccc cactcttcaa 13140gccggcgact ggcttccccc ttggctcctc tctccgtgat tccctctact tcacagacaa 13200tggccagatc atcttcccag agtcagacta ccagattttc tcctacccca acccactccc 13260aacaggcttc acaggccggg accctgtggc cctggtggct ccgttctggg acgatgctga 13320cttctccact ggtcggggga ccacatttta tcaggaatac gagacgttct atggtgaaca 13380cagcctgcta gtccagcagg ccgagtcttg gattagaaag atgacaaaca acgggggcta 13440caaggccagg tgggccctaa aggtcacgtg ggtcaatgcc cacgcctatc ctgcccagtg 13500gaccctcggg agcaacacct accaagccat cctctccacg gacgggagca ggtcctatgc 13560cctgtttctc taccagagcg gtgggatgca gtgggacgtg gcccagcgct caggcaaccc 13620ggtgctcatg ggcttctcta gtggagatgg ctatttcgaa aacagcccac tgatgtccca 13680gccagtgtgg gagaggtatc gccctgatag attcctgaat tccaactcag gcctccaagg 13740gctgcagttc tacaggctac accgggaaga aaggcccaac taccgtctcg agtgcctgca 13800gtggctgaag agccagcctc ggtggcccag ctggggctgg aaccaggtct cctgcccttg 13860ttcctggcag cagggacgac gggacttacg attccaaccc gtcagcatag gtcgctgggg 13920cctcggcagt aggcagctgt gcagcttcac ctcttggcga ggaggcgtgt gctgcagcta 13980cgggccctgg ggagagtttc gtgaaggctg gcacgtgcag cgtccttggc agttggccca 14040ggaactggag ccacagagct ggtgctgccg ctggaatgac aagccctacc tctgtgccct 14100gtaccagcag aggcggcccc acgtgggctg tgctacatac aggcccccac agcccgcctg 14160gatgttcggg gacccccaca tcaccacctt ggatggtgtc agttacacct tcaatgggct 14220gggggacttc ctgctggtcg gggcccaaga cgggaactcc tccttcctgc ttcagggccg 14280caccgcccag actggctcag cccaggccac caacttcatc gcctttgcgg ctcagtaccg 14340ctccagcagc ctgggccccg tcacggtcca atggctcctt gagcctcacg acgcaatccg 14400tgtcctgctg gataaccaga ctgtgacatt tcagcctgac catgaagacg gcggaggcca 14460ggagacgttc aacgccaccg gagtcctcct gagccgcaac ggctctgagg tctcggccag 14520cttcgacggc tgggccaccg tctcggtgat cgcgctctcc aacatcctcc acgcctccgc 14580cagcctcccg cccgagtacc agaaccgcac ggaggggctc ctgggggtct ggaataacaa 14640tccagaggac gacttcagga tgcccaatgg ctccaccatt cccccaggga gccctgagga 14700gatgcttttc cactttggaa tgacctggca gatcaacggg acaggcctcc ttggcaagag 14760gaatgaccag ctgccttcca acttcacccc tgttttctac tcacaactgc aaaaaaacag 14820ctcctgggct gaacatttga tctccaactg tgacggagat agctcatgca tctatgacac 14880cctggccctg cgcaacgcaa gcatcggact tcacacgagg gaagtcagta aaaactacga 14940gcaggcgaac gccaccctca atcagtaccc gccctccatc aatggtggtc gtgtgattga 15000agcctacaag gggcagacca cgctgattca gtacaccagc aatgctgagg atgccaactt 15060cacgctcaga gacagctgca ccgacttgga gctctttgag aatgggacgt tgctgtggac 15120acccaagtcg ctggagccat tcactctgga gattctagca agaagtgcca agattggctt 15180ggcatctgca ctccagccca ggactgtggt ctgccattgc aatgcagaga gccagtgttt 15240gtacaatcag accagcaggg tgggcaactc ctccctggag gtggctggct gcaagtgtga 15300cgggggcacc ttcggccgct actgcgaggg ctccgaggat gcctgtgagg agccgtgctt 15360cccgagtgtc cactgcgttc ctgggaaggg ctgcgaggcc tgccctccaa acctgactgg 15420ggatgggcgg cactgtgcgg ctctggggag ctctttcctg tgtcagaacc agtcctgccc 15480tgtgaattac tgctacaatc aaggccactg ctacatctcc cagactctgg gctgtcagcc 15540catgtgcacc tgccccccag ccttcactga cagccgctgc ttcctggctg ggaacaactt 15600cagtccaact gtcaacctag aacttccctt aagagtcatc cagctcttgc tcagtgaaga 15660ggaaaatgcc tccatggcag aagtcaacgc ctcggtggca tacagactgg ggaccctgga 15720catgcgggcc tttctccgca acagccaagt ggaacgaatc gattctgcag caccggcctc 15780gggaagcccc atccaacact ggatggtcat ctcggagttc cagtaccgcc ctcggggccc 15840ggtcattgac ttcctgaaca accagctgct ggccgcggtg gtggaggcgt tcttatacca 15900cgttccacgg aggagtgagg agcccaggaa cgacgtggtc ttccagccca tctccgggga 15960agacgtgcgc gatgtgacag ccctgaacgt gagcacgctg aaggcttact tcagatgcga 16020tggctacaag ggctacgacc tggtctacag cccccagagc ggcttcacct gcgtgtcccc 16080gtgcagtagg ggctactgtg accatggagg ccagtgccag cacctgccca gtgggccccg 16140ctgcagctgt gtgtccttct ccatctacac ggcctggggc gagcactgtg agcacctgag 16200catgaaactc gacgcgttct tcggcatctt ctttggggcc ctgggcggcc tcttgctgct 16260gggggtcggg acgttcgtgg tcctgcgctt ctggggttgc tccggggcca ggttctccta 16320tttcctgaac tcagctgagg ccttgccttg aaggggcagc tgtggcctag gctacctcaa 16380gactcacctc atccttaccg cacatttaag gcgccattgc ttttgggaga ctggaaaagg 16440gaaggtgact gaaggctgtc aggattcttc aaggagaatg aatactggga atcaagacaa 16500gactatacct tatccatagg cgcaggtgca cagggggagg ccataaagat caaacatgca 16560tggatgggtc ctcacgcaga cacacccaca gaaggacact agcctgtgca cgcgcgcgtg 16620cacacacaca cacacacaca cgagttcata atgtggtgat ggccctaagt taagcaaaat 16680gcttctgcac acaaaactct ctggtttact tcaaattaac tctatttaaa taaagtctct 16740ctgacttttt gtgtct 16756562613DNAHomo sapiens 56aggctgtgac agtcatctgt ctggacgcgc tgggtggatg cggggggctc ctgggaactg 60tgttggagcc gagcaagcgc tagccaggcg caagcgcgca cagactgtag ccatccgagg 120acacccccgc ccccccggcc cacccggaga cacccgcgca gaatcgcctc cggatcccct 180gcagtcggcg ggagtgttgg aggtcggcgc cggcccccgc cttccgcgcc ccccacggga 240aggaagcacc cccggtatta aaacgaacgg ggcggaaaga agccctcagt cgccggccgg 300gaggcgagcc gatgccgagc tgctccacgt ccaccatgcc gggcatgatc tgcaagaacc 360cagacctcga gtttgactcg ctacagccct gcttctaccc ggacgaagat gacttctact 420tcggcggccc cgactcgacc cccccggggg aggacatctg gaagaagttt gagctgctgc 480ccacgccccc gctgtcgccc agccgtggct tcgcggagca cagctccgag cccccgagct 540gggtcacgga gatgctgctt gagaacgagc tgtggggcag cccggccgag gaggacgcgt 600tcggcctggg gggactgggt ggcctcaccc ccaacccggt catcctccag gactgcatgt 660ggagcggctt ctccgcccgc gagaagctgg agcgcgccgt gagcgagaag ctgcagcacg 720gccgcgggcc gccaaccgcc ggttccaccg cccagtcccc gggagccggc gccgccagcc 780ctgcgggtcg cgggcacggc ggggctgcgg gagccggccg cgccggggcc gccctgcccg 840ccgagctcgc ccacccggcc gccgagtgcg tggatcccgc cgtggtcttc ccctttcccg 900tgaacaagcg cgagccagcg cccgtgcccg cagccccggc cagtgccccg gcggcgggcc 960ctgcggtcgc ctcgggggcg ggtattgccg ccccagccgg ggccccgggg gtcgcccctc 1020cgcgcccagg cggccgccag accagcggcg gcgaccacaa ggccctcagt acctccggag 1080aggacaccct gagcgattca gatgatgaag atgatgaaga ggaagatgaa gaggaagaaa 1140tcgacgtggt cactgtggag aagcggcgtt cctcctccaa caccaaggct gtcaccacat 1200tcaccatcac tgtgcgtccc aagaacgcag ccctgggtcc cgggagggct cagtccagcg 1260agctgatcct caaacgatgc cttcccatcc accagcagca caactatgcc gccccctctc 1320cctacgtgga gagtgaggat gcacccccac agaagaagat aaagagcgag gcgtccccac 1380gtccgctcaa gagtgtcatc cccccaaagg ctaagagctt gagcccccga aactctgact 1440cggaggacag tgagcgtcgc agaaaccaca acatcctgga gcgccagcgc cgcaacgacc 1500ttcggtccag ctttctcacg ctcagggacc acgtgccgga gttggtaaag aatgagaagg 1560ccgccaaggt ggtcattttg aaaaaggcca ctgagtatgt ccactccctc caggccgagg 1620agcaccagct tttgctggaa aaggaaaaat tgcaggcaag acagcagcag ttgctaaaga 1680aaattgaaca cgctcggact tgctagacgc ttctcaaaac tggacagtca ctgccacttt 1740gcacattttg attttttttt taaacaaaca ttgtgttgac attaagaatg ttggtttact 1800ttcaaatcgg tcccctgtcg agttcggctc tgggtgggca gtaggaccac cagtgtgggg 1860ttctgctggg accttggaga gcctgcatcc caggatgctg ggtggccctg cagcctcctc 1920cacctcacct ccatgacagc gctaaacgtt ggtgacggtt gggagcctct ggggctgttg 1980aagtcacctt gtgtgttcca agtttccaaa caacagaaag tcattccttc tttttaaaat 2040ggtgcttaag ttccagcaga tgccacataa ggggtttgcc atttgatacc cctggggaac 2100atttctgtaa ataccattga cacatccgcc ttttgtatac atcctgggta atgagaggtg 2160gcttttgcgg ccagtattag actggaagtt catacctaag tactgtaata atacctcaat 2220gtttgaggag catgttttgt atacaaatat attgttaatc tctgttatgt actgtactaa 2280ttcttacact gcctgtatac tttagtatga cgctgataca taactaaatt tgatacttat 2340attttcgtat gaaaatgagt tgtgaaagtt ttgagtagat attactttat cactttttga 2400actaagaaac ttttgtaaag aaatttacta tatatatatg cctttttcct agcctgtttc 2460ttcctgttaa tgtatttgtt catgtttggt gcatagaact gggtaaatgc aaagttctgt 2520gtttaatttc ttcaaaatgt atatatttag tgctgcatct tatagcactt tgaaatacct 2580catgtttatg aaaataaata gcttaaaatt aaa 2613571357DNAHomo sapiens 57acacccaggt ccccagcgat gtctccacca ccgctgctgc aacccctgct gctgctgctg 60cctctgctga atgtggagcc ttccggggcc acactgatcc gcatccctct tcatcgagtc 120caacctggac gcaggatcct gaacctactg aggggatgga gagaaccagc agagctcccc 180aagttggggg ccccatcccc tggggacaag cccatcttcg tacctctctc gaactacagg 240gatgtgcagt attttgggga aattgggctg ggaacgcctc cacaaaactt cactgttgcc 300tttgacactg gctcctccaa tctctgggtc ccgtccagga gatgccactt cttcagtgtg 360ccctgctggt tacaccaccg atttgatccc aaagcctcta gctccttcca ggccaatggg 420accaagtttg ccattcaata tggaactggg cgggtagatg gaatcctgag cgaggacaag 480ctgactattg gtggaatcaa gggtgcatca gtgattttcg gggaggctct ctgggagccc 540agcctggtct tcgcttttgc ccattttgat gggatattgg gcctcggttt tcccattctg 600tctgtggaag gagttcggcc cccgatggat gtactggtgg agcaggggct attggataag 660cctgtcttct ccttttacct caacagggac cctgaagagc ctgatggagg agagctggtc 720ctggggggct cggacccggc acactacatc ccacccctca ccttcgtgcc agtcacggtc 780cctgcctact ggcagatcca catggagcgt gtgaaggtgg gcccagggct gactctctgt 840gccaagggct gtgctgccat cctggatacg ggcacgtccc tcatcacagg acccactgag 900gagatccggg ccctgcatgc agccattggg ggaatcccct tgctggctgg ggagtacatc 960atcctgtgct cggaaatccc aaagctcccc gcagtctcct tccttcttgg gggggtctgg 1020tttaacctca cggcccatga ttacgtcatc cagactactc gaaatggcgt ccgcctctgc 1080ttgtccggtt tccaggccct ggatgtccct ccgcctgcag ggcccttctg gatcctcggt 1140gacgtcttct tggggacgta tgtggccgtc ttcgaccgcg gggacatgaa gagcagcgcc 1200cgggtgggcc tggcgcgcgc tcgcactcgc ggagcggacc tcggatgggg agagactgcg 1260caggcgcagt tccccgggtg acgcccaagt gaagcgcatg cgcagcgggt ggtcgcggag 1320gtcctgctac ccagtaaaaa tccactattt ccattga 1357583278DNAHomo sapiens 58agcggtgcgg gccgggcggg tgcattcagg ccaaggcggg gccgccggga tgctcagggt 60tccggagccg cggcccgggg aggcgaaagc ggagggggcc gcgccgccga ccccgtccaa 120gccgctcacg tccttcctca tccaggacat cctgcgggac ggcgcgcagc ggcaaggcgg 180ccgcacgagc agccagagac agcgcgaccc ggagccggag ccagagccag agccagaggg 240aggacgcagc cgcgccgggg cgcagaacga ccagctgagc accgggcccc gcgccgcgcc 300ggaggaggcc gagacgctgg cagagaccga gccagaaagg cacttggggt cttatctgtt 360ggactctgaa aacacttcag gcgcccttcc aaggcttccc caaaccccta agcagccgca 420gaagcgctcc cgagctgcct tctcccacac tcaggtgatc gagttggaga ggaagttcag 480ccatcagaag tacctgtcgg cccctgaacg ggcccacctg gccaagaacc tcaagctcac 540ggagacccaa gtgaagatat ggttccagaa cagacgctat aagactaagc gaaagcagct 600ctcctcggag ctgggagact tggagaagca ctcctctttg ccggccctga aagaggaggc 660cttctcccgg gcctccctgg tctccgtgta taacagctat ccttactacc catacctgta 720ctgcgtgggc agctggagcc cagctttttg gtaatgccag ctcaggtgac aaccattatg 780atcaaaaact gccttcccca gggtgtctct atgaaaagca caaggggcca aggtcaggga 840gcaagaggtg tgcacaccaa agctattgga gatttgcgtg gaaatctcag attcttcact 900ggtgagacaa tgaaacaaca gagacagtga aagttttaat acctaagtca ttcctccagt 960gcatactgta ggtcattttt tttgcttctg gctacctgtt tgaaggggag agagggaaaa 1020tcaagtggta ttttccagca ctttgtatga ttttggatga gttgtacacc caaggattct 1080gttctgcaac tccatcctcc tgtgtcactg aatatcaact ctgaaagagc aaacctaaca 1140ggagaaagga caaccaggat gaggatgtca ccaactgaat taaacttaag tccagaagcc 1200tcctgttggc cttggaatat ggccaaggct ctctctgtcc ctgtaaaaga gaggggcaaa 1260tagagagtct ccaagagaac gccctcatgc tcagcacata tttgcatggg agggggagat 1320gggtgggagg agatgaaaat atcagctttt cttattcctt tttattcctt ttaaaatggt 1380atgccaactt aagtatttac agggtggccc aaatagaaca agatgcactc gctgtgattt 1440taagacaagc tgtataaaca gaactccact gcaagagggg gggccgggcc aggagaatct 1500ccgcttgtcc aagacagggg cctaaggagg gtctccacac tgctgctagg ggctgttgca 1560tttttttatt agtagaaagt ggaaaggcct cttctcaact tttttccctt gggctggaga 1620atttagaatc agaagtttcc tggagttttc aggctatcat atatactgta tcctgaaagg 1680caacataatt cttccttccc tccttttaaa attttgtgtt cctttttgca gcaattactc 1740actaaagggc ttcattttag tccagatttt tagtctggct gcacctaact tatgcctcgc 1800ttatttagcc cgagatctgg tctttttttt tttttttttt tttttttttc cgtctcccca 1860aagctttatc tgtcttgact ttttaaaaaa gtttgggggc agattctgaa ttggctaaaa 1920gacatgcatt tttaaaacta gcaactctta tttctttcct ttaaaaatac atagcattaa 1980atcccaaatc ctatttaaag acctgacagc ttgagaaggt cactactgca tttataggac 2040cttctggtgg ttctgctgtt acgtttgaag tctgacaatc cttgagaatc tttgcatgca 2100gaggaggtaa gaggtattgg attttcacag aggaagaaca cagcgcagaa tgaagggcca 2160ggcttactga gctgtccagt ggagggctca tgggtgggac atggaaaaga aggcagccta 2220ggccctgggg agcccagtcc actgagcaag caagggactg agtgagcctt ttgcaggaaa 2280aggctaagaa aaaggaaaac cattctaaaa cacaacaaga aactgtccaa atgctttggg 2340aactgtgttt attgcctata atgggtcccc aaaatgggta acctagactt cagagagaat 2400gagcagagag caaaggagaa atctggctgt ccttccattt tcattctgtt atctcaggtg 2460agctggtaga ggggagacat tagaaaaaaa tgaaacaaca aaacaattac taatgaggta 2520cgctgaggcc tgggagtctc ttgactccac tacttaattc cgtttagtga gaaacctttc 2580aattttcttt tattagaagg gccagcttac tgttggtggc aaaattgcca acataagtta 2640atagaaagtt ggccaatttc accccatttt ctgtggtttg ggctccacat tgcaatgttc 2700aatgccacgt gctgctgaca ccgaccggag tactagccag cacaaaaggc agggtagcct 2760gaattgcttt ctgctcttta catttctttt aaaataagca tttagtgctc agtccctact 2820gagtactctt tctctcccct cctctgaatt taattctttc aacttgcaat ttgcaaggat 2880tacacatttc actgtgatgt atattgtgtt gcaaaaaaaa aaaaaaagtg tctttgttta 2940aaattacttg gtttgtgaat ccatcttgct ttttccccat tggaactagt cattaaccca 3000tctctgaact ggtagaaaaa catctgaaga gctagtctat cagcatctga caggtgaatt 3060ggatggttct cagaaccatt tcacccagac agcctgtttc tatcctgttt aataaattag 3120tttgggttct ctacatgcat aacaaaccct gctccaatct gtcacataaa agtctgtgac 3180ttgaagttta gtcagcaccc ccaccaaact ttatttttct atgtgttttt tgcaacatat 3240gagtgttttg aaaataaagt acccatgtct ttattaga 3278594185DNAHomo sapiens 59acactccctg gggcaggcgc tcacgcacgc tacaaacaca cactcctctt tcctccctcg 60cgcgccctct ctcatccttc ttcacgaagc gctcactcgc accctttctc tctctctctc 120tctctctcta acacgcacgc acactcccag ttgttcacac tcgggtcctc tccagcccga 180cgttctcctg gcacccacct gctccgcggc gccctgcgcg cccccctcgg tcgcgcccct 240tgcgctctcg gcccagaccg tcgcagctac agggggcctc gagccccggg gtgagcgtcc 300ccgtcccgct cctgctcctt cccataggga cgcgcctgat gcctgggacc ggccgctgag 360cccaagggga ccgaggaggc catggtagga gcgctcgcct gctgcggtgc ccgctgaggc 420catgccgggg ccccggcgcc ccgctggctc ccgcctgcgc ctgctcctgc tcctgctgct 480gccgccgctg ctgctgctgc tccggggcag ccacgcgggc aacctgacgg tagccgtggt 540actgccgctg gccaatacct cgtacccctg gtcgtgggcg cgcgtgggac ccgccgtgga 600gctggccctg gcccaggtga aggcgcgccc cgacttgctg ccgggctgga cggtccgcac 660ggtgctgggc agcagcgaaa acgcgctggg cgtctgctcc gacaccgcag cgcccctggc 720cgcggtggac ctcaagtggg agcacaaccc cgctgtgttc ctgggccccg gctgcgtgta 780cgccgccgcc ccagtggggc gcttcaccgc gcactggcgg gtcccgctgc tgaccgccgg 840cgccccggcg ctgggcttcg gtgtcaagga cgagtatgcg ctgaccaccc gcgcggggcc 900cagctacgcc aagctggggg acttcgtggc ggcgctgcac cgacggctgg gctgggagcg 960ccaagcgctc atgctctacg cctaccggcc gggtgacgaa gagcactgct tcttcctcgt 1020ggaggggctg ttcatgcggg tccgcgaccg cctcaatatt acggtggacc acctggagtt 1080cgccgaggac gacctcagcc actacaccag gctgctgcgg accatgccgc gcaaaggccg 1140agttatctac atctgcagct cccctgatgc cttcagaacc ctcatgctcc tggccctgga 1200agctggcttg tgtggggagg actacgtttt cttccacctg gatatctttg ggcaaagcct 1260gcaaggtgga cagggccctg ctccccgcag gccctgggag agaggggatg ggcaggatgt 1320cagtgcccgc caggcctttc aggctgccaa aatcattaca tataaagacc cagataatcc 1380cgagtacttg gaattcctga agcagttaaa acacctggcc tatgagcagt tcaacttcac 1440catggaggat ggcctggtga acaccatccc agcatccttc cacgacgggc tcctgctcta 1500tatccaggca gtgacggaga ctctggcaca tgggggaact gttactgatg gggagaacat 1560cactcagcgg atgtggaacc gaagctttca aggtgtgaca ggatacctga aaattgatag 1620cagtggcgat cgggaaacag acttctccct ctgggatatg gatcccgaga atggtgcctt

1680cagggttgta ctgaactaca atgggacttc ccaagagctg gtggctgtgt cggggcgcaa 1740actgaactgg cccctggggt accctcctcc tgacatcccc aaatgtggct ttgacaacga 1800agacccagca tgcaaccaag atcacctttc caccctggag gtgctggctt tggtgggcag 1860cctctccttg ctcggcattc tgattgtctc cttcttcata tacaggaaga tgcagctgga 1920gaaggaactg gcctcggagc tgtggcgggt gcgctgggag gacgttgagc ccagtagcct 1980tgagaggcac ctgcggagtg caggcagccg gctgaccctg agcgggagag gctccaatta 2040cggctccctg ctaaccacag agggccagtt ccaagtcttt gccaagacag catattataa 2100gggcaacctc gtggctgtga aacgtgtgaa ccgtaaacgc attgagctga cacgaaaagt 2160cctgtttgaa ctgaagcata tgcgggatgt gcagaatgaa cacctgacca ggtttgtggg 2220agcctgcacc gaccccccca atatctgcat cctcacagag tactgtcccc gtgggagcct 2280gcaggacatt ctggagaatg agagcatcac cctggactgg atgttccggt actcactcac 2340caatgacatc gtcaagggca tgctgtttct acacaatggg gctatctgtt cccatgggaa 2400cctcaagtca tccaactgcg tggtagatgg gcgctttgtg ctcaagatca ccgactatgg 2460gctggagagc ttcagggacc tggacccaga gcaaggacac accgtttatg ccaaaaagct 2520gtggacggcc cctgagctcc tgcgaatggc ttcaccccct gtgcggggct cccaggctgg 2580tgacgtatac agctttggga tcatccttca ggagattgcc ctgaggagtg gggtcttcca 2640cgtggaaggt ttggacctga gccccaaaga gatcatcgag cgggtgactc ggggtgagca 2700gccccccttc cggccctccc tggccctgca gagtcacctg gaggagttgg ggctgctcat 2760gcagcggtgc tgggctgagg acccacagga gaggccacca ttccagcaga tccgcctgac 2820gttgcgcaaa tttaacaggg agaacagcag caacatcctg gacaacctgc tgtcccgcat 2880ggagcagtac gcgaacaatc tggaggaact ggtggaggag cggacccagg catacctgga 2940ggagaagcgc aaggctgagg ccctgctcta ccagatcctg cctcactcag tggctgagca 3000gctgaagcgt ggggagacgg tgcaggccga agcctttgac agtgttacca tctacttcag 3060tgacattgtg ggtttcacag cgctgtcggc ggagagcaca cccatgcagg tggtgaccct 3120gctcaatgac ctgtacactt gctttgatgc tgtcatagac aactttgatg tgtacaaggt 3180ggagacaatt ggcgatgcct acatggtggt gtcagggctc cctgtgcgga acgggcggct 3240acacgcctgc gaggtagccc gcatggccct ggcactgctg gatgctgtgc gctccttccg 3300aatccgccac cggccccagg agcagctgcg cttgcgcatt ggcatccaca caggacctgt 3360gtgtgctgga gtggtgggac tgaagatgcc ccgttactgt ctctttgggg atacagtcaa 3420cacagcctca agaatggagt ctaatgggga agccctgaag atccacttgt cttctgagac 3480caaggctgtc ctggaggagt ttggtggttt cgagctggag cttcgagggg atgtagaaat 3540gaagggcaaa ggcaaggttc ggacctactg gctccttggg gagaggggga gtagcacccg 3600aggctgacct gcctcctctc ctatccctcc acacctccct accctgtgcc agaagcaaca 3660gaggtgccag gcctcagcct cacccacagc agccccatcg ccaaaggatg gaagtaattt 3720gaatagctca ggtgtgctga ccccagtgaa gacaccagat aggacctctg agaggggact 3780ggcatggggg gatctcagag cttacaggct gagccaagcc cacggccatg cacagggaca 3840ctcacacagg cacacgcacc tgctctccac ctggactcag gccgggctgg gctgtggatt 3900cctgatcccc tcccctcccc atgctctcct ccctcagcct tgctaccctg tgacttactg 3960ggaggagaaa gagtcacctg aaggggaaca tgaaaagaga ctaggtgaag agagggcagg 4020ggagcccaca tctggggctg gcccacaata cctgctcccc cgaccccctc cacccagcag 4080tagacacagt gcacagggga gaagaggggt ggcgcagaag ggttgggggc ctgtatgcct 4140tgcttctacc atgagcagag acaattaaaa tctttattcc agtga 4185604055DNAHomo sapiens 60gggaacaaac ttcagaagga ggagagacac cgggcccagg gcaccctcgc gggcggaccc 60aagcagtgag ggcctgcagc cggccggcca gggcagcggc aggcgcggcc cggacctacg 120ggaggaagcc ccgagccctc ggcgggctgc gagcgactcc ccggcgatgc ctcacaactc 180catcagatct ggccatggag ggctgaacca gctgggaggg gcctttgtga atggcagacc 240tctgccggaa gtggtccgcc agcgcatcgt agacctggcc caccagggtg taaggccctg 300cgacatctct cgccagctcc gcgtcagcca tggctgcgtc agcaagatcc ttggcaggta 360ctacgagact ggcagcatcc ggcctggagt gatagggggc tccaagccca aggtggccac 420ccccaaggtg gtggagaaga ttggggacta caaacgccag aaccctacca tgtttgcctg 480ggagatccga gaccggctcc tggctgaggg cgtctgtgac aatgacactg tgcccagtgt 540cagctccatt aatagaatca tccggaccaa agtgcagcaa ccattcaacc tccctatgga 600cagctgcgtg gccaccaagt ccctgagtcc cggacacacg ctgatcccca gctcagctgt 660aactcccccg gagtcacccc agtcggattc cctgggctcc acctactcca tcaatgggct 720cctgggcatc gctcagcctg gcagcgacaa gaggaaaatg gatgacagtg atcaggatag 780ctgccgacta agcattgact cacagagcag cagcagcgga ccccgaaagc accttcgcac 840ggatgccttc agccagcacc acctcgagcc gctcgagtgc ccatttgagc ggcagcacta 900cccagaggcc tatgcctccc ccagccacac caaaggcgag cagggcctct acccgctgcc 960cttgctcaac agcaccctgg acgacgggaa ggccaccctg accccttcca acacgccact 1020ggggcgcaac ctctcgactc accagaccta ccccgtggtg gcagatcctc actcaccctt 1080cgccataaag caggaaaccc ccgaggtgtc cagttctagc tccacccctt cctctttatc 1140tagctccgcc tttttggatc tgcagcaagt cggctccggg gtcccgccct tcaatgcctt 1200tccccatgct gcctccgtgt acgggcagtt cacgggccag gccctcctct cagggcgaga 1260gatggtgggg cccacgctgc ccggataccc accccacatc cccaccagcg gacagggcag 1320ctatgcctcc tctgccatcg caggcatggt ggcaggaagt gaatactctg gcaatgccta 1380tggccacacc ccctactcct cctacagcga ggcctggcgc ttccccaact ccagcttgct 1440gagttcccca tattattaca gttccacatc aaggccgagt gcaccgccca ccactgccac 1500ggcctttgac catctgtagt tgccatgggg acagtgggag cgactgagca acaggaggac 1560tcagcctggg acaggcccca gagagtcaca caaaggaatc tttatttatt acatgaaaaa 1620taaccacaag tccagcattg cggcacactc cctgtgtggt taatttaatg aaccatgaaa 1680gacaggatga ccttggacaa ggccaaactg tcctccaaga ctccttaatg aggggcagga 1740gtcccaggga aagagaacca tgccatgctg aaaaagacaa aattgaagaa gaaatgtagc 1800ccccagccgg tacccaccaa aggagagaag aagcaatagc cgaggaactt ggggggatgg 1860cgaatggttc ctgcccgggc ccaaggggtg cacagggcac ctccatggct ccattattaa 1920cacaactcta gcaattatgg accataagca cttccctcca gcccacaagt cacagcctgg 1980tgccgaggct ctcctcacca gccacccagg gagtcacctc cctcagcctc ccgcctgccc 2040cacacggagg ctctggctgt cctctttctc cactccattt gcttggctct ttctacacct 2100ccctcttggg catgggctga gggctggagc gagtccctca gaaattccac caggctgtca 2160gctgacctct tttgcctgct gctgtgaagg tatagcacca ccccaggtcc tcctgcagtg 2220cggcatcccc ttggcagctg ccgtcagcca ggccagcccc agggagctta aaacagacat 2280tccacagggc ctgggcccct gggaggtgag gtgtggtgtg cggcttcacc cagggcagaa 2340caaggcagaa tcgcaggaaa cccgcttccc cttcctgaca gctcctgcca agccaaatgt 2400gcttcctgca gctcacgccc accagctact gaagggaccc aaggcacccc ctgaagccag 2460cgatagaggg tccctctctg ctccccagca gctcctgccc ccaaggcctg actgtatata 2520ctgtaaatga aactttgttt gggtcaagct tccttctttc taacccccag actttggcct 2580ctgagtgaaa tgtctctctt tgccctgtgg ggcttctctc cttgatgctt ctttcttttt 2640ttaaagacaa cctgccatta ccacatgact caataaacca ttgctcttca tctcaggctt 2700tggggttggc tggggaagga ggcatcccgg ggctgggctt tctcccaaga acatcagagc 2760tgagtagccg acaaactcac tttggggccg tgggctggaa gggaccatct gatgccccag 2820agctctggct tggccttctc cctctgcctt taattcacgt tgaacgctgg gtacctcact 2880catcccaagt tcttcaacac tgagcaaatg caaggatagc acagtactga gccaaccata 2940gactccccac aaggagttgc tgttgttatt aacaggaagc cagagaatca gcagggtggg 3000ttagtgaggg atccgggaat agctgtgact ggagcctgca taaacagctc tgaagggaga 3060gagaagactg ggctctcttg tgtgccaggc acagtatgga aggcttcata taagttaagc 3120tgaaattagc cctgttttac atacagcttc attttacata tgaggaaact gaggctttga 3180aaaaaatgag atgtcttgtc caagatgaaa agtagtagat tcaaccaagt cctcttactc 3240taagcccaac gcttttaccc aaaaccccag agtcctcatc agggatgcca aatggttcta 3300gacccagtgg aggttctgga gctgccactg gggatttaat ttcttttgat ttgctaaaga 3360tttgacctga ctgaatggag aggtagagtg tagtgtggcc aggacaaggt gagggaggct 3420gtagagactt agcactttag gccaaccacc tccaggaaat ctgggaaatg caatgtgaca 3480gctcgggctc tgcactccag ggggctgtct ggtgtccaca tggaccttct ccatgtggga 3540cacagctgga acaagggggc aggggcctgc agctgggatg cccaggtgaa tatgggcagc 3600tggacaaaca acactgggat tgagtcagat agaaggggcc caaggactcc agggctggga 3660ggacagaggc tgggagagag ggctcttacc tccttaggcc tcccaaagag cggttaggga 3720tgctgccatg gatggcatgg cagggggaac cctcctggaa gaaaatccat ctcttctgaa 3780gggatctgag atgcggctgg tttttcaatg gcagaacttc cctctgcagc gcgactccga 3840atccatgaca tctgagagtc ttcctgacca caaacctctg ggatcccgag ggctccctac 3900ccaagaatca ctttgagcac agcatcccaa ggagcccata gagcgatccc ttgcattcac 3960agccacagcc cctctgggga cactctgtac ccccggcaga ccctttccaa ctcacaacca 4020ataaaggggc ttgggctgtg ctttgactaa ggtga 4055612304DNAHomo sapiens 61acagctcccc cgcagccaga agccgggcct gcagcgcctc agcaccgctc cgggacaccc 60cacccgcttc ccaggcgtga cctgtcaaca ggtctgtatt ggcgacaaaa ggagcagccc 120tgaatgtagg gaaagcaggg cggagtcctc tgcaggctcg ggggagggga ggggcgtgaa 180tgcgtggatt tctgtggaga gtggaaacac ggggagtcga ggggagcatg cgcgggcctc 240agaaagttct gggaaaccga ctcccgggag cagggaggaa cgcgcgctcc agagacaact 300tcgcggtgtg gtgaactctc tgaggaaaaa cacgtgcgtg gcaacaagtg actgagacct 360agaaatccaa gcgttggagg tcctgaggcc agcctaagtc gcttcaaaat ggaacgaagg 420cgtttgtggg gttccattca gagccgatac atcagcatga gtgtgtggac aagcccacgg 480agacttgtgg agctggcagg gcagagcctg ctgaaggatg aggccctggc cattgccgcc 540ctggagttgc tgcccaggga gctcttcccg ccactcttca tggcagcctt tgacgggaga 600cacagccaga ccctgaaggc aatggtgcag gcctggccct tcacctgcct ccctctggga 660gtgctgatga agggacaaca tcttcacctg gagaccttca aagctgtgct tgatggactt 720gatgtgctcc ttgcccagga ggttcgcccc aggaggtgga aacttcaagt gctggattta 780cggaagaact ctcatcagga cttctggact gtatggtctg gaaacagggc cagtctgtac 840tcatttccag agccagaagc agctcagccc atgacaaaga agcgaaaagt agatggtttg 900agcacagagg cagagcagcc cttcattcca gtagaggtgc tcgtagacct gttcctcaag 960gaaggtgcct gtgatgaatt gttctcctac ctcattgaga aagtgaagcg aaagaaaaat 1020gtactacgcc tgtgctgtaa gaagctgaag atttttgcaa tgcccatgca ggatatcaag 1080atgatcctga aaatggtgca gctggactct attgaagatt tggaagtgac ttgtacctgg 1140aagctaccca ccttggcgaa attttctcct tacctgggcc agatgattaa tctgcgtaga 1200ctcctcctct cccacatcca tgcatcttcc tacatttccc cggagaagga agagcagtat 1260atcgcccagt tcacctctca gttcctcagt ctgcagtgcc tgcaggctct ctatgtggac 1320tctttatttt tccttagagg ccgcctggat cagttgctca ggcacgtgat gaaccccttg 1380gaaaccctct caataactaa ctgccggctt tcggaagggg atgtgatgca tctgtcccag 1440agtcccagcg tcagtcagct aagtgtcctg agtctaagtg gggtcatgct gaccgatgta 1500agtcccgagc ccctccaagc tctgctggag agagcctctg ccaccctcca ggacctggtc 1560tttgatgagt gtgggatcac ggatgatcag ctccttgccc tcctgccttc cctgagccac 1620tgctcccagc ttacgacctt aagcttctac gggaattcca tctccatatc tgccctgcag 1680agtctcctgc agcacctcat cgggctgagc aatctgaccc acgtgctgta tcctgtcccc 1740ctggagagtt atgaggacat ccatggtacc ctccacctgg agaggcttgc ctatctgcat 1800gccaggctca gggagttgct gtgtgagttg gggcggccca gcatggtctg gcttagtgcc 1860aacccctgtc ctcactgtgg ggacagaacc ttctatgacc cggagcccat cctgtgcccc 1920tgtttcatgc ctaattagct gggtgcacat atcaaatgct tcattctgca tacttggaca 1980ctaaagccag gatgtgcatg catcttgaag caacaaagca gccacagttt cagacaaatg 2040ttcagtgtga gtgaggaaaa catgttcagt gaggaaaaaa cattcagaca aatgttcagt 2100gaggaaaaaa aggggaagtt gggggtaggc agatgttgac ttgaggagtt aatgtgatct 2160ttggggagat acatcttata gagttagaaa tagaatctga atttctaaag ggagattctg 2220gcttgggaag tacatgtagg agttaatccc tgtgtagact gttgtaaaga aactgttgaa 2280aataaagaga agcaatgtga agca 230462982DNAHomo sapiens 62acagcccacc agtgaccacg aaggctgtgc tgcttgccct gttgatggca ggcttggccc 60tgcagccagg cactgccctg ctgtgctact cctgcaaagc ccaggtgagc aacgaggact 120gcctgcaggt ggagaactgc acccagctgg gggagcagtg ctggaccgcg cgcatccgcg 180cagttggcct cctgaccgtc atcagcaaag gctgcagctt gaactgcgtg gatgactcac 240aggactacta cgtgggcaag aagaacatca cgtgctgtga caccgacttg tgcaacgcca 300gcggggccca tgccctgcag ccggctgctg ccatccttgc gctgctccct gcactcggcc 360tgctgctctg gggacccggc cagctctagg ctctgggggg ccccgctgca gcccacactg 420ggtgtggtgc cccaggcctc tgtgccactc ctcacacacc cggcccagtg ggagcctgtc 480ctggttcctg aggcacatcc taacgcaagt ctgaccatgt atgtctgcgc ccctgtcccc 540caccctgacc ctcccatggc cctctccagg actcccaccc ggcagatcgg ctctattgac 600acagatccgc ctgcagatgg cccctccaac cctctctgct gctgtttcca tggcccagca 660ttctccaccc ttaaccctgt gctcaggcac ctcttccccc aggaagcctt ccctgcccac 720cccatctatg acttgagcca ggtctggtcc gtggtgtccc ccgcacccag caggggacag 780gcactcagga gggcccggta aaggctgaga tgaagtggac tgagtagaac tggaggacag 840gagtcgacgt gagttcctgg gagtctccag agatggggcc tggaggcctg gaggaagggg 900ccaggcctca cattcgtggg gctccctgaa tggcagcctc agcacagcgt aggcccttaa 960taaacacctg ttggataagc ca 982633458DNAHomo sapiens 63gccgtcgttg ttggccacag cgtgggaagc agctctgggg gagctcggag ctcccgatca 60cggcttcttg ggggtagcta cggctgggtg tgtagaacgg ggccggggct ggggctgggt 120cccctagtgg agacccaagt gcgagaggca agaactctgc agcttcctgc cttctgggtc 180agttccttat tcaagtctgc agccggctcc cagggagatc tcggtggaac ttcagaaacg 240ctgggcagtc tgcctttcaa ccatgcccct gtccctggga gccgagatgt gggggcctga 300ggcctggctg ctgctgctgc tactgctggc atcatttaca ggccggtgcc ccgcgggtga 360gctggagacc tcagacgtgg taactgtggt gctgggccag gacgcaaaac tgccctgctt 420ctaccgaggg gactccggcg agcaagtggg gcaagtggca tgggctcggg tggacgcggg 480cgaaggcgcc caggaactag cgctactgca ctccaaatac gggcttcatg tgagcccggc 540ttacgagggc cgcgtggagc agccgccgcc cccacgcaac cccctggacg gctcagtgct 600cctgcgcaac gcagtgcagg cggatgaggg cgagtacgag tgccgggtca gcaccttccc 660cgccggcagc ttccaggcgc ggctgcggct ccgagtgctg gtgcctcccc tgccctcact 720gaatcctggt ccagcactag aagagggcca gggcctgacc ctggcagcct cctgcacagc 780tgagggcagc ccagccccca gcgtgacctg ggacacggag gtcaaaggca caacgtccag 840ccgttccttc aagcactccc gctctgctgc cgtcacctca gagttccact tggtgcctag 900ccgcagcatg aatgggcagc cactgacttg tgtggtgtcc catcctggcc tgctccagga 960ccaaaggatc acccacatcc tccacgtgtc cttccttgct gaggcctctg tgaggggcct 1020tgaagaccaa aatctgtggc acattggcag agaaggagct atgctcaagt gcctgagtga 1080agggcagccc cctccctcat acaactggac acggctggat gggcctctgc ccagtggggt 1140acgagtggat ggggacactt tgggctttcc cccactgacc actgagcaca gcggcatcta 1200cgtctgccat gtcagcaatg agttctcctc aagggattct caggtcactg tggatgttct 1260tgacccccag gaagactctg ggaagcaggt ggacctagtg tcagcctcgg tggtggtggt 1320gggtgtgatc gccgcactct tgttctgcct tctggtggtg gtggtggtgc tcatgtcccg 1380ataccatcgg cgcaaggccc agcagatgac ccagaaatat gaggaggagc tgaccctgac 1440cagggagaac tccatccgga ggctgcattc ccatcacacg gaccccagga gccagccgga 1500ggagagtgta gggctgagag ccgagggcca ccctgatagt ctcaaggaca acagtagctg 1560ctctgtgatg agtgaagagc ccgagggccg cagttactcc acgctgacca cggtgaggga 1620gatagaaaca cagactgaac tgctgtctcc aggctctggg cgggccgagg aggaggaaga 1680tcaggatgaa ggcatcaaac aggccatgaa ccattttgtt caggagaatg ggaccctacg 1740ggccaagccc acgggcaatg gcatctacat caatgggcgg ggacacctgg tctgacccag 1800gcctgcctcc cttccctagg cctggctcct tctgttgaca tgggagattt tagctcatct 1860tgggggcctc cttaaacacc cccatttctt gcggaagatg ctccccatcc cactgactgc 1920ttgaccttta cctccaaccc ttctgttcat cgggagggct ccaccaattg agtctctccc 1980accatgcatg caggtcactg tgtgtgtgca tgtgtgcctg tgtgagtgtt gactgactgt 2040gtgtgtgtgg aggggtgact gtccgtggag gggtgactgt gtccgtggtg tgtattatgc 2100tgtcatatca gagtcaagtg aactgtggtg tatgtgccac gggatttgag tggttgcgtg 2160ggcaacactg tcagggtttg gcgtgtgtgt catgtggctg tgtgtgacct ctgcctgaaa 2220aagcaggtat tttctcagac cccagagcag tattaatgat gcagaggttg gaggagagag 2280gtggagactg tggctcagac ccaggtgtgc gggcatagct ggagctggaa tctgcctccg 2340gtgtgaggga acctgtctcc taccacttcg gagccatggg ggcaagtgtg aagcagccag 2400tccctgggtc agccagaggc ttgaactgtt acagaagccc tctgccctct ggtggcctct 2460gggcctgctg catgtacata ttttctgtaa atatacatgc gccgggagct tcttgcagga 2520atactgctcc gaatcacttt taattttttt cttttttttt tcttgccctt tccattagtt 2580gtatttttta tttattttta tttttatttt tttttagaga tggagtctca ctatgttgct 2640caggctggcc ttgaactcct gggctcaagc aatcctcctg cctcagcctc cctagtagct 2700gggactttaa gtgtacacca ctgtgcctgc tttgaatcct ttacgaagag aaaaaaaaaa 2760ttaaagaaag cctttagatt tatccaatgt ttactactgg gattgcttaa agtgaggccc 2820ctccaacacc agggggttaa ttcctgtgat tgtgaaaggg gctacttcca aggcatcttc 2880atgcaggcag ccccttggga gggcacctga gagctggtag agtctgaaat tagggatgtg 2940agcctcgtgg ttactgagta aggtaaaatt gcatccacca ttgtttgtga taccttaggg 3000aattgcttgg acctggtgac aagggctcct gttcaatagt ggtgttgggg agagagagag 3060cagtgattat agaccgagag agtaggagtt gaggtgaggt gaaggaggtg ctgggggtga 3120gaatgtcgcc tttccccctg ggttttggat cactaattca aggctcttct ggatgtttct 3180ctgggttggg gctggagttc aatgaggttt atttttagct ggcccaccca gatacactca 3240gccagaatac ctagatttag tacccaaact cttcttagtc tgaaatctgc tggatttctg 3300gcctaaggga gaggctccca tccttcgttc cccagccagc ctaggacttc gaatgtggag 3360cctgaagatc taagatccta acatgtacat tttatgtaaa tatgtgcata tttgtacata 3420aaatgatatt ctgtttttaa ataaacagac aaaacttg 345864471DNAHomo sapiens 64acattttctc ggccctgcca gcccccagga ggaaggtggg tctgaatcta gcaccatgac 60ggaactagag acagccatgg gcatgatcat agacgtcttt tcccgatatt cgggcagcga 120gggcagcacg cagaccctga ccaaggggga gctcaaggtg ctgatggaga aggagctacc 180aggcttcctg cagagtggaa aagacaagga tgccgtggat aaattgctca aggacctgga 240cgccaatgga gatgcccagg tggacttcag tgagttcata gtgttcgtgg ctgcaatcac 300gtctgcctgt cacaagtact ttgagaaggc aggactcaaa tgatgccctg gagatgtcac 360agattcctgg cagagccatg gtcccaggct tcccaaaagt gtttgttggc aattattccc 420ctaggctgag cctgctcatg tacctctgat taataaatgc ttatgaaatg a 471655209DNAHomo sapiens 65aattactggg acatgcgcgt tccggccgaa ggggggtaaa tttcccaact ccaggaattt 60gtggcggaga gggcaaataa ctgcggctct cccggcgccc cgatgctcgc accatgtcga 120ggcgcaagca ggcgaaaccc cagcacatca actcggagga ggaccagggc gagcagcagc 180cgcagcagca gaccccggag tttgcagatg cggccccagc ggcgcccgcg gcgggggagc 240tgggtgctcc agtgaaccac ccagggaatg acgaggtggc gagtgaggat gaagccacag 300taaagcggct tcgtcgggag gagacgcacg tctgtgagaa atgctgtgcg gagttcttca 360gcatctctga gttcctggaa cataagaaaa attgcactaa aaatccacct gtcctcatca 420tgaatgacag cgaggggcct gtgccttcag aagacttctc cggagctgta ctgagccacc 480agcccaccag tcccggcagt aaggactgtc acagggagaa tggcggcagc tcagaggaca 540tgaaggagaa gccggatgcg gagtctgtgg tgtacctaaa gacagagaca gccctgccac 600ccacccccca ggacataagc tatttagcca aaggcaaagt ggccaacact aatgtgacct 660tgcaggcact acggggcacc aaggtggcgg tgaatcagcg gagcgcggat gcactccctg 720cccccgtgcc tggtgccaac agcatcccgt gggtcctcga gcagatcttg tgtctgcagc 780agcagcagct acagcagatc cagctcaccg agcagatccg catccaggtg aacatgtggg 840cctcccacgc cctccactca agcggggcag gggccgacac tctgaagacc ttgggcagcc 900acatgtctca gcaggtttct gcagctgtgg ctttgctcag ccagaaagct ggaagccaag 960gtctgtctct ggatgccttg aaacaagcca agctacctca cgccaacatc ccttctgcca

1020ccagctccct gtccccaggg ctggcaccct tcactctgaa gccggatggg acccgggtgc 1080tcccgaacgt catgtcccgc ctcccgagcg ctttgcttcc tcaggccccg ggctcggtgc 1140tcttccagag ccctttctcc actgtggcgc tagacacatc caagaaaggg aaggggaagc 1200caccgaacat ctccgcggtg gatgtcaaac ccaaagacga ggcggccctc tacaagcaca 1260agtgtaagta ctgtagcaag gtttttggga ctgatagctc cttgcagatc cacctccgct 1320cccacactgg agagagaccc ttcgtgtgct ctgtctgtgg tcatcgcttc accaccaagg 1380gcaacctcaa ggtgcacttt caccgacatc cccaggtgaa ggcaaacccc cagctgtttg 1440ccgagttcca ggacaaagtg gcggccggca atggcatccc ctatgcactc tctgtacctg 1500accccataga tgaaccgagt ctttctttag acagcaaacc tgtccttgta accacctctg 1560tagggctacc tcagaatctt tcttcgggga ctaatcccaa ggacctcacg ggtggctcct 1620tgcccggtga cctgcagcct gggccttctc cagaaagtga gggtggaccc acactccctg 1680gggtgggacc aaactataat tccccaaggg ctggtggctt ccaagggagt gggacccctg 1740agccagggtc agagaccctg aaattgcagc agttggtgga gaacattgac aaggccacca 1800ctgatcccaa cgaatgtctc atttgccacc gagtcttaag ctgtcagagc tccctcaaga 1860tgcattatcg cacccacacc ggggagagac cgttccagtg taagatctgt ggccgagcct 1920tttctaccaa aggtaacctg aagacacacc ttggggttca ccgaaccaac acatccatta 1980agacgcagca ttcgtgcccc atctgccaga agaagttcac taatgccgtg atgctgcagc 2040aacatattcg gatgcacatg ggcggtcaga ttcccaacac gcccctgcca gagaatccct 2100gtgactttac gggttctgag ccaatgaccg tgggtgagaa cggcagcacc ggcgctatct 2160gccatgatga tgtcatcgaa agcatcgatg tagaggaagt cagctcccag gaggctccca 2220gcagctcctc caaggtcccc acgcctcttc ccagcatcca ctcggcatca cccacgctag 2280ggtttgccat gatggcttcc ttagatgccc cagggaaagt gggtcctgcc ccttttaacc 2340tgcagcgcca gggcagcaga gaaaacggtt ccgtggagag cgatggcttg accaacgact 2400catcctcgct gatgggagac caggagtatc agagccgaag cccagatatc ctggaaacca 2460catccttcca ggcactctcc ccggccaata gtcaagccga aagcatcaag tcaaagtctc 2520ccgatgctgg gagcaaagca gagagctccg agaacagccg cactgagatg gaaggtcgga 2580gcagtctccc ttccacgttt atccgagccc cgccgaccta tgtcaaggtt gaagttcctg 2640gcacatttgt gggaccctcg acattgtccc cagggatgac ccctttgtta gcagcccagc 2700cacgccgaca ggccaagcaa catggctgca cacggtgtgg gaagaacttc tcgtctgcta 2760gcgctcttca gatccacgag cggactcaca ctggagagaa gccttttgtg tgcaacattt 2820gtgggcgagc ttttaccacc aaaggcaact taaaggttca ctacatgaca cacggggcga 2880acaataactc agcccgccgt ggaaggaagt tggccatcga gaacaccatg gctctgttag 2940gtacggacgg aaaaagagtc tcagaaatct ttcccaagga aatcctggcc ccttcagtga 3000atgtggaccc tgttgtgtgg aaccagtaca ccagcatgct caatggcggt ctggccgtga 3060agaccaatga gatctctgtg atccagagtg ggggggttcc taccctcccg gtttccttgg 3120gggccacctc cgttgtgaat aacgccactg tctccaagat ggatggctcc cagtcgggta 3180tcagtgcaga tgtggaaaaa ccaagtgcta ctgacggcgt tcccaaacac cagtttcctc 3240acttcctgga agaaaacaag attgcggtca gctaagggag aacttgcgtg gaaggagcaa 3300tgcagacaca gtgaaatctc tagaatctgc tttgttttgt aagaactcat ctcctcctgt 3360tttctttttc ttactgatat gcaaatgatg tttactacgt tggttgtgac cacaacctca 3420ggcaagtgct acaatcacga ttgttgctat gctgctttgc aaaaagttga aaaaataaaa 3480aaaaaatgca taccaaaaca aatacagact cttttttttt gagatggagt ctcgctctat 3540cacccaggct ggagtgcagt ggcatgatct cggctcactg caacctcccc attctgggtt 3600caagtgattc tcctgcctta gcctccagag tagctgggat tacaggcagg tgccaccacg 3660cccggctaat tttgtatttt gagtagagac tgggtttcac catgttggtc aggctggtct 3720cgaactgctg acctcgtgat ccacccgcct tggcctccca aagtgctggg attacaggca 3780tgagctacca cgcctggcac tttttttttt tttttctaat tttggaaaga agcgggtctt 3840gcaaagtagc tttgttactt gtaacagacg tatacataga acctttgtac aacctagagt 3900gactttttcc aaagactgtt acctatttca aggtagaatc gttggaactt actgaacaac 3960agtggaaaag acaactacac agcctcattg aggggagatg ggtactgtat acttactggt 4020aactggacac gggtaaaagg acaaggtctg tcatctcttt agggacctgt tttatatgcc 4080ccaaccctgt ccccatctta ttgttttttt ttgaatgtac ttaaaaaagg aacaacaaaa 4140aactagggtt gtagaattat aaaactgctt caaccttaga accttaagta ggaggccctc 4200aaatggactt acgttagtcc ttagggagtc aatgtgtgtg ttgctgctta tttaaataca 4260gttcagttgg agccccgaga gtgccaatgt tttccccaca cctcttggat gccttcctct 4320tcccaaatcc cagaagaggt gggcacctga gcggggaatc tcaggtgact tagtttgcca 4380gtgcctactc tattgaagaa ctgggttttc atgctcgaga agaaactcgt ggaagggcgt 4440gtttcccatc acaggttcac atactgattg cttttgttga atttccttgg tgcgacttat 4500gccaagtaat tatgacgatt ttttgttttg ttttgtttcc ttgctgaata tttcatgaag 4560gctacgaagt tagaacaggc acgtcctggg tgtgaaagct ttaatttatc tacctcattt 4620attttttatt ttttgtagcc atagtgtcta ttttcctatt ttaagaccgc tgaagtattc 4680ccaggccctg tctaaagcct aagagttgat gtattggtgg gaagaggtga acgttcaaga 4740tgattttgtg atgccttttt tttttgtagt ttcctttgta aatgtgatat tgagcaaacg 4800aaacattgct cttggtttaa caagaaagaa agaaaaaaac tctaatttct gggagaaaag 4860tctttcccct ctatgtggaa ggtcctgacg gaaatatgca tccaagacga ttagccaaag 4920tgttgtctct tcatcgttgc acctgacttt aggattccgc cccccttttt tttttttttt 4980tttttttttg ccaagttgtg cctttccttc tggaattgta agtgaacacg ataatagtac 5040ctgtttacac tgtgaagtgg atattgttac agaaaacaca ccagtggctt tctcactgtt 5100gagctaataa tgccttgtga atgtatgatc tacggagaaa cccctgtagt tgtacctgct 5160gatgctgtct gtctgttgga aaataaaatt tgaatgtttt tttttctca 5209661283DNAHomo sapiens 66agtttgcttg gagctcctgg ggcctaacaa aaagaaacct gccatgctgc tcttcctcct 60ctctgcactg gtcctgctca cacagcccct gggctacctg gaagcagaaa tgaagaccta 120ctcccacaga acaatgccca gtgcttgcac cctggtcatg tgtagctcag tggagagtgg 180cctgcctggt cgcgatggac gggatgggag agagggccct cggggcgaga agggggaccc 240aggtttgcca ggagctgcag ggcaagcagg gatgcctgga caagctggcc cagttgggcc 300caaaggggac aatggctctg ttggagaacc tggaccaaag ggagacactg ggccaagtgg 360acctccagga cctcccggtg tgcctggtcc agctggaaga gaaggtcccc tggggaagca 420ggggaacata ggacctcagg gcaagccagg cccaaaagga gaagctgggc ccaaaggaga 480agtaggtgcc ccaggcatgc agggctcggc aggggcaaga ggcctcgcag gccctaaggg 540agagcgaggt gtccctggtg agcgtggagt ccctggaaac acaggggcag cagggtctgc 600tggagccatg ggtccccagg gaagtccagg tgccagggga cccccgggat tgaaggggga 660caaaggcatt cctggagaca aaggagcaaa gggagaaagt gggcttccag atgttgcttc 720tctgaggcag caggttgagg ccttacaggg acaagtacag cacctccagg ctgctttctc 780tcagtataag aaagttgagc tcttcccaaa tggccaaagt gtcggggaga agattttcaa 840gacagcaggc tttgtaaaac catttacgga ggcacagctg ctgtgcacac aggctggtgg 900acagttggcc tctccacgct ctgccgctga gaatgccgcc ttgcaacagc tggtcgtagc 960taagaacgag gctgctttcc tgagcatgac tgattccaag acagagggca agttcaccta 1020ccccacagga gagtccctgg tctattccaa ctgggcccca ggggagccca acgatgatgg 1080cgggtcagag gactgtgtgg agatcttcac caatggcaag tggaatgaca gggcttgtgg 1140agaaaagcgt cttgtggtct gcgagttctg agccaactgg ggtgggtggg gcagtgcttg 1200gcccaggagt ttggccagaa gtcaaggctt agaccctcat gctgccaata tcctaataaa 1260aaggtgacca tctgtgccgg gaa 1283672195DNAHomo sapiens 67cccagcgctc ctccccgcaa atgatcccgc cccaggggcc tatcccagtc cccccagtgc 60ctttggttgc tggagggaag aacacaatgg atctggtgct aaaaagatgc cttcttcatt 120tggctgtgat aggtgctttg ctggctgtgg gggctacaaa agtacccaga aaccaggact 180ggcttggtgt ctcaaggcaa ctcagaacca aagcctggaa caggcagctg tatccagagt 240ggacagaagc ccagagactt gactgctgga gaggtggtca agtgtccctc aaggtcagta 300atgatgggcc tacactgatt ggtgcaaatg cctccttctc tattgccttg aacttccctg 360gaagccaaaa ggtattgcca gatgggcagg ttatctgggt caacaatacc atcatcaatg 420ggagccaggt gtggggagga cagccagtgt atccccagga aactgacgat gcctgcatct 480tccctgatgg tggaccttgc ccatctggct cttggtctca gaagagaagc tttgtttatg 540tctggaagac ctggggccaa tactggcaag ttctaggggg cccagtgtct gggctgagca 600ttgggacagg cagggcaatg ctgggcacac acaccatgga agtgactgtc taccatcgcc 660ggggatcccg gagctatgtg cctcttgctc attccagctc agccttcacc attactgacc 720aggtgccttt ctccgtgagc gtgtcccagt tgcgggcctt ggatggaggg aacaagcact 780tcctgagaaa tcagcctctg acctttgccc tccagctcca tgaccccagt ggctatctgg 840ctgaagctga cctctcctac acctgggact ttggagacag tagtggaacc ctgatctctc 900gggcacttgt ggtcactcat acttacctgg agcctggccc agtcactgcc caggtggtcc 960tgcaggctgc cattcctctc acctcctgtg gctcctcccc agttccaggc accacagatg 1020ggcacaggcc aactgcagag gcccctaaca ccacagctgg ccaagtgcct actacagaag 1080ttgtgggtac tacacctggt caggcgccaa ctgcagagcc ctctggaacc acatctgtgc 1140aggtgccaac cactgaagtc ataagcactg cacctgtgca gatgccaact gcagagagca 1200caggtatgac acctgagaag gtgccagttt cagaggtcat gggtaccaca ctggcagaga 1260tgtcaactcc agaggctaca ggtatgacac ctgcagaggt atcaattgtg gtgctttctg 1320gaaccacagc tgcacaggta acaactacag agtgggtgga gaccacagct agagagctac 1380ctatccctga gcctgaaggt ccagatgcca gctcaatcat gtctacggaa agtattacag 1440gttccctggg ccccctgctg gatggtacag ccaccttaag gctggtgaag agacaagtcc 1500ccctggattg tgttctgtat cgatatggtt ccttttccgt caccctggac attgtccagg 1560gtattgaaag tgccgagatc ctgcaggctg tgccgtccgg tgagggggat gcatttgagc 1620tgactgtgtc ctgccaaggc gggctgccca aggaagcctg catggagatc tcatcgccag 1680ggtgccagcc ccctgcccag cggctgtgcc agcctgtgct acccagccca gcctgccagc 1740tggttctgca ccagatactg aagggtggct cggggacata ctgcctcaat gtgtctctgg 1800ctgataccaa cagcctggca gtggtcagca cccagcttat catgcctggt caagaagcag 1860gccttgggca ggttccgctg atcgtgggca tcttgctggt gttgatggct gtggtccttg 1920catctctgat atataggcgc agacttatga agcaagactt ctccgtaccc cagttgccac 1980atagcagcag tcactggctg cgtctacccc gcatcttctg ctcttgtccc attggtgaga 2040acagccccct cctcagtggg cagcaggtct gagtactctc atatgatgct gtgattttcc 2100tggagttgac agaaacacct atatttcccc cagtcttccc tgggagacta ctattaactg 2160aaataaatac tcagagcctg aaaaaaaaaa aaaaa 2195681222DNAHomo sapiens 68agtattgggg atgctgagct gcggggtacg ggcctgagga gggatgggag taagaagtgc 60tgtggaaacc gtcaggccat gaaccaggct gaccctcggc tcagagcagt gtgcttgtgg 120actctcacat ctgcagccat gagcagaggc gacaactgca cggatctact cgcactggga 180atcccctcca taacccaggc ctggggactg tgggtcctct taggggctgt gacgctgcta 240tttctcatct cgctggctgc acacttgtcc cagtggacca ggggccggag caggagccat 300ccggggcagg gacgctctgg agagtctgtg gaagaggtcc cgctgtatgg gaacctgcat 360tatctacaga caggacggct gtctcaagac ccagagccag accagcagga tccaactctt 420ggaggccctg ccagggctgc agaggaggtg atgtgctata ccagcctgca gctgcggcct 480cctcagggtc ggatccccgg tcctggaacc cccgtcaagt actcggaggt ggtgctggac 540tctgagccaa agtcccaggc ctcgggcccc gagccggagc tctatgcctc agtatgtgcc 600cagacccgca gggcccgggc ctccttcccg gatcaggcct atgccaacag ccagcctgca 660gccagctgag atggagggcc tggcacagcg gggcgtgcac tgccccagcc ccccgtagca 720ggggcatgac tgtttcccaa ccagcaccca aagacgggcg ccattgccaa gtcacaggat 780gtgatctacc ccggacttcc tatctgagct tcaagggaga catctcaggg caaagctttc 840gtgatggagg aggcaaagac agtagccccc tccttatttc ttttttctat ctgttcctct 900tagcccccaa actcccaggt tctcacttcc ttcttctgga gtttaaccag atcctcccca 960cccccgctcc ctcatagtct acccccacgc ctcagtgtct cctcaggcac aggaagtggg 1020cggtggggga ggggtaaggg cctgacagtg ggtgggtggg tatattcctc aggagtccac 1080agactggagt ggacctggaa cttagagacg ggagggaccc gagcctggct tttgacctaa 1140gaaccctagc aggagaatac agtctccatc ctgctgtctc tgtcctgtcc ccaagttttc 1200aaataaaact ttccaaaaag tg 1222694930DNAHomo sapiens 69ctcagccttc ccggttcggg aaaggggaag aatgcaggag gggtaggatt tctttcctga 60taggatcggt tgggaaagac cgcagcctgt gtgtgtcttt cccttcgacc aaggtgtctg 120ttgctccgta aataaaacgt cccactgcct tctgagagcg ctataaaggc agcggaaggg 180tagtccgcgg ggcattccgg gcggggcgcg agcagagaca ggtcatggca gcgccaggcg 240gcaggtcgga gccgccgcag ctccccgagt acagctgcag ctacatggtg tcgcggccgg 300tctacagcga gctcgctttc cagcaacagc acgagcggcg cctgcaggag cgcaagacgc 360tgcgggagag cctggccaag tgctgcagtt gttcaagaaa gagagccttt ggtgtgctaa 420agactcttgt gcccatcttg gagtggctcc ccaaataccg agtcaaggaa tggctgctta 480gtgacgtcat ttcgggagtt agtactgggc tagtggccac gctgcaaggg atggcatatg 540ccctactagc tgcagttcct gtcggatatg gtctctactc tgcttttttc cctatcctga 600catactttat ctttggaaca tcaagacata tctcagttgg accttttcca gtggtgagtt 660taatggtggg atctgttgtt ctgagcatgg cccccgacga acactttctc gtatccagca 720gcaatggaac tgtattaaat actactatga tagacactgc agctagagat acagctagag 780tcctgattgc cagtgccctg actctgctgg ttggaattat acagttgata tttggtggct 840tgcagattgg attcatagtg aggtacttgg cagatccttt ggttggtggc ttcacaacag 900ctgctgcctt ccaagtgctg gtctcacagc taaagattgt cctcaatgtt tcaaccaaaa 960actacaatgg agttctctct attatctata cgctggttga gatttttcaa aatattggtg 1020ataccaatct tgctgatttc actgctggat tgctcaccat tgtcgtctgt atggcagtta 1080aggaattaaa tgatcggttt agacacaaaa tcccagtccc tattcctata gaagtaattg 1140tgacgataat tgctactgcc atttcatatg gagccaacct ggaaaaaaat tacaatgctg 1200gcattgttaa atccatccca agggggtttt tgcctcctga acttccacct gtgagcttgt 1260tctcggagat gctggctgca tcattttcca tcgctgtggt ggcttatgct attgcagtgt 1320cagtaggaaa agtatatgcc accaagtatg attacaccat cgatgggaac caggaattca 1380ttgcctttgg gatcagcaac atcttctcag gattcttctc ttgttttgtg gccaccactg 1440ctctttcccg cacggccgtc caggagagca ctggaggaaa gacacaggtt gctggcatca 1500tctctgctgc gattgtgatg atcgccattc ttgccctggg gaagcttctg gaacccttgc 1560agaagtcggt cttggcagct gttgtaattg ccaacctgaa agggatgttt atgcagctgt 1620gtgacattcc tcgtctgtgg agacagaata agattgatgc tgttatctgg gtgtttacgt 1680gtatagtgtc catcattctg gggctggatc tcggtttact agctggcctt atatttggac 1740tgttgactgt ggtcctgaga gttcagtttc cttcttggaa tggccttgga agcatcccta 1800gcacagatat ctacaaaagt accaagaatt acaaaaacat tgaagaacct caaggagtga 1860agattcttag attttccagt cctattttct atggcaatgt cgatggtttt aaaaaatgta 1920tcaagtccac agttggattt gatgccatta gagtatataa taagaggctg aaagcgctga 1980ggaaaataca gaaactaata aaaagtggac aattaagagc aacaaagaat ggcatcataa 2040gtgatgctgt ttcaacaaat aatgcttttg agcctgatga ggatattgaa gatctggagg 2100aacttgatat cccaaccaag gaaatagaga ttcaagtgga ttggaactct gagcttccag 2160tcaaagtgaa cgttcccaaa gtgccaatcc atagccttgt gcttgactgt ggagctatat 2220ctttcctgga cgttgttgga gtgagatcac tgcgggtgat tgtcaaagaa ttccaaagaa 2280ttgatgtgaa tgtgtatttt gcatcacttc aagattatgt gatagaaaag ctggagcaat 2340gcgggttctt tgacgacaac attagaaagg acacattctt tttgacggtc catgatgcta 2400tactctatct acagaaccaa gtgaaatctc aagagggtca aggttccatt ttagaaacga 2460tcactctcat tcaggattgt aaagataccc ttgaattaat agaaacagag ctgacggaag 2520aagaacttga tgtccaggat gaggctatgc gtacacttgc atcctgaaag tgggttcggg 2580aggtctctat gagcaaggaa tacaagacaa aacttcctca atgcattgac tatttcttca 2640gactcaaaac actcattctt ttttctatta agccattgaa agagaagcac taagactgct 2700tctaggcttt atttataaaa taaacacctt atccctaaca tgggcaaaat ggctagaatt 2760attcagacga tttggcagcg tccagggtaa gctggtgtta taatacgctg ctgatctaca 2820tcacagattt gctaataatg ttcacgtggg ccctggcata tctctgttca gttagagtga 2880gtgctgaccc aacagcctct gtggtcaagc gagtcacgaa tgattaatca taaagaaaaa 2940tcagtttttg actgacctgg atatccatga gctgcactga tcaccatgta aggtcacatt 3000tagtaaatgc tgaaataaaa tgattaatgc atttatcaat aaaagccttt gaaaatactt 3060tggataataa attggagttt taaaaatgca aatttgctta gtatctaata atgaagtgtt 3120attacatata gccggaattg aggatctctt tgatcctgga aatggtttac ctaaaagcta 3180cagaaccagg ccaatatatt ttgaaatatt gatgcagaca aatgaaataa taaagagatt 3240ttcatggttt ataaaaatct tttttgatat gataataatc atgatcacaa ctgagatcaa 3300aaaaatatat gacagattat tttgtttaaa aatgcagttt taattatctt agtctataga 3360aatgatcatt gcatggaggc atgtataggt atgatctgtg taaaatctga cataaaaaca 3420gtgctattct gagtgaaaat ttttttgatg tgcttacata accatggtga ttaaaatgag 3480tttatatttt ttctcaaaaa ttttagcagt gtgtaaagta agtaatcttt aactgaactc 3540tgaccactta aaaaaaaatc taaaaattga actacctata gtagtctgtg tttaaagtga 3600atttttaaag acaaagcatt ctaaatgaac tcaatataaa aacattcatt tggaatgtac 3660atactgaaaa atacaggttt ttttgaccaa aagtttttat atcttttctt tttatttatt 3720tttttcctaa gtgccaacaa ttttctagat attatataca acacaggctt tgatcttggg 3780gacttttccc atatatttca cactggagtg aatgaagttg tacttcattt ctagagaaaa 3840gttataccca ggtccccaat tgagaatgtc ttgcttgatt gaaaacgaca tcatcccttg 3900gtatactcca gggattggtt tcaggacccc tgcatttacc aaaatttgtg cacactcaag 3960tcctgcagtc acccctgcct aaagatagaa tggcttctct gtttttcttc tgaaatacaa 4020ccagaaacaa tgtgtctatt tctgaaagaa taggattaat gatcatacaa atgggttaat 4080cctgaattct ggttgtaaat ctggttacag cataactagg attataatgc tgcctcattt 4140tcacagcact acttgcttat attgacaaca aatcatctcg ctaaagagtg aatgtaggcc 4200aggcgcggtg gctcatgcct gtaatcccag cactttggga ggccgaggcg ggtggatcac 4260gaggtcagga gatcgagacc atcctggcta acatggtaaa accccgtctc tactaaaaat 4320agaaaaaaag aaattagcct agcgtggtgg ctggcgggcg cctgtagtcc cagctatttg 4380ggaggctaag gcaggagaat ggcgtgaacc cgggaggcgg agcttgcagt gagccgaggt 4440cgtgccactg cactccagcc tgggcgacag agcaagactc cgtctcaaaa aaaaaaaaaa 4500aaaaaaaaaa agagtgaatg taatagtctt gcagaaaatg aatgaatacc tttgttcaat 4560aaaggaaata tgcactgctc acttttttga aggaaatgcc aaagttacgt tttacaacaa 4620ggctagagtt tgtaaattct gggttcattt gtgatgacat aagtcagcaa actgcgggaa 4680tactgtctct tctatgtatt ttgtgaatag taagcataat tttagttttg tattatcaat 4740gaaaatttca cttgaaatta aagctgcctt ttgttatatt tttaacctat aggataagat 4800tccagtattg tatatgagtt ttaacaaatt aaaaaatcaa atcatgtaca tttgaaaata 4860tttgcacaca tttaaaaata aatgtaaagt tgtcttttaa actactcgga tgtgtccttt 4920ctgaacaaaa 4930702353DNAHomo sapiens 70aagaccaagc attcagcaag ccactcttcc acctccctta ctgcaggaag gcactccgaa 60gacataagtc ggtgagacat ggctgaagat aaaagcaaga gagactccat cgagatgagt 120atgaagggat gccagacaaa caacgggttt gtccataatg aagacattct ggagcagacc 180ccggatccag gaagctcaac agacaacctg aagcacagca ccaggggcat ccttggctcc 240caggagcccg acttcaaggg cgtccagccc tatgcgggga tgcccaagga ggtgctgttc 300cagttctctg gccaggcccg ctaccgcata cctcgggaga tcctcttctg gctcacagtg 360gcttctgtgc tggtgctcat cgcggccacc atagccatca ttgccctctc tccaaagtgc 420ctagactggt ggcaggaggg gcccatgtac cagatctacc caaggtcttt caaggacagt 480aacaaggatg ggaacggaga tctgaaaggt attcaagata aactggacta catcacagct 540ttaaatataa aaactgtttg gattacttca ttttataaat cgtcccttaa agatttcaga 600tatggtgttg aagatttccg ggaagttgat cccatttttg gaacgatgga agattttgag 660aatctggttg cagccataca tgataaaggt ttaaaattaa tcatcgattt cataccaaac 720cacacgagtg ataaacatat ttggtttcaa ttgagtcgga cacggacagg aaaatatact 780gattattata tctggcatga ctgtacccat gaaaatggca aaaccattcc acccaacaac 840tggttaagtg tgtatggaaa ctccagttgg cactttgacg aagtgcgaaa ccaatgttat 900tttcatcagt ttatgaaaga gcaacctgat ttaaatttcc gcaatcctga tgttcaagaa 960gaaataaaag aaattttacg

gttctggctc acaaagggtg ttgatggttt tagtttggat 1020gctgttaaat tcctcctaga agcaaagcac ctgagagatg agatccaagt aaataagacc 1080caaatcccgg acacggtcac acaatactcg gagctgtacc atgacttcac caccacgcag 1140gtgggaatgc acgacattgt ccgcagcttc cggcagacca tggaccaata cagcacggag 1200cccggcagat acaggttcat ggggactgaa gcctatgcag agagtattga caggaccgtg 1260atgtactatg gattgccatt tatccaagaa gctgattttc ccttcaacaa ttacctcagc 1320atgctagaca ctgtttctgg gaacagcgtg tatgaggtta tcacatcctg gatggaaaac 1380atgccagaag gaaaatggcc taactggatg attggtggac cagacagttc acggctgact 1440tcgcgtttgg ggaatcagta tgtcaacgtg atgaacatgc ttcttttcac actccctgga 1500actcctataa cttactatgg agaagaaatt ggaatgggaa atattgtagc cgcaaatctc 1560aatgaaagct atgatattaa tacccttcgc tcaaagtcac caatgcagtg ggacaatagt 1620tcaaatgctg gtttttctga agctagtaac acctggttac ctaccaattc agattaccac 1680actgtgaatg ttgatgtcca aaagactcag cccagatcgg ctttgaagtt atatcaagat 1740ttaagtctac ttcatgccaa tgagctactc ctcaacaggg gctggttttg ccatttgagg 1800aatgacagcc actatgttgt gtacacaaga gagctggatg gcatcgacag aatctttatc 1860gtggttctga attttggaga atcaacactg ttaaatctac ataatatgat ttcgggcctt 1920cccgctaaaa tgagaataag gttaagtacc aattctgccg acaaaggcag taaagttgat 1980acaagtggca tttttctgga caagggagag ggactcatct ttgaacacaa cacgaagaat 2040ctccttcatc gccaaacagc tttcagagat agatgctttg tttccaatcg agcatgctat 2100tccagtgtac tgaacatact gtatacctcg tgttaggcac ctttatgaag agatgaagac 2160actggcattt cagtgggatt gtaagcattt gtaatagctt catgtacagc atgctgcttg 2220gtgaacaatc attaattctt cgatatttct gtagcttgaa tgtaactgct ttaagaaagg 2280ttctcaaatg ttttgaaaaa aataaaatgt ttaaaagtaa aaaaaaaaaa aaaaaaaaaa 2340aaaaaaaaaa aaa 2353713391DNAHomo sapiens 71gcggagtaac ctggagattt aaaagccgcc ggctggcgcg cgtggggggc aaggaagggg 60gggcggaacc agcctgcacg cgctggctcc gggtgacagc cgcgcgcctc ggccaggatc 120tgagtgatga gacgtgtccc cactgaggtg ccccacagca gcaggtgttg agcatgggct 180gagaagctgg accggcacca aagggctggc agaaatgggc gcctggctga ttcctaggca 240gttggcggca gcaaggagga gaggccgcag cttctggagc agagccgaga cgaagcagtt 300ctggagtgcc tgaacggccc cctgagccct acccgcctgg cccactatgg tccagaggct 360gtgggtgagc cgcctgctgc ggcaccggaa agcccagctc ttgctggtca acctgctaac 420ctttggcctg gaggtgtgtt tggccgcagg catcacctat gtgccgcctc tgctgctgga 480agtgggggta gaggagaagt tcatgaccat ggtgctgggc attggtccag tgctgggcct 540ggtctgtgtc ccgctcctag gctcagccag tgaccactgg cgtggacgct atggccgccg 600ccggcccttc atctgggcac tgtccttggg catcctgctg agcctctttc tcatcccaag 660ggccggctgg ctagcagggc tgctgtgccc ggatcccagg cccctggagc tggcactgct 720catcctgggc gtggggctgc tggacttctg tggccaggtg tgcttcactc cactggaggc 780cctgctctct gacctcttcc gggacccgga ccactgtcgc caggcctact ctgtctatgc 840cttcatgatc agtcttgggg gctgcctggg ctacctcctg cctgccattg actgggacac 900cagtgccctg gccccctacc tgggcaccca ggaggagtgc ctctttggcc tgctcaccct 960catcttcctc acctgcgtag cagccacact gctggtggct gaggaggcag cgctgggccc 1020caccgagcca gcagaagggc tgtcggcccc ctccttgtcg ccccactgct gtccatgccg 1080ggcccgcttg gctttccgga acctgggcgc cctgcttccc cggctgcacc agctgtgctg 1140ccgcatgccc cgcaccctgc gccggctctt cgtggctgag ctgtgcagct ggatggcact 1200catgaccttc acgctgtttt acacggattt cgtgggcgag gggctgtacc agggcgtgcc 1260cagagctgag ccgggcaccg aggcccggag acactatgat gaaggcgttc ggatgggcag 1320cctggggctg ttcctgcagt gcgccatctc cctggtcttc tctctggtca tggaccggct 1380ggtgcagcga ttcggcactc gagcagtcta tttggccagt gtggcagctt tccctgtggc 1440tgccggtgcc acatgcctgt cccacagtgt ggccgtggtg acagcttcag ccgccctcac 1500cgggttcacc ttctcagccc tgcagatcct gccctacaca ctggcctccc tctaccaccg 1560ggagaagcag gtgttcctgc ccaaataccg aggggacact ggaggtgcta gcagtgagga 1620cagcctgatg accagcttcc tgccaggccc taagcctgga gctcccttcc ctaatggaca 1680cgtgggtgct ggaggcagtg gcctgctccc acctccaccc gcgctctgcg gggcctctgc 1740ctgtgatgtc tccgtacgtg tggtggtggg tgagcccacc gaggccaggg tggttccggg 1800ccggggcatc tgcctggacc tcgccatcct ggatagtgcc ttcctgctgt cccaggtggc 1860cccatccctg tttatgggct ccattgtcca gctcagccag tctgtcactg cctatatggt 1920gtctgccgca ggcctgggtc tggtcgccat ttactttgct acacaggtag tatttgacaa 1980gagcgacttg gccaaatact cagcgtagaa aacttccagc acattggggt ggagggcctg 2040cctcactggg tcccagctcc ccgctcctgt tagccccatg gggctgccgg gctggccgcc 2100agtttctgtt gctgccaaag taatgtggct ctctgctgcc accctgtgct gctgaggtgc 2160gtagctgcac agctgggggc tggggcgtcc ctctcctctc tccccagtct ctagggctgc 2220ctgactggag gccttccaag ggggtttcag tctggactta tacagggagg ccagaagggc 2280tccatgcact ggaatgcggg gactctgcag gtggattacc caggctcagg gttaacagct 2340agcctcctag ttgagacaca cctagagaag ggtttttggg agctgaataa actcagtcac 2400ctggtttccc atctctaagc cccttaacct gcagcttcgt ttaatgtagc tcttgcatgg 2460gagtttctag gatgaaacac tcctccatgg gatttgaaca tatgaaagtt atttgtaggg 2520gaagagtcct gaggggcaac acacaagaac caggtcccct cagcccacag cactgtcttt 2580ttgctgatcc acccccctct taccttttat caggatgtgg cctgttggtc cttctgttgc 2640catcacagag acacaggcat ttaaatattt aacttattta tttaacaaag tagaagggaa 2700tccattgcta gcttttctgt gttggtgtct aatatttggg tagggtgggg gatccccaac 2760aatcaggtcc cctgagatag ctggtcattg ggctgatcat tgccagaatc ttcttctcct 2820ggggtctggc cccccaaaat gcctaaccca ggaccttgga aattctactc atcccaaatg 2880ataattccaa atgctgttac ccaaggttag ggtgttgaag gaaggtagag ggtggggctt 2940caggtctcaa cggcttccct aaccacccct cttctcttgg cccagcctgg ttccccccac 3000ttccactccc ctctactctc tctaggactg ggctgatgaa ggcactgccc aaaatttccc 3060ctacccccaa ctttccccta cccccaactt tccccaccag ctccacaacc ctgtttggag 3120ctactgcagg accagaagca caaagtgcgg tttcccaagc ctttgtccat ctcagccccc 3180agagtatatc tgtgcttggg gaatctcaca cagaaactca ggagcacccc ctgcctgagc 3240taagggaggt cttatctctc agggggggtt taagtgccgt ttgcaataat gtcgtcttat 3300ttatttagcg gggtgaatat tttatactgt aagtgagcaa tcagagtata atgtttatgg 3360tgacaaaatt aaaggctttc ttatatgttt a 3391722346DNAHomo sapiens 72gcagtgtcac taggccggct gggggccctg ggtacgctgt agaccagacc gcgacaggcc 60agaacacggg cggcggcttc gggccgggag acccgcgcag ccctcggggc atctcagtgc 120ctcactcccc accccctccc ccgggtcggg ggaggcggcg cgtccggcgg agggttgagg 180ggagcggggc aggcctggag cgccatgagc agcccggatg cgggatacgc cagtgacgac 240cagagccaga cccagagcgc gctgcccgcg gtgatggccg ggctgggccc ctgcccctgg 300gccgagtcgc tgagccccat cggggacatg aaggtgaagg gcgaggcgcc ggcgaacagc 360ggagcaccgg ccggggccgc gggccgagcc aagggcgagt cccgtatccg gcggccgatg 420aacgctttca tggtgtgggc taaggacgag cgcaagcggc tggcgcagca gaatccagac 480ctgcacaacg ccgagttgag caagatgctg ggcaagtcgt ggaaggcgct gacgctggcg 540gagaagcggc ccttcgtgga ggaggcagag cggctgcgcg tgcagcacat gcaggaccac 600cccaactaca agtaccggcc gcggcggcgc aagcaggtga agcggctgaa gcgggtggag 660ggcggcttcc tgcacggcct ggctgagccg caggcggccg cgctgggccc cgagggcggc 720cgcgtggcca tggacggcct gggcctccag ttccccgagc agggcttccc cgccggcccg 780ccgctgctgc ctccgcacat gggcggccac taccgcgact gccagagtct gggcgcgcct 840ccgctcgacg gctacccgtt gcccacgccc gacacgtccc cgctggacgg cgtggacccc 900gacccggctt tcttcgccgc cccgatgccc ggggactgcc cggcggccgg cacctacagc 960tacgcgcagg tctcggacta cgctggcccc ccggagcctc ccgccggtcc catgcacccc 1020cgactcggcc cagagcccgc gggtccctcg attccgggcc tcctggcgcc acccagcgcc 1080cttcacgtgt actacggcgc gatgggctcg cccggggcgg gcggcgggcg cggcttccag 1140atgcagccgc aacaccagca ccagcaccag caccagcacc accccccggg ccccggacag 1200ccgtcgcccc ctccggaggc actgccctgc cgggacggca cggaccccag tcagcccgcc 1260gagctcctcg gggaggtgga ccgcacggaa tttgaacagt atctgcactt cgtgtgcaag 1320cctgagatgg gcctccccta ccaggggcat gactccggtg tgaatctccc cgacagccac 1380ggggccattt cctcggtggt gtccgacgcc agctccgcgg tatattactg caactatcct 1440gacgtgtgac aggtccctga tccgccccag cctgcaggcc agaagcagtg ttacacactt 1500cctggaggag ctaaggaaat cctcagactc ctgggttttt gttgttgctg ttgttgtttt 1560ttaaaaggtg tgttggcata taatttatgg taatttattt tgtctgccac ttgaacagtt 1620tgggggggtg aggtttcatt taaaatttgt tcagagattt gtttcccata gttggattgt 1680caaaacccta tttccaagtt caagttaact agctttgaat gtgtcccaaa acagcttcct 1740ccatttcctg aaagtttatt gatcaaagaa atgttgtcct gggtgtgttt tttcaatctt 1800ctaaaaaata aaatctggaa tcctgctttt ttgctctact agtacctctg tcacactagt 1860cttatcaaaa accagttctt aagatcaatg ttaagtttat tagttaatgt aaatttctca 1920tcctcgaaaa gggtgaacat aaatgccttt aaggagtata tctaaaaata aacattagga 1980tatctaagtt tgatgtaatt gtttcaggaa ggaaaaaaga aaagcattct ggaatgagcc 2040tacttcaagt aatcttagtt tctaaaacta acagttaata ttttcaattc cagtatatca 2100ctttaagtag aaggggatgt ccaagtaatt ttggttttct aactgttgaa tcataagctt 2160gacctgcccc cagaggcttt ttggatgttt ttatctgtgt tttgccatct ctttacactc 2220ctcgacattc agtttacctt aatcttcaca tttttacacc ttgggaagtg gcaagcatcg 2280ctgggtttaa gataaaggag tcacaaaaac taatcaaaat aaaatttgca ttatgacaac 2340ttttaa 2346731910DNAHomo sapiens 73cttcatctcg cggctgtctg acttcctccc agcacattcc tgcactctgc cgtgtccaca 60ctgccccaca gacccagtcc tccaagcctg ctgccagctc cctgcaagcc cctcaggttg 120ggccttgcca cggtgccagc aggcagccct gggctggggg taggggactc cctacaggca 180cgcagccctg agacctcaga gggccacccc ttgagggtgg ccaggccccc agtggccaac 240ctgagtgctg cctctgccac cagccctgct ggcccctggt tccgctggcc ccccagatgc 300ctggctgaga cacgccagtg gcctcagctg cccacacctc ttcccggccc ctgaagttgg 360cactgcagca gacagctccc tgggcaccag gcagctaaca gacacagccg ccagcccaaa 420cagcagcggc atgggcagcg ccagcccggg tctgagcagc gtatccccca gccacctcct 480gctgcccccc gacacggtgt cgcggacagg cttggagaag gcggcagcgg gggcagtggg 540tctcgagaga cgggactgga gtcccagtcc acccgccacg cccgagcagg gcctgtccgc 600cttctacctc tcctactttg acatgctgta ccctgaggac agcagctggg cagccaaggc 660ccctggggcc agcagtcggg aggagccacc tgaggagcct gagcagtgcc cggtcattga 720cagccaagcc ccagcgggca gcctggactt ggtgcccggc gggctgacct tggaggagca 780ctcgctggag caggtgcagt ccatggtggt gggcgaagtg ctcaaggaca tcgagacggc 840ctgcaagctg ctcaacatca ccgcagatcc catggactgg agccccagca atgtgcagaa 900gtggctcctg tggacagagc accaataccg gctgcccccc atgggcaagg ccttccagga 960gctggcgggc aaggagctgt gcgccatgtc ggaggagcag ttccgccagc gctcgcccct 1020gggtggggat gtgctgcacg cccacctgga catctggaag tcagcggcct ggatgaaaga 1080gcggacttca cctggggcga ttcactactg tgcctcgacc agtgaggaga gctggaccga 1140cagcgaggtg gactcatcat gctccgggca gcccatccac ctgtggcagt tcctcaagga 1200gttgctactc aagccccaca gctatggccg cttcattagg tggctcaaca aggagaaggg 1260catcttcaaa attgaggact cagcccaggt ggcccggctg tggggcatcc gcaagaaccg 1320tcccgccatg aactacgaca agctgagccg ctccatccgc cagtattaca agaagggcat 1380catccggaag ccagacatct cccagcgcct cgtctaccag ttcgtgcacc ccatctgagt 1440gcctggccca gggcctgaaa cccgccctca ggggcctctc tcctgcctgc cctgcctcag 1500ccaggccctg agatggggga aaacgggcag tctgctctgc tgctctgacc ttccagagcc 1560caaggtcagg gaggggcaac caactgcccc agggggatat gggtcctctg gggccttcgg 1620gaccctgggg caggggtgct tcctcctcag gcccagctgc tcccctggag gacagaggga 1680gacagggctg ctccccaaca cctgcctctg accccagcat ttccagagca gagcctacag 1740aagggcagtg actcgacaaa ggccacaggc agtccaggcc tctctctgct ccatccccct 1800gcctcccatt ctgcaccaca cctggcatgg tgcagggaga catctgcacc cctgagttgg 1860gcagccagga gtgcccccgg gaatggataa taaagatact agagaactga 1910741688DNAHomo sapiens 74gccattggct ctggcgacct ccgcgcgttg ggaggtgtag cgcggctctg aacgcgctga 60gggccgttga gtgtcgcagg cggcgagggc gcgagtgagg agcagaccca ggcatcgcgc 120gccgagaagg ccgggcgtcc ccacactgaa ggtccggaaa ggcgacttcc gggggctttg 180gcacctggcg gaccctcccg gagcgtcggc acctgaacgc gaggcgctcc attgcgcgtg 240cgcgttgagg ggcttcccgc acctgatcgc gagaccccaa cggctggtgg cgtcgcctgc 300gcgtctcggc tgagctggcc atggcgcagc tgtgcgggct gaggcggagc cgggcgtttc 360tcgccctgct gggatcgctg ctcctctctg gggtcctggc ggccgaccga gaacgcagca 420tccacgactt ctgcctggtg tcgaaggtgg tgggcagatg ccgggcctcc atgcctaggt 480ggtggtacaa tgtcactgac ggatcctgcc agctgtttgt gtatgggggc tgtgacggaa 540acagcaataa ttacctgacc aaggaggagt gcctcaagaa atgtgccact gtcacagaga 600atgccacggg tgacctggcc accagcagga atgcagcgga ttcctctgtc ccaagtgctc 660ccagaaggca ggattctgaa gaccactcca gcgatatgtt caactatgaa gaatactgca 720ccgccaacgc agtcactggg ccttgccgtg catccttccc acgctggtac tttgacgtgg 780agaggaactc ctgcaataac ttcatctatg gaggctgccg gggcaataag aacagctacc 840gctctgagga ggcctgcatg ctccgctgct tccgccagca ggagaatcct cccctgcccc 900ttggctcaaa ggtggtggtt ctggcggggc tgttcgtgat ggtgttgatc ctcttcctgg 960gagcctccat ggtctacctg atccgggtgg cacggaggaa ccaggagcgt gccctgcgca 1020ccgtctggag ctccggagat gacaaggagc agctggtgaa gaacacatat gtcctgtgac 1080cgccctgtcg ccaagaggac tggggaaggg aggggagact atgtgtgagc tttttttaaa 1140tagagggatt gactcggatt tgagtgatca ttagggctga ggtctgtttc tctgggaggt 1200aggacggctg cttcctggtc tggcagggat gggtttgctt tggaaatcct ctaggaggct 1260cctcctcgca tggcctgcag tctggcagca gccccgagtt gtttcctcgc tgatcgattt 1320ctttcctcca ggtagagttt tctttgctta tgttgaattc cattgcctct tttctcatca 1380cagaagtgat gttggaatcg tttcttttgt ttgtctgatt tatggttttt ttaagtataa 1440acaaaagttt tttattagca ttctgaaaga aggaaagtaa aatgtacaag tttaataaaa 1500aggggccttc ccctttagaa taaatttcag catgtgcttt ctttatggga gtcctaattt 1560caaccctacc aaaatgatca caagacacta tctgaggtgt cccattctag aaatagaccc 1620ctcaaaatag cgtctttcag atctttttga atgaatccac aagatgaaat aaatgtccta 1680ttactgag 1688751046DNAHomo sapiens 75accagatccc tgtttccgtg gaggaaggca gacttcagac tgaaggacag agaaggcaac 60tgccctacag ccctgcaggt cttcaagtct gtggttgtgg gcactaaccc agacaagaaa 120aggaaagacc tgcagtatcg gtgcaggaaa ggcaaagaag ggaacatctc aacatggaaa 180agctctacaa agaaaatgaa ggaaagccag agaatgaaag aaacctagaa agtgagggaa 240agccagagga tgagggaagt acagaagatg aaggaaagtc agacgaggaa gaaaagccgg 300acatggaggg gaagacagaa tgcgagggaa agcgagagga tgagggagag ccaggtgatg 360agggacaact ggaagatgag ggaaaccagg aaaagcaggg caagtctgaa ggtgaggaca 420agccacaaag tgagggcaag ccagcctccc aggccaagcc agagagccag ccgcgggccg 480ccgaaaagcg cccggctgaa gattatgtgc cccggaaagc aaaaagaaaa accgacaggg 540ggacggacga ttcccccaag gactctcagg aggacttaca agaaaggcat ctgagcagtg 600aggagatgat gagagaatgt ggagatgtgt caagggctca ggaggagcta aggaaaaaac 660agaaaatggg tggttttcat tggatgcaaa gagatgtaca ggatccattc gccccaaggg 720gccaacgggg tgtgagggga gtgaggggcg gaggtagggg ccagaaagac ttagaagatg 780tcccatatgt ttaatgtctt tggcctttaa ttctgatttc tctgatggga atattgccag 840tcctgctttt cctggcaggc atttgccggc ctatgtgctt taaccttaag ctgatacttt 900cctttaggtg tcactcttgt taccagcaga cttttgaccc aactacagtg ctctgtcttt 960tagtagagga ttttcaccca tgtgcatgga ataaatgttc atggtacatt gtaaaataac 1020aataaaaaag agttttcaga accatg 1046768455DNAHomo sapiens 76aagcagtggt ttctcctcct tcctcccagg aagggccagg aaaatggccc tggtcctgga 60gatcttcacc ctgctggcct ccatctgctg ggtgtcggcc aatatcttcg agtaccaggt 120ggatgcccag ccccttcgtc cctgtgagct gcagagggaa acggcctttc tgaagcaagc 180agactacgtg ccccagtgtg cagaggatgg cagcttccag actgtccagt gccagaacga 240cggccgctcc tgctggtgtg tgggtgccaa cggcagtgaa gtgctgggca gcaggcagcc 300aggacggcct gtggcttgtc tgtcattttg tcagctacag aaacagcaga tcttactgag 360tggctacatt aacagcacag acacctccta cctccctcag tgtcaggatt caggggacta 420cgcgcctgtt cagtgtgatg tgcagcaggt ccagtgctgg tgtgtggacg cagaggggat 480ggaggtgtat gggacccgcc agctggggag gccaaagcga tgtccaagga gctgtgaaat 540aagaaatcgt cgtcttctcc acggggtggg agataagtca ccaccccagt gttctgcgga 600gggagagttt atgcctgtcc agtgcaaatt tgtcaacacc acagacatga tgatttttga 660tctggtccac agctacaaca ggtttccaga tgcatttgtg accttcagtt ccttccagag 720gaggttccct gaggtatctg ggtattgcca ctgtgctgac agccaagggc gggaactggc 780tgagacaggt ttggagttgt tactggatga aatttatgac accatttttg ctggcctgga 840ccttccttcc accttcactg aaaccaccct gtaccggata ctgcagagac ggttcctcgc 900agttcaatca gtcatctctg gcagattccg atgccccaca aaatgtgaag tggagcggtt 960tacagcaacc agctttggtc acccctatgt tccaagctgc cgccgaaatg gcgactatca 1020ggcggtgcag tgccagacgg aagggccctg ctggtgtgtg gacgcccagg ggaaggaaat 1080gcatggaacc cggcagcaag gggagccgcc atcttgtgct gaaggccaat cttgtgcctc 1140cgaaaggcag caggccttgt ccagactcta ctttgggacc tcaggctact tcagccagca 1200cgacctgttc tcttccccag agaaaagatg ggcctctcca agagtagcca gatttgccac 1260atcctgccca cccacgatca aggagctctt tgtggactct gggcttctcc gcccaatggt 1320ggagggacag agccaacagt tttctgtctc agaaaatctt ctcaaagaag ccatccgagc 1380aatttttccc tcccgagggc tggctcgtct tgcccttcag tttaccacca acccaaagag 1440actccagcaa aacctttttg gagggaaatt tttggtgaat gttggccagt ttaacttgtc 1500tggagccctt ggcacaagag gcacatttaa cttcagtcaa tttttccagc aacttggtct 1560tgcaagcttc ttgaatggag ggagacaaga agatttggcc aagccactct ctgtgggatt 1620agattcaaat tcttccacag gaacccctga agctgctaag aaggatggta ctatgaataa 1680gccaactgtg ggcagctttg gctttgaaat taacctacaa gagaaccaaa atgccctcaa 1740attccttgct tctctcctgg agcttccaga attccttctc ttcttgcaac atgctatctc 1800tgtgccagaa gatgtggcaa gagatttagg tgatgtgatg gaaacggtac tcagctccca 1860gacctgtgag cagacacctg aaaggctatt tgtcccatca tgcacgacag aaggaagcta 1920tgaggatgtc caatgctttt ccggagagtg ctggtgtgtg aattcctggg gcaaagagct 1980tccaggctca agagtcagag gtggacagcc aaggtgcccc acagactgtg aaaagcaaag 2040ggctcgcatg caaagcctca tgggcagcca gcctgctggc tccaccttgt ttgtccctgc 2100ttgtactagt gagggacatt tcctgcctgt ccagtgcttc aactcagagt gctactgtgt 2160tgatgctgag ggtcaggcca ttcctggaac tcgaagtgca atagggaagc ccaagaaatg 2220ccccacgccc tgtcaattac agtctgagca agctttcctc aggacggtgc aggccctgct 2280ctctaactcc agcatgctac ccaccctttc cgacacctac atcccacagt gcagcaccga 2340tgggcagtgg agacaagtgc aatgcaatgg gcctcctgag caggtcttcg agttgtacca 2400acgatgggag gctcagaaca agggccagga tctgacgcct gccaagctgc tagtgaagat 2460catgagctac agagaagcag cttccggaaa cttcagtctc tttattcaaa gtctgtatga 2520ggctggccag caagatgtct tcccggtgct gtcacaatac ccttctctgc aagatgtccc 2580actagcagca ctggaaggga aacggcccca gcccagggag aatatcctcc tggagcccta 2640cctcttctgg cagatcttaa atggccaact cagccaatac ccggggtcct actcagactt 2700cagcactcct ttggcacatt ttgatcttcg gaactgctgg tgtgtggatg aggctggcca 2760agaactggaa ggaatgcggt ctgagccaag caagctccca acatgtcctg gctcctgtga 2820ggaagcaaag ctccgtgtac tgcagttcat tagggaaacg gaagagattg tttcagcttc 2880caacagttct cggttccctc tgggggagag tttcctggtg gccaagggaa tccggctgag 2940gaatgaggac ctcggccttc

ctccgctctt cccgccccgg gaggctttcg cggagcagtt 3000tctgcgtggg agtgattacg ccattcgcct ggcggctcag tctaccttaa gcttctatca 3060gagacgccgc ttttccccgg acgactcggc tggagcatcc gcccttctgc ggtcgggccc 3120ctacatgcca cagtgtgatg cgtttggaag ttgggagcct gtgcagtgcc acgctgggac 3180tgggcactgc tggtgtgtag atgagaaagg agggttcatc cctggctcac tgactgcccg 3240ctctctgcag attccacagt gcccgacaac ctgcgagaaa tctcgaacca gtgggctgct 3300ttccagttgg aaacaggcta gatcccaaga aaacccatct ccaaaagacc tgttcgtccc 3360agcctgccta gaaacaggag agtatgccag gctgcaggca tcgggggctg gcacctggtg 3420tgtggaccct gcatcaggag aagagttgcg gcctggctcg agcagcagtg cccagtgccc 3480aagcctctgc aatgtgctca agagtggagt cctctccagg agagtcagcc caggctatgt 3540cccagcctgc agggcagagg atgggggctt ttccccagtg caatgtgacc aggcccaggg 3600cagctgctgg tgtgtcatgg acagcggaga agaggtgcct gggacgcgcg tgaccggggg 3660ccagcccgcc tgtgagagcc cgcggtgtcc gctgccattc aacgcgtcgg aggtggttgg 3720tggaacaatc ctgtgtgaga caatctcggg ccccacaggc tctgccatgc agcagtgcca 3780attgctgtgc cgccagggct cctggagcgt gtttccacca gggccattga tatgtagcct 3840ggagagcgga cgctgggagt cacagctgcc tcagccccgg gcctgccaac ggccccagct 3900gtggcagacc atccagaccc aagggcactt tcagctccag ctcccgccgg gcaagatgtg 3960cagtgctgac tacgcggatt tgctgcagac tttccaggtt ttcatattgg atgagctgac 4020agcccgcggc ttctgccaga tccaggtgaa gacttttggc accctggttt ccattcctgt 4080ctgcaacaac tcctctgtgc aggtgggttg tctgaccagg gagcgtttag gagtgaatgt 4140tacatggaaa tcacggcttg aggacatccc agtggcttct cttcctgact tacatgacat 4200tgagagagcc ttggtgggca aggatctcct tgggcgcttc acagatctga tccagagtgg 4260ctcattccag cttcatctgg actccaagac gttcccagcg gaaaccatcc gcttcctcca 4320aggggaccac tttggcacct ctcccaggac atggtttggg tgctcggaag gattctacca 4380agtcttgaca agtgaggcca gtcaggacgg actgggatgc gttaagtgtc ctgaaggaag 4440ctattcccaa gatgaggaat gcattccttg tcctgttgga ttctaccaag aacaggcagg 4500gagcttggcc tgtgtcccat gtcctgtggg cagaacgacc atttctgctg gagctttcag 4560ccagactcac tgtgtcactg actgtcagag gaacgaagca ggcctgcaat gtgaccagaa 4620tggccagtat cgagccagcc agaaggacag gggcagtggg aaggccttct gtgtggacgg 4680cgaggggcgg aggctgccat ggtgggaaac agaggcccct cttgaggact cacagtgttt 4740gatgatgcag aagtttgaga aggttccaga atcaaaggtg atcttcgacg ccaatgctcc 4800tgtggctgtc agatccaaag ttcctgattc tgagttcccc gtgatgcagt gcttgacaga 4860ttgcacagag gacgaggcct gcagcttctt caccgtgtcc acgacggagc cagagatttc 4920ctgtgatttc tatgcttgga caagtgacaa tgttgcctgc atgacttctg accagaaacg 4980agatgcactg gggaactcaa aggccaccag ctttggaagt cttcgctgcc aggtgaaagt 5040gaggagccat ggtcaagatt ctccagctgt gtatttgaaa aagggccaag gatccaccac 5100aacacttcag aaacgctttg aacccactgg tttccaaaac atgctttctg gattgtacaa 5160ccccattgtg ttctcagcct caggagccaa tctaaccgat gctcacctct tctgtcttct 5220tgcatgcgac cgtgatctgt gttgcgatgg cttcgtcctc acacaggttc aaggaggtgc 5280catcatctgt gggttgctga gctcacccag tgtcctgctt tgtaatgtca aagactggat 5340ggatccctct gaagcctggg ctaatgctac atgtcctggt gtgacatatg accaggagag 5400ccaccaggtg atattgcgtc ttggagacca ggagttcatc aagagtctga cacccttaga 5460aggaactcaa gacaccttta ccaattttca gcaggtttat ctctggaaag attctgacat 5520ggggtctcgg cctgagtcta tgggatgtag aaaagacaca gtgccaaggc cagcatctcc 5580aacagaagca ggtttgacaa cagaactttt ctcccctgtg gacctcaacc aggtcattgt 5640caatggaaat caatcactat ccagccagaa gcactggctt ttcaagcacc tgttttcagc 5700ccagcaggca aacctatggt gcctttctcg ttgtgtgcag gagcactctt tctgtcagct 5760cgcagagata acagagagtg catccttgta cttcacctgc accctctacc cagaggcaca 5820ggtgtgtgat gacatcatgg agtccaatgc ccagggctgc agactgatcc tgcctcagat 5880gccaaaggcc ctgttccgga agaaagttat actggaagat aaagtgaaga acttttacac 5940tcgcctgccg ttccaaaaac tgatggggat atccattaga aataaagtgc ccatgtctga 6000aaaatctatt tctaatgggt tctttgaatg tgaacgacgg tgcgatgcgg acccatgctg 6060cactggcttt ggatttctaa atgtttccca gttaaaagga ggagaggtga catgtctcac 6120tctgaacagc ttgggaattc agatgtgcag tgaggagaat ggaggagcct ggcgcatttt 6180ggactgtggc tctcctgaca ttgaagtcca cacctatccc ttcggatggt accagaagcc 6240cattgctcaa aataatgctc ccagtttttg ccctttggtt gttctgcctt ccctcacaga 6300gaaagtgtct ctggactcgt ggcagtccct ggccctctct tcagtggttg ttgatccatc 6360cattaggcac tttgatgttg cccatgtcag cactgctgcc accagcaatt tctctgctgt 6420ccgagacctc tgtttgtcgg aatgttccca acatgaggcc tgtctcatca ccactctgca 6480aacccaacct ggggctgtga gatgtatgtt ctatgctgat actcaaagct gcacacatag 6540tctgcagggt cagaactgcc gacttctgct tcgtgaagag gccacccaca tctaccggaa 6600gccaggaatc tctctgctca gctatgaggc atctgtacct tctgtgccca tttccaccca 6660tggccggctg ctgggcaggt cccaggccat ccaggtgggt acctcatgga agcaagtgga 6720ccagttcctt ggagttccat atgctgcccc gcccctggca gagaggcgct tccaggcacc 6780agagcccttg aactggacag gctcctggga tgccagcaag ccaagggcca gctgctggca 6840gccaggcacc agaacatcca cgtctcctgg agtcagtgaa gattgtttgt atctcaatgt 6900gttcatccct cagaatgtgg cccctaacgc gtctgtgctg gtgttcttcc acaacaccat 6960ggacagggag gagagtgaag gatggccggc tatcgacggc tccttcttgg ctgctgttgg 7020caacctcatc gtggtcactg ccagctaccg agtgggtgtc ttcggcttcc tgagttctgg 7080gtccggagag gtgagtggca actgggggct gctggaccag gtggcggctc tgacctgggt 7140gcagacccac atccgaggat ttggcgggga ccctcggcgc gtgtccctgg cagcagaccg 7200tggcggggct gatgtggcca gcatccacct tctcacggcc agggccacca actcccaact 7260tttccggaga gctgtgctga tgggaggctc cgcactctcc ccggccgccg tcatcagcca 7320tgagagggct cagcagcagg caattgcttt ggcaaaggag gtcagttgcc ccatgtcatc 7380cagccaagaa gtggtgtcct gcctccgcca gaagcctgcc aatgtcctca atgatgccca 7440gaccaagctc ctggccgtga gtggcccttt ccactactgg ggtcctgtga tcgatggcca 7500cttcctccgt gagcctccag ccagagcact gaagaggtct ttatgggtag aggtcgatct 7560gctcattggg agttctcagg acgacgggct catcaacaga gcaaaggctg tgaagcaatt 7620tgaggaaagt cgaggccgga ccagtagcaa aacagccttt taccaggcac tgcagaattc 7680tctgggtggc gaggactcag atgcccgcgt cgaggctgct gctacatggt attactctct 7740ggagcactcc acggatgact atgcctcctt ctcccgggct ctggagaatg ccacccggga 7800ctactttatc atctgcccta taatcgacat ggccagtgcc tgggcaaaga gggcccgagg 7860aaacgtcttc atgtaccatg ctcctgaaaa ctacggccat ggcagcctgg agctgctggc 7920ggatgttcag tttgccttgg ggcttccctt ctacccagcc tacgaggggc agttttctct 7980ggaggagaag agcctgtcgc tgaaaatcat gcagtacttt tcccacttca tcagatcagg 8040aaatcccaac tacccttatg agttctcacg gaaagtaccc acatttgcaa ccccctggcc 8100tgactttgta ccccgtgctg gtggagagaa ctacaaggag ttcagtgagc tgctccccaa 8160tcgacagggc ctgaagaaag ccgactgctc cttctggtcc aagtacatct cgtctctgaa 8220gacatctgca gatggagcca agggcgggca gtcagcagag agtgaagagg aggagttgac 8280ggctggatct gggctaagag aagatctcct aagcctccag gaaccaggct ctaagaccta 8340cagcaagtga ccagcccttg agctccccaa aaacctcacc cgaggctgcc cactatggtc 8400atctttttct ctaaaatagc cacttacctt caataaagta tctacatgcg gtgaa 8455771352DNAHomo sapiens 77actttgcctt gtgttttcca ccctgaaaga atgttgtggc tgctcttttt tctggtgact 60gccattcatg ctgaactctg tcaaccaggt gcagaaaatg cttttaaagt gagacttagt 120atcagaacag ctctgggaga taaagcatat gcctgggata ccaatgaaga atacctcttc 180aaagcgatgg tagctttctc catgagaaaa gttcccaaca gagaagcaac agaaatttcc 240catgtcctac tttgcaatgt aacccagagg gtatcattct ggtttgtggt tacagaccct 300tcaaaaaatc acacccttcc tgctgttgag gtgcaatcag ccataagaat gaacaagaac 360cggatcaaca atgccttctt tctaaatgac caaactctgg aatttttaaa aatcccttcc 420acacttgcac cacccatgga cccatctgtg cccatctgga ttattatatt tggtgtgata 480ttttgcatca tcatagttgc aattgcacta ctgattttat cagggatctg gcaacgtaga 540agaaagaaca aagaaccatc tgaagtggat gacgctgaag ataagtgtga aaacatgatc 600acaattgaaa atggcatccc ctctgatccc ctggacatga agggagggca tattaatgat 660gccttcatga cagaggatga gaggctcacc cctctctgaa gggctgttgt tctgcttcct 720caagaaatta aacatttgtt tctgtgtgac tgctgagcat cctgaaatac caagagcaga 780tcatatattt tgtttcacca ttcttctttt gtaataaatt ttgaatgtgc ttgaaagtga 840aaagcaatca attataccca ccaacaccac tgaaatcata agctattcac gactcaaaat 900attctaaaat atttttctga cagtatagtg tataaatgtg gtcatgtggt atttgtagtt 960attgatttaa gcatttttag aaataagatc aggcatatgt atatattttc acacttcaaa 1020gacctaagga aaaataaatt ttccagtgga gaatacatat aatatggtgt agaaatcatt 1080gaaaatggat cctttttgac gatcacttat atcactctgt atatgactaa gtaaacaaaa 1140gtgagaagta attattgtaa atggatggat aaaaatggaa ttactcatat acagggtgga 1200attttatcct gttatcacac caacagttga ttatatattt tctgaatatc agcccctaat 1260aggacaattc tatttgttga ccatttctac aatttgtaaa agtccaatct gtgctaactt 1320aataaagtaa taatcatctc tttttgattg tg 1352784944DNAHomo sapiens 78ctatgtctga tagcatttga ccctattgct tttagcctcc cggctttata tctatatata 60cacaggtata tgtgtatatt ttatataatt gttctccgtt cgttgatatc aaagacagtt 120gaaggaaatg aattttgaaa cttcacggtg tgccacccta cagtactgcc ctgaccctta 180catccagcgt ttcgtagaaa ccccagctca tttctcttgg aaagaaagtt attaccgatc 240caccatgtcc cagagcacac agacaaatga attcctcagt ccagaggttt tccagcatat 300ctgggatttt ctggaacagc ctatatgttc agttcagccc attgacttga actttgtgga 360tgaaccatca gaagatggtg cgacaaacaa gattgagatt agcatggact gtatccgcat 420gcaggactcg gacctgagtg accccatgtg gccacagtac acgaacctgg ggctcctgaa 480cagcatggac cagcagattc agaacggctc ctcgtccacc agtccctata acacagacca 540cgcgcagaac agcgtcacgg cgccctcgcc ctacgcacag cccagctcca ccttcgatgc 600tctctctcca tcacccgcca tcccctccaa caccgactac ccaggcccgc acagtttcga 660cgtgtccttc cagcagtcga gcaccgccaa gtcggccacc tggacgtatt ccactgaact 720gaagaaactc tactgccaaa ttgcaaagac atgccccatc cagatcaagg tgatgacccc 780acctcctcag ggagctgtta tccgcgccat gcctgtctac aaaaaagctg agcacgtcac 840ggaggtggtg aagcggtgcc ccaaccatga gctgagccgt gaattcaacg agggacagat 900tgcccctcct agtcatttga ttcgagtaga ggggaacagc catgcccagt atgtagaaga 960tcccatcaca ggaagacaga gtgtgctggt accttatgag ccaccccagg ttggcactga 1020attcacgaca gtcttgtaca atttcatgtg taacagcagt tgtgttggag ggatgaaccg 1080ccgtccaatt ttaatcattg ttactctgga aaccagagat gggcaagtcc tgggccgacg 1140ctgctttgag gcccggatct gtgcttgccc aggaagagac aggaaggcgg atgaagatag 1200catcagaaag cagcaagttt cggacagtac aaagaacggt gatggtacga agcgcccgtt 1260tcgtcagaac acacatggta tccagatgac atccatcaag aaacgaagat ccccagatga 1320tgaactgtta tacttaccag tgaggggccg tgagacttat gaaatgctgt tgaagatcaa 1380agagtccctg gaactcatgc agtaccttcc tcagcacaca attgaaacgt acaggcaaca 1440gcaacagcag cagcaccagc acttacttca gaaacagacc tcaatacagt ctccatcttc 1500atatggtaac agctccccac ctctgaacaa aatgaacagc atgaacaagc tgccttctgt 1560gagccagctt atcaaccctc agcagcgcaa cgccctcact cctacaacca ttcctgatgg 1620catgggagcc aacattccca tgatgggcac ccacatgcca atggctggag acatgaatgg 1680actcagcccc acccaggcac tccctccccc actctccatg ccatccacct cccactgcac 1740acccccacct ccgtatccca cagattgcag cattgtcagt ttcttagcga ggttgggctg 1800ttcatcatgt ctggactatt tcacgaccca ggggctgacc accatctatc agattgagca 1860ttactccatg gatgatctgg caagtctgaa aatccctgag caatttcgac atgcgatctg 1920gaagggcatc ctggaccacc ggcagctcca cgaattctcc tccccttctc atctcctgcg 1980gaccccaagc agtgcctcta cagtcagtgt gggctccagt gagacccggg gtgagcgtgt 2040tattgatgct gtgcgattca ccctccgcca gaccatctct ttcccacccc gagatgagtg 2100gaatgacttc aactttgaca tggatgctcg ccgcaataag caacagcgca tcaaagagga 2160gggggagtga gcctcaccat gtgagctctt cctatccctc tcctaactgc cagcccccta 2220aaagcactcc tgcttaatct tcaaagcctt ctccctagct cctccccttc ctcttgtctg 2280atttcttagg ggaaggagaa gtaagaggct acctcttacc taacatctga cctggcatct 2340aattctgatt ctggctttaa gccttcaaaa ctatagcttg cagaactgta gctgccatgg 2400ctaggtagaa gtgagcaaaa aagagttggg tgtctcctta agctgcagag atttctcatt 2460gacttttata aagcatgttc acccttatag tctaagacta tatatataaa tgtataaata 2520tacagtatag atttttgggt ggggggcatt gagtattgtt taaaatgtaa tttaaatgaa 2580agaaaattga gttgcactta ttgaccattt tttaatttac ttgttttgga tggcttgtct 2640atactccttc ccttaagggg tatcatgtat ggtgataggt atctagagct taatgctaca 2700tgtgagtgac gatgatgtac agattctttc agttctttgg attctaaata catgccacat 2760caaacctttg agtagatcca tttccattgc ttattatgta ggtaagactg tagatatgta 2820ttcttttctc agtgttggta tattttatat tactgacatt tcttctagtg atgatggttc 2880acgttggggt gatttaatcc agttataaga agaagttcat gtccaaacgt cctctttagt 2940ttttggttgg gaatgaggaa aattcttaaa aggcccatag cagccagttc aaaaacaccc 3000gacgtcatgt atttgagcat atcagtaacc cccttaaatt taataccaga taccttatct 3060tacaatattg attgggaaaa catttgctgc cattacagag gtattaaaac taaatttcac 3120tactagattg actaactcaa atacacattt gctactgttg taagaattct gattgatttg 3180attgggatga atgccatcta tctagttcta acagtgaagt tttactgtct attaatattc 3240agggtaaata ggaatcattc agaaatgttg agtctgtact aaacagtaag atatctcaat 3300gaaccataaa ttcaactttg taaaaatctt ttgaagcata gataatattg tttggtaaat 3360gtttcttttg tttggtaaat gtttctttta aagaccctcc tattctataa aactctgcat 3420gtagaggctt gtttaccttt ctctctctaa ggtttacaat aggagtggtg atttgaaaaa 3480tataaaatta tgagattggt tttcctgtgg cataaattgc atcactgtat cattttcttt 3540tttaaccggt aagagtttca gtttgttgga aagtaactgt gagaacccag tttcccgtcc 3600atctccctta gggactaccc atagacatga aaggtcccca cagagcaaga gataagtctt 3660tcatggctgc tgttgcttaa accacttaaa cgaagagttc ccttgaaact ttgggaaaac 3720atgttaatga caatattcca gatctttcag aaatataaca catttttttg catgcatgca 3780aatgagctct gaaatcttcc catgcattct ggtcaagggc tgtcattgca cataagcttc 3840cattttaatt ttaaagtgca aaagggccag cgtggctcta aaaggtaatg tgtggattgc 3900ctctgaaaag tgtgtatata ttttgtgtga aattgcatac tttgtatttt gattattttt 3960tttttcttct tgggatagtg ggatttccag aaccacactt gaaacctttt tttatcgttt 4020ttgtattttc atgaaaatac catttagtaa gaataccaca tcaaataaga aataatgcta 4080caattttaag aggggaggga agggaaagtt tttttttatt atttttttaa aattttgtat 4140gttaaagaga atgagtcctt gatttcaaag ttttgttgta cttaaatggt aataagcact 4200gtaaacttct gcaacaagca tgcagctttg caaacccatt aaggggaaga atgaaagctg 4260ttccttggtc ctagtaagaa gacaaactgc ttcccttact ttgctgaggg tttgaataaa 4320cctaggactt ccgagctatg tcagtactat tcaggtaaca ctagggcctt ggaaattcct 4380gtactgtgtc tcatggattt ggcactagcc aaagcgaggc acccttactg gcttacctcc 4440tcatggcagc ctactctcct tgagtgtatg agtagccagg gtaaggggta aaaggatagt 4500aagcatagaa accactagaa agtgggctta atggagttct tgtggcctca gctcaatgca 4560gttagctgaa gaattgaaaa gtttttgttt ggagacgttt ataaacagaa atggaaagca 4620gagttttcat taaatccttt tacctttttt ttttcttggt aatcccctaa aataacagta 4680tgtgggatat tgaatgttaa agggatattt ttttctatta tttttataat tgtacaaaat 4740taagcaaatg ttaaaagttt tatatgcttt attaatgttt tcaaaaggta ttatacatgt 4800gatacatttt ttaagcttca gttgcttgtc ttctggtact ttctgttatg ggcttttggg 4860gagccagaag ccaatctaca atctcttttt gtttgccagg acatgcaata aaatttaaaa 4920aataaataaa aactaattaa gaaa 4944799859DNAHomo sapiens 79ttcctccgcg aaggctcctt tgatattaat agtgttggtg tcttgaaact gacgtaatgc 60gcggagactg aggtcctgac aagcgataac atttctgata aagacccgat cttactgcaa 120tctctagcgt cctctttttt ggtgctgctg gtttctccag acctcgcgtc ctctcgattg 180ctctctcgcc ttcctatttc tttttttttt ttttaaacaa aaaacaacac cccctcccct 240ctcccacccg gcaccgggca catccttgct ctatttcctt tctctttctc tctctctctc 300tctctctctc ttttttaata agggtggggg agggaaaggg gggggaggca ggaaagacct 360ttttctctcc cccccgcaat aatccaagat caactctgca aacaacagaa gacggttcat 420ggctttggcc gccgcgccac catctttcgg gctgccgagg gtgttcttga cgattaatca 480acagatatgg tccggaaaaa gaacccccct ctgagaaacg ttgcaagtga aggcgagggc 540cagatcctgg agcctatagg tacagaaagc aaggtatctg gaaagaacaa agaattttct 600gcagatcaga tgtcagaaaa tacggatcag agtgatgctg cagaactaaa tcataaggag 660gaacatagct tgcatgttca agatccatct tctagcagta agaaggactt gaaaagcgca 720gttctgagtg agaaggctgg cttcaattat gaaagcccca gtaagggagg aaactttccc 780tcctttccgc atgatgaggt gacagacaga aatatgttgg ctttctcatc tccagctgct 840gggggagtct gtgagccctt gaagtctccg caaagagcag aggcagatga ccctcaagat 900atggcctgca ccccctcagg ggactcactg gagacaaagg aagatcagaa gatgtcacca 960aaggctacag aggaaacagg gcaagcacag agtggtcaag ccaattgtca aggtttgagc 1020ccagtttcag tggcctcaaa aaacccacaa gtgccttcag atgggggtgt aagactgaat 1080aaatccaaaa ctgacttact ggtgaatgac aacccagacc cggcacctct gtctccagag 1140cttcaggact ttaaatgcaa tatctgtgga tatggttact acggcaacga ccccacagat 1200ctgattaagc acttccgaaa gtatcactta ggactgcata accgcaccag gcaagatgct 1260gagctggaca gcaaaatctt ggcccttcat aacatggtgc agttcagcca ttccaaagac 1320ttccagaagg tcaaccgttc tgtgttttct ggtgtgctgc aggacatcaa ttcttcaagg 1380cctgttttac taaatgggac ctatgatgtg caggtgactt caggtggaac attcattggc 1440attggacgga aaacaccaga ttgccaaggg aacaccaagt atttccgctg taaattctgc 1500aatttcactt atatgggcaa ctcatccacc gaattagaac aacattttct tcagactcac 1560ccaaacaaaa taaaagcttc tctcccctcc tctgaggttg caaaaccttc agagaaaaac 1620tctaacaagt ccatccctgc acttcaatcc agtgattctg gagacttggg aaaatggcag 1680gacaagataa cagtcaaagc aggagatgac actcctgttg ggtactcagt gcccataaag 1740cccctcgatt cctctagaca aaatggtaca gaggccacca gttactactg gtgtaaattt 1800tgtagtttca gctgtgagtc atctagctca cttaaactgc tagaacatta tggcaagcag 1860cacggagcag tgcagtcagg cggccttaat ccagagttaa atgataagct ttccaggggc 1920tctgtcatta atcagaatga tctagccaaa agttcagaag gagagacaat gaccaagaca 1980gacaagagct cgagtggggc taaaaagaag gacttctcca gcaagggagc cgaggataat 2040atggtaacga gctataattg tcagttctgt gacttccgat attccaaaag ccatggccct 2100gatgtaattg tagtggggcc acttctccgt cattatcaac agctccataa cattcacaag 2160tgtaccatta aacactgtcc attctgtccc agaggacttt gcagcccaga aaagcacctt 2220ggagaaatta cttatccgtt tgcttgtaga aaaagtaatt gttcccactg tgcactcttg 2280cttctgcact tgtctcctgg ggcggctgga agctcgcgag tcaaacatca gtgccatcag 2340tgttcattca ccacccctga cgtagatgta ctcctctttc actatgaaag tgtgcatgag 2400tcccaagcat cggatgtcaa acaagaagca aatcacctgc aaggatcgga tgggcagcag 2460tctgtcaagg aaagcaaaga acactcatgt accaaatgtg attttattac ccaagtggaa 2520gaagagattt cccgacacta caggagagca cacagctgct acaaatgccg tcagtgcagt 2580tttacagctg ccgatactca gtcactactg gagcacttca acactgttca ctgccaggaa 2640caggacatca ctacagccaa cggcgaagag gacggtcatg ccatatccac catcaaagag 2700gagcccaaaa ttgacttcag ggtctacaat ctgctaactc cagactctaa aatgggagag 2760ccagtttctg agagtgtggt gaagagagag aagctggaag agaaggacgg gctcaaagag 2820aaagtttgga ccgagagttc cagtgatgac cttcgcaatg tgacttggag aggggcagac 2880atcctgcggg ggagtccgtc atacacccaa gcaagcctgg ggctgctgac gcctgtgtct 2940ggcacccaag agcagacaaa gactctaagg gatagtccca atgtggaggc cgcccatctg 3000gcgcgaccta tttatggctt ggctgtggaa accaagggat tcctgcaggg ggcgccagct 3060ggcggagaga agtctggggc cctcccccag cagtatcctg catcgggaga aaacaagtcc 3120aaggatgaat cccagtccct

gttacggagg cgtagaggct ccggtgtttt ttgtgccaat 3180tgcctgacca caaagacctc tctctggcga aagaatgcaa atggcggata tgtatgcaac 3240gcgtgtggcc tctaccagaa gcttcactcg actcccaggc ctttaaacat cattaaacaa 3300aacaacggtg agcagattat taggaggaga acaagaaagc gccttaaccc agaggcactt 3360caggctgagc agctcaacaa acagcagagg ggcagcaatg aggagcaagt caatggaagc 3420ccgttagaga ggaggtcaga agatcatcta actgaaagtc accagagaga aattccactc 3480cccagcctaa gtaaatacga agcccagggt tcattgacta aaagccattc tgctcagcag 3540ccagtcctgg tcagccaaac tctggatatt cacaaaagga tgcaaccttt gcacattcag 3600ataaaaagtc ctcaggaaag tactggagat ccaggaaata gttcatccgt atctgaaggg 3660aaaggaagtt ctgagagagg cagtcctata gaaaagtaca tgagacctgc gaaacaccca 3720aattattcac caccaggcag ccctattgaa aagtaccagt acccactttt tggacttccc 3780tttgtacata atgacttcca gagtgaagct gattggctgc ggttctggag taaatataag 3840ctctccgttc ctgggaatcc gcactacttg agtcacgtgc ctggcctacc aaatccttgc 3900caaaactatg tgccttatcc caccttcaat ctgcctcctc atttttcagc tgttggatca 3960gacaatgaca ttcctctaga tttggcgatc aagcattcca gacctgggcc aactgcaaac 4020ggtgcctcca aggagaaaac gaaggcacca ccaaatgtaa aaaatgaagg tcccttgaat 4080gtagtaaaaa cagagaaagt tgatagaagt actcaagatg aactttcaac aaaatgtgtg 4140cactgtggca ttgtctttct ggatgaagtg atgtatgctt tgcatatgag ttgccatggt 4200gacagtggac ctttccagtg cagcatatgc cagcatcttt gcacggacaa atatgacttc 4260acaacacata tccagagggg cctgcatagg aacaatgcac aagtggaaaa aaatggaaaa 4320cctaaagagt aaaaccttag cacttagcac aattaaatag aaataggttt tcttgatggg 4380aattcaatag cttgtaatgt cttatgaaga cctattaaaa aaatacttca tagagcctgc 4440cttatccaac atgaaattcc cttcttttgt tattctttct tttgatgagt aggttaccaa 4500gattaaaaag tgagataaat ggtcaatgag aaagaatgga agatggtaaa caatcacttt 4560ttaaaacctg ttaagtcaaa accatcttgg ctaatatgta ctggggaaat aatccataag 4620agatatcacc agactagaat taatatattt ataaagaaag agaccaaaac tgtctagaat 4680ttgaaagggt ttacatatta ttatactaaa gcagtactgg actggccatt ggaccatttg 4740ttccaaaacc cataaattgt tgcctaaatt tataatgatc atgaaaccct aggcagagga 4800ggagaaattg aaggtccagg gcaatgaaag aaaaatggcg ccctctcaat ttagtcttct 4860ctcattggcc atgtttcaga ttttgaccta gaaatgcgag ctgtggttag gcttggttag 4920agtgcagcaa gcaacatgac agatggtggc acgctgtttt tacccagccc tgcctgtaca 4980tacacatgca caccctctct gatatttttg tcctttagat gttcaaatac tcagtagtcc 5040ttttgtttgc ggtttagatt cattttgtcc acacatgtac ccattttaaa aaacaatgtc 5100ctcgatgctt ctgtagtgat ttcattttag ccaggtattt ctttcttgtg tgtgatgaac 5160cagtatggat ttgcttttct aagcctcctg ttggttacta atctcacttg gcacattata 5220actaaaggaa tcccctcaat tcaaaagcat agatggatac aaatgtcaga ccgtgggttt 5280aatttgttta gaacacatgg catttcttca caaggtaacc tgctgtattt atttattttc 5340ttttggttaa atataatttc caaactttgt ggtcaggcag cgtctaaggt tacgttacca 5400cagactgaca gttggtatat gtaccagcca atcccttcat taaatgtata cagatttagt 5460taagtagcat taaataggat tcttagaagt atgtcctcat agaactttta atacttaagg 5520ctttgtaaaa actatccatg aagggaaagc tcctcagcat aactgctcag ggaaataggg 5580ctaaataact gaacattaaa taattggtta aaggtgctgt tagtcgagcc tcaatgcttg 5640ctacaaggat gtatgtacaa ggactgactt taataatttg cattatattg tcccaaccag 5700tagtttattt tttgccacgg agatgtagaa gatattacaa gctactggat gcactgtcag 5760attaacttat ttcattaaag aagttgggag aacaaatagg aaaaaaaaaa cttatttttc 5820tagtaaatat taatgtatta catttcaaat aatggtgcct gacatattga ataattattt 5880tctacagtgt acgtatgcaa caaagatatt ccatcatgca ttagagtcag ttctggctct 5940gcctagctgt ttacatttgc aaatgtagca aacaaggtaa tgaagcaact atttctattg 6000cagtagatat ccttttgtgt gtgtgtgtgt gcattaaagt tgtaaacggt aacatgaaac 6060aaatgaaagt tcttgctata atggtatgga aaacaagaag gaaatgaaaa tatttttatg 6120cctacttagg aaaaaaaggg tagcacttat tcattccaag tacttttttt tttttaattt 6180ttaagctctt aactcacatt gttatgctta agatgataaa catatatcct ctttttattg 6240ctttgtctat gtttcatatg aaacatttca gaaattattt tgataagtgt tgctggaatc 6300tgcaacgctg attttttttt gcattctgta gtcgcatttg cactccattt ttacattaat 6360tcgcagttgc tttgtatcat tgttttgttt gggttttgtt tctttttcac agtgccgggt 6420cttcgtttct taaagttgga tggcaggtag agttcaacca gttcgtgact gttgtagcga 6480atgaagttaa aaaaatgtct ttctgatgtt gtgttgtcat tttcattttt gcattttttt 6540gtttgcatat taaaaaaaga gaaaagagaa agcaagagac agaaatcagg actaagtcct 6600ctgcttcagt ttcattgtta acgggcctta ttctgatctc acctgtcgcg tagctctaat 6660attcacataa actgaaataa agaagtggaa tgaggagctt tgacattcaa attatgtgat 6720gtaatttatc ttccttagga attttgatgg atgcatctca aaatgtatag ccagacttga 6780gaggtgacaa ttaaagatct aaaaaagaga ggagattccc ccaaacaaca atatttaatt 6840ttcttagtaa aaagaataac agaatgcatc gtggcaatcc ttaagcaaca ttatctatgt 6900ggactgctta aatcagcaaa acaccagaag tttggttaac ttgggcaata tgacaagtat 6960tactttttgg gcaaaactac tcattaagca atttctctag tgtgtcggac acaaataggt 7020tctttatttt tggcatgtat gcctttttat tttcattcaa tttttttttt ttctcagaca 7080gacatagtag taacgactag cattggaaaa tacatatcac tattcttgga atatttatgg 7140tcagtctact ttttagtaga atatttttgg atagcgttga cacgatagat cttattccat 7200acttctttat tattgataat tttattttca ttttttgctt tcattattat acatattttg 7260gtggagaaga ggttgggctt ttttgaaaga gacaaaaatt tattataaca ctaaacactc 7320cttttttgac atattaaagc ctttattcca tctctcaaga tatattataa aatttatttt 7380tttaatttaa gatttctgaa ttattttatc ttaaattgtg attttaaacg agctattatg 7440gtacggaact ttttttaatg aggaatttca tgatgattta ggaattttct ctcttggaaa 7500aggcttcccc tgtgatgaaa atgatgtgcc agctaaaatt gtgtgccatt taaaaactga 7560aaatatttta aaattatttg tctatattct aaattgagct ttggatcaaa ctttaggcca 7620ggaccagctc atgcgttctc attcttcctt ttctcactct ttctctcatc actcacctct 7680gtattcattc tgttgtttgg gatagaaaaa tcataaagag ccaacccatc tcagaacgtt 7740gtggattgag agagacacta catgactcca agtatatgag aaaaggacag agctctaatt 7800gataactctg tagttcaaaa ggaaaagagt atgcccaatt ctctctacat gacatattga 7860gatttttttt aatcaacttt taagatagtg atgttctgtt ctaaactgtt ctgttttagt 7920gaaggtagat ttttataaaa caagcatggg gattcttttc taaggtaata ttaatgagaa 7980gggaaaaaag tatctttaac agctctttgt tgaagcctgt ggtagcacat tatgtttata 8040attgcacatg tgcacataat ctattatgat ccaatgcaaa tacagctcca aaaatattaa 8100atgtatatat attttaaaat gcctgaggaa atacattttt cttaataaac tgaagagtct 8160cagtatggct attaaaataa ttattagcct cctgttgtgt ggctgcaaaa catcacaaag 8220tgaccggtct tgagacctgt gaactgctgc cctgtttagt aaataaaatt aatgcatttc 8280tagaggggga atatctgcca tccagtggtg gaaatgtgga gtaaagaagc tggtggtctg 8340cttctgtgct gtatgccagc cttttgcctt aagttgagag gaggtcaact ttagctactg 8400tctttggttt gagagccatg gcaaaaaaaa aaaaagaaaa aaagatcaag tcgtctttgg 8460tgagccagta aggtgaaagc ttgctgactg tccaaggcac aagagaaaat tgaggaattg 8520aaatgcaacc tgagtatcaa actaaatatt ctaatcaaag gtaggtactg ttaggtggaa 8580ttctatcagc aggcaactgc aaatgagaag aagatagaag gacgcccgtc gggactttgg 8640agggcattgt tattttccca aagaaagacg gccaagggca gaggcatgga ttctttgcag 8700agcacttcct tttggttttt cagtactgtt tcatagacag tgggctcaca tgttcctgat 8760agtgctgcag ttgcttagaa agcatcccag ttaattgcag taattagaac ttctggaata 8820tgctagggca gaagtatgtc aagtatgtca catgaagaaa atgtgaaatt caagagtaat 8880ccacacgtga gaaactagac aatgtacatt catgtgttct cttgaaagga aagggagagc 8940tgtaagcttc actctgtcct acaccggaga aaagcaggaa taactttacc gtggaaataa 9000tgtttagctt ttatcagaga aaattgtcct tctagagcat agagtcccaa aactcaattc 9060tggttttccc ctgttttttt tttttttttt tttcccaaca tataaactgc agcatatcac 9120tttttctttt tgtgcctcag gttcctcagc tgtaaaattg aaaaatatat gtattaataa 9180tattattaat aataataatg gtaatgtagt acttgtttgt aaagcacttt gagatccttg 9240gttgaaaggc accataggag tgccaagtat tattatgtgg ccaagggggt tatttaaact 9300gtcagttccc aaaggccagg aaaggttggg gtcatttttc ttaaagacga gctgtaaata 9360tcaactaggc agccaatagt gttgactatg aagatgcaaa actattacta ggctgataaa 9420atcatagttt cttaatggct accaataagg caaatatcac aataataaac gccaaattcc 9480ttagggcgga ctatttgaca accacatgga aaactttggg ggaggcatga ggggggaaca 9540tctcaaaatg ccaatgtaaa atttaactta cagcaatatt caccagcaga aaatgtcttt 9600catatggaat gatttcatgt tgctaagaaa aagaattcaa tttgtagtcc tgatttgaat 9660actagaatgt tggctataat agttctgttc ttacaacaca tgaaattttt tcgttttatt 9720ttattttgtt ttcatagtgc atgttcattt ctactcacaa acatgttctt ggtgtatttc 9780ttatgcaaac aatcttcagg cagcaaagat gtctgttaca tctaaacttg aataataaag 9840ttttaccacc agttacaca 9859801131DNAHomo sapiens 80agtgccccag gagctatgac aagcaaagga acatacttgc ctggagatag cctttgcgat 60atttaaatgt ccgtggatac agaaatctct gcaggcaagt tgctccagag catattgcag 120gacaagcctg taacgaatag ttaaattcac ggcatctgga ttcctaatcc ttttccgaaa 180tggcaggtgt gagtgcctgt ataaaatatt ctatgtttac cttcaacttc ttgttctggc 240tatgtggtat cttgatccta gcattagcaa tatgggtacg agtaagcaat gactctcaag 300caatttttgg ttctgaagat gtaggctcta gctcctacgt tgctgtggac atattgattg 360ctgtaggtgc catcatcatg attctgggct tcctgggatg ctgcggtgct ataaaagaaa 420gtcgctgcat gcttctgttg tttttcatag gcttgcttct gatcctgctc ctgcaggtgg 480cgacaggtat cctaggagct gttttcaaat ctaagtctga tcgcattgtg aatgaaactc 540tctatgaaaa cacaaagctt ttgagcgcca caggggaaag tgaaaaacaa ttccaggaag 600ccataattgt gtttcaagaa gagtttaaat gctgcggttt ggtcaatgga gctgctgatt 660ggggaaataa ttttcaacac tatcctgaat tatgtgcctg tctagataag cagagaccat 720gccaaagcta taatggaaaa caagtttaca aagagacctg tatttctttc ataaaagact 780tcttggcaaa aaatttgatt atagttattg gaatatcatt tggactggca gttattgaga 840tactgggttt ggtgttttct atggtcctgt attgccagat cgggaacaaa tgaatctgtg 900gatgcatcaa cctatcgtca gtcaaacccc tttaaaatgt tgctttggct ttgtaaattt 960aaatatgtaa gtgctatata agtcaggagc agctgtcttt ttaaaatgtc tcggctagct 1020agaccacaga tatcttctag acatattgaa cacatttaag atttgaggga tataagggaa 1080aatgatatga atgtgtattt ttactcaaaa taaaagtaac tgtttacgtt g 1131812459DNAHomo sapiens 81gagagactgg gaggggcccc aatccaggct ccgggatggc ctggctggca tctggggttc 60cagtggcccc tctcccttgg ccctggcagt ggggctggat actggcctgc ctcccaccag 120agtcccccca gctcctccct gctgtgggct ggcctgggag gaagggggtg gggtgcactt 180acatttgcag gtctttccag cccctggggc agcctgatta accagcttct ccagggccaa 240gctgttgggg gtgaggtgca gcccgaagca gccagaccag cccctgagcc tcccgggtgc 300tggcagctgt catggggcta ccctgggggc agcctcacct agggctgcag atgctcctcc 360tggcgttgaa ctgtctccgg cccagcctga gcctggagct ggtgccctac acaccacaga 420taacagcttg ggacctggaa gggaaggtca cagccaccac cttctccctg gagcagccgc 480gctgtgtctt cgatgggctt gccagcgcca gcgataccgt ctggctcgtg gtggccttca 540gcaatgcctc caggggcttc cagaacccgg agacactggc tgacattccg gcctccccac 600agctgctgac cgatggccac tacatgacgc tgcccctgtc tccggaccag ctgccctgtg 660gcgaccccat ggcgggcagc ggaggcgccc ccgtgctgcg ggtgggccat gaccacggct 720gccaccagca gcccttctgc aacgcgcccc tccctggccc tggaccctat cgggtgaagt 780tcctcctgat ggacaccagg ggctcaccca gggctgagac caagtggtca gaccccatca 840ctctccacca agggaagacc cccggatcca tcgacacctg gccagggcgg cgaagtggca 900gcatgatcgt cattacctcc atcctctctt ctctggccgg cctcctactc ttggccttct 960tggcagcctc taccatgcgc ttctccagcc tgtggtggcc ggaggaggcc ccggagcagc 1020tgcggatcgg ctccttcatg ggcaagcgct acatgaccca ccacatccca cccagagagg 1080ccgccacact gccggtgggc tgcaagcctg gcctggaccc cctccccagc ctcagcccct 1140agcctggcct ctttgcatgg ggctggggga gatggggcgc tgggagtgag tgcatggtgc 1200tttgtcccag ctcctgcacc cacaggcccc ctcagggctc cttgcctttc ccccccacca 1260gcacaccccg taccctgcct ggaatcccag caccagcccc cctgcctctc ctctgccttt 1320ctggtttctc tccctctcca agcatctgta agttgcactc aggagggttt aggggagggc 1380catgggcagg ctggataccc agtccccacc tccatcccca cctctgtctc acctgacctc 1440ctgcgaggga ggctggagac tgtgtggaca ggccgccctg accgcaagct tccagaccct 1500gggaggaggc ctgcagagga ctgtgctttg cctgatgcag ggagctgggc ccatcctggg 1560gcctatgaga cctgagccac cctccgtccc ccatcccaca catcagtggc tgggcggggt 1620gaggattcag aggcatctct actgcccctg ggcacagcac ctttctgaga gtgggactct 1680ccatggtcat ctgactacca attctggcca ccacctccaa ccctcttgtg catatggatg 1740gctctagccc ttatccaccc cctcaagcat ttattaagca tctgctgtat gctacataca 1800gtgttagact tggggcttca ggcatagccg gtcctgacct tggggagatg ccttctctag 1860acctgagacg accacgtgtc cagatgtgac ctgttgctgt cgggggtcta tcaggccctt 1920agaccgtcac cccagtaggc tctccaggac ccaggagcct ccatcacctg gaaggaccct 1980ctgtgcaaaa cctcaagcgt ccatctgtgc acaaggccgg tggttcccgt cgtcgccact 2040cggggtcgcc ggtgagccgc agccaggccg cctcacggcc agtgtgcatg ctcgctgcta 2100ttcgctgccc cttctgcctc cgaggcggta gcagatgcca cgttggcggg gtcggtgaag 2160gtcaggactc taggcctccc tccgccaagc cagagggatg agcaatcacg cctgagagcc 2220cactgcgtgc catgcagtcc gcacagccgc agcggttttc tagatggaga aactgaggct 2280cagtgacttg cccgctgcac tctgtccacg gccgctgcac acgccccctt gggctgcgct 2340cccggacctt ctaatgtgac cacggctccc ggcatgcagg ccctgccagc ggagggagcc 2400cggtggtgac ccttggtctg cagccctctt tggaggtgaa taaatgcggt ctggagccc 2459821626DNAHomo sapiens 82ctccttccct gtctctgcct ctccctccct tcctcaggca tcagagcgga gacttcaggg 60agaccagagc ccagcttgcc aggcactgag ctagaagccc tgccatggca cccctgagac 120cccttctcat actggccctg ctggcatggg ttgctctggc tgaccaagag tcatgcaagg 180gccgctgcac tgagggcttc aacgtggaca agaagtgcca gtgtgacgag ctctgctctt 240actaccagag ctgctgcaca gactatacgg ctgagtgcaa gccccaagtg actcgcgggg 300atgtgttcac tatgccggag gatgagtaca cggtctatga cgatggcgag gagaaaaaca 360atgccactgt ccatgaacag gtggggggcc cctccctgac ctctgacctc caggcccagt 420ccaaagggaa tcctgagcag acacctgttc tgaaacctga ggaagaggcc cctgcgcctg 480aggtgggcgc ctctaagcct gaggggatag actcaaggcc tgagaccctt catccaggga 540gacctcagcc cccagcagag gaggagctgt gcagtgggaa gcccttcgac gccttcaccg 600acctcaagaa cggttccctc tttgccttcc gagggcagta ctgctatgaa ctggacgaaa 660aggcagtgag gcctgggtac cccaagctca tccgagatgt ctggggcatc gagggcccca 720tcgatgccgc cttcacccgc atcaactgtc aggggaagac ctacctcttc aagggtagtc 780agtactggcg ctttgaggat ggtgtcctgg accctgatta cccccgaaat atctctgacg 840gcttcgatgg catcccggac aacgtggatg cagccttggc cctccctgcc catagctaca 900gtggccggga gcgggtctac ttcttcaagg ggaaacagta ctgggagtac cagttccagc 960accagcccag tcaggaggag tgtgaaggca gctccctgtc ggctgtgttt gaacactttg 1020ccatgatgca gcgggacagc tgggaggaca tcttcgagct tctcttctgg ggcagaacct 1080ctgctggtac cagacagccc cagttcatta gccgggactg gcacggtgtg ccagggcaag 1140tggacgcagc catggctggc cgcatctaca tctcaggcat ggcaccccgc ccctccttgg 1200ccaagaaaca aaggtttagg catcgcaacc gcaaaggcta ccgttcacaa cgaggccaca 1260gccgtggccg caaccagaac tcccgccggc catcccgcgc cacgtggctg tccttgttct 1320ccagtgagga gagcaacttg ggagccaaca actatgatga ctacaggatg gactggcttg 1380tgcctgccac ctgtgaaccc atccagagtg tcttcttctt ctctggagac aagtactacc 1440gagtcaatct tcgcacacgg cgagtggaca ctgtggaccc tccctaccca cgctccatcg 1500ctcagtactg gctgggctgc ccagctcctg gccatctgta ggagtcagag cccacatggc 1560cgggccctct gtagctccct cctcccatct ccttccccca gcccaataaa ggtcccttag 1620ccccga 1626836768DNAHomo sapiens 83agtttcctga agacccggaa gccgatcgcg tggggagccg gtcttggagc agcgggatta 60gcttctaaag tctctttcat ctctcctaag gaagaagcct agaagaggag gaagaggaaa 120gaaaaggagt caggaatgcc tcttagatat ctcttccaaa tgcatgatga aaaaggtggg 180aagattactt gagccaggga gttgaaggct gcagtgagcc ctgtttttgc caccacactc 240cagcttggga ttgatttcta aagactcatg ttacatgagg aagcagctca gaagaggaaa 300ggaaaggagc caggcatggc tcttcctcag ggacgcttga ctttcaggga tgtggctata 360gaattctcat tggcagagtg gaaattcctg aaccctgcgc agagggcttt gtacagggaa 420gtgatgttgg agaactacag gaacctggag gctgtggata tctcttccaa acgcatgatg 480aaggaggtct tgtcaacagg gcaaggcaat acagaagtga tccacacagg gatgttgcaa 540agacatgaaa gttatcacac tggagatttt tgcttccagg aaattgaaaa agatattcat 600gactttgagt ttcagtcaca aaaagatgaa agaaatggcc atgaagcatc catgccaaaa 660atcaaagagt tgatgggtag cacagaccga catgatcaaa ggcatgctgg aaacaagcct 720attaaagatc agcttggatt aagctttcat ttgcatcttc ctgaactcca catatttcag 780cccgaagaga aaattgctaa tcaagtggag aagtctgtca acgatgcttc ctcaatttca 840acatcccaaa gaatttcttg taggcctgaa acacatactc ctaataacta tgggaataat 900tttttccatt catcattact cacacaaaaa caggaagtac acatgagaga aaaatctttc 960caatgtaatg agactggcga agcctttaat tgtagctcat ttgtaaggaa acatcagata 1020atccatttag gagaaaaaca atataaattt gatatatgtg gcaaagtctt taatgagaag 1080cgataccttg cacgccatcg tagatgtcac actagtgaga aaccttacaa gtgtaatgaa 1140tgtggaaagt ccttcagtta caagtcatcc ctgacatgcc atcgtagatg tcacactggt 1200gagaaacctt acaagtgtaa tgaatgtgga aagtccttca gttacaagtc atcccttaca 1260tgccatcata ggtgtcacac tggtgagaaa ccttacaagt gtaatgaatg tggaaagtcc 1320ttcagttaca agtcatccct tagatgccat cgtagacttc atactggaat aaaaccttac 1380aagtgtaatg agtgtggcaa gatgtttggt caaaattcaa cccttgtaat tcataaggca 1440attcatactg gagagaaacc ttacaagtgt aatgaatgtg gcaaggcttt taatcaacaa 1500tcacaccttt cacgtcatca tagacttcat actggagaga aaccttacaa gtgtaatgac 1560tgtggtaagg cttttattca tcagtcaagc cttgcacgtc atcatagact tcatactgga 1620gagaaatctt acaaatgtga agaatgtgac agagttttca gtcagaaatc aaaccttgag 1680agacacaaga taattcatac tggagagaaa ccttacaagt gtaatgagtg tcacaagacc 1740ttcagtcaca ggtcatctct tccatgccat cgtagacttc atagtggtga gaaaccttac 1800aagtgtaatg aatgtgggaa gacttttaat gtacagtcac acctttcacg tcatcataga 1860cttcatactg gagagaaacc ttacaaatgt aaggtttgtg acaaggcttt catgtgccat 1920tcttatctgg caaaccatac tagaattcat agcggagaga aaccttacaa gtgtaatgag 1980tgtggtaagg ctcacaatca cttgattgat tcatcaatca agccttgcat gtcatcatag 2040acttcatact ggagagaaac cttacaaatg tgaagcatgt gacaaagttt tcagtcacag 2100atcacgcctt aaaagacata ggagaattca tactggagag aaaccttaca agtgtaatga 2160gtgtggcaaa gcctttagtg accagtcaac acttaccatc aggccattca tggtgtaggg 2220aaacttgact aatgtaatga ttgtcacaaa gtcttcagta acgctacaac gattgcaaat 2280cattggagaa tccataatga agagagatct tccgagtgta ataaatgtgg caaatttttc 2340agacatcgtt cataccttgc agttcatcag tgaactcata ctggagagaa accttacaaa 2400tgtcatgact gtggcaaggt cttcagtcaa gcttcatcct atgcaaaaca taggagaatt 2460catgcaggag agaaatgtca caagtgtgat gagtgttgca aagcctttac ttcatgttca 2520cacctcatta gacatcagag aatccctact ggagagaaat cttacaaatg tcatcagtgt 2580ggcaaggtct tcagtccgag gtcactcctt gcagaacatc agaaaattca tttttgagat 2640aactgttccc aatgcagtga gtatagcaaa ccatcaagca ttaattgaca ttggagtcaa 2700ttcagcattg acttgagttt gtgttgactt aacattgagt tcaagcctta attgacatgc 2760aggtgtttat gataagagga ttgggccagg tgcagtggat cacgcctgta atcccagcac 2820attgggaggc caaggcacat aggtcacttg aggtcaagag tttgaaacaa gcatggccaa 2880gagatgtgag ccagttttcc cagcctgttt attattattt tttgagatgg agtgttgctc

2940ttgctgccca ggctagagtg caatggtgcg atcttgactc acagcaacct ccgcctcctg 3000ggttcaagcg attcctctgc ctcagcctcc ctagttgctg ggattacagg tatatgccac 3060gacgcctggc taattttttg tatttttagt agggaaaggg tttctccatg ttggtcaggc 3120tggtctcaaa ctcccgatct caggtgatcc gcccacctca gcctcccaaa gtgatgagat 3180tacaggcata tgccaccgcg cctggcattg tttcttcttt tccttttttt tttttttttt 3240tttttttgag atagtacttt ttaaagagat agtacttttt tgagatagta cttttttaaa 3300gggatatacc atagtagttt taaaagggat atcaggctgg gtgtggcagc tcacgccggt 3360aatcccagca ctttgggagg ccaaggcagg cagataacaa agtcaggaga ttgagaccgt 3420cctggctaac acggtgaaac ctcgtctcta ctaaaaatac aaaaacttag ccgggcatgg 3480tggtgggcac ctgtagtctc agctactcag ggggctgagg ctggacaatg gtgtgaaccc 3540aggaggcggt gcttgcaggg agccgagatc gtgccactgc actccaggct gggcgacaga 3600gtgagagtct gtctcaaaaa aaaaaaaaaa aagatatcaa acccggggtg tctcatccca 3660cagcactttg gaagactgaa gtgagtggat catctaagat cagagttcaa gagcaccctg 3720gctaacatgg tgaaacccca tctctactaa aaatacaaaa gttagccagg ggtgggggtg 3780tgcaccttta gttccagcta cttgggacac tgaggcatga gaatcactta aacctgggag 3840gtagaggtta cagcgaatca aaaccgtgcc actgtactgc agcgaggttg gcagagtgag 3900tctccatctc aaacaaacaa atgaaaaaaa cagacatcaa aaatgctttt gttctcgttg 3960tgtcatagac ttcccttttt tttccttctg gttcctcttc agttctctat ttattttttc 4020ttttttgcag attgagtttg agatatatct tagttttaat agttttattt cttaacacat 4080aatgacttct gaaagatgcc tttgcagcat cctgtaatca gctcacatca ttcgtttctg 4140tacttgtata ttttccagtt gttttccggt tgaccccaaa attcgtgaga tttttttcct 4200acaacaattt caaaagagtt gctgtttgaa attagttgca tccagttcag atcgaggtct 4260gcatgctttc tagtctttgt tatttattgg aaggctgtgg tacctactac ttaagtttga 4320ttgttgcagt gtgtacttgg taaagatgtc agtgaccttt taaataaaca tcaaaatgta 4380gtttaagcag ttagtctgtt tttcagtttt ctttccttat gtcatttttt aaaatcttga 4440gctgggagct atttattgtg tgtttccctc aaggccctgt ggtccattct ggaaaaatgt 4500tgaaacatgg gctggagtgg catagagcgc tgctccaaaa gcacccatgt attcttttct 4560tttttggaaa tggagtctcg ctctgtcagc ttggatggag tgcagtggtg cgatctcagc 4620tcactgcaac ctctacctcc ttggatcaag tgatgctcct gcctcagtct cctgaggagc 4680tggaattaca ggcacccacc agcacaccca gctagttttt gtatttttag tagagacagg 4740gtttcaccat gtttgtcagg ctggtctcaa actcctgacc tcgcgatcca cccgactcag 4800cctcccactg tgatgggatt acaggcatga gctaccacgt cgagactctt tttttttttt 4860ttttttagat ggagttttgc ttttgttgct gaggctggag tgcaatggtg cgatctggtg 4920tcactccaat gtcttcctcc tgggttcaag tgatttctcc tgcctcatcc tactgagtag 4980ttgggattac aggtgccctc caccactccc ggctcatttt ttgcattttt agtagagaca 5040gggtttcatc atgttggcag gctggtcttg aactcctgac ttcaggtgat ctgcccacct 5100cgacctccca aaatgctagg attacaagcg tgagccattg tgcctgacca ctcatgtatt 5160cttgattgaa ataatttgct tatttcttag ttctacagct gaccctcttt cactgtttcc 5220aaggtcaata gctgtgtgtt cacacttctg cattttataa atgttcctgt gagttttttg 5280taaggaagaa ttaactgtca ggaatcaatg tcatcagaac cttgcaaaag aagtttcttt 5340agcccaggtt tgtgaaagag gtttctctaa ttttcaagga tgggggtgat aagagcaacc 5400tttgccatta gcccttccag gaccccatgt aagactttag acaccttctc actcatctca 5460gaccttctca gggtaacttg gtgaaaatgt cttccgatct gagccccagt gagcctccct 5520gcaacttggc gacgaggggc ttgaccagaa aaggtcaacc cgagtgtccc tgaccgttga 5580aatgattggc aaaatggagt gcgtgtctgg gtgtggcttt tttttttttg aggagtgccc 5640agttgtgatt agaattttca atgggatgca gtgccctaaa aatgaaaaac aaaagcagaa 5700gaatggaaga aatagaggta gactcagaca cagagaccat cttcaaggcc tttctctgta 5760tgaggacatc acagcaaaat ctaaagcagg tcacgtcaat ccctggcagg gaaccctcca 5820ccggcttccc gtgttcccca ggacaaaagc ccaacccctc actgtggctc cacagccccg 5880tgtgcagggc ccctgccagt gtccagcctc ctcctggcag cttgccctca tctcatgact 5940ccctctgccc cagtcacatt tgcttttctc ttttcccaaa catcaaaacc cttcctgtct 6000caggtcattg tccctgctct taccctatgt accctgtccc tttctcctcc ttcaggtcta 6060ggctcagagc tctctcccat gccctcccac ccctggtctc aagctcctga gctcaagtga 6120tctacccacc tcggcctcct agagtgctgg gatgacaggc atgagccact gcaaccagcc 6180tctgcatggg gtttcctcaa ctttaggtct gtgccctgaa ggggagctca ttccagccca 6240gttcccaact gctgcagcat gtgtgtgtgg gcttctccag aaggggagcc agagtttccc 6300tgtaggagtt tatcctccat ggtgaggagg gccgcagggg ggactgtatt tgctcagggt 6360gaggtctcct ttgtgtcagg cctctgagcc caagctaagc catcgtatcc cctgtcacct 6420gcacgtatac atccagatgg cctgaagcaa ctgaagatcc acgaaagaag tgaaaatacc 6480cttaagtgat gacattccac cattgtgatt tatttctgca ccatcttgac tgatcaatgt 6540gctttgtaat ctcccccacc cttcagaagg ctctttgtaa tcctccccac ccttgagaat 6600ggacttggtg agatccaccc cctgcctgca aagcattgcc cctaactcca ccgcctgtcc 6660caaaagctac aagaactaat gataatccca ccatactttg ctgactctct tttcacactc 6720agcccgcctg cacccaggtg aaataaacag cctcgttgct cacacaaa 6768843341DNAHomo sapiens 84ctttgtctcc ttgcggccgg cggggtgctg ggttcccgtc tgctgcctct cggagagtcc 60cgggtgactg ccgcaggctc catcgccctg tggcctgcag gtattgcgag atttataggg 120aggacgctgg gacccccaaa agctgggaaa tgggactatt ggcattcagg gatgtggctc 180tagaattctc tccagaggag tgggaatgcc tggacccagc tcagcggagt ttgtataggg 240atgtgatgtt agagaactac agaaacctga tctcccttgg tgaggatagc ttcaatatgc 300aattcctatt tcacagtctt gctatgtcta agccagaact gatcatctgt ctggaggcaa 360ggaaagagcc ctggaacgtg aacacagaga agacagccag acactcagtt ttgtcttctt 420atcttactga agacattttg ccagagcagg gcctgcaagt ttcattccaa aaagtgatgc 480tgagaagata tgaaagatgt tgtcttgaga aattacgctt aaggaatgac tgggaaattg 540tgggtgagtg gaaagggcag aaggcaagtt ataatggact tgacctatgc tcagcaacta 600ctcatagcaa aaactttcaa tgcaataaat gtgtgaaagg ttttagtaaa tttgcaaatc 660taaataaatg taagataagc catactggag aaaaaccatt caaatgcaaa gaatgtggca 720atgtctcttg catgtcttta ataatgactc aacagcagag aatccatatt ggagagaacc 780cgtaccaatg taaaaaatgt ggcaaagcct ttaatgagtg ctcatgcttt actgactgta 840agagaattca tgttggagag aaacattgca aatgtgaaga atgtaataac atttttaagt 900cttgctcaag tcttgctgtt gttgagaaaa atcatactga aaagaaaacc tacagatgtg 960aagaatgtgg caaagctttt aacctgtgct cagttcttac taaacataag aaaattcata 1020ctggagagaa accatacaaa tgtgaagaat gtggcaaatc ctttaagttg ttcccatacc 1080ttactcaaca caagagaatt catagtagag agaaacccta caagtgtgaa gaatgtggca 1140aagtctttaa attgttgtca taccttactc aacatagaag aattcatact ggagagaaaa 1200ccttccgatg tgaagaatgt ggaaaagcct ttaaccagag ctcacatctg actgaacata 1260ggagaattca tactggtgag aaaccataca aatgtgagga atgtggcaaa gcttttacct 1320ggttctcata ccttattcag cataagagaa ttcatactgg gcagaaaccc tacaaatgtg 1380aggaatgtgg caaagctttt acctggtttt cataccttac tcaacataag agaattcata 1440ctggagagaa accctacaaa tgtgatgaat gtggcaaagc ttttaactgg ttttcatatc 1500ttactaatca taagagaatt catactggag agaaacccta caaatgtgaa gaatgtggca 1560aagcctttgg ccagagctca cacctttcta aacataagac aattcatacc agagagaaac 1620catacaagtg tgaggaatgt ggcaaagcct ttaaccactc tgcacaactt gctgtacatg 1680agaaaactca tacctgagaa aaaccctaca attctaaaca atatggcata gtctttaata 1740cctattcaca acttcacagc agaatatttt tactgaataa gagtgttaca aatgtaatga 1800ctgtcaaaag gccatttaca gtctatgagc ctttgagtgc actaaaatgt ttaggctacg 1860aacaatacaa atagaccggt tcaacacctc cacttatatc acagctctta ctgtacacag 1920aagaatttat actggaggga aaccctccag ttgctcaaac tgtattcaat ttcaaagact 1980ttgtattgga gagaaaccct acaaatgtaa taaatgcaga aacaacattt gttcaaaaaa 2040tatacctcag aaaacaccag agtgttcaca ctaaaaactg ttttacagat gcagtaaatg 2100tgaaaaaatg tctaatcaaa aattacatca aaacacatcc aagaattcat agtaaaaagc 2160actaagtcac tgacactttc agacattact gtaaatctga gtgttggtta tagagaataa 2220ttcaaagtta agttaaagta agtaggagat tcaccttttg gggaagttat aattacattt 2280caagtatacc ttttggtgcc aggcacggtg gctctttcct atagttgctg cacttttgga 2340tgccgaggtc gggggattgc ttgagcccag gagtttggga ccaggctggg caacatggca 2400aaacctcatc tctacaaaaa gtaaaataaa agccaggctt ggtggcacat gcctgttgtc 2460ccagctactt ggaaggctca ggtgggagga ttgcttgagc ctggaggttg aggatgcagt 2520gagctgctat ctggcaactt cactcctgcc tgggcaacag agcaagaccc tttctcaata 2580ataataataa caacataata ataaagtata ctcggtgcac tgaaagagtt ttagcttttt 2640tgaaaatcac atatttatgt aattcaagtc ttaaatcact tgataccatg ccttcatttc 2700tagtgtttat gtgaaggcat gaggcctact gttgctacat gaaagctgtg agagtttctt 2760ctatattcgg gtgggtgttg ttcatatcct tttctttgga agattatgga cattgcattg 2820taagcttcct gaagaaattt aactggagag gctctttgta cttgtcttat aatagggttg 2880taagtgattc atgagatagg tcttcagagt actattctgc attatattta agaaagaaac 2940atttgagttt tacaagtcag ttgtttttcc tattgcacat taaggtaata aaattcagtg 3000gattttgaaa tgctcttttt agactgtttg aacttaattt gttttaataa gacattgttt 3060taatgtcttt ggaccgttgt acattaagtg atgcgtatcc taccaccaac gttaacctat 3120ctcaccttag ttacggttgt aggtaacaaa tggtaacaat acaatagtgg gtaacatggt 3180ggaatagtat ctctaatgat cccttctccc agtggcatta aacttcaaat aatttgaaaa 3240atattgttcc cacacgttac accttcattc tgtttgctct ttttgtaatg acagtgtcat 3300tattaaggct ataataaagc ctatatagga ttataatcaa a 3341

Claims

1. A method for determining a clustering of cluster assignments (COCA) subtype of a tumor cancer sample obtained from a patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1, wherein the detection of the expression level of the classifier biomarker specifically identifies a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype.

2. The method of claim 1, wherein the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step.

3. The method of claim 2, wherein the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm.

4. The method of claim 1, wherein the C1 COCA subtype indicates that a tumor sample is substantially similar to or is adenocortical carcinoma; the C2 COCA subtype indicates that a tumor sample is substantially similar to or is glioblastoma; the C3 COCA subtype indicates that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer); the C4 COCA subtype indicates that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder; the C6 COCA subtype indicates that a tumor sample is substantially similar to or is lung adenocarcinoma; the C8 COCA subtype indicates that a tumor sample is substantially similar to or is pancreatic adenocarcinoma; the C9 COCA subtype indicates that a tumor sample is substantially similar to or is uterine carcinosarcoma; the C10 COCA subtype indicates that a tumor sample is substantially similar to or is the basal subtype of breast cancer; the C12 COCA subtype indicates that a tumor sample is substantially similar to or is uterine corpus endometrial cancer; the C14 COCA subtype indicates that a tumor sample is substantially similar to or is prostate cancer; the C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer; the C16 COCA subtype indicates that a tumor sample is substantially similar to or is a bladder urothelial carcinoma; the C17 COCA subtype indicates that a tumor sample is substantially similar to or is a testicular germ cell tumor; the C19 COCA subtype indicates that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma; the C20 COCA subtype indicates that a tumor sample is substantially similar to or is a sarcoma; the C21 COCA subtype indicates that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma; the C22 COCA subtype indicates that a tumor sample is substantially similar to or is liver hepatocellular carcinoma; the C24 COCA subtype indicates that a tumor sample is substantially similar to or is the luminal subtype of breast cancer; the C25 COCA subtype indicates that a tumor sample is substantially similar to or is thymoma; the C26 COCA subtype indicates that a tumor sample is substantially similar to or is melanoma; or the C28 COCA subtype indicates that a tumor sample is substantially similar to or is thyroid cancer.

5. The method of claim 1, wherein the expression level of the classifier biomarker is detected at the nucleic acid level.

6. The method of claim 5, wherein the nucleic acid level is RNA or cDNA.

7. The method claim 5 or 6, wherein the detecting an expression level comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

8. The method of claim 7, wherein the expression level is detected by performing RNAseq.

9. The method of claim 8, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1.

10. The method of claim 1, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, a fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

11. The method of claim 10, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

12. The method of claim 1, wherein the at least one classifier biomarker comprises a plurality of classifier biomarkers.

13. The method of claim 12, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 4 classifier biomarkers, at least 6 classifier biomarkers, at least 8 classifier biomarkers, at least 10 classifier biomarkers, at least 12 classifier biomarkers, at least 14 classifier biomarkers, at least 16 classifier biomarkers, at least 18 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

14. The method of claim 1, wherein the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.

15. A method of detecting a biomarker in a tumor sample obtained from a patient, the method comprising measuring the expression level of a plurality of classifier biomarker nucleic acids selected from Table 1 using an amplification, hybridization and/or sequencing assay.

16. The method of claim 15, wherein the patient is suffering from or is suspected of suffering from kidney renal papillary cell carcinoma (KIRP); breast invasive carcinoma (BRCA); thyroid cancer (THCA); bladder urothelial carcinoma (BLCA); prostate adenocarcinoma (PRAD); kidney chromophobe (KICH); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma (LIHC); low grade glioma (LGG); sarcoma (SARC); lung adenocarcinoma (LUAD); colon adenocarcinoma (COAD); head and neck squamous cell carcinoma (HNSC); uterine corpus endometrial carcinoma (UCEC); glioblastoma multiforme (GBM); esophageal carcinoma (ESCA); stomach adenocarcinoma (STAD); ovarian serous cystadenocarcinoma (OV); rectum adenocarcinoma (READ); adrenocortical carcinoma (ACC); uveal melanoma (UVM); mesothelioma (MESO); pheochromocytoma and paraganglioma (PCPG); skin cutaneous melanoma (SKCM); uterine carcinsarcoma (UCS); lung squamous cell carcinoma (LUSC); testicular germ cell tumors (TGCT); cholangiocarcinoma (CHOL); pancreatic adenocarcinoma (PAAD); thymoma (THYM); or Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC).

17. The method of claim 15 or 16, wherein the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

18. The method of claim 17, wherein the expression level is detected by performing RNAseq.

19. The method of claim 18, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers per each of the plurality of biomarker nucleic acids selected from Table 1.

20. The method of claim 15, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

21. The method of claim 20, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

22. The method of claim 15, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

23. The method of claim 15, wherein the plurality of biomarker nucleic acids comprises, consists essentially of or consists of all the classifier biomarker nucleic acids of Table 1.

24. A method of treating cancer in a subject, the method comprising: measuring the expression level of at least one biomarker nucleic acid in a tumor sample obtained from the subject, wherein the at least one biomarker nucleic acid is selected from a set of biomarkers listed in Table 1, wherein the presence, absence and/or level of the at least one biomarker indicates a COCA subtype of the cancer; and administering a therapeutic agent based on the COCA subtype of the cancer.

25. The method of claim 24, wherein the at least one biomarker nucleic acid selected from the set of biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

26. The method of claim 24 or 25, further comprising measuring the expression of at least one biomarker from an additional set of biomarkers.

27. The method of claim 26, wherein the additional set of biomarkers comprises at least an immune cell signature, a cell proliferation signature, or drug target genes.

28. The method of claim 24, wherein the measuring the expression level is conducted using an amplification, hybridization and/or sequencing assay.

29. The method of claim 28, wherein the amplification, hybridization and/or sequencing assay comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

30. The method of claim 29, wherein the expression level is detected by performing RNAseq.

31. The method of claim 24, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

32. The method of claim 31, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

33. The method of claim 24, wherein the subject's COCA subtype is selected from C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28.

34. The method of claim 33, wherein the C1 COCA subtype indicates that a tumor sample is substantially similar to or is adenocortical carcinoma; the C2 COCA subtype indicates that a tumor sample is substantially similar to or is glioblastoma; the C3 COCA subtype indicates that a tumor sample is substantially similar to or is an ovarian serous cystadenocarcinoma (epithelial ovarian cancer); the C4 COCA subtype indicates that a tumor sample is substantially similar to or is squamous cell carcinoma of the lung, the head and neck or the bladder; the C6 COCA subtype indicates that a tumor sample is substantially similar to or is lung adenocarcinoma; the C8 COCA subtype indicates that a tumor sample is substantially similar to or is pancreatic adenocarcinoma; the C9 COCA subtype indicates that a tumor sample is substantially similar to or is uterine carcinosarcoma; the C10 COCA subtype indicates that a tumor sample is substantially similar to or is the basal subtype of breast cancer; the C12 COCA subtype indicates that a tumor sample is substantially similar to or is uterine corpus endometrial cancer; the C14 COCA subtype indicates that a tumor sample is substantially similar to or is prostate cancer; the C15 COCA subtype can indicate that a tumor sample is substantially similar to or is non-squamous cervical cancer; the C16 COCA subtype indicates that a tumor sample is substantially similar to or is a bladder urothelial carcinoma; the C17 COCA subtype indicates that a tumor sample is substantially similar to or is a testicular germ cell tumor; the C19 COCA subtype indicates that a tumor sample is substantially similar to or is a colon, rectal, esophageal or stomach adenocarcinoma; the C20 COCA subtype indicates that a tumor sample is substantially similar to or is a sarcoma; the C21 COCA subtype indicates that a tumor sample is substantially similar to or is a kidney chromophobe, kidney renal papillary cell carcinoma or kidney renal clear cell carcinoma; the C22 COCA subtype indicates that a tumor sample is substantially similar to or is liver hepatocellular carcinoma; the C24 COCA subtype indicates that a tumor sample is substantially similar to or is the luminal subtype of breast cancer; the C25 COCA subtype indicates that a tumor sample is substantially similar to or is thymoma; the C26 COCA subtype indicates that a tumor sample is substantially similar to or is melanoma; or the C28 COCA subtype indicates that a tumor sample is substantially similar to or is thyroid cancer.

35. A method of predicting overall survival in a cancer patient, the method comprising detecting an expression level of at least one classifier biomarker of Table 1 in a tumor sample obtained from a patient, wherein the detection of the expression level of the at least one classifier biomarker specifically identifies a COCA subtype, and wherein identification of the COCA subtype is predictive of the overall survival in the patient.

36. The method of claim 35, wherein the method further comprises comparing the detected levels of expression of the at least one classifier biomarker of Table 1 to the expression of the at least one classifier biomarker of Table 1 in at least one sample training set(s), wherein the at least one sample training set(s) comprises expression data of the at least one classifier biomarker of Table 1 from a reference C1 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C2 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C3 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C4 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C6 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C8 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C9 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C10 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C12 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C14 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C15 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C16 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C17 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C19 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C20 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C21 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C22 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C24 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C25 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C26 sample, expression data of the at least one classifier biomarker of Table 1 from a reference C28 sample or a combination thereof; and classifying the sample as the C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the comparing step.

37. The method of claim 36, wherein the comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample and the expression data from the at least one training set(s); and classifying the sample as a C1, C2, C3, C4, C6, C8, C9, C10, C12, C14, C15, C16, C17, C19, C20, C21, C22, C24, C25, C26 or C28 COCA subtype based on the results of the statistical algorithm.

38. The method of any one of the claims 35-37, wherein the expression level of the classifier biomarker is detected at the nucleic acid level.

39. The method of claim 38, wherein the nucleic acid level is RNA or cDNA.

40. The method of claim 35, wherein the detecting an expression level comprises performing quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR), RNAseq, microarrays, gene chips, nCounter Gene Expression Assay, Serial Analysis of Gene Expression (SAGE), Rapid Analysis of Gene Expression (RAGE), nuclease protection assays, Northern blotting, or any other equivalent gene expression detection techniques.

41. The method of claim 40, wherein the expression level is detected by performing RNAseq.

42. The method of claim 35, wherein the detection of the expression level comprises using at least one pair of oligonucleotide primers specific for at least one classifier biomarker of Table 1.

43. The method of claim 35, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample, fresh or a frozen tissue sample, an exosome, wash fluids, cell pellets, or a bodily fluid obtained from the patient.

44. The method of claim 43, wherein the bodily fluid is blood or fractions thereof, urine, saliva, or sputum.

45. The method of claim 35, wherein the at least one classifier biomarker comprises a plurality of classifier biomarkers.

46. The method of claim 45, wherein the plurality of classifier biomarkers comprises, consists essentially of or consists of at least 2 classifier biomarkers, at least 5 classifier biomarkers, at least 10 classifier biomarkers, at least 20 classifier biomarkers, at least 30 classifier biomarkers, at least 40 classifier biomarkers, at least 50 classifier biomarkers, at least 60 classifier biomarkers, at least 70 classifier biomarkers or at least 80 classifier biomarkers of Table 1.

47. The method of claim 35, wherein the at least one classifier biomarker comprises, consists essentially of or consists of all the classifier biomarkers of Table 1.