US20030236632A1 - Biomarkers for breast cancer - Google Patents

Biomarkers for breast cancer Download PDF

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US20030236632A1
US20030236632A1 US10/282,596 US28259602A US2003236632A1 US 20030236632 A1 US20030236632 A1 US 20030236632A1 US 28259602 A US28259602 A US 28259602A US 2003236632 A1 US2003236632 A1 US 2003236632A1
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cloneid
sequences
cells
population
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Xiao-Jun Ma
Dennis Sgroi
Mark Erlander
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General Hospital Corp
Arcturus Engineering Inc
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Arcturus Engineering Inc
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Priority claimed from US10/028,018 external-priority patent/US20040002067A1/en
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Priority to US10/282,596 priority Critical patent/US20030236632A1/en
Priority to AU2002358279A priority patent/AU2002358279A1/en
Priority to PCT/US2002/041216 priority patent/WO2003060164A1/en
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Priority to US11/381,353 priority patent/US20060263806A1/en
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57415—Specifically defined cancers of breast
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57496—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving intracellular compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/16—Primer sets for multiplex assays

Definitions

  • the invention relates to the identification and use of gene sequences which are differentially expressed in breast cancer.
  • the invention provides the identities of three sets of sequences that may be used to identify the presence of breast cancer in tissue and cell samples.
  • the expression of these sequences are used in the diagnosis and/or treatment of breast cancer as well as for the study and/or determination of prognosis of a patient.
  • the expression levels of these sequences are used to identify the presence of breast cancer and provide guidance as to the treatment thereof.
  • NCI National Cancer Institute
  • the present invention relates to the identification and use of gene sequences identified as differentially expressed in breast cancer.
  • the sequences of two of the genes display increased expression in non-normal (or abnormal) breast cells, such as those that would be identified as atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) by standard pathology techniques based upon cytological criteria.
  • ADH atypical ductal hyperplasia
  • DCIS ductal carcinoma in situ
  • IDC invasive ductal carcinoma
  • CRIP1 human cysteine-rich intestinal protein 1
  • HCRHP human cysteine-rich heart protein
  • HN1 or Hn1 hematological and neurological expressed sequence 1
  • Murine HN1 has been identified as being expressed in mouse hemopoietic and brain tissues (see Tang et al. Mamm. Genome, 8:695-696, 1997).
  • ESE-2 second epithelium restricted Ets transcription factor
  • ELF5 E74 like factor 5
  • the identified sequences may thus be used in methods of detecting the presence of non-normal breast cells in a tissue or cell containing sample from a subject.
  • the presence of non-normal breast cells may also be used in methods of diagnosing the presence of breast cancer in a tissue or cell containing sample from a subject.
  • a subject, from which a sample is taken, may be one afflicted with, or suspected of having, breast cancer.
  • the present invention provides a non-subjective means for detecting the presence of non-normal breast cells. This provides advantages over the use of histomorphological or cytological criteria in standard pathology techniques, which requires some level of interpretation by a pathologist trained in assessing the presence and/or progression of breast cancer.
  • the expression levels of these sequences may also be used as a means to assay small, node negative tumors that are not readily assessed by conventional means.
  • sequences of the identified sequences may be used alone or in combination with other sequences capable of identifying the presence of non-normal cells or of various stages and/or grades of breast cancer.
  • sequences of the invention are used alone or in combination with each other.
  • the present invention provides means for correlating a molecular expression phenotype with a physiological (cellular) stage or state of a non-normal or abnormal breast cell. This correlation provides a way to molecularly diagnose and/or monitor a cell's status in comparison to normal breast cell phenotypes as disclosed herein. Additional uses of the sequences are in the classification of cells and tissues; determination of diagnosis and/or prognosis. Use of the sequences to identify cells of a sample as non-normal or abnormal may also be used to determine the choice, or alteration, of therapy used to treat such cells in the subject from which the sample originated.
  • the ability to identify non-normal and abnormal breast cells is provided by the recognition of the relevancy of the level of expression of the identified sequences and not by the form of the assay used to determine the actual level of expression.
  • An assay may utilize a means related to the expression level of the sequences disclosed herein as long as the assay reflects, quantitatively or qualitatively, expression of the sequence. Preferably, however, a quantitative assay means is preferred. Identifying features of the sequences include, but are not limited to, unique nucleic acid sequences used to encode (DNA), or express (RNA), the disclosed sequences or epitopes specific to, or activities of, proteins encoded by the sequences.
  • Alternative means include detection of nucleic acid amplification as indicative of increased expression levels (CRIP1 and HN1 sequences) and nucleic acid inactivation, deletion, or methylation, as indicative of decreased expression levels (ESE-2 and ELF5 sequences).
  • the invention may be practiced by assaying one or more aspect of the DNA template(s) underlying the expression of the disclosed sequence(s), of the RNA used as an intermediate to express the sequence(s), or of the proteinaceous product expressed by the sequence(s).
  • the detection of the amount of, stability of, or degradation (including rate) of, such DNA, RNA and proteinaceous molecules may be used in the practice of the invention.
  • the practice of the present invention is unaffected by the presence of minor mismatches between the disclosed sequences and those expressed by cells of a subject's sample.
  • minor mismatches are seen in cases of sequence polymorphisms between individuals of a species, such as individual human patients within Homo sapiens.
  • Knowledge that expression of the disclosed sequences (and sequences that vary due to minor mismatches) is correlated with the presence of non-normal or abnormal breast cells and breast cancer is sufficient for the practice of the invention with an appropriate cell containing sample via an assay for expression.
  • the invention provides for the identification of the expression levels of the disclosed sequences by analysis of their expression in a sample containing breast cells.
  • the sample contains single cells or homogenous cell populations which have been dissected away from, or otherwise isolated or purified from, contaminating cells beyond that possible by a simple biopsy.
  • Multiple means for such analysis are available, including detection of expression within an assay for global, or near global, gene expression in a sample (e.g. as part of a gene expression profiling analysis such as on a microarray) or by specific detection, such as quantitative PCR or real time quantitative PCR.
  • the sample is isolated via non-invasive means.
  • the expression of the disclosed sequence(s) in the sample may be determined and compared to the expression of said sequence(s) in reference data of non-normal breast cells.
  • the expression level may be compared to expression levels in normal cells, preferably from the same sample or subject.
  • breast cells are isolated in the practice of the invention, one benefit is that contaminating, non-breast cells (such as infiltrating lymphocytes or other immune system cells) are not present to possibly affect detection of expression of the disclosed sequence(s). Such contamination is present where a biopsy is used to generate gene expression profiles.
  • non-breast cells such as infiltrating lymphocytes or other immune system cells
  • the present invention has been described mainly in the context of human breast cancer, it may be practiced in the context of breast cancer of an animal known to be potentially afflicted by breast cancer by use of the corresponding sequences of the animal.
  • Preferred animals for the application of the present invention are mammals, particularly those important to agricultural applications (such as, but not limited to, cattle, sheep, horses, and other “farm animals”) and for human companionship (such as, but not limited to, dogs and cats).
  • FIG. 1 shows log 2 plots of the ratio of expression in ADH, DCIS, and IDC cells to normal cells for CRIP1 and ELF5 sequences.
  • the horizontal line is at “0” such that the ratio is “1” and all points above the line represent increases in expression relative to normal breast cells while all points below the line represent decreases in expression relative to normal breast cells.
  • FIG. 2 shows the results of in situ hybridization with sense and anti-sense CRIP1 sequences to locate its expression at the cellular level in normal versus IDC cells of the same sample.
  • CRIP1 signal localized to the epithelial cells, and its intensity was markedly increased in the IDC compartment of the same biopsy.
  • FIG. 3 shows the results of in situ hybridization with sense and anti-sense CRIP1 sequences to locate its expression at the cellular level in normal versus DCIS and IDC cells.
  • CRIP1 signal again localized to the epithelial cells, and its intensity was markedly increased in non-normal cells.
  • a “sequence” or “gene sequence” as used herein is a nucleic acid molecule or polynucleotide composed of a discrete order of nucleotide bases.
  • the term includes the ordering of bases that encodes a discrete product (i.e. “coding region”), whether RNA or proteinaceous in nature, as well as the ordered bases that precede or follow a “coding region”. Non-limiting examples of the latter include 5′ and 3′ untranslated regions of a gene. It is appreciated that more than one polynucleotide may be capable of encoding a discrete product.
  • alleles and polymorphisms of the disclosed sequences may exist and may be used in the practice of the invention to identify the expression level(s) of the disclosed sequences or the allele or polymorphism. Identification of an allele or polymorphism depends in part upon chromosomal location and ability to recombine during mitosis.
  • correlate or “correlation” or equivalents thereof refer to an association between expression of one or more sequences and a physiologic state of a breast cell to the exclusion of one or more other states by use of the methods as described herein.
  • the invention provides for the correlation between increases in CRIP1 and HN1 sequences and non-normal or abnormal breast cells. Similarly, the invention provides for the correlation between decreases in ESE-2/ELF5 sequences and non-normal or abnormal breast cells.
  • Increases and decreases may be readily expressed in the form of a ratio between expression in a non-normal cell and a normal cell such that a ratio of one (1) indicates no difference while ratios of two (2) and one-half indicate twice as much, and half as much, expression in the non-normal cell versus the normal cell, respectively.
  • Expression levels can be readily determined by quantitative methods as described below.
  • increases in CRIP1 expression can be indicated by ratios of or about 1.1, of or about 1.2, of or about 1.3, of or about 1.4, of or about 1.5, of or about 1.6, of or about 1.7, of or about 1.8, of or about 1.9, of or about 2, of or about 2.5, of or about 3, of or about 3.5, of or about 4, of or about 4.5, of or about 5, of or about 5.5, of or about 6, of or about 6.5, of or about 7, of or about 7.5, of or about 8, of or about 8.5, of or about 9, of or about 9.5, of or about 10, of or about 15, of or about 20, of or about 30, of or about 40, of or about 50, of or about 60, of or about 70, of or about 80, of or about 90, of or about 100, of or about 150, of or about 200, of or about 300, of or about 400, of or about 500, of or about 600, of or about 700, of or about 800, of or about 900, or of or about 1000.
  • a ratio of 2 is a 100% (or a two-fold) increase in expression. Similar ratios can be used with respect to increases in HN1 expression. Decreases in ESE-2/ELF5 expression can be indicaed by ratios of or about 0.9, of or about 0.8, of or about 0.7, of or about 0.6, of or about 0.5, of or about 0.4, of or about 0.3, of or about 0.2, of or about 0.1, of or about 0.05, of or about 0.01, of or about 0.005, of or about 0.001, of or about 0.0005, of or about 0.0001, of or about 0.00005, of or about 0.00001, of or about 0.000005, or of or about 0.000001. Non-limiting examples of such ratios are shown in FIG. 1.
  • a “polynucleotide” is a polymeric form of nucleotides of any length, either ribonucleotides or deoxyribonucleotides linked by phosphodiester bonds and encompasses the strand of a given sequence as disclosed herein as well as the complementary strand of a given sequence.
  • the term refers only to the primary structure of the molecule. Thus, this term includes double- and single-stranded DNA and RNA as well as analogs thereof comprising a non-phosphodiester backbone.
  • amplify is used in the broad sense to mean creating an amplification product can be made enzymatically with DNA or RNA polymerases.
  • Amplification generally refers to the process of producing multiple copies of a desired sequence, particularly those of a sample. “Amplification” may also be used in the context of DNA amplification wherein copies of coding sequences within the cellular genome are increased. “Multiple copies” mean at least 2 copies. A “copy” does not necessarily mean perfect sequence complementarity or identity to the template sequence.
  • Methods for amplifying mRNA are generally known in the art, and include reverse transcription PCR (RT-PCR) and those described in U.S. patent application Ser. No.
  • nucleic acid molecule shares a substantial amount of sequence identity with another nucleic acid molecule.
  • RNA may be directly labeled as the corresponding cDNA by methods known in the art.
  • a “microarray” is a linear or two-dimensional array of preferably discrete regions, each having a defined area, formed on the surface of a solid support such as, but not limited to, glass, plastic, or synthetic membrane.
  • the density of the discrete regions on a microarray is determined by the total numbers of immobilized polynucleotides to be detected on the surface of a single solid phase support, preferably at least about 50/cm 2 , more preferably at least about 100/cm 2 , even more preferably at least about 500/cm 2 , but preferably below about 1,000/cm 2 .
  • the arrays contain less than about 500, about 1000, about 1500, about 2000, about 2500, or about 3000 immobilized polynucleotides in total.
  • a DNA microarray is an array of oligonucleotides or polynucleotides placed on a chip or other surfaces used to hybridize to amplified or cloned polynucleotides from a sample. Since the position of each particular group of primers in the array is known, the identities of a sample polynucleotides can be determined based on their binding to a particular position in the microarray.
  • one embodiment of the invention involves determining expression by hybridization of mRNA, or an amplified or cloned version thereof, of a sample cell to a polynucleotide of a disclosed sequence.
  • Preferred polynucleotides of this type contain at least about 20, at least about 22, at least about 24, at least about 26, at least about 28, at least about 30, at least about 32, at least about 34, at least about 36, at least about 38, at least about 40, at least about 42, at least about 44, or at least about 46 consecutive bases of a sequence that is not found in other human sequences.
  • polynucleotides may of course contain minor mismatches (e.g. via the presence of mutations) which do not affect hybridization to the nucleic acids of a sample.
  • Such polynucleotides may be label to assist in their detection; alternatively, the nucleic acids to which such polynucleotides will hybridize may be labeled.
  • Such polynucleotides may also be immobilized, such as by attachment to a solid support.
  • the term “about” as used in the preceding sentence refers to an increase or decrease of 10% from the stated numerical value.
  • the polynucleotides may of course contain minor mismatches which do not affect hybridization to the nucleic acids of a sample.
  • all or part of a disclosed sequence may be amplified and detected by methods such as the polymerase chain reaction (PCR) and variations thereof, such as, but not limited to, quantitative PCR (QPCR), reverse transcription PCR (RT-PCR), and real-time PCR, optionally real-time RT-PCR.
  • PCR polymerase chain reaction
  • QPCR quantitative PCR
  • RT-PCR reverse transcription PCR
  • real-time PCR optionally real-time RT-PCR.
  • Such methods would utilize one or two primers that are complementary to portions of a disclosed sequence, where the primers are used to prime nucleic acid synthesis.
  • the newly synthesized nucleic acids are optionally labeled and may be detected directly or by hybridization to a polynucleotide of the invention.
  • the newly synthesized nucleic acids may be contacted with polynucleotides (containing sequences) of the invention under conditions which allow for their hybridization.
  • expression of a sequence may be determined by analysis of expressed protein encoded by said sequence in a cell sample of interest by use of one or more antibodies specific for one or more epitopes of the individual products (proteins) in said cell sample.
  • Such antibodies are preferably labeled to permit their easy detection after binding to the gene product.
  • the assay may modified to use such materials in place of a breast cell containing sample.
  • label refers to a composition capable of producing a detectable signal indicative of the presence of the labeled molecule. Suitable labels include radioisotopes, nucleotide chromophores, enzymes, substrates, fluorescent molecules, chemiluminescent moieties, magnetic particles, bioluminescent moieties, and the like. As such, a label is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means.
  • support refers to conventional supports such as beads, particles, dipsticks, fibers, filters, membranes and silane or silicate supports such as glass slides.
  • a “breast tissue sample” or “breast cell sample” refers to a sample of breast tissue or fluid isolated from an individual, preferably suspected of being afflicted with, or at risk of developing, breast cancer. Such samples are primary isolates (in contrast to cultured cells) and may be collected by a non-invasive means, including, but not limited to, ductal lavage, fine needle aspiration, needle biopsy, the devices and methods described in U.S. Pat. No. 6,328,709, or another suitable means recognized in the art. Alternatively, the “sample” may be collected by an invasive method, including, but not limited to, surgical biopsy.
  • “Expression” and “gene expression” include transcription and/or translation of nucleic acid material, such as the sequences of the invention.
  • Conditions that “allow” an event to occur or conditions that are “suitable” for an event to occur are conditions that do not prevent such events from occurring. Thus, these conditions permit, enhance, facilitate, and/or are conducive to the event.
  • Such conditions known in the art and described herein, depend upon, for example, the nature of the nucleotide sequence, temperature, and buffer conditions. These conditions also depend on what event is desired, such as hybridization, cleavage, strand extension or transcription.
  • Sequence “mutation,” as used herein, refers to any sequence alteration in the sequence of a gene disclosed herein interest in comparison to a reference sequence.
  • a sequence mutation includes single nucleotide changes, or alterations of more than one nucleotide in a sequence, due to mechanisms such as substitution, deletion or insertion.
  • Single nucleotide polymorphism (SNP) is also a sequence mutation as used herein. Because the present invention is based on the relative level of sequence expression, mutations in non-coding regions of genes as disclosed herein may also be assayed in the practice of the invention.
  • Detection includes any means of detecting, including direct and indirect detection of gene expression and changes therein. For example, “detectably less” products may be observed directly or indirectly, and the term indicates any reduction (including the absence of detectable signal). Similarly, “detectably more” product means any increase, whether observed directly or indirectly.
  • Increases and decreases in expression of the disclosed sequences are defined in the following terms based upon percent or fold changes over expression in normal cells. Increases may be of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, or 200% relative to expression levels in normal cells. Alternatively, fold increases may be of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 fold over expression levels in normal cells. Decreases may be of 10, 20, 30, 40, 50, 55, 60, 65, 70, 75, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 99 or 100% relative to expression levels in normal cells.
  • the present invention relates to the identification and use of three sets of sequences for the detection of non-normal and cancerous breast cells.
  • the differential expression of these sequences in non-normal or abnormal breast cells relative to normal breast cells is used to identify a breast cancer cell as being non-normal or otherwise abnormal.
  • the invention is advantageously used to identify breast cells as being those of ADH, DCIS, and IDC as otherwise determinable standard pathological techniques.
  • the invention may also be applied to the identification of breast cells as being those of atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and invasive lobular carcinoma (ILC) as otherwise determinable by standard pathological techniques.
  • ADH atypical lobular hyperplasia
  • LCIS lobular carcinoma in situ
  • IDC invasive lobular carcinoma
  • non-normal or abnormal cells include malignant cells, atypical cells (including reactive and pre-neoplastic), neoplastic cells, tumor cells, and cancer or cancerous cells.
  • the sequences(s) identified by the present invention are expressed in correlation with non-normal breast cells, and thus negatively correlated with normal breast cells.
  • CRIP1 identified by I.M.A.G.E. Consortium CloneID 1323448 and cluster NM — 001311 (“The I.M.A.G.E. Consortium: An Integrated Molecular Analysis of Genomes and their Expression,” Lennon et al., 1996, Genomics 33:151-152; see also image.llnl.gov) has been found to be useful in discriminations between normal and ADH or DCIS or IDC breast cells.
  • any sequence, or unique portion thereof, of the CRIP1 sequences identified by the cluster, as well as UniGene Homo sapiens cluster Hs.17409 maybe used.
  • the 5′ and 3′ untranslated and/or non-coding regions are by reference to the assigned coding region, which is presented as the complementary strand in the 3′ to 5′ direction for some of the sequences.
  • any sequence, or unique portion thereof, of the HN1 sequences identified by the I.M.A.G.E. Consortium CloneID 471568 and cluster NM — 016185, as well as UniGene Homo sapiens cluster Hs.109706, may be used.
  • HN1 sequences are useful in discriminations between normal and DCIS or IDC (of grades I to III) breast cells. Its expression is also increased in grade III relative to grade I breast cancer cells.
  • the 5′ and 3′ untranslated and/or non-coding regions are by reference to the assigned coding region, which is presented as the complementary strand in the 3′ to 5′ direction for some of the sequences.
  • the sequence, or a unique portion thereof, of the ESE-2/ELF5 sequences identified by the I.M.A.G.E. Consortium CloneIDs 1864302 and 4480123 as well as clusters C019657 and NM — 001422 may be used.
  • sequences from the UniGene Homo sapiens cluster Hs.11713 may be used.
  • ESE-2/ELF5 sequences are useful in discriminations between normal and ADH or DCIS or IDC breast cells based upon decreased expression in non-normal breast cells. Human ESE-2/ELF5 has been mapped to 11p13-p15.
  • ESE-2/ELF5 related sequences are as follows, with the assigned coding region (ending with a termination codon) underlined and preceded by the 5′ untranslated and/or non-coding region and followed by the 3′ untranslated and/or non-coding region.
  • the 3′ untranslated and/or non-coding regions are presented as the complementary strand in the 3′ to 5′ direction for some of the sequences.
  • SEQ ID NOS:204-209 are found in the 3′ untranslated and/or non-coding regions of the disclosed ESE-2/ELF5 sequences.
  • CloneID 4480123, ESE-2b/ELF5 CACAAGGCTACAGGTGTCTTTATTTCCACTGCACGCTGGTGCTGGGAGCGCCTGCCTTCTCT SEQ ID NO:201 TGCCTTGAAAGCCTCCTCTTTGGACCTAGCCACCGCTGCCCTCACGGTA ATGTTGGACTCGGTGACACACAGCACCTTCCTGCCTAATGCATCCTTCTGCGATCCCCTGAT GTCGTGGACTGATCTGTTCAGCAATGAAGAGTACTACCCTGCCTTTGAGCATCAGACAGCCT GTGACTCATACTGGACATCAGTCCACCCTGAATACTGGACTAAGCCATGTCCACCCTGAATACTGGACTAAGCCATGTCCACCCTGAATACTGGACTAAGCCATGTGTGGGAGTGG CTCCAGTTCTGCTGCGACCAGTACAAGTTGGACACCAATTGCATCTCCT
  • a segment of CRIP1 composed of a 3′ untranslated region sequence and a sequence from the 3′ end of the coding region may be used as a probe for the detection of CRIP1 expression without being affected by the presence of any inconsistency in the representations of the coding regions provided above.
  • the use of an antibody which specifically recognizes CRIP1 protein to detect its expression would not be affected by the presence of any inconsistency in the representation of the coding regions provided above.
  • sequences include 3′ poly A (or poly T on the complementary strand) stretches that do not contribute to the uniqueness of the disclosed sequences.
  • the invention may thus be practiced with sequences lacking the 3′ poly A (or poly T) stretches.
  • the uniqueness of the disclosed sequences refers to the portions or entireties of the sequences which are found only in CRIP1, HN1, and ESE-2/ELF5 nucleic acids.
  • Preferred unique sequences for the practice of the invention are those which contribute to the consensus sequences for each of the three sets. These preferred unique sequences are of the lengths of polynucleotides of the invention as discussed herein.
  • any method known in the art may be utilized.
  • expression based on detection of RNA which hybridizes to polynucleotides containing the above described sequences is used. This is readily performed by any RNA detection or amplification+detection method known or recognized as equivalent in the art such as, but not limited to, reverse transcription-PCR (optionally real-time PCR), the methods disclosed in U.S. patent application Ser. No. 10/062,857 entitled “Nucleic Acid Amplification” filed on Oct. 25, 2001 as well as U.S. Provisional Patent Application Nos. 60/298,847 (filed Jun.
  • RNA stability resulting in an observation of increased expression
  • decreased RNA stability resulting in an observation of decreased expression
  • methods to identify increased RNA stability (resulting in an observation of increased expression) or decreased RNA stability (resulting in an observation of decreased expression) may also be used. These methods include the detection of sequences that increase or decrease the stability of mRNAs containing the CRIP1, HN1, and ESE-2/ELF5 sequences disclosed herein. These methods also include the detection of increased mRNA degradation.
  • polynucleotides having sequences present in the 3′ untranslated and/or non-coding regions of the above disclosed sequences are used to detect expression or non-expression of CRIP1, HN1, and ESE-2/ELF5 sequences in breast cells in the practice of the invention.
  • Such polynucleotides may optionally contain sequences found in the 3′ portions of the coding regions of the above disclosed sequences.
  • Polynucleotides containing a combination of sequences from the coding and 3′ non-coding regions preferably have the sequences arranged contiguously, with no intervening heterologous sequence(s).
  • the invention may be practiced with polynucleotides having sequences present in the 5′ untranslated and/or non-coding regions of the above CRIP1, HN1, and ESE-2/ELF5 sequences in breast cells to detect their levels of expression.
  • polynucleotides may optionally contain sequences found in the 5′ portions of the coding regions.
  • Polynucleotides containing a combination of sequences from the coding and 5′ non-coding regions preferably have the sequences arranged contiguously, with no intervening heterologous sequence(s).
  • Preferred polynucleotides contain sequences from 3′ or 5′ untranslated and/or non-coding regions of at least about 20, at least about 22, at least about 24, at least about 26, at least about 28, at least about 30, at least about 32, at least about 34, at least about 36, at least about 38, at least about 40, at least about 42, at least about 44, or at least about 46 consecutive nucleotides.
  • the term “about” as used in the previous sentence refers to an increase or decrease of 1 from the stated numerical value.
  • the term “about” as used in the preceding sentence refers to an increase or decrease of 10% from the stated numerical value.
  • Sequences from the 3′ or 5′ end of the above described coding regions as found in polynucleotides of the invention are of the same lengths as those described above, except that they would naturally be limited by the length of the coding region.
  • the 3′ end of a coding region may include sequences up to the 3′ half of the coding region.
  • the 5′ end of a coding region may include sequences up the 5′ half of the coding region.
  • sequences, or the coding regions and polynucleotides containing portions thereof may be used in their entireties.
  • Polynucleotides combining the sequences from a 3′ untranslated and/or non-coding region and the associated 3′ end of the coding region are preferably at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, or at least or about 400 consecutive nucleotides.
  • polynucleotides containing deletions of nucleotides from the 5′ and/or 3′ end of the above disclosed sequences may be used.
  • the deletions are preferably of 1-5, 5-10, 10-15, 15-20, 20-25, 25-30, 30-35, 35-40, 40-45, 45-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-125, 125-150, 150-175, or 175-200 nucleotides from the 5′ and/or 3′ end, although the extent of the deletions would naturally be limited by the length of the disclosed sequences and the need to be able to use the polynucleotides for the detection of expression levels.
  • polynucleotides containing portions of the above disclosed sequences including the 3′ end may be used in the practice of the invention.
  • Such polynucleotides would contain at least or about 50, at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, or at least or about 400 consecutive nucleotides from the 3′ end of the disclosed sequences.
  • the invention thus also includes polynucleotides used to detect CRIP1, HN1, and ESE-2/ELF5 expression in breast cells.
  • the polynucleotides may comprise a shorter polynucleotide consisting of sequences found in the above provided SEQ ID NOS in combination with heterologous sequences not naturally found in combination with CRIP1, HN1, and ESE-2/ELF5 sequences.
  • a polynucleotide of the invention may comprise a polynucleotide consisting of the sequence of SEQ ID NO: 29, with a deletion of one or more nucleotides from the 5′ and/or 3′ end, in combination with one or more non-HN1 sequences.
  • polynucleotides for use in the practice of the invention include those that have sufficient homology to those described above to detect expression by use of hybridization techniques. Such polynucleotides preferably have about or 95%, about or 96%, about or 97%, about or 98%, or about or 99% identity with CRIP1, HN1, or ESE-2/ELF5 sequences as described herein. Identity is determined using the BLAST algorithm, as described above.
  • polynucleotides for use in the practice of the invention may also be described on the basis of the ability to hybridize to polynucleotides of the invention under stringent conditions of about 30% v/v to about 50% formamide and from about 0.01M to about 0.15M salt for hybridization and from about 0.01M to about 0.15M salt for wash conditions at about 55 to about 65° C. or higher, or conditions equivalent thereto.
  • a population of single stranded nucleic acid molecules comprising one or both strands of a human CRIP1 or HN1 sequence is provided as a probe such that at least a portion of said population may be hybridized to one or both strands of a nucleic acid molecule quantitatively amplified from RNA of a non-normal or abnormal breast cell.
  • the population may be only the antisense strand of a human CRIP1 or HN1 sequence such that a sense strand of a molecule from, or amplified from, a non-normal or abnormal breast cell may be hybridized to a portion of said population.
  • the population preferably comprises a sufficiently excess amount of said one or both strands of a human CRIP1 or HN1 sequence in comparison to the amount of expressed (or amplified) nucleic acid molecules containing a complementary CRIP1 or HN1 sequence from a normal breast cell. This condition of excess permits the increased amount of nucleic acid expression in a non-normal or abnormal cell to be readily detectable as an increase.
  • the population of single stranded molecules is equal to or in excess of all of one or both strands of the nucleic acid molecules amplified from a non-normal or abnormal breast cell such that the population is sufficient to hybridize to all of one or both strands.
  • Preferred non-normal cells are ADH, DCIS, or IDC cells.
  • the single stranded molecules may of course be the denatured form of any CRIP1 and/or HN1 sequence containing double stranded nucleic acid molecule or polynucleotide as described herein.
  • the population may also be described as being hybridized to CRIP1 or HN1 sequence containing nucleic acid molecules at a level of at least twice as much as that by nucleic acid molecules of a normal breast cell.
  • the nucleic acid molecules may be those quantitatively amplified from a breast cell such that they reflect the amount of expression in said cell.
  • the population is preferably immobilized on a solid support, optionally in the form of a location on a microarray.
  • a portion of the population is preferably hybridized to nucleic acid molecules quantitatively amplified from a non-normal or abnormal breast cell by real time PCR.
  • the real time PCR may be practiced by use of amplified RNA from a breast cancer cell, as long as the amplification used was quantitative with respect to CRIP1 and/or HN1 containing sequences.
  • ESE-2/ELF5 DNA as methylated, deleted or otherwise inactivated, may be used as an indication of decreased expression as found in non-normal breast cells. This may be readily performed by PCR based methods known in the art.
  • the status of the promoter regions (SEQ ID NOS: 210 and 211) of the ESE-2/ELF5 may also be assayed as an indication of decreased expression of ESE-2/ELF5 sequences.
  • a non-limiting example is the methylation status of sequences found in the promoter region.
  • detection of the DNA of a sequence as amplified may be used for as an indication of increased expression as found in non-normal breast cells. This may be readily performed by PCR based, fluorescent in situ hybridization (FISH) and chromosome in situ hybridization (CISH) methods known in the art.
  • FISH fluorescent in situ hybridization
  • CISH chromosome in situ hybridization
  • a preferred embodiment using a nucleic acid based assay to determine expression is by immobilization of one or more of the sequences identified herein on a solid support, including, but not limited to, a solid substrate as an array or to beads or bead based technology as known in the art.
  • a solid support including, but not limited to, a solid substrate as an array or to beads or bead based technology as known in the art.
  • solution based expression assays known in the art may also be used.
  • the immobilized sequence(s) may be in the form of polynucleotides as described herein such that the polynucleotide would be capable of hybridizing to a DNA or RNA corresponding to the sequence(s).
  • the immobilized polynucleotide(s) may be used to determine the state of nucleic acid samples prepared from sample breast cell(s) for which the pre-cancer or cancer status is not known or for confirmation of a status that is already assigned to the sample breast cell(s). Without limiting the invention, such a cell may be from a patient suspected of being afflicted with, or at risk of developing, breast cancer.
  • the immobilized polynucleotide(s) need only be sufficient to specifically hybridize to the corresponding nucleic acid molecules derived from the sample.
  • the nucleic acid derived from the sample breast cancer cell(s) may be preferentially amplified by use of appropriate primers such that only the sequences to be analyzed are amplified to reduce contaminating background signals from other sequences present in the breast cell.
  • the nucleic acid from the sample may be globally amplified before hybridization to the immobilized polynucleotides.
  • RNA, or the cDNA counterpart thereof may be directly labeled and used, without amplification, by methods known in the art.
  • Sequence expression based on detection of a presence, increase, or decrease in protein levels or activity may also be used. Detection may be performed by any immunohistochemistry (IHC) based, bodily fluid based (where a CRIP1, HN1, and/or ESE-2/ELF5 polypeptide is found in a bodily fluid, such as but not limited to blood), antibody (including autoantibodies against the protein where present) based, ex foliate cell (from the cancer) based, mass spectroscopy based, and image (including used of labeled ligand where available) based method known in the art and recognized as appropriate for the detection of the protein.
  • IHC immunohistochemistry
  • bodily fluid based where a CRIP1, HN1, and/or ESE-2/ELF5 polypeptide is found in a bodily fluid, such as but not limited to blood
  • antibody including autoantibodies against the protein where present
  • ex foliate cell from the cancer
  • mass spectroscopy based
  • image including used of labele
  • Antibody and image based methods are additionally useful for the localization of tumors after determination of cancer by use of cells obtained by a non-invasive procedure (such as ductal lavage or fine needle aspiration), where the source of the cancerous cells is not known.
  • a labeled antibody or ligand may be used to localize the carcinoma(s) within a patient.
  • Antibodies for use in such methods of detection include polyclonal antibodies, optionally isolated from naturally occurring sources where available, and monoclonal antibodies, including those prepared by use of CRIP1, HN1, and/or ESE-2/ELF5 polypeptides as antigens.
  • Such antibodies, as well as fragments thereof function to detect or diagnose non-normal or cancerous breast cells by virtue of their ability to specifically bind CRIP1, HN1, or ESE-2/ELF5 polypeptides to the exclusion of other polypeptides to produce a detectable signal.
  • Recombinant, synthetic, and hybrid antibodies with the same ability may also be used in the practice of the invention.
  • Antibodies may be readily generated by immunization with a CRIP1, HN1, or ESE-2/ELF5 polypeptide, and polyclonal sera may also be used in the practice of the invention.
  • Antibody based detection methods are well known in the art and include sandwich and ELISA assays as well as Western blot and flow cytometry based assays as non-limiting examples.
  • Samples for analysis in such methods include any that contain CRIP1, HN1, or ESE-2/ELF5 polypeptides.
  • Non-limiting examples include those containing breast cells and cell contents as well as bodily fluids (including blood, serum, saliva, lymphatic fluid, as well as mucosal and other cellular secretions as non-limiting examples) that contain the polypeptides.
  • the above assay embodiments may be used in a number of different ways to identify or detect the presence of non-normal breast cells or breast cancer in a breast cancer cell sample from a patient. In some cases, this would reflect a secondary screen for the patient, who may have already undergone mammography or physical exam as a primary screen. If positive from the primary screen, the subsequent needle biopsy, ductal lavage, fine needle aspiration, or other analogous methods may provide the sample for use in the assay embodiments described herein.
  • the present invention is particularly useful in combination with non-invasive protocols, such as ductal lavage or fine needle aspiration, to prepare a breast cell sample.
  • the current analysis of ductal lavage samples is by cytological examination by a trained pathologist who classifies the samples in terms that are at least partly subjective: unsatisfactory (too few cells), benign (including fibrocystic change), atypical (or mild atypia), suspicious (or marked atypia), or malignant.
  • the present invention provides a more objective set of criteria, in the form of gene expression levels of discrete gene sequences, to discriminate (or delineate) between normal and non-normal breast cells.
  • the isolation and analysis of a breast cancer cell sample may be performed as follows:
  • Ductal lavage or other non-invasive procedure is performed on a patient to obtain a sample.
  • Pathologist or image analysis software scans the sample for the presence of atypical cells.
  • RNA is extracted from the harvested cells.
  • RNA is assayed for the expression of CRIP1, HN1, and/or ESE-2/ELF5 sequences.
  • a specific example of the above method would be performing ductal lavage following a primary screen, observing and collecting non-normal cells (or cells suspected of being non-normal) for analysis.
  • the sample may permit the collection of both normal and non-normal cells (or cells suspected of being non-normal) for analysis.
  • the expression levels of CRIP1, HN1, and/or ESE-2/ELF5 sequences in each of these two populations may be compared to each other. This approach can be significantly more powerful than one using the non-normal cells only approach because it utilizes information from the normal cells and the differences between normal and non-normal cells to determine the status of the non-normal cells from the sample.
  • the present invention may also be used with solid tissue biopsies.
  • a solid biopsy may be collected and prepared for visualization followed by determination of increased CRIP1 and/or HN1 expression to identify or diagnose the presence of non-normal cells.
  • One preferred means is by use of in situ hybridization with polynucleotide or protein identifying probe(s) for assaying expression of said gene(s).
  • An analogous method may be used to detect decreased expression of ESE-2/ELF5 sequences.
  • the solid tissue biopsy may be used to extract molecules followed by analysis for expression of the disclosed sequence(s). This provides the possibility of leaving out the need for visualization and collection of only those cells suspected of being non-normal. This method may of course be modified such that only cells suspected of being non-normal are collected and used to extract molecules for analysis. This would require some form of selection as a prerequisite to gene expression analysis.
  • both normal cells and cells suspected of being non-normal are collected and used to extract molecules for analysis of sequence expression.
  • the approach, benefits and results are as described above using non-invasive sampling.
  • sequence(s) identified herein may be used as part of a simple PCR or array based assay simply to determine the presence of non-normal cells in a sample from a non-invasive sampling procedure. If normal expression levels of the disclosed sequences are identified, no further examination may be necessary. If non-normal expression levels are detected, a more comprehensive analysis may follow.
  • sequence expression from samples may be by use of a single microarray able to assay expression of the disclosed sequences as well as other sequences, including sequences known not to vary in expression levels between normal and non-normal breast cells, for convenience and improved accuracy.
  • kits comprising agents (like the polynucleotides and/or antibodies described herein as non-limiting examples) for the detection of expression of the disclosed sequences.
  • agents like the polynucleotides and/or antibodies described herein as non-limiting examples
  • kits optionally comprising the agent with an identifying description or label or instructions relating to their use in the methods of the present invention, are provided.
  • kit may comprise containers, each with one or more of the various reagents (typically in concentrated form) utilized in the methods, including, for example, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more primer complexes of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase).
  • the appropriate nucleotide triphosphates e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP
  • reverse transcriptase e.g., DNA polymerase, RNA polymerase
  • primer complexes of the present invention e.g., appropriate
  • the methods provided by the present invention may also be automated in whole or in part. All aspects of the present invention may also be practiced such that they consist essentially of a subset, or subregion, of the disclosed sequences to the exclusion of material irrelevant to the identification of non-normal or cancerous breast cells.
  • abnormal epithelium from ADH, DCIS and IDC and phenotypically normal epithelium (henceforth referred to as normal) from 36 breast cancer patients and 3 healthy mammoplasty reduction patients were isolated via laser capture microdissection (LCM).
  • LCM laser capture microdissection
  • ADH or DCIS or IDC the expression level of each gene in a disease state
  • DCIS or IDC the expression level of each gene in a disease state
  • Unsupervised hierarchical clustering revealed one sequence cluster demonstrating increased expression in a majority of the diseased samples.
  • CRIP1 was included in the cluster and identified as displaying increased expression levels in ADH with persistence in DCIS and IDC samples. Its increased expression may thus be a potential biomarker for the detection of breast cancer including the pre-malignant stage of ADH.
  • DCIS and IDC were classified (histological grade) according to the European classification (Holland, R. et al.) and by the Nottingham combined histological grade (Elston, C. W. et al.), respectively.
  • ER and PR expression were determined by immunohistochemical staining (negative when none of the tumor cell nuclei showed staining), and Her-2 expression determined by immunohistochemistry or FISH. This study was approved the Massachusetts General Hospital human research committee in accordance with NIH human research study guidelines.
  • RNA isolation and amplification were laser capture microdissected in triplicate (from consecutive tissue sections) as described (Sgroi et al.) using a PixCell II LCM system (Arcturus Engineering Inc., Mountain View, Calif.). Total RNA was extracted from the captured cells using the PicopureTM RNA Isolation Kit (Arcturus). T7-based RNA amplification was carried out using the RiboAmpTM kit (Arcturus). Briefly, the RNA from each sample was primed with an oligo-dT primer containing a T7 promoter sequence, reverse transcribed and then converted to double stranded cDNA.
  • RNA amplified RNA
  • aRNA amplified RNA
  • cDNA was transcribed from aRNA in the presence of 5-(3-aminoallyl)-2′-deoxyuridine 5′-triphosphate (aminoallyl dUTP) using Stratagene's FairPlay kitTM (La Jolla, Calif.). Cy3 or Cy5 mono-reactive dye (Amersham, Piscataway, N.J.) was conjugated onto purified cDNA and the residual dye was removed using QiaQuick PCR Purification columns (Qiagen, Valencia, Calif.).
  • Each Cy5-labeled cDNA was hybridized together with the Cy3-labeled reference probe to a microarray in 40 ⁇ L hybridization solution (5 ⁇ SSC, 0.1 ⁇ g/ ⁇ L COT I, 0.2%SDS, 50% formamide) at a concentration of 25 ng/ ⁇ L per channel for 17 hrs at 42° C. in >60% relative humidity.
  • 40 ⁇ L hybridization solution 5 ⁇ SSC, 0.1 ⁇ g/ ⁇ L COT I, 0.2%SDS, 50% formamide
  • Cluster and discriminant analysis Hierarchical cluster analysis was performed in GeneMaths (v1.5, Applied-Maths, Austin, Tex.) using the cosine correlation coefficient as a measure of similarity between two genes or samples and complete linkage. Linear discriminant analysis with variance was performed within GeneMaths.
  • RNA RT-PCR validation study independently laser captured ( ⁇ 40,000) normal breast epithelial cells from case 215, and ⁇ 40,000 abnormal epithelial cells from DCIS (from cases 89, 178, 179) or IDC (from cases 97, 169, 170) were used. Total RNA was isolated and converted to double-stranded cDNA. For studies using amplified RNA (aRNA), 2 mgs of aRNA from each microdissected sample was converted into double-stranded cDNA.
  • aRNA amplified RNA
  • cDNA derived from non-amplified and amplified RNA the double-stranded cDNA was quantitated with PicoGreen (Molecular Probes) using a spectrofluorometer (Molecular Devices) and quantitative analysis of gene expression performed (RT-PCR) was performed with an ABI 7900HT (Applied Biosystems, Foster City, Calif.) as described (Sgroi et al., 1999).
  • RT-PCR demonstrated over-expression of CRIP1 (>2-fold) in 7 of 8 ADH, 27 of 30 DCIS, and 23 of 25 IDC cases, and under-expression of ELF5 (>2-fold) in 7 of 8 ADH, 28 of 30 DCIS, and 25 of 25 IDC cases (FIG. 1).

Abstract

Methods and compositions are provided for the detection of breast cancer based upon the identification of three biomarkers for non-normal breast cells. The biomarkers were identified based upon multiple sampling of reference breast tissue samples from independent cases of breast cancer. Two biomarkers display increased expression in non-normal cells while the third biomarker displays decreased expression in non-normal cells.

Description

    RELATED APPLICATIONS
  • This application is a continuation-in-part of U.S. patent applications Ser. Nos. 10/028,018, filed Dec. 21, 2001, and 10/211,015, filed Aug. 1, 2002, which are hereby incorporated in their entireties as if fully set forth.[0001]
    • FIELD OF THE INVENTION
  • The invention relates to the identification and use of gene sequences which are differentially expressed in breast cancer. In particular, the invention provides the identities of three sets of sequences that may be used to identify the presence of breast cancer in tissue and cell samples. The expression of these sequences, whether embodied in nucleic acid expression, protein expression, nucleic acid amplification and/or activation, or other formats, are used in the diagnosis and/or treatment of breast cancer as well as for the study and/or determination of prognosis of a patient. When used for diagnosis, the expression levels of these sequences are used to identify the presence of breast cancer and provide guidance as to the treatment thereof. [0002]
    • BACKGROUND OF THE INVENTION
  • Breast cancer is by far the most common cancer among women. Each year, more than 180,000 and 1 million women in the U.S. and worldwide, respectively, are diagnosed with breast cancer. Breast cancer is the leading cause of death for women between ages 50-55, and is the most common non-preventable malignancy in women in the Western Hemisphere. An estimated 2,167,000 women in the United States are currently living with the disease (National Cancer Institute, Surveillance Epidemiology and End Results (NCI SEER) program, [0003] Cancer Statistics Review (CSR), www-seer.ims.nci.nih.gov/Publications/CSR1973 (1998)). Based on cancer rates from 1995 through 1997, a report from the National Cancer Institute (NCI) estimates that about 1 in 8 women in the United States (approximately 12.8 percent) will develop breast cancer during her lifetime (NCI's Surveillance, Epidemiology, and End Results Program (SEER) publication SEER Cancer Statistics Review 1973-1997). Breast cancer is the second most common form of cancer, after skin cancer, among women in the United States. An estimated 250,100 new cases of breast cancer are expected to be diagnosed in the United States in 2001. Of these, 192,200 new cases of more advanced (invasive) breast cancer are expected to occur among women (an increase of 5% over last year), 46,400 new cases of early stage (in situ) breast cancer are expected to occur among women (up 9% from last year), and about 1,500 new cases of breast cancer are expected to be diagnosed in men (Cancer Facts & Figures 2001 American Cancer Society). An estimated 40,600 deaths (40,300 women, 400 men) from breast cancer are expected in 2001. Breast cancer ranks second only to lung cancer among causes of cancer deaths in women. Nearly 86% of women who are diagnosed with breast cancer are likely to still be alive five years later, though 24% of them will die of breast cancer after 10 years, and nearly half (47%) will die of breast cancer after 20 years.
  • Every woman is at risk for breast cancer. Over 70 percent of breast cancers occur in women who have no identifiable risk factors other than age (U.S. General Accounting Office. Breast Cancer, 1971-1991: Prevention, Treatment and Research. GAO/PEMD-92-12; 1991). Only 5 to 10% of breast cancers are linked to a family history of breast cancer (Henderson IC, Breast Cancer. In: Murphy G P, Lawrence W L, Lenhard R E (eds). [0004] Clinical Oncology. Atlanta, Ga.: American Cancer Society; 1995:198-219).
  • The relationship between the expression of cellular factors and breast cancer has been an area of interest. STK15, a centrosomal protein kinase, has been observed as frequently amplified in breast cancer, and its quantitative expression levels positively correlate with tumor grade (Zhou, H. et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. [0005] Nat Genet 20, 189-93, (1998)). RAD51 has recently been shown to interact with the tumor suppressor BRCA1 (Chen, J. J., et al. BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res 59, 1752s-1756s (1999)), and its expression also positively correlates with tumor grade in breast cancer (Maacke, H. et al. Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer. Int J Cancer 88, 907-13 (2000)).
  • Citation of documents herein is not intended as an admission that any is pertinent prior art. All statements as to the date or representation as to the contents of documents is based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of the documents. [0006]
    • SUMMARY OF THE INVENTION
  • The present invention relates to the identification and use of gene sequences identified as differentially expressed in breast cancer. The sequences of two of the genes display increased expression in non-normal (or abnormal) breast cells, such as those that would be identified as atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) by standard pathology techniques based upon cytological criteria. The sequences of the third gene display decreased expression the same non-normal cells. [0007]
  • The first set of sequences found to be more highly expressed in non-normal breast cells are those of human cysteine-rich intestinal protein 1 (CRIP1 or hCRIP1, also known as human cysteine-rich heart protein or HCRHP). CRIP1 has been mapped to human chromosomal segment 7q11.23 (see Garcia-Barcelo et al. Genomics, 47(3):419-422, 1998). [0008]
  • The second set of sequences found to be more highly expressed in non-normal breast cells are those of the “hematological and neurological expressed [0009] sequence 1” (HN1 or Hn1). Murine HN1 has been identified as being expressed in mouse hemopoietic and brain tissues (see Tang et al. Mamm. Genome, 8:695-696, 1997).
  • The set of sequences found to be expressed at lower levels in non-normal breast cells are those expressed with a “second epithelium restricted Ets transcription factor” termed ESE-2 (see Oettgen et al., J. Biol. Chem., 274(41):29439-52, 1999). The coding region sequence of ESE-2b is identical to that of the E74 like [0010] factor 5, termed ELF5 (see Zhou et al., Oncogene, 17(21):2719-32, 1998).
  • The identified sequences may thus be used in methods of detecting the presence of non-normal breast cells in a tissue or cell containing sample from a subject. The presence of non-normal breast cells may also be used in methods of diagnosing the presence of breast cancer in a tissue or cell containing sample from a subject. A subject, from which a sample is taken, may be one afflicted with, or suspected of having, breast cancer. [0011]
  • The present invention provides a non-subjective means for detecting the presence of non-normal breast cells. This provides advantages over the use of histomorphological or cytological criteria in standard pathology techniques, which requires some level of interpretation by a pathologist trained in assessing the presence and/or progression of breast cancer. The expression levels of these sequences may also be used as a means to assay small, node negative tumors that are not readily assessed by conventional means. [0012]
  • The expression levels of the identified sequences may be used alone or in combination with other sequences capable of identifying the presence of non-normal cells or of various stages and/or grades of breast cancer. Preferably, the sequences of the invention are used alone or in combination with each other. [0013]
  • The present invention provides means for correlating a molecular expression phenotype with a physiological (cellular) stage or state of a non-normal or abnormal breast cell. This correlation provides a way to molecularly diagnose and/or monitor a cell's status in comparison to normal breast cell phenotypes as disclosed herein. Additional uses of the sequences are in the classification of cells and tissues; determination of diagnosis and/or prognosis. Use of the sequences to identify cells of a sample as non-normal or abnormal may also be used to determine the choice, or alteration, of therapy used to treat such cells in the subject from which the sample originated. [0014]
  • The ability to identify non-normal and abnormal breast cells is provided by the recognition of the relevancy of the level of expression of the identified sequences and not by the form of the assay used to determine the actual level of expression. An assay may utilize a means related to the expression level of the sequences disclosed herein as long as the assay reflects, quantitatively or qualitatively, expression of the sequence. Preferably, however, a quantitative assay means is preferred. Identifying features of the sequences include, but are not limited to, unique nucleic acid sequences used to encode (DNA), or express (RNA), the disclosed sequences or epitopes specific to, or activities of, proteins encoded by the sequences. Alternative means include detection of nucleic acid amplification as indicative of increased expression levels (CRIP1 and HN1 sequences) and nucleic acid inactivation, deletion, or methylation, as indicative of decreased expression levels (ESE-2 and ELF5 sequences). Stated differently, the invention may be practiced by assaying one or more aspect of the DNA template(s) underlying the expression of the disclosed sequence(s), of the RNA used as an intermediate to express the sequence(s), or of the proteinaceous product expressed by the sequence(s). As such, the detection of the amount of, stability of, or degradation (including rate) of, such DNA, RNA and proteinaceous molecules may be used in the practice of the invention. [0015]
  • The practice of the present invention is unaffected by the presence of minor mismatches between the disclosed sequences and those expressed by cells of a subject's sample. A non-limiting example of the existence of such mismatches are seen in cases of sequence polymorphisms between individuals of a species, such as individual human patients within [0016] Homo sapiens. Knowledge that expression of the disclosed sequences (and sequences that vary due to minor mismatches) is correlated with the presence of non-normal or abnormal breast cells and breast cancer is sufficient for the practice of the invention with an appropriate cell containing sample via an assay for expression.
  • In one aspect, the invention provides for the identification of the expression levels of the disclosed sequences by analysis of their expression in a sample containing breast cells. In one preferred embodiment, the sample contains single cells or homogenous cell populations which have been dissected away from, or otherwise isolated or purified from, contaminating cells beyond that possible by a simple biopsy. Multiple means for such analysis are available, including detection of expression within an assay for global, or near global, gene expression in a sample (e.g. as part of a gene expression profiling analysis such as on a microarray) or by specific detection, such as quantitative PCR or real time quantitative PCR. [0017]
  • Preferably, the sample is isolated via non-invasive means. The expression of the disclosed sequence(s) in the sample may be determined and compared to the expression of said sequence(s) in reference data of non-normal breast cells. Alternatively, the expression level may be compared to expression levels in normal cells, preferably from the same sample or subject. [0018]
  • When individual breast cells are isolated in the practice of the invention, one benefit is that contaminating, non-breast cells (such as infiltrating lymphocytes or other immune system cells) are not present to possibly affect detection of expression of the disclosed sequence(s). Such contamination is present where a biopsy is used to generate gene expression profiles. [0019]
  • While the present invention has been described mainly in the context of human breast cancer, it may be practiced in the context of breast cancer of an animal known to be potentially afflicted by breast cancer by use of the corresponding sequences of the animal. Preferred animals for the application of the present invention are mammals, particularly those important to agricultural applications (such as, but not limited to, cattle, sheep, horses, and other “farm animals”) and for human companionship (such as, but not limited to, dogs and cats).[0020]
    • BRIEF DESCRIPTION OF THE FIGURES
  • FIG. 1 shows log[0021] 2 plots of the ratio of expression in ADH, DCIS, and IDC cells to normal cells for CRIP1 and ELF5 sequences. The horizontal line is at “0” such that the ratio is “1” and all points above the line represent increases in expression relative to normal breast cells while all points below the line represent decreases in expression relative to normal breast cells.
  • FIG. 2 shows the results of in situ hybridization with sense and anti-sense CRIP1 sequences to locate its expression at the cellular level in normal versus IDC cells of the same sample. CRIP1 signal localized to the epithelial cells, and its intensity was markedly increased in the IDC compartment of the same biopsy. [0022]
  • FIG. 3 shows the results of in situ hybridization with sense and anti-sense CRIP1 sequences to locate its expression at the cellular level in normal versus DCIS and IDC cells. CRIP1 signal again localized to the epithelial cells, and its intensity was markedly increased in non-normal cells.[0023]
    • DETAILED DESCRIPTION OF THE SPECIFIC EMBODIMENTS
  • Definitions of terms as used herein: [0024]
  • A “sequence” or “gene sequence” as used herein is a nucleic acid molecule or polynucleotide composed of a discrete order of nucleotide bases. The term includes the ordering of bases that encodes a discrete product (i.e. “coding region”), whether RNA or proteinaceous in nature, as well as the ordered bases that precede or follow a “coding region”. Non-limiting examples of the latter include 5′ and 3′ untranslated regions of a gene. It is appreciated that more than one polynucleotide may be capable of encoding a discrete product. It is also appreciated that alleles and polymorphisms of the disclosed sequences may exist and may be used in the practice of the invention to identify the expression level(s) of the disclosed sequences or the allele or polymorphism. Identification of an allele or polymorphism depends in part upon chromosomal location and ability to recombine during mitosis. [0025]
  • The terms “correlate” or “correlation” or equivalents thereof refer to an association between expression of one or more sequences and a physiologic state of a breast cell to the exclusion of one or more other states by use of the methods as described herein. The invention provides for the correlation between increases in CRIP1 and HN1 sequences and non-normal or abnormal breast cells. Similarly, the invention provides for the correlation between decreases in ESE-2/ELF5 sequences and non-normal or abnormal breast cells. Increases and decreases may be readily expressed in the form of a ratio between expression in a non-normal cell and a normal cell such that a ratio of one (1) indicates no difference while ratios of two (2) and one-half indicate twice as much, and half as much, expression in the non-normal cell versus the normal cell, respectively. Expression levels can be readily determined by quantitative methods as described below. [0026]
  • For example, increases in CRIP1 expression can be indicated by ratios of or about 1.1, of or about 1.2, of or about 1.3, of or about 1.4, of or about 1.5, of or about 1.6, of or about 1.7, of or about 1.8, of or about 1.9, of or about 2, of or about 2.5, of or about 3, of or about 3.5, of or about 4, of or about 4.5, of or about 5, of or about 5.5, of or about 6, of or about 6.5, of or about 7, of or about 7.5, of or about 8, of or about 8.5, of or about 9, of or about 9.5, of or about 10, of or about 15, of or about 20, of or about 30, of or about 40, of or about 50, of or about 60, of or about 70, of or about 80, of or about 90, of or about 100, of or about 150, of or about 200, of or about 300, of or about 400, of or about 500, of or about 600, of or about 700, of or about 800, of or about 900, or of or about 1000. A ratio of 2 is a 100% (or a two-fold) increase in expression. Similar ratios can be used with respect to increases in HN1 expression. Decreases in ESE-2/ELF5 expression can be indicaed by ratios of or about 0.9, of or about 0.8, of or about 0.7, of or about 0.6, of or about 0.5, of or about 0.4, of or about 0.3, of or about 0.2, of or about 0.1, of or about 0.05, of or about 0.01, of or about 0.005, of or about 0.001, of or about 0.0005, of or about 0.0001, of or about 0.00005, of or about 0.00001, of or about 0.000005, or of or about 0.000001. Non-limiting examples of such ratios are shown in FIG. 1. [0027]
  • A “polynucleotide” is a polymeric form of nucleotides of any length, either ribonucleotides or deoxyribonucleotides linked by phosphodiester bonds and encompasses the strand of a given sequence as disclosed herein as well as the complementary strand of a given sequence. The term refers only to the primary structure of the molecule. Thus, this term includes double- and single-stranded DNA and RNA as well as analogs thereof comprising a non-phosphodiester backbone. It also includes known types of modifications including labels known in the art, methylation, “caps”, substitution of one or more of the naturally occurring nucleotides with an analog, and internucleotide modifications such as uncharged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), as well as unmodified forms of the polynucleotide. [0028]
  • The term “amplify” is used in the broad sense to mean creating an amplification product can be made enzymatically with DNA or RNA polymerases. “Amplification,” as used herein, generally refers to the process of producing multiple copies of a desired sequence, particularly those of a sample. “Amplification” may also be used in the context of DNA amplification wherein copies of coding sequences within the cellular genome are increased. “Multiple copies” mean at least 2 copies. A “copy” does not necessarily mean perfect sequence complementarity or identity to the template sequence. Methods for amplifying mRNA are generally known in the art, and include reverse transcription PCR (RT-PCR) and those described in U.S. patent application Ser. No. 10/062,857 entitled “Nucleic Acid Amplification” filed on Oct. 25, 2001 as well as U.S. Provisional Patent Application Nos. 60/298,847 (filed Jun. 15, 2001) and 60/257,801 (filed Dec. 22, 2000), all of which are hereby incorporated by reference in their entireties as if fully set forth. [0029]
  • By corresponding is meant that a nucleic acid molecule shares a substantial amount of sequence identity with another nucleic acid molecule. Substantial amount means at least 95%, usually at least 98% and more usually at least 99%, and sequence identity is determined using the BLAST algorithm, as described in Altschul et al. (1990), J. Mol. Biol. 215:403-410 (using the published default setting, i.e. parameters w=4, t=17). Alternatively, RNA may be directly labeled as the corresponding cDNA by methods known in the art. [0030]
  • A “microarray” is a linear or two-dimensional array of preferably discrete regions, each having a defined area, formed on the surface of a solid support such as, but not limited to, glass, plastic, or synthetic membrane. The density of the discrete regions on a microarray is determined by the total numbers of immobilized polynucleotides to be detected on the surface of a single solid phase support, preferably at least about 50/cm[0031] 2, more preferably at least about 100/cm2, even more preferably at least about 500/cm2, but preferably below about 1,000/cm2. Preferably, the arrays contain less than about 500, about 1000, about 1500, about 2000, about 2500, or about 3000 immobilized polynucleotides in total. As used herein, a DNA microarray is an array of oligonucleotides or polynucleotides placed on a chip or other surfaces used to hybridize to amplified or cloned polynucleotides from a sample. Since the position of each particular group of primers in the array is known, the identities of a sample polynucleotides can be determined based on their binding to a particular position in the microarray.
  • Because the invention relies upon the identification of sequences that are over- or under-expressed, one embodiment of the invention involves determining expression by hybridization of mRNA, or an amplified or cloned version thereof, of a sample cell to a polynucleotide of a disclosed sequence. Preferred polynucleotides of this type contain at least about 20, at least about 22, at least about 24, at least about 26, at least about 28, at least about 30, at least about 32, at least about 34, at least about 36, at least about 38, at least about 40, at least about 42, at least about 44, or at least about 46 consecutive bases of a sequence that is not found in other human sequences. The term “about” as used in the previous sentence refers to an increase or decrease of 1 from the stated numerical value. Longer polynucleotides may of course contain minor mismatches (e.g. via the presence of mutations) which do not affect hybridization to the nucleic acids of a sample. Such polynucleotides may be label to assist in their detection; alternatively, the nucleic acids to which such polynucleotides will hybridize may be labeled. Such polynucleotides may also be immobilized, such as by attachment to a solid support. [0032]
  • Even more preferred are polynucleotides of at least or about 50, at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, at least or about 400, at least or about 450, or at least or about 500 consecutive bases of a sequence that is not found in other sequences in the human genome. The term “about” as used in the preceding sentence refers to an increase or decrease of 10% from the stated numerical value. The polynucleotides may of course contain minor mismatches which do not affect hybridization to the nucleic acids of a sample. [0033]
  • In another embodiment of the invention, all or part of a disclosed sequence may be amplified and detected by methods such as the polymerase chain reaction (PCR) and variations thereof, such as, but not limited to, quantitative PCR (QPCR), reverse transcription PCR (RT-PCR), and real-time PCR, optionally real-time RT-PCR. Such methods would utilize one or two primers that are complementary to portions of a disclosed sequence, where the primers are used to prime nucleic acid synthesis. The newly synthesized nucleic acids are optionally labeled and may be detected directly or by hybridization to a polynucleotide of the invention. The newly synthesized nucleic acids may be contacted with polynucleotides (containing sequences) of the invention under conditions which allow for their hybridization. [0034]
  • Alternatively, and in another embodiment of the invention, expression of a sequence may be determined by analysis of expressed protein encoded by said sequence in a cell sample of interest by use of one or more antibodies specific for one or more epitopes of the individual products (proteins) in said cell sample. Such antibodies are preferably labeled to permit their easy detection after binding to the gene product. In the case of a protein that may be found in the blood, serum or other bodily fluid, the assay may modified to use such materials in place of a breast cell containing sample. [0035]
  • The term “label” refers to a composition capable of producing a detectable signal indicative of the presence of the labeled molecule. Suitable labels include radioisotopes, nucleotide chromophores, enzymes, substrates, fluorescent molecules, chemiluminescent moieties, magnetic particles, bioluminescent moieties, and the like. As such, a label is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. [0036]
  • The term “support” refers to conventional supports such as beads, particles, dipsticks, fibers, filters, membranes and silane or silicate supports such as glass slides. [0037]
  • As used herein, a “breast tissue sample” or “breast cell sample” refers to a sample of breast tissue or fluid isolated from an individual, preferably suspected of being afflicted with, or at risk of developing, breast cancer. Such samples are primary isolates (in contrast to cultured cells) and may be collected by a non-invasive means, including, but not limited to, ductal lavage, fine needle aspiration, needle biopsy, the devices and methods described in U.S. Pat. No. 6,328,709, or another suitable means recognized in the art. Alternatively, the “sample” may be collected by an invasive method, including, but not limited to, surgical biopsy. [0038]
  • “Expression” and “gene expression” include transcription and/or translation of nucleic acid material, such as the sequences of the invention. [0039]
  • As used herein, the term “comprising” and its cognates are used in their inclusive sense; that is, equivalent to the term “including” and its corresponding cognates. [0040]
  • Conditions that “allow” an event to occur or conditions that are “suitable” for an event to occur, such as hybridization, strand extension, and the like, or “suitable” conditions are conditions that do not prevent such events from occurring. Thus, these conditions permit, enhance, facilitate, and/or are conducive to the event. Such conditions, known in the art and described herein, depend upon, for example, the nature of the nucleotide sequence, temperature, and buffer conditions. These conditions also depend on what event is desired, such as hybridization, cleavage, strand extension or transcription. [0041]
  • Sequence “mutation,” as used herein, refers to any sequence alteration in the sequence of a gene disclosed herein interest in comparison to a reference sequence. A sequence mutation includes single nucleotide changes, or alterations of more than one nucleotide in a sequence, due to mechanisms such as substitution, deletion or insertion. Single nucleotide polymorphism (SNP) is also a sequence mutation as used herein. Because the present invention is based on the relative level of sequence expression, mutations in non-coding regions of genes as disclosed herein may also be assayed in the practice of the invention. “Detection” includes any means of detecting, including direct and indirect detection of gene expression and changes therein. For example, “detectably less” products may be observed directly or indirectly, and the term indicates any reduction (including the absence of detectable signal). Similarly, “detectably more” product means any increase, whether observed directly or indirectly. [0042]
  • Increases and decreases in expression of the disclosed sequences are defined in the following terms based upon percent or fold changes over expression in normal cells. Increases may be of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, or 200% relative to expression levels in normal cells. Alternatively, fold increases may be of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 fold over expression levels in normal cells. Decreases may be of 10, 20, 30, 40, 50, 55, 60, 65, 70, 75, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 99 or 100% relative to expression levels in normal cells. [0043]
  • Unless defined otherwise all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs. [0044]
  • Specific Embodiments [0045]
  • The present invention relates to the identification and use of three sets of sequences for the detection of non-normal and cancerous breast cells. The differential expression of these sequences in non-normal or abnormal breast cells relative to normal breast cells is used to identify a breast cancer cell as being non-normal or otherwise abnormal. The invention is advantageously used to identify breast cells as being those of ADH, DCIS, and IDC as otherwise determinable standard pathological techniques. The invention may also be applied to the identification of breast cells as being those of atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and invasive lobular carcinoma (ILC) as otherwise determinable by standard pathological techniques. [0046]
  • Other non-limiting examples of non-normal or abnormal cells include malignant cells, atypical cells (including reactive and pre-neoplastic), neoplastic cells, tumor cells, and cancer or cancerous cells. [0047]
  • The sequences(s) identified by the present invention are expressed in correlation with non-normal breast cells, and thus negatively correlated with normal breast cells. For example, CRIP1, identified by I.M.A.G.E. Consortium CloneID 1323448 and cluster NM[0048] —001311 (“The I.M.A.G.E. Consortium: An Integrated Molecular Analysis of Genomes and their Expression,” Lennon et al., 1996, Genomics 33:151-152; see also image.llnl.gov) has been found to be useful in discriminations between normal and ADH or DCIS or IDC breast cells.
  • In preferred embodiments of the invention, any sequence, or unique portion thereof, of the CRIP1 sequences identified by the cluster, as well as UniGene Homo sapiens cluster Hs.17409, maybe used. The consensus sequence of the I.M.A.G.E. Consortium cluster is as follows, with the assigned coding region (ending with a termination codon) underlined and preceded by the 5′ untranslated and/or non-coding region and followed by the 3′ untranslated and/or non-coding region: [0049]
    (consensus sequence for CRIP1)
    GGCACGAGGGCCCGTGCCGCCCCAGCCGCTGCCGCCTGCACCGGACCCGGAGCCGCC SEQ ID NO:1
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGAAAAAAAAAAAAAAAAAAA
  • The sequences identified as belonging to the I.M.A.G.E. Consortium and UniGene clusters, with the assigned coding region underlined, follow below. The 5′ and 3′ untranslated and/or non-coding regions are by reference to the assigned coding region, which is presented as the complementary strand in the 3′ to 5′ direction for some of the sequences. [0050]
    (CloneID 5103334)
    GGGGATTGGAGATGTTCCCCTCATGGAGGGTGCTGAGGACCTTAGGGTGGGCTGCCAGGCTG SEQ ID NO:2
    GGCGGATGCGGGCTAAGTGCACAGGGCCTTGGGCAGAGCTGGCTGCAAGAGGCGGGTACGCC
    AGTGGTGGGTAGGCGCCCGCG
    TCCTGCAGCGTCTCACCGGGGCCTGTCTGTGCCTCTGCAGCCGAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGAGCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGAAAAAAAAAAAA
    (CloneID 5777677)
    GCACGAGCGCTGGGCTAGGGGCGCGGCTTGAACTCGCCTAAAGAGCTGCGCCCTCTCATCTC SEQ ID NO:3
    GCGCCTGCAGCCCGTGCCGCCCCAGCCGCTGCCGCCTGCACCGGACCCGGAGCCGCC
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCCAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTCGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTCCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGG
    (CloneID 563289)
    GCACGAGCGCTGGGCTACGGGCGCGGCTTGAACTCGCCTAAAGAGCTGCGCCCTCTCATCTC SEQ ID NO:4
    GCGCCTGCACCCCGTGCCGCCCCAGCCGCTGCCCCCTGCACCGGACCCGGAGCCGCC
    ATCCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGCGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCCAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGACCACGAACGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTCTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    T
    (CloneID 1627147 in 3′ to 5′ orientation)
    TGGTTTTCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGAGCCCTGCGCATC SEQ ID NO:5
    TGGGGACAAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTC
    CACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTA
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGCCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCGAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGGCGGCAGCGGCTGGGCCGGCACGGGCTGCAGGCGCGACAC
    TGGGTGGATCCGGCCTGGTCCGCGCCTTTCAGGGACCCCGGGACCCCGCCCCTTGGAGACAC
    CGCCCCTC
    (CloneID 1627139 in 3′ to 5′ orientation)
    TGGTTTTCCAAGTGTTCAGGTTTACTGAGACCATTAGGGGCAACAAGGGAGCCCTGGGCATC SEQ ID NO:6
    TGGGGACAAGGCCTGCCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTC
    CACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCCCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTA
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCCAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGCTGCAGGCGGCAGCGGCTGGGGCGGCACGGGCTGCAGGCGCGAGAC
    TGGGTGGATCCGGCCTGGTCCGCGCCTTTCA
    (CloneID 3296101 in 3′ to 5′ orientation)
    TTGGTTTTCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGCAGCCCTGCGCAT SEQ ID NO:7
    CTGGGGACAAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCT
    CCACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTG
    CGTAGCAGGGCTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCGAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGCCGGCAGCGGCTGGGGCGGCACGCGCTGCATGCGCGAGAC
    TGGGTGGATCCGGCCTGGTCCGCGCCTTTCAGGGACCCCGGGACCCCG
    (CloneID 3631097)
    GCCGCCTGCACCGGACCGGAGCCGCC SEQ ID NO:8
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGG
    CAAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGTG
    GGGCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTG
    GGCCTAAAGGCTTTGGGCGGGGCGGAGCCGAGGAGCCACACTTTCAAGTAA
    AACCAGGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCCACTTGTCCAGGGCAAAAT
    TGCCAGGCCTTTGTCCCCCACAATGCCCAGGGGCTCCCTTTGTTTGGCCCCCTTAATTGCTC
    TCAGTAAACCCTTGAACACTTGGA
    (CloneID 2782288)
    CAGCCCGTGCCGCCCCAGCCGCTGCCGCCTGCACCGGACCCGGAGCCGCC SEQ ID NO:9
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCAAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCACCCATGTTTGGG
    CCTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTCCAGGGCCACTGTCCAGGCAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGT
    (CloneID 3903337)
    CACCGGACCCGGACCCGGCC SEQ ID NO:10
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAAGGCTTTCGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCCTTGTTGCCCCCTAAATGCTCTCCAGGTAAAACCT
    GAAACACTTGGAAAAAAAAAACAAAAAAAAAAA
    (CloneID 2063820 in 3′ to 5′ orientation)
    TCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGACCCCTGGGCATCTGGGGA SEQ ID NO:11
    AAAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAACGATGGGGTCTCCACCAC
    CTGG
    T
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATCGCTA
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCACAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCTGCAGAGGCACAGACAGGCCCCGGTGAGACGCTCCAGGA
    CGCCGCGCCTACCCACCACTGGCGTACCCGCCTCTTGCAGCCAGCTCTGCCCAAGGCCCTGT
    GCACTTAGCCCGCATC
    (CloneID 2568304 in 3′ to 5′ orientation)
    TTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCAAGGGTTCAGGTTTACTGAAAGCATTAGCGG SEQ ID NO:12
    CAACAAGGGAGCCCTGGGCATTTGGGGACAAGGCCTGGCATTTCCCTGGACAGGGGCCCTGC
    AAGCAGCCAAGGATGGGGTCTCCACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATCGCTG
    CGTAACAGGGGGGGGTTGCANTACGGTTTGCCTTCGGGCTCAGCGTGGCCCCCAAAGGTCAG
    CGTCTTCCCACATTTTTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAAAAACGTCA
    CCCTCTCGGCAAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGGCGCCAACGGCTGGGGCGGCA
    (CloneID 2329226 in 3′ to 5′ orientation)
    CCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGAC SEQ ID NO:13
    AAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCACCCAAGGATGGGGTCTCCACCACC
    TGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCCCCCCGCCCAAAGCCTTTAGGCCCAAACATGCCTA
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCACCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGACGTCAC
    CCTCTCGGCGAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGGCGGCACCGGCTGGGGCCGCACGGGCTGCAGGCGCGAGA
    (CloneID 5433206)
    GGCCCCTGCCGCCCCAGCCGCTGCCGCCTGCACCGGACCCGGAGCCGCC SEQ ID NO:14
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGACGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGAAACAAACACACAAAAAAAAAAACAAAACAAAAAAAACACAAACCAAAAAACACGAGA
    AAAGCACAAAAAAAGAGGCAAAGAGAAAAACGCGCGCGGGATATCAGAGGCAGGAGGGGCGA
    AAAGGGGGGAGACAGAGGAGGAACAGCGACAACCGGCACCGCGCGC
    (CloneID 5220536)
    GCCGTGCCGCCCAGCCGCTGCCGCTGCACCGGACCCGGAGCCGC SEQ ID NO:15
    ATGCCCAAGTGTCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGGC
    AAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGGG
    CCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGGC
    CTAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAAA
    CCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCCAGATGCCCAGGGCTTCCCTTTGTTGCCCCTAATGGCTCTCAGTAAACCTTG
    AACAACTTGGAAACACCACACCAAAAACCAACACACAGGG
    (CloneID 2387987 in 3′ to 5′ orientation)
    CAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGACA SEQ ID NO:16
    AGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTCCACCACCT
    GGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTG
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTTAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCGAAGTACACCTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGGCGGCAGCGGCTGGGGCGGCACGGGCTGCAGGCGCGAGAT
    GAGAGGGCGCAGCTCTTTAGGCGAGTTCAAGCCGCGCCCCTAGCCCAGCG
    (CloneID 5186252)
    TGCAGCCGTCCGCCCAGCCTGGTGCGCTGCACGGACCCGGAGCCGCAT SEQ ID NO:17
    GCGACGAGTGTCCAATGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGGC
    AAAGACTGGCATCTGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGG
    CCTAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATTGCCAG
    GGCCTTGTCCCCCAGATTGCCCAGGGCTCCCTCTTGTTGCCCCCTAAATTGCTCTCAGGTTA
    GAACCTTGAAACAGCTTTGCGAACAAGCAAAAGAAGAGAAGGAGGTGCTGATAATAGCAGAC
    GAAGTGAGAAGAGAACACCAATCACATGAACACGAATAGGCAGGCCATACAACGCAGGAGAT
    ATCGAACCCGGCGATAGTGCCCGGT
    (CloneID 3609948)
    CGGACCCGGAGCCGCC SEQ ID NO:18
    ATGCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGG
    CAAGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGG
    GCCACGCTGAGCCAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGGCC
    TAAGCCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGA
    (CloneID 1584777 in 3′ to 5′ orientation)
    CCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGAC SEQ ID NO:19
    AAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTCCACCACC
    TGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCGCCCAAAGCCTTTAGGCCAAACATGGCTGCG
    TAAGAGAGTGGTTGAAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTGAGCGTC
    TTCCCACATTTCTCGCAGTTCAGGCAGGGCAGAGTGCAGTCCTTGCCCAGAGAGGGGACCTC
    TCGGCGAAGAGAACTCCTTGTTGCACTTGGGACACTTGGGCAT
    GGCGGCTCCGGGTCCGGTGCAGGCGGC
    (CloneID 2130246 in 3′ to 5′ orientation)
    AGCGGCCGCCCTTTTTTTTTTTTTTTTTTCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGG SEQ ID NO:20
    CAACAAGGCAGCCCTGGGCATCTGGGGACAAGGCCTGGCATTTGCCTGGACAGTGGCCCTGC
    AAGCAGCCAAGGATGGGGTCTCCACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTG
    CGTAGCAGGGGTCGTTGCAGTACGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGCCGAAGTACACCTCCTTGTTGCACTTGGGACAC
    (CloneID 1908782 in 3′ to 5′ orientation)
    CCAAGTGTTCAGGTTTACTGAGACCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGAC SEQ ID NO:21
    AAGGCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTCCACCACC
    TGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTG
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTCCTCAGCGTGGCCCCCACAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGGGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    TTCTCTCGGCGAAGTCCACCCTCCTTGTTGCACCTTGGGACACCTT
    (CloneID 1323448 in 3′ to 5′ orientation)
    GAGCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGACAAGGCCTGGCATTTGCCTGGA SEQ ID NO:22
    CAGTGGCCCTGCAAGCAGCCAAGGATGGGGTCTCCACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGGCTCCGCCCCCCCAAAGCCTTTAGCCCAAAACATGGCTGC
    GTACGAGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGCGT
    CTTCCCACATTTCTCGCACTTCAGCCAGGGCGANTGCCAGTCCTTGCCCAGAGAGGTCACCC
    TCTCGGCGAAGTACACCTCCTTGTTGC
    (CloneID 1837171 in 3′ to 5′ orientation)
    TTTGGTTTTCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGCACCCCTGGGCA SEQ ID NO:23
    TCTGGGGACAAGCCCTGGCATTTGCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGGGTC
    TCCACCACCTGGT
    TTACTTCAAACTGTGGCTCTCGGCTCCGCCCCGCCCAAAGCCTTTAGGCCCAAACATGGCTG
    CGTAGCAGGGGTGGTTGCAGTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGC
    GTCTTCCCACATTTCTCGCACTTCAGGCAGCGCCGATGCCAGTCCTTGCCCAGAGAGGTCAC
    CCTCTCGGCGAAGTACACCTCCTTGTTGCACTTGGGACACTTGGG
    (CloneID 2802267)
    GCGTCGACCCCCGAGAGGGTCACCTCTCTGGGCAAGGACTGGCATCGGCCCTGCCTGAAGTG SEQ ID NO:24
    CGAGAAATGTGGGAAGACGCTGACCTCTGGGGGCCACGCTGAGCACGAAGGCAAACCCTACT
    GCAACCACCCCTGCTACGCAGCCATGTTTCGGCCTAAAGGCTTTGGGCGGGGCCGAGCCGAG
    AGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCGCTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCT
    (CloneID 2847309)
    AAGGTAGCGAAGCGAGAGGGTGACCTCTCTGGGCAAGGACTGGCATCGGCCCTGCCTGAAGT SEQ ID NO:25
    GCGAGAAATGTGGGAAGACGCTGACCTCTGGGGGCCACGCTGACCACGAAGGCAAACCCTAC
    TGCAACCACCCCTGCTACGCAGCCATGTTTGGGCCTAAAGGCTTTGGGCGGGGCGGAGCCGA
    GAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGACACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATCCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGAAAACCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
    AAAATTTCN
    (CloneID 5018693)
    GCCCAAGTGTCCCAAGTGCAACAAGGAGGTGTACTTCGCCGAGAGGGTGACCTCTCTGGGCA SEQ ID NO:26
    AGGACTGGCATCGGCCCTGCCTGAAGTGCGAGAAATGTGGGAAGACGCTGACCTCTGGGGGC
    CACGCTGAGCACGAAGGCAAACCCTACTGCAACCACCCCTGCTACGCAGCCATGTTTGGGCC
    TAAAGGCTTTGGGCGGGGCGGAGCCGAGAGCCACACTTTCAAGTAA
    ACCAGGTGGTGGAGACCCCATCCTTGGCTGCTTGCAGGGCCACTGTCCAGGCAAATGCCAGG
    CCTTGTCCCCAGATGCCCAGGGCTCCCTTGTTGCCCCTAATGCTCTCAGTAAACCTGAACAC
    TTGGAAAAGCAAAAAAAAAAAAAAAAAA
    (CloneID 155219 in 3′ to 5′ orientation wherein the coding
    and 3′ untranslated and/or non-coding regions are present or
    similar to that in CloneID 563289)
    GCATTAGGGGCAACAAGGGAGCCCTGGGCATCTGGGGACAAGGCCTGGCATTTGCCNGGACA SEQ ID NO:27
    GNGGCCCTGCAAGCAGCCAAGGATGGGGNCTCCACCACCTGGN
    TNACTTGAAAGTGTGGCTCTCGGCTCCGCCCGCCCAAAGCCTTNAGGNCCAAACATGGCTGC
    GNANAGGNGNTGGTTGCAGNAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGGTCAGCG
    TCTTCCCACATTTCTCGCACTTCAGGCAGGGCCANTGCCANTCCTTNCCCAGAGAGGTCACC
    CTCTCGGCGAAGTACACC
    (CloneID 307716 in 3′ to 5′ orientation wherein the coding
    and 3′ untranslated and/or non-coding regions are present or
    similar to that in CloneID 563289) 307716 (3′)
    TTTTTTTTTTTTTTCCAAGTGTTCAGGTTTACTGAGAGCATTAGGGGCAACAAGGGAGCCCT SEQ ID NO:28
    GGNATCTGGGGACAAGGCCTGGCATTTCCTGGACAGTGGCCCTGCAAGCAGCCAAGGATGGG
    GTCTCCACCACCTGGT
    TTACTTGAAAGTGTGGCTCTCGCCTCCGCCCGCCCAAAGCCTTTAGNCNCAAACATGGATAT
    GGCTACGTAGCAGGGGTGGTTGCANTAGGGTTTGCCTTCGTGCTCAGCGTGGCCCCCAGAGG
    TCAGCGTCTTCCCACATTTCTCGCACTTCAGGCAGGGCNAATGCCANTCCTTGCCCAGAGAG
    GTCACCCTCTCGGG
  • In another set of preferred embodiments of the invention, any sequence, or unique portion thereof, of the HN1 sequences identified by the I.M.A.G.E. Consortium CloneID 471568 and cluster NM[0051] —016185, as well as UniGene Homo sapiens cluster Hs.109706, may be used. HN1 sequences are useful in discriminations between normal and DCIS or IDC (of grades I to III) breast cells. Its expression is also increased in grade III relative to grade I breast cancer cells.
  • The consensus sequence of the I.M.A.G.E. Consortium cluster is as follows, with the assigned coding region (ending with a termination codon) underlined and preceded by the 5′ untranslated and/or non-coding region and followed by the 3′ untranslated and/or non-coding region: [0052]
    (consensus sequence for HN1)
    TGCAGCGGTGGTCGGCTGTTGGCTCTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGA SEQ ID NO:29
    GCGTTCTCCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTCCCAGGCAGCCTGCGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCCTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCCTTCTGTCTGTTTCCTCCATGCTTGAGAACTGCACAACT
    TGAGCCTGACTGTACATCTTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTAAAAAA
    AAAAAAAAAAAA
  • The sequences identified as belonging to the I.M.A.G.E. Consortium and UniGene clusters, with the assigned coding region underlined, follow below. The 5′ and 3′ untranslated and/or non-coding regions are by reference to the assigned coding region, which is presented as the complementary strand in the 3′ to 5′ direction for some of the sequences. [0053]
    (Clone ID 4795778)
    AGCGGGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTCTGGAGTTTCCCAGCGCCCCTCGG SEQ ID NO:30
    GTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCGAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGGCCCCAACCCACAGGGAGTCTCTCCGCAGAGCCTTCTTGGTG
    TTGCCCTAACTTGCCAGTGGCCTTTGCTCAG
    AGCCTCCTCCTGTGACATGTGAACAATGAAGAGGCCTGCGCCTCCTGCCTTGCCGCCTGCAA
    AGCAAAGAAACTGCCTTTTATTTTTTAACCTTAACAAGTAGCCAGATAGTAACAAGACTGGC
    TGGCTGATGAGCAAAGCCTTTGCTCTCACGCAGAGGACGGCTTGGATGTACAATGAAACTGG
    CTGGAACTAAAGCAGTGAAGCAGGGGAGGCCATCACACTGAAGCGGGTCTTCCTCCAGGAAC
    GGGTCCACAAGGGTGTGTCTGAATTACCTGATGCTGTGTGCTGATGCTGGCTCTTGACCATG
    GACGGCAAGTTCATCTTAACCGTGCTGTCCTCACACCTGACTGTGCTCCCTTAACATTTCCC
    (Clone ID 5239921)
    CTCCTGCAGCCGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCT SEQ ID NO:31
    TTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGCCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTGTTATCCCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGGC
    CATGGCATGAGTGTTCCTAGTAGTAGATTGGAGGGAAAAGTTTGTGACCCTTAGTACGGGGT
    TTTAAGACGAAATAATTGGGTTCCA
    (CloneID 4623018)
    GGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCA SEQ ID NO:32
    GCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTATTTTTTGCTTTGTGAAGACCAGGTTTCTCTCTGTCCTTGACCTCTGTGGGTCTGTG
    GGCCATGGCATGAGTGTTTCCTAGTAGTAGATGGGAGGGAAAGCTTGTGACCCCTTAGTACT
    GTGTTTTTACAC
    (CloneID 5729213)
    CGGTCCGGAATTCTCCGGATGCTGTTGGGTGTGGAGTTTCTACCGCCCCTCGGGTCCGACCC SEQ ID NO:33
    TTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGGC
    CATGGCATGAGTGTTTTCTAGTAGTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGTG
    TTTTTAAGAAGAAATAATTTGGTTCCAGATGTGTTANAAGATCTTTTGTACTGGAGTTTTTT
    ACACTTTTACTTGGGTTTAACCAGCCTCAACTGGGACGACCATAAACAGTCCACCAGGCACC
    GTTTCCTGCCAGGCCCCAAACCCACGGGAAGTCTCTCGCAAAAACCCCTTCCTGGGGGTTGC
    CCCTAATTTGCCAAGGGGCCTTTTGCTCCGGAGCCTCCCTCCCGGGGAATTGGGGAAACAAT
    GAAAAAGGCCTGTGCCCTCCGTGCCTTG
    (CloneID 5192505)
    CTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTG SEQ ID NO:34
    AGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAACAGAAGCACTTTATGTACTGCT
    GTCTTATATCCTTTTGAAGAACAGGGTTTCTCTCTTGTCCTTGACCTCTGGGGTCTGTGGGC
    CCATGGCATGAAGTGGTTTCTAGTAGTTAGATGGCGCGCAAAGCTTTTGTGGACCCTATGTA
    ACTGGTGGTTTTTACGACAGACACTACTTTGGCTACCAGATGTGTTAGAGGAACCTTGGCAC
    TGGAGGTTTAACCACTTTACTGGGTTTACCAGGCCTTAGTGGCACGGCCCATAACGTCCACA
    GCCCCGATCCTGCCAGCCCAA
    (CloneID 3945044)
    TTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCC SEQ ID NO:35
    AGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGCAAGAACAAAATGGCCTCTAATATCTTGGGACACCTGAACAAAATCAAGCTTCTTGCGCC
    AAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAG
    AAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTC
    ATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCT
    GCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGG
    CGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTGTGGATTGTTCTCATTAAAAAGAAGCACTTTATGTACTGCT
    GTCTTTTTTTTTCCTTTTTGAAGAACCAGGTTTCTCTCTGTCTTGACTCTGGGGTCTGTGGG
    GCCATGGCATGAGTGTTTCTAGTAGTACATTGGCGGGAAACGCTTTGGGACCCTTTACTACC
    TGTGTTTCCACGGAACAAATTACTTTGGGGTCCCCATGTTGTTAA
    (Clone ID 5240530)
    CTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTGTG SEQ ID NO:36
    GGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGCAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTNGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTAATTTTACTTTTGAAGAACAGCTTCTCTCTGTCCTTGACTCTGGGTCTGGGGCCAT
    GG
    (CloneID 3617626)
    TGGCTAGGTACGAGGCTGGGTTTGGGCGGACAGGCGGCAGCGGCGGCTCCTGCAGCGGTGGT SEQ ID NO:37
    CGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCC
    GGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTCCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAGTCCAGCCTCGTCTTGGGTATAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAATGCACAACTT
    GAGCCTGACTGTCATCTCTGGGATTTGTTCATTAACAGAGCCTTATGTAAAAAAAAAAAAAA
    AACGCGGATTCTTCGGGGGGGAACAAGAAGAGGCCAGGGATA
    (CloneID 4814114)
    AGCGGGGGGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCT SEQ ID NO:38
    CGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCTCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCACCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTCTTTCGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGGCCAT
    GGCATTAGT
    (CloneID 4894047)
    TGATGGCAGTAATCTCGGGGTATAAGGTAGCGAGGCTGGGTGGCGCCTGCAGCGGTGGTCGG SEQ ID NO:39
    CTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGC
    GCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGNGCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTTGTGAACTGGACAAG
    TTGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCT
    GTCTATTCAGACCTTTTGAAAGACCAGGTTTCTCTCTGTCCTTGACTCTGGGGCCTGTGGGC
    CATGGACTGAGTGTTTCCTAGATAGCAGAT
    (CloneID 5531619)
    AATTTTCCGAAATCGTCGACCCACGCGTCCGTTTCCAGCGGTGGTCGGCTGTTGGGTGTGGA SEQ ID NO:40
    GTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCG
    CTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTAAAAAAAAAAA
    AAA
    (CloneID 5588318)
    CGGTCCGGAATTCTCCGGATGCTGTTGGGTGTGGAGTTTCCCTGCGCCCCTCGGGTCCGACC SEQ ID NO:41
    CTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTCTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGNGTCTGTGGG
    CCATGGCATGAGTGTTTTCTAGTAGTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGT
    GTTTTTAAGAGGAAATAATTTGGTTCCAGATGTGTTAGAGGATCTTTTGTACTGAAGGTTTT
    ACACCTTTACTTTGGGTTTACCAGCCTCCACTGGAACAGACATAAACAGTCCACAGGCAACC
    GTTCTGCCCAGCCCCAACCCCAGGGAAGTCTCTCCGCAAAACCTTTCTTGGGGTTGCCCTAA
    ACTTGCCAGGGGCCTTTGCTTCAAACCTCCCTCCTGTGAAATGTGTAACAAATGAAAAAGCC
    GTGGGCCTCTCTGCCTTTGCCCCCTTGAAAACAAAAAACCGGGCCTTTTTATTTTTTAACCT
    TAAAAAGAACCCCGATATTAAAAAAAATGGGTTGGGTGTTGAACAAAACCCTGTCCTTCCC
    (CloneID 5768283)
    TGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGA SEQ ID NO:42
    GCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATGCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCT
    GTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTG
    GGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGC
    AGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGT
    GCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCC
    CTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGG
    CCATGGGCATGAGTGTTTTCTAGAAGTAGATTGGAGGGGAAAGCTTTGTGCGCACTTAAAAC
    CGGGGTTTTTAAAAAAAATTAACTTGGGTTCCCGAATGGGTTAGAAGAATCTTTTGGACCTG
    AGGTTTTTTAAACCTTTTAATTGGGGCTTAACCAAGCCTCTACTGGACCGAAATCATTAACA
    GGCCCCCCGGCTCCGCGTTCCTTGCCAGGGCCCCAACCCACAGGGGGAGTTCTCCTCGGCCC
    AAGCCCTTTTTTGGGGGCTCGCCCCCAAAATGTGCAGGGGGGCCTTTGCGCTCAAAACCTCC
    C
    (CloneID 5396994)
    GTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCCCCAGCCTA SEQ ID NO:43
    CCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAACAACAAAATGCCCTCTAATATCCTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAACCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTCAACGCTGTCGTTCTGGTCTGTTTCCTCCATGCTTTGTGAACTGGCACA
    ACTTGAGCCTGACTGGTACATCTCTTTGGATTTGTTTCCATTAAAAAGAAGCACTTTATGTA
    CTGCTCTCTTTATTAGCCCTTTGGAAGAACCGGTTTCTCTCTGTCCTGTGACTCCTGGGGTC
    TGTGGGCCATGGCATGAGGGTCTCTAGTAGTAGATTGAGGGAAAGCTTGTGGCCACTTAATA
    CTGGGTTTAAAGACGAAATACTTGTGGTCCAGATGTGTTACAAGGAACCTTGGCACGGAGGT
    TATAACACCTTTATGGGGTGTCCCAGGCTCCCTGGACGACCCTAAGCGTCCACGGCGCCGGT
    CCGCCGGCCCAC
    (CloneID 3941190)
    TTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTGAGCGTTCTGCTCCGGCGCCA SEQ ID NO:44
    GCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTA
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCCGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAAGAAGCACTTTATGTACTGCT
    GTCTTTTTTTTCCTTTCGAAGAACAGGTTGCTCTCTGCCTTGACTCTGTGGGTCTGTGGCGC
    ATGGATGAGTGTTCCTAGCTAGTAGATGGAGGGCAACTTTGGGGACCCTTAGCGTGGTTTAC
    CAGAAATACCTGGGTCCAGTGGCCCAGGCCTTGGCCGGGGTTCCACCTTCTGGGTTTCAGCT
    CACGGGAACCATAAACCAAGGCGCCGAGGCCACAGGATCCCGCCTTGTGGCATCCGGGGTGA
    CCCGTATGAAAAAGCGCCTCCAAATTTTTAAACACAAGCGCCCGGAGACCAT
    (CloneID 5928395)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:45
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGG
    CCATGGCATGAGTGTTTTCTAGTAATAGATTGGAGGGAAACCTTTGTGACACTTAATACTGT
    GTTTTTAAGAAGAAATAATTTGGTTCCAAATGTGTTAGGAGGATCTTTTTGTACTGAAGTTT
    TTAAAACTTTACTTGGGTTTTACCAAGCCCTCACCTGGGACAGACCCTTAACCGGTCCAACG
    GGCCACCGTTTCTTGCCAGGGCCCCAAACCCACAGGGGAAGTCTTCTCGCAAAAACCCTTCC
    TGGGGGGTTCCCCCTAACTTGCCCAGGGGCCCCTTTGCTCCAAAAC
    (CloneID 4750262)
    CGATCGGCCGGACAGGCGGCAGCGGCGGCTCCTGCAGCGGTGGTCGGCTCTTGGGTGTGGAG SEQ ID NO:46
    TTTCCCACCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGC
    TCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGCAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTCGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGCCAAGTCCAGCCTCGTCTTGGCTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTGGTGTCATTACACAAGAAGCACTTTATGTACTGCT
    GGTCTATAAATATCCTTTGCGACGAACAGGTTCCTCTCTGCCTTGACTCTGGGGCCTGTGGG
    CCACTGGCAGTGAGTTGTGACTAGCTAGTAGATTGGGCGGAAACGCTTGGTGACCCTTAGCC
    CCTGGTTTCTACGACGCCATACTTGGTCCCGATGTGTTACAGGCCTCTTGCGCCGGAGGCTT
    TACACCCTTTACTGCGCTCCCAAGGCTCAGGGGCGACCTAA
    (CloneID 5274910)
    AGCGGAGCGGCGGCTCCTCCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCT SEQ ID NO:47
    CGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCAAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTCACAAAGAAGCACTTTATGTAACTGC
    TGTCTTTTTTACCTTTTGAAGAACCGGTTCCTCTCTGTCCTTGACTCTGGGGTCTGGGGGCC
    AGGCATT
    (CloneID 3140086)
    TTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCCCC SEQ ID NO:48
    GGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCAAATTTTTCATTAGGTTTTGATGAACCAACAGAACAAGGCG
    GTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTG
    GGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGC
    AGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGT
    GCCTTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCC
    CCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGGTTTCCTCCATGCTTGTGAACTGGACAAC
    TTGAGCCTGACTGTACATCTCTTGGATTGTGTTTCATTCAAAAGACGCACTTTATGTAACAC
    AAA
    (CloneID 5286160)
    AGCGGAGGGGCGGCTCCTGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCGAGCGCCCCTC SEQ ID NO:49
    GGGTCCGACCCTTTGAGCGTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCG
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTACAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTCCTTTTGAAGAAC
    (CloneID 5215141)
    GGTACCGGTCCCGAGTTCTTTGGATGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAG SEQ ID NO:50
    CGCCCCTCGGGTCCGACCCTTTGGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGG
    CGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAACGGTGAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGT
    GCCTGCTGCGCCTGTGCCCACACCCGGTGGACCCGGACCCAGTTGCCATCCAGAAGAAATCC
    CCCTGGCGGCAAGTCCAGCCTCGTCTAGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACTT
    GAGCCTGACTGTTACATCTCTTGGATAAGTTTCATTAAAAAGAAGCACTTTATGTACTG
    (Clone ID 4845679)
    GAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCG SEQ ID NO:51
    TTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTCTATGTACTGCTG
    TCTTTTTTTTTCTTTGGAAGAA
    (CloneID 5297866)
    AGCGGAGCGTCGGCTCCTCCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCT SEQ ID NO:52
    CGGGTCCGACCCTTTGACCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAACCAAGCTCCGGAGACTTCTTAGATCTGAAGGGCGACGGTGATA
    TTCATGAACAATGTGGACACCAGACTTCCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCG
    TGCCTGCTGCGCCTTGTGCCCAGACCCGGTTGGCCCCGGCCCCCACTCCCATCCAGAAGAAA
    TCCCCCTCGCGGCATGTCAGCCTCGTCTTGGGTAA
    GCTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTACCTCCATGCTTGTTGAACTTGACA
    ACTTCGAGCCTGACGTGTACATCTCTTGGATTGGTTTCATTAAAAAAGAAGCACTTTATGTA
    CTGGCTGTCTTAAATAACTTTTGAAAGAAC
    (CloneID 5194208)
    CCAATCCCTGGATCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGG SEQ ID NO:53
    GTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAATAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTCATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAACTCTAGTGGTGGCAGGGAAGACTTGCAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGACAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAACAGAAGCCCGTG
    CCTGCTGCGCCTCTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTGTGTGAAACTGGACAA
    CTTGAGCCTGACTGTACATCTCGTTGGATTGGTTTCATTAACAAAGAAGCACTTTATGTACT
    TGCTGTCTTTTGATGCTTTGGAGAGAACAGGTTACTACTCTGGCCCTTGACTCTGGGGTCTG
    TGGGCCATGGCATGAGTGTTTACTACGTAGCACAACTGGCCCGGAAACGCTCCGGTGAGACC
    CATTAGCTACGGGGGTTTTAAGAACGCAAATTAATCGCGTACGCGAATGTGGTACAAGGACA
    CTGTAGGACACGGACGCTGTAACACACTTAACAAGCGGTTTCACCAGGACCTCAACGGAGAC
    CGACCATATAACGGCCACAGGAGCACGGACATGACAGGGCCAAGCC
    (CloneID 5017113)
    GCCTGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:54
    GAGCGTTCTCCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGCAGACTTCTTAGATCTGAAGGCAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCACCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGCCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGCCAAGTCCAGCCTCGTCTGTGGCTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAATTG
    AGCCTGACTGTACATCTCTTGGATTGGGTTTCATTAAAAAGAAGCACTTTAAAAAAAAAAAA
    GAAAAAAAAAAAAAT
    (CloneID 5483414)
    TTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCC SEQ ID NO:55
    AGCCTACCTCGCTCCTCCGCCCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCCAGTTTT
    GCGGCCTCCAGGTGGTCCATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGCCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTCAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAACAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTCCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGG
    CCATGGCATGAGTGTTTTCTAGTAGTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGT
    GTTTTTAGAAGAAATAATTTGGTTCCAAATGTGTTAAAGGATCTTTTGAACTGAGGTTTTTA
    AACACTTTACTTGGGTTTCCCAAGCCTCAACTCGACAGAACATAAACAGTCCACAGGCACCG
    GTTCCTGCCAGGGCCCAAACCCACAGGAAATCCTTTCGCCAAAAACCCCTTCTTGGGGGTGG
    CCCCTACTTGGCCAGTGGCCCTTTGCTCCAAAACCTCCTCCTGGGAACCGGGGGAAAACATT
    GAAAAGGCCCTGGGGCCTCCCT
    (CloneID 5778829)
    GCACGAGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCG SEQ ID NO:56
    TTCTGCTCCGGCGCCAGCCTACCTCCCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    CCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGACACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCACGCAGCCTGGGGCAGAGTGAACAGAAGCCCGTC
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAACAAATCCCCC
    TGGCGGCAAGTCCAGCCTCG
    (CloneID 5778829 in 3′ to 5′ orientation)
    TTTTTTTTTTTTTTTTTTTTTTTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGA SEQ ID NO:57
    TGTACAGTCAGGCTCAAGTTGTGCACTTCACAAGCATGGAGGAAACAGACAGAACGACAGCG
    TTCAGGACACTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGGT
    CGACTCCCTTGAAGGT
    (CloneID 2781859)
    GAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGC SEQ ID NO:58
    TCCCACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATCAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCGCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCCTCTTG
    (CloneID 2781859 in 3′ to 5′ orientation)
    TTTTTTTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGCCTCA SEQ ID NO:59
    AGTTGTGCACTTCACAAGCATGGAGCAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCCCANAACTCGGGAGCTATTCCTGCTGTTGGGGT
    CGACTCCCTTGAAGGTCGTGGTTGTGGTCAT
    (CloneID 3940455)
    GGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGC SEQ ID NO:60
    CTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTC
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGCCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGACACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGACTGAAGAGAAGCCCGTGC
    CTGCTTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTNTCCTCCATGCTTGGTCGAACTCACAAT
    TTGAGCCTGGACTGTACATCTCTGGGAATTGGTTTCATTAAAAAGAAGCACTTTAAAAAAAA
    AAAAAAAAAAAAAAAAAAAGAAAAAAAAAAAAACCGGAGAGATAAAAAGGGGGGGGAGAAAA
    GTGGAAAAAAAGACCAGCCGCAAACATTTGCCGGACCCTTTTTGGCGACACAGGGGAAAACG
    GGAGCCCCAAAGGAGGTAAATGAAACGGTTCTTTTTTTCTTATTTCAGAAAGCAGAAGAAAA
    AGAAATAAAGAAAAGAAAGAAAAAAAAAGAATGATAAAAGAGGAAAAATAAAAAAAAAGAAA
    AAGAGAGAGAATAGAAACTTAAAAAATAAACAGAAAAAAGAA
    (CloneID 5459503)
    GCTGCAGCGGTGGTCCGCTGTTGGCTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:61
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGCACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAACAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGT
    GCCTCCTGCGCCTGTCCCCAGCCCGGTGGCCCGGCCCCAGTCCCATCCAGAACAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTCCCCTTCCCAAACGAAGCACTTTATGTACTGC
    TGTCTTTTTTTTTTCCCTTTGGAACGCCCCCCGGTTCCTCTCTGTCCCTTCACTCCTGGGGT
    CTGGGGGCCTG
    (CloneID 4539292)
    TGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:62
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGCGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGCTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGCCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTGTTTCATTAAAAAGAAGCACTTTATGTAAAAAAAA
    AAAAAA
    (CloneID 5247820)
    CTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCAGCGCCCCTCGGGTCGACCCTTT SEQ ID NO:63
    CAGCGTTCTGCTCCGGCGCCACCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGACTTTT
    CCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTCGAGTCATCTGGACTGCA
    GAGAAGG
    AACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATGA
    AAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAACGAGAAGCCCGTGCCTGCT
    GCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGCCGG
    CAAGTCCAGCCTCGTCTGGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTCGATTTGTTTCATTACAAAGAAGCACTTTATGTACTGCTG
    TCTTTATATTTTGTCCTTTGTGAGAACAGGTCCTCTCGTGTCCTTGACTCTGGGGTCTGTGG
    C
    (CloneID 5397495)
    CTCCTGCAGCGCTGGTCGGCTGTTCCGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCT SEQ ID NO:64
    TTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTACGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGCACACCTGAACGAAAATCAAGCTTCTTG
    GGCCAACTCACCAGGTGCCAACCTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTG
    CAGACAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGCACCAAGGT
    GATACTTCATGAAAACTGTGGACACAGACTTGCCAGGCACCCTGGGGCAGACTGAACAGAAG
    CCCGTGCCTGCTCCCCCTGTGCCCAGCCCGGTGGGCCCTCGCCCAGTGCCATCCACGAACGA
    AATCCCCCTGGCTCGCAATGTCCACCCTCGTCTTGGGTTACG
    CTCTGACTGTCCTGAACGCTGTCCTACTGTCTGTCTCCTCCATGCTCGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGCATTCGTATCATTAACCAAGAACCACTTTATGTACTCCT
    GTCTTTATTTACGCCTTTCGAAGACCG
    (CloneID 5200412)
    CTCCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTG SEQ ID NO:65
    AGCGTTCTGCTCCGGCCCCAGCCTACCTCGCTCCTCGGCCCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACACCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTCCCAAGTCTAGTCGTGGCAGGGAACACTTGGAGTCATCTGCACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTCAAGGGACAACGTGATA
    TTCATGAAAATGTGGACACAGACTTCCCAGGCAGCCTGGGGCACAGTGAAGACAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTGTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGGTACATCTCTTGGATCCGTTTCATTAAAAAGAAGCACTTTATGTACTGCT
    GTCTTTATTTTCACTTTAGACCAACCAGGTGTCTCTCGTGTCCTGGACTCCTGGGACCTGTG
    GGCCATG
    (CloneID 5208934)
    CTGCAGCGCTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTC SEQ ID NO:66
    ACCGTTCTCCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATCAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTC
    TCTTTTTTTTCCTTTTGAAGACCAGGTTCTCTCTGTCCTTGACTCTTGGGCTCTGTGGGCCC
    C
    (CloneID 4156130)
    CCCACCCCTGGCCCCCTCTTGGGTGTGGAGTTTCCCACCCCCCCTCGGGTCCGACCCTTTGA SEQ ID NO:67
    GCCTTCTCCTCCCGCGCCAGCCTACCTCCCTCCTCCCCCCC
    ATGACCACAACCACCACCTTCAACCCAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCCCCCTCCAGGTGGTGGATCCAATTTTTCATTACGTTTGATGAACCAACACAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTACTCGTGGCAGGGAAGACTTCGACTCATCTGGACTGCAG
    ACAAGGAACTCCTCTCAACCAACCTCCCGAGACTTCTTAGATCTGAACGGAGAAGGTGATAT
    TTATGAAAATGTGCACACAGACTTCCCAGGCAGCCTGGGGCACAGTCAAGAGAAGCCCGTGC
    CTGCTGCGCCTCTCCCCACCCCCGTCGCCCCGGCCCCACTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAACTCCACCCTCCTCTTGGGTTAG
    CTCTGACTCTCCTCAACCCTCTCGTTCTGTCTGTTTCCTCCATCCTTGTGAACTGCACAACT
    TGAGCCTCACTGTACATCTCTCTGGATTGTTTCATTAAAAAGAAGCCCTTTATGTACTCCTG
    TCTTTATCTTTCCTTTCCAGGACCCGGTTTCCCCCCCCTCCTGGCCTCTGCCTCCTCGGCCC
    CTGCCTTCGCTCTTC
    (CloneID 4123030)
    GCTCCTGCAGCGGTGGTCGGCTGTGGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCC SEQ ID NO:68
    TTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGCGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTC
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGCC
    AAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAG
    AAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGATATTC
    ATGAAAATGTGGACACAGACTTGCCAGGCAGCTGGGGCAGAGTGAAGAGAAGCCCGTCCCTG
    CTGCGCCTGTGCCCAGCCCGGTGGCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGGGCG
    GCAAGTCCAGCCTCGTCGTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAACTT
    CAGCCTGACTGTACATCTCTGGGATTGTTCATTAAAAGAAGCACTTTATGTACTGCTGTCTT
    TTTTTTCTTTTGAGGACGGTTCTCCCTGTCCTGACTCTGGTTGGGGGGCAGGGTGAGGGTTC
    TAAAAAGGGGG
    (CloneID 5459215)
    GGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTGAG SEQ ID NO:69
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGACAGGAATAGCTCCCGAGTTT
    TGCGGCCTCCAGGTGCTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCT
    GTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTG
    GGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGC
    AGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGAT
    ATTCATGAAAATGTGGACACACACTTGCCAGGCAGCCTGGCGCAGAGTGAAGAGAAGCCCGT
    GCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCGGCCCAGTGCCATCCACAAGAAATCCCCCT
    CGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTTCCTCCATGCTTGTGAACTGCACAAT
    TGAGACCTCACTGCTACATCTCTGCATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCT
    GTCTTTATTTTTCCTTGTGAACA
    (CloneID 4337230)
    GCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTT SEQ ID NO:70
    TGAGCGTTCTGCTCCGCCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGC
    GCCAAGTCAGCAGGTCCCAACTCTAGTGGTGCCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGCGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCCTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAATTG
    AGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTAAAAAAAAAAAAA
    AGAGAAAAGAAAAACCGGGGGTTTTTTGGGGGGGGAAAAGAGGGTTAAAGGCGGGGTAGGTT
    TTTGCCCTTTTTGAAAGGGGAGACGGGGGCCCAGGGGGGGTAATGGAAGGGGACG
    (CloneID 4649355)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:71
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGCTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCACAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGACCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TCAGCCTGACTGTACATCTCTTGCATCTGTTTCATTAAACAGAAGCACTTTATGTACTGCTG
    TCTCACTACAAATACACTATCGAACAACAGGTTACTACTCTGTCCTTGAN
    (CloneID 4126162)
    CCTGCAGCGGTGGTCGGCTGTTGCGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:72
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGCGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTCAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGCGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTCCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTTCTCTCTGTTTCCTCCATGCTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTGGGATTGTTCATTCAAAAGAAGCACTTTATGTACTGCTGTC
    TTTTTTCCCTTGGACACCAGGTTCCCCTCCCTCCTTGACTCCTGGCTTTGGGGCCCGGCCAG
    AGTGTTCCTATAACAATGGGCGGAAAACCTTGGGCACCTAGCCCGGTTAAAGAAAAATGGGC
    CACTGGTAAGC
    (CloneID 2783676 in 3′ to 5′ orientation)
    TTTTTTTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCA SEQ ID NO:73
    AGTTGTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCTTCAGATCTAAGAAGTCTCCGGAGCTTGCTTCAGAG
    GAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGCCACCACTAGACTTGGCACC
    TGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCAAAGATATTAGAGGCCATTT
    TGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAATGAAAAATTGGATCCACCA
    CCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGGTCGACTCCCTTGAAGGTGGT
    GGT
    (CloneID 2783676)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:74
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGAAAATGTGGACAC
    AGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCA
    GCCCGGTGGCCCCGGCCCCAGTGCC
    (CloneID 2822776 in 3′ to 5′ orientation)
    TTTTTTTTTTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGC SEQ ID NO:75
    TCAAGTTGTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCA
    GAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCGCAAAACTCGGGIAAGCATTCCTGCTGTTGG
    (CloneID 2822776)
    GGCACGAGGGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGCTCCGACCCTTTGAGCGT SEQ ID NO:76
    TCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGACTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAACAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAAAAATCCCCC
    TGGCGGCAAGTCCAGC
    (CloneID 2781579)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:77
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAATGAAAAAAACCCGTGC
    CTGCTGCCCTGTGCCCAGCCCGTGGCCCCCGGCCCATGCCATCAAAAAAATCCCCCTGCCGC
    GAACCAACCTTTGCTG
    (CloneID 2781579 in 3′ to 5′ orientation)
    TTTTTTTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCA SEQ ID NO:78
    AGTTGTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGGT
    CGACTCCCTTGAAAGTGGTGGT
    (CloneID 5419867)
    GCAGCGGTGGTCGGCTGTTGGGTGTGCAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:79
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTCGATCCAATTTTTCATTAGGTTTTGATGAACCAACACAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAACTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGTTTTCATAGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAG
    AAGCCCGTGCCTTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGACCCAGTGCCATCCAGAA
    GAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    AGAGCCTGACTGTACATCTCTATGGATATGTTTCATTAAAACAGAAGCACTTTATGTACTGG
    TGTCTTTATTATTTCTTTGGAAGACCAGGTTCTCCTCTGGCCTAGAATCCTGGGGGTCTGAG
    G
    (CloneID 4328715)
    CGCTGATTGGCTGTGGAGTTTCCCAGCGCCCCTCGCGTCCGACCCTTTGAGCGTTCTGCTCC SEQ ID NO:80
    GGCGCCAGCCTACCTCCTCCTCGGGCGCC
    ATGACCACAACCACCACCTTCAAGGGATTCGATCCCAACAGCACGAATAGCTCCCGAGTTGT
    GCGGACTCCAGCGTGGTGGATCCAATTTTATCATTAGGTTTTGATGAACCAACAGAGCAACC
    TGTGAGGAAGAACAAAATGGCCTCTAAATATCTTTGGGACACCTGAAGAAGAATCAAGCGTT
    CTTGGGCCAGAGTCAGTCAGCGTGCCAAGTCTAGATGGTGGCAGGGAACGACTTGGAGTCAT
    CTGGACTGCATGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGG
    AGACCGGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGTGGCAGAGTGAT
    GAGAAGCCCGTGCCTGCTTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCA
    GAAGAAATCCCCCTGGCGGCAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGGATTTGGTTCCCTTTAAAAAGAAGCACTTTATGTTACT
    GCTGTCTTTTTTTTTTCCTTTTGACGGCACGGGTTTCCTCTCGGTCCTTGACTCTGGGGGTC
    TGGGGGCCCAGGGCATGAGTGTTCCTTATATGATGGGGGGAGAGCTTGGGGCCCTTGCACCG
    GTTTTTCGCGAGCAATATTGGGCCCAGTGGTTAGGCTCTTTGGCCGGGGTTCACCTCTTGGG
    TTCCCCCCCGGGGGCCAAGGACGCCGTTTGGTC
    (CloneID 4138051)
    GCTGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTG SEQ ID NO:81
    ACCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTCAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTCCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTATCTGTCTCTTGTCCTCCATGCTTGTGAACTGCACAA
    GTTGAGCCTGACTGTACATCTCTTGGATTCGTTCATTAACAAGAAGCACTTTATGTACTCCT
    GTCTTTTATTTTCCCTTTGAAGACCCGGTCCCCCCAGGCCTGACCTGGGCTGGCGCCAGGAA
    GAGGTTCTCATAAAAAAGGGGGGAACACTTGGGACACTAGACTCGGGTTTCGCAAAAATCTG
    GGTCCAATGTGAAAAGATGGGAGG
    (CloneID 4766330)
    GCTGCAGCCGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:82
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TCAGCAAGAACAAAATGCCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAACTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGAAGACTTGGAGTCATCTCGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAACAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCACTGCCATCCAGAAGAAAATCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATCCTTGTGAACTGCACAAT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAACAAGAAGCACCTTTAAACACAAA
    AAAAAAAA
    (CloneID 3958097)
    GTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCAGACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:83
    CAGTCCTATCCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGT
    GAGGCAAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTG
    GGCCAAGTCACGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTCGACTG
    CAGACAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGCAGAAGGTG
    ATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGCAGTGAACGAGAAGC
    CCGTCCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAAT
    CCCCCTGGCGGGAAGTCCAGCCTCGTCTTGCGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAGCTGCACAACT
    TGAGTCCTGACTGTACATCTCTTGGATTCGTCTCATTGAGAAGAGAAGCACTTTATGTACTG
    TGTCTTTTCTGTCCTTTGGCGGCCCGGTTCTCTCTGTCTTGACCCTGGGGCGGTGGGN
    (CloneID 346318 in 3′ to 5′ orientation)
    TTTTTTTTTTTTTTTTTTTTAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAG SEQ ID NO:84
    TCAGGCTCAAGTTCTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGA
    CAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGCGGATTTCTTCTGGATGGCACTGGGGCCGG
    GGCACCGGGCTCGGGCACAGGCGCANAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTGCC
    TGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTCTC
    CGGAGCTTGCTTCAGAGGAGTTCCTTCTCTCCAGTCCAGATGACTCCAAGTCTTCCCTGCCA
    CCACTNAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCAA
    AGATATTAGAGGCCATT
    (CloneID 346318)
    CGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:85
    CACTANCCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGACTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGCGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGGACTNG
    CAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAAGAAAGGT
    GATATTCATG
    (CloneID 487018 in 3′ to 5′ orientation)
    AAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAAGTTGTGCAGT SEQ ID NO:86
    TCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAC
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGGCACTGGGGGC
    CGGGGCACCGGGCTGNGCCACAGGCGCANAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCT
    GCCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGT
    CTCCGGAGCTTGCTTCAGAGGACTTCCTTCTCTCCAGTCCAGATGACTCCAAGTCTTCCCTG
    CCACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCNGGTGTCCC
    AA
    (CloneID 487018)
    CTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGCGTCCGACCCT SEQ ID NO:87
    TTGAGCGTTCTGCTCCGGCGCCACTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTTGGAGTCATCTTGGACTT
    GCAGAGAAGGAACTCCTCTTGAAGCAAAGCTTCCGGAGACTTCTTTAGATCTTGAAGGGAGA
    AGGTGATATTTG
    (CloneID 3509038)
    AGCTAGGTACGAGGCCTGGGTGTTGCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCC SEQ ID NO:88
    AGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCG
    GCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGACTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTCCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGCTCATCTGCACTGC
    AGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAACGGGCAGAACGGT
    GATATTCATGAAACATCTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGC
    CCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAAT
    CCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTCACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTCATCTCTTGCATTGTTCAC
    (CloneID 5094728)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCCGGTCCGACCCTTTGAG SEQ ID NO:89
    CGTTCTGCTCCGGCCCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCACGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTCGATGAACCAACAGAACAACCTG
    TGACGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    CCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    CAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGTTTTCATAGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAG
    AAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGACCCAGTGCCATCCAGAAG
    AAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATATGTTTCATTAAACAAGAAGCACTTTATGTAC
    (CloneID 5590830)
    GTCCGGAATTCTCCGGATCTCCTGCAGCGGTGGTCGGCTTTTCGGTGTGGAGTTTCCCAGCG SEQ ID NO:90
    CCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGC
    C
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAACAACAAAATGCCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTCG
    GCCAACTCAGCAGGTCCCAAGTCTACTCGTGGCAGGCAAGACTTGGACTCATCTGGACTCCA
    GACAACGAACTCCTCTCAAGCAACCTCCGGAGACTTCTTAGATCTCAAGGGAGAAGGTCATA
    TTCATGAAAATCTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAACCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCCGTGGCCCCGCCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAACTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTCTCCTGAACCCTGTCGTTCTCTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTCACTGTACATCTCTTGGAATTGTTTCATTAAAAAGAAGCACTTTATGTACTCCCT
    GTCTTTTTTTTTTTTCTTTTGAAAGAACAGGGTTTCTCTCTGCCCTTGACTCTTGGGCTCCG
    TGCGCCATGGGCATGACGGGTTTTCCCAGTAGTTACATTGGGAGGGCAAACGTCTCTGTGAC
    CACTTAAATCACCGCCGCTTTTAAACAACAAATTAATTTCGGCTCCCTCAAGGGCCGTTATA
    ACGTACCCTTTTCTCTCTCTGAGCGCCCTGAAAACTCCTTCACCCCCCGCATGAACGCAGGT
    TCCCTACTTGGTTCACCACCTCAACCGCTCTGTACCCCCCAGGGGACCCCTGTCTCCCCCCG
    AGGTGCCCCTCCCTCCCCCCCGGCCCATAATGTTTTCTTCAGCCCAACGAAACTGCCA
    (CloneID 4550156)
    GCGGCTCTTCGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTGACCCTTCTGCTCC SEQ ID NO:91
    GGCGCCACCCTACCTCCCTCCTCGGCGCC
    ATCACCACAACCACCACCTTCAAGGCACTCGACCCCAACAGCAGGAATACCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTCCCACACCTGAAGAAAATCAAGCTTCTTGC
    GCCAAGTCACCAGGTGCCAACTCTAGTGGTGCCACCGAAGACTTGCAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCACGCAGCCTGCCCCAGAGTGAAGAGAAGCCCGTC
    CCTGCTGCCCCTGTGCCCAGCCCGGTGGCCCCCGCCCCACTCCCATCCAGAACAAATCCCCC
    TGGCGGCAACTCCAGCCTCCTCTTGGGTTAG
    CTCTCACTGTCCTGAACCCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTTCAACTGGCACAA
    CTTGGAGCCCTGACTGTACATCTCTTGGATTGTTTCATTAAAAAGAAGCCACTTTAAAAAAA
    AAAAAACCCCTGGAGCACCTACGCAGAGACAGGAGACAAAAAAAATCACAACGCGGGGCCGC
    CCTTTTGCGGGGGGGCGAAAAACGAGTAAAAAAGGCCCCGGGTCTACAGTGTTGTCCGGACA
    CCCACTTTGGTCACAAGGGGGAACGCCCCGCCCACAACGGGGGGAAATAAGCAACCGGGGGA
    TCCTA
    (CloneID 5258724)
    GCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCCACCCTTT SEQ ID NO:92
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTCGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTCGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGGTCTGTTTCCTCCATGCTTGTGAACTGCACAAC
    TTGAGCCTGACTGTACATCTCTTGGATCTGTTCATTAAAAAGAAGCACTTTAAGAAAACCAC
    ACAAAAAAACTCCGAGGCCACTA
    (CloneID 3458066)
    TGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCA SEQ ID NO:93
    GCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTGGGACACCTGAAGAAAATCAAGCTTCTGGGCCA
    AGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAGA
    AGGAACTCCTCTGAAGCAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGAATATTCA
    TGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTG
    CTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGGCG
    GCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTCTCGTTCTGTCTGTTTCCTCCATGCTTTGTGAACTGGCACAA
    CTTTGAGCCTGAGTGTACATCTCCTGTGGTTGTTTCATTAAACAGAAGCACTTTATGTACTG
    TGTCTTTTTTTTGTCCTTCGGAGACCGGTTCTCTCCGGTCCTGACTCTGCGTCTGGGGGCCG
    GCTGGGTGTCTAGCGGCACGGCGGGAGCTTGGCCCCTGCCGGCT
    (CloneID 3940211)
    TGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTAC SEQ ID NO:94
    CTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTGGGAACACCTGAAGAAAATCAAGCTTCTTGGCC
    AAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGCAQTCATCTGGACTGCAGAG
    AAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTC
    ATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCT
    GCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGCC
    GGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAATTG
    AGCCTGACTGTACATCTCTTCGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTGTC
    TTTTTTTTCTTTCGAAGAACAGGTGCCTCTCTCTCCTGACCCTGGGTCTGGGGCATGCATGG
    GTGGTTCTAATAGTAATGGGGGAACTGGGACCTTAGACGGGTGTCAGAGACACACGGGTCCA
    GGTCACGCCTCGGCGGGGTTACACTCAGGGTOCACCGCATGGGCCACAAACCCCGGGCGCTG
    CGGCCCACAGGGGTCCCGCACCGGGGGCCAACGGGGCGGCACCCGGGAAAAAGAGCGCCTCG
    CGCAAAAGTGTATACAAGGGGGGAGCGGCGAAGAACTAGACTCCGCGC
    (CloneID 5015022)
    GGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGC SEQ ID NO:95
    TCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCACGAATAGCTCCCGACTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGACGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGOCAGGGAAGACTTGGAGTCATCTGCACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCCGAGACTTCTTAGATCTGAAGGGACGACCGTGAT
    ATTCATGAACAATGTGGACACACACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCG
    TGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGACCCAGTGCCATCCAGAAGAAATCCC
    CCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTCTGAACTGCACAACT
    TGCACGCCTGACTGTACATCTCTTGGGATTTGTTTCATTACAAAGAAGCACTTTATGTACAA
    ACACCATAAAAAAC
    (CloneID 489924)
    GGCTGTTGGGTGTCGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCG SEQ ID NO:96
    GCGCCACTAGNCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAAGCAGGTGCCAAGTCCAGTNGTTGCAAGGNAGGACTTTGGAGTCATTCTGGGA
    CTGCAGAGANGGAACTCCTCTGAAGGCAAGCTCCCGGACACTTTCTTAGGATCTTGAAAGGG
    AGAAGGTGATATNCCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGAAGAGTGAA
    GAGAAGCCCGTGCCTGCTGCGCCTTGTGCCCAGCCCGGTGGCCCCGGGCCCAGTGCCATCCA
    GNAAAATCCCCCTTGGCGGAANGTCCAGCTNG
    TTTNGGGTTAGCNCTGATTTCCTAACGNGGT
    (CloneID 489924 in 3′ to 5′ orientation)
    ACATAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAAGTTGTG SEQ ID NO:97
    CAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACACTCAGAG
    CTAACCCAAGACGACGCTGGACTTGCCGCCAGGGGATTTCTTCTGGATGGCACTGGGGCCGG
    GGCACCGGGCTGGGCACAGGCGCANAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTGCCT
    GGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAACTCTCC
    GGAGCTTGCTTCAGAGCAGTTCCTTCTCTCCAGTCCAGATGACTCCAAGTCTTCCCTGCCAC
    CACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCAAAG
    ATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCCTAATG
    AAAATTGGATCCANCACCTNGAACCCGCAAACTTCGGGAGCTANTCCTGCTGNTGGGG
    (CloneID 3940896)
    GCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTGAGCGTTCTGCTCCGGC SEQ ID NO:98
    GCCAGCCTACCTCGCTCCTCGCCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTCGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAACAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGCAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGCAGAAGGTGATA
    TTCATGAAAATCTGGACACAGACCTTGCCAGGCAGCCTCGGGCAGACTGAAGAGAAGCCCGT
    CCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCC
    CTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGACCCTCACTGTACATCTCTTGGATNTGTTTCATTAAAAAGAAGCACTTTATGT
    (CloneID 4857040)
    GGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACC SEQ ID NO:99
    TCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGCCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTCATGAACCAACAGAACAACCTG
    TGACGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    CCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAACACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGCTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGCCAGCCTGGGGCACAGTGAAGAGAAGCCCGTG
    CCTGCTCCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TCAGCCTGACTGTACATCTCTTGGATTCGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTAATCCCTTTGGAACGACCAGGTTTCTCCTCTGTCCTTGACTCTAGGGTCCTCTG
    GGCCATCG
    (CloneID 3844688)
    TGTGGGTGTGGAGTTTCCCAGCGCCCCTCGCGTCCGACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:100
    CACCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCAACAGCAGGAATAGCTCCCGAGTTTGC
    GGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATCAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGGC
    GGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTCTACATCTCTTGGATTGTCTCATTGAAACCAGAAGCACTTTATGTACTGCT
    GTCTTTCTTTACCCTTTGGACGGAACAGGTTCCTCTGTCCTGA
    (CloneID 4797137)
    AGCGGAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCT SEQ ID NO:101
    CGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAACGGTCAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGCCAGCCTCCGCCAGAGTCAACAGAAGCCCCT
    GCCTGCTGCGCCTGTGCCCAGCCCGGTCGCCCCGGCCCCACTGCCATCCACAAGAAATCCCC
    CTGGCGCCAACTCCAGCCTCGTCTTGGCTTAC
    CTCTCACTCTCCTGAACCCTCTCGTTCTCTCTGTTTCCTCCATGCTTCTGAACTGCACAACT
    TGACCCTGACTGTACATCTCTTGGCATTTCTCTCCATTACCAAGAACCACTTTTATGTACCT
    CCTCTCTTTCATCCATTATCACTTTCTGAAGAAACACCTTTTCTCCTCTCTCCTTCACTCCT
    CCCGCTCTCTGGGCCCTCCCATGACCTGTCCCTAGCACCTCCCTTGGCCCGCGAACGCTTTG
    TCACACCTAAGTACTGACCATCTCACGAACCA
    (CloneID 4304080)
    GGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGCCG SEQ ID NO:102
    CCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAACACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGACAAGCCCGTGCT
    GCTGCGCCTGTCCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGGC
    GGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTACTGAACCGCTGTCGTTCCTGTCTGTTTCCTCCATGCTTGGTGAACTGACAA
    CTTGAGCCTGATGTACAATCTCTGGGGATTTGTTTCATTAAAAAGAAGCACTTTATGTAAAA
    AAAAGTTCACAAAAAAAAATCGGGGCACAAAGAAGGGGGGGAGAAAAGGGGAGGAAGGGGAC
    ATGGACATAGGTGTTCTGGACAAGTTTTGGCCAGGCGAAATGGGGCCCCAAAGGCGGGATAT
    GAAAGAAGTAAGTA
    (CloneID 5928314)
    GCGGTGGTCCGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGT SEQ ID NO:103
    TCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTC
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGCAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTCCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCACCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAACAAGCACTTTATGTACTGCTC
    TCTTTTTTTTTTTTCTTTTGAAAACAAGTTTCTCTCTGTCCTTCACTCTTGGGTCTGTGGGG
    CCATGGCATGAGTGGTTTTCTAGTACTAGATTGGAGGGAAAAGCTTTGTGGACACTTTAAGA
    ACTGGGGTTTTTTAGAAGAAAATAATTTGGGTTTCCGAAGGTGGGTAAAAAGGATCTTTTTG
    GGAACTGGAGGGGTTTTTAACAACTTTAATTTGGGGGTTTTACCCAAGCCCTCAAACTTCGG
    ACCGAACCCTTTAAACACGTC
    (CloneID 6159735)
    GGACGCCTGGGCGGCTGTTGGCTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:104
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGACGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    CAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATCTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACAACAC
    CCCAACCCNCCCACCACCCCCCACACCATCAAACAAAGGGGGGGCCGGCTCTAAGAATATCC
    CCTCGACGGGGCCCAAAGCCTTACCGCGTAACCCCATCTTTTTCTTGGAACAAAAGGGGTTC
    CCCTTATAGGGGGACGCCGCAAATTATAAAACCTTAGGGCACCCTGCCCCCGCTCCCCTTTT
    TTTAACAAAACCTCTCGTCGGAATCCCCGC
    (CloneID 308502)
    GCTCTTGCCTCTGGAGTTTCCCACCCCCCCTCGGGTCCCACCCTTTGACCGTTCTGCTCCGG SEQ ID NO:105
    CCCCACTANCCTCCCTCCTCCGCCCC
    ATCACCACAACCACCACCTTCAACCGAGTCGACCCCAACAGCAGGAATACCTCCCGAGTTTT
    CCGCCCTCCAGGTGGTCCATNCAATTTTTCAATTACGTTTTGATGAACCAACACGACCANCT
    CTTAACAACGACCAAATTCCCCTCCTAATAATCTTTCCGACACCTGAACAAAATCAAGCTTC
    TTCCCGCCAAGTCAGCACCTCCCAAGTCTAGTCCTCCCAGGGGAAAGACTTCGACTCATCTG
    CACTTGCAGAGAAGGAACTCCTCTTGAAGCAACCTTCCGGAGACTTTCTTTACATCTTGAAA
    GCCCACAAAGCTTGATATTCCATGGAAAATGTTGGACACAGACTTTTN
    (CloneID 308502 in 3′ to 5′ orientation)
    AAAGTCCTTCTTTTTAATGAAACAAATCCAAGAGATCTACACTCAGGCTCAAGTTGTGCAGT SEQ ID NO:106
    TCACAACCATGGAGGAAACAGACACAACGACAGCCTTCACGACAGTCAGAC
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGATTTCTTCTGGATGGCACTGGGGCCGG
    GGCACCGGGCTGGGCACAGGCCCACAGGCACCGGCTTCTCTTCACTCTGCCCCAGGCTGCCT
    GGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTCTCC
    GGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGCCAC
    CACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    (CloneID 4302544)
    GGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCG SEQ ID NO:107
    CCACCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACACCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAACAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTCCCAGGGAAGACTTGCAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCCTGACTGTACATCTCTTGGATTGTCTCATTAAAAAGAAGCACTTTATGTTAAACAA
    AAACAAAAAAAAA
    (CloneID 3937350)
    TTGGCTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCC SEQ ID NO:108
    AGCCTACCTCGCTCCTCCGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACACCAGCAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCACGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGCCAGAGTGAAGAGAACCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGCATTTGTTTCATTAAAAAGAAGCACTTTATGT
    (CloneID 3835958)
    TTCCCAGCGCCCCTCGGGTCAGGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGC SEQ ID NO:109
    TCCTCGGCCCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATACCTCCCGAGTTTG
    CGGCCTCCACGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTCG
    CGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAACTT
    GAGCCTGACTGTACATCTCTTCGATTTGTTTCATTAAAAAGAAGCACTTTAAAAAAAAAAAA
    AAAAAAAAAAAAAACCGGGGGACACAAGGGGGGGGGGGAAAAAG
    (CloneID 5925943)
    TCGGCTCTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTC SEQ ID NO:110
    CGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGCTGCCAAGTCTAGTGGTGGCAGGCAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCACCCTGGGGCAGAGTCAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTANAAAGAAGCACTTTATGTAAAAAAA
    AAAAAAAAAAA
    (CloneID 3936327)
    GTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCCACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:111
    CAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGCAGTCATCTCCACTGCA
    GAGAAGCAACTCCTCTGAACCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGCGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTCCCATCCAGAACAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCCTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTCTTCATTAAAAAGAAGCACTT
    (CloneID 4100301)
    GGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCG SEQ ID NO:112
    ACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGCAAGAACAAAATCGCCTCTAATATCTTTGGGACACCTCAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCCGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCCGCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    TGCTGCGCCCTGTGCCCAGCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTGGGTTAG
    CCTCTGACTGTCCTGAACGCTGTCGTTCTCTCTGTTTCCTCCATGCTTGTGAACTGCACAAT
    TTGAGCTTGACTGTACATCTTCTGGATTTGTGTCATTACCACAGACGCCTTTACAAACAGAA
    AAAAAAATCCGGGGCTTCATTTTCGGGGGGGAACAGGGTATGACG
    (CloneID 3903688)
    GTTGGGTGTGGGAGTGTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCG SEQ ID NO:113
    CCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTCGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    ACAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAACTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGACAATTG
    AGCCTGACTGTACATCTCTGGATTGTTTCATTAAAAAAAGAAGCAC
    (CloneID 4797136)
    AGCGGAGTCGCCTGTCTTGCTCCGGTAGTTGGCTGTGGACTGACCGCTTTCCCAGCGCCCCT SEQ ID NO:114
    CGGGTCCGACCCTTTGATGCGTTGCTGCTCCTGGCAGCCAGCCATACCTCGCTCCTCGGCGG
    CC
    ATGACCACAAGCGACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATATGCTCCCGAGTT
    TTGCGGCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCT
    GTGAGGAAGAACAAAATGGTCTCTAATATCTTTGGGACACCTGAAGAAACATCAAGCTTCTT
    GGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTG
    CAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGACGCTGA
    TATTCATGAAAACTGTGGACACAGACTTGCCAGGCAGCCTGGGGCACGAGTGAAGAGAAGCC
    CGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGGCCCAGTGCCATCCAGAAGAAATC
    CCCCTGGCGGCAAGTCCAGCCTCCTCTATGGGTTAAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACAATCTCTTGGATTGCTCTCATTACAAACAGAAGCACTTTATGTACTG
    CTGTACTTCTCATTTTCGTTTTTCCACAACAGGGTTGCCTCTCTGCACTTTGACTCTTTGGG
    CTCTGTGCGCCCATGGGCATGACTTT
    (CloneID 4120864)
    GCTCCTGCAGCGGTGGTCGGCTGTGGGTGTCGAGTTTCCCAGCGCCCCTCGGGTCCGACCCT SEQ ID NO:115
    TTCAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGCAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTCGGACACCTGAAGAATCAAAAGCTTCTTGGGCC
    AAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAG
    AAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAACGTGATATTC
    ATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCACAGTGAAGAGAAGCCCGTGCCT
    GCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGGC
    GGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTCACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGGCTGACTGTACATCTCTGGATTGTTCTCCATTAACAAAGAAGCACTTTAGGCAACACC
    CACCAAAAAC
    (CloneID 5405894)
    CTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCT SEQ ID NO:116
    TTGAGCGTTCTGCTCCGGCCCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATACCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGCTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGCTCGCCCCGGCCCCAGTGCCATCCAGAAGAAATTCCCC
    TCGCGGCAAGTCCAGCCTCGTCTTGCGTTAG
    CTCTGACTGTCCTGAACGCTGTCCTNCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTCGATTCGTTCCCATTAACAAAGAAGCACTTTAAAACAACC
    CACACACACAACGCGG
    (CloneID 4276593)
    GAGCGCCGGCTCCTGCAGCGGTGGTCGGCTGTTGGCTGTGGAGTTTCCCAGCGCCCCTCGGG SEQ ID NO:117
    TCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTTGATGAACCAACAGAACAACCT
    GTGAGGAAGAACAAAAAATGGCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTT
    GGGCCAAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACT
    GCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTG
    ATATTCATGCACAATGTGGACACAGACTTCCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCC
    CGTGCTGCTCCGCCTGTGCCAGCCCGGTGGTCCGNGCCAGTGCCATCCAGAAGAAATCCCCT
    GGCGGCAAGTCCAGCTCGTCTTTGGGTTAG
    CTCTGACTGTGCCTGAACGCTGTCGTCTGTCTGTTCCTCCCATGCTTGTGAACTGACAATTG
    GGCAGACTGTCATCTCTTGGTATTTGTTCCTTAACAAGAAGCTAAACAAACACAACACACAA
    AAAATTTTGGCGGGCTGGGGCACGAGAAGTTTAACACCACTCTGGGCGCGCGCCCCAGGTGG
    AGAAGGGCGCCGCGGTCACGGAACACCGGCAGACGCGGGGGGGGTTCCCACAAAAACGGGGG
    GCCGGGGGTGAACACCACAGGGGGGGGTCGGTCACACGACCCCACTCAACCCCG
    (CloneID 4127376)
    GGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACC SEQ ID NO:118
    TCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAACAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTCGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTGGTTTCATTAAAGAAAAACACTTTATGTACACAAC
    ACACACACAAAAAC
    (CloneID 5934901)
    CTGTTGGGTCTCGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGC SEQ ID NO:119
    GCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGACTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATCTGGACACACACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCACCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAACTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTANAAACAAGCACTTTATGTAAAAAAA
    AAAAAAAAAAA
    (CloneID 4622938)
    CCACGAGGGGGTGTGGAGTTTCCTACCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCC SEQ ID NO:120
    GGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTCGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTCATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGCCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTCTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTCATCTCTTGGATTTGTTTCATTAAA
    (CloneID 3909220)
    TGTGGAGTTTCCCAGCGCCCCTCCGGTCCGACCCTTTGAGCCTTCTGCTCCGGCGCCAGCCT SEQ ID NO:121
    ACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAACCTTCTTGG
    CCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTCGACTGCA
    GAGAAGGAACTCCTCTGAAGCAACCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGACAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGOTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCTCCATGCTTGTGAACTGGACAACTT
    GAGCCTGACTGTACATCTCTTGGTTTGTTTCATTAAAAGAAGCACTTTATGGTACTGGCTGG
    CCTTTTTTTCTTCCTTTCGGACCAACCGGGTTCCTCTTCTGTCCCTGTACTCTGGGGTCCTG
    GGGGCAGGCTTGGTGTTTCTCGTTGCTTGGGGCGCACAGCTTGTGTCACCTTTTCTGGTCTT
    TCCAGACCACATTGGGGCCCCGTGTTGGGCTCTGTCGCGGTGTACTTTTGGTTCTGCCCCGG
    CACTAACCGGTCTCGGCCCCGGGTTCTCCCTGTGGTCTCGGGGGGCCCCTTAAAGCGTCGGC
    AGTTTAAGGG
    (CloneID 6061001)
    TGCTGTTGGGTCTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCG SEQ ID NO:122
    GCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAACAAAATCAACCTTCTTGG
    GCCAAGTCAGAAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGCTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGCTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    CCTTTTTTTTTTTTCTTTTGAAGAACAGGGTTCCTCTCTGTCCTTGACTCTTGGGGTCTCTG
    GGGCCATGGCATGAGTGGTTTTCTAGTCAGAAGATTGGAAGGGAAGCTTTTGGGACACTTAA
    CCACTGGGGTTTTTTAAGAAGAAATAATTTTGGTTCCCAGAATGTGTTTACAAGGATCT
    (CloneID 4604404)
    GAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGCGTGTGGAGTTTCCCAGCGCCCCTCGGG SEQ ID NO:123
    TCCGACCCTTTGAGCCTTCTGCTCCGGCGCCACCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAACAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTCAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAACCTGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGACGAGAAGCCCGTG
    CCTCCTGCCGCCTGTGCCCCAGCCCGGTGGACCCGGCCCACTGCATCCAGAAGAAAATCCCC
    TGGCGGCAGTCCAGCCTCGTACTTGGGTTAG
    CTCTGACTGTCTGAACGCTGTCGTACTGTCTGTTTCTCCATGCTTGTGAACTGACAATTGAG
    GCTGACTGTACTTCTCCTGGACTTGGGTTGCATTCAAAGAGGAAAGCACCTTTTATTGTACT
    TGGATGGGTATCTATAGTATACATATCGTTAGTGAAGAGACAGGGGTTCATATTAGTGTACC
    TGGACTTTCTGGGGCATTGTGGCGCACTGGATTGAGGTCTATACTAAGAATAAATGAGAGGA
    AACGGTTGTGACAAGTGTGATGGGATTAGAAGGAGACAATAGATGGGTCCAGAATT
    (CloneID 4805717)
    GAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGG SEQ ID NO:124
    TCCGACCCTTTGAGCGTTCTCCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCCACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGCATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TTATGAAAAAATGTGGACACAGACTTGCCAGCCAGCCTGGGGCAGAGTGAAGAGAGGCCCGT
    GCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCC
    CTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTAC
    (CloneID 4109734)
    GGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC SEQ ID NO:125
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGCACACAGACTTGCCAGGCAGCCTCGGGCAGAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTCACAACTT
    GAGCCTGACTGTACATCTCTTGGATTTGTTTCACTTAAAAAGAAGCACTTTATGTACTGTGT
    CTTTTTTTTTTCCTTTGGACGACCGGGTTTCTCTCTGCCTTGACTCTTGGGTCTGTGGGCCC
    TGGCTGAGTGTTCTCATCATGGGGGGCC
    (CloneID 4553496)
    GCTGCAGCGGTGCTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCGACCCTTTG SEQ ID NO:126
    AGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCACCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGACGGAAGGTGA
    TATTCATGAAAATGTGCACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCG
    TGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCC
    CCTGGCGGCAAGTCCACCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTCAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGGCACAAG
    TTGAGCCTCACTGTACATCTCTGGATTGGTCTCATTAAACGAGAAGCACTTTATGTACTGTG
    TCTTTATTTAGCATTTGAGAACAGGGTGCCTCTTGTCCCTGAATCTGGGTTGGGGGCAGGAT
    GAGTGTTACTATAGTAATGCGCGAGGTTGGGCACTAGACGGGTTCAGGAAGAATATTGGGGC
    GATGTGTAAGGATTGGGAGGGGTAACAGTAGGGCGTGACAGCGTAATGGAGGCTATAGTCAG
    GAGCTGGAGGCCACCAGAGTGGGATTGGTATATGAGGTGAAGCTTGGGTGAAAGGCTCGGAC
    GAAGTTAGCAGAA
    (CloneID 4156131)
    CGGACGGCGTGGGCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGA SEQ ID NO:127
    GCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGCTGCCAACTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACGTGCAG
    AGAAGGAACTCCTCTCAAGCAAGCTCCGGACACTTCTTACATCTGAAGGGAGAAGGTGCTAT
    TTATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGCCACAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCACCCGGTCGCCCCGCCCCAGTCCCATCCAGAAGAAATCCCCCTGG
    CGGAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTTCCTCCATGCTTGTGAACTGGACAAA
    TTTGAGCCTGATGGTACATCTCTTTGGATTGGTTCATTAACCAAGAAGCACTTTATGTACGC
    NGGCCTAGATTCCTGTGAGGACCGGTTCTCTCGTGTCCTGGACCTGGTCGGGGGGCCGGATG
    AGGGGTCTAGAGGGATCGGGGGGAACGTGCGGACCTAGACGGGGTCGAACAACACTTCGGGC
    CCACTGGGTGCACAGCTTGGCGGGGGTAACCCAACTGGGGCCCGCCCCGGGGACAAAAAGCA
    AGGCGGCGGCGCGACCCAGCGCCGCCACCTCGCAAGAGGGGGACCCCAAGAAAAGACCCCGG
    CGACAGTATTACAACCGAGG
    (CloneID 5014564)
    GCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:128
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAPAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTCAAGGGAGAACGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTCTGCCCACCCCGGTGGCCCCGGCCCCAGTCGCATCCAGAAGAAATCCCCCT
    CGCGGCAAGTCCAGCCTCGCTCTTGGGTTAG
    TCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCCACCACT
    TGAGCCTGACTGTACATCTCTGTGGATCGTTTCATTAACNACCGACGCACTTTCATGTCACT
    GCGTGGTCGTATTGCTTTCCCCCTCTGCGCAGCAACCGGGTTCCTCCTCGGGGCCCTGAACC
    TCTTGGGACCGTGTGGCCCATGGCCTGAGCGTTCCTACTCGCAACACTCGCCGGCACACCAT
    CGGCGCACCCGCACCGCCCTTCTCCCGCACAACACACTCGGCTCCCAGGTCTCCACCACCTC
    CATCCGGCCCCACACACACCATGCCGTCCCCACG
    (CloneID 3458462)
    CCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTC SEQ ID NO:129
    CTCGGCGCC
    ATCACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTACGTTTCATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTCAAGAAAATCAAGCTTCTTGCG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAC
    AGAAGGAACTCCTCTGAAGCAACCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTGCGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTCTCTGTTTCCTCCATGCTTGTGAACTGACAATTG
    AGCCTGACTGTACATCTCTGGGATTGTTTCATTTACAAAAGAAGCACTT
    (CloneID 3910873)
    TCCCAGCGCCCCTCGGGTCCGACCCTTTCAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTC SEQ ID NO:130
    CTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCCTG
    CCTGCTGCGCCTGTGCCCACCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTCCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTCAAAAAGAAGCACTT
    (CloneID 5928362)
    CCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:131
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    CCCGCCTCCAGGTGGTGCATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGCGAGAAGGTGATA
    TTCATCAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAC
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTAAAAAAAAAAA
    AANAAAAANTAA
    (CloneID 3904371)
    CCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCC SEQ ID NO:132
    TCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCCAGTTTT
    GCGGCCTCCAGGTCGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTCGGCCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCCGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAC
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTCGTTTCATTAAAAAAGAAGC
    (CloneID 4578473)
    GCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAG SEQ ID NO:133
    CGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACACCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTCATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTCAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCACCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGCCCCCGCCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTCGGTTAG
    CTCTGACTGTCTGAACGCTCTCGTTCTGTCTGTNTCCTCCATGCTTGTGAACTCCACAATTG
    AGCTGATCTCATCTCTTGGATTTGTTTCATTAAAAGGAGCACTTATGTACTGCTGGCTTTTT
    TTTCTTGGACACCCGCTCCCCCTGCCTTGCTCTGGGTCTGGGGCACCCTGGAGGGTCCAGTA
    GAATGGGGAGGAACTGCGACCTTGCGGTTTCGAACAACTCGCCCCTGTTACGACTTGGCGGG
    GTACCTCCTGGGTCCGCCCTGGCAGAAGCAGGGCTCGCGCCCGAGCCTTGGCACACGGAACC
    TAGAAAGGCTCGCAATTCACGCCGAGGGTCGGGGGGCTGGG
    (CloneID 4559434)
    GGCTCCTGCAGCGGTGGTCCGCTCTCGGTGTGGAGTTTCCCAGCGCCCCTCGGCTCCGACCC SEQ ID NO:134
    TTTGAGCGTTCTGCTCCGCCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTCTT
    GCGGCCTCCAGGTGGTCGATCCAATTTTTCTTTTAGGTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAACTCAGCAGGTGCCCAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAACACAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGCGGCAGTCCAGCCTCGTCTTGGGTTAC
    CTCTGACTGTTCTGAACGCTGTCGTCTGTCTGTTTCCTTCCATGCTGTGAAACTGCACAACT
    TGGAGCCCTGACGTGTACCTCTCTGGGATCGTTCCATTCACCAGAAGCACTTTTATGTGCTG
    CTGCTATCTTACTCCTGTCCGAGACAGGGTTCTCTCGTCCCTTGACTTCGGGGTCGGGGGCC
    CCGGCCCTGTCTGCTTCCTGACACATTGGGGGCGAGAGTCTGTCTCCCTGCGACGGGTTCAG
    ACAGAATCGGGCCAGTCGGTGGAGCGTGGTCGGGACAACTCGGGAACAGCCAGGAGAATAAC
    GACGCTCGGGCGCCCCAGGCCTCGACTGCGCCTCTCCCGCAACCCCAGACACCCCGCGGAA
    (CloneID 4547048)
    GCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC SEQ ID NO:135
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTC
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAACAACAAAATGGCCTCTAATATCTTTGGGACACCTCAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGCGAGAAGGTGAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGCCAGAGTGAAGAGAAGCCCGT
    GCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCT
    GGCCGGCACAGTCCAGCCTCGTCTCGGGTTAG
    CTCTGACTGTCCTGAACGCTGTACGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAAG
    CTTGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAACGAAGC
    (CloneID 4276268)
    GAGCGGCGGCTCCTGCAGCGGTGCTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGG SEQ ID NO:136
    TCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCCCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGC
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGCTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGGAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CTGCTGCGCCTGTCCCCAGCCGGTGGCCCCGGCCCAGTGCCATCCAGAAGAAATCCCCCTGG
    CGGCAAGTCCACCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTCCTCCATGCTTGTGAACTGCACAATTT
    GAGCCTGACTGTCATCTCTGGGTTTGGTTCTTTAAACAGAAGCCTTTGTGCGCGGCTTCTTT
    CTCTCGAGACCACCGTTCCCTGCGCTGGCCCGGGCTCGGGGCCGGCCAGGGTTTCCCCCACT
    GGCGGCGCCCTCTGGCCCCCCGGTGTCTCCACACAACATGGCGCCCGGTAGGCTCGTCGGCG
    TACCCTCGTGGCCCCCGG
    (CloneID 3659047)
    GTTGGCTCTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:137
    CAGCCTACCTCGTCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGATGTCTGACCCCAACAGCAGGAATAGCTCCCGAGTT
    TCGCGGCCTCCAGGTGGTGGATCCAATTTTTCATATAGGTTTTGATGAACCAACAGAACAAC
    CTGTGAGGAAGAACAAAATGGCCTCTAATATCTTGGGGACACCTGAAGAAAATCAAGCTTCT
    TGGGCCAAGTCATCCAGGTGCCAAGTCTACGTGGTGGCAGGGAAGACTTGCAGTCATCTGGA
    CTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAACGGGAGAAG
    GTGATATTCATGAAAATGTGGACACGAGACTTGCCAGTGCAGCCTGGGGCACAGTGAAGAGA
    AGCCCGTGCCTGCATGCGCCTGTGCCCAGCCCGGTGTGCCCCGTGCCCAGTGCCATCCAGAA
    GAAATCCCCCGTGGCGGCAAGTCCAGCCTCGTGATTGGGTTAG
    CTCTGACTGTCCTGAACCCTGTCGTACTGTCTTGTTCCTCCATGCTTGTGAACTGCACAACT
    TGACCCTGACTGTACA
    (CloneID 3634373)
    GGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGC SEQ ID NO:138
    CTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAACACTTGGAGTCATCTGGACTGCA
    GAGAAGGACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAAGAAGGTGATA
    TTCATGTTTTCATAGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAG
    AAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGCCCCGGCCCCAGTGCCATCCAGAAGA
    AATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAATT
    GAGCCTGACTGTGCTCTCTGGATTTGTTCCTTAACAGAGCCTTTTGTCTGG
    (CloneID 5741030)
    CTCCTCCAGCGGTGGTCGGCTGTTGGGTGTGCAGTTTCCCACCGCCCCTCGGGTCCGACCCT SEQ ID NO:139
    TTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATACCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACACAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGACTCATCTGCACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAGAAGCACTTTAAAAAAAAAAAAA
    AAAAA
    (CloneID 3870232)
    ATCCCATGACGCCCCTCGGGTCCGACCCTTTGAGACGTTCTGCTCCGGACGCCAAGCCTACC SEQ ID NO:140
    TCGCATCCTCGGCGCC
    ATGACCACAACCAACCACCTTCAAGGGAGTCGACCCCAACACCAGTGAATACGCTCCCGAGA
    TTTTGCGGCCTCCAGTGTGGTGGATCCAATTTTTCATTAGGTTTGTCATGAACCAACGAGAA
    CAACCTCTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGC
    TTCTTGGGCCAAGTCACCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTG
    GACTGCAGAGAAGGACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAAGGGAGAA
    GGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAA
    GCCCGTGCCTGCTCCCCCTGTGCCCAGCCCGGTGGACCCGGGCCCAGTGCCATCCAGAAGAA
    ATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTCAACGCTGTCGTTCTGTCTGTTCCTCCATGCTTGTGAACTGCACAACTT
    GAGCCTTGACTGTACATCTCTTGGACTAGGTTCACTTAAAAGAAGCACTTTATGTACTGCTG
    TCTACAGAAAAACACCCCGGCAGACCGGGTACCCCTACAGGACGTGCACCTTGGGCCAGGGG
    CCACGGCCAGCCGGGCCACCAGATCCCACACTGGCAGGCAACCCTGCGACACACCACCACCA
    CGGGAAACACAACACACACAACAGGCCACCGCACGGTAAGAAGGACCTCAGGCCACGAGCAC
    ACACACAAAACAGGGGGCACAAACCACACGTGGACGACCAAACACCACAGCGACCGAAAGGC
    GGCCGACAACAGAGACACTCCCCCACACACCGGGTGCCCCAACACCAAACGCATGACAAACA
    CGTTCAACACACACAAGCCCC
    (CloneID 3905523)
    GTGTGGAGTTTCCCAGCGCGGCCTCCGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCACC SEQ ID NO:141
    CTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGACTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTACGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCACGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGCAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAACATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAACCCCGT
    GCCTGCTGCGCCTGTGCCCAGCACCGGGTGCCCCCGGCCCCAGTCCCATCCAGAAGAAATCC
    CCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACCGCTGTCGTTCTGTCTGTTTCCTCCATCCCTTGTGAACTGCACAA
    TTGAGCCTGACTGTACCTCTCTTGGATCCGGTTGCCATGCACACAGAAGCGCTGGCGAAAAA
    GACACCGAGCCGACCACCGACGC
    (CloneID 5517974)
    CGGACGCGTGGGCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGA SEQ ID NO:142
    GCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAAAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCCATGCTTGTGAACTGCACAAC
    TTGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGCACTGCT
    GTCTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGGCCTTGACTCTTGGGGTCTGTGG
    GCCCTGGCATGAGTGTTTTCCTAGAATAGATTGGAGGGAAAGCTTTGTGACACTTAATACTG
    TGGTTTCAAAAAAAAAATAATTTGGTTCCCAATGTGTTAAAAGGAACTTTTGGTACTGGAGG
    TTTTTAAAACCTTTAATTTGGGTTTAACCAAGGCCTAACCTGGTACGAACCTTAAAACGTGT
    CCCACGGGCCCCCGTTTCCTTGGCACGGGCCCAAACCCCACCGGGGGAGGCCTCTCTCACCA
    AAAACCCTTC
    (CloneID 4124775)
    GCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC SEQ ID NO:143
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGACTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTCTCCTGAACGCTCTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAGAAGCACTTTATGTACTGATGT
    ACTTCTTATTTTTCCTTTGAAAGAACCAGGTTTCTCTCTGTCCCTGATCTGGTCTGTGGCCC
    ATGGCACGGAGTGTTCCTTGTAGTACGATTGCGAGGGCAAGCTTGTGAACTATAGTACGGGT
    TTACGACGAACAATATCTGGCTCCCCAGGTCTCCACGACCTTGACGGGCGTTTCACACCTAC
    TGGGTTCCCAGCTAGTGGCAGCACAAACGCACAGCCCGGTCGCCAGCCACCCAGAGTTCGGG
    ACCCTGGTGTGCTATGCAGGCTGGGACACCCTGGATGTCCAAGGGGCCTGCTGCGGAAAGGT
    TTTATTAGCTAAG
    (CloneID 5832873 in 3′ to 5′ orientation)
    TTTTTTTTTTTTTTTTTTAAACTCCTTCTTTTTAATGAAACAAATCCAAGAGATCTACAGTC SEQ ID NO:144
    ACGCTCAAGTTCTGCAGTTCACAAGCATGCAGCAAACAGACAGAACGACAGCCTTCAGGACA
    CTCACAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGCGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGCAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTNCGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGG
    TCGACTCCCTTGAAGGTGGTGGTTGTGGTCAT
    GGCGCCGAGGAGCGAGGT
    (CloneID 4277604)
    GAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTTGGGTCTGGAGTCTCCCAGCGCCCCTCGGG SEQ ID NO:145
    TCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGACTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGAAGACTTGGAGTCATCTGGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTCAAGGCAGAAGGTGATAT
    TCATGAAAATCTGGACACAGACTTGCCAGGCAGCTGGGGCAGAGTGAAGAGAAGCCGTGGCT
    GCTGCGCCTGTGCCCAGCCGGTGGCCCGGGCCCACTGCATCCAGAAGAAATCCCCTGCGGAA
    GTCCAGCCTCGTTTTGGGTTAG
    TCTGATGTCCTGAAGCTGTCGTTCTGTCTGTTCCTCAAGGTTGTGACTGACATTGAGCTGAT
    GTACTTTCTGGATTGTTCATTAAAAGAGCTTTTGAAAAAAAAAAAAAAAAAATTTGGGGGCC
    GGCCCGAAATTTAACATGGGGGGGGGCCGGGTAGAATGGACGGCAGAAACGGGAAGGGGGTC
    ACAAAACGGGGAGGTGGAACGGGGGGTAGGTAAGGCGTACAG
    (CloneID 5834676 in 3′ to 5′ orientation)
    TTTTTTTTTTTTTTTTTTAAAGAGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTC SEQ ID NO:146
    AGGCTCAACTTGTGCAGTTCACAAGCATGGAGGAAACACACAGAACGACAGGGTTCAGGACA
    CTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGATGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGCTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGG
    TCGACTCCCTTGAAGGTGGTGGTTGTGGTCAT
    GGCGCGGAGGAGCGAG
    (CloneID 5405407)
    GCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGT SEQ ID NO:147
    TCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAAGCAACGCTTCGGAAGACTTCCTTAAAATTCGGACAGGACAAC
    GGGAGAATATCACAGAGAAATGTGTGGCACACAAGATTGGCCAGGGCACCCGTGGGGCAGAT
    GTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGGTGGCCCCGGTCCCAGTTGC
    CATCCAGAAGAGATCCCCCTGGCGGCAAGTCCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGGTCCTGAACCGCTGTCGTTCTGTCTGTGTCCTCCATGCTTGTGACAGTGCACA
    CACTCGAGCCTGACTGTACATCTCTCGGATTCGTTACATTCAGAAACAACGCACTTCTATGT
    ACTGCCTGTCCTTTCTTTCCTTCGCTTTTGGCAGGACCCTGGGTTTCTCTCCTGCCCCTGCA
    CTCTGGGCCTCCGCTGGCCCCAGGCCCTGTGCTGTCTCCCTACGGCCTCCGCATGCCAGCGA
    TTCGCCTGGTCGTGACCCTTAGGCCTGGCGTTTTACCCCCG
    (CloneID 4563923)
    GCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTT SEQ ID NO:148
    GAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGNGTTTTGNATGAACCAANCAGAACAAC
    CTGTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCT
    TGGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACT
    GCAGAGAAGGAACTCCTCCCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGG
    TGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGC
    CCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAAT
    CCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCAT
    (CloneID 5533034)
    CGGCTGTTGGGTCTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCC SEQ ID NO:149
    GGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGCGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTCGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGCCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCCTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTCCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTCTTTTGAAGAACACGGTTTCTCTCTGGCCTTTGACTCTTGGGGTCTGTGG
    GGCCATGGCAATGAATGGTTTTCCTAAGTAGTAAGAATTTGGAGGGAAAAGCTTTTGTTGAC
    CCCTTAATCAACTGGGGTTTTTTAAGAAGGAAAATTAATTTGGGGGTCCCACAAATGGTGTT
    TAAAAAGGAATCTTTTTTGGGACCTGGGGCGGGTTTTTTTAACCCCCTTTTTACTTTGGGGG
    GTTTTTACCCAAGGCCCTTCAAA
    (CloneID 6060969)
    AGCGGTGGTCGGCTGTTCGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCG SEQ ID NO:150
    TTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTCGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCACGCAGCCTGGGCCAGAGTGAACAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGCCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAACTCCAGCCTCGTCTTGGGCTAG
    CTCTGACTCTCCTGAAACGCTGTCGNTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAAC
    TTGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAAGAAGCACTTTATGTACTGC
    TGTCTTTTTTTTTTTTTTCCTTTGAAGAACAGGTTTTCTCTCTGTCCTTTGACTCTTGGGCT
    CTGTGGGCCATGGGCATGAATTGTTTTTCTACTACTAGAATTGGAGGGAAAAGCTTTTGGGA
    CACTTAANACTGGGGTTTTTTAAGAAGAAAATAAT
    (CloneID 3347594)
    TGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTAC SEQ ID NO:151
    CTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAAATAGCTCCCGAGTTTTGC
    GGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCACAGTGAAGAGAAGCCCGTGCC
    TGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    CCGGCAACTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCCTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAA
    (CloneID 3531894)
    TGTGGGTGTGCAGTTTCCAGCGCCCCTCGGGTCAGACCCTTTGAGCGTTCTGCTCCGGCGCC
    AGTCTACCTCGCTCCTCCGCGCC
    ATGACCACAACCACCACCTTCAAGGCAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTAT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTAGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGCTGCCAAGTCTAGTGCTGGCAGGGAACCACTTGGAGTCATCTGGACTGC
    AGAGAACGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGA
    TATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCG
    TCCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGGCCAGTGCCATCCAGAAGAAATCCCC
    CTGGCGGAAGTCCAGCCTCGTCTTGGGTTAC
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTACTCCATGCTTGTGAACTGACCATCC
    GAGACTGAATC
    (CloneID 4276267)
    GAGGGGGGCCTCCTGTAGGGTGGTCCGTGTTGGGTGTGGAGTGTCCCAGCGCCCCTCGGGTC SEQ ID NO:153
    CGACCCTTGAGCGTCTGCTCCGGGCCAGCTACCTCGCTCCTCGGCGCC
    ATGAGCACAATCCAGCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTT
    TGCGGCTCCAGGTGGTGGATCCAATTTTTCATTAGGTGTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGGCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGCAGTCATCTGGACTGCAGA
    CGAAGGAACTCCTCTGGAAGCAAGGCTCCGGAGACTTCTTAGATCTGAAGGGAAGAAGGTGA
    TATTCATGAACAATGTGGACACAGACTTGTCCAGGCACGCCTGGGGCAAGACTGAAGAGAAG
    CCCGTGCTTCTGGGCTGTGCCATCCGGTGGGCCCGGCTCCAGTGCTATCCAGAAGAAATCCC
    CCTGGGGGGAAGTCCAGCCTCGTCTTGGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCCGTCCTGTCGTCGTTACATCCATGCTTGTTGAACTTGGA
    CCAACTTGGAGTCTGATGGGAGATCTCCTGGATTGGTTCATTAACCAAAACGCGGTTAGGGA
    ATGGCCGCCCTTGGGGGAGTCTTCTGACAGACGAAGGTTCACCACTGGGCGAATTCGGCGGG
    TCGGGGGACAGGAACACAGGGTCCACAGGCAATGGGGCAGACCCATTGTC
    (CloneID 4547025)
    GGCGGGTCCGACCCTTTGAGCGTTCCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC SEQ ID NO:154
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTG
    CCGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAATCAAAAGCTTCTTGCG
    CCAAGTCACCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAACAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTG
    GCGGCAAGTCCAGCTCGTTCTTGGGTTAG
    CTCTGACTGTCTGAACGCTGTTCGTTCTGTACTTGTTTCCTCCATGCTTGTGAACTGCACAA
    CTTGAGCTGACTGTACGATCTCTAGGATCTGTCTCATTAAAAAGAAGCCACTTATGTACTGG
    TGTCTTTTTCACCTTAGGAAAAACAGCTTCCCTCAGGCCTTGACCACTTGAGGTCTGGAGCC
    AAGCGCATGAAAGGTCCCTAGGCACCCGATCGGAGGGAAACGCCTGCGACCTTACTACCGCA
    TCTCACACGACACAAGTGCCGTCCCACCTGTCAAAGCACACGTGACCGAGGTCCAACGCATA
    CCGGTTGCCGCCTAATTGCAGACCAAACGCCCCCACCAGCGCGCCCACACGGACTCGACACT
    GCTGCAAGGCGACCGCAACCCCTCACACAAACCCCCCTCCCAACAGATATCCAGCGAACCCA
    CCACGCAGCAAAACGTCCATCACAAAACGTC
    (CloneID 5314132)
    AGCGGAGCGGCGGCTCCTGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTC SEQ ID NO:155
    GGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    CAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAG
    AGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAACAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTCCCATCCACAAGNAATCCCCCT
    GGCGGCAAAGTCCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACCGCTGTCCGTTCCTGTCCTGGTTTCCTCCCATGCTTTTTTTTTCT
    CGTCATCTCGTACGTGAAGGGTGACAGTCACCGACAATACCGTCCGCTGCCGAGAAGACCTC
    AACGCGACGGAGTAACACAACATCAGCATATACCAATGAACCTTCCCGATGGCGTCAGACTC
    TCCACGCGACATATACTAGA
    (CloneID 5576026)
    CTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCT SEQ ID NO:156
    TTCAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATCTGGACACAGACTTGCCAGCCAGCCTGGCGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCCCAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAACACTTTATGTACTGCTG
    GCCTTTTTTTTTTTCCTTTTGGAAAACAGGTTTCCTCCTCTGTCCTTGAACTCCTGGGTCTT
    GGGGGCCCAGGGCCTGAAGGGGTTTTAATTATCAAACTTGGAGGGAAAACCTTTTGGACACT
    CTTTACTTGGGCCTCTTCACAAAACACCACCTCGGTCCCCACAAGGGGTTCGACGGCCTCTT
    TTGTCACGAAGGTTTCCCCAATTTAATATTTGGGCGTTCCATAAACCTCCATTGGCGACGGC
    CCAATACACCGGCCATACGGCCGCCGCTCCTTGTCTAATCCCGCCCCCGGATGGGAGGCTCT
    TCTTCCAGAGGCCCTCATTGGGGCGGCCCCCGCTCTATCACAGC
    (CloneID 5165195)
    GCAGGACAGGCGGCAGCCGCGGCTCCTGCAGCGGTGGTCTGGCTGTTGGGTGTGGAGTTGGG SEQ ID NO:157
    GAGCGCCCCTCGGGTCCGAGCCTTTCAGCTGTTCTGCTCCGGATGCCAGCCTACCTCGCTCC
    TCGGCCCC
    ATGACCACAACCACCACCTTCAAGGGAGTCAGAACCCAACAGTCAGGAATAGCTCCCGAGTT
    TTCCGCGCCTCCAGGTGTGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAA
    CCTGTGAGGAAGAACAAAATGGTCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTC
    TATGGGCCAAACTCACGCAGCTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTG
    GACTGCAGAGAAGGAACTCCTCTGAAGCAAGCATCCGGAGACTTCTTACATCTGAAGGGAGA
    AGGTGACTATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAG
    AAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCTGGTGGACCCTGTGCCCAAGTGCCATCCAG
    AAGAAATCCCCCTGGCGGCAAGTCCAGAACTCGTCTTGGGTAAG
    CTCTGAACTGTACCTGAACCGCTCTCGTTCTGTCTGTATCCTCCATGCTTGTCAACTGCACA
    ACTTGAGCCTGACGCTGTACATTCTCCTGGGGATTTCGCTTCCCACTTAAAAAAGACGCCAC
    TTCACTGTTACCAGCGAAAAAAGGCAGCAGCGAGAACAGAACAAACAATTGGTGAG
    (CloneID 3449557)
    GTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGC SEQ ID NO:158
    CAGCCTACCTCGCTCCTCGCCGCC
    ATGACCACAACCACCACCTTCAAGGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTT
    TGCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTCGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAACCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCCGTGGCCCCGGCCCAGTGCCATCCAGAAGATATCCCCCT
    GGCGGCAAGTCCAGCCTCGTCTTCGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTTGTCTTGTTTCCTCCCATGCTTTGTTGAACCTGC
    ACAAACTTGAAGCCCTTGACGTGGTACAATCTCCTTGGAGTTTGTGTCCACTTTAAAACGAA
    GCACTTTTTAAATAG
    (CloneID 3351305)
    GCTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGTGCGCCAG SEQ ID NO:159
    CCTACCTCGCTCCTCGCCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAACTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAACGGAGAAGGTCATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTCGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCCCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAATT
    TGAGCTGACTGC
    (CloneID 3029189)
    TTGGCTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCC SEQ ID NO:160
    AGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCCGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATCCTT
    (CloneID 5465786)
    GCTGTTCGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCCACCCTTTGAGCGTTCTGCTCCGG SEQ ID NO:161
    CGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAACACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTCCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCCCTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTAAAAACAAAAA
    AAAAAAAAACTCGA
    (CloneID 2819762)
    GGC SEQ ID NO:162
    ACGAGGACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGCAAGACTTGCAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAACCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTCTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGGTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTANNAAAAANAA
    AAANNAAA
    (CloneID 2819762 in 3′ to 5′ orientation)
    TTTTTTTTTTAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAA SEQ ID NO:163
    GTTGTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCCGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTCCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTTGGATCCACCACCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGG
    TCGACTCCCT
    (CloneID 2819763)
    GGC SEQ ID NO:164
    ACGAGGACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTCCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAAAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCAT
    (CloneID 2819763 in 3′ to 5′ orientation)
    TTTTTTTTTTAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAA SEQ ID NO:165
    GTTGTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGGCTGGGCACAGGCGCAGCAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGGT
    CGACTCCCT
    (CloneID 3912245)
    GGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGC SEQ ID NO:166
    CTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACACACTTGCCAGGCAGCTGGGGCAGAGTGAAGAGAAGCCCGTGC
    CTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCT
    GGGCGGCAAGTCCAGGCTCCGTCTTGGGGTTAG
    CTCTGACTGGTCCTGAACGCTGTCGTTCTGTCTGGTGTCCTCCATGCTTTGTGAACTGGGCC
    CAATTTGAGGCCTGGAGTGGTGCCTCTCTTGGGTTTTGGTGCCTCTTAAGGAAGCCTTTTTT
    GTCCGGCGGCCCTTGCCCTTTGCGGCACCCGGTGTTCTCCTGCCCTACACCGCGGGCGGGGG
    CCCGG
    (CloneID 5164014)
    C SEQ ID NO:167
    CGGCGGCCTCCTTACCCTCGCCCTGCCCCCACTCCTTATTCGCACCTACCTCACAGAGTTTT
    GCGGCCTCCAGGTCGTGGATCCAATTTTTCATTAGGTTTTCATGAACCAACAGAACACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAAGTCAGCAGGTGCAACTCTAGTGGTCGCAGGGAACACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATT
    CATGAAAATCTGGACACACACTTGCCAGCCAGCCTGGGGCAGACTGAAGAGAAGCCCGTGCC
    TGCTCCGCCTGTGCCCACCCCGGTGCCCCCGGCCCCAGTGCCATCCAGAACAAATCCCCCTG
    GCGCCAAGTCCAGCTCCTCTTGGGTTAG
    CTCTCACTGTCCTCAACGCTGTCCTTCTGTCTCTTTCCTCCATGCTTGTGAACTGCACAACT
    TCAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAACAGAAGGCACCCTTTAATAAA
    CAAACACAAGAACACAGAACAAAACACAACAAAGAACAACGGCGGG
    (CloneID 4284754)
    GAGCGGGGCTCCTGCAGCGGTGGTCGGCTGTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTC SEQ ID NO:168
    CGACCCTTTCAGCGTTCTGCTCCGGCGCCACCCCTACCTCGCTCCTCGGGCC
    ATGGACCACAACCACCACCTTCAAGGGACTCGACCCCAACAGCAGCAATAGCTCCCCAGTTT
    GGCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTGTGGCACACCTGAAGAAAATCAAGCTTCTGG
    GGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCACCGAAGACTTCGAGTCATCTGGACTCC
    ACACAAGGAACTCCTCTGGAGCAAGCTCCGGAGACTTCTTACATCTGAAGGGAGAAGGTGAT
    ATTCATGAACAATGTCGACACACACTTGCCACGCCGCCTGCCCGCACGACTCAAGAGAAGCC
    CGTGCCTGCTCCCCCTGTGCCCAGCCCGGTGCCCCGGCCCCAGTGCCATCCAAGAATCAAAT
    TCCCCTGCGGGCAGAGTCCAGGCCTCGTCTTGGGTTACG
    CTCTGACTGTCTGAACCGCTGTCGTTCTGGTCTTGTTTTCTTCCATGCTGTGTCAACGTGGA
    CAACTTTGAGGCCTTGATGTACATCTCTGGATGTGTTCACTTAAAAAGAGCAATTATGTATC
    GGTGCCTTTTCATTTCCTTGGACAAACCGGTCTCTCTGACTTCAACTGGGGTTGGGGCAGGC
    ACCACGATGTTTCAACACAATGGAGCACCN
    (CloneID 428337)
    GAGCGGCGGCTCCTGCAGCGGTGGTCCCCTGTTGGGTGTGGAGTTTCCCAGCCCCCCTCGCT SEQ ID NO:169
    CCGACCCTTTGAGCGTCTGCTCCGCCGCCAGCCTACCTCGCTCCTCGGCCCC
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAACAACAAAATGGCCTCTAATATCTTTCCGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGAAGACTTGGAGTCATCTGGACTGCAG
    ACAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATAT
    TCATGAACCATGTGCACACAAGACTTGCCAGGCAGCCTGGGGGCAGAGTGAAGAAGAAGCCC
    GTGCCTGCTTGCGCCTGTGCCCAGCCCGGGTGGCCCCGGCCCCCAGTGCATCCAGAAGAAAT
    CCCCCTGGGCGGCAAGTCCAGCCTCGTCTTGGGTAG
    CTCTGACTGTCTGACGCTGGCCTCTGGCTGTTCCTCCTGCTTGTCAACTGCACACTTGAGCC
    TGACTGGACATCTCTTGGATTCGTTCATAAAAGGAGCTTGCAAAAACAAAAAAAAATTTGCG
    CGCCCCCCAAATTTTAACTCTTGGCGCCCCGGTGAATGGCGCGCCAGACCGCACAGGGGTCA
    CAAACCGGGCGGCGAAACAGGGGTTGTCGCCACACCCCGG
    (CloneID 5936059)
    AGCGAGGCCTGGGTGGCGATCCAAGACGAGGCTGCAGCGGTGGTCGTCTGTTGGGTGTGGAG SEQ ID NO:170
    TTTCCCAGCGCCCCTCGGGTCCCACCCTTTGAGCGTTCTGCTCCGCCGCCAGCCTACCTCGC
    TCCTCCGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGCAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTCATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTCGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGCGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCGGTTTCCCTCCATGCTTGTGAACTGCACAAC
    TTGAGCCTGACCTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTAAGGACTGC
    TGGCCTTTTTTTTTTTTCTTTTGAAAAACAGGTTTCCCCCCGGCCCTTTGATCCTTGGGGTC
    TGGGGGCCCATGGGAATGAAATGGTCTTCTAACTAACAACATTGGGAAGGAAAAAGCCTTGG
    GGACACCTCAACAACGTGGGGTTTTTAAAAAGAAAAAAAATTTGGCTTCCCACAGGGGGTTA
    AAAGGAATCTTTTTGTACCCGAAGGGTTTTTAAACCCTTTTACCTGGGGGGTTACCCAGGCC
    CTCCCACTTGGCACCGGAACCATTTAACCGGTCTCCAGAGGGGCCCCGTTTCCCGGGCCAGA
    CCCCCCCACCCTCACAGGGGAAGTCTCTCCTCCCCAAAAAACTCTCCCTTGGGGGGTGGGCT
    CCCCTACCTTTCGCCCGTGGGGCCCTTTTGTCACAAA
    (CloneID 4280999)
    GAGCGGCGCCTCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTCTCCCAGCGCCCCTCGGG SEQ ID NO:171
    TCCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTGATGAACCAACAGAACAACCTGT
    GAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGG
    CCAACTCAGCAGGTGCCAAGTCTAGTGGGTGGCAGGGGAACGACTTGGAGTCATCTGGACTG
    CAGAGAAGGAACTCCTCTGAAGCAACCTCCGGAGACTTCTTAGATCTGAAGGGAGACGGTGA
    TATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCG
    TGCCTGCTGCGCCTGTGCCCAGCCCGGTCGGCCCGGCCCAGTGCCATCCAGAAGAAAATCCC
    CCTGGCGGGCAACTCCCAGCCTTCCGTCTGTGGGGTTAAG
    CTCTTGACTGGGTCCCTGAACGCTGTCCGTTCCTGTCTGTTTTCCCTCCCATGGCTGGTGAA
    CTGGACCAACTTTGAGCCTGACTTGTACATTCTCCTGGGATTCGTCTCCTTTCACCCAGAAG
    GCCTTTATGACACACAACAACACTCCAAACACACCTTGGGCGCCGCGCGCCCCTCACACATT
    TTAAACCCTCTGTGCGGCCGGCCCACGGTAGGACAGGGCTAGGCCCGGCAACGGGAGGGACG
    GTGGTTACCAAAACCCGGGCGGGCTGCCCCACGGTCCGCTCG
    (CloneID 6154219)
    GGACGCGTGGGCGGACGCGTGGCCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGA SEQ ID NO:172
    CCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAGCAAGCTCCGGAGACTTCTTAGATCTGAAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACCCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTCCACAACT
    TGAGCCTGACTGTACATCTCTTGGGGATTTGTTTCATTAAAAAAGAAGCACTTTTATGTACT
    GCTGGNCTTTTTTTTTTTTTTCTTTTTTGAAGAACAGGTTTTCTCTCCTGTCCCTTGACTCC
    TTTGGGGTCTGTTGGGCCCATGGGGCATGGAGTTGGTTTTCTAAGGTAAAGTAGAAATTGGG
    GAGGGGGAAAAGCCTTTTGGTGGACACCCTTTT
    (CloneID 4045037)
    GGCGGGGCTCACTGACAGCGGTGGTCGGGTGTGGGTCTGGAGTTTCCCAGCTGGCCCCTCGG SEQ ID NO:173
    GTGCGACCCTTGTGAGCGTTTCTGCTCCGGTCGCCAGTCGTTACCTCGCTCCTCGGGCC
    ATGACCACAAGCACCAGCTTCAAGGGAGTCGATCCCAACAGCAGGAATAGCTCCCGAGTGTA
    GCGGTCTCCAGGTGGTGCATCCAATTCACATCAGGTTTGATGAACCAAGAGAACAACCTGTG
    AGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAACCTTCTTGGGC
    CAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCACGGAAGACTTGGAGTCATCTGGACTGCAGA
    GAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGACACGGTGATATT
    CATGACAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCCAGAGTGAAGAGAAGCCCGTGC
    TGCTGCGCCTGTGCCAGCCCGGNTGGCCCGGCCCAGTGCCATCCAGAAGAATCCCCTTGGGG
    AGTCAGCTCGTCTGGGTA
    (CloneID 6048028)
    CCACGCGTCCGCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGT SEQ ID NO:174
    CCGACCCTTTCACCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGCACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCCGAAAAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAA
    CTCTGACTGTCCTGAACGATGTCGGTCTGGCCTGTTTCCTCCATGCTTGGGAACTGCACAAC
    TGGAGCCTGACTGTACATCTCTTGGAATTGGTTTCATTAAAAAGAAACACCTTTAAAAAAAA
    AAAAAAAAAGGGGGGGCCGCTCCAAAAGGAT
    (CloneID 2518214)
    GAGCTCAAGGATCCTTAATTAAATTAATTCCCCCCCCCCCCGAGCGGCGGCTCCTGCAGCGG SEQ ID NO:175
    TGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCCGACCCTTTGAGCGTTCTG
    CTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGNGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCAGTGGCCCCGGTCCCAGTGCCATCCAGAAGAAATCCC
    (CloneID 2820804)
    GGCACGAGGCCTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTC SEQ ID NO:176
    CGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATC
    (CloneID 2519633)
    AGCGGCGGCTCCTGCAGCGGTGGTCGGTTGTTTGGTGTGGAGTTTCCCAGCGCCCCTCGGGT SEQ ID NO:177
    CCGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAACGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACCAGAACAACCT
    GTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTG
    GGCCAAGTCAGCAGGTGCCAACTCTAGTGGTGGCAGGGAACACTTGGAGTCATCTGGACTGC
    AGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAACGTGAT
    ATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTG
    (CloneID 2518293)
    AGCGGATCCTTATATTAAATTAATTCNCTCCCCCCCCCCCAGAGCCGGCGNNNGCTCCTCCG SEQ ID NO:178
    GAGCGTGTGTGTCGGCTTTGTTGGGATGTGCGAGCTTTCCCCAGCTGCACCCTTCGGAGTCC
    CGACGCCTTTTGANNGCGTTCTGCATCCCGGCGCCCAGCCCCTACTCTCGCTCCTCTGGCGC
    CC
    ATGANCCACTATACCACCACCTTCAACTGTGAGTCGACCCCAACNATCCAGGAATAGCTCCC
    GAGTTTTCGCGGCCTCCACCTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGA
    ACAACCTGTGACCAAGAACAAAATGGCCTCTAATATCTTTGCGACACCTCAAGAAAATCAAG
    CTTCTTGCGCCAAGTCAGCACGTGCCAAGTCTAGTGGTGCCAGGGAACACTTGGAGTCATCT
    GGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGA
    AGGTGATATTCATGAAAATCTGGACACAGACTTGCCAGCCAGCCTGNCGCAGAGTGAAGAGA
    AGCCCGTCCCTGCTGCGCCTGTGCCCACCCCAGTGGCCCCGGTCCCAGTGCCATCCAGAAGA
    CATCCCCCTTGCGGCAAGTCCAGCCTCGTCTTG
    (CloneID 2819423)
    GGCACGAGCCCTGCAGCGCTGGTCGGCTGTTGGGTGTGCAGTTTCCCAGCGCCCCTCGCGTC SEQ ID NO:179
    CGACCCTTTGAGCGTTCTCCTCCGGCGCCAGCCTACCTCGCTCCTCCGCGCC
    ATGACCACAACCACCACCTTTAAGGCACTCGACCCCAACAGCAGGAATAGCTACCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGCAAGAACAAAATCGCCCCTAATATCTTTGGGACACCTGAACAAAATCAACCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTCGTGGCAGGGAAGACTTGGAGTCATCTCGACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCC
    (CloneID 2819397)
    GGCACGAGGCCTGCAGCGGTGGTCGGCTGTTCGGTGTGGAGTTTCCCAGCGCCCCTCGGGTC SEQ ID NO:180
    CGACCCTTTGAGCGTTCTGCTCCGGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGCGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGGCCCCTAATATCTTTGGGACACCTGAAGAATCAAAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGCGAAGACTTGGAGTCATCTGCACTGCA
    GAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTATATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGGCC
    (CloneID 2783324)
    CGAGCCGCGGCTCCTGGAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGG SEQ ID NO:181
    GTCCGACCCTTTGAGCCTTCTGCTCCCGCGCCAGCCTACCTCGCTCCTCGGCGCC
    ATGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAAAACAAAATGGCCTCTAATATCTTTGCGACACCTGAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCACGTGCCAAGTCTAGTGCTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    AAGAATGAACTCCTCTGAACCAAGCTCCGCACACTTCTTACATCTGAAGCGACAAGGTGATA
    TTCATTAAAATGTGGACACACACTAGCCATCCAGCCTGTCCCATAGTGAATAGAAGCCCGTG
    CCTGCTGCTCCTGTGCCTATTTCAGTTCATCCAGCACACGCACCGTCCACAACAAATCCCGC
    TGGGGCAACTACAGGCTTGATT
    (CloneID 471568 in 3′ to 5′ orientation)
    TTACATAAAGTGCTTCTTTTTAATGAAACAAATCCAACAGATGTACACTCAGGCTCAAGTTG SEQ ID NO:182
    TGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACCAGGCTGGACTTGCCGCCAGGGGATTTCTTCTGCATGGCACTCGGGCCGG
    GGCACCGGGCTTGGGCACAGCCGCANAGGCACGGGCTTCTCTTCACTCTGCCCCAGGCTGCC
    TGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAAGTCT
    CCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTTGCAGTNCAGATTGACTCCAAGTCTTCCCTG
    CCACCANTAGACTTTGGCANCTGCNGACTTTGGNCCAACAAAGTTGAATTTCTTCAAGNGGT
    CCCAAAGATTT
    (CloneID 471568)
    CTGCAGCGGTGGTCGGCTGTTGGGTGTGGAGTTTCCCAGCGCCCCTCGGGTCTCGACCCTTT SEQ ID NO:183
    GAGCGTTCTGCTCCGGCGCCACTACCTCGCTCCTCGGCGCC
    ATCACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCAGGAATAGCTCCCGAGTTTT
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TTG
    (CloneID 4080434)
    GACCCCAACAGCAGGAATAGCTCCCGAGTTTTGCGGCCTCCAGGTGGTGGATCCAATTTTTC SEQ ID NO:184
    ATTAGGTTTTGATGAACCAACAGAACAACCTGTGAGGAAGAACAAAATGGCCTCTAATATCT
    TTGGGACACCTGAAGAAAATCAAGCTTCTTGGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGT
    GGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGG
    AGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATGAAAATGTGNNNNNNNNNNNNNNNN
    NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN
    NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN
    N
    NNNNNNNNNNNNNNAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGGGGTCTGTGGG
    CCATGGCATGACTGTTTCTAGTAGTAATGGGAGGGAAAGCTTGGTGACACTTAGTACTGTGT
    TTTTAAGACGAAATAATTGGGTTTCCAGATGTGTCACAGGATCTTCGTACTGAGGTTTAACA
    CTTTACTGGGGTTTACCAAGCCTCAATGGAAGACATAACAGTCACAGGCCCGTCTGCAGGCC
    AACCAAGGGAGTTCTCCGAGACCTCTGTTCTGCCTAATGCCATGGCTTGTCAAAGCCCTCTG
    GCTGGC
    (CloneID 4748522)
    CGAGTTTTGCGGCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAA SEQ ID NO:185
    CAACCTGTGAGGAAGAACAAAATGGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGC
    TTCTTGGGCCAAGTCACCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGCAGTCATCTG
    GACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAA
    GGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAA
    GCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAA
    ATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACCCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTATTCCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGTGGGTCTGTG
    GGCCATGGCATGAGTGTTTCCTAGTAGTAGATGGGAGGGAAACCTTGGTGACACTTAGTACT
    GTGTTTTCAAGAAGAAATAATTGGGTCCCAGATGTGTTAGAGGATCTTGGTACTGAGGTTTT
    TAACACTTTACTGTGGCTTTACCAAGCCTCAACTGGACAGACCATAAA
    (CloneID 5187032)
    CTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGGCCAAGTCAGCAGGTGCCAAG SEQ ID NO:186
    TCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGACAAGGAACTCCTCTGAAGC
    AAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATGAAAATGTGGACACAG
    ACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGC
    CCGCTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGT
    CTTGGGTTAG
    CTCTGACTGTCCTCAACGCTGTCCTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTC
    TCTTTTTTTTTTTTCCTTTGGAAGAACAGGTTTCTCTCGTGTCCTTGACTCTGGGGTCTCGG
    GCCCAGGGCATCAGTGTTCCATAGTAGTAGATGGGAGGGAAAGCTTGGCGACACTTAGTACG
    GGGTTTTCAACAAGAAATAATCGGGTTCCAGAGTGTGTAAGAGGACTCTTGGGTACGCAGGT
    TAAAACACTTAACTGGGGTATACCAAGCCTCAACGCGACAGACCATAAACGGTCCACAGGCA
    CCGTTCCGTGCAGGGCCCAAGCCAAAGGGAGTCTCTCCGAAGAGCCTTCTGGGAGTAGCCCT
    AACTTTGCCAGGTGGCCTTGGGTCAAGAGCCTCCTCCTGTGACCTGGTCA
    (CloneID 3895688)
    AATATCTTGGGACACCTGAAGAAAATCAAGCTTCTTGCGCCAAGTCAGCAGGTGCCAAGTCT SEQ ID NO:187
    AGTGGTGGCAGGGAAGACTTGGACTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAG
    CTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTCATATTCATGAAAATGTGGACACAGACT
    TGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCTCCGCCTGTGCCCAGCCCG
    GTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTT
    GGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCCTTTGGAAGAACAGCTTTCTCTCTGTCCTTGACTCTGGGGTCTGTGGG
    CCAGGGCATGAGTGTCTCTAGTAGTAGATCGGAGGGAAAGCTTGGTGACACACTTTACTGGG
    GTTTACCAAGCCTCAACTGACAGACCATAAACAGTCCACAGGCACCGTTCCTGGCAGGCCCA
    ACCCAAGGGAGTCTCTCCGAGAGCCTTCTGGGTGTGGCCTAACTTGCCAGGGGCCTGGCTCA
    GAGCTCCTCTGTGACTGTGACACTGAGCAG
    (CloneID 3938961)
    AATCAAGCTTCTTGGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGCAAGACTTGGAG SEQ ID NO:188
    TCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAA
    GGGAGAAGGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTG
    AAGAGAAGCCCGTGCCTCCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCC
    AGAACAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTCTCCTTGACTCTGTGGGTCTGTGGG
    CCAGTGGCATGAGTGTTTCTAGTACTAGATGGGAGGGAAAGCTTGGTCACACTTAGTACTGT
    GTTTTTAACGAAGAAATAATTGCTTCCAGATGTGTTAGAGGATCTTTCTACTGAGCTTTTTA
    ACACTTTACTGTGGGTTTACCAAGCCTCAATGGACAGACCATAAACACTCCACGAGGCACCG
    TTCCTGCCAGGCCCAACCCAAGAGGGAGTCTCTCCGAAGAGCCTTCTGTGGTGTTGGCCCTA
    ATTTGCCAGGTGGCCTTGGTCAGAGCTCCTCTGTGACTTGTGGACCATGGAAGGGCTGGGCT
    CTTGCTTGCGGCTGGAAACGAAAGAATGGCTTTATTTTTAACCTTAAAGTAGCAGATATGTA
    ACAAGATGGTGGCGTGTTACAA
    (CloneID 4345766)
    GAAGAAAATCAAGCTTCTTGGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGA SEQ ID NO:189
    CTTGGAGTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAG
    ATCTGAAGGGAGAAGGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGG
    CAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTCGCCCCGGCCCCAGT
    GCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTCTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGACCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCCTTTTGAAGAACAGGTTTCTCTCTGTCCTTCACTCTGGGGTCTGTGGG
    CCATGGCATGAGTGTTTCCTAGTAGTAGATGGGAGGGAAAGCTTTGTGACACTTAGTACTGT
    GTTTTTAAGAAGAAATAATTGGGTCCCAGATGTGTCAGAGGATCTTTGGTACTGAGGTTTTT
    AACACCTTTACTGTGCGTTTACCAAGCCTCAACTCGACAGACCATAAACAGTCCACAAGGCA
    CCGTCCTGCCAGGGCCGAACCACAGGGAGTCTCTCCGCAGAGGCTTCTGGTGTTGCCTACTT
    GCCAGTGGCCTTGTCAGAGCCTCTCCTGTGACATGTGAACACACGAAAAGCCTCGGCCACTG
    ACTTGAGTGTGAAGA
    (CloneID 3889866)
    TGGAGTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGAT SEQ ID NO:190
    CTGAAGGCAGAAGGTGATATTCATGAAAATGTGGACACACACTTGCCAGOCAGCCTGGGGCA
    GAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGC
    CATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGGGGTCTGTGGG
    CCATGGCATGAGTGTTTCCTAGTAGTAGATGGGAGGGAAAGCTTGGTGACACTTAGTACTGT
    GTTTTAAGAAGAAATAATTGGGTTCCAGATGTGTCAGAGGATCTTNGTACTGAGGTTTTAAC
    ACTTTACTTGGGTTTACCAAGCCTCAATGGACAGACCATAAACAGTCCACCAGGCACCGTTC
    CTGCCAGGCCAACCCAGAGGGAGTCTCTCCGCGAGAGCCTTCTGTGGTGGTGGCCCTAACTT
    GCAGTGGCTGGTCAGGAGCCCTCCCCTGTGACCTGTGACCCATGAAAGGCTGGGCTCTGCTG
    CCGCTGAAGAAAAACGCTCTTATTTTACCTAAAAGTCCATTTACCGACGCGCGGTGACCCAC
    TGTCCCCCAGAGGCGGGGTCACAACGCCCGACACACCGGCACGGGGCCCGAGGCGCCCAGGC
    CCGTCGAAACATGTGCGCCGAAACACCGGCGCAGGCCA
    (CloneID 4450834)
    TCTTAGATCTGAAGGGAGAAGGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGC SEQ ID NO:191
    CTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGC
    CCCAGTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGGGGTCTGTGGG
    CCAGTGGCATGAGTGTTTTCTAGTAGTAGATGGGAGGGAAACCTTGGTCACACTTAGTACTG
    TGTTTTTAAGAAGAAATAATTGGGTTCCAGATGTGTTAGAGGATCTTTGGTACTGAGGTTTT
    TAACACTTTACTGGCGTTTACCAAGCCTCAACTGGACAGACCATAAACAGTCCACAGGCACC
    GTTCCTGCCAGGCCCAACCCACAGGGAGTCTCTCCGAGAGCCTTCTGTGGTGTGGCCTAAAT
    TGCAGTGGCTTGTGTCAGAGCTCCTCCTGTGACATGTGACATGAAGAGGGCTCGGCTCCTGG
    CTTGGCGGCTGAAAGGAAAGAAACTGGCTTTATTTTTTAACCTTTAAAAGGTTGCGGATAGT
    AACAAGATTGGGTGGGTGATGAGAAGGCTTGGTCTCAGCAACAGAGGTGGTTCAATGAAATG
    CTGGATAAAAGCGTGACAG
    (CloneID 5521426)
    TTACCAACAGAACAACCTGTGAGGAAGAACAAAATGGCCTCTAATATCTTNTGGGACACNCT SEQ ID NO:192
    GAAGAAAATCAAGCTTCTTGGGCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGA
    CTTGGAGTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAG
    ATCTGAAGGGAGAACGTGATATTCATGAAAATGTGGACACAGACTTGCCAGGCAGCCTGGGG
    CAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGCCCCCAGT
    GCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAC
    CTCTGACTGTCCTGAACGCTCTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGG
    CCATGGCATGAGTGTTTTCTAGTACTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGT
    GTTTTTAAGAAGAAATAATTTGGTTCCAGATCTGTTAGAGGATCTTTTCTACTGAGGTTTTT
    AACACTTTACTTGGGTTTACCAAGCCTCAACTGGACAGACCATAAACAGTCCACACGCACCG
    TTCCTGCCAGGCCCCAACCCACAGGGAGTCTCTCCGCAAGCCCTTCTTGGTGTTGCCCTAAC
    TTGCCAGTGGCCCTTTGCTCAGAGCCTCCCTCCTGTGACATGTGGAAACATGAAAGAGGCCC
    TGCGCCCTCCCTGGCTTTTCCCGGCTTGCAAAGAAAAGAAACTGGCCCTTTTTATTTTTTTA
    ACCCTTTAAAAAGGAGGCCAGAATAAGTAACCAGAACTTGGCCTGGGCTTGATGTAAACCAA
    AGCCCTTTGGTTCTCCCACCCCAAAACGAAAAGGCTTTTGGGT
    (CloneID 5267723)
    AGCGGGCGTAGCCATTGGATCCGGAGACCGGATCGATCAGAGTTTTGCGGCCTCCAGGTGGT SEQ ID NO:193
    GGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTGTGAGGAAGAACAAAAT
    GGCCTCTAATATCTTTGGGACACCTGAAGAAAATCAAGCTTCTTGGCCCAAGTCAGCAGGTG
    CCAAGTCTAGTGGTGGCAGCGAAGACTTGGAGTCATCTGGACTGCAGAGAAGGAACTCCTCT
    CAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATGAAAATGTGGA
    CACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGC
    CCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGC
    CTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAACAAAGAAGCACTTTATGTACTGCT
    GTCTTTTTTTTTTTCCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGTGGGTCTGTC
    GGCCATGGCATGAGTGTTTCCTAGTAGTAGAT
    (CloneID 4441495)
    CAGGTGCCAAGTCTAGTGGTGGCAGCGAAGACTTGGAGTCATCTGGACTGCAGAGAAGGAAC SEQ ID NO:194
    TCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATGAAAA
    TCTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTCCTGCGC
    CTGTGCCCAGCCCGGTGGCCCCCGCCCCAGTGCCATCCACAAGAAATCCCCCTGGCGGCAAG
    TCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGGC
    CATGGCATGAGTGTTTTCTAGTAGTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGTG
    TTTTTAAGAGAAATAATTTGGTTCCAGATGTGTTAGAGGATCTTTGTACTGAGGTTTTTTAA
    CACTTTACTTGGGTTTACCAAGCCTCAATCTGGACAGACCATAAAACAGTCCACAGGCACCN
    GTTCCTTGCCAGGGCCCCAACCCACAGGGAGTCTCTCCCGGCAGAGCCTTTCTTGGTGTTTG
    CCTTAAATTGGCAAGTCGGCCTTGGTCAAAGCCTCTTCCTGTGCATGTGAACACTGGAAAGA
    GGCTGGGGCCTCCTGCCGTTGGCGGCTGGCAAAGAAAAAAGCCGTTTTTTTTACCTTAAAGT
    GCCCAAGTTAACAACGGGTGGTGTTGGAAACCTTGTTTCCCCAGAAGGGGGTGTGAAAAGGG
    GGGTACACAGGAACAGGGGAAGCACAGGTCTCTCAACAGAGCACG
    (CloneID 5395070)
    TGACCACAACCACCACCTTCAAGGGAGTCGACCCCAACAGCGAGGAATAGCTCCCGAGTTTT SEQ ID NO:195
    GCGGCCTCCAGGTGGTGGATCCAATTTTTCATTAGGTTTTGATGAACCAACAGAACAACCTG
    TGAGGAAGAACAAAATGCCCTCTAATATCTTTGGGACACCTCAAGAAAATCAAGCTTCTTGG
    GCCAAGTCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCA
    GAGAAGGAACTCCTCTCAAGCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATA
    TTCATGAAAATGTGGACACAGACTTGCCAGGCACCCTGGGGCAGAGTGAAGAGAAGCCCGTG
    CCTGCTGCGCCTGTGCCCAGCCCGGTGGCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCC
    TGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTACTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTCGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTATTCTTTCCCTTTTGAAGACCAGGTTTCTCTCTGTCCTTGACTCTGGGCTCTGTGGG
    CCATTGGCATGCAGTTGTCTCCTAGTACGTAGCATGGGCGGGAAACGCTTTGTGACCCCTTA
    CGTACTCCGCTTCCAAGAACGACATCATGGGGTCGCAGATTGTCGTAGAGGATCTTTGGCTA
    CCTGCCGCGTTCTTCACCGCCTTTTAACTGTGTGGTTATCCCAAGCCCTCCACTTGGACAGA
    ACCATTAACCATGCTCCACAGCGCACCGTCACTTGCAGGCCCAACCCCCAGGGGGGTCTTCC
    GAGAGACCTTTTGGTGTGCCTATTTGCCCAGGGCGTTGTCAACCCCCG
    (CloneID 3445695)
    GCAGAGTGAAGAGAAGCCCGTGCCTGCTGCGCCTGTGCCCAGCCCGGTCGCCCCGGCCCCTA SEQ ID NO:196
    GTGCCATCCAGAAGAAATCCCCCTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTCCTTTGGAAGAACAGGTTTCTCTCTGTCCTTGACTCTGGGGTCTGTGCGC
    CATGGCATGAGTGTTTTCTAGTACTAGATTGGCGGGAAAGCTTTGTGACACTTAGTACTGTG
    TTTTAAGAAGAAATAATTGGGTCCCAGATGTGTTAGAGGATCTTTGGTACTGAGGTTTTTAA
    CACTTTACTTGGGTTTACCAAGCCTCAACTGGACAGACCATAAACAGTCCACAGGCACCGTT
    CCTGCCAGGCCCCAACCCACACGGAGTCTCTCCGCAGAGCCTTCTTGGTGTTGCCCTAACTT
    CCCAGTGGCCTTGGCTCAGAGCCTCCTCCTGTGACCTGTGAACAATGAAGAGGCCTGTGCCT
    CTGCCTTGCCGCTGCAGGCACAGAACTGCCTTTACTTTTTAACCTTAAAAAGTAGCCGATAG
    TACAAGCTGGTTGGCTGTTGAAGCCAAGCCTGGGTCTCACGCCGAGTAAGGCTGCCTGTTCC
    CTGCACACTGGCGGGACCAAAAGCCGTGAACCAGGGGGCCATCCACTGTAAGCGGGTCTCCC
    GGAACGGGCCCCAAGGGTGTTGTTACACTACCCGCGGGGGTGCATAGCTGTGGCTGCCCTCA
    CGAAGCTCCTAACAGGTTTGCTCACCGGCGGGGCCTGAAAATC
    (CloneID 5519819)
    TCAGCAGGTGCCAAGTCTAGTGGTGGCAGGGAAGACTTGGAGTCATCTGGACTGCAGAGAAG SEQ ID NO:197
    GAACTCCTCTGAACCAAGCTCCGGAGACTTCTTAGATCTGAAGGGAGAAGGTGATATTCATG
    AAAATGTGGACACAGACTTGCCAGGCAGCCTGGGGCAGAGTGAAGAGAAGCCCGTGCCTGCT
    GCGCCTGTGCCCAGCCCGGTGCCCCCGGCCCCAGTGCCATCCAGAAGAAATCCCCCTGGCGG
    CAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACGCTGTCGTTCTGTCTGTTTCCTCCATGCTTGTGAACTGCACAACT
    TGAGCCTGACTGTACATCTCTTGGATTTGTTTCATTAAAAAGAAGCACTTTATGTACTGCTG
    TCTTTTTTTTTTTTCTTTTGAAGAACAGGTTTCTCTCTGTCCTTGACTCTTGGGTCTGTGGG
    CCATGGCATGAGTGTTTTCTAGTAGTAGATTGGAGGGAAAGCTTTGTGACACTTAGTACTGT
    GTTTTTAAGAAGACATAATTTGGTTCCAGATGTGTTAGAGGATCTTTTGTACTGAGGTTTTT
    AACACTTTACCTTGGGTTTACCAAGCCTTCCACTGGACAGGACCATAAACAGGTCCACAGGC
    CCCCCGTTTCTTGCCCAGGCCCCAACCCACAGGGGAAGTCTCTTCCGCCACAAACCCTTCCT
    TTGGTCGCCCGCCCTTACCACCTGCCCCCGGCGGGGCTCTTTATGCTTTGGCGGAGCTCTCT
    CCTCTCCTTCATTCGAAGACATGCTGACCAACAACCACGGCCACACCAACGCCCCTCTCTAT
    CTTTCTCATTGCGCCCCTGCGCCCTGTATTGAGCGCGCCCTCAGAATTCGCGGGGCATACAG
    GGCGCGCTGTCAATCCCCGAAACTCCAATATCGGTCTCCCCCCCGCTTTATATTAGCGCGCC
    CCGTCGCTTGTAACGAGCCTAACTCAATTTTTTTTTCCCGCACTCACGCCCCGCTCTCGGTG
    TTACCAACCAACAGAACAGTCCTCCTCCTTCATAATATTCCCCACACTCCCCCTCGCCATCT
    TACTCTTTTATTTNCCCCGCGCGCGTGTTAAAAGCCGCAAAGGNNCCCCCACCGCACACACG
    TATATTGCCCGGATTTTAATCATGAATTTTCCGCACCGGGCAAGACCACCCCCAGCTGCCCC
    ATCGTGTCCCCCGCCGTNCTGCAGAATTCCTCANATCTGGGCCCTCCGCGATAGGTCACTCC
    ATCCTCAGGAGAAAACACCCTCTTGTCCCACGCCGTCCACTCTTAATACCGCCGTACCCTCA
    TGTCCCCTCCGCCACTTCTTTTTACCCCCTCNGCGCTGTAGTTTTGCGGCGCCCCGACTACA
    CTCACACCGATTATTTATTATCCCCCTTCANCCGACGCCGGNNGCCCCGAAAAAATGCCGCC
    CCGGATCGATAACAGCTCACCCCCGCCCCCGCCAGGATGCCCCGCCGCCAGCTAAAAGGCGC
    TCAACCA
    (CloneID 2989794)
    CACGAGCACTGATGCCCAAGAGTTAAATGGCCTCTAATATCTTTGGGACACCATGAAGAAAA SEQ ID NO:198
    TCAAGACTTCTTGGGCCAAGTCAACAGGTGCCAAGTCTAGTGGTGGAAGGGAAGACTTGTGA
    GTCATCTGGACTGCAGAGAAGGAACTCCTCTGAAGCAAGCTCCGGAGACTTCTTAGATCTGA
    AGGGAGAAGGTGATATTCATGAAAATGTGAGACACAGACTTGCCAGTGCAGCCTGGCGCAGA
    GTGAAGAGAAGCCCTGTGCCTGCTGCTGCCTGTGCCCAGCCCTGGTGGACCCAGGCCCCAGT
    GCCATCCAGAAGAAATCCCCACTGGCGGCAAGTCCAGCCTCGTCTTGGGTTAG
    CTCTGACTGTCCTGAACTGCTAGTCAGATATCTAGTCTGTAACCTCCATGCTTGTGAACTGC
    ACAACTTGAGCCTGACTGTACATCTCTTGGAATTTGTTTCATTAAAAAAAAGCACTTATATG
    TACTGCTGTCTTTATTATTAATATACTTTGTGCAAGAACAGGTAAACACATCTGACACATTG
    ACCTCTGTGGACTCTGTGAGAGCCATAGGCATTGAGTTGTGAACTAGCTAGATACATGGCGA
    GGGAACAGCTTTGTGAACACTAAGAACTCAGATCATAACGACAAAATACATGGGTCCAGATG
    TGTAGAGGATCTAAGGAAATGAGGTATAAAACTAACTTGGTTTCCAAGCTCAATGGGCGACA
    (CloneID 1637898 in 3′ to 5′ orientation)
    AAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAAGTTGTGCAGT SEQ ID NO:199
    TCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACCAGGCTGGACTTGCCGCCAGGGGGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCCACCGGCCTGGGCACAGGCGCAGCAGGCACGGCCTTCTCTTCACTCTGCCCCAGGCTG
    CCTGGCAAGTCTGTGTCCACATTTTCATCAATATCACCTTCTCCCTTCAGATCTAAGAAGTC
    TCCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCTTCCCTGC
    CACCACTAGACTTGGCACCTGCTGACTTGGCCCAAGAAGCTTGATTTTCTTCAGGTGTCCCA
    AAGATATTAGAGGCCATTTTGTTCTTCCTCACAGGTTGTTCTGTTGGTTCATCAAAACCTAA
    TGAAAAATTGGATCCACCACCTGGAGGCCGCAAAACTCGGGAGCTATTCCTGCTGTTGGGGT
    CGACTCCCTTGAAGGTGGT
    (CloneID 1132042 in 3′ to 5′ orientation)
    TTTTTTTAAAGTGCTTCTTTTTAATGAAACAAATCCAAGAGATGTACAGTCAGGCTCAAGTT SEQ ID NO:200
    GTGCAGTTCACAAGCATGGAGGAAACAGACAGAACGACAGCGTTCAGGACAGTCAGAG
    CTAACCCAAGACGAGGCTGGACTTCCCGCCAGGGAGATTTCTTCTGGATGGCACTGGGGCCG
    GGGCACCGGGCTGGGCACAGGCGCACGAGGCACGGGCTTCTCTTCACTCTGCCCCACGCTGC
    CTGGCAAGTCTGTGTCCACATTTTCATGAATATCACCTTCTCCCTTCAGATCTAAGAAGTCT
    CCGGAGCTTGCTTCAGAGGAGTTCCTTCTCTGCAGTCCAGATGACTCCAAGTCT
  • In another set of preferred embodiments of the invention, the sequence, or a unique portion thereof, of the ESE-2/ELF5 sequences identified by the I.M.A.G.E. Consortium CloneIDs 1864302 and 4480123 as well as clusters C019657 and NM[0054] —001422 may be used. Similarly, sequences from the UniGene Homo sapiens cluster Hs.11713, may be used. ESE-2/ELF5 sequences are useful in discriminations between normal and ADH or DCIS or IDC breast cells based upon decreased expression in non-normal breast cells. Human ESE-2/ELF5 has been mapped to 11p13-p15.
  • ESE-2/ELF5 related sequences are as follows, with the assigned coding region (ending with a termination codon) underlined and preceded by the 5′ untranslated and/or non-coding region and followed by the 3′ untranslated and/or non-coding region. The 3′ untranslated and/or non-coding regions are presented as the complementary strand in the 3′ to 5′ direction for some of the sequences. [0055]
  • SEQ ID NOS:204-209 are found in the 3′ untranslated and/or non-coding regions of the disclosed ESE-2/ELF5 sequences. [0056]
    (CloneID 4480123, ESE-2b/ELF5)
    CACAAGGCTACAGGTGTCTTTATTTCCACTGCACGCTGGTGCTGGGAGCGCCTGCCTTCTCT SEQ ID NO:201
    TGCCTTGAAAGCCTCCTCTTTGGACCTAGCCACCGCTGCCCTCACGGTA
    ATGTTGGACTCGGTGACACACAGCACCTTCCTGCCTAATGCATCCTTCTGCGATCCCCTGAT
    GTCGTGGACTGATCTGTTCAGCAATGAAGAGTACTACCCTGCCTTTGAGCATCAGACAGCCT
    GTGACTCATACTGGACATCAGTCCACCCTGAATACTGGACTAAGCGCCATGTGTGGGAGTGG
    CTCCAGTTCTGCTGCGACCAGTACAAGTTGGACACCAATTGCATCTCCTTCTGCAACTTCAA
    CATCAGTGGCCTGCAGCTGTGCAGCATGACACAGGAGGAGTTCGTCGAGGCAGCTGGCCTCT
    GCGGCGAGTACCTGTACTTCATCCTCCAGAACATCCGCACACAAGGTTACTCCTTTTTTAAT
    GACGCTGAAGAAAGCAAGGCCACCATCAAAGACTATGCTGATTCCAACTGCTTCAAAACAAG
    TGGCATCAAAAGTCAAGACTGTCACAGTCATAGTAGAACAAGCCTCCAAAGTTCTCATCTAT
    GGGAATTTGTACGAGACCTGCTTCTATCTCCTGAAGAAAACTGTGGCATTCTGGAATGGGAA
    GATAGGGAACAAGGAATTTTTCGGGTGGTTAAATCGGAAGCCCTGGCAAAGATGTGGGGACA
    AAGGAAGAAAAATGACAGAATGACATATGAAAAGTTGAGCAGAGCCCTGAGATACTACTATA
    AAACAGGAATTTTGGAGCGGGTTGACCGAAGGTTAGTGTACAAATTTGGAAAAAATGCACAC
    GGGTGGCAGGAAGACAAGCTATGA
    TCTGCTCCAGGCATCAAGCTCATTTTATGGATTTCTGTCTTTTAAAACAATCAGATTGCAAT
    AGACATTCGAAAGGCTTCATTTTCTTCTCTTTTTTTTTTAACCTGCAAACATGCTGATAAAA
    TTTCTCCACATCTCAGCTTACATTTGGATTCAGAGTTGTTGTCTACGGAGGGTGAGAGCAGA
    AACTCTTAAGAAATCCTTTCTTCTCCCTAAGGGGATGAGGGGATGATCTTTTGTGGTGTCTT
    GATCAAACTTTATTTTCCTAGAGTTGTGGAATGACAACAGCCCATGCCATTGATGCTGATCA
    GAGAAAAACTATTCAATTCTGCCATTAGAGACACATCCAATGCTCCCATCCCAAAGGTTCAA
    AAGTTTTCAAATAACTGTGGCAGCTCACCAAAGGTGGGGGAAAGCATGATTAGTTTGCAGGT
    TATGGTAGGAGAGGGTGAGATATAAGACATACATACTTTAGATTTTAAATTATTAAAGTCAA
    AAATCCATAGAAAAGTATCCCTTTTTTTTTTTTTTGAGACGGGTTCTCACTATGTTGCCCAG
    GGCTGGTCTTGAACTCCTATGCTCAAGTGATCCTCCCACCTCGGCCTCCCAAAGTACTGTGA
    TTACAAGCGTGAGCCACGGCACCTGGGCAGAAAAGTATCTTAATTAATGAAAGAGCTAAGCC
    ATCAAGCTGGGACTTAATTGGATTTAACATAGGTTCACAGAAAGTTTCCTAACCAGAGCATC
    TTTTTGACCACTCAGCAAAACTTCCACAGACATCCTTCTGGACTTAAACACTTAACATTAAC
    CACATTATTAATTGTTGCTGAGTTTATTCCCCCTTCTAACTGATGGCTGGCATCTGATATGC
    AGAGTTAGTCAACAGACACTGGCATCAATTACAAAATCACTGCTGTTTCTGTGATTCAAGCT
    GTCAACACAATAAAATCGAAATTCATTGATTCCATCTCTGGTCCAGATGTTAAACGTTTATA
    AAACCGGAAATGTCCTAACAACTCTGTAATGGCAAATTAAATTGTGTGTCTTTTTTGTTTTG
    TCTTTCTACCTGATGTGTATTCAAGTGCTATAACACGTATTTCCTTGACAAAAATAGTGACA
    GTGAATTCACACTAATAAATGTTCATAGGTTAAAGTCTGCACTGACATTTTCTCATCAATCA
    CTGGTATGTAAGTTATCAGTGACTGACAGCTAGGTGGACTGCCCCTAGGACTTCTGTTTCAC
    CAGAGCAGGAATCAAGTGGTGAGGCACTGAATCGCTGTACAGGCTGAAGACCTCCTTATTAG
    AGTTGAACTTCAAAGTAACTTGTTTTAAAAAATGTGAATTACTGTAAAATAATCTATTTTGG
    ATTCATGTGTTTTCCAGGTGGATATAGTTTGTAAACAATGTGAATAAAGTATTTAACATGTA
    AAAAAAAAAAAAAA
    (ESE-2a)
    GGCTGAGTGGTTTGCTCCTTCCCCTCTCTCTGGGAGGCTGAGCAGGGGTGCCTGGGTTGCTC SEQ ID NO:202
    AGGCCATGGGAGCCACACCTGTTATTGCTGCCTCTGATTTGTGTGACACTGAGAAGCCCACA
    GGCCTGTCCCTCCAACTCGGTGGACCCTCTCTGTGTGCATTTGGTGTGTGAGCCAGCTCTGA
    GAAGGGTTCAGAAGCCACTGGAGGCATCTGGGGACCTCAGCTTCC
    ATGCCATCTCTGCCTCACTCCCACAGGGTAATGTTGGACTCGGTGACACACAGCACCTTCCT
    GCCTAATGCATCCTTCTGCGATCCCCTGATGTCGTGGACTGATCTGTTCAGCAATGAAGAGT
    ACTACCCTGCCTTTGAGCATCAGACAGCCTGTGACTCATACTGGACATCAGTCCACCCTGAA
    TACTGGACTAAGCGCCATGTGTGGGAGTGGCTCCAGTTCTGCTGCGACCAGTACAAGTTGGA
    CACCAATTGCATCTCCTTCTGCAACTTCAACATCAGTGGCCTGCAGCTGTGCAGCATGACAC
    AGGAGGAGTTCGTCGAGGCAGCTGGCCTCTGCGGCGAGTACCTGTACTTCATCCTCCAGAAC
    ATCCGCACACAAGGTTACTCCTTTTTTAATGACGCTGAAGAAAGCAAGGCCACCATCAAAGA
    CTATGCTGATTCCAACTGCTTGAAAACAAGTGGCATCAAAAGTCAAGACTGTCACAGTCATA
    GTAGAACAAGCCTCCAAAGTTCTCATCTATGGGAATTTGTACGAGACCTGCTTCTATCTCCT
    GAAGAAAACTGTGGCATTCTGGAATGGGAAGATAGGGAACAAGGAATTTTTCGGGTGGTTAA
    ATCGGAAGCCCTGGCAAAGATGTGGGGACAAAGGAAGAAAAATGACAGAATGACGTATGAAA
    AGTTGAGCAGAGCCCTGAGATACTACTATAAAACAGGAATTTTGGAGCGGGTTGACCGAAGG
    TTAATGTACAAATTTGGAAAAAATGCACACGGGTGGCAGGAAGACAAGCTATGA
    TCTGCTCCAGGCATCAAGCTCATTTTATGGATTTCTGTCTTTTAAAACAATCAGATTGCAAT
    AGACATTCGAAAGGCTTCATTTTCTTCTCTTTTTTTTTAACCTGCAAACATGCTGATAAAAT
    TTCTCCACATCTCAGCTTACATTTGGATTCAGAGTTGTTGTCTACGGAGGGTGAGAGCAGAA
    ACTCTTAAGAAATCCTTTCTTCTCCCTAAGGGGATGAGGGGATGATCTTTTGTGGTGTCTTG
    ATCAAACTTTATTTTCCTAGAGTTGTGGAATGACAACAGCCCATGCCATTGATGCTGATCAG
    AGAAAAACTATTCAATTCTGCCATTAGAGACACATCCAATGCTCCCATCCCAAAGGTTCAAA
    AGTTTTCAAATAACTGTGGCAGCTCACCAAAGGTGGGGGAAAGCATGATTAGTTTGCAGGTT
    ATGGTAGGAGAGGGTGAGATATAAGACATACATACTTTAGATTTTAAATTATTAAAGTCAAA
    AATCCATAGAAAAGTATCCCTTTTTTTTTTGAGACGGGTTCTCACTATGTTGCCCAGGGCTG
    GTCTTGAACTCCTATGCTCAAGTGATCCTCCCACCTCGGCCTCCCAAAGTACTGTGATTACA
    AGCGTGAGCCACGGCACCTGGGCAGAAAAGTATCTTAATTAATGAAAGAGCTAAGCCATCAA
    GCTGGGACTTAATTGGATTTAACATAGGTTCACAGAAAGTTTCCTAACCAGAGCATCTTTTT
    GACCACTCAGCAAAACTTCCACAGACATCCTTCTGGACTTAAACACTTAACATTAACCACAT
    TATTAATTGTTGCTGAGTTTATTCCCCCTTCTAACTGATGGCTGGCATCTGATATGCAGAGT
    TAGTCAACAGACACTGGCATCAATTACAAAATCACTGCTGTTTCTGTGATTCAAGCTGTCAA
    CACAATAAAATCGAAATTCATTGATTCCATCTCTGGTCCAGATGTTAAACGTTTATAAAACC
    GGAAATGTCCTAACAACTCTGTAATGGCAAATTAAATTGTGTGTCTTTTTTGTTTTGTCTTT
    CTACCTGATGTGTATTCAAGCGCTATAACACGTATTTCCTTGACAAAAATAGTGACAGTGAA
    TTCACACTAATAAATGTTCATAGGTTAAAGTCTGCACTGACATTTTCTCATCAATCACTGGT
    ATGTAAGTTATCAGTGACTGACAGCTAGGTGGACTGCCCCTAGGACTTCTGTTTCACCAGAG
    CAGGAATCAAGTGGTGAGGCACTGAATCGCTGTACAGGCTGAAGACCTCCTTATTAGAGTTG
    AACTTCAAAGTAACTTGTTTTAAAAAATGTGAATTACTGTAAAATAATCTATTTTGGATTCA
    TGTGTTTTCCAGGTGGATATAGTTTGTAAACAATGTGAATAAAGTATTTAACATGCGAA
    (alternative ELF5 encoding sequence)
    CAAGGCTACAGGTGTCTTTATTTCCACTGCACGCTGGTGCTGGGAGCGCCTGCCTTCTCTTG SEQ ID NO:203
    CCTTGAAAGCCTCCTCTTTGGACCTAGCCACCGCTGCCCTCACGGTA
    ATGTTGGACTCGGTGACACACAGCACCTTCCTGCCTAATGCATCCTTCTGCGATCCCCTGAT
    GTCGTGGACTGATCTGTTCAGCAATGAAGAGTACTACCCTGCCTTTGAGCATCAGACAGCCT
    GTGACTCATACTGGACATCAGTCCACCCTGAATACTGGACTAAGCGCCATGTGTGGGAGTGG
    CTCCAGTTCTGCTGCGACCAGTACAAGTTGGACACCAATTGCATCTCCTTCTGCAACTTCAA
    CATCAGTGGCCTGCAGCTGTGCAGCATGACACAGGAGGAGTTCGTCGAGGCAGCTGGCCTCT
    GCGGCGAGTACCTGTACTTCATCCTCCAGAACATCCGCACACAAGGTTACTCCTTTTTTAAT
    GACGCTGAAGAAAGCAAGGCCACCATCAAAGACTATGCTGATTCCAACTGCTTGAAAACAAG
    TGGCATCAAAAGTCAAGACTGTCACAGTCATAGTAGAACAAGCCTCCAAAGTTCTCATCTAT
    GGGAATTTGTACGAGACCTGCTTCTATCTCCTGAAGAAAACTGTGGCATTCTGGAATGGGAA
    GATAGGGAACAAGGAATTTTTCGGGTGGTTAAATCGGAAGCCCTGGCAAAGATGTGGGGACA
    AAGGAAGAAAAATGACAGAATGACATATGAAAAGTTGAGCAGAGCCCTGAGATACTACTATA
    AAACAGGAATTTTGGAGCGGGTTGACCGAAGGTTAGTGTACAAATTTGGAAAAAATGCACAC
    GGGTGGCAGGAAGACAAGCTATGA
    TCTGCTCCAGGCATCAAGCTCATTTTATGGATTTCTGTCTTTTAAAACAATCAGATTGCAAT
    AGACATTCGAAAGGCTTCATTTTCTTCTCTTTTTTTTTAACCTGCAAACATGCTGATAAAAT
    TTCTCCACATCTCAGCTTACATTTGGATTCAGAGTTGTTGTCTACGGAGGGTGAGAGCAGAA
    ACTCTTAAGAAATCCTTTCTTCTCCCTAAGGGGATGAGGGGATGATCTTTTGTGGTGTCTTG
    ATCAAACTTTATTTTCCTAGAGTTGTGGAATGACAACAGCCCATGCCATTGATGCTGATCAG
    AGAAAAACTATTCAATTCTGCCATTAGAGACACATCCAATGCTCCCATCCCAAAGGTTCAAA
    AGTTTTCAAATAACTGTGGCAGCTCACCAAAGGTGGGGGAAAGCATGATTAGTTTGCAGGTT
    ATGGTAGGAGAGGGTGAGATATAAGACATACATACTTTAGATTTTAAATTATTAAAGTCAAA
    AATCCATAGAAAAGTATCCCTTTTTTTTTTGAGACGGGTTCTCACTATGTTGCCCAGGGCTG
    GTCTTGAACTCCTATGCTCAAGTGATCCTCCCACCTCGGCCTCCCAAAGTACTGTGATTACA
    AGCGTGAGCCACGGCACCTGGGCAGAAAAGTATCTTAATTAATGAAAGAGCTAAGCCATCAA
    GCTGGGACTTAATTGGATTTAACATAGGTTCACAGAAAGTTTCCTAACCAGAGCATCTTTTT
    GACCACTCAGCAAAACTTCCACAGACATCCTTCTGGACTTAAACACTTAACATTAACCACAT
    TATTAATTGTTGCTGAGTTTATTCCCCCTTCTAACTGATGGCTGGCATCTGATATGCAGAGT
    TAGTCAACAGACACTGGCATCAATTACAAAATCACTGCTGTTTCTGTGATTCAAGCTGTCAA
    CACAATAAAATCGAAATTCATTGATTCCATCTCTGGTCCAGATGTTAAACGTTTATAAAACC
    GGAAATGTCCTAACAACTCTGTAATGGCA
    (CloneID 377520)
    CAGACACTGGCATCAATTACAAAATCACTGCTGTTTCTGTGATTCAAGCTGTCAACACAATA SEQ ID NO:204
    AAATCGAAATTCATTGATTCCATCTCTGGTCCAGATGTTAAACGTTTATAAAACCGGAAATG
    TCCTAACAACTCTGTAATGGCAAATTAAATTGTGTGTCTTTTTTGTTTTGTCTTTCTACCTG
    ATGTGTATTCAAGCGCTATAACACGTATTTCCTTGACAAAAATAGTGACAGTGAATTCACAC
    TAATAAATGTTCATAAGGTTAAAGTCTGCACTGACATTTTCTCATCAATCACTGGTATGTAA
    GTTATCAGTGACNGACAGCTAAGGTGNGACTGG
    (CloneID 377520 in 3′ to 5′ orientation)
    GAACATGTTAAATACTTTATTCACATTGTTTACAAACTATATCCACCTGGAAAACACATGAA SEQ ID NO:205
    TCCAAAATAGATTATTTTACAGTAATTCACATTTTTTAAAACAAGTTACTTTGAAGTTCAAC
    TCTAATAAGGAGGTCTTCAGCCTGTACAGCGATTCAGTGCCTCACCACTTGATTCCTGCTCT
    GGTGAAACAGAAGTCCTAGGGGCAGTCCACCTAG
    (CloneID 81671)
    TGATTCAAGCTGTCAACACAATAAAATCGAAATTCATTGATTCCATCTCTGGTCCAGATGTT SEQ ID NO:206
    AAACGTTTATAAAACCGGAAATGTCCTAACAACTCTGTAATGGCAAATTAAATTGTGTGTCT
    TTTTTGTTTTGTCTTTCTACCTGATGTGTATTCAAGCGCTATAACAC
    (CloneID 81671 in 3′ to 5′ orientation)
    GCGGTGAAATACTTTATTCACATTGTTTACAAACTATATCCACCTGGAAAACACATGAATCA SEQ ID NO:207
    AAATAGATTATTTTACAGTAATNACATTTTTTAAAACAAGTTACTTTGAAGTCAACTCTAAT
    AAGGAGGTCTTCAGCCTGTACAGCGATTCAGTGCCTCACCACTTGATTCCTGCTCTGGTGAA
    CAGAAGTCCTAGGGGCAATCCACCTAGCTGTCAGTCACTGATAACTTACATACCAGTGATTG
    ATGAGAAAATGTCAGTGCAGACTTTAACCTATGAACATTTATTAGTGTGAATTCACTGTCAC
    TATTTTTGTCAAGGAAATACGTGTTATAGCGCTTGAATACACATCAGGTAGAAAGACAAANC
    AAAAAAGNCACACAATTTAATTTGCCATTACAGAGTTGTTAGGGCCATTTCCGGTTTTATAA
    ACGTTTACATCTGGGCCNGAGATGGGATCAATGAATTTCGNTTTTATTGTGTTGACCGCTTG
    NATCACCTCGTGCCGATTTCCTGCGGCCCGGGGNTCCCCTAGTT
    (CloneID 2956497 in 3′ to 5′ orientation)
    AGACGGGTTCTCACTATGTTGCCCAGGGCTGGTCTTGAACTCCTATGCTCAAGTGATCCTCC SEQ ID NO:208
    CACCTCGGCCTCCCAAAGTACTGTGATTACAAGCGTGAGCCACGGCACCTGGGCAGAAAAGT
    ATCTTAATTAATGAAAGAGCTAAGCCATCAAGCTGGGACTTAATTGGATTTAACATAGGTTC
    ACAGAAAGTTTCCTAACCAGAGCATCTTTTTGACCACTCAGCAAAACTTCCACAGACATCCT
    TCTGGACTTAAACACTTAACATTAACCACATTATTAATTGTTGCTGAGTTTATTCCCCCTTC
    TAACTGATGGCTGGCATCTGATATGCAGAGTTAGTCAACAGACACTGGCATCAATTACAAAA
    TCACTGCTGTTTCTGTGATTCAAGCTGTCAACACAATAAAATCGAAATTCATTGATTCCATC
    TCTGGTCCAGATGTTAAACGTTTATAAAACCGG
    (CloneID 1864302 in 3′ to 5′ orientation)
    TGAACATGTTAAATACTTTATTCACATTGTTTACAAACTATATCCACCTGGAAAACACATGA SEQ ID NO:209
    ATCCAAAATAGATTATTTTACAGTAATTCACATTTTTTAAAACAAGTTACTTTGAAGTTCAA
    CTCTAATAAGGAGGTCTTCAGCCTGTACAGCGATTCAGTGCCTCACCACTTGATTCCTGCTC
    TGGTGAAACAGAAGTCCTAGGGGCAGTCCACCTAGCTGTCAGTCACTGATAACTTACATACC
    AGTGATTGATGAGAAAATGTCAGTGCAGACTTTAACCTATGAACATTTATTAGTGTGAATTC
    ACTGTCACTATTTTTGTCAAGGAAATACGTGTTATAGCACTTGAATACACATCAGGTAGAAA
    GACAAAACAAAAAAGACACACAATTTAATT
    (ESE-2 promoter 1, positions 1-1046, and 5′ untranslated region of ESE-2b,
    positions 1047 to >1106)
    TTCAATCCCACTTCCTCCTTTTGCCACTGGGGAAAAATGAAGCCCAGAGAAGTCCAGGTTAC SEQ ID NO:210
    CCAGCCAAGATAGGGGTCTAGGCAGTCACCTATCTTCCTTCAACAATTTTTCCATGATGACA
    CCCCGAATCCTCTCACGAACTGCCTTTTGTTTCTGCAGACTATATGCGTATTTGTATTTGTG
    TGTTTGTAACCATGCCCGGTGATCCCAAGAAAACATAACAAACCAGTCCTTGCTTTCGCTTT
    AAAGCTTGGAGTCTGCCATTTGAATACAACATCTCGGCTGCCCAAGATGGCTAGAAGCAGAA
    TGCAAAAAGGCACAAGGGTTATAAATACCTGTCTCATAGATGACCCGGGACACTTGTGCTTT
    GCAGCCTAAATTAGGCAGAGTTTCTGTTGTCACGGAGAAGTACTAAAAAGCGGGCAGTTCTC
    AGCGAGACACCTTGAGAGGCTGGCATCCACATGAGGAGAGGCCCCATCACTTACATTACACT
    CATGAAGCCCAAGAGATGTTAAGCTACATTTTTCTAGGTAGCACAGCTAGGAAATGATGGAC
    ACTGAATTTTGAATCTAAAGGCAACTAGCTGCAAAACCTGAGGTCTCAACACTGGGCCTATA
    ATGCTCTTCCTTCTCACCACATGGGAAAAACGGAGAAAGACATGATCTTACAAAAGCACTGG
    GCTCAGCCAGCCTGGGAGAGAGGCAGCGCAAACCGGCACCAGGGTGGAATCTCTGTGTTTCC
    CCTCCAGCTTGCACAGAGGAAAATTCCTCACCAAACGCACGATCCCCGCACAGCTTCCCAGG
    GACAAGAATTTTCTGCTTGTTTACTGAGTCCCCTGGGCTGGGAGTGGGGGGTTTGCAGGGCA
    GGGGTGAGCTGCGCACAAAAGCAGGATAAAGGTAAACTTTCTGCATATGAGAACCATTTCCC
    CCCCTCCATAGGAGCCGTGTCACACTGTATGTCACCGTCATCAAAGGGGCTGTGCGTAAACC
    TGAAAAACCAAACGGACCTGTCTGTAGGTGTCACTTATATCACAAGGTACAGGTGTCTTTAT
    TTCCACTGCACGCTGGTGCTGGGAGCGCCTGCCTTCTCTTGCCTTGAAAGCC
    (ESE-2 promoter 2, positions 1-1879, and 5′ untranslated region of ESE-2a,
    positions 1080 to >1975)
    GTAAGCGCCTTTTCTTTGCTTTTTTGGATGAATCGTAAGGGGTGTCAGGGCTCAGAGGCTCG SEQ ID NO:211
    GCCTGGGGCCTGGGTCTGCTCGTCCATCTCCAGCTCCAGGGCCGGCACCTGCGCTGGGTGCA
    GTCCCAGGGCCTCCGGGAGCTGTTTGACACGGATGTGACGGCTTGCCTCAGAGAGACCTGCT
    TGCCTCCGCAGGCCGTGTGGCCACCAGCCCTCCTCACAGCCACCACTCCCTCTGGATCCCTT
    AGCTGAACCAAGGGGAATTAAGAGAACGCGCCCAGGCGCTCAGTTCTCTATCCTCCCTAAAG
    CTTCTTTAGGAAGGGAAGCTGGATTTTACTCAGAAAAATATTCAGCTTCAAGGAAAGCCCCC
    CACCTACCCTTCTCCCCTGACTGAATTCCTTTCCCCACCGGCCTGCCCACTGTCCCCCACCC
    CCTCGATACAAAGAACTCCCTTATTATAGTTTGGGGCATTTTCAGGAATTTGTACAAAACAG
    TTTTAAAAGAAACCCATTTGCCCTCTGACATCTTCCCCAGAAGAGAATGCTTCCAGAAAAGC
    AATGGTTAGCGTTTTTCCACTGTGTTCTCAGGCCTTGTCAGACTCTGCAGTGTGTGGGGTTT
    CTGTGGGGTTGCCCCCTGCTGACAGCGACAGGTAGCACAAGCTCCCTCCTCAGGCTGAAGCC
    GGGCCTGCGTGTGGATGCCTTTTGTACGCCCGAAAGTGTGTCAGACATCACTAGGTGCAATC
    GCTTCATGTTACAGATGAGGAAACTGAGGCCAGAAAGGCTAGATGACTTAGGGAGGCAGCTC
    TGTGGTTCAGTCTAGTCCAGAGACCCAGGGAAAGGGGTGGTTTGCCCATCCGAGTGAACGGC
    TTGATTCTGTTGTCTTCGTGTTCTCTGCAATACTGTTTTTCATAATCTAAGGTATTCTCGGG
    CCGGAGTTTTCAGTTTGGTCATCTCCCTTTTTCAGAAGTCACCAGAGTGGCAAATTTTTAGA
    TTCATTGTTGATGGCTGATTTTTCCCTCTAAAACAGGATTGAATATATGTATTATGCCCCGT
    CCTTTGCATATATCGGATTGCATGATTTAAAAAAAAAAAAATCCCCATTTTAGAGATGAGGG
    AAACCGTAGTTCGAAGAGGGGCATGAATATTTATATACCACATCTATATGAAAAAAAGCTTA
    AGAATTTCAGCAGTCTGGGTAGTAAGAAATGTGCCCCACGTTCGCAGCAGCAGAGGTAGGAT
    TTAACCCCTGATATATGTAATCCAAAACTGGTAAGCTTTGCATCGAAGCCTACAGCAAACTA
    CATGGCATACCTTTTTGGATCTTCGCTGCACCTTCAGAAAAACAGCTACAAACAAACAAACA
    CGCAAACTCCCTAAGCGAGCTAAAGAAAAATGAGGAATCACTTGACAAGAGGTCAGCAAATT
    GGTTCTCACAGTTGCTAGGGTTCCTCTCAGAAGAACAAACCCTCAAGCACCCACCCTCAATC
    TTTCTTTAGCAGTAAGTGTTGAAATACTCCACTGGGTTCTCCTCAGTGGGCCCCTTCTTAGG
    GAGGTCCAAGGGCTGGGAAATTGACCCTCCCTTGCTCACAAGTCTTGGGACGGAGTGGACAT
    TTGGGTATCACTGAGGCTTTAAGGAAGGAAAACCGATTTTCTTCCCAATGATACCACTCAGA
    GGGTGGGGTTGAGGAAGCCCAATCTTGGCCACTTTTTTCTATATTTTGCACCCTATGGCCTA
    GTTCTGCCCAGTGATGATTCGGCCCGTAAACAGCCAATGTGTAGATGCTTAATTGGGCCAAT
    TTTTGGTCACATGCCCAGAGTGAAGTTGATGATCACCACCAGAGTCAGGAAGGAATTTTCCT
    CCTCTGGCAAACTGGCCAAGGCTGAGTGGTTTGCTCCTTCCCCTCTCTCTGGGAGGCTGAGC
    AGGGGTGCCGGGTTGCTCAGGCCATGGGAGCCACACCTGTTATTGCTGCCTCT
  • All sequences are provided using conventional representations of a DNA strand starting from the 5′ phosphate linked end to the 3′ hydroxyl linked end. The above assignment of coding regions is generally by comparison to available consensus sequence(s) and therefore may contain inconsistencies. These have no effect on the practice of the invention because the invention can be practiced by use of shorter segments (or combinations thereof) of sequences unique to each of the three sets described above and not affected by inconsistencies. As a non-limiting example, a segment of CRIP1 composed of a 3′ untranslated region sequence and a sequence from the 3′ end of the coding region may be used as a probe for the detection of CRIP1 expression without being affected by the presence of any inconsistency in the representations of the coding regions provided above. Similarly, the use of an antibody which specifically recognizes CRIP1 protein to detect its expression would not be affected by the presence of any inconsistency in the representation of the coding regions provided above. [0057]
  • As will be appreciated by those skilled in the art, some of the above sequences include 3′ poly A (or poly T on the complementary strand) stretches that do not contribute to the uniqueness of the disclosed sequences. The invention may thus be practiced with sequences lacking the 3′ poly A (or poly T) stretches. The uniqueness of the disclosed sequences refers to the portions or entireties of the sequences which are found only in CRIP1, HN1, and ESE-2/ELF5 nucleic acids. Preferred unique sequences for the practice of the invention are those which contribute to the consensus sequences for each of the three sets. These preferred unique sequences are of the lengths of polynucleotides of the invention as discussed herein. [0058]
  • To determine the (increased or decreased) expression levels of the above described sequences in the practice of the present invention, any method known in the art may be utilized. In one preferred embodiment of the invention, expression based on detection of RNA which hybridizes to polynucleotides containing the above described sequences is used. This is readily performed by any RNA detection or amplification+detection method known or recognized as equivalent in the art such as, but not limited to, reverse transcription-PCR (optionally real-time PCR), the methods disclosed in U.S. patent application Ser. No. 10/062,857 entitled “Nucleic Acid Amplification” filed on Oct. 25, 2001 as well as U.S. Provisional Patent Application Nos. 60/298,847 (filed Jun. 15, 2001) and 60/257,801 (filed Dec. 22, 2000), the methods disclosed in U.S. Pat. No. 6,291,170, and quantitative PCR. Methods to identify increased RNA stability (resulting in an observation of increased expression) or decreased RNA stability (resulting in an observation of decreased expression) may also be used. These methods include the detection of sequences that increase or decrease the stability of mRNAs containing the CRIP1, HN1, and ESE-2/ELF5 sequences disclosed herein. These methods also include the detection of increased mRNA degradation. [0059]
  • In particularly preferred embodiments of the invention, polynucleotides having sequences present in the 3′ untranslated and/or non-coding regions of the above disclosed sequences are used to detect expression or non-expression of CRIP1, HN1, and ESE-2/ELF5 sequences in breast cells in the practice of the invention. Such polynucleotides may optionally contain sequences found in the 3′ portions of the coding regions of the above disclosed sequences. Polynucleotides containing a combination of sequences from the coding and 3′ non-coding regions preferably have the sequences arranged contiguously, with no intervening heterologous sequence(s). [0060]
  • Alternatively, the invention may be practiced with polynucleotides having sequences present in the 5′ untranslated and/or non-coding regions of the above CRIP1, HN1, and ESE-2/ELF5 sequences in breast cells to detect their levels of expression. Such polynucleotides may optionally contain sequences found in the 5′ portions of the coding regions. Polynucleotides containing a combination of sequences from the coding and 5′ non-coding regions preferably have the sequences arranged contiguously, with no intervening heterologous sequence(s). [0061]
  • Preferred polynucleotides contain sequences from 3′ or 5′ untranslated and/or non-coding regions of at least about 20, at least about 22, at least about 24, at least about 26, at least about 28, at least about 30, at least about 32, at least about 34, at least about 36, at least about 38, at least about 40, at least about 42, at least about 44, or at least about 46 consecutive nucleotides. The term “about” as used in the previous sentence refers to an increase or decrease of 1 from the stated numerical value. Even more preferred are polynucleotides containing sequences of at least or about 50, at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, or at least or about 400 consecutive nucleotides. The term “about” as used in the preceding sentence refers to an increase or decrease of 10% from the stated numerical value. [0062]
  • Sequences from the 3′ or 5′ end of the above described coding regions as found in polynucleotides of the invention are of the same lengths as those described above, except that they would naturally be limited by the length of the coding region. The 3′ end of a coding region may include sequences up to the 3′ half of the coding region. Conversely, the 5′ end of a coding region may include sequences up the 5′ half of the coding region. Of course the above described sequences, or the coding regions and polynucleotides containing portions thereof, may be used in their entireties. [0063]
  • Polynucleotides combining the sequences from a 3′ untranslated and/or non-coding region and the associated 3′ end of the coding region are preferably at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, or at least or about 400 consecutive nucleotides. [0064]
  • In another embodiment of the invention, polynucleotides containing deletions of nucleotides from the 5′ and/or 3′ end of the above disclosed sequences may be used. The deletions are preferably of 1-5, 5-10, 10-15, 15-20, 20-25, 25-30, 30-35, 35-40, 40-45, 45-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-125, 125-150, 150-175, or 175-200 nucleotides from the 5′ and/or 3′ end, although the extent of the deletions would naturally be limited by the length of the disclosed sequences and the need to be able to use the polynucleotides for the detection of expression levels. [0065]
  • In yet another embodiment of the invention, polynucleotides containing portions of the above disclosed sequences including the 3′ end may be used in the practice of the invention. Such polynucleotides would contain at least or about 50, at least or about 100, at least about or 150, at least or about 200, at least or about 250, at least or about 300, at least or about 350, or at least or about 400 consecutive nucleotides from the 3′ end of the disclosed sequences. [0066]
  • The invention thus also includes polynucleotides used to detect CRIP1, HN1, and ESE-2/ELF5 expression in breast cells. The polynucleotides may comprise a shorter polynucleotide consisting of sequences found in the above provided SEQ ID NOS in combination with heterologous sequences not naturally found in combination with CRIP1, HN1, and ESE-2/ELF5 sequences. As a non-limiting example, a polynucleotide of the invention may comprise a polynucleotide consisting of the sequence of SEQ ID NO: 29, with a deletion of one or more nucleotides from the 5′ and/or 3′ end, in combination with one or more non-HN1 sequences. [0067]
  • Other polynucleotides for use in the practice of the invention include those that have sufficient homology to those described above to detect expression by use of hybridization techniques. Such polynucleotides preferably have about or 95%, about or 96%, about or 97%, about or 98%, or about or 99% identity with CRIP1, HN1, or ESE-2/ELF5 sequences as described herein. Identity is determined using the BLAST algorithm, as described above. The other polynucleotides for use in the practice of the invention may also be described on the basis of the ability to hybridize to polynucleotides of the invention under stringent conditions of about 30% v/v to about 50% formamide and from about 0.01M to about 0.15M salt for hybridization and from about 0.01M to about 0.15M salt for wash conditions at about 55 to about 65° C. or higher, or conditions equivalent thereto. [0068]
  • In a further embodiment of the invention, a population of single stranded nucleic acid molecules comprising one or both strands of a human CRIP1 or HN1 sequence is provided as a probe such that at least a portion of said population may be hybridized to one or both strands of a nucleic acid molecule quantitatively amplified from RNA of a non-normal or abnormal breast cell. The population may be only the antisense strand of a human CRIP1 or HN1 sequence such that a sense strand of a molecule from, or amplified from, a non-normal or abnormal breast cell may be hybridized to a portion of said population. The population preferably comprises a sufficiently excess amount of said one or both strands of a human CRIP1 or HN1 sequence in comparison to the amount of expressed (or amplified) nucleic acid molecules containing a complementary CRIP1 or HN1 sequence from a normal breast cell. This condition of excess permits the increased amount of nucleic acid expression in a non-normal or abnormal cell to be readily detectable as an increase. [0069]
  • Alternatively, the population of single stranded molecules is equal to or in excess of all of one or both strands of the nucleic acid molecules amplified from a non-normal or abnormal breast cell such that the population is sufficient to hybridize to all of one or both strands. Preferred non-normal cells are ADH, DCIS, or IDC cells. The single stranded molecules may of course be the denatured form of any CRIP1 and/or HN1 sequence containing double stranded nucleic acid molecule or polynucleotide as described herein. [0070]
  • The population may also be described as being hybridized to CRIP1 or HN1 sequence containing nucleic acid molecules at a level of at least twice as much as that by nucleic acid molecules of a normal breast cell. As in the embodiments described above, the nucleic acid molecules may be those quantitatively amplified from a breast cell such that they reflect the amount of expression in said cell. [0071]
  • The population is preferably immobilized on a solid support, optionally in the form of a location on a microarray. A portion of the population is preferably hybridized to nucleic acid molecules quantitatively amplified from a non-normal or abnormal breast cell by real time PCR. The real time PCR may be practiced by use of amplified RNA from a breast cancer cell, as long as the amplification used was quantitative with respect to CRIP1 and/or HN1 containing sequences. [0072]
  • In another embodiment of the invention, expression based on detection of DNA status may be used. Detection of the ESE-2/ELF5 DNA as methylated, deleted or otherwise inactivated, may be used as an indication of decreased expression as found in non-normal breast cells. This may be readily performed by PCR based methods known in the art. The status of the promoter regions (SEQ ID NOS: 210 and 211) of the ESE-2/ELF5 may also be assayed as an indication of decreased expression of ESE-2/ELF5 sequences. A non-limiting example is the methylation status of sequences found in the promoter region. [0073]
  • Conversely, detection of the DNA of a sequence as amplified may be used for as an indication of increased expression as found in non-normal breast cells. This may be readily performed by PCR based, fluorescent in situ hybridization (FISH) and chromosome in situ hybridization (CISH) methods known in the art. [0074]
  • A preferred embodiment using a nucleic acid based assay to determine expression is by immobilization of one or more of the sequences identified herein on a solid support, including, but not limited to, a solid substrate as an array or to beads or bead based technology as known in the art. Alternatively, solution based expression assays known in the art may also be used. The immobilized sequence(s) may be in the form of polynucleotides as described herein such that the polynucleotide would be capable of hybridizing to a DNA or RNA corresponding to the sequence(s). [0075]
  • The immobilized polynucleotide(s) may be used to determine the state of nucleic acid samples prepared from sample breast cell(s) for which the pre-cancer or cancer status is not known or for confirmation of a status that is already assigned to the sample breast cell(s). Without limiting the invention, such a cell may be from a patient suspected of being afflicted with, or at risk of developing, breast cancer. The immobilized polynucleotide(s) need only be sufficient to specifically hybridize to the corresponding nucleic acid molecules derived from the sample. [0076]
  • In embodiments where only one or a few sequences are to be analyzed, the nucleic acid derived from the sample breast cancer cell(s) may be preferentially amplified by use of appropriate primers such that only the sequences to be analyzed are amplified to reduce contaminating background signals from other sequences present in the breast cell. Alternatively, and where the disclosed sequences are to be analyzed in combination with other sequences or where very few cells (or one cell) is used, the nucleic acid from the sample may be globally amplified before hybridization to the immobilized polynucleotides. Of course RNA, or the cDNA counterpart thereof may be directly labeled and used, without amplification, by methods known in the art. [0077]
  • Sequence expression based on detection of a presence, increase, or decrease in protein levels or activity may also be used. Detection may be performed by any immunohistochemistry (IHC) based, bodily fluid based (where a CRIP1, HN1, and/or ESE-2/ELF5 polypeptide is found in a bodily fluid, such as but not limited to blood), antibody (including autoantibodies against the protein where present) based, ex foliate cell (from the cancer) based, mass spectroscopy based, and image (including used of labeled ligand where available) based method known in the art and recognized as appropriate for the detection of the protein. Antibody and image based methods are additionally useful for the localization of tumors after determination of cancer by use of cells obtained by a non-invasive procedure (such as ductal lavage or fine needle aspiration), where the source of the cancerous cells is not known. A labeled antibody or ligand may be used to localize the carcinoma(s) within a patient. [0078]
  • Antibodies for use in such methods of detection include polyclonal antibodies, optionally isolated from naturally occurring sources where available, and monoclonal antibodies, including those prepared by use of CRIP1, HN1, and/or ESE-2/ELF5 polypeptides as antigens. Such antibodies, as well as fragments thereof (including but not limited to Fab fragments) function to detect or diagnose non-normal or cancerous breast cells by virtue of their ability to specifically bind CRIP1, HN1, or ESE-2/ELF5 polypeptides to the exclusion of other polypeptides to produce a detectable signal. Recombinant, synthetic, and hybrid antibodies with the same ability may also be used in the practice of the invention. Antibodies may be readily generated by immunization with a CRIP1, HN1, or ESE-2/ELF5 polypeptide, and polyclonal sera may also be used in the practice of the invention. [0079]
  • Antibody based detection methods are well known in the art and include sandwich and ELISA assays as well as Western blot and flow cytometry based assays as non-limiting examples. Samples for analysis in such methods include any that contain CRIP1, HN1, or ESE-2/ELF5 polypeptides. Non-limiting examples include those containing breast cells and cell contents as well as bodily fluids (including blood, serum, saliva, lymphatic fluid, as well as mucosal and other cellular secretions as non-limiting examples) that contain the polypeptides. [0080]
  • The above assay embodiments may be used in a number of different ways to identify or detect the presence of non-normal breast cells or breast cancer in a breast cancer cell sample from a patient. In some cases, this would reflect a secondary screen for the patient, who may have already undergone mammography or physical exam as a primary screen. If positive from the primary screen, the subsequent needle biopsy, ductal lavage, fine needle aspiration, or other analogous methods may provide the sample for use in the assay embodiments described herein. The present invention is particularly useful in combination with non-invasive protocols, such as ductal lavage or fine needle aspiration, to prepare a breast cell sample. The current analysis of ductal lavage samples is by cytological examination by a trained pathologist who classifies the samples in terms that are at least partly subjective: unsatisfactory (too few cells), benign (including fibrocystic change), atypical (or mild atypia), suspicious (or marked atypia), or malignant. [0081]
  • The present invention provides a more objective set of criteria, in the form of gene expression levels of discrete gene sequences, to discriminate (or delineate) between normal and non-normal breast cells. [0082]
  • In one embodiment of the invention, the isolation and analysis of a breast cancer cell sample may be performed as follows: [0083]
  • (1) Ductal lavage or other non-invasive procedure is performed on a patient to obtain a sample. [0084]
  • (2) Sample is prepared and coated onto a microscope slide. Note that ductal lavage results in clusters of cells that are cytologically examined as stated above. [0085]
  • (3) Pathologist or image analysis software scans the sample for the presence of atypical cells. [0086]
  • (4) If atypical cells are observed, those cells are harvested (e.g. by microdissection such as LCM). [0087]
  • (5) RNA is extracted from the harvested cells. [0088]
  • (6) RNA is assayed for the expression of CRIP1, HN1, and/or ESE-2/ELF5 sequences. [0089]
  • A specific example of the above method would be performing ductal lavage following a primary screen, observing and collecting non-normal cells (or cells suspected of being non-normal) for analysis. Alternatively, the sample may permit the collection of both normal and non-normal cells (or cells suspected of being non-normal) for analysis. The expression levels of CRIP1, HN1, and/or ESE-2/ELF5 sequences in each of these two populations may be compared to each other. This approach can be significantly more powerful than one using the non-normal cells only approach because it utilizes information from the normal cells and the differences between normal and non-normal cells to determine the status of the non-normal cells from the sample. [0090]
  • While many clinical settings focus on identification of the highest stage or grade of breast cancer, the detection of non-normal breast cells of any stage or grade is also important to identify with confidence the presence of, or susceptibility to, breast cancer as early as possible. With use of the present invention, skilled clinicians will be apprised of the presence of non-normal cells quickly and may begin treatment or additional testing based on such information. [0091]
  • The present invention may also be used with solid tissue biopsies. As a non-limiting example, a solid biopsy may be collected and prepared for visualization followed by determination of increased CRIP1 and/or HN1 expression to identify or diagnose the presence of non-normal cells. One preferred means is by use of in situ hybridization with polynucleotide or protein identifying probe(s) for assaying expression of said gene(s). An analogous method may be used to detect decreased expression of ESE-2/ELF5 sequences. [0092]
  • In an alternative method, the solid tissue biopsy may be used to extract molecules followed by analysis for expression of the disclosed sequence(s). This provides the possibility of leaving out the need for visualization and collection of only those cells suspected of being non-normal. This method may of course be modified such that only cells suspected of being non-normal are collected and used to extract molecules for analysis. This would require some form of selection as a prerequisite to gene expression analysis. [0093]
  • In a further modification of the above, both normal cells and cells suspected of being non-normal are collected and used to extract molecules for analysis of sequence expression. The approach, benefits and results are as described above using non-invasive sampling. [0094]
  • In a further alternative to all of the above, the sequence(s) identified herein may be used as part of a simple PCR or array based assay simply to determine the presence of non-normal cells in a sample from a non-invasive sampling procedure. If normal expression levels of the disclosed sequences are identified, no further examination may be necessary. If non-normal expression levels are detected, a more comprehensive analysis may follow. [0095]
  • The detection of sequence expression from samples may be by use of a single microarray able to assay expression of the disclosed sequences as well as other sequences, including sequences known not to vary in expression levels between normal and non-normal breast cells, for convenience and improved accuracy. [0096]
  • Other uses of the present invention include providing the ability to identify breast cancer cell samples as being non-normal for further research or study. This provides a particular advantage in many contexts requiring the identification of non-normal or cancerous cells based on objective genetic or molecular criteria rather than cytological observation. [0097]
  • The materials and methods of the present invention are ideally suited for preparation of kits produced in accordance with well known procedures. The invention thus provides kits comprising agents (like the polynucleotides and/or antibodies described herein as non-limiting examples) for the detection of expression of the disclosed sequences. Such kits, optionally comprising the agent with an identifying description or label or instructions relating to their use in the methods of the present invention, are provided. Such a kit may comprise containers, each with one or more of the various reagents (typically in concentrated form) utilized in the methods, including, for example, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more primer complexes of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase). A set of instructions will also typically be included. [0098]
  • The methods provided by the present invention may also be automated in whole or in part. All aspects of the present invention may also be practiced such that they consist essentially of a subset, or subregion, of the disclosed sequences to the exclusion of material irrelevant to the identification of non-normal or cancerous breast cells. [0099]
  • To identify changes in sequence expression in non-normal or cancerous breast cells, abnormal epithelium from ADH, DCIS and IDC and phenotypically normal epithelium (henceforth referred to as normal) from 36 breast cancer patients and 3 healthy mammoplasty reduction patients were isolated via laser capture microdissection (LCM). The resulting 300 independently microdissected samples were used to interrogate a microarray containing approximately 12,000 human genes. [0100]
  • One important advantage provided by LCM use is the ability to procure both normal and diseased cell populations from the same biopsy. Therefore, the expression level of each gene in a disease state (ADH or DCIS or IDC) is represented as the ratio to the patient-matched normal, which highlights differences due to disease state as opposed to the genetic background of a particular patient. Unsupervised hierarchical clustering revealed one sequence cluster demonstrating increased expression in a majority of the diseased samples. CRIP1 was included in the cluster and identified as displaying increased expression levels in ADH with persistence in DCIS and IDC samples. Its increased expression may thus be a potential biomarker for the detection of breast cancer including the pre-malignant stage of ADH. [0101]
  • Sequences of another cluster demonstrated decreased expression in all three pathological stages. The epithelium-specific transcription factor ELF5 was included, and loss of expression of ELF5 in ADH may be an important first step in the initiation of breast malignancy. [0102]
  • Additional experiments resulted in the identification of increased expression of HN1 sequences in grade III DCIS and IDC cells. [0103]
  • Having now generally described the invention, the same will be more readily understood through reference to the following examples which are provided by way of illustration, and are not intended to be limiting of the present invention, unless specified. [0104]
    • EXAMPLES Example I
  • Materials and Methods [0105]
  • Clinical specimen collection and clinicopathological parameters. All breast specimens were obtained from the Massachusetts General Hospital between 1998 and 2001. Thirty-six breast cancer patients were selected, 31 of which were diagnosed with two or more pathological stages of breast cancer progression, and 5 of which were diagnosed with pre-invasive disease only. Three healthy women who underwent elective mammoplasty reduction were selected as disease-free normal controls. Tissue specimens that demonstrated one or more pathological lesions (ADH, DCIS and IDC) were selected for the study. Cases of ADH were selected as proliferative epithelial lesions that possessed some, but not all, of the features of carcinoma in situ (Page, D. L. et al. (1992)) and most closely resemble those lesions described as CAPSS (Oyama, T. et al. and Fraser, J. L. et al.). DCIS and IDC were classified (histological grade) according to the European classification (Holland, R. et al.) and by the Nottingham combined histological grade (Elston, C. W. et al.), respectively. ER and PR expression were determined by immunohistochemical staining (negative when none of the tumor cell nuclei showed staining), and Her-2 expression determined by immunohistochemistry or FISH. This study was approved the Massachusetts General Hospital human research committee in accordance with NIH human research study guidelines. [0106]
  • LCM and RNA isolation and amplification. Each component (Normal, ADH, DCIS or IDC) was laser capture microdissected in triplicate (from consecutive tissue sections) as described (Sgroi et al.) using a PixCell II LCM system (Arcturus Engineering Inc., Mountain View, Calif.). Total RNA was extracted from the captured cells using the Picopure™ RNA Isolation Kit (Arcturus). T7-based RNA amplification was carried out using the RiboAmp™ kit (Arcturus). Briefly, the RNA from each sample was primed with an oligo-dT primer containing a T7 promoter sequence, reverse transcribed and then converted to double stranded cDNA. The cDNA templates were then used in an in vitro transcription reaction using T7 RNA polymerase to generate amplified RNA (aRNA). To obtain enough aRNA for a microarray experiment, a second round of RNA amplification was performed on all samples. To serve as reference in microarray hybridizations, a human universal reference RNA from Stratagene (La Jolla, Calif.) was amplified identically. [0107]
  • Fabrication of microarrays. Sequence-verified human cDNA clones were obtained from Research Genetics (Huntsville, Ala.). cDNA clones (from the I.M.A.G.E. Consortium via Research Genetics) inserts were amplified by PCR, gel-purified, and spotted onto a 1×3-inch SuperAmine™ (TeleChem International, Sunnyvale, Calif.) glass microscope slide using an OmniGrid™ robotic arrayer (GeneMachines, San Carlos, Calif.). As used herein, the I.M.A.G.E. Consortium CloneID, or the IMAGE CloneID, lists the identifiers of the cDNA clones on the microarrays according to the I.M.A.G.E. Consortium and Research Genetics (www.resgen.com/). This provides a unique single identifier for each clone. Descriptive names of clones (or genes) use the UniGene symbols and titles (www.ncbi.nlm.nih.gov/UniGene/). [0108]
  • Probe labeling and hybridization. cDNA was transcribed from aRNA in the presence of 5-(3-aminoallyl)-2′-[0109] deoxyuridine 5′-triphosphate (aminoallyl dUTP) using Stratagene's FairPlay kit™ (La Jolla, Calif.). Cy3 or Cy5 mono-reactive dye (Amersham, Piscataway, N.J.) was conjugated onto purified cDNA and the residual dye was removed using QiaQuick PCR Purification columns (Qiagen, Valencia, Calif.). Each Cy5-labeled cDNA was hybridized together with the Cy3-labeled reference probe to a microarray in 40 μL hybridization solution (5×SSC, 0.1 μg/μL COT I, 0.2%SDS, 50% formamide) at a concentration of 25 ng/μL per channel for 17 hrs at 42° C. in >60% relative humidity.
  • Washing, scanning and image analysis. After hybridization, slides were washed as follows: 1×SSC, 0.2% SDS at 42° for 5 min (two times), 1×SSC, 0.2% SDS at 55° C. for 5 min, 0.1×SSC, 0.2% SDS at 55° C. for 5 min and 0.1×SSC at RT for 2 min. Washed slides were scanned using ScanArray 5000 (PerkinElmer, Billerica, Mass.), and Cy5/Cy3-signals were quantitated using ImaGene 4.2 (BioDiscovery, Los Angeles, Calif.). [0110]
  • Data processing. Fluorescent intensities of Cy5 and Cy3 channels on each slide were subjected to spot filtering and normalization. Spots flagged by ImaGene were excluded from further analysis. Normalization was performed using a robust nonlinear local regression method (Yang, Y. H. et al.). The normalized ratios of Cy5/Cy3 were used to represent the relative gene expression levels in the experimental samples. Measurements from replicate samples were averaged after normalization. [0111]
  • Cluster and discriminant analysis. Hierarchical cluster analysis was performed in GeneMaths (v1.5, Applied-Maths, Austin, Tex.) using the cosine correlation coefficient as a measure of similarity between two genes or samples and complete linkage. Linear discriminant analysis with variance was performed within GeneMaths. [0112]
    • Example II
  • Analysis of Over and Under Expression [0113]
  • Quantitative real-time PCR analysis of CRIP1 and ELF5 was conducted to confirm their over and under expression in non-normal breast cells. [0114]
  • For the non-amplified RNA RT-PCR validation study, independently laser captured (˜40,000) normal breast epithelial cells from case 215, and ˜40,000 abnormal epithelial cells from DCIS (from cases 89, 178, 179) or IDC (from cases 97, 169, 170) were used. Total RNA was isolated and converted to double-stranded cDNA. For studies using amplified RNA (aRNA), 2 mgs of aRNA from each microdissected sample was converted into double-stranded cDNA. In all cases (cDNA derived from non-amplified and amplified RNA), the double-stranded cDNA was quantitated with PicoGreen (Molecular Probes) using a spectrofluorometer (Molecular Devices) and quantitative analysis of gene expression performed (RT-PCR) was performed with an ABI 7900HT (Applied Biosystems, Foster City, Calif.) as described (Sgroi et al., 1999). [0115]
  • Each reaction was performed in triplicate using 2.5 ng of double stranded cDNA from each sample as template. The relative standard curve method was used for linear regression analysis of unknown samples and data presented as fold change between samples. The sequences of the PCR primer pairs and fluorogenic probe (5′ to 3′), respectively, that were used for each gene are as follows: [0116]
    CRIP1:
    CCTGCTACGCAGCCATGTT,
    GGATGGGTCTCCACCACCT,
    VIC-CGGAGCCGAGAGCCACACTTTCAAGT-TAMRA;
    ELF5:
    TGATTCCTGCTCTGGTGAAACA,
    ACATTTTCTCATCAATCA CTGGTATGT,
    VIC-CAGTCCACCTAGCTGTCAGTCACTGATA-TAMRA;
  • In agreement with microarray results used to initial identify sequences that were over and under expressed in non-normal breast cells, RT-PCR demonstrated over-expression of CRIP1 (>2-fold) in 7 of 8 ADH, 27 of 30 DCIS, and 23 of 25 IDC cases, and under-expression of ELF5 (>2-fold) in 7 of 8 ADH, 28 of 30 DCIS, and 25 of 25 IDC cases (FIG. 1). [0117]
  • In addition, we performed in-situ hybridization for CRIP1 to confirm its cellular specificity. As expected from the use of LCM, CRIP1 signal localized to the epithelial cells, and its intensity was markedly increased in the IDC compartment of the same biopsy (FIGS. 2 and 3), thus verifying the microarray-derived results at the level of cellular resolution. [0118]
  • All references cited herein, including patents, patent applications, and publications, are hereby incorporated by reference in their entireties, whether previously specifically incorporated or not. [0119]
  • Having now fully described this invention, it will be appreciated by those skilled in the art that the same can be performed within a wide range of equivalent parameters, concentrations, and conditions without undue experimentation. This application is intended to cover any variations, uses, or adaptations of the invention, following in general the principles of the invention, that include such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth. [0120]

Claims (34)

We claim:
1. A method to determine the presence of non-normal or abnormal breast cells in a sample from a human subject comprising assaying said sample for increased expression of one or more human CRIP1 or HN1 sequences.
2. The method of claim 1 wherein said assaying is for increased expression of human CRIP1 sequences.
3. The method of claim 1 wherein said assaying is for increased expression of human HN1 sequences.
4. The method of claim 1 wherein said sample is from a subject afflicted with, or suspected of having, breast cancer.
5. The method of claim 1 wherein said sample is obtained by solid tissue biopsy or a non-invasive procedure.
6. The method of claim 5 wherein said non-invasive procedure is selected from ductal lavage, fine needle aspiration, or a needle biopsy.
7. The method of claim 5 wherein microdissection is used to isolate breast cells from said sample before assaying for nucleic acid expression.
8. The method of claim 1 wherein said assaying is by hybridization to a polynucleotide comprising sequences of at least 24 nucleotides from the 3′ untranslated region, the coding region, or the 5′ untranslated region, of human CRIP1.
9. The method of claim 1 wherein said assaying is by hybridization to a polynucleotide comprising sequences of at least 24 nucleotides from the 3′ untranslated region, the coding region, or the 5′ untranslated region, of human HN1.
10. The method of claim 1 wherein said assaying is by PCR amplification of said sequences.
11. The method of claim 10 wherein said PCR is quantitative PCR.
12. The method of claim 1 wherein said non-normal cells are ADH, DCIS, or IDC cells.
13. A method to determine the presence of non-normal or abnormal breast cells in a sample from a human subject comprising assaying said sample for decreased expression of human ESE-2/ELF5 sequences.
14. The method of claim 13 wherein said sample is from a subject afflicted with, or suspected of having, breast cancer.
15. The method of claim 13 wherein said sample is obtained by solid tissue biopsy or a non-invasive procedure.
16. The method of claim 15 wherein said non-invasive procedure is selected from ductal lavage, fine needle aspiration, or a needle biopsy.
17. The method of claim 16 wherein microdissection is used to isolate breast cells from said sample before assaying for nucleic acid expression.
18. The method of claim 17 wherein said assaying is by hybridization to a polynucleotide comprising sequences of at least 24 nucleotides from the 3′ untranslated region, the coding region, or the 5′ untranslated region, of human ESE-2/ELF5.
19. The method of claim 13 wherein said assaying is by PCR amplification of said ESE-2/ELF5 sequence.
20. The method of claim 19 wherein said assaying is by quantitative PCR.
21. The method of claim 13 wherein said assaying is for inactivation or methylation of ESE-2/ELF5 sequences.
22. The method of claim 13 wherein said assaying comprises detection of increased mRNA degradation.
23. The method of claim 13 wherein said non-normal cells are ADH, DCIS, or IDC cells.
24. A polynucleotide comprising
a segment consisting of a fragment of an HN I sequence selected from SEQ ID NOS: 29-83 of between 24 and 500 nucleotides and
one or more non-HN1 nucleic acid molecules.
25. A polynucleotide consisting of a fragment of an HN1 sequence selected from SEQ ID NOS: 29-83 of between 24 and 500 nucleotides.
26. A population of singled stranded nucleic acid molecules comprising one or both strands of a human CRIP1 or HN1 sequence wherein at least a portion of said population is hybridized to one or both strands of a nucleic acid molecule quantitatively amplified from RNA of a non-normal or abnormal breast cell.
27. The population of claim 26 wherein the population is immobilized on a solid support.
28. The population of claim 27 wherein said solid support is a microarray.
29. The population of claim 26 wherein said nucleic acid molecules amplified from a non-normal or abnormal breast cell are amplified by quantitative real time PCR (RT-PCR).
30. The population of claim 29 wherein said quantitative RT-PCR is of amplified RNA of said breast cancer cell.
31. The population of claim 26 wherein said population of single stranded molecules is equal to or in excess of all of one or both strands of the nucleic acid molecules amplified from a non-normal or abnormal breast cell such that the population is sufficient to hybridize to all of one or both strands.
32. The population of claim 26 wherein said population of single stranded molecules comprising sequences of at least 24 nucleotides from the 3′ untranslated region, the coding region, or the 5′ untranslated region, of human CRIP1.
33. The population of claim 26 wherein said population of single stranded molecules comprising sequences of at least 24 nucleotides from the 3′ untranslated region, the coding region, or the 5′ untranslated region, of human HN1.
34. The population of claim 26 wherein said non-normal cells are ADH, DCIS, or IDC cells.
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