# Patent

## Title
Thyroid tumors identified

## Abstract

The invention relates to methods and kits for detecting thyroid cancer by detecting differences in the expression of genes that are differentially expressed in thyroid cancer cells.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This patent application is a continuation of U.S. patent application Ser. No. 13/063,429, filed Jun. 2, 2011, which is a National Stage application under 35 U.S.C. 371 of PCT/US2009/005091, filed Sep. 11, 2009 and published as WO 2010/030365 A2 on Mar. 18, 2010 which claims the benefit of priority, under 35 U.S.C. Section 119(e), to U.S. Provisional Patent Application Ser. No. 61/191,845 filed on Sep. 12, 2008, and U.S. Provisional Patent Application Ser. No. 61/207,812 filed Feb. 17, 2009, the contents of all of which applications are specifically incorporated by reference herein in their entireties.


FIELD OF THE INVENTION
The invention relates to detection and diagnosis of thyroid cancer. In some embodiments, the methods of the invention can be used to distinguish between benign thyroid cells or tissues, malignant thyroid cells or tissues, and follicular adenomas with nuclear atypia (FANA).
BACKGROUND OF THE INVENTION
Thyroid nodules are common in the United States, occurring in greater than 60% of individuals. Moreover, their incidence is steadily increasing, mainly because of the increased detection of smaller, asymptomatic nodules. Although the majority of these nodules are benign, a significant numbers of patients undergo surgical excision. Upon pathologic review of such thyroid tumors, clear-cut benign or malignant diagnoses often can be rendered. However, follicular lesions of the thyroid often pose a diagnostic challenge.
A particular diagnostic dilemma is presented in a subset of encapsulated follicular lesions with partial nuclear features of papillary thyroid carcinoma (PTC) (occasional nuclear grooves, focal nuclear clearing, and overlapping nuclei) and with histological features that fail to place them reliably in either the benign category or the malignant category. In the inventors' experience, these tumors represent approximately 10% of all follicular-patterned lesions observed at surgical pathology (see also, Arora et al. World J Surg. 32:1237-1246 (2008)). The difficulty of classifying this group of tumors is exemplified further by several studies in which poor inter-observer agreement was demonstrated among expert endocrine pathologists ranging from 39% to 58% when they reviewed follicular-patterned lesions of the thyroid (Chan et al., Am J Clin Pathol. 117:16-18 (2002); Franc et al., Hum Pathol. 34:1092-1100 (2003); Lloyd et al., Am J Surg Pathol. 28:1336-1340 (2004); Saxen et al. Acta Pathol Microbiol Scand [A]. 1978; 86A:483-4864-8 (1978); Hirokawa et al. Am J Surg Pathol. 26:1508-1514 (2002)). This diagnostic difficulty in classifying such borderline tumors with standard terminology led Williams to propose the term well differentiated tumor of uncertain malignant potential (WDT-UMP) as a separate diagnostic category (Int J Surg Pathol. 8:181-183 (2000).
No matter what terminology is used for these tumors, additional tools are needed to determine whether thyroid nodules and/or tumors are actually malignant or simply benign, and/or whether such nodules and/or tumors can progress to become malignant tumors.
SUMMARY OF THE INVENTION
The invention relates to methods for improved diagnosis of thyroid cancer that can distinguish not only benign nodules from malignant thyroid tumors but can also identify borderline, pre-cancerous tumors (e.g., encapsulated follicular lesions that may have partial nuclear features of PTC) that may not need aggressive treatment. For example, in one study conducted by the inventors using the methods described herein, the majority of histologically uncertain tumors (66.7%) were determined to be premalignant tumors, while a smaller number of tumors were determined to be benign tumors (26.7%) and only a even smaller number of tumors were actually malignant tumors (6.7%). By using the methods and kits of the invention, the malignant thyroid tumors can be identified with greater certainty, thereby avoiding unnecessary, expensive and invasive medical procedures that might otherwise have been used to treat histologically uncertain tumors.
Thus, one aspect of the invention is a method of detecting whether thyroid cancer cells are present in a test tissue or cell sample which comprises (a) observing test levels of RNA or protein expression in the test tissue or cell sample for any differentially expressed gene, and (b) comparing the test levels of expression to one or more standard or control levels of expression, to ascertain whether higher or lower levels of expression of any of the genes is present in the test tissue or cell sample, and thereby detecting whether thyroid cancer cells are present in the test tissue or cell sample; wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.
In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof.
Any methods available to one of skill in the art can be used to detect and/or quantify the test levels of RNA. For example, the test levels of RNA expressed can be detected by microarray analysis or by nucleic acid amplification. In some embodiments, the test levels of RNA expressed are detected by microarray analysis that includes use of one or more probes on the microarray that can hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes. For example, such methods can employ one or more probes that can hybridize to any of SEQ ID NO:119-172. In some embodiments, the one or more probes hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions. For example, the hybridization conditions can be highly stringent hybridization conditions.
In other embodiments, nucleic acid amplification can be employed. Such nucleic acid amplification can include reverse transcription polymerase chain reaction, real time polymerase chain reaction, or quantitative polymerase chain reaction. For example, the test levels of RNA expressed can be detected by nucleic acid amplification using one or more primers that hybridize to one or more of the differentially expressed genes, or an RNA or DNA copy of the one or more differentially expressed genes under moderate to highly stringent hybridization conditions. The one or more primers employed can, for example, hybridize to any of SEQ ID NO:119-172. Such hybridization conditions can in some instances be highly stringent hybridization conditions.
The one or more standard or control levels of expression can include: an expression level observed for a malignant thyroid cancer cell or tissue; an expression level observed for a benign thyroid cell or tissue; an expression level observed for a follicular adenoma with nuclear atypia; an expression level observed for a borderline thyroid cell or tissue; an expression level observed for a normal non-cancerous thyroid cell or tissue; or an expression level observed for a constitutively expressed gene.
These methods can distinguish between benign, malignant and borderline thyroid cells or tissues. For example, these methods can distinguish between benign thyroid cells or tissues, malignant thyroid cells or tissues, and follicular adenomas with nuclear atypia (FANA). For example, the test tissue or cell sample is obtained from a patient with thyroid cancer or suspected of having thyroid cancer.
Another aspect of the invention is a kit comprising: (a) at least one set of oligonucleotide primers, wherein a first primer in the set contains a sequence complementary to a region in one strand of a nucleic acid sequence template and primes the synthesis of a first extension product, and a second primer contains a sequence complementary to a region in said first extension product and primes the synthesis of a nucleic acid strand complementary to said first extension product, and wherein the template is a differentially expressed gene, or an RNA or DNA copy of the differentially expressed gene; and (b) instructions for using the at least one set of oligonucleotide primers; wherein the differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.
In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof. The first primer and/or the second primer can include a label. A container of nucleotides can also be included in the kit where the nucleotides are used as subunits in the synthesis of and amplified product. For example, the nucleotides can be ribonucleotides and/or deoxyribonucleotides. One or more of such nucleotides can include a label.
The instructions can describe a method for amplifying an mRNA, cRNA or cDNA corresponding to the differentially expressed gene(s). In some embodiments, the first primer and/or the second primer may hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. For example, the hybridization conditions can be highly stringent hybridization conditions in some instances.
Another aspect of the invention is a kit that includes (a) a microarray with covalently attached probes that can hybridize to a differentially expressed gene selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof; and (b) instructions for using the microarray.
In some embodiments, the differentially expressed gene can be selected from the group consisting of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 and a combination thereof. In other embodiments, the differentially expressed gene can be selected from the group consisting of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 and a combination thereof. In further embodiments, the differentially expressed gene can be selected from the group consisting of C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 and a combination thereof. Such probes can, in some embodiments, hybridize to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene, for example, under moderate to highly stringent hybridization conditions. In some embodiments, the hybridization conditions are highly stringent hybridization conditions. Such a kit can also include one or more standard or control probes. For example, the kit can include one or more probes for a constitutively expressed gene.
Another aspect of the invention is a method of detecting a mutation in a human BRAF gene that includes: (a) obtaining a test sample of genomic DNA from a human; (b) amplifying a segment of BRAF DNA from the genomic DNA using primers with SEQ ID NO: 1 and SEQ ID NO:2; and (c) detecting whether the mutation exists in the segment amplified; wherein the mutation consists of a glutamate substituted for valine at codon 600.
Such a method can also include detecting or confirming whether the human has thyroid cancer by observing test levels of RNA or protein expression in the test tissue or cell sample for any of the differentially expressed genes described herein, using any of the methods and/or kits described herein.



DESCRIPTION OF THE DRAWINGS
FIG. 1 is an image of a histologically borderline lesion. Note the follicular architecture with focal nuclear clearing and occasional nuclear grooves.
FIG. 2 is a graphic generated by an unsupervised hierarchical cluster analysis. FA indicates follicular adenoma; HYP, hyperplastic lesion; BOR, borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma.
FIG. 3 is a graphic generated by a 2-group K-means cluster analysis. FA indicates follicular adenoma; BOR, borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma; HYP, hyperplastic lesion.
FIG. 4 is graphic generated by three-group K-means cluster analysis that identified 3 distinct groups of tumors based upon their gene expression patterns: malignant (left), benign (center), and intermediate (right). BOR indicates borderline tumor; FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma; FA, follicular adenoma; HYP, hyperplastic lesion.
FIG. 5 shows a Venn diagram illustrating the differentially expressed genes relating 61 genes to benign, borderline, and malignant tumors.
FIG. 6 is a schematic diagram showing proposed gene expression changes during tumorigenesis of follicular-patterned lesions of the thyroid.



DETAILED DESCRIPTION OF THE INVENTION
The invention relates to methods of detecting malignant thyroid tumors and/or distinguishing whether thyroid tumors are benign, malignant, and/or pre-cancerous borderline tumors. While currently available histological and/or cytological procedures can sometimes distinguish benign and malignant thyroid tumors, there are many thyroid tumors that cannot readily be classified as either malignant or benign by such histological procedures. Patients with such unclassified tumors are often aggressively treated as though their tumors were malignant. However, by employing the methods and kits described herein, these unclassified tumors can be properly identified as either benign, malignant, or pre-cancerous borderline tumors, thereby reducing the need for expensive, invasive and unpleasant medical treatment when it is unnecessary.
The application describes an analysis of fifty histologically-unequivocal benign and malignant tumors, which led to the identification of a list of sixty-one genes that are differentially expressed in benign and malignant thyroid tumors. These differentially expressed genes are listed in Table 1.
By using probes for the fifty to sixty differentially expressed genes described herein, forty additional tumors were evaluated, including 15 histologically intermediate tumors, 11 benign tumors, and 14 papillary thyroid carcinomas (PTCs). Differential gene expression was used to detect whether the histologically intermediate thyroid tumors were malignant or not. As illustrated herein, the majority of histologically intermediate tumors (66.7%) were actually borderline, premalignant tumors that exhibited gene expression similarities with benign tumors (26.7%) and malignant tumors (6.7%) (FIG. 4). This third category of borderline tumors (encapsulated follicular tumors with cytological atypia) does not fit into previously proposed benign or malignant classification schemes using standard histological, immuno-histochemical, or mutation analyses. Instead, these borderline tumors are premalignant tumors that may warrant monitoring but do not generally need immediate aggressive medical treatment.
Twenty-seven genes were expressed differentially between the benign and borderline groups, including the cyclic AMP response element binding protein/p300-interactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain 1 or CITED1 gene and the fibroblast growth factor receptor 2 or FGFR2 gene. Fourteen genes were expressed differentially between the borderline group and malignant tumors, for example, the met proto-oncogene and of the high-mobility group adenine/thymine-hook 2 or HMGA2 gene in malignancies. Mutations of the v-raf murine sarcoma viral oncogene homolog B1 or BRAF gene were identified in 4 of 14 malignant tumors but not in benign or borderline tumors.
Patients who had histologically or molecularly borderline tumors did not have metastasis or recurrences. These data indicate that encapsulated thyroid follicular lesions with partial nuclear features of PTC are biologically borderline tumors that are molecularly distinct from benign and malignant tumors. Moreover, the data indicate that such borderline tumors identified by the methods and kits of the invention are pre-cancerous with no immediate need for aggressive cancer treatment.
The gene expression profiling methods described herein are more accurate than existing procedures for diagnosing problematic thyroid tumors. For example, the methods of the invention can identify malignant thyroid tumors with greater than 90% sensitivity and 80% specificity. In some embodiments, the methods of the invention can identify malignant thyroid tumors with greater than 93% sensitivity and greater than 82% specificity.
DEFINITIONS
“Genes” are the units of heredity in living organisms. They are encoded in the organism's genetic material (DNA or RNA), and control the physical development and behavior of the organism. Genes encode the information necessary to construct the proteins (etc.) needed for the organism to function. The term “genes” generally refers to the region of DNA (or RNA, in the case of some viruses) that determines the structure of a protein (the coding sequence), together with the region of DNA that controls when and where the protein will be produced (the regulatory sequences).
As used herein, the phrase “expression profiling” refers to differential gene expression analysis/techniques. Examples of such techniques include microarray analyses, real time PCR and qPCR. Microarray technology allows for the comparison of gene expression between, for example, normal and diseased (e.g., cancerous) cells or cells which express different cell markers. There are several names for microarray technology including DNA microarrays, DNA arrays, DNA chips, gene chips, and others.
In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “includes,” “including,” and the like; “consisting essentially of” or “consists essentially” likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not deleteriously changed by the presence of more than that which is recited.
Other definitions may appear throughout this disclosure in the appropriate context.
Genes that are Differentially Expressed in Benign and Malignant Thyroid Tumors
The expression levels of one or more of the genes listed in Table 1 can be detected using the methods and kits of the invention. In some embodiments, the expression levels of two or more, or three or more, or four or more, or five or more of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells. In other embodiments, the expression levels of seven or more, or eight or more, or ten or more, or twelve or more of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells. In further embodiments, the expression levels of no more than ten, no more than twelve, no more than fifteen, no more than twenty of the genes listed in Table 1 are detected to assess whether a thyroid nodule contains benign or malignant cancer cells.
Differential expression of these genes means that the mRNA or transcript levels produced by these genes increases or decreases in a test tissue or cell sample (e.g., a thyroid tissue biopsy) relative to a control, thereby indicating the presence of benign thyroid cells or tissues, malignant thyroid cells or tissues, and/or borderline tumors (e.g., encapsulated thyroid follicular lesions with partial nuclear features of PTC) in the test tissue or cell sample from which the RNA/transcripts were obtained.
Genes whose expression changes in thyroid tumor cells include one or more of the following genes: ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC4A4, SLC25A15, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof.
The following genes were expressed at higher levels in malignant thyroid cancer tissues and cells than in benign thyroid lesions: CAPN3, CITED 1, DAPK2, DPP4, DUSP4, DTX4, GALNT7, HMGA2, IGFBP6, LRP4, MET, MYH10, PFAAP5, PROS1, PSD3, QPCT, RAB27A, RXRG, SERPINA1, SLIT1, SPTAN1, TIAM1, TIMP1, and UPP1. Thus, detection of an increase in the expression of one or more of these genes in a tissue or cell sample, relative to a benign control tissue sample, is indicative of thyroid cancer.
On the other hand, the following genes are expressed at lower levels in malignant thyroid cancer tissues than in benign thyroid lesions: ANK2, ARHGAP6, C11orf17, CDH16, CITED 2, COL9A3, ChGn, CKB, CSRP2, DIO1, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, HGD, KIT, MATN2, NAUK2, PGF, PIP3-E, PKNOX2, PRKACB, SDC4, SLC4A4, SLC25A15, TFCP2L1, TNS3, and TSPAN12. Thus, detection of a decrease in the expression of one or more of these genes in a tissue or cell sample, relative to a benign control tissue sample, is indicative of thyroid cancer.
However, as described herein, the inventors have discovered a third type of thyroid tumor that is pre-cancerous and may not need aggressive medical treatment when initially detected. As described herein, these borderline tumors can be distinguished from benign and malignant by their expression patterns.
The following genes are differentially expressed between malignant and borderline/benign tumors: DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, and/or UPP1. Each of these genes exhibit increased expression in malignant tumors relative to borderline and benign tumors, except DIO1, SDC4, and SLC4A4, which are expressed at lower levels in malignant thyroid tissues and cells when compared to their expression in benign and borderline tumors. Thus, when differential expression of one or more of these genes is detected in a thyroid test or cell sample, such differential expression is indicative of the presence of malignant tumor cells.
The following genes are differentially expressed between benign and borderline/malignant lesions: ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, and/or TIAM1. Each of these genes exhibit decreased expression in malignant tumors relative to borderline/malignant tumors, except CITED 1, DUSP4, LRP4, PSD3, SLIT1, SPTAN1, and TIAM1, which are expressed at higher levels in malignant tissues and cells compared to borderline/malignant tissues and cells. Thus, benign thyroid lesions can be identified and distinguished from borderline/malignant tumors by their differential expression patterns in a thyroid test tissue or cell sample.
The following genes are differentially expressed between benign and malignant lesions: C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15. Each of these genes are expressed at higher levels in malignant thyroid tumors relative to their expression levels in benign thyroid lesions, except the following genes: C11orf17, CKB, CSRP2, HGD, PGF, PKNOX2, PRKACB, and SLC25A15, which are expressed at lower levels in malignant thyroid tissues relative to benign thyroid lesions. Thus, to definitively distinguish between benign and malignant thyroid tissues, the expression of these genes can be evaluated.
The difference in expression levels between a differentially expressed gene in malignant thyroid tissues relative to the expression levels for that gene in a control (e.g., normal thyroid tissues) can be at least a 20% difference in expression levels, at least a 30% difference in expression levels, at least a 40% difference in expression levels, at least a 50% difference in expression levels, at least a 60% difference in expression levels, at least a 70% difference in expression levels, at least an 80% difference in expression levels, at least a 90% difference in expression levels, at least a 100% difference in expression levels, and/or a more than a 100% difference in expression levels. Thus, in some embodiments, the difference in expression levels between a differentially expressed gene in malignant thyroid tissues relative to the expression levels for that gene in a control (e.g., normal thyroid tissues) can be at least 1.5 fold, at least 1.7 fold, at least 1.8 fold, at least 2-fold, at least 2.2 fold, at least at least 2.3 fold, at least 2.4 fold, at least 2.5 fold, or more than 2.5 fold. Table 1 provides examples of the differences in expression levels that can readily be determined and observed.
Gene expression data may be gathered in any way that is available to one of skill in the art. For example, gene expression levels can be detected and quantified by employing an array of probes that hybridize to the different transcripts of one or more of the genes listed in Table 1, by using nucleic acid amplification (e.g., quantitative polymerase chain reaction) and through nucleic acid hybridization procedures. Other methods of determining expression of the genes include traditional Northern blotting, nuclease protection, RT-PCR and differential display methods can be used for detecting gene expression levels. Such methods are described in the following sections and in the Examples.
Probes and primers that can hybridize to an RNA, cDNA corresponding to any of the following genes can be used to detect differential gene expression: ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC4A4, SLC25A15, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof.
Sequences for these differentially expressed genes are available and can be used to make probes and primers for detecting expression levels. Examples of sequences that can be used to make probes and primers for these are provided hereinbelow. Any probe or primer that can hybridize to an RNA or cDNA of any of these genes can be used in the methods of the invention. In some embodiments, such a probe or primer hybridizes such to an RNA or cDNA of a differentially expressed gene under moderately stringent conditions. In other embodiments, such a probe or primer hybridizes such to an RNA or cDNA of a differentially expressed gene under highly stringent conditions. Such conditions are known to one of skill in the art and are described herein.
RNA Manipulation
One of skill in the art will appreciate that in order to assess the mRNA transcript levels (and thereby the expression levels) of a gene or genes, it is desirable to provide a RNA sample or a nucleic acid sample derived from the mRNA transcript(s). As used herein, a nucleic acid derived from an mRNA transcript refers to a nucleic acid ultimately synthesized from the mRNA transcript. Thus, the original mRNA obtained from a test tissue or cell sample can serve as a template for generating a nucleic acid derived from an mRNA. For example, such a nucleic acid derived from an mRNA can be a cDNA reverse transcribed from an mRNA, an RNA transcribed from the cDNA, a DNA amplified from the cDNA, an RNA transcribed from the amplified DNA, and the like. Detection of such derived products is indicative of the presence and abundance of the original mRNA transcript in a test tissue or cell sample. Thus, suitable samples include, but are not limited to, mRNA transcripts of the gene or genes, cDNA reverse transcribed from the mRNA, cRNA transcribed from the cDNA, and the like.
Where it is desired to quantify the transcription level of one or more genes in a sample, the concentration of the mRNA transcript(s) of the gene or genes is proportional to the transcription level of that gene. Similarly, when hybridization is employed to quantify transcription levels, the hybridization signal intensity can be proportional to the amount of hybridized nucleic acid. As described herein, controls can be run to correct for variations introduced during sample preparation and/or hybridization.
The nucleic acid may be isolated from a test tissue or cell sample (and/or a control tissue sample) according to any of a number of methods well known to those of skill in the art. One of skill in the art will appreciate that where expression levels of a gene or genes are to be detected, RNA (mRNA) is isolated. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in Sambrook et al. (1989) MOLECULAR CLONING: A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press; and Sambrook et al. (2001). MOLECULAR CLONING: A LABORATORY MANUAL (3rd ed.). Cold Spring Harbor Laboratory Press, which are both incorporated herein by reference in their entireties. Filter based methods for the isolation of mRNA are also available in the art and can be used for isolating mRNA from biological samples. Examples of commercially available filter-based RNA isolation systems include RNAqueousTM (Ambion) and RNeasyTM (Qiagen). One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates of biological samples soon after obtaining the samples so that the mRNA is not degraded by nucleases during testing.
Frequently, it is desirable to amplify the nucleic acid sample prior to evaluation. If a quantitative result is desired care can be taken to use an amplification method that maintains or controls for the relative frequencies of the amplified nucleic acids.
Methods of “quantitative” amplification are well known to those of skill in the art. For example, quantitative PCR involves simultaneously co-amplifying a known quantity of an internal control nucleic acid. This provides an internal standard that may be used to calibrate the PCR reaction. Detection of the internal control sequence along with the mRNAs of interest (e.g., those from any of the genes in Table 1) allows one of skill in the art to monitor whether the mRNA isolation, purification and quantification procedures accurately reflect actual expression levels or whether there is a problem with any of these procedures (e.g., the mRNA has become degraded during one of the procedures).
Suitable amplification methods include, but are not limited to polymerase chain reaction (PCR) (Innis & Gelfand, Optimization of PCRs. In: PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS (eds. M. A. Innis, et al.), pp. 3-12. Academic Press, San Diego (1990); ligase chain reaction (LCR) (see, Wu and Wallace, Genomics (1989)); Landegren, et al., Science 241: 1077-1080 (1988); Barringer, et al., Gene 89: 117-122 (1990); transcription amplification (Kwoh, et al., Proc. Natl. Acad. Sci. USA 86, 1173-1177 (1989)), and self-sustained sequence replication (Guatelli, et al., Proc. Natl. Acad. Sci. 87: 1874-1878 (1990)).
In one embodiment, a nucleic acid sample is the total mRNA isolated from a biological sample (e.g., a test tissue or cell sample). The term “biological sample,” as used herein, refers to a sample obtained from an organism or from components (e.g., cells) of an organism, including normal tissue (e.g., as a control) and diseased tissue such as a tumor, a neoplasia or a hyperplasia. The sample may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. The biological sample may also be referred to as a “clinical sample” derived from a patient. Such samples include, but are not limited to, tissue biopsy or fine needle aspiration biopsy samples, blood, blood cells (e.g., white cells), urine, peritoneal fluid, and pleural fluid, or cells therefrom. Biological samples may also include sections of tissues such as frozen sections or formalin fixed sections taken for histological purposes.
In some embodiments, the sample mRNA is reverse transcribed with a reverse transcriptase, such as SuperScript II (Invitrogen), and a primer consisting of an oligo-dT to generate first-strand cDNA. Other desirable sequences can be incorporsated into the first-strand cDNA by linking those sequences onto the oligo-dT primer (e.g., a restriction site sequence, a sequence encoding a promoter such as a phage T7 promoter, etc.). A second-strand DNA is polymerized in the presence of a DNA polymerase, DNA ligase, and RNase H. The resulting double-stranded cDNA may be blunt-ended using T4 DNA polymerase and purified by phenol/chloroform extraction. The double-stranded cDNA can then be then transcribed into cRNA or amplified to generate a pool of amplified cDNAs. Methods for the in vitro transcription of RNA are known in the art and describe in, for example, Van Gelder, et al. (1990) and U.S. Pat. Nos. 5,545,522; 5,716,785; and 5,891,636, all of which are incorporated herein by reference.
If desired, a label may be incorporated into the cRNA or cDNA when it is transcribed. Those of skill in the art are familiar with methods for labeling nucleic acids. For example, the cRNA may be transcribed in the presence of biotin-ribonucleotides or the cDNA may be synthesized in the presence of biotin-deoxyribonucleotides. The BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics) is a commercially available kit for biotinylating cRNA.
It will be appreciated by one of skill in the art that the direct transcription method described above provides an antisense (aRNA) pool. Where antisense RNA is used with a microarray for detection, the antisense RNA can be the “target nucleic acid” that is hybridized to an array of the oligonucleotide probes provided in the microarray. In that case the oligonucleotide probes on the microarray are chosen to be complementary to subsequences of the antisense nucleic acids. Conversely, where the target nucleic acid pool is a pool of sense nucleic acids, the oligonucleotide probes are selected to be complementary to subsequences of the sense nucleic acids. Finally, where the nucleic acid pool is double stranded, the probes may be of either sense, or both senses, as the target nucleic acids include both sense and antisense strands.
To detect hybridization, it may be advantageous to employ nucleic acids in combination with an appropriate detection means. Recognition moieties incorporated into primers, incorporated into the amplified product during amplification, or attached to probes that can hybridize to the amplified product are useful in the identification of nucleic acid molecules. A number of different labels may be used for this purpose including, but not limited to, fluorophores, chromophores, radiophores, enzymatic tags, antibodies, chemiluminescence, electroluminescence, and affinity labels. One of skill in the art will recognize that these and other labels can be used with success in this invention.
Examples of affinity labels include, but are not limited to the following: an antibody, an antibody fragment, a receptor protein, a hormone, biotin, Dinitrophenyl (DNP), or any polypeptide/protein molecule that binds to an affinity label. Examples of enzyme tags include enzymes such as urease, alkaline phosphatase or peroxidase to mention a few. Colorimetric indicator substrates can be employed to provide a detection means visible to the human eye or spectrophotometrically, to identify specific hybridization with complementary nucleic acid-containing samples. Examples of fluorophores include, but are not limited to, Alexa 350, Alexa 430, AMCA, BODIPY 630/650, BODIPY 650/665, BODIPY-FL, BODIPY-R6G, BODIPY-TMR, BODIPY-TRX, Cascade Blue, Cy2, Cy3, Cy5, 6-FAM, Fluoroscein, HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, REG, Rhodamine Green, Rhodamine Red, ROX, TAMRA, TET, Tetramethylrhodamine, and Texas Red.
Means of detecting such labels are well known to those of skill in the art. For example, radiolabels may be detected using photographic film or scintillation counters. In other examples, fluorescent markers may be detected using a photodetector to detect emitted light. In still further examples, enzymatic labels are detected by providing the enzyme with a substrate and detecting the reaction product produced by the action of the enzyme on the substrate, and colorimetric labels are detected by simply visualizing the colored label or by use of spectrometer.
So called “direct labels” are detectable labels that are directly attached to or incorporated into the target (sample) nucleic acid prior to hybridization to a probe or microarray. In contrast, so called “indirect labels” are joined to the hybrid duplex after hybridization. In some embodiments, the indirect label is attached to a binding moiety that has been attached to the target nucleic acid prior to the hybridization. Thus, for example, the target nucleic acid may be biotinylated before the hybridization. After hybridization, an avidin-conjugated fluorophore will bind the biotin-bearing hybrid duplexes providing a label that is easily detected. For a detailed review of methods of labeling nucleic acids and detecting labeled hybridized nucleic acids see, for example, Peter C. van der Vliet & Shiv Pillai, eds., LABORATORY TECHNIQUES IN BIOCHEMISTRY AND MOLECULAR BIOLOGY (1993).
Methods for Detecting Differential Expression
The present invention includes a method for detecting and/or quantifying expression of any combination of the genes listed in Table 1 (e.g., a target nucleic acid) in a biological sample.
Such detection and quantification methods can involve nucleic acid amplification (e.g., reverse transcription PCR, quantitative PCR and/or real-time PCR), wherein a sample containing a target nucleic acid that is to be amplified (e.g. a cDNA generated from an RNA sample by reverse transcription) is mixed with 1) primers that are complementary to sequences within the target sequence to be amplified, 2) a thermostable polymerase, and 3) four different nucleoside triphosphates. The normal steps of nucleic acid amplification are then followed—melting, annealing and synthesis—by thermal cycling of the mixture. The primers employed can be linked to a label. In some embodiments, a fluorescent intercalating agent is used in the reaction. The labeled primers and/or fluorescent intercalating agents allow quantification of the amounts of amplified products generated in various test reactions.
When nucleic acid amplification is used to detect gene expression, any procedure that amplifies RNA can be used, for example, reverse transcription-polymerase chain reaction (RT-PCR) assays, strand displacement amplification and other amplification procedures. Strand displacement amplification can be used as described in Walker et al (1992) Nucl. Acids Res. 20, 1691-1696. The term “polymerase chain reaction” (“PCR”) refers to the method of K. B. Mullis U.S. Pat. Nos. 4,683,195; 4,683,202; and 4,965,188, hereby incorporated by reference, which describe a method for increasing the concentration of target nucleic acid in a mixture of genomic DNA or other DNA or RNA without cloning or purification.
The steps involved in PCR nucleic acid amplification method are described in more detail below. For ease of discussion, the nucleic acid to be amplified is described as being double-stranded. However, the process is readily adapted to amplify a single-stranded nucleic acid, such as an mRNA from any of the genes listed in Table 1. In the amplification of a single-stranded nucleic acid, the first step involves the synthesis of a complementary strand, for example, by reverse transcription so that two complementary target strands are available for amplification.
When PCR is performed on double-stranded DNA or cDNA generated from one or more of the RNAs expressed from the genes of Table 1, two primers are employed, each primer hybridizing to a different DNA strand at opposite ends of the DNA target. One of skill in the art can readily make and use probes and primers for the genes listed in Table 1, for example, by examining available nucleic acid sequences for these genes that are available in the sequence database maintained by the National Center for Biotechnology Information (see website at ncbi“dot”nlm“dot”nih“dot”). Examples of some sequences for the genes listed in Table 1 are provided herein and below.
The PCR process for amplifying a target nucleic acid consists of introducing a large excess of the two primers to a mixture that may contain the mRNA (or cDNA generated therefrom) from any of the genes listed in Table 1, followed by a precise sequence of thermal cycling in the presence of a nucleic acid polymerase. For PCR amplification, each of the two primers is complementary to a distinct region in one of the two strands of the double stranded target sequence. Primers are selected so that they hybridize just outside the region of interest to be amplified and so that, upon primer extension, one primer will be extended towards the hybridization site of a second primer hybridized on the opposite target strand.
To effect amplification, the nucleic acid (RNA or cDNA) is denatured to open up double-stranded target sites and the temperature is lowered so that the primers anneal to their complementary sequences within the target molecule. Following annealing, the primers are extended with a polymerase. Such primer extension forms a new pair of complementary strands that likely have different ends than the original target. Such complementary strands can hybridize together to form an “amplicon” that can also be a target for amplification. The steps of denaturation, primer annealing and primer extension can be repeated many times. Each round of denaturation, annealing and extension constitutes one “cycle.” There can be numerous cycles, and the amount of amplified DNA produced increases with the number of cycles. Hence, to obtain a high concentration of an amplified target nucleic acid, many cycles are performed.
The following steps are generally employed during nucleic acid amplification with the inhibitors of the invention:
(a) Each target nucleic acid strand is contacted with four different nucleoside triphosphates and one oligonucleotide primer, wherein each primer is selected to be substantially complementary to a portion the nucleic acid strand to be amplified (hmgn3), such that the extension product synthesized from one primer, when it is separated from its complement, can serve as a template for synthesis of the extension product of the other primer. To promote the proper annealing of primer(s) and the nucleic acid strands to be amplified, a selected primer-hybridization temperature is used that allows hybridization of each primer to a complementary nucleic acid strand. The inhibitors of the invention can be added or included in this melting/annealing reaction.
(b) After primer annealing, a nucleic acid polymerase is used for primer extension. The nucleic acid polymerase incorporates the nucleoside triphosphates into a growing nucleic acid strand to form a new strand that is complementary to the template strand hybridized by the primer. In general, this primer extension reaction is performed at a temperature and for a time effective to promote the activity of the nucleic acid enzyme and to synthesize a “full length” complementary nucleic acid strand that extends into and through a complete second primer binding site. However, the temperature is not so high as to separate each extension product from its nucleic acid template strand. The polymerase may be added after the first melting/annealing reaction.
(c) The mixture from step (b) is then heated for a time and at a temperature sufficient to separate the primer extension products from their complementary templates. The temperature chosen is not so high as to irreversibly denature the nucleic acid polymerase present in the mixture.
(d) The mixture from (c) is cooled for a time and at a temperature effective to promote hybridization of a primer to each of the single-stranded molecules produced in step (b).
(e) The mixture from step (d) is maintained at a temperature and for a time sufficient to promote primer extension by the polymerase to produce a “full length” extension product. The temperature used is not so high as to separate each extension product from the complementary strand template. Steps (c)-(e) are repeated until the desired level of amplification is obtained.
In some embodiments, real-time polymerase chain reaction (real time PCR; also called quantitative real time polymerase chain reaction (Q-PCR/qPCR) or kinetic polymerase chain reaction) is employed to quantify the expression of genes. Real-time PCR amplifies and simultaneously quantifies a targeted nucleic acid (e.g., an RNA expressed by one of the genes listed in Table 1). Thus, real-time PCR permits both detection and quantification (as absolute number of copies or relative amount when normalized to DNA input or additional normalizing genes) of a specific nucleic acid (e.g., RNA) in a sample.
Real-time PCR employs many of the same steps as polymerase chain reaction but the amplified DNA product is quantified as it accumulates in the reaction in real time after each amplification cycle. Methods that are often used to quantify the amplified DNA include the use of fluorescent dyes intercalate with double-stranded DNA product, and the use of modified DNA primers that fluoresce when hybridized with a complementary nucleic acid template.
For example, any of the SEQ ID NO:3-118 primers can be used in a real-time PCR assay for evaluating expression levels of the differentially expressed genes. One type of real-time PCR assay that can be employed involves use of SYBRGreen dye. SYBR Green is a dye that binds the minor groove of double stranded DNA. When SYBR Green dye binds to double stranded DNA, the intensity of the fluorescent emissions increases. As more double stranded amplicons are produced, SYBR Green dye signal will increase. During the PCR assay, such a fluorescent signal is directly proportional to the number of amplicons generated.
To detect RNA expression levels, real-time polymerase chain reaction is combined with reverse transcription PCR, where the RNA in a sample is first treated with reverse transcriptase to generate a cDNA that can then be amplified.
Reverse transcription PCR and real-time PCR can be used to quantify relative levels of expression from any of the genes listed in Table 1.
The present invention therefore includes a method for detecting and/or quantifying expression of any of the genes listed in Table 1 (a target nucleic acid) that involves nucleic acid amplification (e.g., reverse transcription PCR and real-time PCR), wherein a sample containing a target nucleic acid that is to be amplified (e.g. a cDNA generated from an RNA sample by reverse transcription) is mixed with 1) primers that are complementary to sequences within the target sequence to be amplified, 2) a thermostable polymerase, and 3) four different nucleoside triphosphates. The normal steps of nucleic acid amplification are then followed—melting, annealing and synthesis—by thermal cycling of the mixture. The primers employed can be linked to a label. In some embodiments, a fluorescent intercalating agent is used in the reaction. The labeled primers and/or fluorescent intercalating agents allow quantification of the amounts of amplified products generated in various test reactions.
Microarrays exploit the preferential binding of complementary nucleic acid sequences. A microarray is typically a glass slide, on to which DNA molecules are attached at fixed locations (spots or features). There may be tens of thousands of spots on an array, each containing a huge number of identical DNA molecules (or fragments of identical molecules), of lengths from twenty to hundreds of nucleotides. The spots on a microarray are either printed on the microarrays by a robot, or synthesized by photo-lithography (similar to computer chip productions) or by ink-jet printing. There are commercially available microarrays, however many labs produce their own microarrays.
Hybridization
Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing (see Lockhart et al., 1999, WO 99/32660, for example). The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, for example, through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature and/or decreasing the salt concentration of the buffer containing the nucleic acids.
Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA-DNA, RNA-RNA or RNA-DNA) will form even where the annealed sequences are not perfectly complementary. Thus specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization occurs with fewer mismatches.
One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).
In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in some embodiments, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. To better distinguish between the signal and the background, the hybridized sequences (e.g., on a microarray) may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.
As used herein, the terms “hybridize” and “hybridization” refer to the annealing of a complementary sequence to the target nucleic acid, i.e., the ability of two polymers of nucleic acid (polynucleotides) containing complementary sequences to anneal through base pairing. The terms “annealed” and “hybridized” are used interchangeably throughout, and are intended to encompass any specific and reproducible interaction between a complementary sequence and a target nucleic acid, including binding of regions having only partial complementarity. Certain bases not commonly found in natural nucleic acids may be included in the nucleic acids of the present invention and include, for example, inosine and 7-deazaguanine. Those skilled in the art of nucleic acid technology can determine duplex stability empirically considering a number of variables including, for example, the length of the complementary sequence, base composition and sequence of the oligonucleotide, ionic strength and incidence of mismatched base pairs. The stability of a nucleic acid duplex is measured by the melting temperature, or “Tm”. The Tm of a particular nucleic acid duplex under specified conditions is the temperature at which on average half of the base pairs have disassociated.
The term “stringency” is used in reference to the conditions of temperature, ionic strength, and the presence of other compounds, under which nucleic acid hybridizations are conducted. With “high stringency” conditions, nucleic acid base pairing will occur only between nucleic acid fragments that have a high frequency of complementary base sequences. Thus, conditions of “medium” or “low” stringency are often required when it is desired that nucleic acids which are not completely complementary to one another be hybridized or annealed together. The art knows well that numerous equivalent conditions can be employed to comprise medium or low stringency conditions. The choice of hybridization conditions is generally evident to one skilled in the art and is usually guided by the purpose of the hybridization, the type of hybridization (DNA-DNA or DNA-RNA), and the level of desired relatedness between the sequences (e.g., Sambrook et al. (1989); NUCLEIC ACID HYBRIDIZATION, A PRACTICAL APPROACH, IRL Press, Washington D.C. 1985, for a general discussion of the methods).
The stability of nucleic acid duplexes is known to decrease with an increased number of mismatched bases, and further to be decreased to a greater or lesser degree depending on the relative positions of mismatches in the hybrid duplexes. Thus, the stringency of hybridization can be used to maximize or minimize stability of such duplexes. Hybridization stringency can be altered by: adjusting the temperature of hybridization; adjusting the percentage of helix destabilizing agents, such as formamide, in the hybridization mix; and adjusting the temperature and/or salt concentration of the wash solutions. For filter hybridizations, the final stringency of hybridizations often is determined by the salt concentration and/or temperature used for the post-hybridization washes.
“High stringency conditions” when used in reference to nucleic acid hybridization include conditions equivalent to binding or hybridization at 42° C. in a solution consisting of 5×SSPE (43.8 g/l NaCl, 6.9 g/l NaH2PO4 H2O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.5% SDS, 5×Denhardt's reagent and 100 μg/ml denatured salmon sperm DNA followed by washing in a solution comprising 0.1×SSPE, 1.0% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.
“Medium stringency conditions” when used in reference to nucleic acid hybridization include conditions equivalent to binding or hybridization at 42° C. in a solution consisting of 5×SSPE (43.8 g/1 NaCl, 6.9 g/l NaH2PO4 H2O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.5% SDS, 5×Denhardt's reagent and 100 μg/ml denatured salmon sperm DNA followed by washing in a solution comprising 1.0×SSPE, 1.0% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.
“Low stringency conditions” include conditions equivalent to binding or hybridization at 42EC in a solution consisting of 5×SSPE (43.8 g/l NaCl, 6.9 g/l NaH2PO4 H2O and 1.85 g/l EDTA, pH adjusted to 7.4 with NaOH), 0.1% SDS, 5×Denhardt's reagent [50×Denhardt's contains per 500 ml: 5 g Ficoll (Type 400, Pharmacia), 5 g BSA (Fraction V; Sigma)] and 100 g/ml denatured salmon sperm DNA followed by washing in a solution comprising 5×SSPE, 0.1% SDS at 42° C. when a probe of about 500 nucleotides in length is employed.
The term “homology” refers to a degree of sequence identity. There may be partial homology or complete homology (i.e., identity). Homology is often measured using sequence analysis software (e.g., Sequence Analysis Software Package of the Genetics Computer Group. University of Wisconsin Biotechnology Center. 1710 University Avenue. Madison, Wis. 53705). Such software matches similar sequences by assigning degrees of homology to various substitutions, deletions, insertions, and other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.
It is also understood that these ranges, compositions and conditions for hybridization are mentioned by way of non-limiting examples only, and that the desired stringency for a particular hybridization reaction is often determined empirically by comparison to one or more positive or negative controls. Depending on the application envisioned it is preferred to employ varying conditions of hybridization to achieve varying degrees of selectivity of a nucleic acid towards a target sequence. In a non-limiting example, identification or isolation of a related target nucleic acid that does not hybridize to a nucleic acid under stringent conditions may be achieved by hybridization at low temperature and/or high ionic strength. Such conditions are termed “low stringency” or “low stringency conditions,” and non-limiting examples of low stringency include hybridization performed at about 0.15 M to about 0.9 M NaCl at a temperature range of about 20° C. to about 50° C. Of course, it is within the skill of one in the art to further modify the low or high stringency conditions to suite a particular application.
The hybridization conditions selected also depend on the particular circumstances (depending, for example, on the G+C content, type of target nucleic acid, source of nucleic acid, and size of hybridization probe). Optimization of hybridization conditions for the particular application of interest is well known to those of skill in the art. Representative solid phase hybridization methods are disclosed in U.S. Pat. Nos. 5,843,663, 5,900,481, and 5,919,626, which are incorporated herein by reference in their entireties. Other methods of hybridization that may be used in the practice of the present invention are disclosed in U.S. Pat. Nos. 5,849,481, 5,849,486, and 5,851,772, which are also incorporated herein by reference in their entireties.
Signal Detection
The hybridized nucleic acids are typically detected by detecting one or more labels attached to either the nucleic acids derived from a test sample (e.g., an amplified product) or to a probe that is hybridized to the mRNA or an amplified product of the mRNA. The labels may be incorporated by any of a number of means well known to those of skill in the art (for example, see Affymetrix GeneChipTM Expression Analysis Technical Manual).
DNA arrays and gene chip technology provide a means of rapidly screening a large number of nucleic acid samples for their ability to hybridize to a variety of single stranded DNA probes immobilized on a solid substrate. These techniques involve quantitative methods for analyzing large numbers of genes rapidly and accurately. The technology capitalizes on the complementary binding properties of single stranded DNA to screen nucleic acid samples by hybridization (Pease et al., 1994; Fodor et al., 1991). Basically, a DNA array or gene chip consists of a solid substrate with an attached array of single-stranded DNA molecules. For screening, the chip or array is contacted with a single stranded nucleic acid sample (e.g., cRNA or cDNA), which is allowed to hybridize under stringent conditions. The chip or array is then scanned to determine which probes have hybridized.
Methods for directly synthesizing on or attaching polynucleotide probes to solid substrates are available in the art. See, e.g., U.S. Pat. Nos. 5,837,832 and 5,837,860, both of which are expressly incorporated by reference herein in their entireties. A variety of methods have been utilized to either permanently or removably attach the probes to the substrate. Exemplary methods include: the immobilization of biotinylated nucleic acid molecules to avidin/streptavidin coated supports (Holmstrom, 1993), the direct covalent attachment of short, 5′-phosphorylated primers to chemically modified polystyrene plates (Rasmussen et al., 1991), or the precoating of the polystyrene or glass solid phases with poly-L-Lys or poly L-Lys, Phe, followed by the covalent attachment of either amino- or sulfhydryl-modified oligonucleotides using bifunctional crosslinking reagents (Running et al., 1990; Newton et al., 1993). When immobilized onto a substrate, the probes are stabilized and therefore may be used repeatedly.
In general terms, hybridization is performed on an immobilized nucleic acid target or a probe molecule that is attached to a solid surface such as nitrocellulose, nylon membrane or glass. Numerous other matrix materials may be used, including reinforced nitrocellulose membrane, activated quartz, activated glass, polyvinylidene difluoride (PVDF) membrane, polystyrene substrates, polyacrylamide-based substrate, other polymers such as poly(vinyl chloride), poly(methyl methacrylate), poly(dimethyl siloxane), photopolymers (which contain photoreactive species such as nitrenes, carbenes and ketyl radicals capable of forming covalent links with target molecules).
The Affymetrix GeneChip system may be used for hybridization and evaluation of the probe arrays, where the probes have been selected to hybridize to any combination of the genes listed in Table 1 (or a cRNA or cDNA obtained from an mRNA generated by any of those genes). In some embodiments, the Affymetrix U95A or U133A array is used in conjunction with Microarray Suite 5.0 for data acquisition and preliminary analysis of gene expression patterns and/or levels.
Normalization Controls
Normalization controls are oligonucleotide probes that are complementary to labeled reference oligonucleotides that are added to the nucleic acid sample. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the hybridization signal to vary between arrays. For example, signals read from all other probes in the array can be divided by the signal from the control probes thereby normalizing the measurements.
Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array, however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few normalization probes are used and they are selected such that they hybridize well (i.e. no secondary structure) and do not match any target-specific probes. Normalization probes can be localized at any position in the array or at multiple positions throughout the array to control for spatial variation in hybridization efficiently.
In a some embodiments, a standard probe cocktail supplied by Affymetrix is added to the hybridization to control for hybridization efficiency when using Affymetrix Gene Chip arrays.
Expression Level Controls
Expression level controls are probes that hybridize specifically with constitutively expressed genes in the sample. The expression level controls can be used to evaluate the efficiency of cRNA preparation.
Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes.”
In one embodiment, the ratio of the signal obtained for a 3′ expression level control probe and a 5′ expression level control probe that specifically hybridize to a particular housekeeping gene is used as an indicator of the efficiency of cRNA preparation. A ratio of 1-3 indicates an acceptable preparation.
Databases
Any appropriate computer platform may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in a database or provided as an input. For example, a large number of computer workstations and programs are available from a variety of manufacturers, such as those available from Affymetrix.
Statistical Methods
Combining profiles of gene expression over a wide array of transcripts has potentially more classification prediction power than relying on any single gene. The significance of the difference between the levels of gene expression between tissue sample types can be assessed using expression data and any number of statistical tests such as those described in the Examples and by using published methods (e.g., the Significance Analysis of Microarrays (SAM) method, see, Tusher V G, et al., 2001, Proc. Natl. Acad. Sci. USA 98(9):5116-21). SAM identifies genes with statistically significant changes in expression by assimilating a set of gene-specific t-tests. Each gene is assigned a score on the basis of its change in gene expression relative to the standard deviation of repeated measurements for that gene. Genes with scores greater than a threshold are deemed potentially significant. The percentage of such genes identified by chance is the false discovery rate (FDR). To estimate the FDR, nonsense genes are identified by analyzing permutations of the measurements. The threshold can be adjusted to identify smaller or larger sets of genes, and FDRs are calculated for each set.
Kits
The methods described herein can be practiced using a kit. Such kits generally include probes and/or primers for detecting and/or quantifying expression of the differentially expressed genes described herein, and instructions for performing the detection and/or quantification methods.
Thus, one aspect of the invention is a kit that includes, for example, (a) at least one set of oligonucleotide primers, wherein a first primer in the set contains a sequence complementary to a region in one strand of a nucleic acid sequence template and primes the synthesis of a first extension product, and a second primer contains a sequence complementary to a region in said first extension product and primes the synthesis of a nucleic acid strand complementary to said first extension product, and wherein the template is a differentially expressed gene, or an RNA or DNA copy of the differentially expressed gene; and (b) instructions for using the at least one set of oligonucleotide primers; wherein differentially expressed gene is selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof.
The first primer and/or the second primer provided in the kit can have a covalently attached label. For example, the first primer and/or the second primer can be selected from any of SEQ ID NO:3-118.
Another kit that can be made and/or used for detecting differential expression can include (a) a microarray with covalently attached probes that can hybridize to a differentially expressed gene selected from the group consisting of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, and a combination thereof; and (b) instructions for using the microarray.
Probes useful in the microarray of this kit can hybridize to any of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, UPP1, or a combination thereof
The kit can include other useful components. For example, the kit can include a container of nucleotides for use as subunits in the synthesis of and amplified product. In some embodiments, the one or more nucleotides provided can have a covalently attached label. The nucleotides provided with the kit can be ribonucleotides or deoxyribonucleotides. Other components provided by the kit include reagents or devices for isolating and/or purifying mRNA, enzymes such as reverse transcriptase, ligase, DNA polymerase (e.g., Taq polymerase), solutions and buffers for performing enzymatic reaction, and/or solutions for performing hybridization. Thus, the kits can include one or more buffers, such as a DNA isolation buffers, an amplification buffer or a hybridization buffer. The kit may also contain compounds and reagents to prepare DNA templates and isolate RNA from a test sample. The kit may also include various labeling reagents and compounds.
The kit of can also include one or more standard or control probes. For example, one or more of the standard or control probes can be a probe or probes for one or more constitutively expressed genes.
In some embodiments the instructions provided with the kit can describe a method for amplifying an mRNA, cRNA or cDNA corresponding to the differentially expressed gene(s). One of skill in the art may choose to utilize the kit for detecting differential expression by hybridization of a first primer and/or a second primer to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. When using the kit with the microarray, one of skill in the art may choose to utilize the kit for detecting differential expression by hybridization of a probe to an mRNA, cRNA or cDNA corresponding to the differentially expressed gene under moderate to highly stringent hybridization conditions. For example, the instructions provided in the kit can inform one of skill in the art to employ hybridization conditions that are moderately to highly stringent hybridization conditions.
The kit can include primers and/or probes for detecting some or all of the differentially expressed genes. For example, the kits can detect and/or quantify expression of a subset of differentially expressed genes such as any one of DIO1, DTX4, GALNT7, HMGA2, IGFBP6, MET, PROS1, SDC4, SERPINA1, SLC4A4, TIAM1, TIMP1, UPP1 or a combination thereof. The kits can detect and/or quantify expression of other subsets of differentially expressed genes, for example, any one of ANK2, ARHGAP6, CDH16, CITED 1, CITED 2, COL9A3, ChGn, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GATM, KIT, LRP4, MATN2, SLIT1, SPTAN1, TFCP2L1, PIP3-E, PSD3, TNS3, TSPAN12, TIAM1 or a combination thereof. Alternatively, for example, the kits can be used to detect another subset of differentially expressed genes such as one or more of the following genes C11orf17, CAPN3, CAPN3, CKB, CSRP2, DAPK2, DPP4, HGD, MYH10, NAUK2, PFAAP5, PGF, PKNOX2, PRKACB, QPCT, RAB27A, RXRG, and SLC25A15 or a combination thereof.
Thus, probes and/or primers for detecting mRNA expression of any of the genes listed in Table 1 may be included in a kit. The kit may further include individual nucleic acids that can be amplified with the nucleic acids of interest. The kit can also include probes and/or primers for detecting particular control nucleic acid sequences. The control nucleic acids included in the kit can be mRNA(s) and/or control cDNA(s). The probes, primers and/or control RNA and/or DNA sequences can be provided on a microarray. Alternatively, the probes, primers and/or control RNA and/or DNA sequences can be provided in separate vials or wells of an assay plate (e.g., a microtiter plate).
Some of the components of the kits may be packaged either in aqueous media or in lyophilized form. When the components of the kit are provided in one and/or more liquid solutions, the liquid solution is an aqueous solution, with a sterile aqueous solution being particularly preferred. However, the components of the kit may also be provided as dried powder(s). When reagents and/or components are provided as a dry powder, the powder can be reconstituted by the addition of a suitable solvent. It is envisioned that the solvent may also be provided in another container or by the user.
The containers for the kits can include at least one vial, test tube, flask, bottle, syringe or other container means, into which a component may be placed, and/or suitably aliquoted. A labeling reagent and label may be included and packaged separately or together. There can be more than one component or container in the kit. For example, the kit can also contain a second, third or other additional container into which the additional components may be separately placed. However, various combinations of components may be included together in a vial. The kits of the present invention can also include a means for containing the nucleic acids, and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which the desired vials are retained.
A kit will also include instructions for employing the kit components as well the use of any other reagent not included in the kit. Instructions may include variations that can be implemented.
The following non-limiting examples further illustrate aspects of the invention.
EXAMPLE 1
Materials and Methods
Tumor Samples
Tissue samples were collected at time of surgery, snap-frozen in liquid nitrogen, and stored at −80° C. Representative slides for all tumors were reviewed by two dedicated pathologists. A total of 90 thyroid tumor samples, including 16 papillary thyroid carcinoma (PTC), 22 follicular variants of papillary thyroid carcinoma (FVPTC), 15 hyperplastic nodules, 22 follicular adenomas, and 15 histologically borderline tumors were analyzed in this study. This study was approved by our Institutional Review Board.
Borderline tumors were defined as encapsulated lesions with follicular architecture in which the morphologic features of papillary thyroid carcinoma were qualitatively incomplete and the lesions did not demonstrate evidence of capsular and/or vascular invasion. The incomplete features of papillary thyroid carcinoma were widespread in the lesions that were analyzed in this study and did not represent focal findings in an otherwise benign nodule. An example of such a borderline tumor sample is shown in FIG. 1. In essence, these cases could be classified as well differentiated tumors of uncertain malignant potential (WDT-UMP) as proposed by Williams et al. (Int J Surg Pathol. 8:181-183 (2000)). The officially reported final diagnosis of the 15 borderline tumors, all rendered prior to the onset of this study, was 7 follicular adeonomas and 8 FVPTCs.
RNA Isolation and GeneChip Hybridization
RNA was extracted using RNeasy Mini kit (Qiagen, Valencia, Calif.) from frozen tissue following manufacturer's protocol. RNA purity was confirmed by spectrophotometry. Total RNA was reverse transcribed to complementary DNA (cDNA) according to manufacturer's protocol (NuGEN Ovation RNA Amplification System V2) and then labeled with biotin. cDNA was then hybridized to genechips for microarray analysis, using either GeneChip U95A or U133A (Affymetrix, Santa Clara, Calif.).
Microarray Data Analysis
ArrayAssist 5.2.2 (Stratagene, Inc., La Jolla, Calif.) was used for gene chip analysis. Interchip and intrachip normalization was performed via robust multichip analysis (RMA). After RMA, hybridization signals underwent variance stabilization, log transformation, and baseline transformation. Advanced significance analysis was performed on 50 U95A GeneChips including 10 hyperplastic nodules, 16 follicular adenomas, 13 follicular variants of papillary thyroid carcinomas (FVPTCs), and 11 papillary thyroid carcinomas. This formed the training set. Gene expression of benign tumors was compared to that of malignant tumors. After Benjamini-Hochberg correction for false-discovery, gene probe sets with significant differential expression (2-fold or more with p<0.05) were identified. This probe list was then converted to correspond to probes on the U133A Gene Chips (array comparison software; available from Affymetrix.com). The remaining 40 tumor samples, all analyzed with U133A Gene Chips, formed the test set. The test set was then assessed using unsupervised hierarchical cluster analysis and K-means cluster analysis with both 2- and 3-group cluster algorithms. Genes that were differentially expressed between borderline tumors and classic benign and malignant tumors were further identified with advanced significance analysis.
Detection of BRAF Mutations
All 40 tumors forming the test group were analyzed for v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in which glutamate was substituted for valine at codon 600. One microgram of RNA was reverse-transcribed in a 20 μl reaction and a 1 μl aliquot of cDNA was used for polymerase chain reaction (PCR). The following PCR primers were used:









(SEQ ID NO: 1)



forward primer, 5′-TGCTTGCTCTGATAGGAAAATG-3′;



and



 



(SEQ ID NO: 2)



reverse primer, 5′-GACTTTCTAGTAACTCAGCAGC-3′.






Amplification was carried out for 35 cycles (at 94° C. for 15 seconds, at 60° C. for 1 minute, and at 72° C. for 1 minute). All PCR products were visualized by electrophoresis on a 2% agarose gel and purified using a PCR purification kit (Qiagen Inc). BRAF mutations were detected by direct sequencing of PCR products. All sequencing was performed bidirectionally using the Big Dye Terminator cycle-sequencing kit and the Applied Biosystems Automated 3730 DNA Analyzer (Applied Biosystems, Foster City, Calif.).
EXAMPLE 2
Accurate Diagnosis of Thyroid Tumors as Benign or Malignant
This Example illustrates that gene expression analysis can be used to identify whether tumors of uncertain malignancy are benign or malignant. Based on their benign clinical behavior, it is proposed that these encapsulated thyroid follicular lesions with partial nuclear features of papillary thyroid carcinoma be called ‘follicular adenomas with nuclear atypia’ and the data indicate that these lesions may not need to be treated as cancers.
Differentiation of Benign and Malignant Tumors
The training set consisted of 50 tumors including 26 unequivocal benign tumors (16 follicular adenoma and 10 hyperplastic nodules) and 24 unequivocal malignancies (11 PTC and 13 FVPTC). A total of 66 probe sets corresponding to 56 genes showed significant differential expression between benign and malignant tumors. Thirty-one genes had up-regulated expression in malignancies compared to benign tumors, and 30 genes were down-regulated (Table 1).







TABLE 1







Genes differentially expressed between benign,


borderline, and/or malignant thyroid lesions











Gene
Fold



Gene Name
Symbol
Change*
P





Differentially expressed between benign





and borderline/malignant lesions


Ankyrin 2, neuronal
ANK2
−2.70
.0281


Rho GTPase activating protein 6
ARHGAP6
−2.42
.0329


Cadherin 16, kidney-specific cadherin
CDH16
−2.28
.0185


Cbp/p300-interacting
CITED1
+6.44
.0252


Cbp/p300-interacting
CITED2
−2.06
.0261


Cbp/p300-interacting
CITED2
−2.76
.0182


Collagen, type IX, alpha 3
COL9A3
−5.87
.0160


Chondroitin beta 1,4
ChGn
−3.72
.0111


Dual-specificity phosphatase 4
DUSP4
+3.69
.0206


EGF-containing fibulin-like
EFEMP1
−2.60
.0464


engulfment and cell motility 1
ELMO1
−2.60
.0261


Fibroblast growth factor receptor 2
FGFR2
−2.13
.0343


Fibronectin leucine rich transmembrane
FLRT1
−2.10
.0252


protein 1


Fibromodulin
FMOD
−3.09
.0063


Glycine amidinotransferase
GATM
−2.41
.0482


V-kit Hardy-Zuckerman 4 feline
KIT
−3.85
.0039


Low-density lipoprotein
LRP4
+5.89
.016


Matrilin 2
MATN2
−3.38
.0127


Slit homolog 1 (Drosophila)
SLIT1
+3.35
.0258


Spectrin, alpha, nonerythrocytic 1
SPTAN1
+2.66
.0160


Transcription factor CP2-like 1
TFCP2L1
−3.54
.0029


Phosphoinositide-binding protein
PIP3-E
−3.14
.0343


Pleckstrin and Sec7 domain
PSD3
+2.40
.0169


Pleckstrin and Sec7 domain
PSD3
+2.55
.0214


Tensin 3
TNS3
−2.41
.0029


Tetraspanin 12
TSPAN12
−2.35
.0047


T-cell lymphoma invasion and
TIAM1
+3.91
.0160


metastasis


Differentially expressed between


malignant and borderline/benign lesions


Deiodinase, iodonthyronine, type 1
DIO1
−4.47
.0321


Deltex 4 homolog (Drosophila)
DTX4
+3.68
.0111


Uridine diphosphate-N-acetyl-alpha-D-
GALNT7
+2.07
.0213


galactosamine


High-mobility group AT-hook 2
HMGA2
+3.56
.0204


Insulin-like growth factor binding
IGFBP6
+3.18
.0160


protein 6


Met proto-oncogene
MET
+2.35
.0182


Protein S
PROS1
+3.97
.0089


Syndecan 4
SDC4
−3.26
.0049


Serpin peptidase inhibitor, clade A
SERPINA1
+5.64
.0252


Serpin peptidase inhibitor, clade A
SERPINA1
+4.81
.0233


Solute carrier family 4
SLC4A4
−4.03
.0034


TIMP metallopeptidase inhibitor 1
TIMP1
+2.72
.0446


Uridine phosphorylase 1
UPP1
+2.25
.0127


T-cell lymphoma invasion and
TIAM1
+3.91
.0160


metastasis 1


Differentially expressed only between


benign and malignant lesions


Chromosome 11 open reading frame 17
C11orf17
−2.12
.0239


Calpain 3
CAPN3
+2.00
.0263


Calpain 3
CAPN3
+2.10
.0410


Creatine kinase, brain
CKB
−2.46
.0189


Cysteine and glycine-rich protein 2
CSRP2
−2.41
.0189


Death-associated protein kinase
DAPK2
+2.23
.0322


Dipeptidyl-peptidase 4
DPP4
+2.83
.0127


Dipeptidyl-peptidase 4
DPP4
+2.51
.0117


Homogentisate 1,2-dioxygenase
HGD
−3.17
.0149


Myosin, heavy chain 10
MYH10
+2.73
.0214


Phosphonoformate immunoassociated
PFAAP5
+2.59
.0189


protein 5


Phosphonoformate immunoassociated
PFAAP5
+2.28
.0258


protein 5


Placental growth factor
PGF
−2.22
.0301


Myosin, heavy chain 10
MYH10
+2.73
.0214


PBX/knotted 1 homeobox 2
PKNOX2
−2.31
.0455


Protein kinase, cAMP-dependent
PRKACB
−2.20
.0241


Glytaminyl-peptide cyclotransferase
QPCT
+3.43
.0136


RAB27A, member RAS oncogene
RAB27A
+2.41
.0111


RAB27A, member RAS oncogene
RAB27A
+2.08
.0063


Retinoid X receptor, gamma
RXRG
+2.57
.0261


Solute carrier family 25
SLC25A15
−2.75
.0261





GTP indicates guanine triphosphate; Cpb, cyclic adenosine monophosphate response element-binding protein; EGF, epidermal growth factor; Sec7, a guanine-nucleotide-exchange factor (also called ARNO3 and cytohesion 3); AT, adenine and thymine; TIMP, tissue inhibitor of metalloproteinase; cAMP, cyclic adenosine monophosphate.


*Fold change is shown relative to benign lesions.






Unsupervised Hierarchical Cluster Analysis

An independent set of 40 test samples was then characterized by observing the expression of genes from the list generated by the training set. The test set included 15 borderline tumors as well as a second group of unequivocal benign (n=11) and malignant (n=14) tumors, including 6 follicular adenomas, 5 hyperplastic nodules, 9 FVPTCs and 5 PTCs. In an unsupervised hierarchical cluster analysis, all benign tumors were distinguished from malignant tumors as expected (FIG. 2).
In addition to these two groups of tumor types, a third intermediate group was identified. This tumor group involved 15 tumors, where the vast majority (10 cases) were histologically borderline tumors. Three FVPTCs and 2 follicular adenomas were also identified in this borderline group of tumor types. Of the 5 remaining borderline tumors, 4 clustered with the benign group and 1 with the malignant group. It is noteworthy that these tumors were the most peripheral nodes in these two groups, indicating an expression profile closer to the intermediate group than other benign and malignant tumors (FIG. 2).
K-Means Cluster Analysis
To help elucidate the differences in gene expression between the three groups of tumors (benign, borderline and malignant), the test set was also subjected to K-means cluster analysis using both 2- and 3-groups. In the 2-group cluster algorithm, tumors were separated into two groups based on their gene expression of the genes of interest. This algorithm distinguished benign and malignant tumors with 93% sensitivity and 82% specificity (FIG. 3). Borderline tumors were divided, with four tumors (27%) grouped with benign tumors while eleven (73%) were grouped with the malignant tumors.
In the 3-group cluster algorithm, tumors were separated into three designated groups based on their expression profile. With this algorithm, malignant tumors primarily formed one group (with 1 borderline tumors), benign tumors formed a second group (with 4 borderline tumors), and a third group was composed of 10 borderline tumors, 2 follicular adenoma, and 3 FVPTC (FIG. 4). These 2 follicular adenomas were previously grouped with malignancies in the 2-group algorithm (FA-3 and FA-4) and one of the three FVPTCs that was grouped with the borderline tumors (FVPTC-3) had previously clustered with the benign tumors in the 2-group algorithm.
Correlation with Final Clinical Diagnosis and Patient Follow-Up
Of 15 borderline tumors included in this study, 7 tumors were officially diagnosed and reported as follicular adenomas (47%) and 8 (53%) as FVPTCs. Upon review of the 2-group K-means cluster analysis of these 15 borderline tumors, a correlation between the reported diagnosis and cluster group was observed in only 6 out of 15 tumors (40%), underscoring the diagnostic dilemmas that pathologists face with these tumors (Table 2).







TABLE 2







Comparison of Final Diagnosis with 2-Group Clustering


of Borderline Tumor Samples BOR1-15













Pathologic
Cluster




Sample
Diagnosis
Group
Concordance







BOR 1
FVPTC
Benign
No



BOR 2
FA
Benign
Yes



BOR 3
FA
Malignant*
No



BOR 4
FVPTC
Malignant*
Yes



BOR 5
FA
Malignant*
No



BOR 6
FA
Malignant*
No



BOR 7
FVPTC
Malignant*
Yes



BOR 8
FVPTC
Malignant*
Yes



BOR 9
FA
Malignant*
No



BOR 10
FA
Malignant
No



BOR 11
FVPTC
Malignant*
Yes



BOR 12
FVPTC
Malignant*
Yes



BOR 13
FA
Malignant*
No



BOR 14
FVPTC
Benign
No



BOR 15
FVPTC
Benign
No










None of the borderline tumors were associated with lymph node metastasis or distant metastasis. Of the 9 patients with histologically borderline tumors who were followed, 6 patients were officially diagnosed with FVPTC, and none developed a recurrence after surgery (mean follow-up 1.7 years; range 2 months to 4.4 years) based on thyroglobulin level, ultrasound studies, or a combination of both methods. Similarly, among the 3 patients with FVPTC in the molecularly intermediate group (FVPTC-1, FVPTC-2, and FVPTC-3), none had lymph node metastasis, extranodal extension, or recurrent disease at follow-up periods of 23 months, 23 months, and 25 months, respectively.
Gene Signature of Borderline Tumors
To identify gene expression profiles that distinguish borderline tumors from either benign or malignant tumors, another advanced significance analysis was performed. Twenty-seven of the 61 genes had significant differential expression between benign and borderline tumors, while 14 of the 61 genes had significant differential expression between malignancies and borderline tumors. Only one of these genes, T-cell lymphoma invasion and metastasis 1 (TIAM1), overlapped between the two comparisons (FIG. 5). Of the 27 genes that distinguished benign from borderline tumors, 8 genes had up-regulated expression in borderline tumors including, CITED-1, and 19 genes were down-regulated including fibroblast growth factor receptor 2 (FGFR-2) (Table 1). Of the 14 genes that distinguished malignant tumors from borderline tumors, 11 genes were up-regulated in malignant tumors, including met proto-oncogene (MET) and the high-mobility group adenine/thymine-hook 2 gene (HMGA2), whereas 2 genes were relatively down-regulated, notably deiodinase-1 (DIO1) (Table 1).
Mutational Analysis of v-Raf Murine Sarcoma Viral Oncogene Homolog B1
BRAF mutational analysis was performed on all tumors in the test set. BRAF mutations were identified in 4 of 14 of the malignant tumors (29%) (Table 3). No borderline tumors or benign tumors had BRAF mutations.







TABLE 3







Presence of BRAF mutation in tumors










BRAF mutation
Percent















PTC (n = 5)
3
60% 



FVPTC (n = 9)
1
11% 



BOR (n = 15)
0
0%



Follicular Adenoma
0
0%



(n = 6)



Hyperplastic Nodule
0
0%



(n = 5)







PTC = papillary thyroid carcinoma;



FVPTC = follicular variant of papillary thyroid carcinoma;



BOR = borderline tumor






Encapsulated follicular lesions with cytologic atypia remain a diagnostic challenge for pathologists. The foregoing experiments employed molecular profiling to identify a third category of thyroid tumors that, based on gene expression data, is likely to be premalignant. This third category of encapsulated follicular tumors with cytologic atypia typically did not fit into previously proposed benign or malignant classification schemes using standard histology, immunohistochemistry, or mutation analysis. The majority of histologically borderline tumors (66.7%) fell into an intermediate group and only a small number share gene expression similarities with benign tumors (26.7%) or malignant tumors (6.7%; Kmeans cluster analysis) (FIG. 4).
Many genes that were expressed differentially between benign tumors and malignant tumors in the training set were classic markers of PTC, including CITED1; dipeptidyl-peptidase 4 (DPP4); FGFR2; and serpin peptidase inhibitor, Glade A (SERPINA1) (see also, Prasad et al., Mod. Pathol. 2005; 18:48-57 (2005); Huang et al., Proc. Natl. Acad. Sci. USA. 98:15044-49 (2001); Jarzab et al., Cancer Res. 65:1587-1597 (2005)).
It is noteworthy that borderline tumors, like malignant tumors, exhibited up-regulated gene expression of CITED1 and pleckstrin and Sec7 domain 3 (PSD3) and down-regulated gene expression of FGFR2 relative to benign tumors (Table 1). These genes and others listed in Table 1 are potential markers of early tumorigenesis.
In contrast, some genes with expression that was consistently altered in malignant tumors exhibited unchanged expression in the borderline group of tumors. For example, DIO1, a differentiation marker that was consistently lost in PTC, was retained in this borderline group. Conversely, MET, SERPINA1, tissue inhibitor of metalloproteinase 1 (TIMP1), and HMGA2, which are genes that were often activated or over-expressed in PTC, exhibited lower expression in the borderline group of tumors relative to the malignant group. These genes may represent gene expression changes that are involved in the later stages of cancer development. These findings indicate that the histologically borderline tumors are premalignant and still lack the complete phenotype of PTC.
The results of BRAF mutation analysis also were in agreement with other studies (see, Nikiforova et al., J Clin Endocrinol Metab. 2003; 88:5399-5404 (2003)), with mutations identified in 29% of malignancies. To date, BRAF mutations have not been identified in benign lesions or in borderline encapsulated follicular tumors (see, Arora et al., World J Surg. 32:1237-1246 (2008); Fontaine et al., Oncogene 27:2228-2236 (2008)). Some studies indicate that BRAF mutations are associated with more aggressive tumors (Frasca et al., Endocr Relat Cancer. 15:191-205 (2008); Kebebew et al., Ann Surg. 246:466-471 (2007)) indicating that borderline tumors are more likely to be indolent tumors.
The finding that BRAF mutation is more frequent in classic PTC than in FVPTC also indicates that, for FVPTCs derived from FAs, BRAF either is uninvolved in carcinogenesis or is involved only as a late event. In addition, because of its higher frequency in classic PTC versus FVPTC, BRAF mutational analysis remains of limited usefulness in the diagnostic evaluation of these lesions.
Of the 15 histologically-defined borderline tumors in this study, 10 were clustered in an intermediate group, separate from benign and malignant clusters (FIG. 3). It is noteworthy that not all borderline tumors were separated into this third group: One tumor was clustered with malignant tumors, and 4 tumors were clustered with benign tumors. Conversely, 3 histologically-unequivocal FVPTCs and 2 FAs were identified in the molecularly intermediate group. Given the data provided herein that FAs, borderline tumors, and FVPTCs are stages of a biologic continuum, such an imperfect correlation between the histological classification and molecular data illustrates that accurate diagnosis should not be based on histological analysis alone.
Immunohistochemical markers have been studied in a few well differentiated tumors of uncertain malignant potential (WDT-UMP) with variable results. Papotti et al. (Mod Pathol. 18:541-546 (2005)) studied the expression of galectin-3 and HBME1 in 13 WDT-UMPs and noted some degree of staining with either antibody in 12 of 13 tumors. Immunohistochemical staining for HBME1, Galectin-3, and CK19 (data not shown) in the histologically borderline tumors that were studied as described herein revealed heterogeneous staining patterns. This variability, again, may reflect the biologically borderline nature of these tumors.
Unfortunately, part of the problem with standard diagnostic tools is the need by clinicians to separate tumors into benign or malignant categories. Partially for that reason, the term WDT-UMP proposed by Williams and by Rosai has not been embraced in practice and certainly is not in use at most institutions (Williams et al., Int J Surg Pathol. 8:181-183 (2000); Rosai, Endocr Pathol. 16:279-283 (2005)). Consequently, the majority of borderline tumors, as in the current study, probably are diagnosed as FVPTCs because of pathologists' general preference to err on the side of over-diagnosis for potential legal concerns. Patients are then often subjected, perhaps unnecessarily, to completion thyroidectomies, central neck dissections, and even radioactive iodine therapy. With the current 2-tiered classification (benign and malignant), our 2-Kmeans cluster would place 73% of histologically borderline tumors in the malignant category. However, such classification is somewhat simplistic and does not correlate with the clinical behavior of these tumors.
Several groups have reviewed the outcome of patients with encapsulated PTC, including both classic PTC and FVPTC (Liu et al., Cancer. 107:1255-1264 (2006); Vickery et al., Am J Surg Pathol. 7: 797-807 (1983); Evans et al., Am J Surg Pathol. 11:592-597 (1987). Liu et al. reviewed the outcome data from 42 patients with encapsulated, noninvasive FVPTCs who had a median 10-year follow-up and reported that no patients had recurrences and that none had lymph node metastasis. Vickery identified 10 patients who had encapsulated papillary cancers; in those patients, none had a recurrence, and only 1 patient had developed lymph node metastasis at a median follow-up of 15 years. Evans identified 7 patients who had encapsulated PTC and reported no recurrences or distant metastases at a median follow-up of 13.5 years. The number of studies that specifically have investigated tumors with borderline features is limited, although no tumor recurrences have been reported (Fusco et al., Am J Pathol. 160:2157-2167 (2002)). Likewise, none of the patients with borderline tumors in the current study had lymph node metastasis, and none of those with clinical follow-up developed recurrent disease or distant metastasis. The data presented here provide evidence that borderline tumors represent a molecularly distinct group of tumors that may not need aggressive treatment.
EXAMPLE 3
Real Time PCR Methods
This example describes procedures for performing reverse transcription, real-time, quantitative PCR (RT-qPCR).
Total RNA from human cells is isolated by a standard mini-column method, RNAeasy® Mini Kit (Qiagen, Valencia, Calif.). RNA sample quality is evaluated based on electrophoretic integrity of 18S and 28S rRNA bands on a 2100 Bioanalyzer instrument (Agilent, Santa Clara, Calif.) and by standard spectrophotometric absorbance methods at 230, 260 and 280 nm wavelengths on a NanoDrop 1000 (NanoDrop/Thermo Scientific, Wilmington, Del.).
Preparation of cDNA from the RNA samples is carried out using 1.0 μg of total RNA into a standard 20 μl MMLV reverse transcriptase (Promega, Madison, Wis.) reaction according to the manufacturer's instructions using Promega buffers with a combination of 50 μg/ml random hexamers (Integrated DNA Technologies, Coralville, Iowa) and 2.5 ng/μl oligo d(T16) (Integrated DNA Technologies, Coralville, Iowa) to prime the first strand synthesis. Upon completion of the reverse transcription protocol, the cDNA sample is diluted with 91 μl nuclease-free water ( ̃5 fold) so that 1 μl ( ̃ 1/100) is used as the template for individual 25 μl PCR reactions.
SYBR® Green real-time PCR is set up by combining 12.5 μl 2× SYBR® Green PCR Master Mix (Applied Biosystems, Foster City, Calif.) with 1 μl cDNA sample, 1 μl PCR primer mix (10 μM each forward and reverse primers from Tables 4 and 5) and 10 μl nuclease-free water in an appropriate reaction tube or plate. Real-time PCR thermal cycling and detection is performed on either an ABI 7500 (Applied Biosystems, Foster City, Calif.) or Stratagene Mx3005P (Agilent, Santa Clara, Calif.) instrument for 1 cycle of 10 minutes at 95° C., then 40 cycles of 15 seconds at 95° C. and 60 seconds at 60° C., followed by the instrument specific dissociation analysis steps.
Using the instrument's software and a consistent selection of measurement variables, Ct values are determined and relative expression measurements obtained by the ΔΔCt calculation method (Livak, K J, Schmittgen, T D. 2001, Methods 25, 402-408).
EXAMPLE 4
Primers and Probes for Detection of Differential Expression
This Example describes primers and probes for detecting expression of the differentially expressed genes described herein.
Thus, the sequences of primers with SEQ ID NO:3-118 are shown below in Tables 4 and 5.
Examples of human sequences (SEQ ID NO:119-172) for the differentially expressed genes ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, and UPP1 are shown in Table 6.







TABLE 4







Forward Primers for Nucleic Acid Amplification


Of Differentially Expressed Genes










Gene Symbol





HGNC
NIH/NCBI




Standard
Transcript ID
Forward Primer Sequence
SEQ ID NO:













ANK2
NM_001127493
AATACTGTGAGAAGAAGTG
3


 


ARHGAP6
NM_001174
GTGCCAAAGGCTGAGGAAATG
4


 


C11orf17
NM_182901
CTCATGTGGTAGCAGTTGATTC
5


 


NAUK2
NM_030952
GAAGTCCCGCAAGGAGAATG
6


 


CAPN3
NM_173090
AGGCTGGCCTCATCCAAAG
7


 


CDH16
NM_004062
GATCGTGTGTCGCTGCAAC
8


 


CSGALNACT1
NR_024040
AGGAAACTCATTCAGACTG
9


(ChGn)





 


CITED1
NM_004143
ATGCCAACCAAGAGATGAG
10


 


CITED2
NM_006079
AATGGGCGAGCACATACAC
11


 


CITED2
NM_006079
TAATAGGGTGTGGAATGTC
12


 


CKB
NM_001823
CTTCCTAACTTATTGCCTG
13


 


COL9A3
NM_001853
GGATCTGCGACACCTCAGC
14


 


CSRP2
NM_001321
GGCCTACAACAAATCCAAAC
15


 


DAPK2
NM_014326
TAGGACACGCAGGAAAGACCAC
16


 


DIO1
NM_000792
TTAAACCTGTCCACATTGGTG
17


 


DPP4
NM_001935
GATAAGAGGGATTAGGGAG
18


 


DTX4
NM_015177
ATTTCCTTTCTAACACTGTG
19


 


DUSP4
NM_001394
TCTAGTTACAGTGGATTTAG
20


 


EFEMP1
NM_001039348
ATCCAGAGTGACAGTGAAC
21


 


ELMO1
NM_001039459
GACTAAACCTAAATGCCTC
22


 


FGFR2
NM_000141
ATCCAGCCTCATACCTACATCAG
23


 


FLRT1
NM_013280
GCTTATTCCATACCATTTC
24


 


FMOD
NM_002023
GGCTCTTCTCCCTCTCCCAG
25


 


GALNT7
NM_017423
GTTGGTAATATCACTATGC
26


 


GATM
NM_001482
GTAATTGGATTTCGCTATC
27


 


HGD
NM_000187
GATGAGAACTACCACAAGTGCTG
28


 


HMGA2
NM_003483
TGTACTTTGAATCGCTTGCTTGTTG
29


 


IGFBP6
NM_002178
TGCAGCAACTCCAGACTGAG
30


 


KIT
NM_001093772
TTGTGTGTTGTCTTGAAAG
31


 


LRP4
NM_002334
GAAGCGATTCTCCCATGCTC
32


 


MATN2
NM_030583
TACGATAAAGTTTGCACAG
33


 


MET
NM_001127500
GAAAGAACTGTCTCTACCAG
34


 


MYH10
NM_005964
ACTACAAGCAGAGACTGAG
35


 


PFAAP5
U50535
CAAGGCAGGCAGATTGTTTG
36


 


PFAAP5
CR601845
TTAGCGGACATGGGTCAATTTC
37


 


PGF
NM_002632
GCTTGTACTGGGACATTGTTC
38


 


IPCEF1
NM_001130700
GATCCAGGACATCTATCAG
39


(PIP3-E)





 


PKNOX2
NM_022062
AGCACGGACACACTGGCAC
40


 


PRKACB
NM_002731
GTGAAAGCACCTTGTAAAC
41


 


PROS1
NM_000313
AGTAAGGAGGTAAGATTGC
42


 


PSD3
NM_206909
GGTAGTGTCTAAGTGGTATG
43


 


PSD3
NM_206909
TGACTTTCAACTAACCTTG
44


 


QPCT
NM_012413
GATATTGTGTCCTAAATTGC
45


 


RAB27A
NM_183236
TGCCAATGGGACAAACATAAG
46


 


RAB27A
NM_183236
GATGCCTGTTTGCTATTTGGTGGAAG
47


 


RXRG
NM_006917
ATTGTACTCTTTAACCCAG
48


 


SDC4
NM_002999
CTTCCTCAGTTGCACTAACCAC
49


 


SERPINA1
NM_000295
TCTGCCAGCTTACATTTACCCAAAC
50


 


SLC25A15
NM_014252
GTGACCGCTCTTGCTCTTG
51


 


SLC4A4
NM_003759
AAGAGTGAATAGTTGCCTC
52


 


SLIT1
NM_003061
CTAGAGGCTGGTTTAGAAC
53


 


SPTAN1
NM_003127
AGTTTGTAGCCAATGTGGAAG
54


 


TFCP2L1
NM_014553
TGATTTCCTGTTATGAGTC
55


 


TIAM1
NM_003253
TTCCATATCATCTCCGGTTCG
56


 


TIMP1
NM_003254
GACTCTTGCACATCACTAC
57


 


TNS3
NM_022748
TGTGCCCAACGCATGTTATAG
58


 


TSPAN12
NM_012338
AGAAAGGACTTGTATGCTG
59


 


UPP1
NM_181597
GTGTGTGTCACCCTCCTGAAC
60
















TABLE 5







Reverse Primers for Nucleic Acid Amplification


of Differentially Expressed Genes










Gene Symbol





HGNC
NIH/NCBI




Standard
Transcript ID
Reverse Primer Sequence
SEQ ID NO:













ANK2
NM_001127493
TTGCAGCTATGTATTGTTAG
61


 


ARHGAP6
NM_001174
GATGGCGATACGCTTCAGTA
62


 


C11orf17
NM_182901
AAGGTGATGTGATGGCAGTG
63


 


NAUK2
NM_030952
TTGGCAGCTTGAGGTTGCTC
64


 


CAPN3
NM_173090
CTTGATCGGTCATGCCTAGCC
65


 


CDH16
NM_004062
GTAGGCACCCTGGTAGCAA
66


 


CSGALNACT1
NR_024040
AAGAGATTGTTTGGTTCAC
67


(ChGn)





 


CITED1
NM_004143
CTCGGGATCTCCAATAGGCTCTC
68


 


CITED2
NM_006079
GTGCCCTCCGTTCACAGTC
69


 


CITED2
NM_006079
AGCTTTCAACACAGTAGTATC
70


 


CKB
NM_001823
ATAAACTCTACCAAGGGTG
71


 


COL9A3
NM_001853
CGTGAGGAAGCAAGTGACA
72


 


CSRP2
NM_001321
GAGAAGATAATTGGAGCTGGAA
73


 


DAPK2
NM_014326
CAATCTTAGACTCTGGCCTCAA
74


 


DIO1
NM_000792
GCTCTCTGTACCCTGAAATCTTC
75


 


DPP4
NM_001935
GTTTGAATAGTCTTTCTCAG
76


 


DTX4
NM_015177
GTCAAGGTAGTAGATGCAC
77


 


DUSP4
NM_001394
GCTACCTTGCACATATCTAC
78


 


EFEMP1
NM_001039348
GATACATCAAAGTAAAGCAG
79


 


ELMO1
NM_001039459
ATGATGTAAACTTGGATGTC
80


 


FGFR2
NM_000141
CAATAGCCGTGCAAGATGAATG
81


 


FLRT1
NM_013280
ATCGACTACATGATTGTTC
82


 


FMOD
NM_002023
GTATGAGACCTACGAGCCTTACC
83


 


GALNT7
NM_017423
ACCCAGAATTAAGATATACG
84


 


GATM
NM_001482
CTTAGATGACCAAAGATGC
85


 


HGD
NM_000187
CTTTCTGGTAGTATTGGAGGAGG
86


 


HMGA2
NM_003483
CAGAGGCTGTTATGTTTATTGTG
87


 


IGFBP6
NM_002178
CATCGAGGCTTCTACCGGAA
88


 


KIT
NM_001093772
AGAGCATAGAACTCCAGTG
89


 


LRP4
NM_002334
CACTGGAGAGATTGGACTTTC
90


 


MATN2
NM_030583
TATATCAAGGTAAAGTCCAG
91


 


MET
NM_001127500
CAAGTGTGTAGTCCTGTTG
92


 


MYH10
NM_005964
GGTTTCTTTCTTCTTCTTC
93


 


PFAAP5
U50535
AATGGCACGATCATGGGTC
94


 


PFAAP5
CR601845
AAGTGTAGCCCAGGTTAAGAAC
95


 


PGF
NM_002632
GAGAAACAGCTCAGCCAGTGG
96


 


IPCEF1
NM_001130700
AAGGTGATTTCTTGAGTTC
97


(PIP3-E)





 


PKNOX2
NM_022062
CTGATGTATCCACCAAACCAGTAC
98


 


PRKACB
NM_002731
CAGTAGTGCATAGGAAATTC
99


 


PROS1
NM_000313
CAGTGAAACATCTGATACAC
100


 


PSD3
NM_206909
ATAGTCATGGACATTTACAG
101


 


PSD3
NM_206909
AAGTTACTAAGACTGCACAG
102


 


QPCT
NM_012413
CTATCGTTGAATGAATGAAC
103


 


RAB27A
NM_183236
CTGAAGGAGTGGTGCGATCAA
104


 


RAB27A
NM_183236
GAAGACACTTTGGCAATGCAGCGG
105


 


RXRG
NM_006917
GATACTTCTGCTTGGTGTAG
106


 


SDC4
NM_002999
GACGACCCTTGTCTCCCTG
107


 


SERPINA1
NM_000295
GCATCACTAAGGTCTTCAGCA
108


 


SLC25A15
NM_014252
GTGGTCAGTAGCCTTATGCACCT
109


 


SLC4A4
NM_003759
ATCATTTCTCTCTCCAAAG
110


 


SLIT1
NM_003061
GGAAGACAACAGACAATATC
111


 


SPTAN1
NM_003127
GATTATGGCGACACTCTTGCC
112


 


TFCP2L1
NM_014553
TACAGTGATGACAGACAGC
113


 


TIAM1
NM_003253
CTTGGAGAGGGTGCCATTGTC
114


 


TIMP1
NM_003254
GATAAACAGGGAAACACTG
115


 


TNS3
NM_022748
CTTGTAACGTCTTCTCTGCCT
116


 


TSPAN12
NM_012338
TATTGACTTGGAGACTATTG
117


 


UPP1
NM_181597
GAAGAAACTGAGCAAGGCC
118









Sequences of the coding regions of ANK2, ARHGAP6, C11orf17, CAPN3, CDH16, ChGn, CITED 1, CITED 2, CKB, COL9A3, CSRP2, DAPK2, DIO1, DPP4, DTX4, DUSP4, EFEMP1, ELMO1, FGFR2, FLRT1, FMOD, GALNT7, GATM, HGD, HMGA2, IGFBP6, KIT, LRP4, MATN2, MET, MYH10, NAUK2, PFAAP5, PGF, PIP3-E, PKNOX2, PRKACB, PROS1, PSD3, QPCT, RAB27A, RXRG, SDC4, SERPINA1, SLC25A15, SLC4A4, SLIT1, SPTAN1, TFCP2L1, TIAM1, TIMP1, TNS3, TSPAN12, and/or UPP1 can be used to develop probes and primers for detecting differential expression of these genes. Such sequences are available in the database maintained by the National Center for Biotechnology Information (NCBI). See website at ncbi.nlm.nih.gov. A few examples of such sequences are provided below.
One example of a nucleic acid sequence for human ANK2 is available as NCBI accession number NM_001148 (gi: 188595661). This sequence is recited below for easy reference as SEQ ID NO:119.









1
ctcctcctcc tgctttcctc cagtaagtgc atacccgcta gtggtctgta caggcggcac



 


61
ggtttgatgg cagagatatt ttctttccaa actgttcaaa atgatgaacg aagatgcagc


 


121
tcagaaaagc gacagtggag agaagttcaa cggcagtagt cagaggagaa aaagacccaa


 


181
gaagtctgac agcaatgcaa gcttcctccg tgctgccaga gcaggcaacc tggacaaagt


 


241
tgtggaatat ctgaaggggg gcatagacat caatacctgc aatcagaatg gactcaacgc


 


301
tctccatctg gctgccaagg aaggccacgt ggggctggtg caggagctgc tgggaagagg


 


361
gtcctctgtg gattctgcca ctaagaaggg aaataccgct cttcacattg catctttggc


 


421
tggacaagca gaagttgtca aagttcttgt taaggaagga gccaatatta atgcacagtc


 


481
tcagaatggc tttactcctt tatacatggc tgcccaagag aatcacattg atgttgtaaa


 


541
atatttgctg gaaaatggag ctaatcagag cactgctaca gaggatggct ttactcctct


 


601
agctgtggca ctccagcaag gacacaacca ggcggtggcc atcctcttgg agaatgacac


 


661
caaagggaaa gtgaggctgc cagctctgca tattgccgct aggaaagacg acaccaaatc


 


721
tgccgcactt ctgcttcaga atgaccacaa tgctgacgta caatccaaga tgatggtgaa


 


781
taggacaact gagagtggtt ttaccccttt gcacatagct gcacattacg gaaatgtcaa


 


841
cgtggcaact cttcttctaa accggggagc tgctgtggac ttcacagcca ggaatggaat


 


901
cactcctctg catgtggctt ccaaaagagg aaatacaaac atggtgaagc tcttactgga


 


961
tcgaggcggt cagatcgatg ccaaaactag ggatgggttg acaccacttc actgtgctgc


 


1021
acgaagtggg catgaccaag tggtggaact tctgttggaa cggggtgccc ccttgctggc


 


1081
aaggactaag aatgggctgt ctccactaca catggctgcc cagggagacc acgtggaatg


 


1141
tgtgaagcac ctgttacagc acaaggcacc tgttgatgat gtcaccctag actacctgac


 


1201
agccctccac gttgctgcgc actgtggcca ctaccgtgta accaaactcc ttttagacaa


 


1261
gagagccaat ccgaacgcca gagccctgaa tggttttact ccactgcaca ttgcctgcaa


 


1321
gaaaaaccgc atcaaagtca tggaactgct ggtgaaatat ggggcttcaa tccaagctat


 


1381
aacagagtct ggcctcacac caatacatgt ggctgccttc atgggccact tgaacattgt


 


1441
cctccttctg ctgcagaacg gagcctctcc agatgtcact aacattcgtg gtgagacggc


 


1501
actacacatg gcagcccgag ccgggcaggt ggaagtggtc cgatgcctcc tgagaaatgg


 


1561
tgcccttgtt gatgccagag ccagggagga acagacacct ttacatattg cctcccgcct


 


1621
gggtaagaca gaaattgtcc agctgcttct acaacatatg gctcatccag atgcggccac


 


1681
tacaaatggg tacacaccac tgcacatctc tgcccgggag ggccaggtgg atgtggcatc


 


1741
agtcctattg gaagcaggag cagcccactc cttagctacc aagaagggtt ttactcccct


 


1801
gcatgtagca gccaagtatg gaagcctgga tgtggcaaaa cttctcttgc aacgccgtgc


 


1861
tgccgcagat tctgcaggga agaacggcct taccccgctc catgttgctg ctcattatga


 


1921
caaccagaag gtggcgctgc tgttactgga gaagggtgct tcccctcatg ccactgccaa


 


1981
gaatggctat actccgttac atattgctgc caagaagaat caaatgcaga tagcttccac


 


2041
actcctgaac tatggagcag agacaaacat tgtgacaaag caaggagtaa ctccactcca


 


2101
tctggcctcg caggaggggc acacagatat ggttaccttg cttctggata agggagccaa


 


2161
tatccacatg tcaactaaga gtggactcac atccttacac cttgcagccc aggaagataa


 


2221
agtgaatgtt gctgatattc tcaccaagca tggagctgat caggatgctc atacaaagct


 


2281
tggttacaca cctttaattg tggcctgtca ctatggaaat gtgaaaatgg tcaactttct


 


2341
tctgaagcag ggagcaaatg ttaacgcaaa aaccaagaac ggctacacgc ctttgcacca


 


2401
ggccgctcag cagggtcaca cgcacatcat caacgtcctg ctccagcatg gggccaagcc


 


2461
caacgccacc actgcgaatg gcaacactgc cttggcgatt gctaagcgtc tgggctacat


 


2521
ctccgtggtc gacaccctga aggttgtgac tgaggaggtc accaccacca ccacaactat


 


2581
tacagaaaaa cacaaactaa atgtacctga gacgatgact gaggttcttg atgtttctga


 


2641
tgaagagggt gatgacacaa tgactggtga tgggggagaa taccttaggc ctgaggacct


 


2701
aaaagaactg ggtgatgact cactacccag cagtcagttc ctggatggta tgaattacct


 


2761
gcgatacagc ttggagggag gacgatctga cagccttcga tccttcagtt ccgacaggtc


 


2821
tcacactctg agccatgcct cctacctgag ggacagtgcc gtgatggatg actcagttgt


 


2881
gattcccagt caccaggtgt caactctagc caaggaggca gaaaggaatt cttatcgcct


 


2941
aagctggggc actgagaact tagacaacgt ggctctttct tctagtccta ttcattcagg


 


3001
tttcctggtt agttttatgg tggatgcccg aggtggtgct atgcgaggat gcagacacaa


 


3061
tgggctccga atcattattc cacctcggaa atgtactgct ccaacgcgag tcacctgccg


 


3121
actggtcaag cgccacagac tggcaacaat gcctccaatg gtggaaggag aaggcctggc


 


3181
cagtcgcctg atcgaagttg gaccttctgg tgctcagttc cttggtaaac ttcacctgcc


 


3241
aacggctcct cccccactta atgagggaga aagtttggtc agccgcattc ttcagctggg


 


3301
gcctcctgga accaaattcc ttgggcctgt gatcgtggag atccctcact ttgcggccct


 


3361
tcgaggaaag gaaagggaac tggtggtcct gcgcagtgag aatggggaca gctggaaaga


 


3421
gcatttctgt gactacactg aagatgaatt gaatgaaatt cttaacggca tggatgaagt


 


3481
actggatagc ccagaagacc tagaaaagaa acgaatctgc cgcatcatca cccgagactt


 


3541
cccacagtac tttgcagtgg tgtctcgtat caaacaggac agcaatctga ttggcccaga


 


3601
aggaggtgta ctgagcagca cagtggtgcc ccaggtgcag gccgtcttcc cagagggggc


 


3661
actcaccaag cggatccgcg taggcctgca ggctcaacct atgcacagtg agctggttaa


 


3721
gaagatccta ggcaacaaag ctaccttcag ccctatagtc actttggaac ctagaagaag


 


3781
aaaattccac aaaccaatta ccatgaccat tcctgtcccc aaagcttcaa gtgatgtcat


 


3841
gttgaatggt tttgggggag atgcaccaac cttaagatta ctatgcagca taacaggtgg


 


3901
aaccacccct gcccagtggg aagatattac aggaactacg ccattaacat ttgtcaatga


 


3961
atgtgtttcc tttacaacaa acgtgtctgc caggttctgg ctgatagatt gtcgacagat


 


4021
ccaggaatcc gttacttttg catcacaagt atacagagaa attatctgcg taccttatat


 


4081
ggccaaattt gtagtgtttg ccaaatcaca tgaccccatt gaagccaggt tgaggtgttt


 


4141
ctgcatgact gatgataaag tggataagac ccttgaacaa caagaaaatt ttgctgaggt


 


4201
ggccagaagc agggatgtgg aggtgttaga aggaaaaccc atctacgttg attgtttcgg


 


4261
caacttggta ccattaacta aaagtggcca gcatcatata ttcagttttt ttgccttcaa


 


4321
agaaaataga cttcctctat ttgtcaaggt acgcgatacg actcaggaac cttgcggacg


 


4381
actatcattt atgaaggagc caaaatccac gagaggcctg gtgcatcaag ctatttgcaa


 


4441
cttaaacatc actttgccga tttatacaaa ggaatcagag tcagatcaag aacaggagga


 


4501
agagatcgat atgacatcag aaaaaaatga tgagacagaa tctacagaaa catctgtcct


 


4561
gaaaagtcac ctggttaatg aagttcctgt cctagcaagt ccggacttgc tctctgaagt


 


4621
ttctgagatg aaacaagatt tgatcaaaat gaccgccatc ttgaccacag atgtgtctga


 


4681
taaggcaggt tctattaaag tgaaggagct ggtgaaggct gctgaggaag agccaggaga


 


4741
gccttttgaa atcgttgaaa gagttaaaga ggacttagag aaagtgaatg aaatcctgag


 


4801
aagtggaacc tgcacaagag atgaaagcag tgtgcagagc tctcggtctg agagaggatt


 


4861
agttgaagag gaatgggtta ttgtcagtga tgaggaaata gaagaggcta ggcaaaaagc


 


4921
acctttagaa atcactgaat atccatgtgt agaagttaga atagataaag agatcaaagg


 


4981
aaaagtagag aaagactcaa ctgggctagt gaactacctt actgatgatc tgaatacctg


 


5041
tgtgcctctt cccaaagagc agctgcagac agttcaagat aaggcaggga agaaatgtga


 


5101
ggctctggct gttggcagga gctctgaaaa ggaagggaaa gacatacccc cagatgagac


 


5161
acagagtaca cagaaacagc acaaaccaag cttgggaata aagaagccag taagaaggaa


 


5221
attaaaagaa aagcagaaac aaaaagagga aggtttacaa gctagtgcag agaaagctga


 


5281
acttaaaaaa ggtagttcag aagagtcatt aggtgaagac ccaggtttag cccctgaacc


 


5341
ccttcccact gtcaaggcca catctccttt gatagaagaa actcccattg gttccataaa


 


5401
ggacaaagta aaggcccttc agaagcgagt ggaagatgaa cagaaaggtc gaagcaagtt


 


5461
gcccatcaga gtcaaaggca aggaggacgt gccaaaaaag accacccaca ggccacatcc


 


5521
agctgcgtca ccctctctga agtcagagag acatgcgcca gggtctccct cccctaaaac


 


5581
agaaagacac tctactcttt cctcttccgc aaaaactgaa aggcaccctc cagtatcacc


 


5641
atcaagtaaa actgagaaac actcacctgt gtcaccctct gcaaaaacgg aaagacattc


 


5701
acctgcgtca tcatcgagta aaactgagaa acactcacct gtatcaccct cgacaaaaac


 


5761
tgaaaggcac tctcctgtgt catctacaaa aacagaaaga cacccacctg tttcgccttc


 


5821
aggcaaaaca gacaaacgtc cacctgtatc gccctccggg aggacagaaa aacacccgcc


 


5881
agtatcgcct gggagaacag aaaaacgctt gcctgtttca ccctccggaa gaacggacaa


 


5941
gcaccaacct gtatcaacag ctgggaaaac tgagaagcac ctgcctgtgt caccttctgg


 


6001
caaaacagaa aagcaaccac ctgtatcccc cacttcaaaa acagagagga ttgaggaaac


 


6061
catgtctgtt cgggagctga tgaaggcttt ccagtcaggt caggaccctt ctaaacataa


 


6121
aactggactc tttgagcaca aatcagcaaa acaaaagcag ccacaagaga aaggtaaagt


 


6181
tcgggtagaa aaagaaaagg ggccgatact aacccagaga gaagctcaga aaacagagaa


 


6241
tcagacaatc aaacgaggcc agagactccc ggtaacgggc acagcagaat ccaaaagagg


 


6301
agttcgtgtt tcctccatag gagttaagaa agaagatgca gctggaggaa aggagaaagt


 


6361
tctcagccac aaaatacctg aacctgttca gtcagtgcct gaagaagaaa gccacagaga


 


6421
gagcgaagtg cccaaagaaa agatggctga tgagcaggga gacatggatc tacagatcag


 


6481
cccagatagg aaaacctcca ctgacttctc tgaggtcatt aagcaagagt tggaagacaa


 


6541
tgacaaatac caacaattcc gcctgagtga ggagacagaa aaggcacagc ttcacttaga


 


6601
ccaagtactc actagtcctt tcaacacaac atttccactc gactacatga aagatgagtt


 


6661
ccttccagct ctgtctttac aaagcggtgc tttagatggc agttctgaaa gcctaaagaa


 


6721
tgagggggta gccggctctc cgtgtggcag cctgatggag gggacccctc agattagttc


 


6781
agaagaaagc tataagcatg aaggcctagc agagacccct gagacgagcc cagaaagcct


 


6841
ttctttctca ccaaagaaaa gtgaggagca aactggggaa acaaaggaaa gcaccaagac


 


6901
agaaaccacc acagaaattc gttcagaaaa agagcatccc acgaccaaag acattactgg


 


6961
tggctctgaa gagcgaggtg ccacagtcac tgaggactca gagacctcta ctgagagttt


 


7021
tcagaaagag gccactctag gctctcccaa agacacaagc cctaaaagac aagatgattg


 


7081
cacaggcagc tgtagtgtag cattagctaa agagacacct acaggactga ctgaggaggc


 


7141
agcctgtgat gaaggtcaac gtacctttgg tagttcagcc cacaagacac aaactgatag


 


7201
tgaggttcaa gaatccacag ccacctcaga cgagacaaag gccttgccgc tgcctgaggc


 


7261
ttctgtaaag acagatacag gaactgaatc aaaacctcag ggagtcatta gaagtcccca


 


7321
agggttagaa cttgcactcc ctagccgaga tagcgaagtc ctcagcgctg tggctgatga


 


7381
ctcattagca gtgagccaca aagactctct ggaagccagc cctgtgctag aagataactc


 


7441
ttcacacaaa acccctgatt ctctggagcc aagtcctctg aaagaatccc cttgccgtga


 


7501
ctctctggaa agcagccctg ttgaaccaaa gatgaaggct ggaatttttc caagtcactt


 


7561
tcctcttcct gcagctgttg ccaaaacaga actcttgacg gaagtggcct ctgtgcggtc


 


7621
ccggctactc cgagaccctg atggcagtgc tgaggatgac agtcttgagc agacatcgct


 


7681
catggagagc tcagggaaga gccccctttc tcctgacacc cccagctctg aagaagtcag


 


7741
ctatgaggtt acacccaaaa ccacagatgt aagtacacca aaaccagctg tgattcatga


 


7801
atgtgcagag gaggatgatt cagaaaacgg ggagaaaaag aggttcacac ctgaagagga


 


7861
gatgtttaaa atggtaacca aaatcaaaat gtttgatgaa cttgaacaag aagcaaagca


 


7921
gaaaagggac tacaaaaaag aacccaaaca agaagaatct tcttcatctt ctgacccaga


 


7981
tgctgactgt tcagtagatg tggatgaacc aaaacataca ggcagtgggg aggatgaaag


 


8041
tggtgtccct gtgttagtaa cttcggagag caggaaggtg tcttcctcct cagaaagtga


 


8101
acctgagttg gcacagctta aaaaaggtgc tgactcaggc cttttaccag aaccagtgat


 


8161
tcgagtacaa cctccttctc cacttccatc aagcatggac tccaattcca gtccagaaga


 


8221
agtacaattc cagcctgtcg tttccaaaca atatactttc aagatgaatg aagatactca


 


8281
ggaagagcca ggcaaatcag aagaagaaaa agattctgaa tcccatttag ctgaagaccg


 


8341
tcatgctgtt tccactgagg ctgaagacag gtcttatgat aagctaaaca gagacactga


 


8401
tcagccaaaa atctgtgatg gccatggatg tgaggccatg agtcctagca gctcagctgc


 


8461
tcctgtctct tcaggtctac agagtccgac tggtgatgat gttgatgaac agccagtcat


 


8521
ctataaagaa tcattagctc tccaaggcac tcatgaaaaa gacacagagg gagaagagct


 


8581
tgatgtttct agagcagaat ctccacaagc agattgcccc agtgaaagct tttcatcttc


 


8641
atcctctttg cctcattgtt tggtatctga aggaaaagaa ttagatgaag acatatctgc


 


8701
cacatcttct attcaaaaaa cagaggtcac aaaaactgat gaaacatttg agaacttacc


 


8761
aaaggactgc ccctctcaag actcatccat tactactcaa acagatagat tttccatgga


 


8821
tgttcccgtg tctgacctag ctgagaatga tgaaatctat gatccacaaa tcactagccc


 


8881
ttatgaaaat gtcccttccc aatctttttt ctctagtgaa gaaagcaaaa cccaaacaga


 


8941
tgcaaatcac accacaagtt ttcactcttc tgaagtgtat tctgttacca tcacatcccc


 


9001
tgttgaagac gttgtagtgg caagctcctc tagtggaact gttttaagca aagaatctaa


 


9061
ttttgagggc caggacataa aaatggaatc ccaacaggaa agtaccttgt gggaaatgca


 


9121
atcagacagt gtctcttcat ctttcgagcc tactatgtcc gctacaacaa cagttgttgg


 


9181
tgaacaaata agcaaagtca tcatcacaaa aactgatgtg gattctgatt cttggagtga


 


9241
aattcgggaa gacgatgaag cctttgaggc tcgtgtgaaa gaggaagaac aaaagatatt


 


9301
tggtttgatg gtagacagac aatcacaggg taccacccct gacaccactc ctgctaggac


 


9361
cccaactgaa gaggggaccc caacaagtga gcaaaaccca tttctgtttc aggaaggaaa


 


9421
attgtttgaa atgacccgaa gtggtgccat tgatatgacc aaaaggtcct atgcagatga


 


9481
aagttttcac tttttccaaa ttggtcaaga atccagggaa gagactctct ctgaagatgt


 


9541
gaaagaaggg gctactgggg ctgatcccct accgctggag acatcagctg aatcactagc


 


9601
actttcagaa tcaaaagaaa cagtggatga tgaggcagac ttacttccag atgacgtgag


 


9661
tgaggaagta gaggaaatac ctgcttcgga tgctcaactt aactcccaaa tggggatttc


 


9721
agcctccact gaaacaccta caaaagaagc tgttagtgta gggaccaagg acctccccac


 


9781
cgtgcaaacg ggtgatatac ctcctctctc tggtgtaaag cagatatcct gccccgactc


 


9841
ttctgaacca gctgtacaag tccagttaga tttttccaca ctcaccaggt ctgtttattc


 


9901
agataggggt gatgattctc ccgattcttc cccagaagaa cagaaatcag taatcgagat


 


9961
tcctactgca cccatggaga atgtgccttt tactgaaagc aaatccaaaa ttcctgtaag


 


10021
gactatgccc acttccaccc cagcacctcc atctgcagag tatgagagtt cagtttctga


 


10081
agattttcta tccagtgtag atgaggaaaa taaggcggat gaagcaaaac caaagtccaa


 


10141
actccctgtc aaagtacccc tccaaagagt tgaacagcag ctctcagatc tagacacctc


 


10201
tgtccagaag acagtggctc ctcagggaca ggacatggca agcatcgcac cagataatag


 


10261
aagcaaatct gaatctgatg ctagttcttt ggattcaaag accaaatgcc cagtaaaaac


 


10321
ccgaagttac actgagacag aaacagagag cagagagagg gccgaggaac ttgagttaga


 


10381
atcagaagaa ggggccacaa gaccaaagat acttacatcc cgattgccag ttaagagcag


 


10441
aagcactaca tcttcctgca gggggggcac gagccccaca aaagaaagta aggagcattt


 


10501
ctttgacctt tacagaaatt ccatagaatt ctttgaggag attagtgatg aggcttccaa


 


10561
attagtggat aggctgacac agtcagagag ggagcaggaa atagtttcag acgatgaaag


 


10621
tagtagtgcc ctggaagtat cagtaattga aaatctgcca cctgttgaga ccgagcactc


 


10681
agttcctgag gacatctttg acacaaggcc catttgggat gagtctattg agactctgat


 


10741
tgaacgcatc cctgatgaaa atggccatga ccatgctgaa gatccacagg atgagcagga


 


10801
acggatcgag gaaaggctgg cttatattgc tgatcacctt ggcttcagct ggacagaatt


 


10861
agcaagagaa ctggatttca ctgaggagca aattcatcaa attcgaattg aaaatcccaa


 


10921
ctctcttcaa gaccagagtc atgcactgtt gaagtactgg ctagagaggg atgggaaaca


 


10981
tgctacagat accaacctcg ttgaatgtct caccaagatc aaccgaatgg atattgttca


 


11041
tctcatggag accaacacag aacctctcca ggagcgcatc agtcatagtt atgcagaaat


 


11101
tgaacagacc attacactgg atcatagtga agggttctcg gtacttcaag aggagttatg


 


11161
cactgcacag cacaagcaga aagaggagca agctgtttct aaagaaagtg agacctgcga


 


11221
tcaccctcct atcgtctcag aggaagacat ttctgttggt tattccactt ttcaggatgg


 


11281
cgtccccaaa actgaggggg acagctcagc aacagcactc tttccccaaa ctcacaagga


 


11341
gcaagttcaa caggatttct cagggaaaat gcaagacctg cctgaagagt catctctgga


 


11401
atatcagcag gaatattttg tgacaactcc aggaacagaa acatcagaga ctcagaaggc


 


11461
tatgatagta cccagctctc ccagcaagac acctgaggaa gttagcaccc ctgcagagga


 


11521
ggagaagctg tacctccaga ccccaacatc cagcgagcgg ggaggctctc ccatcataca


 


11581
agaacccgaa gagccctcag agcacagaga ggagagctct ccgcggaaaa ccagcctcgt


 


11641
aatagtggag tctgccgata accagcctga gacctgtgaa agactcgatg aagatgcagc


 


11701
ttttgaaaag ggagacgata tgcctgaaat acccccagaa acagtcacag aagaagaata


 


11761
cattgatgag catggacaca ccgtggtaaa gaaggttact aggaaaatca ttaggcggta


 


11821
tgtatcctct gaaggcacag agaaagaaga gattatggtg cagggaatgc cacaggaacc


 


11881
tgtcaacatc gaggaagggg atggctattc caaagttata aagcgtgttg tattgaagag


 


11941
tgacaccgag cagtcagagg acaacaatga gtaaagccat cacacagaag agggctgtgg


 


12001
tgaaggacca gcatggaaaa cgcattgact tggagcacct ggaggatgta ccagaagcac


 


12061
tagaccagga cgacctccag cgcgatctcc agcagctcct tcggcatttc tgcaaggagg


 


12121
acttgaagca agaggccaag tgaggggctg cccagttctc acaccagaaa ccacacattc


 


12181
actcaatatg cagcttcctg tttcagtagg ggagtgacct aactggccta attaatggga


 


12241
taccccgaca tttccactgt tagcaaatat acggcatttt gctttagttt tcccccatcc


 


12301
tctttaacta taaagctaat ttgtgaccaa agatggcatc cttcatactg gatgctgtat


 


12361
ccaatacttt gttgtgtctg tgctaacctg ggaactggcc acctccattg ttctttgctt


 


12421
ctgcacaaga tccatgaaaa tccattgatc agaagaactt cacctgcaga cctcttcaag


 


12481
tgacactatg taggaatcct tccaaggaat atctatgtac aatgtatata gctgaaatgc


 


12541
tcagatgaac aacatattaa aattaaaacc actgcctatt gtaactacac tgggcatcag


 


12601
aataaaaggc ctctagaaat tgctgaacaa tggttaatta agatattgct aacacaatcg


 


12661
agtgataata cagttttact gcaaaagaag cacttcaaac ctattatgtc cttagaactt


 


12721
ccagagtagc cactgctccc agttaaaggt gggtcagtag ccttgcagaa ctgtcctgag


 


12781
aagttattgc tggtgctggc cagccatggc ttaggactcc aacagccact ctgagggagg


 


12841
ggagaaggga gcagaggcca cgcagaatga accgatgggg tattcagttg ctggcagcta


 


12901
cattgtgtgg cattctagca tcttcaggtc tttagatctt ggacaagttg gcagggtatt


 


12961
ttaaaagcta taactactgt agttttccag ttttcattgc tgctttagca aaccacgctg


 


13021
tcttacagtg gtactttctt ctggccactg cactgtagat aattcattgg aaacaagatt


 


13081
tacccactac ataaaaggtt aaactccttc agtatgttgg agtggtttct tttttttttt


 


13141
ctttctttct tttttttctt caggtttata tcttctctaa tacctgcatg tggcgtttaa


 


13201
aaatcaagac cacggtcaaa cccctcttct aatcacatta attgtttcca ttctttttac


 


13261
cctgagtgag cacttttcac tttccagcta ggtctgtttt tcagcttgca gacaagattg


 


13321
agaaatcctt gaaaatttgg ttttggttaa aatttttggt ttatttattt gaaatccaca


 


13381
ctcccttgga aactcttaag tgcatttgtg cacttctgtt tgtttgtctc aaagaaggga


 


13441
ctgtaacaat ctgagtaatt tccatgtcct cttccttatt cctctagtgg ttgaagctgt


 


13501
gtagcatttt aacatatata tattcacaaa tatattcata taaacagtat acattttgaa


 


13561
tcagtcattt gttaaagaaa agtatattca atgaagatga aatttaaata aaaaaggaca


 


13621
gagtctatcc tccagggatt gaacattttc caattatctg gtcttttcct gttgtgcaaa


 


13681
aatgactcat tgctccgaat gtcaaaaaca aatgcgacaa acaatggcac ttcatcattt


 


13741
aaagtaatgt tgccaagaga aaaaatttcc tgggagggag gtttcccaca agccaaatct


 


13801
cctaagcctc aaatgctagc actttttggc agttggatag gaaatgagac attctttggc


 


13861
agccaaaata agagaggccg atggtgaaac tttttgagac accctatggc cttcttgtca


 


13921
aaaccttcac tggagctcaa gaaaagcatt tctgttgtgt tatttgcagt gcagatgatg


 


13981
tctgtgtaac aacataatgg ttattcacct ttttttgatt ttgatttttg ctgtgttatc


 


14041
aaaaacttga atactgtgag aagaagtgaa ttttcagttg acgaatcagc atcttgttcc


 


14101
catggtgata acactaattg aatatatcta tgagggcatg tattagttaa tggaaaaaaa


 


14161
aatacaacac taacaataca tagctgcaat gtgtacaatg gctgatttaa ttaaataaaa


 


14221
tgtacaagtg ttaaatgtgg caa






One example of a nucleic acid sequence for human ARHGAP6 is available as NCBI accession number NM_013427 (gi: 95091874). This sequence is recited below for easy reference as SEQ ID NO:120.









1
ggctgggctg cgaatagcgt gttcctctcc ggcggaacac acacacccgg ccttggggct



 


61
gtctcctgag ctccctcctc cacggagagc gctgagcgcc gccgggaatt ccatcccacc


 


121
gtgggcacgc agtctttgga ggtcccgggc gcagcacgct cggtgtcccc acactgcagc


 


181
aagacagaga ccccgcggga accttgagct tggaacaacc cttgagcctc tgcagtcgga


 


241
agagtgggcg cagcagccca gcggaggcca ggcgcgcaac ctcgggcgcc ggggcaagga


 


301
gagagtgcag ggaggcgcag ctcaggcgcc cggctcagga gcgggaggaa gttctcgcgg


 


361
cgccgggagc gcggtggacg cgccctgggc gcacgcccag gcagccttct ccctggccct


 


421
cgggactgtc ctcgggccgc aaggaggagc ttgctggagt cttagaggcc atccagagcc


 


481
agcgagcagg agcgctgcgt ctcccgcctc agctaggaag ggggagtggc gctggcaggc


 


541
tggagctggg aacccagcga gcgcctgacc ttcctcctcc tcttcctgac cctcttcgcg


 


601
tcttgggctc cggaggaagg ttctagcggc tgcaggaggt ccccagaccc attttcctag


 


661
aaggctggtg atggatctgc tgctcctgcc gccgccgggg cacttggagc gcaccggcgg


 


721
cgcgtgagct gggctttgct ctccactgcc ctgggcaaac cccgggccag ccccgcctgg


 


781
cacctttgcc tgagtccctt tcggttcccg acccaaagcc accagcgtcc agggagggag


 


841
gaggaggtgg tcctcaggtg cagccccgcc gagatgtccg cgcagagcct gctccacagc


 


901
gtcttctcct gttcctcgcc cgcttcaagt agcgcggcct cggccaaggg cttctccaag


 


961
aggaagctgc gccagacccg cagcctggac ccggccctga tcggcggctg cgggagcgac


 


1021
gaggcgggcg cggagggcag tgcgcgggga gccacggcgg gccgcctcta ctccccatca


 


1081
ctcccagccg agagtctcgg ccctcgcttg gcgtcctctt cccggggtcc gccccccagg


 


1141
gccaccaggc taccgcctcc tggacctctt tgctcgtcct tctccacacc cagcaccccg


 


1201
caggagaagt caccatccgg cagctttcac tttgactatg aggttcccct gggtcgcggc


 


1261
ggcctcaaga agagcatggc ctgggacctg ccttctgtcc tggccgggcc agccagtagc


 


1321
cgaagcgctt ccagcatcct ctgttcatcc gggggaggcc ccaatggcat cttcgcttct


 


1381
cctaggaggt ggctccagca gaggaagttc cagtccccac ccgacagtcg cgggcacccc


 


1441
tacgtcgtgt ggaaatccga gggtgatttc acctggaaca gcatgtcagg ccgcagtgta


 


1501
cggctgaggt cagtccccat ccagagtctc tcagagctgg agagggcccg gctgcaggaa


 


1561
gtggcttttt atcagttgca acaggactgt gacctgagct gtcagatcac cattcccaaa


 


1621
gatggacaaa agagaaagaa atctttaaga aagaaactgg attcactagg aaaggagaaa


 


1681
aacaaagaca aagaattcat cccacaggca tttggaatgc ccttatccca agtcattgcg


 


1741
aatgacaggg cctataaact caagcaggac ttgcagaggg acgagcagaa agatgcatct


 


1801
gactttgtgg cttccctcct cccatttgga aataaaagac aaaacaaaga actctcaagc


 


1861
agtaactcat ctctcagctc aacctcagaa acaccgaatg agtcaacgtc cccaaacacc


 


1921
ccggaaccgg ctcctcgggc taggaggagg ggtgccatgt cagtggattc tatcaccgat


 


1981
cttgatgaca atcagtctcg actactagaa gctttacaac tttccttgcc tgctgaggct


 


2041
caaagtaaaa aggaaaaagc cagagataag aaactcagtc tgaatcctat ttacagacag


 


2101
gtccctaggc tggtggacag ctgctgtcag cacctagaaa aacatggcct ccagacagtg


 


2161
gggatattcc gagttggaag ctcaaaaaag agagtgagac aattacgtga ggaatttgac


 


2221
cgtgggattg atgtctctct ggaggaggag cacagtgttc atgatgtggc agccttgctg


 


2281
aaagagttcc tgagggacat gccagacccc cttctcacca gggagctgta cacagctttc


 


2341
atcaacactc tcttgttgga gccggaggaa cagctgggca ccttgcagct cctcatatac


 


2401
cttctacctc cctgcaactg cgacaccctc caccgcctgc tacagttcct ctccatcgtg


 


2461
gccaggcatg ccgatgacaa catcagcaaa gatgggcaag aggtcactgg gaataaaatg


 


2521
acatctctaa acttagccac catatttgga cccaacctgc tgcacaagca gaagtcatca


 


2581
gacaaagaat tctcagttca gagttcagcc cgggctgagg agagcacggc catcatcgct


 


2641
gttgtgcaaa agatgattga aaattatgaa gccctgttca tggttccccc agatctccag


 


2701
aacgaagtgc tgatcagcct gttagagacc gatcctgatg tcgtggacta tttactcaga


 


2761
agaaaggctt cccaatcatc aagccctgac atgctgcagt cggaagtttc cttttccgtg


 


2821
ggagggaggc attcatctac agactccaac aaggcctcca gcggagacat ctccccttat


 


2881
gacaacaact ccccagtgct gtctgagcgc tccctgctgg ctatgcaaga ggacgcggcc


 


2941
ccggggggct cggagaagct ttacagagtg ccagggcagt ttatgctggt gggccacttg


 


3001
tcgtcgtcaa agtcaaggga aagttctcct ggaccaaggc ttgggaaaga tctgtcagag


 


3061
gagcctttcg atatctgggg aacttggcat tcaacattaa aaagcggatc caaagaccca


 


3121
ggaatgacag gttcctctgg agacattttt gaaagcagct ccctaagagc ggggccctgc


 


3181
tccctttctc aagggaacct gtccccaaat tggcctcggt ggcaggggag ccccgcagag


 


3241
ctggacagcg acacgcaggg ggctcggagg actcaggccg cagcccccgc gacggagggc


 


3301
agggcccacc ctgcggtgtc gcgcgcctgc agcacgcccc acgtccaggt ggcagggaaa


 


3361
gccgagcggc ccacggccag gtcggagcag tacttgaccc tgagcggcgc ccacgacctc


 


3421
agcgagagtg agctggatgt ggccgggctg cagagccggg ccacacctca gtgccaaaga


 


3481
ccccatggga gtgggaggga tgacaagcgg cccccgcctc catacccggg cccagggaag


 


3541
cccgcggcag cggcagcctg gatccagggg cccccggaag gcgtggagac acccacggac


 


3601
cagggaggcc aagcagccga gcgagagcag caggtcacgc agaaaaaact gagcagcgcc


 


3661
aactccctgc cagcgggcga gcaggacagt ccgcgcctgg gggacgctgg ctggctcgac


 


3721
tggcagagag agcgctggca gatctgggag ctcctgtcga ccgacaaccc cgatgccctg


 


3781
cccgagacgc tggtctgagc ccgcacccag ccgagccccc cctgccccga gccccccgcc


 


3841
ctccagccca ggggggaccg tgggtggtgg ccactggcac acttagtgtt cttctttcac


 


3901
acttctcaaa agtgacacaa gagaaatcca gttcacctac agaggtagag cactcacgcc


 


3961
cccgccattg agaataaggt tccattgcgt agccagcctt aggaaaaaca aacagaaccc


 


4021
aaaccagatg gcaatgtcca atctaaaaac gtccctcttg gctctataat ataagataca


 


4081
actcttgctt ggtatagcct aaccgtattt atgtgtcttc ggttttgact attgtgtatt


 


4141
ctgtaacaga ttatgtataa tcatatatga tatattcaca aagagaaaac aaaaggaact


 


4201
tttaaaaaaa aaatcacttc acttatatta agcaatgaga tatactaaac aatgagattc


 


4261
tatagaatgt tctagaatgt gcacaagcgg gtttctgtgc ttttgccata gctttataac


 


4321
tggggataac ccttccttcg ataccaaaca ctaacaagag gaagcagaat atgagaagcc


 


4381
atatttttac ataggagtca gatacaaaaa gaaaaatcac tgaatgcttt tagatattga


 


4441
atacgttttc aggaaaatgc taaatctgat agattacgaa atatattttt agaacttgtt


 


4501
tagaaaggat tcagttaacc aaacaagaaa aaggcagtgc ctcacaaaga aattaagaag


 


4561
ttgtccgtcc cacgttacat caaattcagt tttatatagg ccatatataa tatatattta


 


4621
taatgtataa tttttatgta tttttcaaaa ctacaaactg gaatccaact ataaagtgtt


 


4681
taagaatcta cacagaatat tcaaattata gaacatgttt tttccctttg ccccataatc


 


4741
agtatttgcc aaattacatg caattcctta aaaactaaat cacatttggt aaaaggccta


 


4801
cagctttgta cttacattgt gccaaaggct gaggaaatgt tttctttcgt aattttatgt


 


4861
gtattgtaaa atgttctacc gtactttagt agtttgaagt ttttcaagtg cataactatt


 


4921
tttgaccagc agatggcgat acgcttcagt attttatgca attttttttc acttctgaag


 


4981
ggaaagtgta ttataaaaaa agattttttt tttttttata aaacatgcta ctcttaattt


 


5041
tcatgttggt gatgaaattc ccagtggtgt ttcttaaggt tctatcttgt gccatgatga


 


5101
ataaaaagtt aagcaaag






One example of a nucleic acid sequence for human C11orf17 is available as NCBI accession number NM_182901 (gi: 116174739). This sequence is recited below for easy reference as SEQ ID NO:121.









1
agatgaaaat ggaaggggcg ggcgcgctag gcctagtcct ggctgggctc ccgctggagt



 


61
gtgcgttggg ggcggaccag gagcggtggt ctccagggag gtcgaggctg gggctcccac


 


121
ccggatttgg agcagggtcg ccgcggccca gctgacccgc cggcgtttgt acgttgtgtg


 


181
cccactcagg gagccatgga caactgtttg gcggccgcag cgctgaatgg ggtggaccga


 


241
cgttccctgc agcgttcagc aaggctggct ctagaagtgc tggagagggc caagaggagg


 


301
gcggtggact ggcatgccct ggagcgtccc aaaggctgca tgggggtcct tgcccgggag


 


361
gcgccccacc tagagaaaca gccggcagcc ggcccgcagc gcgttctccc gggagagaga


 


421
gaagagagac ccccaaccct tagtgcttcc ttcagaacaa tggctgaatt catggactat


 


481
acttcaagtc agtgtgggaa atattattca tctgtgccag aggaaggagg ggcaacccat


 


541
gtctatcgtt atcacagagg cgagtcgaag ctgcacatgt gcttggacat agggaatggt


 


601
cagagaaaag acagaaaaaa gacatccctt ggtcctggag gcagctatca aatatcagag


 


661
catgctccag aggcatccca gcctgctgag aacatctcta aggacctcta catagaagta


 


721
tatccaggga cctattctgt cactgtgggc tcaaatgact taaccaagaa gactcatgtg


 


781
gtagcagttg attctggaca aagcgtggac ctggtcttcc ctgtgtgatg ttgaccatca


 


841
ctgccatcac atcacctttt tttaagtagt aagaataaag ccactgtatg attctcttaa


 


901
tagctataca ttaatcctgt ttttagtgct gactgggtca gccttccggg aactggagtc


 


961
tgtctctttc agtgcttttt tgtttgtttg gttggttttt ttttgagaca gtctcactct


 


1021
gttgcccagg ctggagtgca gtggcgtgat ctcggctcac tgcaagttcc gcctcccggg


 


1081
ttcacaccat tctcctgcct cagcctcccg agtagctggc actacaggca cccgccacca


 


1141
tgcccggcta ttttttttgt atttttagta gagacggggt ttcaccatgt tggccaggat


 


1201
ggtctcgatc tcttgacctc gtgatccacc caccttggcc tcccaaagtg ttgggattac


 


1261
aggcgtgagc caccgcgccc ggcctcagtg ccttttttaa cttgagggtg tagaggtcct


 


1321
ccacgcttgt ttgcctgaaa gtaatataat gatgctgtct gaacaggttt tactgcttgc


 


1381
tttccaagta aaggttaatt atgataataa agagatttgg aaatgaa






One example of a nucleic acid sequence for human CAPN3 is available as NCBI accession number NM_000070 (gi: 27765081). This sequence is recited below for easy reference as SEQ ID NO:122.









1
cactctcttt ctctctccct ctggcatgca tgctgctggt aggagacccc caagtcaaca



 


61
ttgcttcaga aatcctttag cactcatttc tcaggagaac ttatggcttc agaatcacag


 


121
ctcggttttt aagatggaca taacctgtac gaccttctga tgggctttca actttgaact


 


181
ggatgtggac acttttctct cagatgacag aattactcca acttcccctt tgcagttgct


 


241
tcctttcctt gaaggtagct gtatcttatt ttctttaaaa agctttttct tccaaagcca


 


301
cttgccatgc cgaccgtcat tagcgcatct gtggctccaa ggacagcggc tgagccccgg


 


361
tccccagggc cagttcctca cccggcccag agcaaggcca ctgaggctgg gggtggaaac


 


421
ccaagtggca tctattcagc catcatcagc cgcaattttc ctattatcgg agtgaaagag


 


481
aagacattcg agcaacttca caagaaatgt ctagaaaaga aagttcttta tgtggaccct


 


541
gagttcccac cggatgagac ctctctcttt tatagccaga agttccccat ccagttcgtc


 


601
tggaagagac ctccggaaat ttgcgagaat ccccgattta tcattgatgg agccaacaga


 


661
actgacatct gtcaaggaga gctaggggac tgctggtttc tcgcagccat tgcctgcctg


 


721
accctgaacc agcaccttct tttccgagtc ataccccatg atcaaagttt catcgaaaac


 


781
tacgcaggga tcttccactt ccagttctgg cgctatggag agtgggtgga cgtggttata


 


841
gatgactgcc tgccaacgta caacaatcaa ctggttttca ccaagtccaa ccaccgcaat


 


901
gagttctgga gtgctctgct ggagaaggct tatgctaagc tccatggttc ctacgaagct


 


961
ctgaaaggtg ggaacaccac agaggccatg gaggacttca caggaggggt ggcagagttt


 


1021
tttgagatca gggatgctcc tagtgacatg tacaagatca tgaagaaagc catcgagaga


 


1081
ggctccctca tgggctgctc cattgatgat ggcacgaaca tgacctatgg aacctctcct


 


1141
tctggtctga acatggggga gttgattgca cggatggtaa ggaatatgga taactcactg


 


1201
ctccaggact cagacctcga ccccagaggc tcagatgaaa gaccgacccg gacaatcatt


 


1261
ccggttcagt atgagacaag aatggcctgc gggctggtca gaggtcacgc ctactctgtc


 


1321
acggggctgg atgaggtccc gttcaaaggt gagaaagtga agctggtgcg gctgcggaat


 


1381
ccgtggggcc aggtggagtg gaacggttct tggagtgata gatggaagga ctggagcttt


 


1441
gtggacaaag atgagaaggc ccgtctgcag caccaggtca ctgaggatgg agagttctgg


 


1501
atgtcctatg aggatttcat ctaccatttc acaaagttgg agatctgcaa cctcacggcc


 


1561
gatgctctgc agtctgacaa gcttcagacc tggacagtgt ctgtgaacga gggccgctgg


 


1621
gtacggggtt gctctgccgg aggctgccgc aacttcccag atactttctg gaccaaccct


 


1681
cagtaccgtc tgaagctcct ggaggaggac gatgaccctg atgactcgga ggtgatttgc


 


1741
agcttcctgg tggccctgat gcagaagaac cggcggaagg accggaagct aggggccagt


 


1801
ctcttcacca ttggcttcgc catctacgag gttcccaaag agatgcacgg gaacaagcag


 


1861
cacctgcaga aggacttctt cctgtacaac gcctccaagg ccaggagcaa aacctacatc


 


1921
aacatgcggg aggtgtccca gcgcttccgc ctgcctccca gcgagtacgt catcgtgccc


 


1981
tccacctacg agccccacca ggagggggaa ttcatcctcc gggtcttctc tgaaaagagg


 


2041
aacctctctg aggaagttga aaataccatc tccgtggatc ggccagtgaa aaagaaaaaa


 


2101
accaagccca tcatcttcgt ttcggacaga gcaaacagca acaaggagct gggtgtggac


 


2161
caggagtcag aggagggcaa aggcaaaaca agccctgata agcaaaagca gtccccacag


 


2221
ccacagcctg gcagctctga tcaggaaagt gaggaacagc aacaattccg gaacattttc


 


2281
aagcagatag caggagatga catggagatc tgtgcagatg agctcaagaa ggtccttaac


 


2341
acagtcgtga acaaacacaa ggacctgaag acacacgggt tcacactgga gtcctgccgt


 


2401
agcatgattg cgctcatgga tacagatggc tctggaaagc tcaacctgca ggagttccac


 


2461
cacctctgga acaagattaa ggcctggcag aaaattttca aacactatgacacagaccag


 


2521
tccggcacca tcaacagcta cgagatgcga aatgcagtca acgacgcagg attccacctc


 


2581
aacaaccagc tctatgacat cattaccatg cggtacgcag acaaacacat gaacatcgac


 


2641
tttgacagtt tcatctgctg cttcgttagg ctggagggca tgttcagagc ttttcatgca


 


2701
tttgacaagg atggagatgg tatcatcaag ctcaacgttc tggagtggct gcagctcacc


 


2761
atgtatgcct gaaccaggct ggcctcatcc aaagccatgc aggatcactc aggatttcag


 


2821
tttcaccctc tatttccaaa gccatttacc tcaaaggacc cagcagctac acccctacag


 


2881
gcttccaggc acctcatcag tcatgctcct cctccatttt accccctacc catccttgat


 


2941
cggtcatgcc tagcctgacc ctttagtaaa gcaatgaggt aggaagaaca aacccttgtc


 


3001
cctttgccat gtggaggaaa gtgcctgcct ctggtccgag ccgcctcggt tctgaagcga


 


3061
gtgctcctgc ttaccttgct ctaggctgtc tgcagaagca cctgccggtg gcactcagca


 


3121
cctccttgtg ctagagccct ccatcacctt cacgctgtcc caccatgggc caggaaccaa


 


3181
accagcactg ggttctactg ctgtggggta aactaactca gtggaatagg gctggttact


 


3241
ttgggctgtc caactcataa gtttggctgc attttgaaaa aagctgatct aaataaaggc


 


3301
atgtgtatgg ctggtc






One example of a nucleic acid sequence for human CDH16 is available as NCBI accession number NM_004062 (gi: 16507958). This sequence is recited below for easy reference as SEQ ID NO:123.









1
gaaggagctc tcttcttgct tggcagctgg accaagggag ccagtcttgg gcgctggagg



 


61
gcctgtcctg accatggtcc ctgcctggct gtggctgctt tgtgtctccg tcccccaggc


 


121
tctccccaag gcccagcctg cagagctgtc tgtggaagtt ccagaaaact atggtggaaa


 


181
tttcccttta tacctgacca agttgccgct gccccgtgag ggggctgaag gccagatcgt


 


241
gctgtcaggg gactcaggca aggcaactga gggcccattt gctatggatc cagattctgg


 


301
cttcctgctg gtgaccaggg ccctggaccg agaggagcag gcagagtacc agctacaggt


 


361
caccctggag atgcaggatg gacatgtctt gtggggtcca cagcctgtgc ttgtgcacgt


 


421
gaaggatgag aatgaccagg tgccccattt ctctcaagcc atctacagag ctcggctgag


 


481
ccggggtacc aggcctggca tccccttcct cttccttgag gcttcagacc gggatgagcc


 


541
aggcacagcc aactcggatc ttcgattcca catcctgagc caggctccag cccagccttc


 


601
cccagacatg ttccagctgg agcctcggct gggggctctg gccctcagcc ccaaggggag


 


661
caccagcctt gaccacgccc tggagaggac ctaccagctg ttggtacagg tcaaggacat


 


721
gggtgaccag gcctcaggcc accaggccac tgccaccgtg gaagtctcca tcatagagag


 


781
cacctgggtg tccctagagc ctatccacct ggcagagaat ctcaaagtcc tatacccgca


 


841
ccacatggcc caggtacact ggagtggggg tgatgtgcac tatcacctgg agagccatcc


 


901
cccgggaccc tttgaagtga atgcagaggg aaacctctac gtgaccagag agctggacag


 


961
agaagcccag gctgagtacc tgctccaggt gcgggctcag aattcccatg gcgaggacta


 


1021
tgcggcccct ctggagctgc acgtgctggt gatggatgag aatgacaacg tgcctatctg


 


1081
ccctccccgt gaccccacag tcagcatccc tgagctcagt ccaccaggta ctgaagtgac


 


1141
tagactgtca gcagaggatg cagatgcccc cggctccccc aattcccacg ttgtgtatca


 


1201
gctcctgagc cctgagcctg aggatggggt agaggggaga gccttccagg tggaccccac


 


1261
ttcaggcagt gtgacgctgg gggtgctccc actccgagca ggccagaaca tcctgcttct


 


1321
ggtgctggcc atggacctgg caggcgcaga gggtggcttc agcagcacgt gtgaagtcga


 


1381
agtcgcagtc acagatatca atgatcacgc ccctgagttc atcacttccc agattgggcc


 


1441
tataagcctc cctgaggatg tggagcccgg gactctggtg gccatgctaa cagccattga


 


1501
tgctgacctc gagcccgcct tccgcctcat ggattttgcc attgagaggg gagacacaga


 


1561
agggactttt ggcctggatt gggagccaga ctctgggcat gttagactca gactctgcaa


 


1621
gaacctcagt tatgaggcag ctccaagtca tgaggtggtg gtggtggtgc agagtgtggc


 


1681
gaagctggtg gggccaggcc caggccctgg agccaccgcc acggtgactg tgctagtgga


 


1741
gagagtgatg ccacccccca agttggacca ggagagctac gaggccagtg tccccatcag


 


1801
tgccccagcc ggctctttcc tgctgaccat ccagccctcc gaccccatca gccgaaccct


 


1861
caggttctcc ctagtcaatg actcagaggg ctggctctgc attgagaaat tctccgggga


 


1921
ggtgcacacc gcccagtccc tgcagggcgc ccagcctggg gacacctaca cggtgcttgt


 


1981
ggaggcccag gatacagatg agccgagact gagcgcttct gcacccctgg tgatccactt


 


2041
cctaaaggcc cctcctgccc cagccctgac tcttgcccct gtgccctccc aatacctctg


 


2101
cacaccccgc caagaccatg gcttgatcgt gagtggaccc agcaaggacc ccgatctggc


 


2161
cagtgggcac ggtccctaca gcttcaccct tggtcccaac cccacggtgc aacgggattg


 


2221
gcgcctccag actctcaatg gttcccatgc ctacctcacc ttggccctgc attgggtgga


 


2281
gccacgtgaa cacataatcc ccgtggtggt cagccacaat gcccagatgt ggcagctcct


 


2341
ggttcgagtg atcgtgtgtc gctgcaacgt ggaggggcag tgcatgcgca aggtgggccg


 


2401
catgaagggc atgcccacga agctgtcggc agtgggcatc cttgtaggca ccctggtagc


 


2461
aataggaatc ttcctcatcc tcattttcac ccactggacc atgtcaagga agaaggaccc


 


2521
ggatcaacca gcagacagcg tgcccctgaa ggcgactgtc tgaatggccc aggcagctct


 


2581
agctgggagc ttggcctctg gctccatctg agtcccctgg gagagagccc agcacccaag


 


2641
atccagcagg ggacaggaca gagtagaagc ccctccatct gccctggggt ggaggcacca


 


2701
tcaccatcac caggcatgtc tgcagagcct ggacaccaac tttatggact gcccatggga


 


2761
gtgctccaaa tgtcagggtg tttgcccaat aataaagccc cagagaactg ggctgggccc


 


2821
tatgggattg gta






One example of a nucleic acid sequence for human ChGn is available as NCBI accession number BC060772 (gi: 38174239). This sequence is recited below for easy reference as SEQ ID NO:124.









1
tggggcttgt tccgggatcc gcagccttgc tcaggctgtg cattggtgtg gccccgaatt



 


61
gcacggagct gccttcctat ttcaaggaaa gacgccaagg taattttgac ccagaggagc


 


121
aatgatgtag ccacctccta accttccctt cttgaacccc caggtcccct cttgctgttg


 


181
gctgcacatc aggaaggctg tgatgggaat gaaggtgaaa acttggagat ttcacttcag


 


241
tcattgcttc tgcctgcaag atcatccttt aaaagtagag aagctgctct gtgtggtggt


 


301
taactccaag aggcagaact cgttctagaa ggaaatggat gcaagcagct ccgggggccc


 


361
caaacgcatg cttcctgtga tctagcccag ggaagccctt ccgtgggggc cccggctttg


 


421
agggatgcca ccggttctgg acgcatggct gattcctgaa tgatgatggt tcgccggggg


 


481
ctgcttgcgt ggatttcccg ggtggtggtt ttgctggtgc tcctctgctg tgctatctct


 


541
gtcctgtaca tgttggcctg caccccaaaa ggtgacgagg agcagctggc actgcccagg


 


601
gccaacagcc ccacggggaa ggaggggtac caggccgtcc ttcaggagtg ggaggagcag


 


661
caccgcaact acgtgagcag cctgaagcgg cagatcgcac agctcaagga ggagctgcag


 


721
gagaggagtg agcagctcag gaatgggcag taccaagcca gcgatgctgc tggcctgggt


 


781
ctggacagga gccccccaga gaaaacccag gccgacctcc tggccttcct gcactcgcag


 


841
gtggacaagg cagaggtgaa tgctggcgtc aagctggcca cagagtatgc agcagtgcct


 


901
ttcgatagct ttactctaca gaaggtgtac cagctggaga ctggccttac ccgccacccc


 


961
gaggagaagc ctgtgaggaa ggacaagcgg gatgagttgg tggaagccat tgaatcagcc


 


1021
ttggagaccc tgaacaatcc tgcagagaac agccccaatc accgtcctta cacggcctct


 


1081
gatttcatag aagggatcta ccgaacagaa agggacaaag ggacattgta tgagctcacc


 


1141
ttcaaagggg accacaaaca tgaattcaaa cggctcatct tatttcgacc attcggcccc


 


1201
atcatgaaag tggaaaatga aaagctcaac atggccaaca cgcttatcaa tgttatcgtg


 


1261
cctctagcaa aaagggtgga caagttccgg cagttcatgc agaatttcag gcctgctgat


 


1321
gaagttttta gatgtgtgcc tttaagccct tgattgtgcg gtgttggatc ttagaagctg


 


1381
tgatggctca gatgcacata ttggctgagg ataaccagct aagtgatttc accagcttgt


 


1441
tttaaacata gaaaatccta ctgtctaatt ataaatcttg aaagatcaag ctgatttttt


 


1501
atttcttttt ttttgagatg gagtcttact ctgtcaccca ggctggagtg cagtggcacg


 


1561
aactctgctc actgcaacct tcacctccca ggttcaggga gatgtgcatt gagcaggatg


 


1621
ggagagtcca tctcactgtt gtttactttg ggaaagaaga aataaatgaa gtcaaaggaa


 


1681
tacttgaaaa cacttccaaa gctgccaact tcaggaactt taccttcatc cagctgaatg


 


1741
gagaattttc tcggggaaag ggacttgatg ttggagcccg cttctggaag ggaagcaacg


 


1801
tccttctctt tttctgtgat gtggacatct acttcacatc tgaattcctc aatacgtgta


 


1861
ggctgaatac acagccaggg aagaaggtat tttatccagt tcttttcagt cagtacaatc


 


1921
ctggcataat atacggccac catgatgcag tccctccctt ggaacagcag ctggtcataa


 


1981
agaaggaaac tggattttgg agagactttg gatttgggat gacgtgtcag tatcggtcag


 


2041
acttcatcaa tataggtggg tttgatctgg acatcaaagg ctggggcgga gaggatgtgc


 


2101
acctttatcg caagtatctc cacagcaacc tcatagtggt acggacgcct gtgcgaggac


 


2161
tcttccacct ctggcatgag aagcgctgca tggacgagct gacccccgag cagtacaaga


 


2221
tgtgcatgca gtccaaggcc atgaacgagg catcccacgg ccagctgggc atgctggtgt


 


2281
tcaggcacga gatagaggct caccttcgca aacagaaaca gaagacaagt agcaaaaaaa


 


2341
catgaactcc cagagaagga ttgtgggaga cactttttct ttccttttgc aattactgaa


 


2401
agtggctgca acagagaaaa gacttccata aaggacgaca aaagaattgg actgatgggt


 


2461
cagagatgag aaagcctccg atttctctct gttgggcttt ttacaacaga aatcaaaatc


 


2521
tccgctttgc ctgcaaaagt aacccagttg caccctgtga agtgtctgac aaaggcagaa


 


2581
tgcttgtgag attataagcc taatggtgtg gaggttttga tggtgtttac aatacactga


 


2641
gacctgttgt tttgtgtgct cattgaaata ttcatgattt aagagcagtt ttgtaaaaaa


 


2701
ttcattagca tgaaaggcaa gcatatttct cctcatatga atgagcctat cagcagggct


 


2761
ctagtttcta ggaatgctaa aatatcagaa ggcaggagag gagataggct tattatgata


 


2821
ctagtgagta cattaagtaa aataaaatgg accagaaaag aaaagaaacc ataaatatcg


 


2881
tgtcatattt tccccaagat taaccaaaaa taatctgctt atctttttgg ttgtcctttt


 


2941
aactgtctcc gtttttttct tttatttaaa aatgcacttt ttttcccttg tgagttatag


 


3001
tctgcttatt taattaccac tttgcaagcc ttacaagaga gcacaagttg gcctacattt


 


3061
ttatattttt taagaagata ctttgagatg cattatgaga actttcagtt caaagcatca


 


3121
aattgatgcc atatccaagg acatgccaaa tgctgattct gtcaggcact gaatgtcagg


 


3181
cattgagaca tagggaagga atggtttgta ctaatacaga cgtacagata ctttctctga


 


3241
agagtatttt cgaagaggag caactgaaca ctggaggaaa agaaaatgac actttctgct


 


3301
ttacagaaaa ggaaactcat tcagactggt gatatcgtga tgtacctaaa agtcagaaac


 


3361
cacattttct cctcagaagt agggaccgct ttcttacctg tttaaataaa ccaaagtata


 


3421
ccgtgtgaac caaacaatct cttttcaaaa cagggtgctc ctcctggctt ctggcttcca


 


3481
taagaagaaa tggagaaaaa tatatatata tatatatata ttgtgaaaga tcaatccatc


 


3541
tgccagaatc tagtgggatg gaagtttttg ctacatgtta tccaccccag gccaggtgga


 


3601
agtaactgaa ttatttttta aattaagcag ttctactcga tcaccaagat gcttctgaaa


 


3661
attgcatttt attaccattt caaactattt tttaaaaata aatacagtta acatagagtg


 


3721
gtttcttcat tcatgtgaaa attattagcc agcaccagat gcatgagcta attatctctt


 


3781
tgagtccttg cttctgtttg ctcacagtaa actcattgtt taaaagcttc aagaacattc


 


3841
aagctgttgg tgtgttaaaa aatgcattgt attgatttgt actggtagtt tatgaaattt


 


3901
aattaaaaca caggccatga atggaaggtg gtattgcaca gctaataaaa tatgatttg


 


3961
ggatatgaaa aaaaaaaaaa aa






One example of a nucleic acid sequence for human CITED1 is available as NCBI accession number NM_004143 (gi: 222136685). This sequence is recited below for easy reference as SEQ ID NO:125.









1
acgagccagg acatgtgcta ataatgccct aagccggtta taaagacgtg gaaattgagg



 


61
ggagaaaaaa aaagggaaaa aaagggtctg tccttcctgg gattcctagc cgaggccagt


 


121
ctgctgccgt gtgcgtgtgc gtcagggctc tccgggcggc aatgggggct tgagagccgg


 


181
gtccccagcg ccgggaaggg agcgcggtgg ccgccaccgc caccgccccg gagtccggcg


 


241
ccgaagctgc gggcgggcgg gcgggcacca gctcggtcag gggctgcttg gcgcggcact


 


301
gtgcggtgca gcggcggcgc ggcgcggtgc gggcttttcc caggcgcccc ggggtcgggt


 


361
ggccaacggc gcggccgcgg gcgctgagcg cgaccggttc gcggtagcgg tggcggcggc


 


421
gtgcgtgcca ggggctgggg gctccgccgc ctctcttgcg gctcaccgag ctccgcgctt


 


481
ccctctctcc agggcaggcg gcttctcaga gcacaacagc tccagctggc agcatcactt


 


541
cccgccaatt tatccaactt ctgccaaggc tctgaaatgc caacaacgtc gaggcctgca


 


601
cttgatgtca agggtggcac ctcacctgcg aaggaggatg ccaaccaaga gatgagctcc


 


661
gtggcctact ccaaccttgc ggtgaaagat cgcaaagcag tggccattct gcactaccct


 


721
ggggtagcct caaatggaac caaggccagt ggggctccca ctagttcctc gggatctcca


 


781
ataggctctc ctacaaccac ccctcccact aaacccccat ccttcaacct gcaccccgcc


 


841
cctcacttgc tggctagtat gcacctgcag aaacttaata gccagtatca ggggatggct


 


901
gctgccactc caggccaacc cggggaggca ggacccctgc aaaactggga ctttggggcc


 


961
caggcgggag gggcagaatc actctctcct tctgctggtg cccagagccc tgctatcatc


 


1021
gattcggacc cagtggatga ggaagtgctg atgtcgctgg tggtggaact ggggttggac


 


1081
cgagccaatg agcttccgga gctgtggctg gggcagaatg agtttgactt cactgcggac


 


1141
tttccatcta gctgctaatg ccaagtgtcc ctaaagatgg aggaataaag ccaccaattc


 


1201
tgttgtaaat aaaaataaag ttacttacaa agagacgggc caaaaaaaaa a






One example of a nucleic acid sequence for human CITED2 is available as NCBI accession number NM_006079 (gi: 51807294). This sequence is recited below for easy reference as SEQ ID NO:126.









1
acagctcatt gttggcagct gccgggcggt cctgccgagc tgtgagggca acggagggga



 


61
aataaaaggg aacggctccg aatctgcccc agcggccgct gcgagacctc ggcgccgaca


 


121
tcgcgacagc gaagcgcttt gcacgccagg aaggtcccct ctatgtgctg ctgagccggt


 


181
cctggacgcg acgagcccgc cctcggtctt cggagcagaa atcgcaaaaa cggaaggact


 


241
ggaaatggca gaccatatga tggccatgaa ccacgggcgc ttccccgacg gcaccaatgg


 


301
gctgcaccat caccctgccc accgcatggg catggggcag ttcccgagcc cccatcacca


 


361
ccagcagcag cagccccagc acgccttcaa cgccctaatg ggcgagcaca tacactacgg


 


421
cgcgggcaac atgaatgcca cgagcggcat caggcatgcg atggggccgg ggactgtgaa


 


481
cggagggcac cccccgagcg cgctggcccc cgcggccagg tttaacaact cccagttcat


 


541
gggtcccccg gtggccagcc agggaggctc cctgccggcc agcatgcagc tgcagaagct


 


601
caacaaccag tatttcaacc atcaccccta cccccacaac cactacatgc cggatttgca


 


661
ccctgctgca ggccaccaga tgaacgggac aaaccagcac ttccgagatt gcaaccccaa


 


721
gcacagcggc ggcagcagca cccccggcgg ctcgggcggc agcagcaccc ccggcggctc


 


781
tggcagcagc tcgggcggcg gcgcgggcag cagcaacagc ggcggcggca gcggcagcgg


 


841
caacatgccc gcctccgtgg cccacgtccc cgctgcaatg ctgccgccca atgtcataga


 


901
cactgatttc atcgacgagg aagttcttat gtccttggtg atagaaatgg gtttggaccg


 


961
catcaaggag ctgcccgaac tctggctggg gcaaaacgag tttgatttta tgacggactt


 


1021
cgtgtgcaaa cagcagccca gcagagtgag ctgttgactc gatcgaaacc ccggcgaaag


 


1081
aaatcaaacc cccaacttct tcggcgtgaa ttaaaagaaa cattccctta gacacagtat


 


1141
ctcacttttc agatcttgaa aggtttgaga acttggaaac aaagtaaact ataaacttgt


 


1201
acaaattggt tttaaaaaaa attgctgcca cttttttttc ctgtttttgt ttcgtttttg


 


1261
tagccttgac attcacccac ctcccttatg tagttgaaat atctagctaa cttggtcttt


 


1321
ttcgttgttt gtttttactc ctttccctca ctttctccag tgctcaactg ttagatatta


 


1381
atcttggcaa actgcttaat cttgtggatt ttgtagatgg tttcaaatga ctgaactgca


 


1441
ttcagattta cgagtgaaag gaaaaattgc attagttggt tgcatgaact tcgaagggca


 


1501
gatattactg cacaaactgc catctcgctt cattttttta actatgcatt tgagtacaga


 


1561
ctaattttta aaatatgcta aactggaaga ttaaacagat gtgggccaaa ctgttctgga


 


1621
tcaggaaagt catactgttc actttcaagt tggctgtccc ccccgccgcc ccccccaccc


 


1681
ccatatgtac agatgataat agggtgtgga atgtcgtcag tggcaaacat ttcacagatt


 


1741
tttattttgt ttctgtcttc aacatttttg acactgtgct aatagttata ttcagtacat


 


1801
gaaaagatac tactgtgttg aaagcttttt aggaaatttt gacagtattt ttgtacaaaa


 


1861
catttttttg aaaaaatact tgttaattta ttctatttta atttgccaat gtcaataaaa


 


1921
agttaagaaa






One example of a nucleic acid sequence for human CKB is available as NCBI accession number M16451 (gi: 180571). This sequence is recited below for easy reference as SEQ ID NO:127.









1
ccggccgccc gcccgccgcc gccatgccct tctccaacag ccacaacgca ctgaagctgc



 


61
gcttcccggc cgaggacgag ttccccgacc tgagcgccca caacaaccac atggccaagg


 


121
tgctgacccc cgagctgtac gcggacgtgc gcgccaagag cacgccgagc ggcttcacgc


 


181
tggacgacgt catccagaca ggcgtggaca acccgggcca cccgtacatc atgaccgtgg


 


241
gctgcgtggc gggcgacgag gagtcctacg aagtgttcaa ggatctcttc gaccccatca


 


301
tcgaggaccg gcaccggcgc tacaagccca gcgatgacga caagaccgac ctcaaccccg


 


361
acaacctgca gggcggcgac gacctggacc ccaactacgt gctgagctcg cgggtggcca


 


421
cgggccgcag catccgtggc ttctgcctcc ccccgcactg cagccgcggg gagcgccgag


 


481
ccatcgagaa gctcgcggtg gaagccctgt ccagcctgga cggcgacctg gcgggccgat


 


541
actacgcgct caagagcatg acggaggcgg agcagcagca gctcatcgac gaccacttcc


 


601
tcttcgacaa gcccgtgtcg cccctgctgc tggcctcggg catggcccgc gactggcccg


 


661
acgccgcgcg tatctggcac aatgacaata agaccttcct ggtgtgggtc aacgaggagg


 


721
accacctgcg ggtcatctcc atgcagaagg ggggcaacat gaaggaggtg ttcacccgct


 


781
tctgcaccgg cctcacccag attgaaactc tcttcaagtc taaggactat gagttcatgt


 


841
ggaaccctca cctgggctac atcctcacct gcccatccaa cctgggcacc gggctgcggg


 


901
caggtgtcga tatcaagctg cccaacctgg gcaagcatga gaagttctcg gaggtgctta


 


961
agcggctgcg acttcagaag cgaggcacag gcggtgtgga cacggctgcg gtgggcgggg


 


1021
tcttcgacgt ctccaacgct gaccgcctgg gcttctcaga ggtggagctg gtgcagatgg


 


1081
tggtggacgg agtgaagctg ctcatcgaga tggaacagcg gctggagcag ggccaggcca


 


1141
tcgacgacct catgcctgcc cagaaatgaa gcccggccca cacccgacac cagccctgct


 


1201
gcttcctaac ttattgcctg cagtgcccac catgcacccc tcgatgttgc cgtctggcga


 


1261
gcccttagcc ttgctgtaag gaaggcttcc gtcacccttg gtagagttta tttttttgat


 


1321
ggctaagata ctgctgatgc tgaaataaac tagggttttg gcctgcaaaa aa






One example of a nucleic acid sequence for human COL9A3 is available as NCBI accession number NM_001853 (gi: 119508425). This sequence is recited below for easy reference as SEQ ID NO:128.









1
gccatggccg ggccgcgcgc gtgcgccccg ctcctgctcc tgctcctgct cggggagctt



 


61
ctggcggccg ccggggcgca gagagtggga ctccccggcc cccccggccc cccagggccg


 


121
cccgggaagc ccggccagga cggcattgac ggagaagctg gtcctccagg tctgcctggg


 


181
cccccgggac caaagggggc cccaggaaag ccggggaaac caggagaggc tgggctgccg


 


241
ggactgccgg gtgtggatgg tctgactgga cgagatggac cccctggacc caagggtgcc


 


301
cctggggaac ggggaagtct gggacccccg gggccgcccg ggctgggggg caaaggcctc


 


361
cctggacccc ccggagaggc aggagtgagc ggccccccag gtgggatcgg cctccgcggc


 


421
cccccgggac cttctggact ccccggcctc cctggtcccc caggacctcc cggaccccct


 


481
ggacacccag gagtcctccc tgaaggcgct actgaccttc agtgcccaag tatctgcccg


 


541
ccaggtcccc cagggccccc tggaatgcca gggttcaagg gacccactgg ctacaaaggc


 


601
gagcaggggg aagtcggcaa ggacggcgag aagggtgacc ctggcccccc tgggcccgcc


 


661
ggcctcccgg gcagcgtggg gctgcagggc ccccggggat tacgaggact gccagggcca


 


721
ctcgggcccc ctggggaccg gggtcccatt gggttccgag ggccgcctgg gatcccagga


 


781
gcgcctggga aagcgggtga ccgaggcgag aggggcccag aagggttccg cggccccaag


 


841
ggtgacctcg gcagacctgg tcccaaggga acccccggag tggccgggcc aagcggagag


 


901
ccgggcatgc cgggcaagga cggccagaat ggcgtgccag gactcgatgg ccagaaggga


 


961
gaggctggtc gcaacggtgc tccgggagag aagggcccca acgggctgcc gggcctccct


 


1021
ggacgagcgg ggtccaaagg cgagaaggga gaacggggca gagctgggga gctgggtgag


 


1081
gccggcccct ctggagagcc aggcgtccct ggagatgctg gcatgcctgg ggagcgcggt


 


1141
gaggctggcc accggggctc agcgggggcc ctcggcccac aaggccctcc cggagcccct


 


1201
ggtgtccgag gcttccaggg ccagaagggc agcatgggag accccggcct tccaggcccc


 


1261
cagggcctcc gaggtgacgt gggcgaccgg ggtccgggag gtgccgcagg ccctaaggga


 


1321
gaccagggta ttgcaggttc cgacggtctt cctggggata aaggagaact gggtcccagc


 


1381
ggcctggtcg gacccaaagg agagtctggc agtcgagggg agctgggccc caaaggcacc


 


1441
cagggtccca acggcaccag cggtgttcag ggtgtccccg ggccccccgg tcctctgggc


 


1501
ctgcagggcg tcccgggtgt tcctggcatc acggggaagc cgggagttcc ggggaaggag


 


1561
gccagcgagc agcgcatcag ggagctgtgt ggggggatga tcagcgaaca aattgcacag


 


1621
ttagccgcgc acctaaggaa gcctttggca cccgggtcca ttggtcggcc cggtccagct


 


1681
ggcccccctg ggcccccagg acccccaggc tccattggtc accctggcgc tcgaggaccc


 


1741
cctggatacc gcggtcccac tggggagctg ggagaccccg ggcccagagg aaaccagggt


 


1801
gacagaggag acaaaggcgc ggcaggagca gggctggacg ggcctgaagg agaccagggg


 


1861
ccccaaggac cccaaggcgt gcccggcacc agcaaggacg gccaggacgg tgctcccggc


 


1921
gagcctgggc ctcccggaga tcctgggctt ccaggtgcca ttggggccca ggggacaccg


 


1981
gggatctgcg acacctcagc ctgccaagga gccgtgttag gaggggtcgg ggagaaatca


 


2041
ggctctcgaa gctcataaaa ttcaacgtga ggaagcaagt gacaaggacg cccgaagcac


 


2101
agtggacggt catgaaggag cgggggtgtg gcaggcgggt gacgtccagg agagggagcg


 


2161
cccctggctg cccctcggcc gccgactgga cgcgcgggcc ttgccagcga gcaccctcat


 


2221
cgggctgtcg cctgacagca tacctcaaaa ggccctagct aataaacctg taagcccagc


 


2281
atttgagaga aggtagggtg tgtatatata aaaggttgtg tacaactcca cgaggtgaaa


 


2341
aatattcagt aacttgttta catagcattt gtgtaaagac tatgatctca tcccaataaa


 


2401
atgatatatt aaaccttcag attaatgact ggctacagag taacaaaaaa taaagaattt


 


2461
aatgtacagt aaattctctc ccata






One example of a nucleic acid sequence for human CSRP2 is available as NCBI accession number NM_001321 (gi: 4503100). This sequence is recited below for easy reference as SEQ ID NO:129.









1
gggatctcgg actccctgga ccctccctcc agcccagcct cgctagctcc gcctgcggta



 


61
cgtgctcccg cctccgactc aaaatgcctg tctggggagg tggaaacaag tgtggggcct


 


121
gtgggaggac cgtgtaccac gcagaagagg tgcagtgtga tggcaggagc ttccaccgct


 


181
gctgctttct ctgcatggtt tgcaggaaaa atttagatag cacaacagtg gcaattcacg


 


241
atgaagagat ctactgcaaa tcctgctacg gaaagaagta tgggccaaaa ggctacggtt


 


301
atggccaggg cgctggcacg cttaacatgg accgtggcga gaggctgggc atcaaaccag


 


361
agagtgttca gcctcacagg cctacaacaa atccaaacac ttctaaattt gctcagaaat


 


421
atggaggtgc tgagaagtgt tccagatgtg gggattctgt atatgctgcc gagaagataa


 


481
ttggagctgg aaagccctgg cacaaaaact gtttccgatg tgcaaagtgt gggaagagtc


 


541
ttgaatcaac aactctgact gaaaaagaag gtgaaatcta ttgtaaagga tgctatgcaa


 


601
agaactttgg gcccaaggga tttggctatg gccaaggagc aggggctctt gttcatgccc


 


661
agtaagatgt aaaccctgaa ctaaacatca cacactgaga atctcttcat aatctaggca


 


721
cagataatct ttaacactaa actactgtga aattctacca gcattaagta ctgtatatcg


 


781
ccctgtactt ggataggctg gctaactcgt aggaagagag cactgtatgg tatccttttg


 


841
ctttattcac cagcattttg ggggaacatt tcttttacat tttaaataaa acttcagctt


 


901
g






One example of a nucleic acid sequence for human DAPK2 is available as NCBI accession number NM_0014326 (gi: 71774012). This sequence is recited below for easy reference as SEQ ID NO:130.









1
gaccgcggca gctcagcctc ccgccgattg tatgttccag gcctcaatga ggagtccaaa



 


61
catggagcca ttcaagcagc agaaggtgga ggacttttat gacatcggag aggagctggg


 


121
gagtggccag tttgccatcg tgaagaagtg ccgggagaag agcacggggc ttgagtatgc


 


181
agccaagttc atcaagaagc ggcagagccg ggcgagccgg cgcggtgtga gccgggagga


 


241
gatcgagcgg gaggtgagca tcctgcggca ggtgctgcac cacaatgtca tcacgctgca


 


301
cgacgtctat gagaaccgca ccgacgtggt gctcatcctt gagctagtgt ctggaggaga


 


361
gctcttcgat ttcctggccc agaaggagtc actgagtgag gaggaggcca ccagcttcat


 


421
taagcagatc ctggatgggg tgaactacct tcacacaaag aaaattgctc actttgatct


 


481
caagccagaa aacattatgt tgttagacaa gaatattccc attccacaca tcaagctgat


 


541
tgactttggt ctggctcacg aaatagaaga tggagttgaa tttaagaata tttttgggac


 


601
gccggaattt gttgctccag aaattgtgaa ctacgagccc ctgggtctgg aggctgacat


 


661
gtggagcata ggcgtcatca cctacatcct cttaagtgga gcatcccctt tcctgggaga


 


721
cacgaagcag gaaacactgg caaatatcac agcagtgagt tacgactttg atgaggaatt


 


781
cttcagccag acgagcgagc tggccaagga ctttattcgg aagcttctgg ttaaagagac


 


841
ccggaaacgg ctcacaatcc aagaggctct cagacacccc tggatcacgc cggtggacaa


 


901
ccagcaagcc atggtgcgca gggagtctgt ggtcaatctg gagaacttca ggaagcagta


 


961
tgtccgcagg cggtggaagc tttccttcag catcgtgtcc ctgtgcaacc acctcacccg


 


1021
ctcgctgatg aagaaggtgc acctgaggcc ggatgaggac ctgaggaact gtgagagtga


 


1081
cactgaggag gacatcgcca ggaggaaagc cctccaccca cggaggagga gcagcacctc


 


1141
ctaactggcc tgacctgcag tggccgccag ggaggtctgg gcccagcggg gctcccttct


 


1201
gtgcagactt ttggacccag ctcagcacca gcacccgggc gtcctgagca ctttgcaaga


 


1261
gagatgggcc caaggaattc agaagagctt gcaggcaagc caggagaccc tgggagctgt


 


1321
ggctgtcttc tgtggaggag gctccagcat tcccaaagct cttaattctc cataaaatgg


 


1381
gctttcctct gtctgccatc ctcagagtct ggggtgggag tgtggactta ggaaaacaat


 


1441
ataaaggaca tcctcatcat cacggggtga aggtcagact aaggcagcct tcttcacagg


 


1501
ctgagggggt tcagaaccag cctggccaaa aattacacca gagagacaga gtcctcccca


 


1561
ttgggaacag ggtgattgag gaaagtgaac cttgggtgtg agggaccaat cctgtgacct


 


1621
cccagaacca tggaagccag gacgtcaggc tgaccaacac ctcagacctt ctgaagcagc


 


1681
ccattgctgg cccgccatgt tgtaattttg ctcattttta ttaaacttct ggtttacctg


 


1741
atgcttggct tcttttaggg ctacccccat ctcatttcct ttagcccgtg tgcctgtaac


 


1801
tctgaggggg ggcacccagt ggggtgctga gtgggcagaa tctcagaagg tcctcctgaa


 


1861
ccgtccgcgc aggcctgcag tgggcctgcc tcctccttgc ttccctaaca ggaaggtgtc


 


1921
cagttcaaga gaacccaccc agagactggg agtggtggct cacgcctata atccctgcgc


 


1981
tttggcagtc cgaggcaggg gaattgcttg aactcaggag ttggagacca gcctgggcaa


 


2041
catggcaaaa cgcagtctgt acaaaaaata caaaaaatta gccaggtgta ggggtaggca


 


2101
cctggcatcc cagctactcc aggggctgag gtgacagcat tgcttaagcc cagaaggtcg


 


2161
aggctgcagt gagctgagat cacgccactg cactccagtc tgggtgacag agagagacca


 


2221
tatccaaaaa aaaaaaaagt tgccagagac gagtatgccc atgctccctc tacctcactg


 


2281
ccaccactcc tgctgttagg agctgagtgt gtctccctaa aatttctatg ttgaagtctt


 


2341
aacccttggt accacagaat atcactgtat ttggagatgg ggtctttaga aaggcactta


 


2401
aattaaaatg agctcactga tatgggcccc gatgcaatat aattggtgtc cttataagaa


 


2461
ggggaggtta ggacacgcag gaaagaccac atgaaggccc aggagtggga gggggaatag


 


2521
ccatcgacaa actaaggggg cctcagagga aaccaaccct gctgacacct caatcttaga


 


2581
ctctggcctc aaaaattgta agaaaataaa cttctgtctt ttaagcca






One example of a nucleic acid sequence for human DIO1 is available as NCBI accession number NM_00972 (gi: 89357933). This sequence is recited below for easy reference as SEQ ID NO:131.









1
gagcttactc tggctttgcc gagatggggc tgccccagcc agggctgtgg ctgaagaggc



 


61
tctgggtgct cttggaggtg gctgtgcatg tggtcgtggg taaagtgctt ctgatattgt


 


121
ttccagacag agtcaagcgg aacatcctgg ccatgggcga gaagacgggt atgaccagga


 


181
acccccattt cagccacgac aactggatac caaccttttt cagcacccag tatttctggt


 


241
tcgtcttgaa ggtccgttgg cagcgactag aggacacgac tgagctaggg ggtctggccc


 


301
caaactgccc ggtggtccgc ctctcaggac agaggtgcaa catttgggag tttatgcaag


 


361
gtaataggcc actggtgctg aattttggaa gttgtacctg accttcattt atgttcaaat


 


421
ttgaccagtt caagaggctt attgaagact ttagttccat agcagatttt cttgtcattt


 


481
acattgaaga agcacatgca tcagatggct gggcttttaa gaacaacatg gacatcagaa


 


541
atcaccagaa ccttcaggat cgcctgcagg cagcccatct actgctggcc aggagccccc


 


601
agtgccctgt ggtggtggac accatgcaga accagagcag ccagctctac gcagcactgc


 


661
ctgagaggct ctacataatc caggagggca ggatcctcta caagggtaaa tctggccctt


 


721
ggaactacaa cccagaggaa gttcgtgctg ttctggaaaa gctccacagt taatctggac


 


781
agatacctca attctaggtg accaacggga gggcttctca aggcttagct ctccctgaga


 


841
cccagctggc ttttaccctt gacctgtgtc cctagctgaa tcactagctc agatttttct


 


901
gatctaagca aacaactccc agctgaggaa tgcaggccac agcacccaat caagacaaat


 


961
tgttattatc agaaaatgaa gcaacacttg agctgttcag gccagttccc tgttgaagaa


 


1021
acagttccct gttgaagaaa gtagagcctg acactgctcc cactttggag accacattcc


 


1081
ctgcacacgg tctttgagag agcagttgca ctctacaggc acacttctga ggtacggtat


 


1141
ctctctccag ccactctgat accaagtaat tcaagctggc attccttcta ttagggaaat


 


1201
tcattttacc caatttgcat ttatggaatt gatcatttaa gacactaaat tagtttttag


 


1261
aaccaattat gggaagaatt ccagttgtta ggaagagatg aggagttgga agaggaggga


 


1321
ttagaaacag gaggaggcag tcatcctctc cttgccaaaa gatttaaacc tgtccacatt


 


1381
ggtggtgatg atgggtgagt ttccatggta acacatccct aattttacca gggaagagga


 


1441
gagtactcac tttaccatct ttgaatatat ttcatagaaa tctagctctc tgtaccctga


 


1501
aatcttccac tagcctcact tttcaacaga gtcatctaga agggagggtt ggcttcccaa


 


1561
aagcataacc ttgaccaaac caaacaatag gcaccagcaa tgctgtcatt cagttatgca


 


1621
gaagctcatt tgtgaaattc tgtttctctg atttcttcgc aagtctctta atggtcattt


 


1681
gtgttagatt acatcaaact gatggatagc cattggtatt catctatttt aactctgtgt


 


1741
ctttacatat ttgtttatga tggccacagc ctaaagtaca cacggctgtg acttgattca


 


1801
aaagaaaatg ttataagatg cagtaaacta ataacagaat tattaaaata tatcaggcta


 


1861
aaaaaaaaaa aaaaaa






One example of a nucleic acid sequence for human DPP4 is available as NCBI accession number NM_001935 (gi: 47078262). This sequence is recited below for easy reference as SEQ ID NO:132.









1
ctttcactgg caagagacgg agtcctgggt ttcagttcca gttgcctgcg gtgggctgtg



 


61
tgagtttgcc aaagtcccct gccctctctg ggtctcggtt ccctcgcctg tccacgtgag


 


121
gttggaggag ctgaacgccg acgtcatttt tagctaagag ggagcagggt ccccgagtcg


 


181
ccggcccagg gtctgcgcat ccgaggccgc gcgccctttc ccctccccca cggctcctcc


 


241
gggccccgca ctctgcgccc cggctgccgc ccagcgccct acaccgccct cagggggccc


 


301
tcgcgggctc cccccggccg ggatgccagt gccccgcgcc acgcgcgcct gctcccgcgc


 


361
cgcctgccct gcagcctgcc cgcggcgcct ttatacccag cgggctcggc gctcactaat


 


421
gtttaactcg gggccgaaac ttgccagcgg cgagtgactc caccgcccgg agcagcggtg


 


481
caggacgcgc gtctccgccg cccgcggtga cttctgcctg cgctccttct ctgaacgctc


 


541
acttccgagg agacgccgac gatgaagaca ccgtggaagg ttcttctggg actgctgggt


 


601
gctgctgcgc ttgtcaccat catcaccgtg cccgtggttc tgctgaacaa aggcacagat


 


661
gatgctacag ctgacagtcg caaaacttac actctaactg attacttaaa aaatacttat


 


721
agactgaagt tatactcctt aagatggatt tcagatcatg aatatctcta caaacaagaa


 


781
aataatatct tggtattcaa tgctgaatat ggaaacagct cagttttctt ggagaacagt


 


841
acatttgatg agtttggaca ttctatcaat gattattcaa tatctcctga tgggcagttt


 


901
attctcttag aatacaacta cgtgaagcaa tggaggcatt cctacacagc ttcatatgac


 


961
atttatgatt taaataaaag gcagctgatt acagaagaga ggattccaaa caacacacag


 


1021
tgggtcacat ggtcaccagt gggtcataaa ttggcatatg tttggaacaa tgacatttat


 


1081
gttaaaattg aaccaaattt accaagttac agaatcacat ggacggggaa agaagatata


 


1141
atatataatg gaataactga ctgggtttat gaagaggaag tcttcagtgc ctactctgct


 


1201
ctgtggtggt ctccaaacgg cactttttta gcatatgccc aatttaacga cacagaagtc


 


1261
ccacttattg aatactcctt ctactctgat gagtcactgc agtacccaaa gactgtacgg


 


1321
gttccatatc caaaggcagg agctgtgaat ccaactgtaa agttctttgt tgtaaataca


 


1381
gactctctca gctcagtcac caatgcaact tccatacaaa tcactgctcc tgcttctatg


 


1441
ttgatagggg atcactactt gtgtgatgtg acatgggcaa cacaagaaag aatttctttg


 


1501
cagtggctca ggaggattca gaactattcg gtcatggata tttgtgacta tgatgaatcc


 


1561
agtggaagat ggaactgctt agtggcacgg caacacattg aaatgagtac tactggctgg


 


1621
gttggaagat ttaggccttc agaacctcat tttacccttg atggtaatag cttctacaag


 


1681
atcatcagca atgaagaagg ttacagacac atttgctatt tccaaataga taaaaaagac


 


1741
tgcacattta ttacaaaagg cacctgggaa gtcatcggga tagaagctct aaccagtgat


 


1801
tatctatact acattagtaa tgaatataaa ggaatgccag gaggaaggaa tctttataaa


 


1861
atccaactta gtgactatac aaaagtgaca tgcctcagtt gtgagctgaa tccggaaagg


 


1921
tgtcagtact attctgtgtc attcagtaaa gaggcgaagt attatcagct gagatgttcc


 


1981
ggtcctggtc tgcccctcta tactctacac agcagcgtga atgataaagg gctgagagtc


 


2041
ctggaagaca attcagcttt ggataaaatg ctgcagaatg tccagatgcc ctccaaaaaa


 


2101
ctggacttca ttattttgaa tgaaacaaaa ttttggtatc agatgatctt gcctcctcat


 


2161
tttgataaat ccaagaaata tcctctacta ttagatgtgt atgcaggccc atgtagtcaa


 


2221
aaagcagaca ctgtcttcag actgaactgg gccacttacc ttgcaagcac agaaaacatt


 


2281
atagtagcta gctttgatgg cagaggaagt ggttaccaag gagataagat catgcatgca


 


2341
atcaacagaa gactgggaac atttgaagtt gaagatcaaa ttgaagcagc cagacaattt


 


2401
tcaaaaatgg gatttgtgga caacaaacga attgcaattt ggggctggtc atatggaggg


 


2461
tacgtaacct caatggtcct gggatcggga agtggcgtgt tcaagtgtgg aatagccgtg


 


2521
gcgcctgtat cccggtggga gtactatgac tcagtgtaca cagaacgtta catgggtctc


 


2581
ccaactccag aagacaacct tgaccattac agaaattcaa cagtcatgag cagagctgaa


 


2641
aattttaaac aagttgagta cctccttatt catggaacag cagatgataa cgttcacttt


 


2701
cagcagtcag ctcagatctc caaagccctg gtcgatgttg gagtggattt ccaggcaatg


 


2761
tggtatactg atgaagacca tggaatagct agcagcacag cacaccaaca tatatatacc


 


2821
cacatgagcc acttcataaa acaatgtttc tctttacctt agcacctcaa aataccatgc


 


2881
catttaaagc ttattaaaac tcatttttgt tttcattatc tcaaaactgc actgtcaaga


 


2941
tgatgatgat ctttaaaata cacactcaaa tcaagaaact taaggttacc tttgttccca


 


3001
aatttcatac ctatcatctt aagtagggac ttctgtcttc acaacagatt attaccttac


 


3061
agaagtttga attatccggt cgggttttat tgtttaaaat catttctgca tcagctgctg


 


3121
aaacaacaaa taggaattgt ttttatggag gctttgcata gattccctga gcaggatttt


 


3181
aatctttttc taactggact ggttcaaatg ttgttctctt ctttaaaggg atggcaagat


 


3241
gtgggcagtg atgtcactag ggcagggaca ggataagagg gattagggag agaagatagc


 


3301
agggcatggc tgggaaccca agtccaagca taccaacacg agcaggctac tgtcagctcc


 


3361
cctcggagaa gagctgttca cagccagact ggcacagttt tctgagaaag actattcaaa


 


3421
cagtctcagg aaatcaaata tgcaaagcac tgacttctaa gtaaaaccac agcagttgaa


 


3481
aagactccaa agaaatgtaa gggaaactgc cagcaacgca ggcccccagg tgccagttat


 


3541
ggctataggt gctacaaaaa cacagcaagg gtgatgggaa agcattgtaa atgtgctttt


 


3601
aaaaaaaaat actgatgttc ctagtgaaag aggcagcttg aaactgagat gtgaacacat


 


3661
cagcttgccc tgttaaaaga tgaaaatatt tgtatcacaa atcttaactt gaaggagtcc


 


3721
ttgcatcaat ttttcttatt tcatttcttt gagtgtctta attaaaagaa tattttaact


 


3781
tccttggact cattttaaaa aatggaacat aaaatacaat gttatgtatt attattccca


 


3841
ttctacatac tatggaattt ctcccagtca tttaataaat gtgccttcat tttttcagaa


 


3901
aaaaaaaaaa aaa






One example of a nucleic acid sequence for human DTX4 is available as NCBI accession number NM_015177 (gi: 148237497). This sequence is recited below for easy reference as SEQ ID NO:133.









1
gagcagcggc agcagcagcg gaccccggcg gcggcggcgg cgcgcggtcc cagccaggcg



 


61
gccccggtgt cccggccccg gtggatgcac ggctggggag gagcccatgg gccggagctg


 


121
aggctgcccg gggcggcggg gcgcggggca gggggcgcgg tcgaggcccg gaggcggcgg


 


181
cgcaggagga agcggaggag gtcgggcgct cggggcccgg gaggcgggcc gcgcagcgcc


 


241
gcagccccgg gctcgccatg ctcctggcct cggccgtggt ggtctgggaa tggctgaacg


 


301
agcacggccg ctggcgtccc tacagcccag cggtgagcca ccacatcgag gcggtggtcc


 


361
gcgccggccc ccgcgcgggg ggcagcgtgg tgctgggcca ggtggacagc cgtctcgcgc


 


421
cctacatcat cgacctgcag tccatgaacc agttccgcca agacacggga actctccgcc


 


481
cagttcgccg caactactac gacccctcct cggcccctgg gaagggcgtg gtgtgggagt


 


541
gggagaacga caatggctcc tggacgccct acgacatgga agtgggcatc accatccagc


 


601
atgcctatga gaagcagcac ccctggatcg acctcacttc cattggcttt agctacgtaa


 


661
ttgacttcaa caccatgggc cagatcaacc gtcagaccca gcgccaacgc cgcgtccgcc


 


721
ggcgcctcga cctcatctac cccatggtca cagggacctt gcctaaggct cagtcctggc


 


781
cagtcagccc tgggccagcc acctcgcccc ccatgtcccc ctgctcctgt ccccagtgtg


 


841
tcttggtgat gagtgttaag gcagccgtgg tcaatggcag cactgggccc ctacagctgc


 


901
cagtgacccg caagaacatg ccgcctcctg gagtggtcaa gctaccccca ctgccaggct


 


961
ctggggccaa gccactggac agcacaggca ccattcgagg cccactgaag accgccccat


 


1021
cgcaggtgat ccggagacaa gcctccagca tgcccactgg gacaaccatg ggctctcctg


 


1081
ccagtccccc aggacccaac agcaagaccg gaagggtggc cctggccacc ttgaatcgta


 


1141
ccaacctgca gcgactggcc attgcccagt cccgggtgct gatcgcctct ggggtcccca


 


1201
cagtcccagt gaagaaccta aatgggtcca gtcctgtcaa ccctgccttg gcaggaatca


 


1261
ctgggatcct catgagtgca gcggggctgc ctgtgtgtct caccaggcca ccaaagctgg


 


1321
tcctacaccc accccccgtc agcaagagtg aaataaaatc catcccaggg gtttccaaca


 


1381
caagccgcaa gaccaccaaa aaacaagcca agaaaggtaa aaccccagag gaagtgctaa


 


1441
aaaaatatct acagaaagtc cggcacccac cagatgagga ctgcaccatc tgtatggaac


 


1501
gcctcacggc cccctcaggc tacaagggcc cgcagcctac ggtaaaacct gacctggtag


 


1561
ggaagctgtc cagatgcggc cacgtctacc acatctactg cttggttgcc atgtacaaca


 


1621
atgggaacaa ggatggaagt ttgcagtgtc caacctgcaa gaccatttat ggggtgaaga


 


1681
caggcaccca acctccaggg aagatggagt accacctcat cccccactcc ttgcctggcc


 


1741
acccagactg caaaaccatc cggatcatct acagcatccc ccccggcatt cagggaccgg


 


1801
aacacccgaa tcctgggaag agtttcagcg cccgaggctt cccacgacac tgttaccttc


 


1861
cggacagcga gaaagggaga aaagttctga agctgctgct cgtggcctgg gatcgccgcc


 


1921
tcatttttgc cattggcacc tccagcacca caggcgagtc agacaccgtc atctggaatg


 


1981
aggtccacca caagacagag tttggctcta atctcactgg ccatggctac ccagatgcca


 


2041
attacctgga taatgtgctg gctgaactgg ctgcccaggg catctctgag gacagcactg


 


2101
cccaggagaa ggactgaggc cagaaaagct ttgaggtggg aggggccatg gagactgcag


 


2161
gacaggaagt gaggagagtg agtcaatgta gaagaagttg gtgtcctgcc ctcccaactt


 


2221
tctatcctcc cctcctgccc tgtgtccatc cctcatccct cccaaccaca gtgggagcca


 


2281
gactgaatat agcgacatca ttcataaatc tcatccaaca caaagggaga tgggatgagg


 


2341
gccatcctgg gtctgttccc atggagtttt tggtgctggg taggcaggaa tcccctccct


 


2401
accccacctc ccaagtaggg gcatggtcag cacacctagg gtatgggcag tgcttaggca


 


2461
ctccatatcc tggctttggg aagccggggt ttcttgcctc agccggcttc ttgctacttc


 


2521
cactctgctt tgagactgga gtttctgcta ttctccctct gctggaggca gggagctctc


 


2581
actgtgcaag gttggggggt gggcaaaggg gtgaatcact aaactgctgt gacatcagaa


 


2641
actgatgcct tggtgtagag caaggaagca cttcttccca agagggtcgg agaaggaaaa


 


2701
gcctctggga gcacattctg ctgtcatcac agtccttggc ttctctgggc cctcctctcc


 


2761
tcctcacagc tctcacctgt ccaaagaggc atctggttct ctcatgtgga tggatggact


 


2821
ctggggttcc tctttggagt ggcatcccat gatgctgttt ctagaccctc tctgatcaaa


 


2881
ccagagcctg catcccactg agcatctgaa ctgtcctcag ggagaggagc ccacagcctt


 


2941
cttcccaact cattctagac cagctcaaag attccatgag tttcatcgag tcactgtgag


 


3001
tggagcccat gctgggctct gtgccctctg tgtctgtgca tgcgcgtgtg tgtgtgggcg


 


3061
tgtgtgcatt gctgggccag cttgaaggga aggcccgtca tgtccctgca ctctgttttg


 


3121
caagatgcca aaccccagtt ctgatggggc tccaacagcc aggctgtggt cctttgacgt


 


3181
tcctcacctg ttgccaacct atcccgtagt gaactgaaac cccaatgaag acagaactgt


 


3241
gcctggggag atgcaatgag gtgagggctg aactcatcct tttatatttc ttttcaagat


 


3301
tggatcagag ctcatctcca tccagtcttg tttctatgaa ggcttcaatc tgtttccatg


 


3361
caaatttgct aatcagagcc cagagctgct gggtccctca tctccctcat ctattataga


 


3421
ttgacttaca gcagggagag aatctcttta gctcattcct aatggagttg ggatcacaat


 


3481
atggtctggt ccaatctgca tcttgttgtg tcccaagacc ctatctcctc cccaacattc


 


3541
ttattgcctt tggctcccag taaggaacga attgggggcc agggaggaga acagggggga


 


3601
tcaagaaggg aaacccaatt ccccctttga aagtgggttc tttgaactat gtgtttgggg


 


3661
gaagttcctc tggatactaa tttgaattta tatacctcat gttttggggg tttgacgtat


 


3721
atatatatat atatatatgc atatatattt cataatattt ggaaggtttt tgatgctaga


 


3781
aaaatggaaa caagagaacc ttcaaaaatg gtacttagat gggaactgga ggccaatctt


 


3841
tcataaagcc agccccatag ctgcttgctg ttaggcctcc agccattttg acattggggt


 


3901
ggatagtcga ttcacctgcc tgtcagtcga ttcacctgcc tgtcacccag ttctgtggat


 


3961
gtgctggtgc tgagcctttg ctctctttcc aaatggttac agggatgttg atcagctcca


 


4021
ccagagggag ctctgatggg aggaattgct ctgccatcct tgtccctgtg tctcctgtcg


 


4081
gcaggcagcc attgtatctc accagcagac caggagactg gtcccaaggt tactgcacca


 


4141
cagggcaatt tcctgccata gttaggaagg aaacacctga actaaatgga agagacatcc


 


4201
ctgcggtgtt taatatcaca cccatgccct ttgtcaggtt accatgtaca gagattactt


 


4261
ggagagcctc atgccgtctc taccttcgca cactggtcaa gtatctgctg agcttcttgg


 


4321
ccgcaaggat gcagaaatag gctgagggtc catgggaaga aagacacaat gaggcagtag


 


4381
gaggtgggga agaaaagaag acagactttc aaaatggaat taggcactgg ggagagatca


 


4441
gtttccccac atcagggaga agaaggtata ggtggggaag ggggtggcca ggagcagaag


 


4501
gaagaagact caagatggaa agggagccgc tgtgcctgtg gcaataccac ttggagaggt


 


4561
cgacttcata ccttcaagcc ttttcccctg ggcttttgat tgtgtctgtg ccccctttct


 


4621
tgtcctctct gcagatgccc agtaggggct acctcatcct cgtgctgttc ttgtgtggct


 


4681
ttctgggcag tagggatctt gaatttcctt tctaacactg tgcccggcaa ggcggggagc


 


4741
attcctctgc cctttgtctt gtgccaacct ggaaaggtgc agtctagatt tcagtgagaa


 


4801
ccctgccagc tgagccctgt gcatctacta ccttgacaca gagtgttttc ccactagaag


 


4861
ctctgctctg ctctcctggc ccaagtaggg gattccatgc cttccctttc atggtcttag


 


4921
caccagcagc ctagtttctc ccttccagag tctccaggga tgacaaattg gattggagac


 


4981
aaacctcgtc agatgctcat cccctaaaag gttaattgtg tatttgtggc tgcgtgtgcc


 


5041
tttgtgtttt cattctcttc ccatttttgt acattttggt cttctctgtg gttttatact


 


5101
tggtcaaaag tactcgtctt ggtattgcac tgttgtgtgc atgagaaaac tgggggaagg


 


5161
ctcactggta caagaaagga cccctgaccc ctttccttct ctgtggtccc cggcattaga


 


5221
ttgggggttc tgggagaggc aggtgaatgt cctaagtgaa ttgttctgtt tgtaactgga


 


5281
atgtttttga agtctttggt gttgctccgt gaaaggacat cgccacctgg tgctcatgag


 


5341
gtgtctttgc agaacaataa atggcaaatg aacaaccaca aaattgttac tcttgttggc


 


5401
cttctgctgt ttgtagatta gtgcacctat ctgtgaggga tttgggttac ctccctgagt


 


5461
ctgtaagcaa ccacaagccc tgccactggg tgggggaagt ccctccccaa ccacttaaaa


 


5521
acaaattttc cacatattac ccacccacac atttgacctg gctagacttt gtttgcctaa


 


5581
aggaacagac cacattgctg ggaaaatgag taagtgaacg tgtgggagaa aaacactttt


 


5641
agaatcacga atattcactt ttaaaggtct ctttgcctgg ctgcaatata gtgtgtgttt


 


5701
aaattattta caggctgttg tttctcaaat aaatgtttaa tattaatcat tcccaaactg


 


5761
acaagaacac aaaaataaaa tgcaaataca gagcc






One example of a nucleic acid sequence for human DUSP4 is available as NCBI accession number NM_001394 (gi: 58331238). This sequence is recited below for easy reference as SEQ ID NO:134.









1
gctgagcgcc ggaggagcgt aggcagggca gcgctggcgc cagtggcgac aggagccgcg



 


61
cgaccggcaa aaatacacgg gaggccgtcg ccgaaaagag tccgcggtcc tctctcgtaa


 


121
acacactctc ctccaccggc gcctccccct ccgctctgcg cgccgcccgg ctgggcgccc


 


181
gaggccgctc cgactgctat gtgaccgcga ggctgcggga ggaaggggac agggaagaag


 


241
aggctctccc gcgggagccc ttgaggacca agtttgcggc cacttctgca ggcgtccctt


 


301
cttagctctc gcccgcccct ttctgcagcc taggcggccc gggttctctt ctcttcctcg


 


361
cgcgcccagc cgcctcggtt cccggcgacc atggtgacga tggaggagct gcgggagatg


 


421
gactgcagtg tgctcaaaag gctgatgaac cgggacgaga atggcggcgg cgcgggcggc


 


481
agcggcagcc acggcaccct ggggctgccg agcggcggca agtgcctgct gctggactgc


 


541
agaccgttcc tggcgcacag cgcgggctac atcctaggtt cggtcaacgt gcgctgtaac


 


601
accatcgtgc ggcggcgggc taagggctcc gtgagcctgg agcagatcct gcccgccgag


 


661
gaggaggtac gcgcccgctt gcgctccggc ctctactcgg cggtcatcgt ctacgacgag


 


721
cgcagcccgc gcgccgagag cctccgcgag gacagcaccg tgtcgctggt ggtgcaggcg


 


781
ctgcgccgca acgccgagcg caccgacatc tgcctgctca aaggcggcta tgagaggttt


 


841
tcctccgagt acccagaatt ctgttctaaa accaaggccc tggcagccat cccacccccg


 


901
gttcccccca gtgccacaga gcccttggac ctgggctgca gctcctgtgg gaccccacta


 


961
cacgaccagg ggggtcctgt ggagatcctt cccttcctct acctcggcag tgcctaccat


 


1021
gctgcccgga gagacatgct ggacgccctg ggcatcacgg ctctgttgaa tgtctcctcg


 


1081
gactgcccaa accactttga aggacactat cagtacaagt gcatcccagt ggaagataac


 


1141
cacaaggccg acatcagctc ctggttcatg gaagccatag agtacatcga tgccgtgaag


 


1201
gactgccgtg ggcgcgtgct ggtgcactgc caggcgggca tctcgcggtc ggccaccatc


 


1261
tgcctggcct acctgatgat gaagaaacgg gtgaggctgg aggaggcctt cgagttcgtt


 


1321
aagcagcgcc gcagcatcat ctcgcccaac ttcagcttca tggggcagct gctgcagttc


 


1381
gagtcccagg tgctggccac gtcctgtgct gcggaggctg ctagcccctc gggacccctg


 


1441
cgggagcggg gcaagacccc cgccaccccc acctcgcagt tcgtcttcag ctttccggtc


 


1501
tccgtgggcg tgcactcggc ccccagcagc ctgccctacc tgcacagccc catcaccacc


 


1561
tctcccagct gttagagccg ccctgggggc cccagaacca gagctggctc ccagcaaggg


 


1621
taggacgggc cgcatgcggg cagaaagttg ggactgagca gctgggagca ggcgaccgag


 


1681
ctccttcccc atcatttctc cttggccaac gacgaggcca gccagaatgg caataaggac


 


1741
tccgaataca taataaaagc aaacagaaca ctccaactta gagcaataac ggctgccgca


 


1801
gcagccaggg aagaccttgg tttggtttat gtgtcagttt cacttttccg atagaaattt


 


1861
cttacctcat ttttttaagc agtaaggctt gaagtgatga aacccacaga tcctagcaaa


 


1921
tgtgcccaac cagctttact aaagggggag gaagggaggg caaagggatg agaagacaag


 


1981
tttcccagaa gtgcctggtt ctgtgtactt gtccctttgt tgtcgttgtt gtagttaaag


 


2041
gaatttcatt ttttaaaaga aatcttcgaa ggtgtggttt tcatttctca gtcaccaaca


 


2101
gatgaataat tatgcttaat aataaagtat ttattaagac tttcttcaga gtatgaaagt


 


2161
acaaaaagtc tagttacagt ggatttagaa tatatttatg ttgatgtcaa acagctgagc


 


2221
accgtagcat gcagatgtca aggcagttag gaagtaaatg gtgtcttgta gatatgtgca


 


2281
aggtagcatg atgagcaact tgagtttgtt gccactgaga agcaggcggg ttgggtggga


 


2341
ggaggaagaa agggaagaat taggtttgaa ttgcttttta aaaaaaaaag aaaagaaaaa


 


2401
gacagcatct cactatgttg ccaaggctca tcttgagaag caggcgggtt gggtgggagg


 


2461
aggaagaaag ggaagaatta ggtttgaatt gctttttt






One example of a nucleic acid sequence for human EFEMP1 is available as NCBI accession number NM_004105 (gi: 86787911). This sequence is recited below for easy reference as SEQ ID NO:135.









1
cgaaggtagc gtgtcgggga cccagactga taagacaaaa gagaatcagt cgctttgggc



 


61
tgcccctcca cacaacctgg gacttttaaa caaagctgtg cgcagagaaa ggcgtggaaa


 


121
tgccactttg agagtttgtg ctgggggatg tgagaagctc tgagacatgt gagaaggtct


 


181
agtattctac tagaactgga agattgctct ccgagttttg ttttgttatt ttgtttaaaa


 


241
aataaaaagc ttgaggccaa ggcaattcat attggctcac aggtattttt gctgtgctgt


 


301
gcaaggaact ctgctagctc aagattcaca atgttgaaag cccttttcct aactatgctg


 


361
actctggcgc tggtcaagtc acaggacacc gaagaaacca tcacgtacac gcaatgcact


 


421
gacggatatg agtgggatcc tgtgagacag caatgcaaag atattgatga atgtgacatt


 


481
gtcccagacg cttgtaaagg tggaatgaag tgtgtcaacc actatggagg atacctctgc


 


541
cttccgaaaa cagcccagat tattgtcaat aatgaacagc ctcagcagga aacacaacca


 


601
gcagaaggaa cctcaggggc aaccaccggg gttgtagctg ccagcagcat ggcaaccagt


 


661
ggagtgttgc ccgggggtgg ttttgtggcc agtgctgctg cagtcgcagg ccctgaaatg


 


721
cagactggcc gaaataactt tgtcatccgg cggaacccag ctgaccctca gcgcattccc


 


781
tccaaccctt cccaccgtat ccagtgtgca gcaggctacg agcaaagtga acacaacgtg


 


841
tgccaagaca tagacgagtg cactgcaggg acgcacaact gtagagcaga ccaagtgtgc


 


901
atcaatttac ggggatcctt tgcatgtcag tgccctcctg gatatcagaa gcgaggggag


 


961
cagtgcgtag acatagatga atgtaccatc cctccatatt gccaccaaag atgcgtgaat


 


1021
acaccaggct cattttattg ccagtgcagt cctgggtttc aattggcagc aaacaactat


 


1081
acctgcgtag atataaatga atgtgatgcc agcaatcaat gtgctcagca gtgctacaac


 


1141
attcttggtt cattcatctg tcagtgcaat caaggatatg agctaagcag tgacaggctc


 


1201
aactgtgaag acattgatga atgcagaacc tcaagctacc tgtgtcaata tcaatgtgtc


 


1261
aatgaacctg ggaaattctc atgtatgtgc ccccagggat accaagtggt gagaagtaga


 


1321
acatgtcaag atataaatga gtgtgagacc acaaatgaat gccgggagga tgaaatgtgt


 


1381
tggaattatc atggcggctt ccgttgttat ccacgaaatc cttgtcaaga tccctacatt


 


1441
ctaacaccag agaaccgatg tgtttgccca gtctcaaatg ccatgtgccg agaactgccc


 


1501
cagtcaatag tctacaaata catgagcatc cgatctgata ggtctgtgcc atcagacatc


 


1561
ttccagatac aggccacaac tatttatgcc aacaccatca atacttttcg gattaaatct


 


1621
ggaaatgaaa atggagagtt ctacctacga caaacaagtc ctgtaagtgc aatgcttgtg


 


1681
ctcgtgaagt cattatcagg accaagagaa catatcgtgg acctggagat gctgacagtc


 


1741
agcagtatag ggaccttccg cacaagctct gtgttaagat tgacaataat agtggggcca


 


1801
ttttcatttt agtcttttct aagagtcaac cacaggcatt taagtcagcc aaagaatatt


 


1861
gttaccttaa agcactattt tatttataga tatatctagt gcatctacat ctctatactg


 


1921
tacactcacc cataattcaa acaattacac catggtataa agtgggcatt taatatgtaa


 


1981
agattcaaag tttgtcttta ttactatatg taaattagac attaatccac taaactggtc


 


2041
ttcttcaaga gagctaagta tacactatct ggtgaaactt ggattctttc ctataaaagt


 


2101
gggaccaagc aatgatgatc ttctgtggtg cttaaggaaa cttactagag ctccactaac


 


2161
agtctcataa ggaggcagcc atcataacca ttgaatagca tgcaagggta agaatgagtt


 


2221
tttaactgct ttgtaagaaa atggaaaagg tcaataaaga tatatttctt tagaaaatgg


 


2281
ggatctgcca tatttgtgtt ggtttttatt ttcatatcca gcctaaaggt ggttgtttat


 


2341
tatatagtaa taaatcattg ctgtacaata tgctggtttc tgtagggtat ttttaatttt


 


2401
gtcagaaatt ttagattgtg aatattttgt aaaaaacagt aagcaaaatt ttccagaatt


 


2461
cccaaaatga accagatatc ccctagaaaa ttatactatt gagaaatcta tggggaggat


 


2521
atgagaaaat aaattccttc taaaccacat tggaactgac ctgaagaagc aaactcggaa


 


2581
aatataataa catccctgaa ttcaggactt ccacaagatg cagaacaaaa tggataaaag


 


2641
gtatttcact ggagaagttt taatttctaa gtaaaattta aatcctaaca cttcactaat


 


2701
ttataactaa aatttctcat cttcgtactt gatgctcaca gaggaagaaa atgatgatgg


 


2761
tttttattcc tggcatccag agtgacagtg aacttaagca aattaccctc ctacccaatt


 


2821
ctatggaata ttttatacgt ctccttgttt aaaatgtcac tgctttactt tgatgtatca


 


2881
tatttttaaa taaaaataaa tattccttta gaagatcaaa aaaaaaaaaa aaaaaa






One example of a nucleic acid sequence for human ELMO1 is available as NCBI accession number NM_014800 (gi: 86787650). This sequence is recited below for easy reference as SEQ ID NO:136.









1
aagtgagagc agcggcagcc ggcggtgcag cagccggccg acccagagtg taagtgcgtg



 


61
tgctggggcg agcgggagcg ggcgaggatg ggcacaggat agaggcagag ccacccacgc


 


121
cgccgcggcc ccacgctggg cgacagagcc tccagttccc cttcaatggt ggcgggtcgc


 


181
cggagctctg atcgccggga acccttgccg ctgctgtcct gcgaccccaa gcaggtatag


 


241
acacgtgtgg ccgtttacgc tgtaggatcc tcattcccac tggctttgaa cattttgggg


 


301
acttacaatg ccgccacccg cggacatcgt caaggtggcc atagaatggc cgggcgccta


 


361
ccccaaactc atggaaattg atcagaaaaa accactgtct gcaataataa aggaagtctg


 


421
tgatgggtgg tctcttgcca accatgaata ttttgcactc cagcatgccg atagttcaaa


 


481
cttctatatc acagaaaaga accgcaatga gataaaaaat ggcactatcc ttcgattaac


 


541
cacatctcca gctcagaacg cccagcagct ccatgaacga atccagtcct cgagtatgga


 


601
tgccaagctg gaagccctga aggacttggc cagcctctcc cgggatgtca cgtttgccca


 


661
ggagtttata aacctggacg gtatctctct cctcacgcag atggtggaga gcggcactga


 


721
gcgataccag aaattgcaga agatcatgaa gccttgcttt ggagacatgc tgtccttcac


 


781
cctgacggcc ttcgttgagc tgatggacca tggcatagtg tcctgggata cattttcggt


 


841
ggcgttcatt aagaagatag caagttttgt gaacaagtca gccatagaca tctcgatcct


 


901
gcagcggtcc ttggccattt tggagtcgat ggtgctcaat agccatgacc tctaccagaa


 


961
agtggcgcag gagatcacca tcggccagct cattccacac ctgcaagggt cagatcaaga


 


1021
aatccaaacc tatactattg cagtgattaa tgcgcttttc ctgaaggctc ctgatgagag


 


1081
gaggcaggag atggcgaata ttttggctca gaagcaactg cgttccatca ttttaacaca


 


1141
tgtcatccga gcccagcggg ccatcaacaa tgagatggcg caccagctgt atgttctaca


 


1201
agtgctcacc tttaacctcc tggaagacag gatgatgacc aaaatggacc cccaggacca


 


1261
ggctcagagg gacatcatat ttgaacttcg aagaattgct tttgatgctg agtctgaacc


 


1321
taacaacagc agtggcagca tggagaaacg caagtccatg tacacgcgag attataagaa


 


1381
gcttgggttc attaatcatg tcaaccctgc catggacttc acgcagactc cacctgggat


 


1441
gttggctctg gacaacatgc tgtactttgc caagcaccac caagatgcct acatccggat


 


1501
tgtgcttgag aacagtagtc gagaagacaa gcatgaatgt ccctttggcc gcagtagtat


 


1561
agagctgacc aagatgctat gtgagatctt gaaagtgggc gagttgccta gtgagacctg


 


1621
caacgacttc cacccgatgt tcttcaccca cgacagatcc tttgaggagt ttttctgcat


 


1681
ctgtatccag ctcctgaaca agacatggaa ggaaatgagg gcaacttctg aagacttcaa


 


1741
caaggtaatg caggtggtga aggagcaggt tatgagagca cttacaacca agcctagctc


 


1801
cctggaccag ttcaagagca aactgcagaa cctgagctac actgagatcc tgaaaatccg


 


1861
ccagtccgag aggatgaacc aggaagattt ccagtcccgc ccgattttgg aactaaagga


 


1921
gaagattcag ccagaaatct tagagctgat caaacagcaa cgcctgaacc gccttgtgga


 


1981
agggacctgc tttaggaaac tcaatgcccg gcggaggcaa gacaagtttt ggtattgtcg


 


2041
gctttcgcca aatcacaaag tcctgcatta cggagactta gaagagagtc ctcagggaga


 


2101
agtgccccac gattccttgc aggacaaact gccggtggca gatatcaaag ccgtggtgac


 


2161
gggaaaggac tgccctcata tgaaagagaa aggtgccctt aaacaaaaca aggaggtgct


 


2221
tgaactcgct ttctccatct tgtatgactc aaactgccaa ctgaacttca tcgctcctga


 


2281
caagcatgag tactgtatct ggacggatgg actgaatgcg ctactcggga aggacatgat


 


2341
gagcgacctg acgcggaatg acctggacac cctgctcagc atggaaatca agctccgcct


 


2401
cctggacctg gaaaacatcc agatccctga cgcacctccg ccgattccca aggagcccag


 


2461
caactatgac ttcgtctatg actgtaactg aagtggccgg gcccagacat gccccttcca


 


2521
aaactggaac acctagctaa caggagagag gaatgaaaac acacccacgc cttggaaccg


 


2581
tcctttggta aagggaagct gtgggtccac attcccttca gcatcacctc tagccctggc


 


2641
aactttcagc ccctagctgg catcttgctc accgccctga ttctgttcct cggctccact


 


2701
gcttcaggtc acttcccatg gctgcagtcc actggtggga caagagcaaa gcccactgcc


 


2761
agtaagaagg ccaaagggcc cttccatcct agccctctgc aggcatgccc ttccttccct


 


2821
tgggcaggaa agccagcagc cccagactgc ccaaaaactt gcccaccaga ccaagggcag


 


2881
tgccccaagg cccctgtctg gaggaaatgg cctagctatt tgatgagaag accaaacccc


 


2941
acatcctcct ttcccctctc tctagaatca tctcgcacca ccagttacac ttgaattaag


 


3001
atctgcgctc aaatctcctc ccacctctct ccctgctttt gccttgctct gttcctcttt


 


3061
ggtcccaaga gcagcagccg cagcctcctc gtgatcctcc ctagcataaa tttcccaaac


 


3121
agtccacagg tcccatgccc actttgcgtc tgcactgtga tcgtgacaaa tcttccctcc


 


3181
tcaccagcta gtctggggtt tcctctccct gccccaggcc agaactgcct tcttcatttc


 


3241
cacccacgct cccagcctct tagctgaaag cacaaatggt gaaatcagta gtctcgctcc


 


3301
atctctaata gactaaacct aaatgcctct aggacggact gttgctatcc aagcgtttgg


 


3361
tgttaccttc tcctgggagg tcctgctgca actcaagttc cacaggatgg tcaagctgtc


 


3421
agacatccaa gtttacatca ttgtaattat tactggtatt tacaatttgc aagagttttg


 


3481
ggttagtttt tttttttttt tttgctttgt ttttgtacaa aagagtctaa cattttttgc


 


3541
caaacagata tatatttaat gaaaagaaga gatacataaa tgtgtgaatt tccagttttt


 


3601
ttttaattat tttaatccca aacatcttcc tgaaaataac attcccttaa acatgctgtg


 


3661
gaataaaatg gattgtgatg atttggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa


 


3721
aaaaaaa






One example of a nucleic acid sequence for human FGFR2 is available as NCBI accession number NM_000141 (gi: 189083823). This sequence is recited below for easy reference as SEQ ID NO:137.









1
ggcggcggct ggaggagagc gcggtggaga gccgagcggg cgggcggcgg gtgcggagcg



 


61
ggcgagggag cgcgcgcggc cgccacaaag ctcgggcgcc gcggggctgc atgcggcgta


 


121
cctggcccgg cgcggcgact gctctccggg ctggcggggg ccggccgcga gccccggggg


 


181
ccccgaggcc gcagcttgcc tgcgcgctct gagccttcgc aactcgcgag caaagtttgg


 


241
tggaggcaac gccaagcctg agtcctttct tcctctcgtt ccccaaatcc gagggcagcc


 


301
cgcgggcgtc atgcccgcgc tcctccgcag cctggggtac gcgtgaagcc cgggaggctt


 


361
ggcgccggcg aagacccaag gaccactctt ctgcgtttgg agttgctccc cgcaaccccg


 


421
ggctcgtcgc tttctccatc ccgacccacg cggggcgcgg ggacaacaca ggtcgcggag


 


481
gagcgttgcc attcaagtga ctgcagcagc agcggcagcg cctcggttcc tgagcccacc


 


541
gcaggctgaa ggcattgcgc gtagtccatg cccgtagagg aagtgtgcag atgggattaa


 


601
cgtccacatg gagatatgga agaggaccgg ggattggtac cgtaaccatg gtcagctggg


 


661
gtcgtttcat ctgcctggtc gtggtcacca tggcaacctt gtccctggcc cggccctcct


 


721
tcagtttagt tgaggatacc acattagagc cagaagagcc accaaccaaa taccaaatct


 


781
ctcaaccaga agtgtacgtg gctgcgccag gggagtcgct agaggtgcgc tgcctgttga


 


841
aagatgccgc cgtgatcagt tggactaagg atggggtgca cttggggccc aacaatagga


 


901
cagtgcttat tggggagtac ttgcagataa agggcgccac gcctagagac tccggcctct


 


961
atgcttgtac tgccagtagg actgtagaca gtgaaacttg gtacttcatg gtgaatgtca


 


1021
cagatgccat ctcatccgga gatgatgagg atgacaccga tggtgcggaa gattttgtca


 


1081
gtgagaacag taacaacaag agagcaccat actggaccaa cacagaaaag atggaaaagc


 


1141
ggctccatgc tgtgcctgcg gccaacactg tcaagtttcg ctgcccagcc ggggggaacc


 


1201
caatgccaac catgcggtgg ctgaaaaacg ggaaggagtt taagcaggag catcgcattg


 


1261
gaggctacaa ggtacgaaac cagcactgga gcctcattat ggaaagtgtg gtcccatctg


 


1321
acaagggaaa ttatacctgt gtagtggaga atgaatacgg gtccatcaat cacacgtacc


 


1381
acctggatgt tgtggagcga tcgcctcacc ggcccatcct ccaagccgga ctgccggcaa


 


1441
atgcctccac agtggtcgga ggagacgtag agtttgtctg caaggtttac agtgatgccc


 


1501
agccccacat ccagtggatc aagcacgtgg aaaagaacgg cagtaaatac gggcccgacg


 


1561
ggctgcccta cctcaaggtt ctcaaggccg ccggtgttaa caccacggac aaagagattg


 


1621
aggttctcta tattcggaat gtaacttttg aggacgctgg ggaatatacg tgcttggcgg


 


1681
gtaattctat tgggatatcc tttcactctg catggttgac agttctgcca gcgcctggaa


 


1741
gagaaaagga gattacagct tccccagact acctggagat agccatttac tgcatagggg


 


1801
tcttcttaat cgcctgtatg gtggtaacag tcatcctgtg ccgaatgaag aacacgacca


 


1861
agaagccaga cttcagcagc cagccggctg tgcacaagct gaccaaacgt atccccctgc


 


1921
ggagacaggt aacagtttcg gctgagtcca gctcctccat gaactccaac accccgctgg


 


1981
tgaggataac aacacgcctc tcttcaacgg cagacacccc catgctggca ggggtctccg


 


2041
agtatgaact tccagaggac ccaaaatggg agtttccaag agataagctg acactgggca


 


2101
agcccctggg agaaggttgc tttgggcaag tggtcatggc ggaagcagtg ggaattgaca


 


2161
aagacaagcc caaggaggcg gtcaccgtgg ccgtgaagat gttgaaagat gatgccacag


 


2221
agaaagacct ttctgatctg gtgtcagaga tggagatgat gaagatgatt gggaaacaca


 


2281
agaatatcat aaatcttctt ggagcctgca cacaggatgg gcctctctat gtcatagttg


 


2341
agtatgcctc taaaggcaac ctccgagaat acctccgagc ccggaggcca cccgggatgg


 


2401
agtactccta tgacattaac cgtgttcctg aggagcagat gaccttcaag gacttggtgt


 


2461
catgcaccta ccagctggcc agaggcatgg agtacttggc ttcccaaaaa tgtattcatc


 


2521
gagatttagc agccagaaat gttttggtaa cagaaaacaa tgtgatgaaa atagcagact


 


2581
ttggactcgc cagagatatc aacaatatag actattacaa aaagaccacc aatgggcggc


 


2641
ttccagtcaa gtggatggct ccagaagccc tgtttgatag agtatacact catcagagtg


 


2701
atgtctggtc cttcggggtg ttaatgtggg agatcttcac tttagggggc tcgccctacc


 


2761
cagggattcc cgtggaggaa ctttttaagc tgctgaagga aggacacaga atggataagc


 


2821
cagccaactg caccaacgaa ctgtacatga tgatgaggga ctgttggcat gcagtgccct


 


2881
cccagagacc aacgttcaag cagttggtag aagacttgga tcgaattctc actctcacaa


 


2941
ccaatgagga atacttggac ctcagccaac ctctcgaaca gtattcacct agttaccctg


 


3001
acacaagaag ttcttgttct tcaggagatg attctgtttt ttctccagac cccatgcctt


 


3061
acgaaccatg ccttcctcag tatccacaca taaacggcag tgttaaaaca tgaatgactg


 


3121
tgtctgcctg tccccaaaca ggacagcact gggaacctag ctacactgag cagggagacc


 


3181
atgcctccca gagcttgttg tctccacttg tatatatgga tcagaggagt aaataattgg


 


3241
aaaagtaatc agcatatgtg taaagattta tacagttgaa aacttgtaat cttccccagg


 


3301
aggagaagaa ggtttctgga gcagtggact gccacaagcc accatgtaac ccctctcacc


 


3361
tgccgtgcgt actggctgtg gaccagtagg actcaaggtg gacgtgcgtt ctgccttcct


 


3421
tgttaatttt gtaataattg gagaagattt atgtcagcac acacttacag agcacaaatg


 


3481
cagtatatag gtgctggatg tatgtaaata tattcaaatt atgtataaat atatattata


 


3541
tatttacaag gagttatttt ttgtattgat tttaaatgga tgtcccaatg cacctagaaa


 


3601
attggtctct ctttttttaa tagctatttg ctaaatgctg ttcttacaca taatttctta


 


3661
attttcaccg agcagaggtg gaaaaatact tttgctttca gggaaaatgg tataacgtta


 


3721
atttattaat aaattggtaa tatacaaaac aattaatcat ttatagtttt ttttgtaatt


 


3781
taagtggcat ttctatgcag gcagcacagc agactagtta atctattgct tggacttaac


 


3841
tagttatcag atcctttgaa aagagaatat ttacaatata tgactaattt ggggaaaatg


 


3901
aagttttgat ttatttgtgt ttaaatgctg ctgtcagacg attgttctta gacctcctaa


 


3961
atgccccata ttaaaagaac tcattcatag gaaggtgttt cattttggtg tgcaaccctg


 


4021
tcattacgtc aacgcaacgt ctaactggac ttcccaagat aaatggtacc agcgtcctct


 


4081
taaaagatgc cttaatccat tccttgagga cagaccttag ttgaaatgat agcagaatgt


 


4141
gcttctctct ggcagctggc cttctgcttc tgagttgcac attaatcaga ttagcctgta


 


4201
ttctcttcag tgaattttga taatggcttc cagactcttt ggcgttggag acgcctgtta


 


4261
ggatcttcaa gtcccatcat agaaaattga aacacagagt tgttctgctg atagttttgg


 


4321
ggatacgtcc atctttttaa gggattgctt tcatctaatt ctggcaggac ctcaccaaaa


 


4381
gatccagcct catacctaca tcagacaaaa tatcgccgtt gttccttctg tactaaagta


 


4441
ttgtgttttg ctttggaaac acccactcac tttgcaatag ccgtgcaaga tgaatgcaga


 


4501
ttacactgat cttatgtgtt acaaaattgg agaaagtatt taataaaacc tgttaatttt


 


4561
tatactgaca ataaaaatgt ttctacagat attaatgtta acaagacaaa ataaatgtca


 


4621
cgcaacttat ttttttaata aaaaaaaaaa aaaa






One example of a nucleic acid sequence for human FLRT1 is available as NCBI accession number NM_013280 (gi: 48762940). This sequence is recited below for easy reference as SEQ ID NO:138.









1
caaggaggct gctgattgtg gcccacagcc tcatctgaac gccaggagac caggataccg



 


61
aggcaccgga tcccctctct gtgccctggg gagccccagt gctgcccagt caccccaggg


 


121
ctgaggtctg cgtccctagt ggtgcaaggc ctggtaggac cacggggcag ggaatgtgag


 


181
cgccatctga gctcacggtg tcctgagtcg cggcttcgtg actttggcag gggcctccgg


 


241
accagtgacc ccagtcaaac ccagagggtc ttgggcggca gcgacgaagg aggtattcag


 


301
gctccaggcc aggtggggcc ggacgccccc agccatccac catggtggtg gcacacccca


 


361
ccgccactgc caccaccacg cccactgcca ctgtcacggc caccgttgtg atgaccacgg


 


421
ccaccatgga cctgcgggac tggctgttcc tctgctacgg gctcatcgcc ttcctgacgg


 


481
aggtcatcga cagcaccacc tgcccctcgg tgtgccgctg cgacaacggc ttcatctact


 


541
gcaacgaccg gggactcaca tccatccccg cagatatccc tgatgatgcc accaccctct


 


601
acctgcagaa caaccagatc aacaacgccg gcatccccca ggacctcaag accaaggtca


 


661
acgtgcaggt catctaccta tacgagaatg acctggatga gttccccatc aacctgcccc


 


721
gctccctccg ggagctgcac ctgcaggaca acaatgtgcg caccattgcc agggactcgc


 


781
tggcccgcat cccgctgctg gagaagctgc acctggatga caactccgtg tccaccgtca


 


841
gcattgagga ggacgccttc gccgacagca aacagctcaa gctgctcttc ctgagccgga


 


901
accacctgag cagcatcccc tcggggctgc cgcacacgct ggaggagctg cggctggatg


 


961
acaaccgcat ctccaccatc ccgctgcatg ccttcaaggg cctcaacagc ctgcggcgcc


 


1021
tggtgctgga cggtaacctg ctggccaacc agcgcatcgc cgacgacacc ttcagccgcc


 


1081
tacagaacct cacagagctc tcgctggtgc gcaattcgct ggccgcgcca cccctcaacc


 


1141
tgcccagcgc ccacctgcag aagctctacc tgcaggacaa tgccatcagc cacatcccct


 


1201
acaacacgct ggccaagatg cgtgagctgg agcggctgga cctgtccaac aacaacctga


 


1261
ccacgctgcc ccgcggcctg ttcgacgacc tggggaacct ggcccagctg ctgctcagga


 


1321
acaacccttg gttttgtggc tgcaacctca tgtggctgcg ggactgggtg aaggcacggg


 


1381
cggccgtggt caacgtgcgg ggcctcatgt gccagggccc tgagaaggtc cggggcatgg


 


1441
ccatcaagga cattaccagc gagatggacg agtgttttga gacggggccg cagggcggcg


 


1501
tggccaatgc ggctgccaag accacggcca gcaaccacgc ctctgccacc acgccccagg


 


1561
gttccctgtt taccctcaag gccaaaaggc cagggctgcg cctccccgac tccaacattg


 


1621
actaccccat ggccacgggt gatggcgcca agaccctggc catccacgtg aaggccctga


 


1681
cggcagactc catccgcatc acgtggaagg ccacgctccc cgcctcctct ttccggctca


 


1741
gttggctgcg cctgggccac agcccagccg tgggctccat cacggagacc ttggtgcagg


 


1801
gggacaagac agagtacctg ctgacagccc tggagcccaa gtccacctac atcatctgca


 


1861
tggtcaccat ggagaccagc aatgcctacg tagctgatga gacacccgtg tgtgccaagg


 


1921
cagagacagc cgacagctat ggccctacca ccacactcaa ccaggagcag aacgctggcc


 


1981
ccatggcgag cctgcccctg gcgggcatca tcggcggggc agtggctctg gtcttcctct


 


2041
tcctggtcct gggggccatc tgctggtacg tgcaccaggc tggcgagctg ctgacccggg


 


2101
agagggccta caaccggggc agcaggaaaa aggatgacta tatggagtca gggaccaaga


 


2161
aggataactc catcctggaa atccgcggcc ctgggctgca gatgctgccc atcaacccgt


 


2221
accgcgccaa agaggagtac gtggtccaca ctatcttccc ctccaacggc agcagcctct


 


2281
gcaaggccac acacaccatt ggctacggca ccacgcgggg ctaccgggac ggcggcatcc


 


2341
ccgacataga ctactcctac acatgatgcc cgcccacccg ggctgccccg cctcagcccc


 


2401
agctgccctg gcgtggccat gtggctttgc ccagcctgct gcaatccaag agagcaagga


 


2461
agagaaattc catgggtgac tttcctccgc agaaagcaaa gtttggggag ggctgacgat


 


2521
tttgtagaac acaacagtga caattttttt taaaagaata gaaggcagga gggggaattc


 


2581
gacattgttg aagacataat ttataccaag ttatgccagt tggggaggga aggactaaaa


 


2641
ataatattgc aggcagggct gggttgggtt tttttttttt cccccctgaa ctggaaggat


 


2701
actacctgta caacatctgt ggacacctca tgctctgttc aaggccatca caaaggaacc


 


2761
gccagggaga agcagccggc tctcaaagct cccacgcagc tctcccgcca ctggccactc


 


2821
gctggcgacc cgatggaagg ttttcaggct cctcacaaag gagagaggga agaaaagatc


 


2881
ttttgccctg gagatatggt cctgaaatct ctcccctggc ttattccata ccatttccct


 


2941
tgcagatttg cagaaacatg gcatctttca ctgcattctt tgaacaatca tgtagtcgat


 


3001
taaaaaaaaa aaacaaactt ttttttccta ggctgaagcc ctcttcagtt ccatgcacca


 


3061
cgctccgtag aagccccggc ggaagccgta gctttccctg ccacctggag gtgcatctgt


 


3121
ctgcctgtct atccctgtcg cggtgtctct aagtacagat gggtagatag agccacatgc


 


3181
acggtcctta ccgttcttct tgggtcagtt cttaccattt cctgaacaat agaattgtga


 


3241
aagtgttaaa aa






One example of a nucleic acid sequence for human FMOD is available as NCBI accession number NM_002023 (gi: 71040110). This sequence is recited below for easy reference as SEQ ID NO:139.









1
ggtctggcac aggcacgcac actctcagta gactctttca ctcctctctc tcttcctctc



 


61
tcacacgttc tccaacccaa ggaggccaga cagagggacg tggtcactct ctgaaaagtt


 


121
caacttgaga gacaaaatgc agtggacctc cctcctgctg ctggcagggc tcttctccct


 


181
ctcccaggcc cagtatgaag atgaccctca ttggtggttc cactacctcc gcagccagca


 


241
gtccacctac tacgatccct atgaccctta cccgtatgag acctacgagc cttaccccta


 


301
tggggtggat gaagggccag cctacaccta cggctctcca tcccctccag atccccgcga


 


361
ctgcccccag gagtgcgact gcccacccaa cttccccacg gccatgtact gtgacaatcg


 


421
caacctcaag tacctgccct tcgttccctc ccgcatgaag tatgtgtact tccagaacaa


 


481
ccagatcacc tccatccagg aaggcgtctt tgacaatgcc acagggctgc tctggattgc


 


541
tctccacggc aaccagatca ccagtgataa ggtgggcagg aaggtcttct ccaagctgag


 


601
gcacctggag aggctgtacc tggaccacaa caacctgacc cggatgcccg gtcccctgcc


 


661
tcgatccctg agagagctcc atctcgacca caaccagatc tcacgggtcc ccaacaatgc


 


721
tctggagggg ctggagaacc tcacggcctt gtacctccaa cacaatgaga tccaggaagt


 


781
gggcagttcc atgaggggcc tccggtcact gatcttgctg gacctgagtt ataaccacct


 


841
tcggaaggtg cctgatgggc tgccctcagc tcttgagcag ctgtacatgg agcacaacaa


 


901
tgtctacacc gtccccgata gctacttccg gggggcgccc aagctgctgt atgtgcggct


 


961
gtcccacaac agtctaacca acaatggcct ggcctccaac accttcaatt ccagcagcct


 


1021
ccttgagcta gacctctcct acaaccagct gcagaagatc cccccagtca acaccaacct


 


1081
ggagaacctc tacctccaag gcaataggat caatgagttc tccatcagca gcttctgcac


 


1141
cgtggtggac gtcgtgaact tctccaagct gcaggtgctg cgcctggacg ggaacgagat


 


1201
caagcgcagc gccatgcctg ccgacgcgcc cctctgcctg cgccttgcca gcctcatcga


 


1261
gatctgagca gccctggcac cgggtactgg gcggagagcc cccgtggcat ttggcttgat


 


1321
ggtttggttt ggcttttgct ggaaggtcca ggatggacca tgtgacagaa gtccacgggc


 


1381
accctctgta gtcttctttc ctgtaggtgg ggttaggggg ggcgatcagg gacaggcagc


 


1441
cttctgctga ggacataggc agaagctcac tcttttccag ggacagaagt ggtggtagat


 


1501
ggaaggatcc ctggatgttc caaccccata aatctcacgg ctcttaagtt cttcccaatg


 


1561
atctgaggtc atggaacttc aaaagtggca tgggcaatag tatataacca tacttttcta


 


1621
acaatccctg gctgtctgtg agcagcactt gacagctctc cctctgtgct gggctggtcg


 


1681
tgcagttact ctgggctccc atttgttgct tctcaaaata tacctcttgc ccagctgcct


 


1741
cttctgaaat ccacttcacc cactccactt tcctccacag atgcctcttc tgtgccttaa


 


1801
gcagagtcag gagaccccaa ggcatgtgag catctgccca gcaacctgtg gagacaaccc


 


1861
acactgtgtc tgagggtgaa aggacaccag gagtcacttc tatacctccc taacctcacc


 


1921
cctggaaagc caccagattg gaggtcacca gcatgatgat aatattcatg acctgatgtg


 


1981
ggaggagaca gccaacctca ggcttagatc aatgtatagg gctatatttt ggcagctggg


 


2041
tagctctttg aaggtggata agacttcaga agaggaaagg ccagactttg cttaccatca


 


2101
gcatctgcaa tgggccaaac acacctcaaa ttggctgagt tgagaaagca gccccagtag


 


2161
ttccattctt gcccagcact ttctgcattc caaacagcat cctacctggg tttttatcca


 


2221
caaaggtagc ggccacatgg tttttaaagt atgagaaaca cagtttgtcc tctcctttta


 


2281
tccaagcagg aagattctat atcctgatgg tagagacaga ctccaggcag ccctggactt


 


2341
gctagcccaa agaaggagga tgtggttaat ctgtttcacc tggtttgtcc taaggccata


 


2401
gttaaaaagt accagctctg gctggggtcc gtgaagccca ggccaggcag ccaaatcttg


 


2461
cctgtgctgg gcatacaacc ctctgctttc acatctctga gctatatcct cattagtgaa


 


2521
ggtggctttt gctttatagt ttggctgggg agcacttaat tcttcccatt tcaaaaggta


 


2581
atgttgcctg gggcttaacc cacctgccct ttgggcaagg ttgggacaaa gccatctggg


 


2641
cagtcagggg caaggactgt tggaggagag ttagcccaag tataggctct gcccagatgc


 


2701
catcacatcc ctgatactgt gtatgctttg aagcaccttc cctgagaagg gaagagggga


 


2761
tctttggact acgttcttgg ctccagacct ggaatccaca aaagccaaac cagctcattt


 


2821
caacaaagga gctccgatgt gaggggcaag gctgccccct gccccagggc tcttcagaaa


 


2881
gcatctgcat gtgaacacca tcatgccttt ataaaggatc cttattacag gaaaagcatg


 


2941
agtggtggct aacctgacca ataaagttat tttatgattg catctaaaaa aaaaaaaaaa


 


3001
aaaaa






One example of a nucleic acid sequence for human GALNT7 is available as NCBI accession number NM_017423 (gi: 157502211). This sequence is recited below for easy reference as SEQ ID NO:140.









1
agagccggag gagggggaag gagggagggg agagcggtgg cggcggctgc gccgggctgt



 


61
gagtctctcg ccgccggagg aagatgaggc tgaagattgg gttcatctta cgcagtttgc


 


121
tggtggtggg aagcttcctg gggctagtgg tcctctggtc ttccctgacc ccgcggccgg


 


181
acgacccaag cccgctgagc aggatgaggg aagacagaga tgtcaatgac cccatgccca


 


241
accgaggcgg caatggacta gctcctgggg aggacagatt caaacctgtg gtaccatggc


 


301
ctcatgttga aggagtagaa gtggacttag agtctattag aagaataaac aaggccaaaa


 


361
atgaacaaga gcaccatgct ggaggagatt cccagaaaga tatcatgcag aggcagtatc


 


421
tcacatttaa gcctcagaca ttcacctacc atgatcctgt gcttcgccca gggatcctcg


 


481
gtaactttga acccaaagaa cctgagcctc ctggagtggt tggtggccct ggagagaaag


 


541
ccaagccatt ggttttggga ccagaattca aacaagcaat tcaagccagc attaaagagt


 


601
ttggatttaa catggtggca agtgacatga tctcactgga ccgcagcgtc aatgacttac


 


661
gccaagaaga atgcaagtat tggcattatg atgaaaactt gctcacttcg agcgttgtca


 


721
ttgtcttcca taatgaagga tggtcaaccc tcatgagaac agtccacagt gtaattaaaa


 


781
ggactccaag gaaatattta gcagaaattg tgttaattga cgatttcagt aataaagaac


 


841
acttaaaaga aaaactggat gaatatatta agctgtggaa tggcctagtg aaggtatttc


 


901
gaaatgaaag aagggaaggt ttaattcaag cacgaagtat tggtgctcag aaggctaaac


 


961
ttggacaggt tttgatatac cttgatgccc actgtgaggt ggcagttaac tggtatgcac


 


1021
cacttgtagc tcccatatct aaggacagaa ccatttgcac tgtgccgctt atagatgtca


 


1081
taaatggcaa cacatatgaa attatacccc aagggggtgg tgatgaagat gggtatgccc


 


1141
gaggagcatg ggattggagt atgctctgga aacgggtgcc tctgacccct caagagaaga


 


1201
gactgagaaa gacaaaaact gaaccgtatc ggtccccagc catggctggg ggattatttg


 


1261
ccattgaacg agagttcttc tttgaattgg gtctctatga tccaggtctc cagatttggg


 


1321
gtggtgaaaa ctttgagatc tcatacaaga tatggcagtg tggtggcaaa ttattatttg


 


1381
ttccttgttc tcgtgttgga catatctacc gtcttgaggg ctggcaagga aatcctccgc


 


1441
ccatttatgt tgggtcttct ccaactctga agaattatgt tagagttgtg gaggtttggt


 


1501
gggatgaata taaagactac ttctatgcta gtcgtcctga atcgcaggca ttaccatatg


 


1561
gggatatatc ggagctgaaa aaatttcgag aagatcacaa ctgcaaaagt tttaagtggt


 


1621
tcatggaaga aatagcttat gatatcacct cacactaccc tttgccaccc aaaaatgttg


 


1681
actggggaga aatcagaggc ttcgaaactg cttactgcat tgatagcatg ggaaaaacaa


 


1741
atggaggctt tgttgaacta ggaccctgcc acaggatggg agggaatcag cttttcagaa


 


1801
tcaatgaagc aaatcaactc atgcagtatg accagtgttt gacaaaggga gctgatggat


 


1861
caaaagttat gattacacac tgtaatctaa atgaatttaa ggaatggcag tacttcaaga


 


1921
acctgcacag atttactcat attccttcag gaaagtgttt agatcgctca gaggtcctgc


 


1981
atcaagtatt catctccaat tgtgactcca gtaaaacgac tcaaaaatgg gaaatgaata


 


2041
acatccatag tgtttagaga gaaaaaaata aaccaataac ctacctactg acaagtaaat


 


2101
ttatacagga ctgaaaaccg cctgaaacct gctgcaacta ttgttattaa ctctgtatag


 


2161
ctccaaacct ggaacctcct gatcagtttg aaggacattg ataaactgtg attttacaat


 


2221
aacattatca tctgcagtta ctgtttacaa gactgctttt accttaaact ttgtagatgt


 


2281
ttacatcttt ttgttgtgtt ttaagatgat gttggtaatt tgtgccttta gctctgtttt


 


2341
attagacaga gttaaagcat gttgtcttct ttgggattac actcaggggt ctgaaaggca


 


2401
gtttgatttt tatttttaac acacttgaaa aaaggttgga gtagccagac tttcatatat


 


2461
aacttggtga ttatcaacct gttgtgtctt tatttaattt tacatctttt tgaagcactg


 


2521
ccacaggtta ttagccaagg tggccttcct tcacagtcat gctgcttttt tgaaaggtga


 


2581
atttcaacac atttagtgcc tctttcattt ctcagtatat atttcaagag cttgtgatga


 


2641
aatctatagg atggtaatga tggacttgtc acctgtatgg ggaatacttt tactactcag


 


2701
aaatgaattt atgtgctgcc atttgctata aagttgaact ttgtatggct tgaaaaagaa


 


2761
atgacaatat ggaacatccc aaggctgtcc catagggttg gaagttgtgt agcattcact


 


2821
cccttaccta ctggcattcc cagtgccctc tgtccatacc tacttctagg attgcaaagg


 


2881
agtcttccaa ctagagaaaa attgtccact gacatttggg atttactttt ctccaatacc


 


2941
tgccaataca gaaaactatt atcagttgtt attgttatcc cttgaaagcg agggtgacaa


 


3001
aaacaacaaa acaccgttat aaacacatca aaggttcatt ctgactgagg taagactttc


 


3061
caagcccttg ttagattagg ccttataaaa cttgtgtgca ttataaccta agctgtgcaa


 


3121
cctgtgaagc caagagtgaa ctgatgtttc atttatattt tcatccaaat gacattatct


 


3181
gcacgttttt aaaatttaaa aacaaaggac tatttaaaaa tacagtttat taacaaacgt


 


3241
gaactacttt ctgttacatt aggtgttccc tagtgtttct taatttcttt ttagaaagtg


 


3301
tatttttatt agtatttttc cggtgaacag aagatttgtt tggatttaaa catttactaa


 


3361
gacagtacct attaggaaaa ccaaatattg caaatggtca attcgatttt aatttctcaa


 


3421
aagatactct gttatccaga agattaaaat gcctacattg agtgcttaaa aaaaaaaaaa


 


3481
caactgtgat gatgtgagca gaatggcaag taagttaagc atttttgatc ctgtaatcat


 


3541
ggtatcatta caatgaaagg aattcacaaa ctactgccag aggaagtttg ttttttaatt


 


3601
taagagggaa atataaccta taaatttgtt tcttccaagc ttagctctta aatttggaga


 


3661
ctcaaagtta aacatcctca acagagtttt atttataatt ttgaattgtc aatttgtatt


 


3721
ttgctactga tctgtgatca accattttaa ctttcatctc tagggatgtt taacatttat


 


3781
aattgcaaaa taaaccaact ataaaaaaag aaactaagag agaattggta ctttaattac


 


3841
ttgtgtgttt gcaaataggc tccattttcc atgttgagta gattataacc ttattaacta


 


3901
tgcataggcc taagaaaggt ggcaatgaac tgtgcatgta aattttaaat gggtactttg


 


3961
tgcaattcgt taaaagaaga tactctatga atatgattct atatattgaa atcagaaaac


 


4021
ctaccaaaca aaaacatcag aagctgctgc cataatgact attttctact gtaggctgct


 


4081
ttggaaataa ttcccatatc cttgctttgt aagttggtaa tatcactatg catttctaca


 


4141
cattttataa atttgattta tgcagatttt gatacactgt atgtttctgt agaaattgta


 


4201
taaatattca aaattttatt aggataaatt tgagaaactt acgtatatct taattctggg


 


4261
ttgcttgttt tttaggtgac aaaaataaaa tattgtattt taattcaaaa aaaaaaaaaa


 


4321
aaaaaaaaaa aaaaaaaaa






One example of a nucleic acid sequence for human GATM is available as NCBI accession number NM_001482 (gi: 126090880). This sequence is recited below for easy reference as SEQ ID NO:141.









1
ttgcgacgct cgggtctggg tccgggtccg gacgtgcaac agaagccgtc agtggccccg



 


61
ctggctaaaa aagggcaagc atcggaggct cgagccagcg gccgcggcgc ttcccgacag


 


121
ttcctaattc ggggcgctac gccggcccca ccacctgttc ccggcagcca atggggccgc


 


181
ggggggcggc cggggcggag cgcggctaca aaaggcctcg ggccccgcgc gcccgcccac


 


241
cccgctccgg gcgcgctctc gggaaggctt ggaccgacgc ggcccagagg ccaggaacat


 


301
tccgcgcgtg gaccagccgg gccagggcga tgctgcgggt gcggtgtctg cgcggcggga


 


361
gccgcggcgc cgaggcggtg cactacatcg gatctcggct tggacgaacc ttgacaggat


 


421
gggtgcagcg aactttccag agcacccagg cagctacggc ttcctcccgg aactcctgtg


 


481
cagctgacga caaagccact gagcctctgc ccaaggactg ccctgtctct tcttacaacg


 


541
aatgggaccc cttagaggaa gtgatagtgg gcagagcaga aaacgcctgt gttccaccgt


 


601
tcaccatcga ggtgaaggcc aacacatatg aaaagtactg gccattttac cagaagcaag


 


661
gagggcatta ttttcccaaa gatcatttga aaaaggctgt tgctgaaatt gaagaaatgt


 


721
gcaatatttt aaaaacggaa ggagtgacag taaggaggcc tgaccccatt gactggtcat


 


781
tgaagtataa aactcctgat tttgagtcta cgggtttata cagtgcaatg cctcgagaca


 


841
tcctgatagt tgtgggcaat gagattatcg aggctcccat ggcatggcgt tcacgcttct


 


901
ttgagtaccg agcgtacagg tcaattatca aagactactt ccaccgtggc gccaagtgga


 


961
caacagctcc taagcccaca atggctgatg agctttataa ccaggattat cccatccact


 


1021
ctgtagaaga cagacacaaa ttggctgctc agggaaaatt tgtgacaact gagtttgagc


 


1081
catgctttga tgctgctgac ttcattcgag ctggaagaga tatttttgca cagagaagcc


 


1141
aggttacaaa ctacctaggc attgaatgga tgcgtaggca tcttgctcca gactacagag


 


1201
tgcatatcat ctcctttaaa gatcccaatc ccatgcatat tgatgctacc ttcaacatca


 


1261
ttggacctgg tattgtgctt tccaaccctg accgaccatg tcaccagatt gatcttttca


 


1321
agaaagcagg atggactatc attactcctc caacaccaat catcccagac gatcatccac


 


1381
tctggatgtc atccaaatgg ctttccatga atgtcttaat gctagatgaa aaacgtgtta


 


1441
tggtggatgc caatgaagtt ccaattcaaa agatgtttga aaagctgggt atcactacca


 


1501
ttaaagttaa cattcgtaat gccaattccc tgggaggagg cttccattgc tggacctgcg


 


1561
atgtccggcg ccgaggcacc ttacagtcct acttggactg aacaggcctg atggagcttg


 


1621
tggctggcct cagatacacc taagaagctt aggggcaagg ttcattctcc tgctttaaaa


 


1681
agtgcatgaa ctgtagtgct ttaaacaatc atctccttaa caggggtcgt aagcctggtt


 


1741
tgcttctatt acttttcttt gacataaaga aaataacttc tgctaggtat tactctctac


 


1801
tcctaaagtt atttactatt tggcttcaag tataaaattt tggtgaatgt gtaccaagaa


 


1861
aaaattagtc acctgagtaa cttggccact aataattaac catctacctc tgtttttaat


 


1921
tttctttcca aaaggcagct tgaaatgttg gtcctaatct taattttttt tcctcttcta


 


1981
tagacttgag aatgtttttc tctaaatgag agaaagactt agaatgtaca cagatccaaa


 


2041
atagaatcag attatctctt tttttctaaa ggagagaaag acttagaaca tacacagatc


 


2101
ctaagtagaa ccaggtaatt gtctcttttt ctaataagga atttgggtaa tttttaattt


 


2161
tttgtttttt aaaaaataac ctagactatg caaaacatca aagtgaattt tccatgaatg


 


2221
tttttaatat tctcatctca acattgtgat atatgctact aaaaaccttt tcatatacat


 


2281
cttacctcat ttcaagtgaa ttattttaat ctttttctct ctttccaaaa atttaggaat


 


2341
gtttagtgta attggatttc gctatcagtt cccatcctta agttttgata ttcaatatct


 


2401
gatagataca ctgcatcttt ggtcatctaa gatttgttta caaatgtgca aattatttag


 


2461
agcatagact ttataagcat taaaaaaaac taatggaggt aaaacctaaa tgcgatgtga


 


2521
aataatttta gtgttgatac cgtatgtgta tttttattct aataaacttt tgtgttccag


 


2581
attgaaaaaa aaaaaaaaaa aa






One example of a nucleic acid sequence for human HGD is available as NCBI accession number NM_000187 (gi: 115527116). This sequence is recited below for easy reference as SEQ ID NO:142.









1
ccacagttcc tttccccgat agcttcaaat tctctgcctt ttgaaataag cctactttta



 


61
actggaataa ataattggtc aatctctacc tcaggtgaag aggaaccaag cctctggaaa


 


121
cacttaggaa caaactgtaa aaaccaaagg caattgtgta accggttaaa taagcttgct


 


181
ggactttgtc cctgtgtatg agttagacaa ttctttcagc tagtttgagt gacgcactga


 


241
ccagtgaagc gcagtgaagc agtgggaacc ggaatatcca aagagtggtt tgaaggagaa


 


301
agaagcattg tggctttata tcctctgggc ctgggtttcc tgaagtcacc acacatagag


 


361
gagagagaaa atggctgagt taaagtacat ttctggattt gggaatgagt gttcttcaga


 


421
ggatcctcgc tgcccaggtt ccctgccaga aggacagaat aatcctcagg tctgccccta


 


481
caatctctat gctgagcagc tctcaggatc ggctttcact tgtccacgga gcaccaataa


 


541
gagaagctgg ctgtatagga ttctaccttc agtttctcac aagccctttg aatccattga


 


601
cgaaggccaa gtcactcaca actgggatga agttgatcct gatcctaacc agcttagatg


 


661
gaaaccattt gagattccaa aagcatctca gaagaaagta gactttgtga gtggcctgca


 


721
taccttgtgt ggagctggag acataaagtc taacaatggg cttgctatcc acattttcct


 


781
ctgcaatacc tccatggaga acagatgctt ttacaattca gatggggact tcttgattgt


 


841
tccgcagaaa gggaaccttc tcatttacac cgagtttggc aagatgcttg tacagcccaa


 


901
tgagatctgc gtcattcaga gaggaatgcg gttcagcata gatgtctttg aggagaccag


 


961
gggctacatc ttggaggtct atggtgtcca ctttgagtta cctgaccttg gaccaattgg


 


1021
ggccaatggc ttggccaatc ctcgtgattt cttgataccc attgcctggt atgaggatcg


 


1081
ccaagtacca ggtggttaca cggtcattaa taaataccag ggcaagctgt ttgctgccaa


 


1141
acaggatgtc tccccgttca atgttgtggc ctggcacggg aattatacac cctacaagta


 


1201
caacctgaag aatttcatgg ttatcaactc agtggccttt gaccatgcag acccatccat


 


1261
tttcacagta ttgactgcta agtctgtccg ccctggagtg gccattgctg attttgtcat


 


1321
cttcccacct cgatgggggg ttgctgataa gaccttcagg cctccttatt accataggaa


 


1381
ctgcatgagt gagttcatgg gactcatccg aggtcactat gaggcaaagc aaggtgggtt


 


1441
cctgccaggg ggagggagtc tacacagcac aatgaccccc catggacctg atgctgactg


 


1501
ctttgagaag gccagcaagg tcaagctggc acctgagagg attgccgatg gcaccatggc


 


1561
atttatgttt gaatcatctt taagtctggc ggtcacaaag tggggactca aggcctccag


 


1621
gtgtttggat gagaactacc acaagtgctg ggagccactc aagagccact tcactcccaa


 


1681
ctccaggaac ccagcagaac ctaattgaga ctggaacatt gctaccataa ttaagagtag


 


1741
atttgtgaag atttcttcag aatctcatgc tttctggtag tattggagga gggggttggt


 


1801
taaaatgaaa attcactttt catagtcaag taactcagaa cttttatgga aacgcatttg


 


1861
caaagttcta tggctgtcac cttaattact caataaactt gctggtgttc tgtggacgta






One example of a nucleic acid sequence for human HMGA2 is available as NCBI accession number NM_003483 (gi: 62912480). This sequence is recited below for easy reference as SEQ ID NO:143.









1
cttgaatctt ggggcaggaa ctcagaaaac ttccagcccg ggcagcgcgc gcttggtgca



 


61
agactcagga gctagcagcc cgtccccctc cgactctccg gtgccgccgc tgcctgctcc


 


121
cgccacccta ggaggcgcgg tgccacccac tactctgtcc tctgcctgtg ctccgtgccc


 


181
gaccctatcc cggcggagtc tccccatcct cctttgcttt ccgactgccc aaggcacttt


 


241
caatctcaat ctcttctctc tctctctctc tctctctctc tctctctctc tctctctctc


 


301
tctctctctc gcagggtggg gggaagagga ggaggaattc tttccccgcc taacatttca


 


361
agggacacaa ttcactccaa gtctcttccc tttccaagcc gcttccgaag tgctcccggt


 


421
gcccgcaact cctgatccca acccgcgaga ggagcctctg cgacctcaaa gcctctcttc


 


481
cttctccctc gcttccctcc tcctcttgct acctccacct ccaccgccac ctccacctcc


 


541
ggcacccacc caccgccgcc gccgccaccg gcagcgcctc ctcctctcct cctcctcctc


 


601
ccctcttctc tttttggcag ccgctggacg tccggtgttg atggtggcag cggcggcagc


 


661
ctaagcaaca gcagccctcg cagcccgcca gctcgcgctc gccccgccgg cgtccccagc


 


721
cctatcacct catctcccga aaggtgctgg gcagctccgg ggcggtcgag gcgaagcggc


 


781
tgcagcggcg gtagcggcgg cgggaggcag gatgagcgca cgcggtgagg gcgcggggca


 


841
gccgtccact tcagcccagg gacaacctgc cgccccagcg cctcagaaga gaggacgcgg


 


901
ccgccccagg aagcagcagc aagaaccaac cggtgagccc tctcctaaga gacccagggg


 


961
aagacccaaa ggcagcaaaa acaagagtcc ctctaaagca gctcaaaaga aagcagaagc


 


1021
cactggagaa aaacggccaa gaggcagacc taggaaatgg ccacaacaag ttgttcagaa


 


1081
gaagcctgct caggaggaaa ctgaagagac atcctcacaa gagtctgccg aagaggacta


 


1141
gggggcgcca acgttcgatt tctacctcag cagcagttgg atcttttgaa gggagaagac


 


1201
actgcagtga ccacttattc tgtattgcca tggtctttcc actttcatct ggggtggggt


 


1261
ggggtggggt gggggagggg ggggtggggt ggggagaaat cacataacct taaaaaggac


 


1321
tatattaatc accttctttg taatcccttc acagtcccag gtttagtgaa aaactgctgt


 


1381
aaacacaggg gacacagctt aacaatgcaa cttttaatta ctgttttctt ttttcttaac


 


1441
ctactaatag tttgttgatc tgataagcaa gagtgggcgg gtgagaaaaa ccgaattggg


 


1501
tttagtcaat cactgcactg catgcaaaca agaaacgtgt cacacttgtg acgtcgggca


 


1561
ttcatatagg aagaacgcgg tgtgtaacac tgtgtacacc tcaaatacca ccccaaccca


 


1621
ctccctgtag tgaatcctct gtttagaaca ccaaagataa ggactagata ctactttctc


 


1681
tttttcgtat aatcttgtag acacttactt gatgattttt aactttttat ttctaaatga


 


1741
gacgaaatgc tgatgtatcc tttcattcag ctaacaaact agaaaaggtt atgttcattt


 


1801
ttcaaaaagg gaagtaagca aacaaatatt gccaactctt ctatttatgg atatcacaca


 


1861
tatcagcagg agtaataaat ttactcacag cacttgtttt caggacaaca cttcattttc


 


1921
aggaaatcta cttcctacag agccaaaatg ccatttagca ataaataaca cttgtcagcc


 


1981
tcagagcatt taaggaaact agacaagtaa aattatcctc tttgtaattt aatgaaaagg


 


2041
tacaacagaa taatgcatga tgaactcacc taattatgag gtgggaggag cgaaatctaa


 


2101
atttcttttg ctatagttat acatcaattt aaaaagcaaa aaaaaaaaag gggggggcaa


 


2161
tctctctctg tgtctttctc tctctctctt cctctccctc tctcttttca ttgtgtatca


 


2221
gtttccatga aagacctgaa taccacttac ctcaaattaa gcatatgtgt tacttcaagt


 


2281
aatacgtttt gacataagat ggttgaccaa ggtgcttttc ttcggcttga gttcaccatc


 


2341
tcttcattca aactgcactt ttagccagag atgcaatata tccccactac tcaatactac


 


2401
ctctgaatgt tacaacgaat ttacagtcta gtacttatta catgctgcta tacacaagca


 


2461
atgcaagaaa aaaacttact gggtaggtga ttctaatcat ctgcagttct ttttgtacac


 


2521
ttaattacag ttaaagaagc aatctcctta ctgtgtttca gcatgactat gtatttttct


 


2581
atgttttttt aattaaaaat ttttaaaata cttgtttcag cttctctgct agatttctac


 


2641
attaacttga aaatttttta accaagtcgc tcctaggttc ttaaggataa ttttcctcaa


 


2701
tcacactaca catcacacaa gatttgactg taatatttaa atattaccct ccaagtctgt


 


2761
acctcaaatg aattctttaa ggagatggac taattgactt gcaaagacct acctccagac


 


2821
ttcaaaagga atgaacttgt tacttgcagc attcatttgt tttttcaatg tttgaaatag


 


2881
ttcaaactgc agctaaccct agtcaaaact atttttgtaa aagacatttg atagaaagga


 


2941
acacgttttt acatactttt gcaaaataag taaataataa ataaaataaa agccaacctt


 


3001
caaagaaact tgaagctttg taggtgagat gcaacaagcc ctgcttttgc ataatgcaat


 


3061
caaaaatatg tgtttttaag attagttgaa tataagaaaa tgcttgacaa atattttcat


 


3121
gtattttaca caaatgtgat ttttgtaata tgtctcaacc agatttattt taaacgcttc


 


3181
ttatgtagag tttttatgcc tttctctcct agtgagtgtg ctgacttttt aacatggtat


 


3241
tatcaactgg gccaggaggt agtttctcat gacggctttt gtcagtatgg cttttagtac


 


3301
tgaagccaaa tgaaactcaa aaccatctct cttccagctg cttcagggag gtagtttcaa


 


3361
aggccacata cctctctgag actggcagat cgctcactgt tgtgaatcac caaaggagct


 


3421
atggagagaa ttaaaactca acattactgt taactgtgcg ttaaataagc aaataaacag


 


3481
tggctcataa aaataaaagt cgcattccat atctttggat gggcctttta gaaacctcat


 


3541
tggccagctc ataaaatgga agcaattgct catgttggcc aaacatggtg caccgagtga


 


3601
tttccatctc tggtaaagtt acacttttat ttcctgtatg ttgtacaatc aaaacacact


 


3661
actacctctt aagtcccagt atacctcatt tttcatactg aaaaaaaaag cttgtggcca


 


3721
atggaacagt aagaacatca taaaattttt atatatatag tttatttttg tgggagataa


 


3781
attttatagg actgttcttt gctgttgttg gtcgcagcta cataagactg gacatttaac


 


3841
ttttctacca tttctgcaag ttaggtatgt ttgcaggaga aaagtatcaa gacgtttaac


 


3901
tgcagttgac tttctccctg ttcctttgag tgtcttctaa ctttattctt tgttctttat


 


3961
gtagaattgc tgtctatgat tgtactttga atcgcttgct tgttgaaaat atttctctag


 


4021
tgtattatca ctgtctgttc tgcacaataa acataacagc ctctgtgatc cccatgtgtt


 


4081
ttgattcctg ctctttgtta cagttccatt aaatgagtaa taaagtttgg tcaaaacaga


 


4141
aaaaaaaaaa






One example of a nucleic acid sequence for human IGFBP6 is available as NCBI accession number NM_002178 (gi: 49574524). This sequence is recited below for easy reference as SEQ ID NO:144.









1
gcggcggcgg gcagcagctg cgctgcgact gctctggaag gagaggacgg ggcacaaacc



 


61
ctgaccatga ccccccacag gctgctgcca ccgctgctgc tgctgctagc tctgctgctc


 


121
gctgccagcc caggaggcgc cttggcgcgg tgcccaggct gcgggcaagg ggtgcaggcg


 


181
ggttgtccag ggggctgcgt ggaggaggag gatggggggt cgccagccga gggctgcgcg


 


241
gaagctgagg gctgtctcag gagggagggg caggagtgcg gggtctacac ccctaactgc


 


301
gccccaggac tgcagtgcca tccgcccaag gacgacgagg cgcctttgcg ggcgctgctg


 


361
ctcggccgag gccgctgcct tccggcccgc gcgcctgctg ttgcagagga gaatcctaag


 


421
gagagtaaac cccaagcagg cactgcccgc ccacaggatg tgaaccgcag agaccaacag


 


481
aggaatccag gcacctctac cacgccctcc cagcccaatt ctgcgggtgt ccaagacact


 


541
gagatgggcc catgccgtag acatctggac tcagtgctgc agcaactcca gactgaggtc


 


601
taccgagggg ctcaaacact ctacgtgccc aattgtgacc atcgaggctt ctaccggaag


 


661
cggcagtgcc gctcctccca ggggcagcgc cgaggtccct gctggtgtgt ggatcggatg


 


721
ggcaagtccc tgccagggtc tccagatggc aatggaagct cctcctgccc cactgggagt


 


781
agcggctaaa gctgggggat agaggggctg cagggccact ggaaggaaca tggagctgtc


 


841
atcactcaac aaaaaaccga ggccctcaat ccaccttcag gccccgcccc atgggcccct


 


901
caccgctggt tggaaagagt gttggtgttg gctggggtgt caataaagct gtgcttgggg


 


961
tcgctgaaaa aaaaaaaaaa






One example of a nucleic acid sequence for human KIT is available as NCBI accession number NM_000222 (gi: 148005048). This sequence is recited below for easy reference as SEQ ID NO:145.









1
tctgggggct cggctttgcc gcgctcgctg cacttgggcg agagctggaa cgtggaccag



 


61
agctcggatc ccatcgcagc taccgcgatg agaggcgctc gcggcgcctg ggattttctc


 


121
tgcgttctgc tcctactgct tcgcgtccag acaggctctt ctcaaccatc tgtgagtcca


 


181
ggggaaccgt ctccaccatc catccatcca ggaaaatcag acttaatagt ccgcgtgggc


 


241
gacgagatta ggctgttatg cactgatccg ggctttgtca aatggacttt tgagatcctg


 


301
gatgaaacga atgagaataa gcagaatgaa tggatcacgg aaaaggcaga agccaccaac


 


361
accggcaaat acacgtgcac caacaaacac ggcttaagca attccattta tgtgtttgtt


 


421
agagatcctg ccaagctttt ccttgttgac cgctccttgt atgggaaaga agacaacgac


 


481
acgctggtcc gctgtcctct cacagaccca gaagtgacca attattccct caaggggtgc


 


541
caggggaagc ctcttcccaa ggacttgagg tttattcctg accccaaggc gggcatcatg


 


601
atcaaaagtg tgaaacgcgc ctaccatcgg ctctgtctgc attgttctgt ggaccaggag


 


661
ggcaagtcag tgctgtcgga aaaattcatc ctgaaagtga ggccagcctt caaagctgtg


 


721
cctgttgtgt ctgtgtccaa agcaagctat cttcttaggg aaggggaaga attcacagtg


 


781
acgtgcacaa taaaagatgt gtctagttct gtgtactcaa cgtggaaaag agaaaacagt


 


841
cagactaaac tacaggagaa atataatagc tggcatcacg gtgacttcaa ttatgaacgt


 


901
caggcaacgt tgactatcag ttcagcgaga gttaatgatt ctggagtgtt catgtgttat


 


961
gccaataata cttttggatc agcaaatgtc acaacaacct tggaagtagt agataaagga


 


1021
ttcattaata tcttccccat gataaacact acagtatttg taaacgatgg agaaaatgta


 


1081
gatttgattg ttgaatatga agcattcccc aaacctgaac accagcagtg gatctatatg


 


1141
aacagaacct tcactgataa atgggaagat tatcccaagt ctgagaatga aagtaatatc


 


1201
agatacgtaa gtgaacttca tctaacgaga ttaaaaggca ccgaaggagg cacttacaca


 


1261
ttcctagtgt ccaattctga cgtcaatgct gccatagcat ttaatgttta tgtgaataca


 


1321
aaaccagaaa tcctgactta cgacaggctc gtgaatggca tgctccaatg tgtggcagca


 


1381
ggattcccag agcccacaat agattggtat ttttgtccag gaactgagca gagatgctct


 


1441
gcttctgtac tgccagtgga tgtgcagaca ctaaactcat ctgggccacc gtttggaaag


 


1501
ctagtggttc agagttctat agattctagt gcattcaagc acaatggcac ggttgaatgt


 


1561
aaggcttaca acgatgtggg caagacttct gcctatttta actttgcatt taaaggtaac


 


1621
aacaaagagc aaatccatcc ccacaccctg ttcactcctt tgctgattgg tttcgtaatc


 


1681
gtagctggca tgatgtgcat tattgtgatg attctgacct acaaatattt acagaaaccc


 


1741
atgtatgaag tacagtggaa ggttgttgag gagataaatg gaaacaatta tgtttacata


 


1801
gacccaacac aacttcctta tgatcacaaa tgggagtttc ccagaaacag gctgagtttt


 


1861
gggaaaaccc tgggtgctgg agctttcggg aaggttgttg aggcaactgc ttatggctta


 


1921
attaagtcag atgcggccat gactgtcgct gtaaagatgc tcaagccgag tgcccatttg


 


1981
acagaacggg aagccctcat gtctgaactc aaagtcctga gttaccttgg taatcacatg


 


2041
aatattgtga atctacttgg agcctgcacc attggagggc ccaccctggt cattacagaa


 


2101
tattgttgct atggtgatct tttgaatttt ttgagaagaa aacgtgattc atttatttgt


 


2161
tcaaagcagg aagatcatgc agaagctgca ctttataaga atcttctgca ttcaaaggag


 


2221
tcttcctgca gcgatagtac taatgagtac atggacatga aacctggagt ttcttatgtt


 


2281
gtcccaacca aggccgacaa aaggagatct gtgagaatag gctcatacat agaaagagat


 


2341
gtgactcccg ccatcatgga ggatgacgag ttggccctag acttagaaga cttgctgagc


 


2401
ttttcttacc aggtggcaaa gggcatggct ttcctcgcct ccaagaattg tattcacaga


 


2461
gacttggcag ccagaaatat cctccttact catggtcgga tcacaaagat ttgtgatttt


 


2521
ggtctagcca gagacatcaa gaatgattct aattatgtgg ttaaaggaaa cgctcgacta


 


2581
cctgtgaagt ggatggcacc tgaaagcatt ttcaactgtg tatacacgtt tgaaagtgac


 


2641
gtctggtcct atgggatttt tctttgggag ctgttctctt taggaagcag cccctatcct


 


2701
ggaatgccgg tcgattctaa gttctacaag atgatcaagg aaggcttccg gatgctcagc


 


2761
cctgaacacg cacctgctga aatgtatgac ataatgaaga cttgctggga tgcagatccc


 


2821
ctaaaaagac caacattcaa gcaaattgtt cagctaattg agaagcagat ttcagagagc


 


2881
accaatcata tttactccaa cttagcaaac tgcagcccca accgacagaa gcccgtggta


 


2941
gaccattctg tgcggatcaa ttctgtcggc agcaccgctt cctcctccca gcctctgctt


 


3001
gtgcacgacg atgtctgagc agaatcagtg tttgggtcac ccctccagga atgatctctt


 


3061
cttttggctt ccatgatggt tattttcttt tctttcaact tgcatccaac tccaggatag


 


3121
tgggcacccc actgcaatcc tgtctttctg agcacacttt agtggccgat gatttttgtc


 


3181
atcagccacc atcctattgc aaaggttcca actgtatata ttcccaatag caacgtagct


 


3241
tctaccatga acagaaaaca ttctgatttg gaaaaagaga gggaggtatg gactgggggc


 


3301
cagagtcctt tccaaggctt ctccaattct gcccaaaaat atggttgata gtttacctga


 


3361
ataaatggta gtaatcacag ttggccttca gaaccatcca tagtagtatg atgatacaag


 


3421
attagaagct gaaaacctaa gtcctttatg tggaaaacag aacatcatta gaacaaagga


 


3481
cagagtatga acacctgggc ttaagaaatc tagtatttca tgctgggaat gagacatagg


 


3541
ccatgaaaaa aatgatcccc aagtgtgaac aaaagatgct cttctgtgga ccactgcatg


 


3601
agcttttata ctaccgacct ggtttttaaa tagagtttgc tattagagca ttgaattgga


 


3661
gagaaggcct ccctagccag cacttgtata tacgcatcta taaattgtcc gtgttcatac


 


3721
atttgagggg aaaacaccat aaggtttcgt ttctgtatac aaccctggca ttatgtccac


 


3781
tgtgtataga agtagattaa gagccatata agtttgaagg aaacagttaa taccattttt


 


3841
taaggaaaca atataaccac aaagcacagt ttgaacaaaa tctcctcttt tagctgatga


 


3901
acttattctg tagattctgt ggaacaagcc tatcagcttc agaatggcat tgtactcaat


 


3961
ggatttgatg ctgtttgaca aagttactga ttcactgcat ggctcccaca ggagtgggaa


 


4021
aacactgcca tcttagtttg gattcttatg tagcaggaaa taaagtatag gtttagcctc


 


4081
cttcgcaggc atgtcctgga caccgggcca gtatctatat atgtgtatgt acgtttgtat


 


4141
gtgtgtagac aaatatttgg aggggtattt ttgccctgag tccaagaggg tcctttagta


 


4201
cctgaaaagt aacttggctt tcattattag tactgctctt gtttcttttc acatagctgt


 


4261
ctagagtagc ttaccagaag cttccatagt ggtgcagagg aagtggaagg catcagtccc


 


4321
tatgtatttg cagttcacct gcacttaagg cactctgtta tttagactca tcttactgta


 


4381
cctgttcctt agaccttcca taatgctact gtctcactga aacatttaaa ttttaccctt


 


4441
tagactgtag cctggatatt attcttgtag tttacctctt taaaaacaaa acaaaacaaa


 


4501
acaaaaaact ccccttcctc actgcccaat ataaaaggca aatgtgtaca tggcagagtt


 


4561
tgtgtgttgt cttgaaagat tcaggtatgt tgcctttatg gtttccccct tctacatttc


 


4621
ttagactaca tttagagaac tgtggccgtt atctggaagt aaccatttgc actggagttc


 


4681
tatgctctcg cacctttcca aagttaacag attttggggt tgtgttgtca cccaagagat


 


4741
tgttgtttgc catactttgt ctgaaaaatt cctttgtgtt tctattgact tcaatgatag


 


4801
taagaaaagt ggttgttagt tatagatgtc taggtacttc aggggcactt cattgagagt


 


4861
tttgtcttgg atattcttga aagtttatat ttttataatt ttttcttaca tcagatgttt


 


4921
ctttgcagtg gcttaatgtt tgaaattatt ttgtggcttt ttttgtaaat attgaaatgt


 


4981
agcaataatg tcttttgaat attcccaagc ccatgagtcc ttgaaaatat tttttatata


 


5041
tacagtaact ttatgtgtaa atacataagc ggcgtaagtt taaaggatgt tggtgttcca


 


5101
cgtgttttat tcctgtatgt tgtccaattg ttgacagttc tgaagaattc taataaaatg


 


5161
tacatatata aatcaaaaaa aaaaaaaaaa






One example of a nucleic acid sequence for human LRP4 is available as NCBI accession number NM_002334 (gi: 157384997). This sequence is recited below for easy reference as SEQ ID NO:146.









1
gcggcggcgg cccgagggcg acttgcgggg cgcgcaggcc gccgtgcacc cgggacgctt



 


61
ccccctcggg gaccctccgc gggcttctcc gccgcgccgt ccggcgggag ccggcgggac


 


121
cccgggcgag cggcgcgggc ggcaccatga ggcggcagtg gggcgcgctg ctgcttggcg


 


181
ccctgctctg cgcacacggc ctggccagca gccccgagtg tgcttgtggt cggagccact


 


241
tcacatgtgc agtgagtgct cttggagagt gtacctgcat ccctgcccag tggcagtgtg


 


301
atggagacaa tgactgcggg gaccacagcg atgaggatgg atgtatacta cctacctgtt


 


361
cccctcttga ctttcactgt gacaatggca agtgcatccg ccgctcctgg gtgtgtgacg


 


421
gggacaacga ctgtgaggat gactcggatg agcaggactg tcccccccgg gagtgtgagg


 


481
aggacgagtt tccctgccag aatggctact gcatccggag tctgtggcac tgcgatggtg


 


541
acaatgactg tggcgacaac agcgatgagc agtgtgacat gcgcaagtgc tccgacaagg


 


601
agttccgctg tagtgacgga agctgcattg ctgagcattg gtactgcgac ggtgacaccg


 


661
actgcaaaga tggctccgat gaggagaact gtccctcagc agtgccagcg cccccctgca


 


721
acctggagga gttccagtgt gcctatggac gctgcatcct cgacatctac cactgcgatg


 


781
gcgacgatga ctgtggagac tggtcagacg agtctgactg ctcctcccac cagccctgcc


 


841
gctctgggga gttcatgtgt gacagtggcc tgtgcatcaa tgcaggctgg cgctgcgatg


 


901
gtgacgcgga ctgtgatgac cagtctgatg agcgcaactg caccacctcc atgtgtacgg


 


961
cagaacagtt ccgctgtcac tcaggccgct gtgtccgcct gtcctggcgc tgtgatgggg


 


1021
aggacgactg tgcagacaac agcgatgaag agaactgtga gaatacagga agcccccaat


 


1081
gtgccttgga ccagttcctg tgttggaatg ggcgctgcat tgggcagagg aagctgtgca


 


1141
acggggtcaa cgactgtggt gacaacagcg acgaaagccc acagcagaat tgccggcccc


 


1201
ggacgggtga ggagaactgc aatgttaaca acggtggctg tgcccagaag tgccagatgg


 


1261
tgcggggggc agtgcagtgt acctgccaca caggctaccg gctcacagag gatgggcaca


 


1321
cgtgccaaga tgtgaatgaa tgtgccgagg aggggtattg cagccagggc tgcaccaaca


 


1381
gcgaaggggc tttccaatgc tggtgtgaaa caggctatga actacggccc gaccggcgca


 


1441
gctgcaaggc tctggggcca gagcctgtgc tgctgttcgc caatcgcatc gacatccggc


 


1501
aggtgctgcc acaccgctct gagtacacac tgctgcttaa caacctggag aatgccattg


 


1561
cccttgattt ccaccaccgc cgcgagcttg tcttctggtc agatgtcacc ctggaccgga


 


1621
tcctccgtgc caacctcaac ggcagcaacg tggaggaggt tgtgtctact gggctggaga


 


1681
gcccaggggg cctggctgtg gattgggtcc atgacaaact ctactggacc gactcaggca


 


1741
cctcgaggat tgaggtggcc aatctggatg gggcccaccg gaaagtgttg ctgtggcaga


 


1801
acctggagaa gccccgggcc attgccttgc atcccatgga gggtaccatt tactggacag


 


1861
actggggcaa caccccccgt attgaggcct ccagcatgga tggctctgga cgccgcatca


 


1921
ttgccgatac ccatctcttc tggcccaatg gcctcaccat cgactatgcc gggcgccgta


 


1981
tgtactgggt ggatgctaag caccatgtca tcgagagggc caatctggat gggagtcacc


 


2041
gtaaggctgt cattagccag ggcctcccgc atcccttcgc catcacagtg tttgaagaca


 


2101
gcctgtactg gacagactgg cacaccaaga gcatcaatag cgctaacaaa tttacgggga


 


2161
agaaccagga aatcattcgc aacaaactcc acttccctat ggacatccac accttgcacc


 


2221
cccagcgcca acctgcaggg aaaaaccgct gtggggacaa caacggaggc tgcacgcacc


 


2281
tgtgtctgcc cagtggccag aactacacct gtgcctgccc cactggcttc cgcaagatca


 


2341
gcagccacgc ctgtgcccag agtcttgaca agttcctgct ttttgcccga aggatggaca


 


2401
tccgtcgaat cagctttgac acagaggacc tgtctgatga tgtcatccca ctggctgacg


 


2461
tgcgcagtgc tgtggccctt gactgggact cccgggatga ccacgtgtac tggacagatg


 


2521
tcagcactga taccatcagc agggccaagt gggatggaac aggacaggag gtggtagtgg


 


2581
ataccagttt ggagagccca gctggcctgg ccattgattg ggtcaccaac aaactgtact


 


2641
ggacagatgc aggtacagac cggattgaag tagccaacac agatggcagc atgagaacag


 


2701
tactcatctg ggagaacctt gatcgtcctc gggacatcgt ggtggaaccc atgggcgggt


 


2761
acatgtattg gactgactgg ggtgcgagcc ccaagattga acgagctggc atggatgcct


 


2821
caggccgcca agtcattatc tcttctaatc tgacctggcc taatgggtta gctattgatt


 


2881
atgggtccca gcgtctatac tgggctgacg ccggcatgaa gacaattgaa tttgctggac


 


2941
tggatggcag taagaggaag gtgctgattg gaagccagct cccccaccca tttgggctga


 


3001
ccctctatgg agagcgcatc tattggactg actggcagac caagagcata cagagcgctg


 


3061
accggctgac agggctggac cgggagactc tgcaggagaa cctggaaaac ctaatggaca


 


3121
tccatgtctt ccaccgccgc cggcccccag tgtctacacc atgtgctatg gagaatggcg


 


3181
gctgtagcca cctgtgtctt aggtccccaa atccaagcgg attcagctgt acctgcccca


 


3241
caggcatcaa cctgctgtct gatggcaaga cctgctcacc aggcatgaac agtttcctca


 


3301
tcttcgccag gaggatagac attcgcatgg tctccctgga catcccttat tttgctgatg


 


3361
tggtggtacc aatcaacatt accatgaaga acaccattgc cattggagta gacccccagg


 


3421
aaggaaaggt gtactggtct gacagcacac tgcacaggat cagtcgtgcc aatctggatg


 


3481
gctcacagca tgaggacatc atcaccacag ggctacagac cacagatggg ctcgcggttg


 


3541
atgccattgg ccggaaagta tactggacag acacgggaac aaaccggatt gaagtgggca


 


3601
acctggacgg gtccatgcgg aaagtgttgg tgtggcagaa ccttgacagt ccccgggcca


 


3661
tcgtactgta ccatgagatg gggtttatgt actggacaga ctggggggag aatgccaagt


 


3721
tagagcggtc cggaatggat ggctcagacc gcgcggtgct catcaacaac aacctaggat


 


3781
ggcccaatgg actgactgtg gacaaggcca gctcccaact gctatgggcc gatgcccaca


 


3841
ccgagcgaat tgaggctgct gacctgaatg gtgccaatcg gcatacattg gtgtcaccgg


 


3901
tgcagcaccc atatggcctc accctgctcg actcctatat ctactggact gactggcaga


 


3961
ctcggagcat ccaccgtgct gacaagggta ctggcagcaa tgtcatcctc gtgaggtcca


 


4021
acctgccagg cctcatggac atgcaggctg tggaccgggc acagccacta ggttttaaca


 


4081
agtgcggctc gagaaatggc ggctgctccc acctctgctt gcctcggcct tctggcttct


 


4141
cctgtgcctg ccccactggc atccagctga agggagatgg gaagacctgt gatccctctc


 


4201
ctgagaccta cctgctcttc tccagccgtg gctccatccg gcgtatctca ctggacacca


 


4261
gtgaccacac cgatgtgcat gtccctgttc ctgagctcaa caatgtcatc tccctggact


 


4321
atgacagcgt ggatggaaag gtctattaca cagatgtgtt cctggatgtt atcaggcgag


 


4381
cagacctgaa cggcagcaac atggagacag tgatcgggcg agggctgaag accactgacg


 


4441
ggctggcagt ggactgggtg gccaggaacc tgtactggac agacacaggt cgaaatacca


 


4501
ttgaggcgtc caggctggat ggttcctgcc gcaaagtact gatcaacaat agcctggatg


 


4561
agccccgggc cattgctgtt ttccccagga aggggtacct cttctggaca gactggggcc


 


4621
acattgccaa gatcgaacgg gcaaacttgg atggttctga gcggaaggtc ctcatcaaca


 


4681
cagacctggg ttggcccaat ggccttaccc tggactatga tacccgcagg atctactggg


 


4741
tggatgcgca tctggaccgg atcgagagtg ctgacctcaa tgggaaactg cggcaggtct


 


4801
tggtcagcca tgtgtcccac ccctttgccc tcacacagca agacaggtgg atctactgga


 


4861
cagactggca gaccaagtca atccagcgtg ttgacaaata ctcaggccgg aacaaggaga


 


4921
cagtgctggc aaatgtggaa ggactcatgg atatcatcgt ggtttcccct cagcggcaga


 


4981
cagggaccaa tgcctgtggt gtgaacaatg gtggctgcac ccacctctgc tttgccagag


 


5041
cctcggactt cgtatgtgcc tgtcctgacg aacctgatag ccggccctgc tcccttgtgc


 


5101
ctggcctggt accaccagct cctagggcta ctggcatgag tgaaaagagc ccagtgctac


 


5161
ccaacacacc acctaccacc ttgtattctt caaccacccg gacccgcacg tctctggagg


 


5221
aggtggaagg aagatgctct gaaagggatg ccaggctggg cctctgtgca cgttccaatg


 


5281
acgctgttcc tgctgctcca ggggaaggac ttcatatcag ctacgccatt ggtggactcc


 


5341
tcagtattct gctgattttg gtggtgattg cagctttgat gctgtacaga cacaaaaaat


 


5401
ccaagttcac tgatcctgga atggggaacc tcacctacag caacccctcc taccgaacat


 


5461
ccacacagga agtgaagatt gaagcaatcc ccaaaccagc catgtacaac cagctgtgct


 


5521
ataagaaaga gggagggcct gaccataact acaccaagga gaagatcaag atcgtagagg


 


5581
gaatctgcct cctgtctggg gatgatgctg agtgggatga cctcaagcaa ctgcgaagct


 


5641
cacggggggg cctcctccgg gatcatgtat gcatgaagac agacacggtg tccatccagg


 


5701
ccagctctgg ctccctggat gacacagaga cggagcagct gttacaggaa gagcagtctg


 


5761
agtgtagcag cgtccatact gcagccactc cagaaagacg aggctctctg ccagacacgg


 


5821
gctggaaaca tgaacgcaag ctctcctcag agagccaggt ctaaatgccc acattctctt


 


5881
ccctgcctgc ctgttccttc tcctttatgg acgtctagtc cttgtgctcg cttacaccgc


 


5941
aggccccgct tctgtgtgct tgtcctcctc ctcctcccac cccataactg ttcctaagcc


 


6001
ttcaccggag ctgtttacca cgtgagtcca taactacctg tgcacaagaa atgatggcac


 


6061
atcacgagaa tttagacctg gattttacca tgaacctcac atcttgtact ccatcctggg


 


6121
ccccctgaaa ctgcttattc gtgattcctc accagcgtag agctccacct cccctttccc


 


6181
cagtaccctc agtgcctgct tctcagtgct gatgcagctg atgacccagg actgcgctct


 


6241
gccccatcac agccagcatg actgcttctc tgagagaact tgcccatcag gggctgggac


 


6301
atgggggtgt gggtaaagac agggatgaag gatagaggct gagagaagaa ggaagaatca


 


6361
gcccagcagg tatgggcatc tgggaaacct ccagcctcaa gtgtgttggt aacatgaaaa


 


6421
agctttgggg ggtagttgga tctgggtgtc tggtccattg ctggcagtgg acattattct


 


6481
tgccctaaga gacactgcct tttcagcagc agatactggt gagatggggg tggctcaggc


 


6541
tgttcttcct cctcctagaa tgtctggagc tgtttctaca ttcagataac tgggtcccct


 


6601
atcacaaggc tactggctaa taggaattcc ctcctggtgc caccactggc cagtaccttt


 


6661
cctaagtctt tgctcaaatt aaccaggttg tgagccagtg gcttgagtga atgttaggcc


 


6721
ttgggggctg agtctctgaa aagtctaaga agctctgcct agaccaaata tggtatacct


 


6781
cctgacccct ctctccctca tgtcctggga ttctggggaa gagacctaga aacaagcttt


 


6841
caaagaaaaa ccagaagttg tcataaatgg tcagaaagaa cgatcaggtt ggagacttgg


 


6901
gaaacccagg gcctaaagag aagtatccat gagggtcaaa cttcctgttg aacttcctat


 


6961
gttctttctc aagtgctcag ggatctaagt tagtggacag caagcctgtg gctacggggt


 


7021
ggtgatgttc ctcttccagc tgtcccctca gctaaggggc ttagtttcca tgtgggatgc


 


7081
catcacttgg ttcatgctca ttcacacaaa gggcacgtgt ctcagcctgg tatcagggaa


 


7141
attgagactt atttttgccc taaaacgtct ccctagctgt tcttcgtggg gtttttttgt


 


7201
ttgttttttt gcctaatttg ctttttctga ccaagccttg tggcaccagc aatctccaaa


 


7261
gtcctgtggt gggagggctg aataaataaa aatacaaaga ggtgggtaag gagtaggaag


 


7321
gtagagagca ccactgatga ggccctccta gcccatggca gacccagacc tcttctcccc


 


7381
caggaattag aagtggcagg agagaacaac aggggctggg aatggagggg agaatttcta


 


7441
ggggaagttt cctgagttga aacttctcct gtggttactg gtattgagaa atcagctacc


 


7501
aaagtgaaaa aggacaagat caattctttt ctagtcagtt ctaagactgc tagagagaga


 


7561
taccaggccc ttagccttgc tctcagtagc gtcagcccca gttctgagcc tccccacatt


 


7621
acacttaaca agcagtaaag gagtgagcac tttgggtcct tagactcatg tctggggagg


 


7681
aagagcaagt agaaaagtgg cattttcttg attggaaagg gggaaggatc ttattgcact


 


7741
tgggctgttc agaatgtaga aaggacatat ttgaggaagt atctatttga gcactgattt


 


7801
actctgtaaa aagcaaaatc tctctgtcct aaactaatgg aagcgattct cccatgctca


 


7861
tgtgtaatgg ttttaacgtt actcactgga gagattggac tttctggagt tatttaacca


 


7921
ctatgttcag tattttagga ctttatgata atttaatata aatttagctt ttcttaatca


 


7981
aaaaaaaaaa aaaaaaaa






One example of a nucleic acid sequence for human MATN2 is available as NCBI accession number NM_002380 (gi: 62548859). This sequence is recited below for easy reference as SEQ ID NO:147.









1
gcgagcgaag ggagcgctct gggatgggac ttggagcaag cggcggcggc ggagacagag



 


61
gcagaggcag aagctggggc tccgtcctcg cctcccacga gcgatccccg aggagagccg


 


121
cggccctcgg cgaggcgaag aggccgacga ggaagacccg ggtggctgcg cccctgcctc


 


181
gcttcccagg cgccggcggc tgcagccttg cccctcttgc tcgccttgaa aatggaaaag


 


241
atgctcgcag gctgctttct gctgatcctc ggacagatcg tcctcctccc tgccgaggcc


 


301
agggagcggt cacgtgggag gtccatctct aggggcagac acgctcggac ccacccgcag


 


361
acggcccttc tggagagttc ctgtgagaac aagcgggcag acctggtttt catcattgac


 


421
agctctcgca gtgtcaacac ccatgactat gcaaaggtca aggagttcat cgtggacatc


 


481
ttgcaattct tggacattgg tcctgatgtc acccgagtgg gcctgctcca atatggcagc


 


541
actgtcaaga atgagttctc cctcaagacc ttcaagagga agtccgaggt ggagcgtgct


 


601
gtcaagagga tgcggcatct gtccacgggc accatgactg ggctggccat ccagtatgcc


 


661
ctgaacatcg cattctcaga agcagagggg gcccggcccc tgagggagaa tgtgccacgg


 


721
gtcataatga tcgtgacaga tgggagacct caggactccg tggccgaggt ggctgctaag


 


781
gcacgggaca cgggcatcct aatctttgcc attggtgtgg gccaggtaga cttcaacacc


 


841
ttgaagtcca ttgggagtga gccccatgag gaccatgtct tccttgtggc caatttcagc


 


901
cagattgaga cgctgacctc cgtgttccag aagaagttgt gcacggccca catgtgcagc


 


961
accctggagc ataactgtgc ccacttctgc atcaacatcc ctggctcata cgtctgcagg


 


1021
tgcaaacaag gctacattct caactcggat cagacgactt gcagaatcca ggatctgtgt


 


1081
gccatggagg accacaactg tgagcagctc tgtgtgaatg tgccgggctc cttcgtctgc


 


1141
cagtgctaca gtggctacgc cctggctgag gatgggaaga ggtgtgtggc tgtggactac


 


1201
tgtgcctcag aaaaccacgg atgtgaacat gagtgtgtaa atgctgatgg ctcctacctt


 


1261
tgccagtgcc atgaaggatt tgctcttaac ccagataaaa aaacgtgcac aaagatagac


 


1321
tactgtgcct catctaatca cggatgtcag cacgagtgtg ttaacacaga tgattcctat


 


1381
tcctgccact gcctgaaagg ctttaccctg aatccagata agaaaacctg cagaaggatc


 


1441
aactactgtg cactgaacaa accgggctgt gagcatgagt gcgtcaacat ggaggagagc


 


1501
tactactgcc gctgccaccg tggctacact ctggacccca atggcaaaac ctgcagccga


 


1561
gtggaccact gtgcacagca ggaccatggc tgtgagcagc tgtgtctgaa cacggaggat


 


1621
tccttcgtct gccagtgctc agaaggcttc ctcatcaacg aggacctcaa gacctgctcc


 


1681
cgggtggatt actgcctgct gagtgaccat ggttgtgaat actcctgtgt caacatggac


 


1741
agatcctttg cctgtcagtg tcctgaggga cacgtgctcc gcagcgatgg gaagacgtgt


 


1801
gcaaaattgg actcttgtgc tctgggggac cacggttgtg aacattcgtg tgtaagcagt


 


1861
gaagattcgt ttgtgtgcca gtgctttgaa ggttatatac tccgtgaaga tggaaaaacc


 


1921
tgcagaagga aagatgtctg ccaagctata gaccatggct gtgaacacat ttgtgtgaac


 


1981
agtgatgact catacacgtg cgagtgcttg gagggattcc ggctcgctga ggatgggaaa


 


2041
cgctgccgaa ggaaggatgt ctgcaaatca acccaccatg gctgcgaaca catttgtgtt


 


2101
aataatggga attcctacat ctgcaaatgc tcagagggat ttgttctagc tgaggacgga


 


2161
agacggtgca agaaatgcac tgaaggccca attgacctgg tctttgtgat cgatggatcc


 


2221
aagagtcttg gagaagagaa ttttgaggtc gtgaagcagt ttgtcactgg aattatagat


 


2281
tccttgacaa tttcccccaa agccgctcga gtggggctgc tccagtattc cacacaggtc


 


2341
cacacagagt tcactctgag aaacttcaac tcagccaaag acatgaaaaa agccgtggcc


 


2401
cacatgaaat acatgggaaa gggctctatg actgggctgg ccctgaaaca catgtttgag


 


2461
agaagtttta cccaaggaga aggggccagg cccctttcca caagggtgcc cagagcagcc


 


2521
attgtgttca ccgacggacg ggctcaggat gacgtctccg agtgggccag taaagccaag


 


2581
gccaatggta tcactatgta tgctgttggg gtaggaaaag ccattgagga ggaactacaa


 


2641
gagattgcct ctgagcccac aaacaagcat ctcttctatg ccgaagactt cagcacaatg


 


2701
gatgagataa gtgaaaaact caagaaaggc atctgtgaag ctctagaaga ctccgatgga


 


2761
agacaggact ctccagcagg ggaactgcca aaaacggtcc aacagccaac agaatctgag


 


2821
ccagtcacca taaatatcca agacctactt tcctgttcta attttgcagt gcaacacaga


 


2881
tatctgtttg aagaagacaa tcttttacgg tctacacaaa agctttccca ttcaacaaaa


 


2941
ccttcaggaa gccctttgga agaaaaacac gatcaatgca aatgtgaaaa ccttataatg


 


3001
ttccagaacc ttgcaaacga agaagtaaga aaattaacac agcgcttaga agaaatgaca


 


3061
cagagaatgg aagccctgga aaatcgcctg agatacagat gaagattaga aatcgcgaca


 


3121
catttgtagt cattgtatca cggattacaa tgaacgcagt gcagagcccc aaagctcagg


 


3181
ctattgttaa atcaataatg ttgtgaagta aaacaatcag tactgagaaa cctggtttgc


 


3241
cacagaacaa agacaagaag tatacactaa cttgtataaa tttatctagg aaaaaaatcc


 


3301
ttcagaattc taagatgaat ttaccaggtg agaatgaata agctatgcaa ggtattttgt


 


3361
aatatactgt ggacacaact tgcttctgcc tcatcctgcc ttagtgtgca atctcatttg


 


3421
actatacgat aaagtttgca cagtcttact tctgtagaac actggccata ggaaatgctg


 


3481
tttttttgta ctggacttta ccttgatata tgtatatgga tgtatgcata aaatcatagg


 


3541
acatatgtac ttgtggaaca agttggattt tttatacaat attaaaattc accacttcag


 


3601
agaatggtat tcagtgcaaa aattcttagt ttaactttaa atggaagata tgtatgtatg


 


3661
agaaatggcc aacatgccta tgaaaaaaat gctgaatctc atcagtaatc aggaaaatgc


 


3721
aggttaaaac aataccattt ttcacccatc agcttagcaa aaatgagtat attttttaac


 


3781
aagtgttggt aaggatgtgg aaatgtgagg ttcttgtagt aagaatgcaa atggcactct


 


3841
ttgtagagta agtctgttga catctcataa aactgaaaat gcacacaacc ctgtaaatct


 


3901
agcaactgca ctcagttgat ttcagcccat acatacaaag agacctgcat aagaatgtta


 


3961
ctaggctttg taaaagcaaa aaataaggaa caacttaaac atcatcagaa ggggaactga


 


4021
taaactctgg tgtaatccat accacagaaa tacaacaccg catgtacagg aatgtgctac


 


4081
atctatacaa ataaatggtc aaactcaaaa aaaaaaaaaa aa






One example of a nucleic acid sequence for human MET is available as NCBI accession number NM_001127500 (gi: 188595715). This sequence is recited below for easy reference as SEQ ID NO:148.









1
gccctcgccg cccgcggcgc cccgagcgct ttgtgagcag atgcggagcc gagtggaggg



 


61
cgcgagccag atgcggggcg acagctgact tgctgagagg aggcggggag gcgcggagcg


 


121
cgcgtgtggt ccttgcgccg ctgacttctc cactggttcc tgggcaccga aagataaacc


 


181
tctcataatg aaggcccccg ctgtgcttgc acctggcatc ctcgtgctcc tgtttacctt


 


241
ggtgcagagg agcaatgggg agtgtaaaga ggcactagca aagtccgaga tgaatgtgaa


 


301
tatgaagtat cagcttccca acttcaccgc ggaaacaccc atccagaatg tcattctaca


 


361
tgagcatcac attttccttg gtgccactaa ctacatttat gttttaaatg aggaagacct


 


421
tcagaaggtt gctgagtaca agactgggcc tgtgctggaa cacccagatt gtttcccatg


 


481
tcaggactgc agcagcaaag ccaatttatc aggaggtgtt tggaaagata acatcaacat


 


541
ggctctagtt gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag


 


601
agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac agtcggaggt


 


661
tcactgcata ttctccccac agatagaaga gcccagccag tgtcctgact gtgtggtgag


 


721
cgccctggga gccaaagtcc tttcatctgt aaaggaccgg ttcatcaact tctttgtagg


 


781
caataccata aattcttctt atttcccaga tcatccattg cattcgatat cagtgagaag


 


841
gctaaaggaa acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt


 


901
acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa gcaacaattt


 


961
tatttacttc ttgacggtcc aaagggaaac tctagatgct cagacttttc acacaagaat


 


1021
aatcaggttc tgttccataa actctggatt gcattcctac atggaaatgc ctctggagtg


 


1081
tattctcaca gaaaagagaa aaaagagatc cacaaagaag gaagtgttta atatacttca


 


1141
ggctgcgtat gtcagcaagc ctggggccca gcttgctaga caaataggag ccagcctgaa


 


1201
tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg aaccaatgga


 


1261
tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac gacttcttca acaagatcgt


 


1321
caacaaaaac aatgtgagat gtctccagca tttttacgga cccaatcatg agcactgctt


 


1381
taataggaca cttctgagaa attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac


 


1441
agagtttacc acagctttgc agcgcgttga cttattcatg ggtcaattca gcgaagtcct


 


1501
cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc ttgggacatc


 


1561
agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga ccatcaaccc ctcatgtgaa


 


1621
ttttctcctg gactcccatc cagtgtctcc agaagtgatt gtggagcata cattaaacca


 


1681
aaatggctac acactggtta tcactgggaa gaagatcacg aagatcccat tgaatggctt


 


1741
gggctgcaga catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg


 


1801
tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga catggactca


 


1861
acagatctgt ctgcctgcaa tctacaaggt tttcccaaat agtgcacccc ttgaaggagg


 


1921
gacaaggctg accatatgtg gctgggactt tggatttcgg aggaataata aatttgattt


 


1981
aaagaaaact agagttctcc ttggaaatga gagctgcacc ttgactttaa gtgagagcac


 


2041
gatgaataca ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat


 


2101
aattatttca aatggccacg ggacaacaca atacagtaca ttctcctatg tggatcctgt


 


2161
aataacaagt atttcgccga aatacggtcc tatggctggt ggcactttac ttactttaac


 


2221
tggaaattac ctaaacagtg ggaattctag acacatttca attggtggaa aaacatgtac


 


2281
tttaaaaagt gtgtcaaaca gtattcttga atgttatacc ccagcccaaa ccatttcaac


 


2341
tgagtttgct gttaaattga aaattgactt agccaaccga gagacaagca tcttcagtta


 


2401
ccgtgaagat cccattgtct atgaaattca tccaaccaaa tcttttatta gtacttggtg


 


2461
gaaagaacct ctcaacattg tcagttttct attttgcttt gccagtggtg ggagcacaat


 


2521
aacaggtgtt gggaaaaacc tgaattcagt tagtgtcccg agaatggtca taaatgtgca


 


2581
tgaagcagga aggaacttta cagtggcatg tcaacatcgc tctaattcag agataatctg


 


2641
ttgtaccact ccttccctgc aacagctgaa tctgcaactc cccctgaaaa ccaaagcctt


 


2701
tttcatgtta gatgggatcc tttccaaata ctttgatctc atttatgtac ataatcctgt


 


2761
gtttaagcct tttgaaaagc cagtgatgat ctcaatgggc aatgaaaatg tactggaaat


 


2821
taagggaaat gatattgacc ctgaagcagt taaaggtgaa gtgttaaaag ttggaaataa


 


2881
gagctgtgag aatatacact tacattctga agccgtttta tgcacggtcc ccaatgacct


 


2941
gctgaaattg aacagcgagc taaatataga gtggaagcaa gcaatttctt caaccgtcct


 


3001
tggaaaagta atagttcaac cagatcagaa tttcacagga ttgattgctg gtgttgtctc


 


3061
aatatcaaca gcactgttat tactacttgg gtttttcctg tggctgaaaa agagaaagca


 


3121
aattaaagat ctgggcagtg aattagttcg ctacgatgca agagtacaca ctcctcattt


 


3181
ggataggctt gtaagtgccc gaagtgtaag cccaactaca gaaatggttt caaatgaatc


 


3241
tgtagactac cgagctactt ttccagaaga tcagtttcct aattcatctc agaacggttc


 


3301
atgccgacaa gtgcagtatc ctctgacaga catgtccccc atcctaacta gtggggactc


 


3361
tgatatatcc agtccattac tgcaaaatac tgtccacatt gacctcagtg ctctaaatcc


 


3421
agagctggtc caggcagtgc agcatgtagt gattgggccc agtagcctga ttgtgcattt


 


3481
caatgaagtc ataggaagag ggcattttgg ttgtgtatat catgggactt tgttggacaa


 


3541
tgatggcaag aaaattcact gtgctgtgaa atccttgaac agaatcactg acataggaga


 


3601
agtttcccaa tttctgaccg agggaatcat catgaaagat tttagtcatc ccaatgtcct


 


3661
ctcgctcctg ggaatctgcc tgcgaagtga agggtctccg ctggtggtcc taccatacat


 


3721
gaaacatgga gatcttcgaa atttcattcg aaatgagact cataatccaa ctgtaaaaga


 


3781
tcttattggc tttggtcttc aagtagccaa aggcatgaaa tatcttgcaa gcaaaaagtt


 


3841
tgtccacaga gacttggctg caagaaactg tatgctggat gaaaaattca cagtcaaggt


 


3901
tgctgatttt ggtcttgcca gagacatgta tgataaagaa tactatagtg tacacaacaa


 


3961
aacaggtgca aagctgccag tgaagtggat ggctttggaa agtctgcaaa ctcaaaagtt


 


4021
taccaccaag tcagatgtgt ggtcctttgg cgtgctcctc tgggagctga tgacaagagg


 


4081
agccccacct tatcctgacg taaacacctt tgatataact gtttacttgt tgcaagggag


 


4141
aagactccta caacccgaat actgcccaga ccccttatat gaagtaatgc taaaatgctg


 


4201
gcaccctaaa gccgaaatgc gcccatcctt ttctgaactg gtgtcccgga tatcagcgat


 


4261
cttctctact ttcattgggg agcactatgt ccatgtgaac gctacttatg tgaacgtaaa


 


4321
atgtgtcgct ccgtatcctt ctctgttgtc atcagaagat aacgctgatg atgaggtgga


 


4381
cacacgacca gcctccttct gggagacatc atagtgctag tactatgtca aagcaacagt


 


4441
ccacactttg tccaatggtt ttttcactgc ctgaccttta aaaggccatc gatattcttt


 


4501
gctcttgcca aaattgcact attataggac ttgtattgtt atttaaatta ctggattcta


 


4561
aggaatttct tatctgacag agcatcagaa ccagaggctt ggtcccacag gccacggacc


 


4621
aatggcctgc agccgtgaca acactcctgt catattggag tccaaaactt gaattctggg


 


4681
ttgaattttt taaaaatcag gtaccacttg atttcatatg ggaaattgaa gcaggaaata


 


4741
ttgagggctt cttgatcaca gaaaactcag aagagatagt aatgctcagg acaggagcgg


 


4801
cagccccaga acaggccact catttagaat tctagtgttt caaaacactt ttgtgtgttg


 


4861
tatggtcaat aacatttttc attactgatg gtgtcattca cccattaggt aaacattccc


 


4921
ttttaaatgt ttgtttgttt tttgagacag gatctcactc tgttgccagg gctgtagtgc


 


4981
agtggtgtga tcatagctca ctgcaacctc cacctcccag gctcaagcct cccgaatagc


 


5041
tgggactaca ggcgcacacc accatccccg gctaattttt gtattttttg tagagacggg


 


5101
gttttgccat gttgccaagg ctggtttcaa actcctggac tcaagaaatc cacccacctc


 


5161
agcctcccaa agtgctagga ttacaggcat gagccactgc gcccagccct tataaatttt


 


5221
tgtatagaca ttcctttggt tggaagaata tttataggca atacagtcaa agtttcaaaa


 


5281
tagcatcaca caaaacatgt ttataaatga acaggatgta atgtacatag atgacattaa


 


5341
gaaaatttgt atgaaataat ttagtcatca tgaaatattt agttgtcata taaaaaccca


 


5401
ctgtttgaga atgatgctac tctgatctaa tgaatgtgaa catgtagatg ttttgtgtgt


 


5461
atttttttaa atgaaaactc aaaataagac aagtaatttg ttgataaata tttttaaaga


 


5521
taactcagca tgtttgtaaa gcaggataca ttttactaaa aggttcattg gttccaatca


 


5581
cagctcatag gtagagcaaa gaaagggtgg atggattgaa aagattagcc tctgtctcgg


 


5641
tggcaggttc ccacctcgca agcaattgga aacaaaactt ttggggagtt ttattttgca


 


5701
ttagggtgtg ttttatgtta agcaaaacat actttagaaa caaatgaaaa aggcaattga


 


5761
aaatcccagc tatttcacct agatggaata gccaccctga gcagaacttt gtgatgcttc


 


5821
attctgtgga attttgtgct tgctactgta tagtgcatgt ggtgtaggtt actctaactg


 


5881
gttttgtcga cgtaaacatt taaagtgtta tattttttat aaaaatgttt atttttaatg


 


5941
atatgagaaa aattttgtta ggccacaaaa acactgcact gtgaacattt tagaaaaggt


 


6001
atgtcagact gggattaatg acagcatgat tttcaatgac tgtaaattgc gataaggaaa


 


6061
tgtactgatt gccaatacac cccaccctca ttacatcatc aggacttgaa gccaagggtt


 


6121
aacccagcaa gctacaaaga gggtgtgtca cactgaaact caatagttga gtttggctgt


 


6181
tgttgcagga aaatgattat aactaaaagc tctctgatag tgcagagact taccagaaga


 


6241
cacaaggaat tgtactgaag agctattaca atccaaatat tgccgtttca taaatgtaat


 


6301
aagtaatact aattcacaga gtattgtaaa tggtggatga caaaagaaaa tctgctctgt


 


6361
ggaaagaaag aactgtctct accagggtca agagcatgaa cgcatcaata gaaagaactc


 


6421
ggggaaacat cccatcaaca ggactacaca cttgtatata cattcttgag aacactgcaa


 


6481
tgtgaaaatc acgtttgcta tttataaact tgtccttaga ttaatgtgtc tggacagatt


 


6541
gtgggagtaa gtgattcttc taagaattag atacttgtca ctgcctatac ctgcagctga


 


6601
actgaatggt acttcgtatg ttaatagttg ttctgataaa tcatgcaatt aaagtaaagt


 


6661
gatgcaacat cttgtaaaaa aaaaaaaaaa aaaaa






One example of a nucleic acid sequence for human MYH10 is available as NCBI accession number NM_005964 (gi: 41406063). This sequence is recited below for easy reference as SEQ ID NO:149.









1
actgaggcgc tggatctgtg gtcgcggctg gggacgtgcg cccgcgccac catcttcggc



 


61
tgaagaggca attgcttttg gatcgttcca tttacaatgg cgcagagaac tggactcgag


 


121
gatccagaga ggtatctctt tgtggacagg gctgtcatct acaaccctgc cactcaagct


 


181
gattggacag ctaaaaagct agtgtggatt ccatcagaac gccatggttt tgaggcagct


 


241
agtatcaaag aagaacgggg agatgaagtt atggtggagt tggcagagaa tggaaagaaa


 


301
gcaatggtca acaaagatga tattcagaag atgaacccac ctaagttttc caaggtggag


 


361
gatatggcag aattgacatg cttgaatgaa gcttccgttt tacataatct gaaggatcgc


 


421
tactattcag gactaatcta tacttattct ggactcttct gtgtagttat aaacccttac


 


481
aagaatcttc caatttactc tgagaatatt attgaaatgt acagagggaa gaagcgtcat


 


541
gagatgcctc cacacatcta tgctatatct gaatctgctt acagatgcat gcttcaagat


 


601
cgtgaggacc agtcaattct ttgcacgggt gagtcaggtg ctgggaagac agaaaataca


 


661
aagaaagtta ttcagtacct tgcccatgtt gcttcttcac ataaaggaag aaaggaccat


 


721
aatattcctg gggaacttga acggcagctt ttgcaagcaa atccaattct ggaatcattt


 


781
ggaaatgcga agactgtgaa aaatgataac tcatctcgtt ttggcaaatt tattcggatc


 


841
aactttgatg taactggcta tatcgttggg gccaacattg aaacatacct tctggaaaag


 


901
tctcgtgctg ttcgtcaagc aaaagatgaa cgtacttttc atatctttta ccagttgtta


 


961
tctggagcag gagaacacct aaagtctgat ttgcttcttg aaggatttaa taactacagg


 


1021
tttctctcca atggctatat tcctattccg ggacagcaag acaaagataa tttccaggag


 


1081
accatggaag caatgcacat aatgggcttc tcccatgaag agattctgtc aatgcttaaa


 


1141
gtagtatctt cagtgctaca gtttggaaat atttctttca aaaaggagag aaatactgat


 


1201
caagcttcca tgccagaaaa tacagttgcg cagaagctct gccatcttct tgggatgaat


 


1261
gtgatggagt ttactcgggc catcctgact ccccggatca aggtcggccg agactatgtg


 


1321
caaaaagccc agaccaaaga acaggcagat tttgcagtag aagcattggc aaaagctacc


 


1381
tatgagcggc tctttcgctg gctcgttcat cgcatcaata aagctctgga taggaccaaa


 


1441
cgtcagggag catctttcat tggaatcctg gatattgctg gatttgaaat ttttgagctg


 


1501
aactcctttg aacaactttg catcaactac accaatgaga agctgcagca gctgttcaac


 


1561
cacaccatgt ttatcctaga acaagaggaa taccagcgcg aaggcatcga gtggaacttc


 


1621
atcgatttcg ggctggatct gcagccatgc atcgacctaa tagagagacc tgcgaaccct


 


1681
cctggtgtac tggccctttt ggatgaagaa tgctggttcc ctaaagccac agataaaacc


 


1741
tttgttgaaa aactggttca agagcaaggt tcccactcca agtttcagaa acctcgacaa


 


1801
ttaaaagaca aagctgattt ttgcattata cattatgcag ggaaggtgga ctataaggca


 


1861
gatgagtggc tgatgaagaa tatggacccc ctgaatgaca acgtggccac ccttttgcac


 


1921
cagtcatcag acagatttgt ggcagagctt tggaaagatg tggaccgtat cgtgggtctg


 


1981
gatcaagtca ctggtatgac tgagacagct tttggctccg catataaaac caagaagggc


 


2041
atgtttcgta ccgttgggca actctacaaa gaatctctca ccaagctgat ggcaactctc


 


2101
cgaaacacca accctaactt tgttcgttgt atcattccaa atcacgagaa gagggctgga


 


2161
aaattggatc cacacctagt cctagatcag cttcgctgta atggtgtcct ggaagggatc


 


2221
cgaatctgtc gccagggctt ccctaaccga atagttttcc aggaattcag acagagatat


 


2281
gagatcctaa ctccaaatgc tattcctaaa ggttttatgg atggtaaaca ggcctgtgaa


 


2341
cgaatgatcc gggctttaga attggaccca aacttgtaca gaattggaca gagcaagata


 


2401
tttttcagag ctggagttct ggcacactta gaggaagaaa gagatttaaa aatcaccgat


 


2461
atcattatct tcttccaggc cgtttgcaga ggttacctgg ccagaaaggc ctttgccaag


 


2521
aagcagcagc aactaagtgc cttaaaggtc ttgcagcgga actgtgccgc gtacctgaaa


 


2581
ttacggcact ggcagtggtg gcgagtcttc acaaaggtga agccgcttct acaagtgact


 


2641
cgccaggagg aagaacttca ggccaaagat gaagagctgt tgaaggtgaa ggagaagcag


 


2701
acgaaggtgg aaggagagct ggaggagatg gagcggaagc accagcagct tttagaagag


 


2761
aagaatatcc ttgcagaaca actacaagca gagactgagc tctttgctga agcagaagag


 


2821
atgagggcaa gacttgctgc taaaaagcag gaattagaag agattctaca tgacttggag


 


2881
tctagggttg aagaagaaga agaaagaaac caaatcctcc aaaatgaaaa gaaaaaaatg


 


2941
caagcacata ttcaggacct ggaagaacag ctagacgagg aggaaggggc tcggcaaaag


 


3001
ctgcagctgg aaaaggtgac agcagaggcc aagatcaaga agatggaaga ggagattctg


 


3061
cttctcgagg accaaaattc caagttcatc aaagaaaaga aactcatgga agatcgcatt


 


3121
gctgagtgtt cctctcagct ggctgaagag gaagaaaagg cgaaaaactt ggccaaaatc


 


3181
aggaataagc aagaagtgat gatctcagat ttagaagaac gcttaaagaa ggaagaaaag


 


3241
actcgtcagg aactggaaaa ggccaaaaga aaactcgacg gggagacgac cgacctgcag


 


3301
gaccagatcg cagagctgca ggcgcagatt gatgagctca agctgcagct ggccaagaag


 


3361
gaggaggagc tgcagggcgc actggccaga ggtgatgatg aaacactcca taagaacaat


 


3421
gcccttaaag ttgtgcgaga gctacaagcc caaattgctg aacttcagga agactttgaa


 


3481
tccgagaagg cttcacggaa caaggccgaa aagcagaaaa gggacttgag tgaggaactg


 


3541
gaagctctga aaacagagct ggaggacacg ctggacacca cggcagccca gcaggaacta


 


3601
cgtacaaaac gtgaacaaga agtggcagag ctgaagaaag ctcttgagga ggaaactaag


 


3661
aaccatgaag ctcaaatcca ggacatgaga caaagacacg caacagccct ggaggagctc


 


3721
tcagagcagc tggaacaggc caagcggttc aaagcaaatc tagagaagaa caagcagggc


 


3781
ctggagacag ataacaagga gctggcgtgt gaggtgaagg tcctgcagca ggtcaaggct


 


3841
gagtctgagc acaagaggaa gaagctcgac gcgcaggtcc aggagctcca tgccaaggtc


 


3901
tctgaaggcg acaggctcag ggtggagctg gcggagaaag caagtaagct gcagaatgag


 


3961
ctagataatg tctccaccct tctggaagaa gcagagaaga agggtattaa atttgctaag


 


4021
gatgcagcta gtcttgagtc tcaactacag gatacacagg agcttcttca ggaggagaca


 


4081
cgccagaaac taaacctgag cagtcggatc cggcagctgg aagaggagaa gaacagtctt


 


4141
caggagcagc aggaggagga ggaggaggcc aggaagaacc tggagaagca agtgctggcc


 


4201
ctgcagtccc agttggctga taccaagaag aaagtagatg acgacctggg aacaattgaa


 


4261
agtctggaag aagccaagaa gaagcttctg aaggacgcgg aggccctgag ccagcgcctg


 


4321
gaggagaagg cactggcgta tgacaaactg gagaagacca agaaccgcct gcagcaggag


 


4381
ctggacgacc tcacggtgga cctggaccac cagcgccagg tcgcctccaa cttggagaag


 


4441
aagcagaaga agtttgacca gctgttagca gaagagaaga gcatctctgc tcgctatgcc


 


4501
gaagagcggg accgggccga agccgaggcc agagagaaag aaaccaaagc cctgtcactg


 


4561
gcccgggccc tcgaggaagc cctggaggcc aaggaggagt ttgagaggca gaacaagcag


 


4621
ctccgagcag acatggaaga cctcatgagc tccaaagatg atgtgggaaa aaacgttcac


 


4681
gaacttgaaa aatccaaacg ggccctagag cagcaggtgg aggaaatgag gacccagctg


 


4741
gaggagctgg aagacgaact ccaggccacg gaagatgcca agcttcgtct ggaggtcaac


 


4801
atgcaggcca tgaaggcgca gttcgagaga gacctgcaaa ccagggatga gcagaatgaa


 


4861
gagaagaagc ggctgctgat caaacaggtg cgggagctcg aggcggagct ggaggatgag


 


4921
aggaaacagc gggcgcttgc tgtagcttca aagaaaaaga tggagataga cctgaaggac


 


4981
ctcgaagccc aaatcgaggc tgcgaacaaa gctcgggatg aggtgattaa gcagctccgc


 


5041
aagctccagg ctcagatgaa ggattaccaa cgtgaattag aagaagctcg tgcatccaga


 


5101
gatgagattt ttgctcaatc caaagagagt gaaaagaaat tgaagagtct ggaagcagaa


 


5161
atccttcaat tgcaggagga acttgcctca tctgagcgag cccgccgaca cgccgagcag


 


5221
gagagagatg agctggcgga cgagatcacc aacagcgcct ctggcaagtc cgcgctgctg


 


5281
gatgagaagc ggcgtctgga agctcggatc gcacagctgg aggaggagct ggaagaggag


 


5341
cagagcaaca tggagctgct caacgaccgc ttccgcaaga ccactctaca ggtggacaca


 


5401
ctgaacgccg agctagcagc cgagcgcagc gccgcccaga agagtgacaa tgcacgccag


 


5461
caactggagc ggcagaacaa ggagctgaag gccaagctgc aggaactcga gggtgctgtc


 


5521
aagtctaagt tcaaggccac catctcagcc ctggaggcca agattgggca gctggaggag


 


5581
cagcttgagc aggaagccaa ggaacgagca gccgccaaca aattagtccg tcgcactgag


 


5641
aagaagctga aagaaatctt catgcaggtt gaggatgagc gtcgacacgc ggaccagtat


 


5701
aaagagcaga tggagaaggc caacgctcgg atgaagcagc ttaaacgcca gctggaggaa


 


5761
gcagaagaag aagcgacgcg tgccaacgca tctcggcgta aactccagcg ggaactggat


 


5821
gatgccaccg aggccaacga gggcctgagc cgcgaggtca gcaccctgaa gaaccggctg


 


5881
aggcggggtg gccccatcag cttctcttcc agccgatctg gccggcgcca gctgcacctt


 


5941
gaaggagctt ccctggagct ctccgacgat gacacagaaa gtaagaccag tgatgtcaac


 


6001
gagacgcagc caccccagtc agagtaaagt tgcaggaagc cagaggaggc aatacagtgg


 


6061
gacagttagg aatgcacccg gggcctcctg cagatttcgg aaattggcaa gctacgggat


 


6121
tccttcctga aagatcaact gtgtcttaag gctctccagc ctatgcatac tgtatcctgc


 


6181
ttcagactta ggtacaattg ctcccctttt tatatataga cacacacagg acacatatat


 


6241
taaacagatt gtttcatcat tgcatctatt ttccatatag tcatcaagag accattttat


 


6301
aaaacatggt aagacccttt ttaaaacaaa ctccaggccc ttggttgcgg gtcgctgggt


 


6361
tattggggca gcgccgtggt cgtcactcag tcgctctgca tgctctctgt catacagaca


 


6421
ggtaacctag ttctgtgttc acgtggcccc cgactcctca gccacatcaa gtctcctaga


 


6481
ccactgtgga ctctaaactg cacttgtctc tctcatttcc ttcaaataat gatcaatgct


 


6541
atttcagtga gcaaactgtg aaaggggctt tggaaagagt aggaggggtg ggctggatcg


 


6601
gaagcaacac ccatttgggg ttaccatgtc catcccccaa ggggggccct gcccctcgag


 


6661
tcgatggtgt cccgcatcta ctcatgtgaa ctggccttgg cgagggctgg tctgtgcata


 


6721
gaagggatag tggccacact gcagctgagg ccccaggtgg cagccatgga tcatgtagac


 


6781
ttccagatgg tctcccgaac cgcctggctc tgccggcgcc ctcctcacgt caggagcaag


 


6841
cagccgtgga cccctaagcc gagctggtgg aaggcccctc cctgtcgcca gccgggccct


 


6901
catgctgacc ttgcaaattc agccgctgct ttgagcccaa aatgggaata ttggttttgt


 


6961
gtccgaggct tgttccaagt ttgtcaatga ggtttatgga gcctccagaa cagatgccat


 


7021
cttcctgaat gttgacatgc cagtgggtgt gactccttca tttttccttc tcccttccct


 


7081
ttggacagtg ttacagtgaa cacttagcat cctgtttttg gttggtagtt aagcaaactg


 


7141
acattacgga aagtgcctta gacactacag tactaagaca atgttgaata tatcattcgc


 


7201
ctctataaca atttaatgta ttcagttttg actgtgcttc atatcatgta cctctctagt


 


7261
caaagtggta ttacagacat tcagtgacaa tgaatcagtg ttaattctaa atccttgatc


 


7321
ctctgcaatg tgcttgaaaa cacaaacctt ttgggttaaa agctttaaca tctattagga


 


7381
agaatttgtc ctgtgggttt ggaatcttgg attttccccc tttatgaact gtactggctg


 


7441
ttgaccacca gacacctgac cgcaaatatc ttttcttgta ttcccatatt tctagacaat


 


7501
gatttttgta agacaataaa tttattcatt atagatattt gcgcctgctc tgtttacttg


 


7561
aagaaaaaag cacccgtgga gaataaagag acctcaataa acaagaataa tcatgtgaa






One example of a nucleic acid sequence for human PFAAP5 is available as NCBI accession number AF530063 (gi: 33329092). This sequence is recited below for easy reference as SEQ ID NO:150.









1
atgtcttatg gtgaaattga aggtaaattc ttgggaccta gagaagaagt aacgagtgag



 


61
ccacgctgta aaaaattgaa gtcaaccaca gagtcgtatg tttttcacaa tcatagtaat


 


121
gctgattttc acagaatcca agagaaaact ggaaatgatt gggtccctgt gaccatcatt


 


181
gatgtcagag gacatagtta tttgcaggag aacaaaatca aaactacaga tttgcataga


 


241
cctttgcatg atgagatgcc tggtaataga ccagatgtta ttgaatccat tgattcacag


 


301
gttttacagg aagcacgtcc tccattagta tccgcagacg atgagatata tagcacaagt


 


361
aaagcattta taggacccat ttacaaaccc cctgagaaaa agaaacgtaa tgaagggagg


 


421
aatgaggcac atgttctaaa tggtataaat gacagaggag gacaaaaaga gaaacagaaa


 


481
tttaactctg aaaaatcaga gattgacaat gaattattcc agttttacaa agaaattgaa


 


541
gagcttgaaa aggaaaaaga tggttttgag aacagttgta aagaatctga accttctcag


 


601
gaacaatttg ttccatttta tgagggtcat aataatggtc tcttaaaacc tgatgaagaa


 


661
aagaaagatc ttagtaataa agctatgcca tcacattgtg attatcagca gaacttgggg


 


721
aatgagccag acaaatatcc ctgtaatgga caagtaatac ctacattttg tgacacttca


 


781
tttacttctt tcaggcctga atggcagtca gtatatcctt ttatagtgcc ctatggtccc


 


841
cctcttccca gtttgaacta tcatttaaac attcagagat tcagtggtcc accaaatcca


 


901
ccatcaaata ttttccaagc ccaagatgac tctcagatac aaaatggata ttatgtaaat


 


961
aattgtcatg ttaactggaa ttgcatgact tttgatcaga acaatgaata tactgactgt


 


1021
agtgagaata ggagtagtgt tcatccctct ggaaatggct gcagtatgca agatcgatat


 


1081
gtgagtaatg gtttctgtga agtcagagaa agatgctgga aagatcattg tatggacaag


 


1141
cataatggaa cagacaggtt tgtgaaccag cagtttcaag aggaaaagtt aaataaattg


 


1201
cagaagttac ttattctttt aagaggtctg cctggttctg ggaaaacaac attgtctcga


 


1261
attctgcttg gtcagaatcg tgatggcatt gtgttcagca ctgatgacta ttttcaccat


 


1321
caagatgggt acaggtataa tgttaatcaa cttggtgatg cccatgactg gaaccagaac


 


1381
agagcaaaac aagctatcga tcagggaaga tctccagtta taatagataa cactaatata


 


1441
caagcttggg aaatgaagcc atatgtggaa gtggccatag gaaaaggata cagagtagag


 


1501
tttcatgaac ctgaaacttg gtggaaattt gatcctgaag aattagaaaa gaggaataaa


 


1561
catggtgtgt ctcgaaagaa gattgctcag atgttggatc gttatgaata tcaaatgtcc


 


1621
atttctattg taatgaattc agtggaacca tcacacaaaa gcacacaaag acctcctcct


 


1681
ccacagggga gacagaggtg gggaggctct cttggctcac ataatcgtgt ctgtgtcaca


 


1741
aataatcatt aa






One example of a nucleic acid sequence for human PGF is available as NCBI accession number NM_002632 (gi: 56676307). This sequence is recited below for easy reference as SEQ ID NO:151.









1
ctgctgtctg cggaggaaac tgcatcgacg gacggccgcc cagctacggg aggacctgga



 


61
gtggcactgg gcgcccgacg gaccatcccc gggacccgcc tgcccctcgg cgccccgccc


 


121
cgccgggccg ctccccgtcg ggttccccag ccacagcctt acctacgggc tcctgactcc


 


181
gcaaggcttc cagaagatgc tcgaaccacc ggccggggcc tcggggcagc agtgagggag


 


241
gcgtccagcc ccccactcag ctcttctcct cctgtgccag gggctccccg ggggatgagc


 


301
atggtggttt tccctcggag ccccctggct cgggacgtct gagaagatgc cggtcatgag


 


361
gctgttccct tgcttcctgc agctcctggc cgggctggcg ctgcctgctg tgccccccca


 


421
gcagtgggcc ttgtctgctg ggaacggctc gtcagaggtg gaagtggtac ccttccagga


 


481
agtgtggggc cgcagctact gccgggcgct ggagaggctg gtggacgtcg tgtccgagta


 


541
ccccagcgag gtggagcaca tgttcagccc atcctgtgtc tccctgctgc gctgcaccgg


 


601
ctgctgcggc gatgagaatc tgcactgtgt gccggtggag acggccaatg tcaccatgca


 


661
gctcctaaag atccgttctg gggaccggcc ctcctacgtg gagctgacgt tctctcagca


 


721
cgttcgctgc gaatgccggc ctctgcggga gaagatgaag ccggaaagga ggagacccaa


 


781
gggcaggggg aagaggagga gagagaagca gagacccaca gactgccacc tgtgcggcga


 


841
tgctgttccc cggaggtaac ccaccccttg gaggagagag accccgcacc cggctcgtgt


 


901
atttattacc gtcacactct tcagtgactc ctgctggtac ctgccctcta tttattagcc


 


961
aactgtttcc ctgctgaatg cctcgctccc ttcaagacga ggggcaggga aggacaggac


 


1021
cctcaggaat tcagtgcctt caacaacgtg agagaaagag agaagccagc cacagacccc


 


1081
tgggagcttc cgctttgaaa gaagcaagac acgtggcctc gtgaggggca agctaggccc


 


1141
cagaggccct ggaggtctcc aggggcctgc agaaggaaag aagggggccc tgctacctgt


 


1201
tcttgggcct caggctctgc acagacaagc agcccttgct ttcggagctc ctgtccaaag


 


1261
tagggatgcg gatcctgctg gggccgccac ggcctggctg gtgggaaggc cggcagcggg


 


1321
cggaggggat ccagccactt ccccctcttc ttctgaagat cagaacattc agctctggag


 


1381
aacagtggtt gcctgggggc ttttgccact ccttgtcccc cgtgatctcc cctcacactt


 


1441
tgccatttgc ttgtactggg acattgttct ttccggccaa ggtgccacca ccctgccccc


 


1501
cctaagagac acatacagag tgggccccgg gctggagaaa gagctgcctg gatgagaaac


 


1561
agctcagcca gtggggatga ggtcaccagg ggaggagcct gtgcgtccca gctgaaggca


 


1621
gtggcagggg agcaggttcc ccaagggccc tggcaccccc acaagctgtc cctgcagggc


 


1681
catctgactg ccaagccaga ttctcttgaa taaagtattc tagtgtggaa aaaaaaaaaa


 


1741
aaaaaaaaaa aaaaaaaa






One example of a nucleic acid sequence for human PIP3-E is available as NCBI accession number AJ310566 (gi: 18307480). This sequence is recited below for easy reference as SEQ ID NO:152.









1
gtttaagtag aatcctcaag cttggcctca gagtactatg aggcttctga atccaggaat



 


61
aagactgctc ttggatttac tctctttgta ttgcatgtca aaggcaacag aactggacca


 


121
agaaaattca taactttttg cgtttgtttc tactaagatg acatcataca tggctattga


 


181
tggcagtgct cttgttccct tgcgtcagaa gcccaggagg aaaactcaag gttttctcac


 


241
gatgagtcgg aggaggatat cgtgtaaaga tctgggccat gctgactgcc aagggtggct


 


301
gtataagaaa aaggaaaagg gaagtttcct aagcaacaaa tggaaaaagt tctgggtgat


 


361
actgaagggg tcgtcactgt actggtatag caatcaaatg gcagagaaag ctgatggatt


 


421
tgtcaacctg cctgatttca ctgtggaaag agcatctgaa tgcaagaaaa agcatgcttt


 


481
taagatcagc catccacaga tcaagacctt ttattttgca gctgagaatg tgcaggaaat


 


541
gaacgtgtgg ttaaataaac ttggatcggc tgtaatccat caggaatcca ctacaaagga


 


601
tgaagaatgt tacagtgaaa gtgaacagga agatccagaa atagctgcgg agacaccacc


 


661
ccctcctcac gcttcccaga ctcagtcttt gactgcacag caggcatctt catcctcacc


 


721
cagcctgagt ggaacgtcgt attctttctc ttccctggaa aatacagtga agacacccag


 


781
cagttttcct tcctccttat ctaaagagag acaatccttg cctgacacag ttaacagttt


 


841
gtctgctgct gaagatgagg gacaaccaat aacgtttgct gtgcaagttc attcacctgt


 


901
accctcagag gcaggcatcc acaaggccct ggaaaacagt tttgtcacat cagaaagtgg


 


961
atttttgaac tctttatcta gtgatgatac ttcttcattg agtagcaatc atgaccatct


 


1021
tactgtccca gataagcctg ctggatcaaa gatcatggac aaagaagaga caaaagtgtc


 


1081
tgaagatgat gaaatggaga agctgtacaa atcattagag caagctagtc tatctcctct


 


1141
tggggaccga cgaccttcga ctaaaaagga gttgagaaaa tcctttgtta agcggtgtaa


 


1201
aaatccatct ataaacgaga aactccacaa aatccgaaca ttgaatagca cattaaagtg


 


1261
taaagaacat gatctggcca tgattaacca gttgctggat gacccgaagc tgacagccag


 


1321
gaaatacaga gagtggaaag tcatgaacac cctgctgatc caggacatct atcagcagca


 


1381
gcgggcttcg cctgcccctg atgacactga tgacaccccc caggaactca agaaatcacc


 


1441
ttcttctccc tctgttgaaa attccatttg agacaaagtc agggttttct cctcttatat


 


1501
tttatcacaa gcaactcttc aagatgttgc aaaagcttac atttttcctt aaaaggaaaa


 


1561
ctgaaaccca gtccttcaag catcagcttc ccatctaaag atgcacgtta gatgaagata


 


1621
at






One example of a nucleic acid sequence for human PKNOX2 is available as NCBI accession number NM_022062 (gi: 116812643). This sequence is recited below for easy reference as SEQ ID NO:153.









1
gtgtgaaggg ggggtccggg gggcgggtcc ctgtgccgct gacgtcccga gcagtgctgg



 


61
gaagtatagg ctgtgttgtc acgccggtgt cagtctgatg aagattggca tcaggtgaag


 


121
tctggagcag gacttctgag gctttctatc ctccatgctg ctcactagaa aaggggctgt


 


181
gaactgtgct ttggctctag cagacaggaa gaaattctgg cccagctgga agtagaaaga


 


241
ggggagtgag tctcctgagg accatctcag aggccccggg atcacccgaa cagtcctcca


 


301
tgtgaatcaa tcccatgatg caacatgcct ccccagcccc cgctctgacg atgatggcca


 


361
cgcagaatgt cccgccccca ccctaccagg acagcccaca gatgacggca accgcccagc


 


421
caccctccaa ggcccaggct gtccacatct ctgccccctc agctgctgcc agcacacctg


 


481
tgcccagtgc ccccatcgac ccccaggccc agctggaggc tgacaagcga gctgtataca


 


541
ggcaccctct tttcccgctc ctgacgctgc tgtttgagaa atgtgaacag gccacccagg


 


601
gctctgagtg catcacctcc gccagctttg atgtggacat cgagaacttt gtccaccagc


 


661
aggaacagga gcacaaaccc ttcttcagcg atgacccaga actggacaat ctgatggtga


 


721
aggcaatcca ggtcctgaga atccacctgc tggagctgga gaaagtcaat gaactctgca


 


781
aggacttttg taaccgttac atcacctgcc tcaaaaccaa gatgcacagc gacaacctgc


 


841
tcaggaatga tctagggggg ccctactccc ccaaccagcc ctccatcaac cttcactcac


 


901
aggacctcct gcagaattcc cccaattcca tgtccggagt ctccaataac ccccagggga


 


961
ttgtggtccc agcctcagcg ctccagcagg gcaacatcgc catgacaacc gtcaactcac


 


1021
aagttgtgtc aggtggagcc ttataccaac cggttaccat ggtaacctcc cagggtcagg


 


1081
tggtcaccca agcaatcccc cagggagcca tccagatcca gaacacacag gttaaccttg


 


1141
acctcacctc cctcctggac aatgaggata agaagtccaa gaacaaacga ggagtcttgc


 


1201
ccaagcatgc caccaatata atgcgttctt ggctcttcca gcatctcatg cacccctacc


 


1261
ccacggagga tgagaagagg cagatcgcag cccagaccaa cctcaccctc ctgcaagtaa


 


1321
acaactggtt catcaatgcc cggaggcgca tcctgcagcc catgcttgat gccagcaacc


 


1381
cagatcctgc ccccaaagcc aagaagatca agtctcagca ccggcccacc caaagattct


 


1441
ggcccaactc catcgctgcg ggggtgctgc agcagcaggg cggtgcccca gggacaaacc


 


1501
ccgatggttc catcaacttg gacaacctgc agtccctgtc ctcagacagt gccaccatgg


 


1561
ccatgcagca ggctatgatg gctgcacacg atgactcatt ggatgggaca gaagaagagg


 


1621
atgaggatga gatggaagag gaggaggagg aggagctgga ggaggaggtc gacgagctgc


 


1681
agacgacaaa tgtcagcgac ctgggcttgg aacacagtga ctccctggag tagtcgggca


 


1741
gcccagatgg cactgatcac tgagcaggag aggagtgtcg ccgggaggcc ttcagggtgg


 


1801
gggggaaggg gacatgggca ggaagcaccg agggagttgg gccctagctt ccccaaatca


 


1861
gtagcttgaa gaaaggcaaa ggagacacct gttccttccc aaccaccgag cttcaatgag


 


1921
gaccccagcc ccacttccct ggaactgccg aggactctgt ttggcggggc cagtcgagca


 


1981
gcctgtgtgg aaagacagga gtgagatctg gactcaccaa atccctgagg atagatggca


 


2041
cccatggccc ccacccacgg aaggacttga gttgtttaca agccctgcac tgaggcagat


 


2101
tggtgctgtt cgcagagtag gcctttgccc gggggcagac ttagaaggaa ggggagagac


 


2161
aaagggggac tgagtttcat ccccagaagt ttctcagctc ctttgacaga cattcaaggg


 


2221
caggagggag ccccaaagca taaccagtgg ccagaggagt gggagggcct gaggcatcac


 


2281
atcttgcaga tcagaatggg atggaatcca ccaggctcca gctcatccct ccaaggccct


 


2341
gtctctgcgc acagcaacca tggacatggg agaaagggat gggagccaca gtgcccttca


 


2401
ctctctcctg gaaaccaact gtaagctggt gggctcaacc tgtgggaggt taagaggagt


 


2461
cccttctggg ttgactccaa gagccaagga gatggcagac cctgggctag gaaccatatg


 


2521
gaggtgactt tgaggccaca gctgtcccta ggtgatcaca gaacttagct cctttaacaa


 


2581
caggacaatg gttttttacc ctagatgttc ccaccttcag tgctccacgc cctccataga


 


2641
ccttcagaga aggtgaaacc aggttatctg ggaatctttc cagcccgcag gtcgccacgg


 


2701
ccatcccttt gctcccagcc tggctccatc agcctccagc ttcctttctt cattctgtcc


 


2761
ttcagggaag gcagaagaaa cattggaaag catctagtcc agtgggaagc caggggttgg


 


2821
agaaggtgct acatccctct tcccatcaat atcctaaatg tgggggaggg cccagagaat


 


2881
ggcacccaag agcctgcggg gatgcccatc ccacacaccc cacccagctg ttctaaccct


 


2941
gctatccaca gccctggagg aactggggct cctggaagga ggaggaggct ctccactgtc


 


3001
caccctaaca cataccctcc cacccacctt ccagaccccc ttggttggca ccctctcctc


 


3061
cggttccctc tcaccccatg gctgtgaatg acaggacagg tcacacgtgt gttttccatt


 


3121
gggtttaatt taatggacgt gcagtttcat ttgtaaattg tgcattggcc acctccttca


 


3181
gtggcaggat gtgagtggct acctggctca actggagggg accccttggg ccctctgggg


 


3241
cttcccctcc cccacctggt tggggtagag caaaaggatg gtcactcttc cgaggtctcc


 


3301
ctgaaatgaa tgtatttctc ccccaaaaga gctgatattt aatgttttaa taaggatttt


 


3361
tgagaaacaa ataaccttat ttataatctg ggtgatccaa tcatttttta ctcccttttg


 


3421
atgccataca tagaggaaag tctagctttt ttggcgtgag acttttgcaa tgtgcagtgg


 


3481
gataaaatgc atttcctttt ctggttcgtt tttcttgtta acacgcgcac acagacacac


 


3541
acacacaccg ttccactcac cacctggaca ggcgtccccc agcacggaca cactggcaca


 


3601
caggtgccca catctcttcc tctcagcccc tccacctgcc taatgttatg caacctcctt


 


3661
ctgatgtatc caccaaacca gtactgaatg tggccgagac gttttcagta aatcttatta


 


3721
cctaccgtaa






One example of a nucleic acid sequence for human PRKACB is available as NCBI accession number NM_182948 (gi: 46909585). This sequence is recited below for easy reference as SEQ ID NO:154.









1
acacatgcat agctcttagc ttctgtgtaa gaagttgtga gctccttctg gaaacatttg



 


61
cagttacatt aagtaaagtg taaatgcaca tgaatggcag cttatagaga accaccttgt


 


121
aaccagtata caggtacaac tacagctctt cagaaattgg aaggttttgc tagccggtta


 


181
tttcatagac actctaaagg tactgcacat gatcagaaaa cagctctgga aaatgacagc


 


241
cttcatttct ctgaacatac tgccttatgg gacagatcaa tgaaagagtt tctagccaaa


 


301
gccaaagaag actttttgaa aaaatgggag aatccaactc agaataatgc cggacttgaa


 


361
gattttgaaa ggaaaaaaac ccttggaaca ggttcatttg gaagagtcat gttggtaaaa


 


421
cacaaagcca ctgaacagta ttatgccatg aagatcttag ataagcagaa ggttgttaaa


 


481
ctgaagcaaa tagagcatac tttgaatgag aaaagaatat tacaggcagt gaattttcct


 


541
ttccttgttc gactggagta tgcttttaag gataattcta atttatacat ggttatggaa


 


601
tatgtccctg ggggtgaaat gttttcacat ctaagaagaa ttggaaggtt cagtgagccc


 


661
catgcacggt tctatgcagc tcagatagtg ctaacattcg agtacctcca ttcactagac


 


721
ctcatctaca gagatctaaa acctgaaaat ctcttaattg accatcaagg ctatatccag


 


781
gtcacagact ttgggtttgc caaaagagtt aaaggcagaa cttggacatt atgtggaact


 


841
ccagagtatt tggctccaga aataattctc agcaagggct acaataaggc agtggattgg


 


901
tgggcattag gagtgctaat ctatgaaatg gcagctggct atcccccatt ctttgcagac


 


961
caaccaattc agatttatga aaagattgtt tctggaaagg tccgattccc atcccacttc


 


1021
agttcagatc tcaaggacct tctacggaac ctgctgcagg tggatttgac caagagattt


 


1081
ggaaatctaa agaatggtgt cagtgatata aaaactcaca agtggtttgc cacgacagat


 


1141
tggattgcta tttaccagag gaaggttgaa gctccattca taccaaagtt tagaggctct


 


1201
ggagatacca gcaactttga tgactatgaa gaagaagata tccgtgtctc tataacagaa


 


1261
aaatgtgcaa aagaatttgg tgaattttaa agaggaacaa gatgacatct gagctcacac


 


1321
tcagtgtttg cactctgttg agagataagg tagagctgag accgtccttg ttgaagcagt


 


1381
tacctagttc cttcattcca acgactgagt gaggtcttta ttgccatcat cccgtgtgcg


 


1441
cactctgcat ccacctatgt aacaaggcac cgctaagcaa gcattgtctg tgccataaca


 


1501
cagtactaga ccactttctt acttctcttt gggttgtctt tctcctctcc tatatccatt


 


1561
tcttcctttt ccaatttcat tggttttctc taaacagtgc tccattttat tttgttggtg


 


1621
tttcagatgg gcagtgttat ggctacgtga tatttgaagg gaaggataag tgttgctttc


 


1681
agtagttatt gccaatattg ttgttggtca atggcttgaa gataaacttt ctaataatta


 


1741
ttatttcttt gagtagctca gacttggttt tgccaaaact cttggtaatt tttgaagata


 


1801
gactgtctta tcaccaagga aatttataca aattaagact aactttcttg gaattcacta


 


1861
ttctggcaat aaattttggt agactaatac agtacagcta gacccagaaa tttggaaggc


 


1921
tgtagatcag aggttctagt tccctttccc tccttttata tcctcctctc cttgagtaat


 


1981
gaagtgacca gcctgtgtag tgtgacaaac gtgtctcatt cagcaggaaa aactaatgat


 


2041
atggatcatc acccagattc tctcacttgg taccagcatt tctgtaggta ttagagaaga


 


2101
gttctaagtt ttctaaacct taactgttcc ttaaggattt tagccagtat tttaatagaa


 


2161
catgattaat gaaagtgaca aattttaaat tttctctaat agtcctcatc ataaactttt


 


2221
taaaggaaaa taagcaaact aaaaagaaca ttggtttaga taaatactta tactttgcaa


 


2281
agtcaaaaat ggcttgattt ttggaaacaa tatagaggta ttcatattta aatgagggtt


 


2341
tacatttgtt ttgttttgta accgttaaaa agaagttgtt tccagctaat tattgtggtg


 


2401
tactatattt gtgagcctag ggtaggggca ctgctgcaac ttctgctttc atcccatgcc


 


2461
tcatcaatga ggaaagggaa caaagtgtat aaaactgcca caattgtatt ttaattttga


 


2521
ggtatgatat tttcagatat ttcataattt ctaacctctg ttctctcagt aaacagaatg


 


2581
tctgatcgat catgcagata caatgttggt atttgagagg ttagtttttt tcctacactt


 


2641
ttttttgcca actgacttaa caacattgct gtcaggtgga aatttcaagc acttttgcac


 


2701
atttagttca gtgtttgttg agaatccatg gcttaaccca cttgttttgc tatttttttc


 


2761
tttgctttta attttcccca tctgatttta tctctgcgtt tcagtgacct accttaaaac


 


2821
aacacacgag aagagttaaa ctgggttcat tttaatgatc aatttacctg catataaaat


 


2881
ttatttttaa tcaagctgat cttaatgtat ataatcattc tatttgcttt attatcggtg


 


2941
caggtaggtc attaacacca cttcttttca tctgtaccac accctggtga aacctttgaa


 


3001
gacataaaaa aaacctgtct gagatgttct ttctaccaat ctatatgtct ttcggttatc


 


3061
aagtgtttct gcatggtaat gtcatgtaaa tgctgatatt gatttcactg gtccatctat


 


3121
atttaaaacg tgcaagaaaa aaataaaata ctctgctcta gcaagttttg tgtaacaaag


 


3181
gcatatcgtc atgttaataa atttaaaaca tcattcgtat aaaatatttt aattttcttg


 


3241
tatttcattt agacccaaga acatgctgac caatgtgttc tatatgtaaa ctacaaattc


 


3301
tatggtagct ttgttgtata ttattgtaaa attattttaa taagtcatgg ggatgacaat


 


3361
ttgattatta caatttagtt ttcagtaatc aaaaagattt ctatgaattc taaaaaatat


 


3421
ttttttctat gaaattacta gtgcccagct gtagaatcta ccttaggtag atgatcccta


 


3481
gacatacgtt ggttttgagg gctattcagc cattccattt tactctctat ttaaaggccg


 


3541
tgagcaagct tgtcatgagc aaatatgtca agggagtcaa tttctgacca atcaagtaca


 


3601
ctaaattaga atatttttaa agtatgtaac attcccagtt tcagccacaa tttagccaag


 


3661
aataagataa aaacttgaat aagaagtaag tagcataaat cagtatttaa cctaaaatta


 


3721
catatttgaa acagaagata ttatgttatg ctcagtaaat aattaagaga tggcattgtg


 


3781
taagaaggag ccctagactg aaagtcaaga catctgaatt tcaggctgga aaactatcag


 


3841
tatgatctca gcctcagttc tcttgtctgt aaaatggaag aactggatta ggcagtttgt


 


3901
aagattcctc ctaactttca cagtcgatga caagattgtc tttttatctg atattttgaa


 


3961
gggtatattg ctttgaagta agtctcaata aggcaatata ttttagggca tctttcttct


 


4021
tatctctgac agtgttctta aaattatttg aatatcataa gagccttggt gtctgtccta


 


4081
attcctttct cactcaccga tgctgaatac ccagttgaat caaactgtca acctaccaaa


 


4141
aacgatattg tggcttatgg gtattgctgt ctcattcttg gtatattctt gtgttaactg


 


4201
cccattggcc tgaaaatact cattgtaagc ctgaaaaaaa aaatctttcc cactgttttt


 


4261
tctgcttgtt gtaagaatca aatgaaataa tgtatgtgaa agcaccttgt aaactgtaac


 


4321
ctatcaatgt aaaatgttaa ggtgtgttgt tatttcatta attacttctt tgtttagaat


 


4381
ggaatttcct atgcactact gtagctagga aatgctgaaa acaactgtgt tttttaatta


 


4441
atcaataact gcaaaattaa agtaccttca atggataaga caaaaaaaaa aaaaaaaaa






One example of a nucleic acid sequence for human PROS1 is available as NCBI accession number NM_000313 (gi: 223671900). This sequence is recited below for easy reference as SEQ ID NO:155.









1
tttggaaacg tcacactgtg gaggaaaagc agcaactagg gagctggtga agaaggatgt



 


61
ctcagcagtg tttactaggc ctccaacact agagcccatc ccccagctcc gaaaagcttc


 


121
ctggaaatgt ccttgttatc acttcccctc tcgggctggg cgctgggagc gggcggtctc


 


181
ctccgccccc ggctgttccg ccgaggctcg ctgggtcgct ggcgccgccg cgcagcacgg


 


241
ctcagaccga ggcgcacagg ctcgcagctc cgcggcgcct agcgctccgg tccccgccgc


 


301
gacgcgccac cgtccctgcc ggcgcctccg cgcgcttcga aatgagggtc ctgggtgggc


 


361
gctgcggggc gctgctggcg tgtctcctcc tagtgcttcc cgtctcagag gcaaactttt


 


421
tgtcaaagca acaggcttca caagtcctgg ttaggaagcg tcgtgcaaat tctttacttg


 


481
aagaaaccaa acagggtaat cttgaaagag aatgcatcga agaactgtgc aataaagaag


 


541
aagccaggga ggtctttgaa aatgacccgg aaacggatta tttttatcca aaatacttag


 


601
tttgtcttcg ctcttttcaa actgggttat tcactgctgc acgtcagtca actaatgctt


 


661
atcctgacct aagaagctgt gtcaatgcca ttccagacca gtgtagtcct ctgccatgca


 


721
atgaagatgg atatatgagc tgcaaagatg gaaaagcttc ttttacttgc acttgtaaac


 


781
caggttggca aggagaaaag tgtgaatttg acataaatga atgcaaagat ccctcaaata


 


841
taaatggagg ttgcagtcaa atttgtgata atacacctgg aagttaccac tgttcctgta


 


901
aaaatggttt tgttatgctt tcaaataaga aagattgtaa agatgtggat gaatgctctt


 


961
tgaagccaag catttgtggc acagctgtgt gcaagaacat cccaggagat tttgaatgtg


 


1021
aatgccccga aggctacaga tataatctca aatcaaagtc ttgtgaagat atagatgaat


 


1081
gctctgagaa catgtgtgct cagctttgtg tcaattaccc tggaggttac acttgctatt


 


1141
gtgatgggaa gaaaggattc aaacttgccc aagatcagaa gagttgtgag gttgtttcag


 


1201
tgtgccttcc cttgaacctt gacacaaagt atgaattact ttacttggcg gagcagtttg


 


1261
caggggttgt tttatattta aaatttcgtt tgccagaaat cagcagattt tcagcagaat


 


1321
ttgatttccg gacatatgat tcagaaggcg tgatactgta cgcagaatct atcgatcact


 


1381
cagcgtggct cctgattgca cttcgtggtg gaaagattga agttcagctt aagaatgaac


 


1441
atacatccaa aatcacaact ggaggtgatg ttattaataa tggtctatgg aatatggtgt


 


1501
ctgtggaaga attagaacat agtattagca ttaaaatagc taaagaagct gtgatggata


 


1561
taaataaacc tggacccctt tttaagccgg aaaatggatt gctggaaacc aaagtatact


 


1621
ttgcaggatt ccctcggaaa gtggaaagtg aactcattaa accgattaac cctcgtctag


 


1681
atggatgtat acgaagctgg aatttgatga agcaaggagc ttctggaata aaggaaatta


 


1741
ttcaagaaaa acaaaataag cattgcctgg ttactgtgga gaagggctcc tactatcctg


 


1801
gttctggaat tgctcaattt cacatagatt ataataatgt atccagtgct gagggttggc


 


1861
atgtaaatgt gaccttgaat attcgtccat ccacgggcac tggtgttatg cttgccttgg


 


1921
tttctggtaa caacacagtg ccctttgctg tgtccttggt ggactccacc tctgaaaaat


 


1981
cacaggatat tctgttatct gttgaaaata ctgtaatata tcggatacag gccctaagtc


 


2041
tatgttccga tcaacaatct catctggaat ttagagtcaa cagaaacaat ctggagttgt


 


2101
cgacaccact taaaatagaa accatctccc atgaagacct tcaaagacaa cttgccgtct


 


2161
tggacaaagc aatgaaagca aaagtggcca catacctggg tggccttcca gatgttccat


 


2221
tcagtgccac accagtgaat gccttttata atggctgcat ggaagtgaat attaatggtg


 


2281
tacagttgga tctggatgaa gccatttcta aacataatga tattagagct cactcatgtc


 


2341
catcagtttg gaaaaagaca aagaattctt aaggcatctt ttctctgctt ataatacctt


 


2401
ttccttgtgt gtaattatac ttatgtttca ataacagctg aagggtttta tttacaatgt


 


2461
gcagtctttg attattttgt ggtcctttcc tgggattttt aaaaggtcct ttgtcaagga


 


2521
aaaaaattct gttgtgatat aaatcacagt aaagaaattc ttacttctct tgctatctaa


 


2581
gaatagtgaa aaataacaat tttaaatttg aatttttttc ctacaaatga cagtttcaat


 


2641
ttttgtttgt aaaactaaat tttaatttta tcatcatgaa ctagtgtcta aatacctatg


 


2701
tttttttcag aaagcaagga agtaaactca aacaaaagtg cgtgtaatta aatactatta


 


2761
atcataggca gatactattt tgtttatgtt tttgtttttt tcctgatgaa ggcagaagag


 


2821
atggtggtct attaaatatg aattgaatgg agggtcctaa tgccttattt caaaacaatt


 


2881
cctcaggggg aacagctttg gcttcatctt tctcttgtgt ggcttcacat ttaaaccagt


 


2941
atctttattg aattagaaaa caagtgggac atattttcct gagagcagca caggaatctt


 


3001
cttcttggca gctgcagtct gtcaggatga gatatcagat taggttggat aggtggggaa


 


3061
atctgaagtg ggtacatttt ttaaattttg ctgtgtgggt cacacaaggt ctacattaca


 


3121
aaagacagaa ttcagggatg gaaaggagaa tgaacaaatg tgggagttca tagttttcct


 


3181
tgaatccaac ttttaattac cagagtaagt tgccaaaatg tgattgttga agtacaaaag


 


3241
gaactatgaa aaccagaaca aattttaaca aaaggacaac cacagaggga tatagtgaat


 


3301
atcgtatcat tgtaatcaaa gaagtaagga ggtaagattg ccacgtgcct gctggtactg


 


3361
tgatgcattt caagtggcag ttttatcacg tttgaatcta ccattcatag ccagatgtgt


 


3421
atcagatgtt tcactgacag tttttaacaa taaattcttt tcactgtatt ttatatcact


 


3481
tataataaat cggtgtataa ttttaaaatg catgtgaata tctttattat atcaactgtt


 


3541
tgaataaaac aaaattacat aatagacatt taactcttca aaaaaaaaaa aaaaa






One example of a nucleic acid sequence for human PSD3 is available as NCBI accession number NM_015310 (gi: 117606359). This sequence is recited below for easy reference as SEQ ID NO:156.









1
aacaaagagc acgcggcgct ggccgccggc actcgcgccc tgaggctgcg gccccggagc



 


61
gcccggcggc ggtttcggcg cgcggccggg ctggcgatgg aagatggaag gaaggagcgc


 


121
agcggcagag acatttgttt gggtgaacaa tgcatctgca cattcccaga gtgttgccaa


 


181
ggccaaatat gaatttttat ttggcagatc tgaagggaaa gctccagata ctagtgatca


 


241
tggaggaagc actttactcc caccaaatgt cacaaatgaa tttccagaat atgggaccat


 


301
ggaggaaggt ggagaaggcc taagggcttc tctggaattt gatggtgagg ctctgccatg


 


361
ccacccacaa gagcagcagg gtgtccagcc tcttactggc tgccactctg ggctcgacag


 


421
tgttacagaa ggaccaaaag atgtcagaga ggccccctct caaagtcatc tcaaggaaca


 


481
aagtttacag cccattgact ctttgatttc agctctgaaa gccacagaag ccagaatcat


 


541
ttccggaaca ttacaggcta caaaggtact ggaccaagat gctgtttcta gtttttcagt


 


601
tcagcaggtg gaaaaagagc tggacactgc cagtcgtaaa acacagagag tcaacaaaac


 


661
gctccctgct ggccaaaaaa atttaccaga aatacctctt tcagctgaag taacaacgga


 


721
ggaaagtttt tatttgagca tccagaaaga tctcaccgcg ctgttaactg gagacactca


 


781
ggcagagatt tcccagataa tgaataatgg gaggaaaggg gctgtctgtg tgcaggagcc


 


841
atcttgtcct ttggcctccc tcgggagctc agcagtgacc tgccactctg caggcagtgt


 


901
tggtttcttg aaagagcaga ggtctgctct tgggagagag cacccagggg gatgtgatcg


 


961
aagcagctcc atgggacgcc caggccgggt caaacatgtg gaatttcaag gagtggaaat


 


1021
actgtggaca ggaggagaca agagagagac ccagcatcct atagattttg agacatcact


 


1081
gcaaagaaca gcctctcctg acagcaaaga gtcttccaaa gtgccacgcc atctcatctc


 


1141
atcagctggt ttgtgtaatt caagtagttt aactgagaat gtttgggatg aatcctggaa


 


1201
agctccttca gagaggcctg gcactagctc ggggacattt tcccctgtgc gtcttgatga


 


1261
gagtggagag gatgaagtct tcctacagga aaacaaacag catcttgaga agacacctaa


 


1321
accagagaga gacagggaaa ggatcagcga acaagaggag cacgttaagg gggaagatga


 


1381
agacatcctt gggcctggat atacggagga ctccaccgac gtgtacagct cccagtttga


 


1441
aaccattttg gacaacactt ctttatacta cagtgcagag tccctggaga cattatactc


 


1501
agagcctgat agctatttta gctttgaaat gcccctcact ccaatgatac aacagcgcat


 


1561
taaagaaggt ggtcagttct tggagaggac atcaggggga ggacatcagg atatcctgag


 


1621
tgtgtctgca gatggtggca tcgtgatggg ctattctagt ggcgtcacca atgggctgaa


 


1681
tgatgccagc gactccatct acacgaaagg caccccggag attgctttct ggggaagcaa


 


1741
tgctggggtg aaaacaacac ggctagaagc tcattctgaa atggggagca ctgaaatttt


 


1801
ggaaaaggag accccagaaa atctcagtaa tggtaccagc agcaatgtgg aagcagccaa


 


1861
aaggttggcc aaacgccttt atcagctgga cagattcaaa agatcagatg ttgcaaaaca


 


1921
ccttggcaag aacaacgaat ttagcaaact agttgcagaa gaatatctga agttttttga


 


1981
ttttacagga atgacgctgg atcagtcact caggtatttc tttaaagcat tctctcttgt


 


2041
gggagaaact caagaacgag agagagtttt aatacacttc tccaatagat atttttattg


 


2101
taacccagat accattgctt cacaagatgg agtccattgc cttacctgtg caataatgct


 


2161
tcttaatacc gatctacatg gccacaatat tggaaagaag atgacctgtc aggagttcat


 


2221
tgcaaatctg caaggggtaa atgagggtgt tgatttctcc aaggatctgc tgaaagctct


 


2281
gtacaactca atcaagaatg agaagcttga atgggcagta gatgatgaag agaaaaaaaa


 


2341
gtctccctca gaaagtactg aggagaaagc taacggaaca catccaaaga ccatcagtcg


 


2401
tattggaagt actactaacc catttttgga cattcctcat gatccaaatg ctgctgtgta


 


2461
caaaagtgga ttcttggctc ggaaaattca tgcagatatg gatggaaaga agactccaag


 


2521
aggaaaacga ggatggaaaa ccttttatgc tgtactgaag ggaacagttc tttacttgca


 


2581
aaaggatgaa tacaagccag aaaaggcctt gtctgaagag gacttgaaaa acgctgtgag


 


2641
tgtgcaccac gcattggcat ccaaggccac ggactatgag aagaaaccaa acgtgtttaa


 


2701
acttaaaact gccgactgga gggtcttgct ttttcaaact cagagcccag aggaaatgca


 


2761
agggtggata aacaaaatca attgtgtggc agctgtattt tctgcaccac catttccagc


 


2821
agcaatcggc tctcagaaga agtttagccg cccacttctg cctgccacta caacaaaact


 


2881
gtctcaggag gagcaactga agtcacatga aagtaagctg aagcagatca ccaccgagct


 


2941
ggccgagcac cgctcatatc cccccgacaa gaaggtcaaa gccaaggacg tcgatgagta


 


3001
caaactgaaa gaccactatc tggagtttga gaaaacccgc tatgaaatgt atgtcagcat


 


3061
tctcaaggaa ggaggcaaag agctactgag taacgatgaa agcgaggctg caggactgaa


 


3121
gaagtcgcac tcgagtcctt cgctgaaccc ggatacttct ccaatcactg ccaaagtcaa


 


3181
gcgtaacgtg tcagagagga aggatcaccg acctgaaaca ccaagcatta agcaaaaagt


 


3241
tacttagagt ccatctgcgg ccaggaagtg ctggtcatgg agcaaaatag ggtttttcaa


 


3301
gatctttctg gtaatccgtg aatatattta aaaaaaaaaa gtctgtgaca aaacggtgca


 


3361
ttagtaattt tttctattgt atatttttgt tagtttctgt acagattgtc tttgctcttg


 


3421
atttcttttg ctttgatgat ttttgcaact tgatagctaa tgcacctttt ctgtgaggag


 


3481
gaggggatcg tgatttcaga atgaattatg tatcccttct cttttggttt tctcttgttt


 


3541
gcagtctgct cagttgtttt atgtattctc atatcaactg ttaaactttt ttttaaggtt


 


3601
aaagaattta atccattgtg aaacacttaa ctggacaaac tgtagtttta gtaaattcta


 


3661
gctggagtta atatacgcct ttatatgtga aatcttgccc agtcacagag gtagaattga


 


3721
gcactcacag atgctccagt aagaatcaca gtgctgggaa tctagttgct ccaatatgag


 


3781
gcagcttcat gtgcagctta gcacttgttg ttgagatcgg accctgctgg aagcagggaa


 


3841
aagaagcgtg aagatcgtag gattgagaac ttagggaagc acattagctt gcttgaagtg


 


3901
ctgattccat ttcagccaag caagggaaag aggaagtgga gtcattttgc ctttgaaggc


 


3961
tgaggaaaga ttgataccca gttaattttg tttgctaaag gatgggggca ataatcggcc


 


4021
cttgaggagc tgcagcagta ggcatgtgct cagtctgcag gaattgttac ctcactccca


 


4081
cagggtctag actagaaatc catcatctct atcgttgata tccttccatc caggaataga


 


4141
tttttcttac tctacatatg tgtgtgtgcg tgcgtgtgtg tgcgtgtgtg ggcatggggt


 


4201
tgtgtcctgg ttgtgatatt gaggtcttcc ttcctaacaa attaatacta aaatgaaaca


 


4261
gcttttcttg tgtccttaag acaaaataag gaaggaaaac gtagctgcag ttgtccacga


 


4321
tggatattgg ttctttaaaa tatatctgaa agtagtagtc agaatgaatt atggttggaa


 


4381
aactgaggaa tcttctggtt gcaggtgcaa agtgactttg tttattcttg tctcagtctc


 


4441
cttgatagcc acttcactct gctactactc aactttctcc taaaaatact tcatctattt


 


4501
tcagtccttt ctttctgtct actcaaaatg gttctattaa ctttgcagtc atgagcttgt


 


4561
tccagttaca gtccctttga agttcagggt gataaacaga atattcttct gtagaggaag


 


4621
agaaaggagt gaaagtttag cccactgaga cctagagctt tgtgatttcc taaccttgaa


 


4681
actctgtaat ccctaaagtt aaaatctccg caagtggcac aacttcagaa ctaatagtat


 


4741
cactttgatt tttctttttc ctcccttaga aagtttctct agttctatag tttatttgtt


 


4801
gaaggtacta tgaccaaaga atcagctgct ctacaggaat agcatggttc cagtgaatta


 


4861
gagaaaacct gctgtaaagc catggtagtg tctaagtggt atgttattat gatgtactag


 


4921
catttattta cagaattatt tattaacgtt tacttccttc ccctctgtaa atgtccatga


 


4981
ctattgccca gagaaggctt acccctctct agggttgcag ttgctttctt tgtaataagt


 


5041
attttgccac acctgtaaaa aaaaaaacct cacttttaac tctctgcctt gtttgggtaa


 


5101
aggcagtaac taagtttatg tttcagaact gcaaaacaaa caggatagtt accaatatgg


 


5161
cccatgtatc agattgattt ttgtagcctc tcactgaatc caacatatcc acaagcaagt


 


5221
tatctgtctt tctacctgat aatctaaatt atcaggatat ttgttttctg cctaaatgtt


 


5281
tatactaagc cgaggggaga gaggtaccta gaccatgtca tctacaagct tcagtaacta


 


5341
aagaaaaagg aacttccctg agtggcttga atgtgtttgc ccacagtcta tatctatgta


 


5401
tatagaatgt ctgtatgtat tttacttatt taatatacat tgaatggtac cttgctacag


 


5461
tatttctgac atttagagta gtgttgaaat actcggctag catcagcacc actatagcac


 


5521
tgtccgtgtc atatgagtca ctaatattaa ctccagggac ttctggatag gctaatagat


 


5581
cattggatac gaagggctct tttgaagctt cagtatacca tgtttgcata gtttatcttt


 


5641
aaaaacaact ttaaaggttc ttttgtgagc caggatctca gactgccgta gcatgatgct


 


5701
gtccatcttt agcgcatggg ctgagaacac ctcttccctg aggcttctga aggttgctgt


 


5761
ctgtcatgag tgcatgaagg aggccaagag tttatgctat gggaggaaac agtcactgat


 


5821
ttgcctagat tctgagagtc tggcccatag ccaaccacat tttcctttgg gataatttat


 


5881
ttcctgtggc atctagccag aagaaattga ggatgtttcc tttcacagct gctccaagcc


 


5941
tgttgcccaa ttcacggtac aagggagcac cccttccctt tcctctgaag gtacgccacc


 


6001
cacctccgtc gcccacctca gcgcccagga gccttgggac ttccttccat atgataaatc


 


6061
attcttcttc acgtcaatac acttcatatt aatttctagt acagaaaatc ttgacagcta


 


6121
tcagaatgcc ttggtcatag tgttgttgca aaattgacca tacaggtggc ccatgtataa


 


6181
aatctgaatt ttaggggttt gtccccacct cgcatgctgg cttttacagg gaggtgtctg


 


6241
ggattcctca ttagcaatca aaacttaatt actgggatgc agagtcctta ctttatcgcc


 


6301
agcccgtagg catttctgaa gtgcactttt ttgaaacatc attttgctaa ctctcagcag


 


6361
tgtctaatta aactgagcaa tacttttgtg aattttaatt aatctcagca aaaccatgat


 


6421
gggagagagt cctctgatgg aaatgtagtc cctggattat gtgtaacctt tttattcctc


 


6481
ttagatgcag aggatagaaa gcattttttg gtgcagtggt cttgtggcaa acacaagacc


 


6541
ctctatgcgt ctccaactgt tatcctaatc tagaaaatga ggactggccc ctgggcaaaa


 


6601
gtgacatgag gaatttactc tggaagagga aaatctgggt ggctttccaa ggctaagata


 


6661
ggtttgtatt tcaccctgtg gccaagctac agaacttctg agattgtgga agaatttttg


 


6721
caaccagcag ggaaagaggc ctcttactgc ctaaacacaa agttacactg agcttttcta


 


6781
ctgtcctttg cctattgctc cctctatcat gtaaagatct gggaaggatg agaggcaggg


 


6841
cctgcttgtc atgagctgca ctcttttctt tttaactaat cattgacaat tggaagaaaa


 


6901
ttgacgttaa agaagtttct ccattgtctt actaacaaaa ccttttgggt ttcattaatt


 


6961
gtccttgaaa ttgagttcct ttggcatttt tccttgcagt catcagttaa gcatgttgca


 


7021
tcctgaattc acagaagttt agctttgcag gtttgaatct ctgtaattta actcccgtgg


 


7081
acttggtcga gttttcagca ggttgggagc cacctctctt catttcagca gtgagtcatc


 


7141
ccttgacttt tcaaatgaca gaattttttc caattgtaaa attagcactg taaaacaaag


 


7201
aaccaaagtg gcatcctaag agttgttaaa cctgaagtct agtttatgag gaattgtcca


 


7261
agttggagtt taaatagtat ctgcttttgt ctcaaagcat ctaagttatt ctgacagaaa


 


7321
atggtaagtc agctttgcag gcagatgcgc ctctgggcct cctaccttgc tccacagctt


 


7381
tctggccatc ttgtctccca ggccatgcca ctgctctgcc acatgtcagc aaatttcttt


 


7441
ccaccagtct tatagcatct tacatgatca aatcatcaca gaataacccc gtgatagatt


 


7501
attgatagca atagagaggg gctttgtcac tgatttttct ctcagattcc ttttccatct


 


7561
ctcatccata aaggaaggac tgaaatccaa aggcattctc cttttgtacc tacagtatcc


 


7621
agaacccacg tgggcagcct tctgcttatg acaataattg gcccattgca tgcagagaga


 


7681
atgtcttcat agagagaatg tcattaaata cttgaatctg catgacagtt tgacttgaat


 


7741
gcaacagcag gaaaattttg caagttacat aattgtatat acagtaggtt ttcttaagtc


 


7801
tcttcggttc atcctttgta atttgtgtgt gtatctgtag tattgcaggc ttttggagac


 


7861
tattcttaca ggcagtatgt cagtcatcaa agaaaatgct gtcacctgcc attgttgtat


 


7921
ttgtgggtat ttatagttgt atgtatgtaa atgcatcagt gtgtagattg catatcagtg


 


7981
tatggtacat gtacatcaaa attatttttg tccttaatca gtgtgatatg aaaagcaagt


 


8041
acaacctcat aggactgatt atataatgaa gttgttgaga gtatatatag tggtattgtt


 


8101
ttattaaact taaactcaaa taatattttg attaaaattt ttaataagac tttatgctag


 


8161
aaaattcttt gagctttgaa tcaccagggc aaaaatgact ttcaactaac cttgtgaatc


 


8221
ttttgcagtg tactgtgtgc aataccaagg gcatagctcc ctgtaatttg ggaaatacag


 


8281
aaagaaaaga aaaaaaaaaa aaaaggcagc ctgtgcagtc ttagtaactt tagtattaag


 


8341
agcacttaaa gtcaaactga caattttggg cttattacaa aatgtgatgc tttaaagcac


 


8401
acgttcttta ttgttgttgt aattagtcca taaaaaatat agctttcgga agaattaagt


 


8461
acccaccata tcatttatgt atttgtgtat gttttacggg agatcaaacc actctcgtgg


 


8521
tgccgcatcc gtactcgctt gacttggaag aaatatcaca agcactaaag tatatcaggg


 


8581
catcccagga ttgggtactg tatcctaggt ttgcagttgc agaaattagc atctagtgtc


 


8641
acaggtaaaa gaatttcagg accaggttta aactttattt taaatatttt tatacttagg


 


8701
tctctttttc ctgcctctcc ccaaagaaga gccactggcc ttagttgttt gagcttactg


 


8761
cttatattat agagtgtaaa taggtaacta gagactaaaa ttttattaac cagcatgttt


 


8821
ggtatattta aagcagtgac tgagtgtgtt tgagtgagtg gctgagtgca gtgtcttttg


 


8881
tttaaacaca ctgcctcgtg tctttgtagc tgattcagag agtttgaatt gtggggtggg


 


8941
agactaactt cagctccagg ctgcagtaat gtgttggtag ttacacttga ggcatttttt


 


9001
tgttgttgtt aattaactct atagtctcaa actatttttg caaatatatc atttttccta


 


9061
attggttctt gacgtgcagt ggactggctc tgtgaatgat tggcagggtc ttagttttgc


 


9121
gagagtattt ccttctaaga attattgtga tctgcagaaa cagccatttg attcaaaaat


 


9181
catgtagaaa aggagtagga gaagcaaaac gtttcatttt tgggccttaa ccatttgaaa


 


9241
tgtttggact ttaaacataa agccatggag tttataaagc caagtaacca tttgatatgg


 


9301
ataataatat ctactctaga gagagtatat atatgcacat tgatttttaa tgctgttaag


 


9361
atacttttgt aaaactgtag gaacaagagt aattagacca aattgaagct taggggacag


 


9421
taaagtggtt gctttccatt tagggtaacc atgcatgtgg ttagtcctct cctcctgaga


 


9481
ttcagaacca gttgactgtc cccttaggtg tataaggaga aaagttgaca tgtctgggac


 


9541
ctctgacatg tgtacacatg cttgcacaca tgcacacaca gtgaatgttt taagttatac


 


9601
aaacataaga ccttaagatg caaagagcca gaatattcta aagaggtgat gaacagaggg


 


9661
ggtggaaact gcatcacaga tgttttccaa gggccagggt ggaatctgag ctctagtgtc


 


9721
tgactttgag atgcattata tttttaacac ataaatgagg ggatccatat cacattcttt


 


9781
cttgtggacc accaaattga aggctttctt gtaattcaca agcagcagct ctccagcatc


 


9841
tctccgtagc ctgggtgaag tcccagaagc tggtgtgcat cattttccaa ggtggcagag


 


9901
ctgcttgctc tgcagatcat tcctttgaga gaggagtaca agtgaagaaa caaggaggca


 


9961
cttcctgtag gagcactgat gtgccttgtc cacactcccc tctgagcttt actggtaaga


 


10021
gagctccgac tgaacatgct gagcagttga gcacttttcc atcagcaaca acagcgagga


 


10081
tggaaatgga aaggaaccga actaaaatgc atttcccttt gcagggcaga gagctaagct


 


10141
cttaggaata gtgttataga aataagcacc ctaacttcaa ttcctgaaaa tgttggttaa


 


10201
tggagagaat tttggagttt cacttaatat tttcccatcg gtcgccataa ataagtcttc


 


10261
aggcgctcct agaagagtcc cagcccaagg ctcgattaag gaccacactg caggtctgag


 


10321
gctcactgct ctgagtcctg aacaccagag ccctgcagag agtggtgata acacatcatc


 


10381
tctgcaaaga ggaacctctc ccccggccgc cacttcactc aggcttctac tgagcagcaa


 


10441
ggacagcctg ggtttcaaat gccacttccc ctgctttagg gatccaggtg tcctgatagc


 


10501
gtgaccctgc tgaggcaagg tatcaactcc gagagtgact gagtcactga gcgtggcaca


 


10561
tgaacaaacg tcatgacaaa gattctctga gtgaagttaa caccacgtat tttacctttg


 


10621
caaaaaacaa actggcaccc tgagttctaa ctacggacgg acgatatctt tgcctccaca


 


10681
cccagattcc tggaaatggc taacgtttcc tttctagggg aagggtcgag gaatactcaa


 


10741
gtgctagctt agcagctttg ttcagtccag atcagagctg ttaggtaaag gcctaaccac


 


10801
ctccctgcag tctcttatat ctcaagcttt aggaacccat ttctaaatgt acactagcgg


 


10861
agaatttata ttgtcagcct tgattaccat aggacaggca gaaaggcgat aatttgtatc


 


10921
ttttaatata aaagaagctt ttaacttttc cagcctatta taataactga gttatattca


 


10981
ctgtggctca aactaattgg cattgtggaa catttcttta ccttcaaagt tttctccacc


 


11041
aatcatttca gttctattgc agtcctggtg ccatatgtcc cctgcaaatt gtgaaagtaa


 


11101
ttagtgacaa aatagcagcc tgctcctttt caatggcgaa actgtcggca ttagcagttt


 


11161
tgggtaagct ggcggtacta taacacgtac tggaaacctg ttcctcatca ccacctacca


 


11221
gattctggaa atgccgtctt ctagaaaacg atggcgtttg tggtggtctt cttttgaaag


 


11281
gaacagtaat ttgtgtggat attgttaaag tgtttaaaga atattttgac aattaagttt


 


11341
acattttaca attgctttat tttttattaa aatagttgta tataaatatt accctatttc


 


11401
actgttgttc aagtaaatct aaaccttgta gacaagtgag tcatctgata tgtatagaag


 


11461
ctgtgatata tagagtacat ttattgtgta aatgtttatg aatataattg ttcctgtgtt


 


11521
tttataagtt ggggatattt tgttgtttta cggcaacaaa atttattgca tttaaatggt


 


11581
ttttatgtaa tagaaatcac gcaaaatagt gaaggattta aaatatgtat atgatacatg


 


11641
taaatgtaca aactttagaa agaaataaat ccaacaaatt tcaatca






One example of a nucleic acid sequence for human QPCT is available as NCBI accession number NM_012413 (gi: 68216098). This sequence is recited below for easy reference as SEQ ID NO:157.









1
ggcgatggga aggcgggcgc agtcgaccca agggtggaga agagggaagg cgaaggacgc



 


61
gcgttcccgg gctcgtgacc gccagcggcc cggggaaccc gctcccagac agactcggag


 


121
agatggcagg cggaagacac cggcgcgtcg tgggcaccct ccacctgctg ctgctggtgg


 


181
ccgccctgcc ctgggcatcc aggggggtca gtccgagtgc ctcagcctgg ccagaggaga


 


241
agaattacca ccagccagcc attttgaatt catcggctct tcggcaaatt gcagaaggca


 


301
ccagtatctc tgaaatgtgg caaaatgact tacagccatt gctgatagag cgatacccgg


 


361
gatcccctgg aagctatgct gctcgtcagc acatcatgca gcgaattcag aggcttcagg


 


421
ctgactgggt cttggaaata gacaccttct tgagtcagac accctatggg taccggtctt


 


481
tctcaaatat catcagcacc ctcaatccca ctgctaaacg acatttggtc ctcgcctgcc


 


541
actatgactc caagtatttt tcccactgga acaacagagt gtttgtagga gccactgatt


 


601
cagccgtgcc atgtgcaatg atgttggaac ttgctcgtgc cttagacaag aaactccttt


 


661
ccttaaagac tgtttcagac tccaagccag atttgtcact ccagctgatc ttctttgatg


 


721
gtgaagaggc ttttcttcac tggtctcctc aagattctct ctatgggtct cgacacttag


 


781
ctgcaaagat ggcatcgacc ccgcacccac ctggagcgag aggcaccagc caactgcatg


 


841
gcatggattt attggtctta ttggatttga ttggagctcc aaacccaacg tttcccaatt


 


901
tttttccaaa ctcagccagg tggttcgaaa gacttcaagc aattgaacat gaacttcatg


 


961
aattgggttt gctcaaggat cactctttgg aggggcggta tttccagaat tacagttatg


 


1021
gaggtgtgat tcaggatgac catattccat ttttaagaag aggtgttcca gttctgcatc


 


1081
tgataccgtc tcctttccct gaagtctggc acaccatgga tgacaatgaa gaaaatttgg


 


1141
atgaatcaac cattgacaat ctaaacaaaa tcctacaagt ctttgtgttg gaatatcttc


 


1201
atttgtaata ctctgattta gtttaggata attggttcta gaattgaatt caaaagtcaa


 


1261
ggcatcattt aaaataatct gatttcagac aaatgctgtg tggaaacatc tatcctatag


 


1321
atcatcctat tcttatgtgt ctttggttat cagatcaatt acagaataat tgtgttgtga


 


1381
tattgtgtcc taaattgctc attaattttt atttacagat tgaaaaagag ggaccgtgta


 


1441
aagaaaatgg aaaataaata tctttcaaag actcttttag ataaacacga tgaggcaaaa


 


1501
tcaggttcat tcattcaacg atagtttctc aacagtactt aaatagcggt tggaaaacgt


 


1561
agccttcatt ttatgatttt ttcatatgtg gaaatctatt acatgtaata caaaacaaac


 


1621
atgtagtttg aaggcggtca gatttctttg agaaatcttt gtagagttaa ttttatggaa


 


1681
attaaaatca gaattaaatg ctaaaaaaaa aaaaaaaaa






One example of a nucleic acid sequence for human RAB27A is available as NCBI accession number NM_004580 (gi: 34485707). This sequence is recited below for easy reference as SEQ ID NO:158.









1
gttttgaaag ttgatggagc gaactgcttt tccaaagact cttttgaaaa actttttaag



 


61
taggccattc tgactttaac atttctcttt gtcttaacat tagacaaaaa gtaaccttcc


 


121
tgaagaggac atgtgattgg aagttgtcaa ttgttgaagc attggtaact ccagtctcta


 


181
acgttttaga aaatcataac aagcggttct ctaccctgta aaggtgaact actgagttct


 


241
tcattatgtc tgatggagat tatgattacc tcatcaagtt tttagctttg ggagactctg


 


301
gtgtagggaa gaccagtgta ctttaccaat atacagatgg taaatttaac tccaaattta


 


361
tcacaacagt gggcattgat ttcagggaaa aaagagtggt gtacagagcc agtgggccgg


 


421
atggagccac tggcagaggc cagagaatcc acctgcagtt atgggacaca gcagggcagg


 


481
agaggtttcg tagcttaacg acagcgttct tcagagatgc tatgggtttt cttctacttt


 


541
ttgatctgac aaatgagcaa agtttcctca atgtcagaaa ctggataagc cagctacaga


 


601
tgcatgcata ttgtgaaaac ccagatatag tgctgtgtgg aaacaagagt gatctggagg


 


661
accagagagt agtgaaagag gaggaagcca tagcactcgc agagaaatat ggaatcccct


 


721
actttgaaac tagtgctgcc aatgggacaa acataagcca agcaattgag atgcttctgg


 


781
acctgataat gaagcgaatg gaacggtgtg tggacaagtc ctggattcct gaaggagtgg


 


841
tgcgatcaaa tggtcatgcc tctacggatc agttaagtga agaaaaggag aaaggggcat


 


901
gtggctgttg agaagtcaag taagcgacat agtagttcag gtggcccatg cctgggatct


 


961
tctctatgat tgatacatgg cacagtgaga gattaatggg cattgtgtac aaattgcttc


 


1021
tcaccatccc cattagacct acgaataaag catccggttc taaaattaat ttgttgcagc


 


1081
tttgtaaata tttctttaag attcagcctg agagttagga gaaatatttc agagccaaaa


 


1141
gtgccttata caaccttagc ctattatagt aaatcattca aggattcaga attttgcagt


 


1201
cacagaagag tgtatttatt atgtagaatg aatgagggta ctgtcacctg ccttaatgta


 


1261
ggtaggccca gagtcttaca tttaagatct tacatgcagt tataaaaccg ccacagtctt


 


1321
caatccagat ttgaagactc atgccatagg tgacattcta aaataccatt aaagccactt


 


1381
aaatgttaaa taagaatata catgcacatc agctcaatgt ctttgagtat taattttatg


 


1441
taagcattct atttaacatg aatataggac aaatcatggc tatatctata gaccttggat


 


1501
aaactggatt gaccaattat acactcacgg tgactttttt attggtggga aggggattgg


 


1561
ggtggggcag gctggcttaa tgtaatatga gcaaccaaag tgggacttct gtctccccgc


 


1621
tatattccca ttgctctgaa tggttgattg aagggtcagg gaactagatt ttatggcttt


 


1681
agttcactgt gattgtacat ttatacttgg cctatgtgct ggccgcacct gaacatagct


 


1741
ggtgcttatg ccgagttatt tgcgatgagt aaatatttag tttctttttc ttcatattta


 


1801
taatgttgat ctggcatcct caggctgcag ctttattagc ttataactta ctcatctcta


 


1861
tctttaccag caggctctgt attgttgata tttgcaactt gttttgcttt tccattggtg


 


1921
gaattgaaat aattagtttt taattacata agatgcctgt ttgctatttg gtggaagata


 


1981
gatgttcata ttgaagcagt cacatttgta ctgtagttca ataaaagaaa aatgaagtat


 


2041
tctgtagcct atatttttca tagagctcat gagcatttac tgtacttgct gggtcttgcc


 


2101
aagatcattt attccgctgc attgccaaag tgtcttcata ccaaattaaa ggtggtttta


 


2161
atatatgttt catggaagtt gtttataaaa ttcaaaggta tttcatttag gtgaaaagtc


 


2221
ttatttatta aagtggtttg aataaagtag atcaaaactt ccagagatct taatggctat


 


2281
ataggaagaa atatcactca ccataattta aataaagaat aaaaatactt gtattttgtg


 


2341
gtggcaaatg tttggtagaa ctgtaattag aaaaatacaa gtatatttgc gtgatggtta


 


2401
cactagaagc ccagacttta cgactacaca atatattcat gtatctaaac tgtacttgta


 


2461
ccccctaaat ttatttttaa aaaaggaaaa ataaaagtat catgaaaaaa cctatttttt


 


2521
tttccactgt ccttccacta ctcccataac aaacttatcc atggttggta aaattttaca


 


2581
tatttctatc cttgaaatga aggcttcttt taaattccaa agaagtcatg gaggcctgtg


 


2641
catttgaatt gtatatgcta gtgaggaaaa gatttagaca tttcaagagc agggttggcc


 


2701
aggcgcggtg gctcacacct gtaatcccag cactttggga ggccgaggag ggcggatcac


 


2761
gaggtcagga gatcgagacc atcctggcta acacagtgaa accccatctc tactaaaaaa


 


2821
aaaa






One example of a nucleic acid sequence for human RXRG is available as NCBI accession number NM_006917 (gi: 58331205). This sequence is recited below for easy reference as SEQ ID NO:159.









1
gtggcaagag tagcggtgac ggcggcggcg gcggcggcgg cagcattatg cgtgattact



 


61
gacaggcacc agctgctgcc gccacagccg tctcaaacgc actatgtgga ctctccgatc


 


121
tagaggcaga ttcctgacta atcccagagg gctggcccag cctgtgctcc ccgggctgct


 


181
aggaagcgat gaccactctt gttagcccaa gttgaagaaa gccgggctgt gcctgggagc


 


241
cgagagaggc ggtaatattt agaagctgca caggagagga acatgaactg acgagtaaac


 


301
atgtatggaa attattctca cttcatgaag tttcccgcag gctatggagg ctcccctggc


 


361
cacactggct ctacatccat gagcccatca gcagccttgt ccacagggaa gccaatggac


 


421
agccacccca gctacacaga taccccagtg agtgccccac ggactctgag tgcagtgggg


 


481
acccccctca atgccctggg ctctccatat cgagtcatca cctctgccat gggcccaccc


 


541
tcaggagcac ttgcagcgcc tccaggaatc aacttggttg ccccacccag ctctcagcta


 


601
aatgtggtca acagtgtcag cagttcagag gacatcaagc ccttaccagg gcttcccggg


 


661
attggaaaca tgaactaccc atccaccagc cccggatctc tggttaaaca catctgtgcc


 


721
atctgtggag acagatcctc aggaaagcac tacggggtat acagttgtga aggctgcaaa


 


781
gggttcttca agaggacgat aaggaaggac ctcatctaca cgtgtcggga taataaagac


 


841
tgcctcattg acaagcgtca gcgcaaccgc tgccagtact gtcgctatca gaagtgcctt


 


901
gtcatgggca tgaagaggga agctgtgcaa gaagaaagac agaggagccg agagcgagct


 


961
gagagtgagg cagaatgtgc taccagtggt catgaagaca tgcctgtgga gaggattcta


 


1021
gaagctgaac ttgctgttga accaaagaca gaatcctatg gtgacatgaa tatggagaac


 


1081
tcgacaaatg accctgttac caacatatgt catgctgctg acaagcagct tttcaccctc


 


1141
gttgaatggg ccaagcgtat tccccacttc tctgacctca ccttggagga ccaggtcatt


 


1201
ttgcttcggg cagggtggaa tgaattgctg attgcctctt tctcccaccg ctcagtttcc


 


1261
gtgcaggatg gcatccttct ggccacgggt ttacatgtcc accggagcag tgcccacagt


 


1321
gctggggtcg gctccatctt tgacagagtc ctaactgagc tggtttccaa aatgaaagac


 


1381
atgcagatgg acaagtcgga actgggatgc ctgcgagcca ttgtactctt taacccagat


 


1441
gccaagggcc tgtccaaccc ctctgaggtg gagactctgc gagagaaggt ttatgccacc


 


1501
cttgaggcct acaccaagca gaagtatccg gaacagccag gcaggtttgc caagctgctg


 


1561
ctgcgcctcc cagctctgcg ttccattggc ttgaaatgcc tggagcacct cttcttcttc


 


1621
aagctcatcg gggacacccc cattgacacc ttcctcatgg agatgttgga gaccccgctg


 


1681
cagatcacct gagccccacc agccacagcc tccccaccca ggatgacccc tgggcaggtg


 


1741
tgtgtggacc cccaccctgc actttcctcc acctcccacc ctgaccccct tcctgtcccc


 


1801
aaaatgtgat gcttataata aagaaaacct ttctacacat gaaaaaaaaa aaaaaa






One example of a nucleic acid sequence for human SDC4 is available as NCBI accession number NM_002999 (gi: 38201674). This sequence is recited below for easy reference as SEQ ID NO:160.









1
actcgccgca gcctgcgcgc cttctccagt ccgcggtgcc atggcccccg cccgtctgtt



 


61
cgcgctgctg ctgttcttcg taggcggagt cgccgagtcg atccgagaga ctgaggtcat


 


121
cgacccccag gacctcctag aaggccgata cttctccgga gccctaccag acgatgagga


 


181
tgtagtgggg cccgggcagg aatctgatga ctttgagctg tctggctctg gagatctgga


 


241
tgacttggaa gactccatga tcggccctga agttgtccat cccttggtgc ctctagataa


 


301
ccatatccct gagagggcag ggtctgggag ccaagtcccc accgaaccca agaaactaga


 


361
ggagaatgag gttatcccca agagaatctc acccgttgaa gagagtgagg atgtgtccaa


 


421
caaggtgtca atgtccagca ctgtgcaggg cagcaacatc tttgagagaa cggaggtcct


 


481
ggcagctctg attgtgggtg gcatcgtggg catcctcttt gccgtcttcc tgatcctact


 


541
gctcatgtac cgtatgaaga agaaggatga aggcagctat gacctgggca agaaacccat


 


601
ctacaagaaa gcccccacca atgagttcta cgcgtgaagc ttgcttgtgg gcactggctt


 


661
ggactttagc ggggagggaa gccaggggat tttgaagggt ggacattagg gtagggtgag


 


721
gtcaacctaa tactgacttg tcagtatctc cagctctgat tacctttgaa gtgttcagaa


 


781
gagacattgt cttctactgt tctgccaggt tcttcttgag ctttgggcct cagttgccct


 


841
ggcagaaaaa tggattcaac ttggcctttc tgaaggcaag actgggattg gatcacttct


 


901
taaacttcca gttaagaatc taggtccgcc ctcaagccca tactgaccat gcctcatcca


 


961
gagctcctct gaagccaggg ggctaacgga tgttgtgtgg agtcctggct ggaggtcctc


 


1021
ccccagtggc cttcctccct tcctttcaca gccggtctct ctgccaggaa atgggggaag


 


1081
gaactagaac cacctgcacc ttgagatgtt tctgtaaatg ggtacttgtg atcacactac


 


1141
gggaatctct gtggtatata cctggggcca ttctaggctc tttcaagtga cttttggaaa


 


1201
tcaacctttt ttatttgggg gggaggatgg ggaaaagagc tgagagttta tgctgaaatg


 


1261
gatttataga atatttgtaa atctattttt agtgtttgtt cgttttttta actgttcatt


 


1321
cctttgtgca gagtgtatat ctctgcctgg gcaagagtgt ggaggtgccg aggtgtcttc


 


1381
attctctcgc acatttccac agcacctgct aagtttgtat ttaatggttt ttgtttttgt


 


1441
ttttgtttgt ttcttgaaaa tgagagaaga gccggagaga tgatttttat taattttttt


 


1501
tttttttttt tttttttact atttatagct ttagataggg cctcccttcc cctcttcttt


 


1561
ctttgttctc tttcattaaa ccccttcccc agtttttttt ttatacttta aaccccgctc


 


1621
ctcatggcct tggccctttc tgaagctgct tcctcttata aaatagcttt tgccgaaaca


 


1681
tagttttttt ttagcagatc ccaaaatata atgaagggga tggtgggata tttgtgtctg


 


1741
tgttcttata atatattatt attcttcctt ggttctagaa aaatagataa atatattttt


 


1801
ttcaggaaat agtgtggtgt ttccagtttg atgttgctgg gtggttgagt gagtgaattt


 


1861
tcatgtggct gggtgggttt ttgccttttt ctcttgccct gttcctggtg ccttctgatg


 


1921
gggctggaat agttgaggtg gatggttcta ccctttctgc cttctgtttg ggacccagct


 


1981
ggtgttcttt ggtttgcttt cttcaggctc tagggctgtg ctatccaata cagtaaccac


 


2041
atgcggctgt ttaaagttaa gccaattaaa atcacataag attaaaaatt ccttcctcag


 


2101
ttgcactaac cacgtttcta gaggcgtcac tgtatgtagt tcatggctac tgtactgaca


 


2161
gcgagagcat gtccatctgt tggacagcac tattctagag aactaaactg gcttaacgag


 


2221
tcacagcctc agctgtgctg ggacgaccct tgtctccctg ggtagggggg ggggaatggg


 


2281
ggagggctga tgaggcccca gctggggcct gttgtctggg accctccctc tcctgagagg


 


2341
ggaggcctgg tggcttagcc tgggcaggtc gtgtctcctc ctgaccccag tggctgcggt


 


2401
gaggggaacc accctccctt gctgcaccag tggccattag ctcccgtcac cactgcaacc


 


2461
cagggtccca gctggctggg tcctcttctg cccccagtgc ccttcccctt gggctgtgtt


 


2521
ggagtgagca cctcctctgt aggcacctct cacactgttg tctgttactg attttttttg


 


2581
ataaaaagat aataaaacct ggtactttct aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa






One example of a nucleic acid sequence for human SERPINA1 is available as NCBI accession number NM_001127707 (gi: 189163541). This sequence is recited below for easy reference as SEQ ID NO:161.









1
tgggcaggaa ctgggcactg tgcccagggc atgcactgcc tccacgcagc aaccctcaga



 


61
gtcctgagct gaaccaagaa ggaggagggg gtcgggcctc cgaggaaggc ctagccgctg


 


121
ctgctgccag gaattccagg ttggaggggc ggcaacctcc tgccagcctt caggccactc


 


181
tcctgtgcct gccagaagag acagagcttg aggagagctt gaggagagca ggaaagcctc


 


241
ccccgttgcc cctctggatc cactgcttaa atacggacga ggacagggcc ctgtctcctc


 


301
agcttcaggc accaccactg acctgggaca gtgaatcgac aatgccgtct tctgtctcgt


 


361
ggggcatcct cctgctggca ggcctgtgct gcctggtccc tgtctccctg gctgaggatc


 


421
cccagggaga tgctgcccag aagacagata catcccacca tgatcaggat cacccaacct


 


481
tcaacaagat cacccccaac ctggctgagt tcgccttcag cctataccgc cagctggcac


 


541
accagtccaa cagcaccaat atcttcttct ccccagtgag catcgctaca gcctttgcaa


 


601
tgctctccct ggggaccaag gctgacactc acgatgaaat cctggagggc ctgaatttca


 


661
acctcacgga gattccggag gctcagatcc atgaaggctt ccaggaactc ctccgtaccc


 


721
tcaaccagcc agacagccag ctccagctga ccaccggcaa tggcctgttc ctcagcgagg


 


781
gcctgaagct agtggataag tttttggagg atgttaaaaa gttgtaccac tcagaagcct


 


841
tcactgtcaa cttcggggac accgaagagg ccaagaaaca gatcaacgat tacgtggaga


 


901
agggtactca agggaaaatt gtggatttgg tcaaggagct tgacagagac acagtttttg


 


961
ctctggtgaa ttacatcttc tttaaaggca aatgggagag accctttgaa gtcaaggaca


 


1021
ccgaggaaga ggacttccac gtggaccagg tgaccaccgt gaaggtgcct atgatgaagc


 


1081
gtttaggcat gtttaacatc cagcactgta agaagctgtc cagctgggtg ctgctgatga


 


1141
aatacctggg caatgccacc gccatcttct tcctgcctga tgaggggaaa ctacagcacc


 


1201
tggaaaatga actcacccac gatatcatca ccaagttcct ggaaaatgaa gacagaaggt


 


1261
ctgccagctt acatttaccc aaactgtcca ttactggaac ctatgatctg aagagcgtcc


 


1321
tgggtcaact gggcatcact aaggtcttca gcaatggggc tgacctctcc ggggtcacag


 


1381
aggaggcacc cctgaagctc tccaaggccg tgcataaggc tgtgctgacc atcgacgaga


 


1441
aagggactga agctgctggg gccatgtttt tagaggccat acccatgtct atcccccccg


 


1501
aggtcaagtt caacaaaccc tttgtcttct taatgattga acaaaatacc aagtctcccc


 


1561
tcttcatggg aaaagtggtg aatcccaccc aaaaataact gcctctcgct cctcaacccc


 


1621
tcccctccat ccctggcccc ctccctggat gacattaaag aagggttgag ctggtccctg


 


1681
cctgcatgtg actgtaaatc cctcccatgt tttctctgag tctccctttg cctgctgagg


 


1741
ctgtatgtgg gctccaggta acagtgctgt cttcgggccc cctgaactgt gttcatggag


 


1801
catctggctg ggtaggcaca tgctgggctt gaatccaggg gggactgaat cctcagctta


 


1861
cggacctggg cccatctgtt tctggagggc tccagtcttc cttgtcctgt cttggagtcc


 


1921
ccaagaagga atcacagggg aggaaccaga taccagccat gaccccaggc tccaccaagc


 


1981
atcttcatgt ccccctgctc atcccccact cccccccacc cagagttgct catcctgcca


 


2041
gggctggctg tgcccacccc aaggctgccc tcctgggggc cccagaactg cctgatcgtg


 


2101
ccgtggccca gttttgtggc atctgcagca acacaagaga gaggacaatg tcctcctctt


 


2161
gacccgctgt cacctaacca gactcgggcc ctgcacctct caggcacttc tggaaaatga


 


2221
ctgaggcaga ttcttcctga agcccattct ccatggggca acaaggacac ctattctgtc


 


2281
cttgtccttc catcgctgcc ccagaaagcc tcacatatct ccgtttagaa tcaggtccct


 


2341
tctccccaga tgaagaggag ggtctctgct ttgttttctc tatctcctcc tcagacttga


 


2401
ccaggcccag caggccccag aagaccatta ccctatatcc cttctcctcc ctagtcacat


 


2461
ggccataggc ctgctgatgg ctcaggaagg ccattgcaag gactcctcag ctatgggaga


 


2521
ggaagcacat cacccattga cccccgcaac ccctcccttt cctcctctga gtcccgactg


 


2581
gggccacatg cagcctgact tctttgtgcc tgttgctgtc cctgcagtct tcagagggcc


 


2641
accgcagctc cagtgccacg gcaggaggct gttcctgaat agcccctgtg gtaagggcca


 


2701
ggagagtcct tccatcctcc aaggccctgc taaaggacac agcagccagg aagtcccctg


 


2761
ggcccctagc tgaaggacag cctgctccct ccgtctctac caggaatggc cttgtcctat


 


2821
ggaaggcact gccccatccc aaactaatct aggaatcact gtctaaccac tcactgtcat


 


2881
gaatgtgtac ttaaaggatg aggttgagtc ataccaaata gtgatttcga tagttcaaaa


 


2941
tggtgaaatt agcaattcta catgattcag tctaatcaat ggataccgac tgtttcccac


 


3001
acaagtctcc tgttctctta agcttactca ctgacagcct ttcactctcc acaaatacat


 


3061
taaagatatg gccatcacca agccccctag gatgacacca gacctgagag tctgaagacc


 


3121
tggatccaag ttctgacttt tccccctgac agctgtgtga ccttcgtgaa gtcgccaaac


 


3181
ctctctgagc cccagtcatt gctagtaaga cctgcctttg agttggtatg atgttcaagt


 


3241
tagataacaa aatgtttata cccattagaa cagagaataa atagaactac atttcttgca






One example of a nucleic acid sequence for human SLC25A15 is available as NCBI accession number NM_014252 (gi: 237649033). This sequence is recited below for easy reference as SEQ ID NO:162.









1
tgggggcggt ggcagggccg gtgggcggtg gcggctcccg gtctcggctc gggcacggcc



 


61
ctgggcaggc cgcccgccag ccgcaggggc gctcctgagc ttcgcggggc cgcagtccgg


 


121
gatgcctgcg cgaagggagg ggcgaagggc cggccgttgc cgacgtgggt gttaagtggc


 


181
cgccccagcc ggcgacccgg agccgagagc gggcggcgga gcctgagctg gacgcggcca


 


241
cgccggcgcg gcgggatatg tggtgcctgt cataagctcc agagagctgc cttccacaag


 


301
accagcagaa gagtgggcaa acatgaaatc caatcctgct atccaggctg ccattgacct


 


361
cacagcgggg gctgcaggag gtacagcatg tgtactgacc gggcagccct ttgacacaat


 


421
gaaagtgaag atgcagacgt tccctgacct gtaccggggc ctcaccgact gctgcctgaa


 


481
gacttactcc caggtgggct tccgtggctt ctacaagggt accagtccag cactaatcgc


 


541
caacatcgct gagaactcag tcctcttcat gtgctacggc ttctgccagc aggtggtgcg


 


601
gaaagtggct ggattggaca agcaggcaaa gctgagtgat ctgcagaatg cagccgccgg


 


661
ttccttcgcc tctgcctttg ctgcactggt gctctgcccc acggagctcg tgaagtgccg


 


721
gctgcagacc atgtatgaga tggagacatc agggaagata gccaagagcc agaatacagt


 


781
gtggtctgtc atcaaaagta ttcttaggaa agatggcccc ttggggttct accatggact


 


841
ctcaagcact ttacttcgag aagtaccagg ctatttcttc ttcttcggtg gctatgaact


 


901
gagccggtcc ttttttgcat cagggagatc aaaagatgaa ttaggccctg tacctttgat


 


961
gttaagtggt ggagttggtg ggatttgcct ctggcttgcg gtatacccag tggattgtat


 


1021
caaatccaga attcaagttc tttccatgtc tggaaaacag gcaggattta tcagaacctt


 


1081
tataaatgtt gtgaaaaatg aaggaataac ggccttatat tctggactga aacctactat


 


1141
gattcgagca ttccctgcca atggagcact ctttttggcc tacgaatata gcaggaagtt


 


1201
gatgatgaac cagttggaag catactgaag tgtcttggtg ggcctgagcc aagcacaggt


 


1261
gtttgaggac tacagttcat ctcagggttt cttggagtac aagaccagtg tgaagttatt


 


1321
ctgatttctt gggaattttg ctttttgtct tcccttctac cctacatctt aaactttatg


 


1381
gaagaacctc tattttgcat catatcattt ctgtccataa ttgtactgaa atagaaaagt


 


1441
gaccgctctt gctcttggta aaatatagag tggtcagtag ccttatgcac ctaattcaaa


 


1501
aggtggaata tagttctgtc agggctttta cgtaaacctc cacttgtaca tgcaatttgg


 


1561
acagttatgt gttgagggaa atacagtttg gtaccttgtt tatttcaaat atcagaaaaa


 


1621
cccagaggtg atcatttctc atgaagatgc ttataaatgg ttgcttaacc cattctagat


 


1681
gtagggtctg cttaatgtgt gtacttttct aagtggttga ttatttttta tttttttgat


 


1741
acagagtctc actctgtcac ccagactgga gtgcagtggc acgatctcgg ctcactgcaa


 


1801
cctccgcctc ctgggttcaa gcgattctct cacctcagcc tcctgagtag ctgggattac


 


1861
aggtacgcgc caccatgtcc agctaatttt ttttggtatt ttttgtagag acgaggtttc


 


1921
accatgttgt ccaggttggt ctcgaactcc tgacctcaag tgatccgccc acctcggcct


 


1981
cccaaagtgc tgggattact ggtgtgagcc accatgccca gccagtggtt gaatttttta


 


2041
aaaagtgttc atggggtgct tgaaaactaa aatatccttc tagatttgta agacagtata


 


2101
cctgcatact ggtgtggctt ccacacttga gtaaaagctt cagagtaggt atcctagatt


 


2161
tccccaagat gctctactct taaaatagtg ccattcattt tctaggtggg atcatattcc


 


2221
acgctgacta tattgctagg ggtggcccag agggtcaggc ctttgggaaa tagcatggcc


 


2281
tttaccagct tcccttctct cccaaagaac ttcccttctt gggctttaga ttgaggaagg


 


2341
ggctgagtgg taggcggtgc tgctgtgctc tgatgaagac ccatgtggct agcaacagcg


 


2401
cttacctttt gtctctgggt cctggcctgg ggccatcaat ccactttggg ccactcactg


 


2461
tctgctctgc ctccaccaat cagaaaccct tccaaggaac agtgagagcc aaagccaaga


 


2521
gaagccttct tccctgtttg gtgattgtgt gacagtgggt gaacctctct cagagagaac


 


2581
tagaaagaac tcagtgcttg tactccacag tgagtaatgt caggtctgac ccatcctgaa


 


2641
gcctgtcttg ccatgctttt acagtgttgg aggcttctac atttggtact tgcagtcagt


 


2701
aagtcttaat gatgactgta tatgtgatat gagtttataa agcaatggaa cataagaaaa


 


2761
gcaattgtag gccaggcgca gtggctcacg cctataatcc cagcactttg ggaggctgag


 


2821
gcgggcgggt cacaaggtca ggagttcgag aacagcctga ccaacatggt gaaaccccat


 


2881
ctctactaaa aatacaaaaa ttagctgggc gtggtggcac gtgcctgtaa tcccagctac


 


2941
tcaggaggct gaggcaggag aatcgcttga acccgggagg cagaggttgc agtgaactga


 


3001
gattgtgcca ctgcactcca gactgggtga cacagcgaga cttcatctca aaaaaaaaaa


 


3061
gaaaagaaaa gcaattgtac ttcactatgc catatgtatg tattcactga ccaaaaattc


 


3121
actgaccaac caaccaaact ccacacttca tctgatcccc catagacttg gggatggaca


 


3181
gctgttcttt ggccatatgg tataagagga tcattcttgt cactacttaa gttagcctca


 


3241
tcattttgtg ctgctccaac accagcaggg tatctcccaa taaagtgttc ctaagcagcc


 


3301
tgtatactga gtgcaagcag gctatcaatt ttaataatag tccataccat gtatgtgttt


 


3361
ctgtcagcag aatgtacatg ttgtacaaaa cctccaggtt ccttaagctt tttgctgtcc


 


3421
atgaatcctc tgtggcaact gtaatcacag agccagaagc cagagggcca gggatatgag


 


3481
aggctgacaa acatcagggg acatctgggg aggagatccc tgtcatgtct cttgtgccat


 


3541
ggagctatta tggctggtct tccatttgct ttttctttaa gtgaaaacca tttttctact


 


3601
ttgcttttct ctccatactt aaatggtcag tagctactga gtggtgcttt atctgaatag


 


3661
gcctggatcg aagtaaaata gaaatgggac tggctttcca caggaagtaa actgcttcag


 


3721
agcccacagt cccctgctca gtgtccggaa agaagtcagt catccctgtt ggcagtaaat


 


3781
cttcccacag gccgtccatt agagatttaa ctagatatgt tcaatagaaa gagtctgagg


 


3841
caagtggaaa tgaggaacgg aaacttaggt tgggagaata tttttttttt attcattctg


 


3901
tttgcttaat tcagagtaca gtttgtgcta tttcatatct gtactccagg cagaaatata


 


3961
acttgaaaat actgtgtcta aagaaatttc agtgttctat cattaaatta tttacttaat


 


4021
aaaaaaaaaa aaaaaaaa






One example of a nucleic acid sequence for human SLC4A4 is available as NCBI accession number NM_001098484 (gi: 197927157). This sequence is recited below for easy reference as SEQ ID NO:163.









1
gcggcggcgg ccgcggtggc agcgaaggcg gcggcggcgg cggcagtggc agtggccgct



 


61
gcagccccac actccgccgc caaactggag gagcgacgga agccagaccc caggaggatg


 


121
gaggatgaag ctgtcctgga cagaggggct tccttcctca agcatgtgtg tgatgaagaa


 


181
gaagtagaag gccaccatac catttacatc ggagtccatg tgccgaagag ttacaggaga


 


241
aggagacgtc acaagagaaa gacagggcac aaagaaaaga aggaaaagga gagaatctct


 


301
gagaactact ctgacaaatc agatattgaa aatgctgatg aatccagcag cagcatccta


 


361
aaacctctca tctctcctgc tgcagaacgc atccgattca tcttgggaga ggaggatgac


 


421
agcccagctc cccctcagct cttcacggaa ctggatgagc tgctggccgt ggatgggcag


 


481
gagatggagt ggaaggaaac agccaggtgg atcaagtttg aagaaaaagt ggaacagggt


 


541
ggggaaagat ggagcaagcc ccatgtggcc acattgtccc ttcatagttt atttgagctg


 


601
aggacatgta tggagaaagg atccatcatg cttgatcggg aggcttcttc tctcccacag


 


661
ttggtggaga tgattgttga ccatcagatt gagacaggcc tattgaaacc tgaacttaag


 


721
gataaggtga cctatacttt gctccggaag caccggcatc aaaccaagaa atccaacctt


 


781
cggtccctgg ctgacattgg gaagacagtc tccagtgcaa gtaggatgtt taccaaccct


 


841
gataatggta gcccagccat gacccatagg aatctgactt cctccagtct gaatgacatt


 


901
tctgataaac cggagaagga ccagctgaag aataagttca tgaaaaaatt gccacgtgat


 


961
gcagaagctt ccaacgtgct tgttggggag gttgactttt tggatactcc tttcattgcc


 


1021
tttgttaggc tacagcaggc tgtcatgctg ggtgccctga ctgaagttcc tgtgcccaca


 


1081
aggttcttgt tcattctctt aggtcctaag gggaaagcca agtcctacca cgagattggc


 


1141
agagccattg ccaccctgat gtctgatgag gtgttccatg acattgctta taaagcaaaa


 


1201
gacaggcacg acctgattgc tggtattgat gagttcctag atgaagtcat cgtccttcca


 


1261
cctggggaat gggatccagc aattaggata gagcctccta agagtcttcc atcctctgac


 


1321
aaaagaaaga atatgtactc aggtggagag aatgttcaga tgaatgggga tacgccccat


 


1381
gatggaggtc acggaggagg aggacatggg gattgtgaag aattgcagcg aactggacgg


 


1441
ttctgtggtg gactaattaa agacataaag aggaaagcgc cattttttgc cagtgatttt


 


1501
tatgatgctt taaatattca agctctttcg gcaattctct tcatttatct ggcaactgta


 


1561
actaatgcta tcacttttgg aggactgctt ggggatgcca ctgacaacat gcagggcgtg


 


1621
ttggagagtt tcctgggcac tgctgtctct ggagccatct tttgcctttt tgctggtcaa


 


1681
ccactcacta ttctgagcag caccggacct gtcctagttt ttgagaggct tctatttaat


 


1741
ttcagcaagg acaataattt tgactatttg gagtttcgcc tttggattgg cctgtggtcc


 


1801
gccttcctat gtctcatttt ggtagccact gatgccagct tcttggttca atacttcaca


 


1861
cgtttcacgg aggagggctt ttcctctctg attagcttca tctttatcta tgatgctttc


 


1921
aagaagatga tcaagcttgc agattactac cccatcaact ccaacttcaa agtgggctac


 


1981
aacactctct tttcctgtac ctgtgtgcca cctgacccag ctaatatctc aatatctaat


 


2041
gacaccacac tggccccaga gtatttgcca actatgtctt ctactgacat gtaccataat


 


2101
actacctttg actgggcatt tttgtcgaag aaggagtgtt caaaatacgg aggaaacctc


 


2161
gtcgggaaca actgtaattt tgttcctgat atcacactca tgtcttttat cctcttcttg


 


2221
ggaacctaca cctcttccat ggctctgaaa aaattcaaaa ctagtcctta ttttccaacc


 


2281
acagcaagaa aactgatcag tgattttgcc attatcttgt ccattctcat cttttgtgta


 


2341
atagatgccc tagtaggcgt ggacacccca aaactaattg tgccaagtga gttcaagcca


 


2401
acaagtccaa accgaggttg gttcgttcca ccgtttggag aaaacccctg gtgggtgtgc


 


2461
cttgctgctg ctatcccggc tttgttggtc actatactga ttttcatgga ccaacaaatt


 


2521
acagctgtga ttgtaaacag gaaagaacat aaactcaaga aaggagcagg gtatcacttg


 


2581
gatctctttt gggtggccat cctcatggtt atatgctccc tcatggctct tccgtggtat


 


2641
gtagctgcta cggtcatctc cattgctcac atcgacagtt tgaagatgga gacagagact


 


2701
tctgcacctg gagaacaacc aaagtttcta ggagtgaggg aacaaagagt cactggaacc


 


2761
cttgtgttta ttctgactgg tctgtcagtc tttatggctc ccatcttgaa gtttataccc


 


2821
atgcctgtac tctatggtgt gttcctgtat atgggagtag catcccttaa tggtgtgcag


 


2881
ttcatggatc gtctgaagct gcttctgatg cctctgaagc atcagcctga cttcatctac


 


2941
ctgcgtcatg ttcctctgcg cagagtccac ctgttcactt tcctgcaggt gttgtgtctg


 


3001
gccctgcttt ggatcctcaa gtcaacggtg gctgctatca tttttccagt aatgatcttg


 


3061
gcacttgtag ctgtcagaaa aggcatggac tacctcttct cccagcatga cctcagcttc


 


3121
ctggatgatg tcattccaga aaaggacaag aaaaagaagg aggatgagaa gaaaaagaaa


 


3181
aagaagaagg gaagtctgga cagtgacaat gatgattctg actgcccata ctcagaaaaa


 


3241
gttccaagta ttaaaattcc aatggacatc atggaacagc aacctttcct aagcgatagc


 


3301
aaaccttctg acagagaaag atcaccaaca ttccttgaac gccacacatc atgctgataa


 


3361
aattcctttc cttcagtcac tcggtatgcc aagtcctcct agaactccag taaaagttgt


 


3421
gcctcaaatt agaatagaac ttgaacctga agacaatgat tatttctgga ggagcaaggg


 


3481
aacagaaact acattgtaac ctgtttgtct ttcttaaaac tgacatttgt tgttaatgtc


 


3541
atttgttttt gtttggctgt ttgtttattt tttaactttt atttcgtctc agtttttggt


 


3601
cacaggccaa ataatacagc gctctctctg cttctctctt gcatagatac aatcaagaca


 


3661
atagtgcacc gttccttaaa aacagcatct gaggaatccc ccttttgttc ttaaactttc


 


3721
agatgtgtcc tttgataacc aaattctgtc actcaagaca cagacacgca cagaccctgt


 


3781
cctttgcctc tattaagcag aggatggaag tattaaggat tttgtaacac cttttatgaa


 


3841
aatgttgaag gaacttaaaa ctttagcttt ggagctgtgc ttactggctt gtctttgtct


 


3901
ggtagaacaa accttgacct ccagacagag tcccttctca cttatagagc tctccaggac


 


3961
tggaaaaagt gctgctattt taacttgctc ttgcttgtaa atcctaatct tagagttatc


 


4021
aaaagaagaa aaaactgaag gtactttact ccctatagag aaaccattgc catcattgta


 


4081
gcaagtgctg gaatgtccct tttttcctat gcaacttttt ttaacccttt aatgaactta


 


4141
tctgttgagt acattgaaga atatttttct tcctagattt tgttgtttaa attatggggc


 


4201
ctaacctgcc acttattttt tgtcaatttt taaaactttt ttttaattac tgtaaagaaa


 


4261
atgaattttt tcctgcagca ggaaacatag ttttgagtag ttctacctct tatttgtagc


 


4321
tgccaggctt tctgtaaaaa ttgtattgta tataatgtga tttttacaca tacatacaca


 


4381
cacaaataca caatctctag ggtaagccag aaggcaagat cagattaaaa acaccatgtt


 


4441
tctaagcatc catttttccc tttctttaaa agaaacttaa ctgttctatg aaggagattg


 


4501
agggagaaga gacaaactcc tatgtcatga gaataaccga tgttctgata atagtagcat


 


4561
ctaggtacag atgctggttg tattaccacg tcaatgtcct atgcagtatt gttagacatt


 


4621
ttctcatttt gaaatatttg tgtgtttgtg tatgtgctct gtgccatggc tggtgtatat


 


4681
atgtgcaatg ttagaaggca aaagagtgat ggtaggcaga gggcaaagtc attgaatctc


 


4741
ttatgccagt tttcataaaa cccaaaccac atatgaaaaa atccattaag ggtccaagaa


 


4801
gtctgtccat atgaaaatga gggtaaatat agtttatttc ccaggtatca gtcattataa


 


4861
ttgatataat agctctaaca tgcaatataa aattcatagg agtattaata gcccatttac


 


4921
acatctataa aatgtaatgg gattgcagag ctgcagagta cagtgtaaca gtactctcat


 


4981
gcaatttttt tcaggatgca aaggcaatta ttctttgtaa gcgggacatt tagaatatat


 


5041
ttgtgtacat attatatgta tgtatatttc aaagtaccac actgaaaatt agacatttat


 


5101
taaccaaatt taacgtggta tttaaaggta atatttttaa tatgatacat tacatattgt


 


5161
gaatgtatac taaaaaaaca ttttaaatgt taaaattata atttcagatt catataacca


 


5221
caactgtgat atatcctaac tataaccagt tgttgagggg tatactagaa gcagaatgaa


 


5281
accacatttt ttggtttgat aatatgcact tattgactcc cactcattgt tatgttaatt


 


5341
aagttattat tctgtctcct tgtaattttg attacaaaaa ttttattatc ctgagttagc


 


5401
tgttactttt acagtacctg atactcctaa aacttttaac ttatacaaat tagtcaataa


 


5461
tgaccccaat tttttcatta aaataatagt ggtgaattat atgttattgt gttaaaacct


 


5521
cacttgccaa attctggctt cacatttgta tttagggcta tccttaaaat gatgagtcta


 


5581
tattatctag ctttctatta ccctaatata aactggtata agaagacttt ccttttttct


 


5641
ttatgcatgg aagcatcaat aaattgttta aaaaccatgt atagtaaatt cagcttaacc


 


5701
cgtgatcttc ttaagttaaa ggtacttttg ttttataaaa gctctagata aaactttctt


 


5761
ttctgatcat gaatcaagta tctgtggttt catgcccctc tctatacctt tcaaagaact


 


5821
cctgaagcaa cttaactcat catttcagcc tctgagtaga ggtaaaacct atgtgtactt


 


5881
ctgtttatga tccatattga tatttatgac atgaacacag aatagtacct tacatttgct


 


5941
aaacagacag ttaatatcaa atcctttcaa tattctggga acccagggaa gtttttaaaa


 


6001
atgtcattac tttcaaagga acagaagtag ttaaccaaac taacaagcaa aacctgaggt


 


6061
ttacctagtg acaccaaatt atcggtattt taactgaatt tacccattga ctaagaatga


 


6121
accagatttg gtggtggttt tgtttctatg caaactggac acaaattaca acagtaaatt


 


6181
tttttataag tgcttctccc ttctccatga tgtgacttcc ggagataaag gattcaaaag


 


6241
ataaagacaa agtacgctca gagttgttaa ccagaaagtc ctggctgtgg ttgcagaaac


 


6301
actgttggaa gaaaagagat gactaagtca agtgtctgcc ttatcaaaag agcaaaaatg


 


6361
cctctggttt tgtgtttggg agaaaaatat cttggacgca ctgttttcct tgataaaagt


 


6421
catcttctct actgtgtgaa atgaatactt ggaattctaa ttgttttgtg tgccaggggc


 


6481
agtaatgtcc ctgcctcttc tcccaatcaa ggttgaggag tggggctggg gagaggactt


 


6541
aactgactta agaagtagga aaacaaaaac ctctctcctc agccttccac ctccaagaga


 


6601
ggaggaaaaa cagttgtctg ctgtctgtaa ttcagtttgc gtgtatttta tgctcatgca


 


6661
ccaacccata cagagtaaat cttttatcaa ctatatactg gtgtttaata gagaatgatt


 


6721
gtcttccgag ttttttggtt ccttttttaa ctgtgttaaa gtacttgaaa tgtattgact


 


6781
gctgactata ttttaaaaac aaaatgaaat aatttgagtt gtattacaga ggttgacatt


 


6841
gttcagggat gggacaaagc cttcttcaat ccttttcata ctacttaatg attttggtgc


 


6901
aggaacctga gattttctga tttatatttc atgatatttc acatttgctc ttcacagcat


 


6961
gagcatgaag cccagtggca ccaaatggct gggtacaatc aagtgatatt ttgtagcacc


 


7021
tcactatctg aaaggccatg agttttcaga tgatttcatt gagcttcatt gcagcctgaa


 


7081
attttaaaaa agttgtgtaa tacgccaacc agtcaagttg tgttttggcc agagatttag


 


7141
atatgtccaa tttcctggct catttcattg tgctctatgg gtacgtataa aaagcaagaa


 


7201
ttctgtttcc taggcaaaca ttgcaactca gggctaaagt catccagtga aacttttaga


 


7261
gccagaagta actttgtccc agtcctacaa tgtgaaaaga gtgaatagtt gcctcttttt


 


7321
agccattttc atggctggta catattcgta cgcattactt ttcagaatca atacgcactt


 


7381
tcagatattc ttatttttat tctcttaagt ctttattaac tttggagaga gaaatgatgc


 


7441
atctttttat tttaaatgaa gtagatcaac atggtggaac aaaatgataa agaacagaaa


 


7501
acatttcaat atattactaa taactttttc caatataaat cctaaaattc ctataacata


 


7561
gtattttaca gttttatgaa gctttctatt gtgactttta tggaattaag agatgaagaa


 


7621
gatgagatat tttagcattt atatttttca aaattatatg tatacttaaa aataaagtaa


 


7681
ctttatgcat tta






One example of a nucleic acid sequence for human SLIT1 is available as NCBI accession number NM_003061 (gi: 188528674). This sequence is recited below for easy reference as SEQ ID NO:164.









1
gggagaggga gacgcaggcg gcgaaacggc agaggagccg agccccctcc gcccaaggcg



 


61
ccctccctcc gtccgcgcac aggcgccgtc gcttggagga gcaaggtgcc tcccagcccg


 


121
caggggcgcc gcgcgcaagc ccgcgggctc ttcggtggct ctgccccggg actgcacctg


 


181
gaggcggccc cggacgggga tggtcagcgg ctgctgccgt ctggctcgcg agcgggacgc


 


241
tgtgagggca ccatggcgct gactcccggg tgggggtcct cggcggggcc ggtccggccg


 


301
gagctctggc tgctgctgtg ggcagccgcg tggcgcctgg gtgcctcggc gtgccccgcc


 


361
ctctgcacct gcaccggaac cacggtggac tgccacggca cggggctgca ggccattccc


 


421
aagaatatac ctcggaacac cgagcgcctg gaactcaatg gcaacaacat cactcggatc


 


481
cataagaatg actttgcggg gctcaagcag ctgcgggtgc tgcagctgat ggagaaccag


 


541
attggagcag tggaacgtgg tgcttttgat gacatgaagg agctggagcg gctgcgactg


 


601
aaccgaaacc agctgcacat gttaccggaa ctgctgttcc agaacaacca ggctttgtca


 


661
agactggact tgagtgagaa cgccatccag gccatcccca ggaaagcttt tcggggagct


 


721
acggacctta aaaatttaca gctggacaag aaccagatca gctgcattga ggaaggggcc


 


781
ttccgtgctc tgcgggggct ggaggtgctg accctgaaca acaacaatat caccaccatc


 


841
cccgtgtcca gcttcaacca tatgcccaag ctacggacct tccgcctgca ctccaaccac


 


901
ctgttttgcg actgccacct ggcctggctc tcgcagtggc tgaggcagcg gccaaccatc


 


961
gggctcttca cccagtgctc gggcccagcc agcctgcgtg gcctcaatgt ggcagaggtc


 


1021
cagaagagtg agttcagctg ctcaggccag ggagaagcgg ggcgcgtgcc cacctgcacc


 


1081
ctgtcctccg gctcctgccc ggccatgtgc acctgcagca atggcatcgt ggactgtcgt


 


1141
ggaaaaggcc tcactgccat cccggccaac ctgcccgaga ccatgacgga gatacgcctg


 


1201
gagctgaacg gcatcaagtc catccctcct ggagccttct caccctacag aaagctacgg


 


1261
aggatagacc tgagcaacaa tcagatcgct gagattgcac ccgacgcctt ccagggcctc


 


1321
cgctccctga actcgctggt cctctatgga aacaagatca cagacctccc ccgtggtgtg


 


1381
tttggaggcc tatacaccct acagctcctg ctcctgaatg ccaacaagat caactgcatc


 


1441
cggcccgatg ccttccagga cctgcagaac ctctcactgc tctccctgta tgacaacaag


 


1501
atccagagcc tcgccaaggg cactttcacc tccctgcggg ccatccagac tctgcacctg


 


1561
gcgcagaacc ctttcatttg cgactgtaac ctcaagtggc tggcagactt cctgcgcacc


 


1621
aatcccatcg agacgagtgg tgcccgctgt gccagtcccc ggcgcctcgc caacaagcgc


 


1681
atcgggcaga tcaagagcaa gaagttccgg tgctcagcca aagagcagta cttcattcca


 


1741
ggcacggagg attaccagct gaacagcgag tgcaacagcg acgtggtctg tccccacaag


 


1801
tgccgctgtg aggccaacgt ggtggagtgc tccagcctga agctcaccaa gatccctgag


 


1861
cgcatccccc agtccacggc agaactgcga ttgaataaca atgagatttc catcctggag


 


1921
gccactggga tgtttaaaaa acttacacat ctgaagaaaa tcaatctgag caacaacaag


 


1981
gtgtcagaaa ttgaagatgg ggccttcgag ggcgcagcct ctgtgagcga gctgcaccta


 


2041
actgccaacc agctggagtc catccggagc ggcatgttcc ggggtctgga tggcttgagg


 


2101
accctaatgc tgcggaacaa ccgcatcagc tgcatccaca acgacagctt cacgggcctg


 


2161
cgcaacgtcc ggctcctctc gctctacgac aaccagatca ccaccgtatc cccaggagcc


 


2221
ttcgacaccc tccagtccct ctccacactg aatctcctgg ccaacccttt caactgcaac


 


2281
tgccagctgg cctggctagg aggctggcta cggaagcgca agatcgtgac ggggaacccg


 


2341
cgatgccaga accctgactt tttgcggcag attcccctgc aggacgtggc cttccctgac


 


2401
ttcaggtgtg aggaaggcca ggaggagggg ggctgcctgc cccgcccaca gtgcccacag


 


2461
gagtgcgcct gcctggacac cgtggtccga tgcagcaaca agcacctgcg ggccctgccc


 


2521
aagggcattc ccaagaatgt cacagaactc tatttggacg ggaaccagtt cacgctggtt


 


2581
ccgggacagc tgtctacctt caagtacctg cagctcgtgg acctgagcaa caacaagatc


 


2641
agttccttaa gcaattcctc cttcaccaac atgagccagc tgaccactct gatcctcagc


 


2701
tacaatgccc tgcagtgcat cccgcctttg gccttccagg gactccgctc cctgcgcctg


 


2761
ctgtctctcc acggcaatga catctccacc ctccaagagg gcatctttgc agacgtgacc


 


2821
tccctgtctc acctggccat tggtgccaac cccctatact gtgactgcca cctccgctgg


 


2881
ctgtccagct gggtgaagac tggctacaag gaaccgggca ttgctcgttg tgctgggccc


 


2941
caggacatgg agggcaagct gctcctcacc acgcctgcca agaagtttga atgccaaggt


 


3001
cctccaacgc tggctgtcca ggccaagtgt gatctctgct tgtccagtcc gtgccagaac


 


3061
cagggcacct gccacaacga cccccttgag gtgtacaggt gcgcctgccc cagcggctat


 


3121
aagggtcgag actgtgaggt gtccctggac agctgttcca gtggcccctg tgaaaatggg


 


3181
ggcacctgcc atgcacagga gggcgaggat gccccgttca cgtgctcctg tcccaccggc


 


3241
tttgaaggac caacctgtgg ggtgaacaca gatgactgtg tggatcatgc ctgtgccaat


 


3301
gggggcgtct gtgtggatgg tgtgggcaac tacacctgcc agtgccccct gcagtatgag


 


3361
ggaaaggcct gtgagcagct ggtggacttg tgctctccgg atctgaaccc atgtcaacac


 


3421
gaggcccagt gtgtgggcac cccggatggg cccaggtgtg agtgcatgcc aggttatgca


 


3481
ggtgacaact gcagtgagaa ccaggatgac tgcagggacc accgctgcca gaatggggcc


 


3541
cagtgtatgg atgaagtcaa cagctactcc tgcctctgtg ctgagggcta cagtggacag


 


3601
ctctgtgaga tccctcccca tctgcctgcc cccaagagcc cctgtgaggg gactgagtgc


 


3661
cagaatgggg ccaactgtgt ggaccagggc aacaggcctg tgtgccagtg cctcccaggc


 


3721
ttcggtggcc ctgagtgtga gaagttgctc agtgtcaact ttgtggatcg ggacacttac


 


3781
ctgcagttca ctgacctgca aaactggcca cgggccaaca tcacgttgca ggtctccacg


 


3841
gcagaggaca atgggatcct tctgtacaac ggggacaacg accacattgc agttgagctg


 


3901
taccagggcc atgtgcgtgt cagctacgac ccaggcagct accccagctc tgccatctac


 


3961
agtgctgaga cgatcaacga tgggcaattc cacaccgttg agctggttgc ctttgaccag


 


4021
atggtgaatc tctccattga tggcgggagc cccatgacca tggacaactt tggcaaacat


 


4081
tacacgctca acagcgaggc gccactctat gtgggaggga tgcccgtgga tgtcaactca


 


4141
gctgccttcc gcctgtggca gatcctcaac ggcaccggct tccacggttg catccgaaac


 


4201
ctgtacatca acaacgagct gcaggacttc accaagacgc agatgaagcc aggcgtggtg


 


4261
ccaggctgcg aaccctgccg caagctctac tgcctgcatg gcatctgcca gcccaatgcc


 


4321
accccagggc ccatgtgcca ctgcgaggct ggctgggtgg gcctgcactg tgaccagccc


 


4381
gctgacggcc cctgccatgg ccacaagtgt gtccatgggc aatgcgtgcc cctcgacgct


 


4441
ctttcctaca gctgccagtg ccaggatggg tactcggggg cactgtgcaa ccaggccggg


 


4501
gccctggcag agccctgcag aggcctgcag tgcctgcatg gccactgcca ggcctcaggc


 


4561
accaaggggg cacactgtgt gtgtgacccc ggcttttcgg gcgagctgtg tgagcaagag


 


4621
tccgagtgcc ggggggaccc tgtccgggac tttcaccagg tccagagggg ctatgccatc


 


4681
tgccagacca cgcgccccct gtcatgggtg gagtgccggg gctcgtgccc aggccagggc


 


4741
tgctgccagg gccttcggct gaagcggagg aagttcacct ttgagtgcag cgatgggacc


 


4801
tcttttgccg aggaggtgga aaagcccacc aagtgtggct gtgccctctg cgcatagcgc


 


4861
tgggcgtgga caggccggtg agggcgggca aggggcccca gccgctgcag cagcggagac


 


4921
agtcgccagc agctgggctg gggtgcaggt catcacagga cggctcctgg gcagctgggc


 


4981
cctcctgggt ggggtggtgc cagagcagcc ttttaaaagc aaattgcgcc atagctgggg


 


5041
gcagcggggg tgggcgaggc ctgagctgcg ggctgccctc tccggaagtg ccttgcacaa


 


5101
ataggcgctt aataaatatt tgttgagtga atgtgtgcgt gaggtcaggc caagaagtgc


 


5161
agaacgatga cacccctcct tacctgctat ctgaatctgg agaagaaaaa tgacagcctt


 


5221
ccaaaccaac ccttcccttt ggcctgtggc ccaggctggc ttggaactgg gtctgtggcc


 


5281
ccagaagcct cttacccctc tgcgggcaac catgaagtac tgtcagcctc cccgggaagc


 


5341
cagcctggtt cattctgctg ctacagaatc tgctggtggt aggccaggct ctggagcggg


 


5401
ggtgccgcct cctgctggcc agggagggtc ggacccttgc cccctgggct gactggcagc


 


5461
tctgcagcca cggcttggga acgaggctgt gggtggaggt ggttcttagg accaggcctc


 


5521
tgaatcctaa agttctagca tgactactgt agctgcgagg gcttatgtgg aggaaacagt


 


5581
cacaggggct gctcagggtg gcagacccca ctaaagaggg cagagggttc tttgctctag


 


5641
ataaacaaac atcatctgcc tccagacact ggccacagta ggagtattgg tcctgggctt


 


5701
ccccagccac cagtcagcca caagctgtcg gtgacctatt ggtagaggga ctgggtgtga


 


5761
gggtctgggc cagggtgctt gacctgggag cagctggttc agagtccttc acaccgcagg


 


5821
ccagtaggga gcagtggaag ggacagtgct ccaggcattg ggaagtccct gctggctcta


 


5881
tcactcgggg caaacttctc cccacctggg ccttgggttc ttcagctata aaatggccag


 


5941
aggtgggggg cgggatgact aaaggaacag tgcagactcc cccactgtgg tcttgggagg


 


6001
ccagaggagt tagaagacct atctatctat ctatctatct acattgatca catcaaaagt


 


6061
atttatgtgc ctaacccggg gctggggatt gtggacgttc tggcctaatg gacagatgtg


 


6121
aactcatccc agagcatcgc aggaatgacc aggatgcccg ggaagagttg agctgagtgg


 


6181
gggctccagc cacagacagc ggcccaggcc agggagttgc tggcaacgaa ggagccagtg


 


6241
gtggaagaag aagaggccct gaatatacga ttgcctgccc acgttgtctt ctcttccata


 


6301
cacagtgaaa atgtagaaag atggtttgtg aggccaaact gtgaatgggc taaagggagg


 


6361
caaagttgca ctctccttcc ccagagggct caccaagagg gcacaccccc gggggttctg


 


6421
gtgggcaacg ggggtgagca tgtccctgcc ctggctccct ccatctgtga ccaggaggca


 


6481
tggctgggtg tatgttcagg tgaggctcag agtggcattg tgtccctgtc ccctgcccag


 


6541
ggcagtgagg ggagcccttg atgctgatta gaaggctaga actggggtag aggtgcctgg


 


6601
catgtctcat gccatgggga ctcaatctag caactgtgag tcctggggtc cctgtgatgg


 


6661
gaagagggca gtgccctgcc caatgtggca ggtgtcctca tggcaggatc tgcccctcac


 


6721
cagggggctg ggatctactt gcttggagct ctgagcaagg ccacaatgcc cgcccccacc


 


6781
cccaagtaga ctgcagcctg ggcctcatgg ggcttctccc aggcccacat ggcatccctc


 


6841
tctgagtttc caggccaccg tgggaccctg cagagcatct gcaccgggct ggatagggca


 


6901
gaaaagctca agggcagcta gcttgcctct tccctggaag aaaggtgctc tgggactcac


 


6961
caaccctgag aaagatagct ttcctggcca ccaccattcc ccaccaccct ggagaagcca


 


7021
attcccaggc ttgaagggca ctggctggca ggaggcctct tcattctgca ggaggtggaa


 


7081
aggacacctg tagacaggtg atgctcaccc ctcacctggc gccatggggc tgggaggtga


 


7141
gcggctggca tgtttgttcc tagggagcac catgtgagct taaggctccc ctgaccggcc


 


7201
ccaccacatg gcccagcctc ctagcacagc agcgctgacc tcagtgcagt ctgaggattg


 


7261
gaatccacca tgagatgatg tgagagctgt gtgccccagg atcaactttt tctccaactt


 


7321
ggccatcagc cagcgagttg ctaaggacct gagtcagcac tcacgttgcc tattcacact


 


7381
ccgcttgaaa gtccggaagg tggctactgc aaaatcaccc ctctgagaag tcctctctcc


 


7441
acatcttgtc cccctttgtg aagaccccta gttcgctctg cattttaggc atgaagagat


 


7501
acagcagggt gcgtccggag ggagctgtgg ccttgcaaca ccactggcaa cagggccggg


 


7561
gctcccggtg aaggtgtcag gaagtggaaa aggctggact ttgtctcctc tttgcctgct


 


7621
ggtagcctaa ccgcaaaagt atctctttat acagaatact tacagattct aatatatatt


 


7681
tgtatttcat tttgttacag tatttttata tgttaaagtc aacatccagc gtcttgtttt


 


7741
gcctttcaga tgctatgtgg tcgtggcacg ttttgttggg ggtttctgta gtcgtcttgt


 


7801
ttggatcaac tcctagaggc tggtttagaa caggcccatg agggagctgc acctgccctg


 


7861
gaagtattgt tttagactat gtcgatattg tctgttgtct tccatgtgaa catgacattg


 


7921
agtcactctg caaaaaaaaa aaaaaaaaa






One example of a nucleic acid sequence for human SPTAN1 is available as NCBI accession number NM_001130438 (gi: 194595508). This sequence is recited below for easy reference as SEQ ID NO:165.









1
gccactaccc gctgcggagt gaacggtgtg gagcggaggc cgcggaggct cctcggtcct



 


61
tcagcacccc tcggcccgac gcacccacgc ccctcacccc ccgagagccg aaaatggacc


 


121
caagtggggt caaagtgctg gaaacagcag aggacatcca ggagaggcgg cagcaggtcc


 


181
tagaccgata ccaccgcttc aaggaactct caacccttag gcgtcagaag ctggaagatt


 


241
cctatcgatt ccagttcttt caaagagatg ctgaagagct ggagaaatgg atacaggaaa


 


301
aacttcagat tgcatctgat gagaattata aagacccaac caacttgcag ggaaagcttc


 


361
agaagcatca agcatttgaa gctgaagtgc aggccaactc aggagccatt gttaagctgg


 


421
atgaaactgg aaacctgatg atctcagaag ggcattttgc atctgaaacc atacggaccc


 


481
gtttgatgga gctgcaccgc cagtgggaat tacttttgga gaagatgcga gaaaaaggaa


 


541
tcaaactgct gcaggcccag aagttggtgc agtacttacg agaatgtgag gacgtgatgg


 


601
actggatcaa tgacaaggaa gcaattgtta cttctgaaga gctgggccag gatctggagc


 


661
atgtagaggt tttacagaag aaatttgaag agtttcaaac agatatggct gctcatgaag


 


721
aaagagttaa tgaagtgaac cagtttgctg ccaaactcat acaggagcag caccctgagg


 


781
aggaactgat caagactaag caggatgaag tcaatgcagc ctggcagcgg ctgaagggcc


 


841
tggctctgca gaggcagggg aagctctttg gggcagcaga agttcagcgc tttaacaggg


 


901
atgtggatga gactatcagt tggattaagg aaaaggagca gttaatggcc tctgatgatt


 


961
ttggccgaga cctggcaagt gttcaggctc tgcttcggaa gcacgagggt ctggagagag


 


1021
atcttgctgc tctagaagac aaggtcaaag ccctgtgtgc tgaggctgac cgcctgcaac


 


1081
agtcccaccc tctgagtgca acacagattc aagtgaagcg agaggaactg attacaaact


 


1141
gggagcagat ccgcaccttg gcggcagaga gacatgcacg gctcaatgat tcatacaggc


 


1201
ttcaacgctt ccttgctgac ttccgtgacc tcaccagctg ggtgactgag atgaaagccc


 


1261
tcatcaatgc agatgagctt gccagtgatg tggctggggc tgaagccctg ctagatagac


 


1321
accaagagca caagggtgaa attgatgccc atgaagacag cttcaaatct gcagatgaat


 


1381
ctggacaggc actgcttgct gctggtcact atgcctcaga tgaagtgagg gagaagctga


 


1441
ccgtcctttc cgaggagaga gcggcgctgc tggagctgtg ggagctgcgc aggcagcagt


 


1501
acgagcagtg catggacctg cagctcttct accgggacac tgagcaggtg gacaactgga


 


1561
tgagcaagca ggaggcgttc ctgttgaatg aagacttggg agattccttg gatagtgtgg


 


1621
aagcgcttct taagaagcac gaagactttg agaaatccct tagtgcccag gaggaaaaga


 


1681
ttacagcatt agatgaattt gcaaccaagc taattcagaa caaccactat gcaatggaag


 


1741
atgtggccac tcgccgagat gctctgttga gccgccgcaa tgcccttcac gagagagcca


 


1801
tgcgtcgccg ggcccagcta gccgattctt tccatctgca gcagtttttc cgtgattctg


 


1861
atgagctcaa gagttgggtc aatgagaaga tgaaaactgc cacagatgaa gcttataaag


 


1921
atccatccaa cctacaagga aaagtacaga agcatcaggc ttttgaggct gagctctcag


 


1981
caaaccagag ccgaattgat gccttggaga aagctggcca aaagctgatt gatgtcaacc


 


2041
actatgccaa ggatgaagtg gcagctcgta tgaatgaggt gatcagtttg tggaagaaac


 


2101
tgctagaggc cactgaactg aaaggaataa agcttcgtga agccaaccag caacagcaat


 


2161
ttaatcgcaa tgttgaggat attgaattgt ggctatatga agtagaaggt cacttggctt


 


2221
cggatgatta cggcaaagat cttaccaatg tgcagaacct ccagaagaaa catgccctgc


 


2281
tagaggcaga tgtggctgct caccaggacc gaattgatgg catcaccatt caggcccgcc


 


2341
agttccaaga tgctggccat tttgatgcag aaaacatcaa gaagaaacag gaagccctcg


 


2401
tggctcgcta tgaggcactc aaggagccca tggttgcccg gaagcagaag ctggccgatt


 


2461
ctctgcggtt gcagcagctc ttccgggatg ttgaggatga ggagacgtgg attcgagaga


 


2521
aagagcccat tgccgcatct accaacagag gtaaggattt aattggggtc cagaatctgc


 


2581
taaagaaaca tcaagcctta caagcagaaa ttgctggaca tgaaccacgc atcaaagcag


 


2641
ttacacagaa ggggaatgcc atggtggagg aaggccattt tgctgcagag gatgtgaagg


 


2701
ccaagcttca cgagctgaac caaaagtggg aggcactgaa agccaaagct tcccagcgtc


 


2761
ggcaggacct ggaggactct ctgcaggccc agcagtactt tgctgatgct aacgaggctg


 


2821
aatcctggat gcgggagaag gaacccattg tgggcagcac tgactatggc aaggacgaag


 


2881
actctgctga ggctctactg aagaaacacg aagctttgat gtcagatctc agtgcctacg


 


2941
gcagcagcat ccaggctttg cgagaacaag cacagtcctg ccggcaacaa gtggccccca


 


3001
cggatgatga gactgggaag gagctggtct tggctctcta cgactatcag gagaagagtc


 


3061
cccgagaggt caccatgaag aagggagata tccttacctt actcaacagc accaacaagg


 


3121
attggtggaa agtggaagtg aacgatcgtc agggttttgt gccggctgcg tacgtgaaga


 


3181
aattggaccc cgcccagtca gcctcccggg agaatctcct ggaggagcaa ggcagcatag


 


3241
cactgcggca ggagcagatt gacaatcaga cacgcataac taaggaggcc ggcagtgtat


 


3301
ctctgcgtat gaagcaggtg gaagaactat atcattctct gctggaactg ggtgagaagc


 


3361
gtaaaggcat gttggagaag agttgcaaga agtttatgtt gttccgtgaa gcgaatgaac


 


3421
tacagcaatg gatcaatgag aaggaagccg ctctgacaag tgaggaggtc ggagcagact


 


3481
tggagcaggt tgaggtgctc cagaagaagt ttgatgactt ccagaaggac ctgaaggcca


 


3541
atgagtcacg gttgaaggac attaacaagg tagctgaaga cctggagtct gaaggtctca


 


3601
tggcagagga ggtgcaggct gtgcaacaac aggaagtgta tggcatgatg cccagggatg


 


3661
aaactgattc caagacagcc tccccgtgga agtctgctcg tctgatggtt cacaccgtgg


 


3721
ccacctttaa ttccatcaag gagctgaatg agcgctggcg gtccctacag cagctggccg


 


3781
aggaacggag ccagctcttg ggcagcgccc atgaagtaca gaggttccac agagatgctg


 


3841
atgaaaccaa agaatggatt gaagagaaga atcaagctct aaacacagac aattatggac


 


3901
atgatctcgc cagtgtccag gccctgcaac gcaagcatga gggcttcgag agggaccttg


 


3961
cggctctcgg tgacaaggta aactcccttg gtgaaacagc agagcgcctg atccagtccc


 


4021
atcccgagtc agcagaagac ctgcaggaaa agtgcacaga gttaaaccag gcctggagca


 


4081
gcctggggaa acgtgcagat cagcgcaagg caaagttggg tgactcccac gacctgcagc


 


4141
gcttccttag cgatttccgg gacctcatgt cttggatcaa tggaatacgg gggttggtgt


 


4201
cctcagatga gctagccaag gatgtcaccg gagctgaggc attgctggag cgacaccagg


 


4261
aacaccggac agaaatcgat gccagggctg gcactttcca ggcatttgag cagtttggac


 


4321
agcagctgtt ggctcacgga cactatgcca gccctgagat caagcagaaa cttgatattc


 


4381
ttgaccagga gcgtgcagac ctggagaagg cctgggttca gcgcaggatg atgctggatc


 


4441
agtgccttga actgcagctg ttccatcggg actgtgagca agctgagaac tggatggctg


 


4501
cccgggaggc cttcttgaat accgaagaca aaggagactc actggacagc gtagaggctc


 


4561
tgatcaaaaa acatgaagac tttgacaaag cgattaacgt ccaggaagag aagattgctg


 


4621
ctctgcaggc ctttgccgac cagctcatcg ctgccggcca ttatgccaag ggagacattt


 


4681
ctagccggcg caatgaggtc ttggacaggt ggcgacgtct gaaagcccag atgattgaga


 


4741
aaaggtcaaa gctaggagaa tctcaaaccc tccaacagtt cagccgggat gtggatgaga


 


4801
ttgaggcttg gatcagtgaa aaattgcaaa cagcgagtga tgagtcgtac aaggatccca


 


4861
ccaacatcca gctttccaag ctgctgagca agcaccagaa gcaccaggct tttgaagcag


 


4921
agctgcatgc caacgctgac cggatccgtg gggttatcga catgggcaac tccctcattg


 


4981
aacgtggagc ctgtgccggc agtgaggatg ctgtcaaggc ccgcctggct gccttagctg


 


5041
accagtggca gttcttggtg caaaagtcag cggaaaagag ccagaaactg aaagaagcca


 


5101
acaagcagca gaacttcaac acagggatca aggactttga cttctggctg tctgaggtgg


 


5161
aggccctgct ggcatccgaa gattatggca aagacctggc ttctgtgaac aacctgctga


 


5221
aaaagcatca actgctggaa gcagatatat ctgcccatga ggatcgcctg aaggacctga


 


5281
acagccaggc agacagcctg atgaccagca gtgccttcga cacctcccaa gtaaaggaca


 


5341
agagggacac catcaacggg cgcttccaga agatcaagag catggcggcc tcccggcgag


 


5401
ccaagctgaa tgaatcccat cgcctgcacc agttcttccg ggacatggat gacgaggagt


 


5461
cctggatcaa ggagaagaag ctgctggtgg gctcagagga ctacggccgg gacctaaccg


 


5521
gcgtgcagaa cctgaggaag aagcacaagc ggctggaagc agaactggct gcgcatgagc


 


5581
cggctattca gggtgtcctg gacactggca agaagctgtc cgatgacaac accatcggga


 


5641
aagaggagat ccagcagcgg ctggcgcagt ttgtggagca ctggaaagag ctgaagcagc


 


5701
tggcagctgc ccggggtcag cggctggaag agtccttgga atatcagcag tttgtagcca


 


5761
atgtggaaga ggaagaagcc tggatcaatg agaaaatgac cctggtggcc agcgaagatt


 


5821
atggcgacac tcttgccgcc atccagggct tactgaagaa acatgaagct tttgagacag


 


5881
acttcaccgt ccacaaggat cgcgtgaatg atgtctgcac caatggacaa gacctcatta


 


5941
agaagaacaa tcaccatgag gagaacatct cttcaaagat gaagggcctg aacgggaaag


 


6001
tgtcagacct ggagaaagct gcagcccaga gaaaggcgaa gctggatgag aactcggcct


 


6061
tccttcagtt caactggaag gcggacgtgg tggagtcctg gatcggtgaa aaggagaaca


 


6121
gcttgaagac agatgattat ggccgagacc tgtcttctgt gcagacgctc ctcaccaaac


 


6181
aggaaacttt tgacgctggg ctgcaggcct tccagcagga aggcattgcc aacatcactg


 


6241
ccctcaaaga tcagcttctc gccgccaaac acgttcagtc caaggccatc gaggcccggc


 


6301
acgcctccct catgaagagg tggagccagc ttctggccaa ctcagccgcc cgcaagaaga


 


6361
agcttctgga ggctcagagt cacttccgca aggtggagga cctcttcctg accttcgcca


 


6421
aaaaggcttc tgccttcaac agctggtttg aaaatgcaga ggaggactta acagaccccg


 


6481
tgcgctgcaa ctccttggaa gaaatcaaag ctttgcgcga ggcccacgac gccttccgct


 


6541
cctccctcag ctctgcccag gctgacttca accagctggc cgagctggac cgccagatca


 


6601
agagcttccg cgtagcctcc aacccctaca cctggtttac catggaggcc ctggaggaga


 


6661
cctggaggaa cctacagaaa atcatcaagg agagggagct ggagctgcag aaggaacagc


 


6721
ggcggcagga ggagaacgac aagctgcgcc aggagtttgc ccagcacgcc aacgccttcc


 


6781
accagtggat ccaagagacc aggacatacc tcctcgatgg gtcctgtatg gtggaagagt


 


6841
cggggaccct cgaatcccag cttgaagcta ccaaacgcaa gcaccaggaa atccgagcca


 


6901
tgagaagtca gctcaaaaag atcgaggacc tgggggccgc catggaggag gccctcatcc


 


6961
tggacaacaa gtacacggag cacagcaccg tgggcctcgc ccagcagtgg gaccagctgg


 


7021
accagctggg catgcgcatg cagcacaacc tggagcagca gatccaggcc aggaacacaa


 


7081
caggtgtgac tgaggaggcc ctcaaagaat tcagcatgat gtttaaacac tttgacaagg


 


7141
acaagtctgg caggctgaac catcaggagt tcaaatcttg cctgcgctcc ctgggctatg


 


7201
acctgcccat ggtggaggaa ggggaacctg accctgagtt cgaggcaatc ctggacacgg


 


7261
tggatccgaa cagagatggc catgtctcct tgcaagaata catggctttc atgatcagcc


 


7321
gcgaaactga gaacgtcaag tccagcgagg agattgagag cgccttccgg gccctcagct


 


7381
cagagggaaa gccttacgtg accaaggagg agctctacca gaacctgacc cgggaacaag


 


7441
ccgactactg cgtctcccac atgaagccct acgtggacgg caagggccgc gagctcccca


 


7501
ccgcgttcga ctacgtggag ttcacccgct cgcttttcgt gaactgagcc actccctggg


 


7561
tcacccaccc ctcgctgctt gccctgcgtc gccttgctgc atgtccgctc ctctgtgtgc


 


7621
tctcactttc cactgtaacc ttaagcctgc ttagcttgga ataagactta ggagaaaatg


 


7681
gtgcttcact aacccgcttc cggtccagtc acaatcatca tgtcactgtg gggacccaga


 


7741
tctgtgtctt gaagcagctg ccctcattcc gacttcagaa aatcgaagca gctggctcct


 


7801
ccccttgttc tctctcccac cctcccccaa atctgttttc atgtaaaaga caaataaatg


 


7861
atgacttccc ccaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa


 


7921
aaaa






One example of a nucleic acid sequence for human TFCP2L1 is available as NCBI accession number NM_014553 (gi: 212276201). This sequence is recited below for easy reference as SEQ ID NO:166.









1
gggttcggag cgcgaagccg ccgctgggtc ctcggcgcgc cccgcgtctg cgcttgctgc



 


61
cgcgccccgg tcggcgcgct gggagttcca gccatgctct tctggcacac gcagcccgag


 


121
cactacaacc agcacaactc cggcagctac ctgcgtgatg tgctcgctct gcccatcttc


 


181
aagcaggagg aaccccagct gtcccccgag aacgaggccc gcctgccacc cctgcaatat


 


241
gtgttgtgtg ctgccacgtc cccagccgtg aagctgcatg aagagacgct gacctacctc


 


301
aaccaaggtc agtcttatga aatccgacta ctggagaatc ggaagctggg agactttcaa


 


361
gatctgaaca caaaatatgt caagagcatc atccgtgtgg tcttccatga ccgccggctg


 


421
cagtatacgg agcaccagca gctggagggc tggcggtgga gtcggccagg ggaccggatc


 


481
ctggacatcg atattccact gtctgttggt atcttggacc ccagggccag cccgacccag


 


541
ctgaatgcag tcgagttttt gtgggaccct gcgaagagag cttctgcatt cattcaggta


 


601
cactgcatca gcacagaatt cacccccagg aagcacgggg gcgagaaggg agtgcccttt


 


661
cgagtccaga ttgacacgtt taagcagaac gagaatgggg agtacacgga gcacctgcac


 


721
tcagccagct gccagatcaa ggtgttcaag ccgaagggag ccgatcggaa acagaagact


 


781
gaccgggaga agatggagaa aagaactgcc caagagaagg agaaatacca gccgtcctat


 


841
gaaaccacca tcctcacaga gtgctctcca tggcccgacg tggcctacca ggtgaacagc


 


901
gccccgtccc caagctacaa tggttctcca aacagctttg gcctcggcga aggcaacgcc


 


961
tctccgaccc acccggtgga ggccctgccc gtgggcagtg accacctgct cccatcagct


 


1021
tcgatccagg atgcccagca gtggcttcac cgcaacaggt tctcgcagtt ctgccggctc


 


1081
tttgccagct tctcaggtgc tgacttgctg aagatgtccc gagatgattt ggtccagatc


 


1141
tgtggtcccg cagatgggat ccggctcttc aacgccatca aaggccggaa tgtgaggcca


 


1201
aagatgacca tttatgtctg tcaggagctg gagcagaatc gagtgcccct gcagcagaag


 


1261
cgggacggca gtggagacag caacctgtct gtgtaccacg ccatcttcct ggaagagctg


 


1321
accaccttgg agctgattga gaagatcgcc aacctgtaca gcatctcccc ccagcacatc


 


1381
caccgagtct accggcaggg ccccacgggc atccatgtgg tggtgagcaa cgagatggtg


 


1441
cagaacttcc aagatgaatc ctgttttgtc ctcagcacaa ttaaagctga gagcaatgat


 


1501
ggctaccaca tcatcctgaa atgtggactc tgagcagcag tggacctcat acctgtctcc


 


1561
agctcccagc cctgtggatc cccgtggatg tagacattgc cccactgtaa gctgtggcct


 


1621
caccaggcaa gctgaggcca ggagggaccc tgcccagtct gtgaaagcta cagagcacca


 


1681
accagcagaa gcctgtggac accaagtacg gtgtacagaa agccagtggc tcctttctcc


 


1741
cttcctcttg gcctccagat tttgaatggt tccttgttct tttctattgg tccaaccctg


 


1801
acgttctaaa agggcaaaca gtggagacgt ctgctctgaa atccctcatc ccttagttgg


 


1861
aagctgattg ggtatcttgg tgctgcctgt attggtccct tctgaccact ctcctgcctc


 


1921
cagagaaagc tctgcttcac cctggaagct ggtaccttta cctcctcctc tgggagttgg


 


1981
ctgcatggcc agcactgccg acttgatggg agcagtttgc cctcattctc ctgtttcagg


 


2041
tttgcttccc ttctcagtga ccctggtgag catccgcctt tcctgttctt ggatgaattg


 


2101
atgggagtgg ggctattctg tgccttctac ctctttcttc tctacgttgt ttctaaggat


 


2161
ctgctgctgc ggaacccaaa gatgtgctcc tgtctctgca ctggcgcatt ggcatggtag


 


2221
atgccacaat gtatgtgcac ggcctttctc agagacatta gttctgaggc cctttgtggg


 


2281
gaggttaggg ggatggtaat agaaaaagac tattttattt cctggcaatc acgggtaagg


 


2341
aggattagga atgagtattc cattcctagg tgtcatcaga tgaccttgac caccacaata


 


2401
ccaggccctc ttggatggac ttatagaaag ttagagaaga ccttgttgaa ccgctgctaa


 


2461
acttgccaca ggagcgatgt gttttctctg agtgcccctc acttacatgt ttatctttgt


 


2521
ttgtagaggc tatgtttagg atattttgcc tgcatcagaa tgggtgcatc atctttctta


 


2581
atggcctaac tatcgggaaa tttgagtgtc agtaactgtg gtagactcag aaattcgtct


 


2641
ttgtcttgcc tctggttcct gggatccagt gatctctact ggcccagggc ttcagctctt


 


2701
ggttaattta ggttcatggg gaaccctctg accacctgaa tgggatgtca tagcttctaa


 


2761
atggagcttc tgtggaatga agtgctagac tgaaggacta ccagaataaa acagggtcta


 


2821
caatggggag aacttgtttt atagatgagg aaaccaaggc tcagaggggc aaagtcacct


 


2881
gcatggtagc acatagtgat agggtagcga tataaattta tcatataaac caggacatct


 


2941
cggaataaaa ggggctctgt tagtcattat gttgggtaat agccgtggca ttcctacaga


 


3001
acagagtgag gacaggctcc tgattcctct tccttcttta gaggagaagc ggggagtggg


 


3061
ttaactaaca gctttattga gatgtcattc acatgccatt cagtttaccc attgctagtg


 


3121
tccaattgta ttcacagaac caccatcaat tcacagaatt acagtcaacg ttggtacatt


 


3181
ttcatcaccc ccagtaaaac cccgtaccct tggtctgtca ctcctgcttt cctaactcct


 


3241
gcagtccaag gcagccatga atctactttc tatgtaagat taacctactc tggacatttc


 


3301
atatatctgg aatcatgtga tatctctttt gtgactggct tcttccactg aatgttttct


 


3361
agggccgtcc aagttgagga tgtatcagta cttcattctt ttgtattgct gaataatact


 


3421
tcattgtata gatagaccac atttgtttat tgattcatca gttgatggac atttgtgtgt


 


3481
ttttactttt tggctactct gaatgatgct gctatgaaca tatttctaca agattttgtg


 


3541
tggacatatg ttttcatttc ttttagcaat atacatagga gtggaattgc taggtcttac


 


3601
agtaactccg tgttttaact ttttgagaaa ctgccagact gttttctata gcagctgtac


 


3661
cattttacat tcccaccagc aatgtatcca ggtttcaatt tgtctacatc ctcatcaaca


 


3721
cttgctatta tctgtctttt tgcttttagc atcctaatga gtatgaaatg ctatcttgtg


 


3781
gttttgattt gcattcccct gatggcaact gatgctgagt gtcttttcct gtgcttacgg


 


3841
gccatgcgta tttctttgga gaaaggtcta tccaggtcct ttgcctattt ttaattgagt


 


3901
tgtctttttt tttttaagtt ttctgttttc ctaaccacta gactaccagg gatgagcctt


 


3961
ctttttatta ttgagttggg tgagctattt gtatattcta gacgccagtc ttttatcagg


 


4021
tatatgactg gtaaaaatgt tctccccttc tgtggattgt tttcagtttc ttgttggtgt


 


4081
cctttgagac acaaaacttt ttaactttga tgatttccaa gatacgtatt ttttttctat


 


4141
tgtcacttgt gcttttggtg ccatatctag aaaaccattg cctaatccaa ggtcaagaag


 


4201
attaatgcct gtgttttctt ctaagaacta tacttttagt tctcacaatg gtctttgatc


 


4261
catttcgagt atatttttat atatgatgtg atgtaggggt ccagcttcat tcttttgctt


 


4321
gtggatctcc acttgtccca ctgctgatta ttgagaaaaa tatcctttct ccacggaatt


 


4381
gtcttggcat ccttgctaaa ggcctctgct tcttactgga tcttctttcc tgggacatgg


 


4441
tgtcgttggg aagcttacct tttttttttt tttacttagt ctgtgtttgg ttccaccagt


 


4501
tttatgctgc ctttctactc tgttcttgct gtctccctct ttacctgagt caacggtact


 


4561
gagtcctatc tctctctgat gttccccagt cttccttggt gcatgttcta gctccacaca


 


4621
ctagtccttg gaggaaggtt gagaccaatg atttcctgtt atgagtcatg aggaaactga


 


4681
atcacctaga agtggaataa tgtgctcagg gtcaccatag cccattagtg gaaggaccag


 


4741
gactagacct ttagtcttct gaggtccagc cccttaggct gtctgtcatc actgtaccca


 


4801
agtgatgtca ctaccaaggc caaatgatgg tgggctaaat tttaattctc aaaagtgtag


 


4861
gaggctaata ttgtcttcta agttccaaaa gaagatgtaa taaaagtctg ttaccttaag


 


4921
tgtgctatta gtagagtctt ccatttttct ggcatgcccc tggcatctgc tcttcttacc


 


4981
ttctcgtggt tgtagttaaa gcttatagct tatgaaagaa tagaaaataa taaataccaa


 


5041
aaaaaagtac acatggtaat ttggtaccaa aatatctcag ctgcctaatt tagcagctca


 


5101
tcccttccac aggggtcaga tgagctaaag ctccaggttt tatttttcat ttgattgaca


 


5161
tacagaaaag ccatagccct tcccacagct gtccagggtc tttcctgtga gtccggaggt


 


5221
gctggcctat tgagcaggac agctcttccc agggcattcc caccaacctg tggcttctga


 


5281
actgtagctt ctttttacag tgaaccccag agggaaataa gacagacaca tgtgctcagg


 


5341
ccaccatctt gaactggaag cccaaagctg agttccttac tcttaggtcg tcacggtttt


 


5401
tgcggggtat ctgcaaggtt gagataaacc ctttcctgtt taccaggttg tcctttctgg


 


5461
atgaagggac agaggctgtt gaatggagga ataataggtt tgctggagga ggggcatggt


 


5521
atgcctgtgg aaaggacagg atggggtggg gaggtcgagg ctttgacttg gggtcctaaa


 


5581
caaaggtcag gtgttgccct agtgacctct tgcccagaca gcccagagcc ccttacacag


 


5641
agctattaac ctagggaagg ctttaccagc agtggactgg agccagccag ggtcacaagt


 


5701
ttccaagtcc agcattgctt caggggctgg cctgagtaac tgaagatctg aaaatcatta


 


5761
acaagtcgat gaaataaacg gaaaagcctc ttaggctgtt gtcagtggag cagagggaga


 


5821
aagtccctag gcgctcagag ggggtgagaa agcagtggat gattgggcgg gggtggggga


 


5881
ttagatgttg acactgcctg gggtgtagga agaggaacag agaacccaga gtcagggtcc


 


5941
tagatcccag accctcgctc agtatgagtc tctttgcctc tctgggtctc tatctcctcc


 


6001
tcttacaaat acaggcttgg tgatctctga agatggcacc aacctgccat gaaatgaatc


 


6061
tgaggggttt tcccattttt ccctccatca aaatcgtaca aaaagctgga cgtggtggcc


 


6121
catgcctcta atcctagcat tttgggaggc cgaggtggga gaatcacttg acgccaagag


 


6181
ttcgagacca gcctgggcat cgtagtgaga ctccatctct gtctttttga aaataaaaaa


 


6241
tctttgaaaa ttgcacaaca ggcaggagac ctttacgtgt gcccatcctg gttgtacaca


 


6301
gtgccaccag tgctcctgca gtgcaaggcg gcatgcttct tgacatgggt cagattgtgt


 


6361
ccatcgtgtc tttgggaatc agccctagct cctaactggg ctgactactt cctccgcaaa


 


6421
cttatggggg ctcccagata ttccttgcca gccaggggcc agacacagtg caggcacagt


 


6481
ctgtgtcatt ggtgcacatg tgcgtgttta catgtgtacc tgggttcctt cccttgccca


 


6541
tgaatttgcc atgagcacag ccagaagcag cctcagcttg gcaaggtgtg gagatgactg


 


6601
ctgttccctt cgcatttggg gaaaacaggc tccctcggta gctcgatgat cctcttttga


 


6661
tcttgtgtga cctcctggag agtggatgaa gctggtggcc ttagcttttc tagacagtgt


 


6721
aagtggcact gggcaaggcc cccagagcag ggcaaggtct ctagagcggg tctcccacat


 


6781
gactggcttc acacaggcac ttccgctcgg gttgcatgct ctgtgtcatc ttaccggtcc


 


6841
agggttgcag gtaggaaatg tttgtaccct cttctgattg ccacctcctt cccatcgccc


 


6901
cttagggaca gggcttgagg gccagtgagg cgctggtcag gcaccccagg cctccttggg


 


6961
acctgcccag gggcaccctg agagctcctg aaacccccac ttagcttcca gacctttctg


 


7021
caaaagctcc tcctggcttt cctccctccc ccaatctatg ggtcacagct aacagatctg


 


7081
agggcaactg ctgtgctagt ggccagggct gcacctgcca tccccggctc tgccacttta


 


7141
gggccttcta gaggcagtgt ccttaggaag tagctctgag gcatgggttt tctgctcctg


 


7201
tgcagggcag ctgatgggat aaggtgggga aggacggtca gtgcttgggc cccagctggc


 


7261
cagcctggcg atggggaaac caaaccatgt cccccagcga agggccagag tgggaacctg


 


7321
tcctcatgcc cttcgtcctg aggagccctg aggtgggcag caggggccag gggaagtttt


 


7381
caggccttca tcaaagagaa caacatcctc agctccgcac ccctcatcct gtatcagcac


 


7441
ttaccggtgt gtgactgccc ttgtcagcta gcatacggtg ggcccacctg gcccactggc


 


7501
tgtttatgcc actgatttat gatagggaat attatctttg aacccaatga agtgttttct


 


7561
cccccatcac aaaaaaaaaa attcttattt ttagtagaca tgtatttacc aaaaatatgt


 


7621
actcaattat tgtattttgg attttatcaa tttaaaaatt gtggaaattt gtttgctctt


 


7681
acgccaacat aatattgatt ttgcctcttg gctctgaaag cccaaaatat ttaccgtcta


 


7741
gcccgttaca gaaaaagtct gctgactact gagccagacc tccattacct ccatccctgt


 


7801
tggattattt aaagaaagcc tcagacagta agggcttttt taaaagaata aaatgacttg


 


7861
gtttgcgctt ggaagcaggg gaagcattca gatgagcggt ttctgcatta accctgccta


 


7921
tcacgcatct cgtgtcctgt gtggctggcg agcccccctt ggaaggttct ggtgcttcag


 


7981
ctggctcctg cagagtccac cccgcctcgt ggtgggaatg cagagccctt tgctttcctt


 


8041
cttgccgcct gcttcctgtt cctggggacc cgctgggcct ttggtctgca tcccctggcc


 


8101
aggtccctca gggttgatgc gtggagaagg actttgagca gtggtgggca gcagtggcct


 


8161
cctggccagc tcacactctt gtcctgggag gggcagcctg atctcacctc cacctagtac


 


8221
cttggggact gaggaccttt tggcttctct ggagcctgca agcctcttcc catgtgtcca


 


8281
gctgctcttc ctgctacaaa ggggactgct cacagtggcc tcagcttggt ggttttgagg


 


8341
ggccgccccc cggccctcca taagggtatc ctgggcctga gaattctgca tctgccattg


 


8401
gaggatggac agcctcaaat ggaaggagtc ccacgggaga tgggtccgag gtccggctgt


 


8461
ggccatccag ccccctgtgg cttgtccagc ctctgtgcac ccctggtgtc ttcactccag


 


8521
gggcagacag cagccactgc agttcctttc ttcgtgagta acagtagtga tagcagctgg


 


8581
ggctaacagg ctaggctttg tgttctgcgc atttggtcag cttctcactc gatcctccct


 


8641
aaagcaatgg ggaggccccc actagcccag ttttcaggaa gtcaactggg aggttagatg


 


8701
ggggccaggg tcccacagct actgatggcc cgagccaggt tgagcttcct ggtgtccagt


 


8761
ccggatccca cttgcagatc tcatgctctc agataggtgg gacaagttct tttgtcacag


 


8821
tgctggctct gtcctgaggc ctcattgctg gctgggtgtg ctctgctggg aaaagctttg


 


8881
cggggcttgc ttggttaacc acagaagaga aggggactgt ttggggtgcc tctctgcagc


 


8941
ctccccgtgc tgggtggaag cacggttact gtgttctcta atgttcatgt atttaaaatg


 


9001
atttctttct aaagatgtaa cctccacacc tttctccaga ttgggtgact cttttctaaa


 


9061
ggtggtggga gtatctgtcg gggtggtgtg gcccttggat gggtcaggtg ggtgtgagag


 


9121
gtcctgggga ggtgggcgtt gagctcaaag ttgtcctact gccatgtttt tgtacctgaa


 


9181
ataaagcata ttttgcactt gttactgtac catagtgcgg acgagaagtc tgtatgtggg


 


9241
atctgtgctt gggttagaat gcaaataaaa ctcacatttg taagaaaaaa aaaaaaaaaa


 


9301
aaaaaa






One example of a nucleic acid sequence for human TIAM1 is available as NCBI accession number NM_003253 (gi: 115583669). This sequence is recited below for easy reference as SEQ ID NO:167.









1
gccccgcatc gtgcccggcc ccgtcgcgga gatcccggac gaccgtcgcg ggttgatggt



 


61
cgcattccag atgtaaacag cttcagaagc ctgacggtca tatggtagaa tcactgtgga


 


121
ctgagaccca cctttctaga cctgaagccc aggaggagga agaggaggct ggttggtacc


 


181
atgggcataa tgctctgaat cctagtctct cacctagtat gtgagcagtc cctgcagatg


 


241
gcccatttgg agatcttgac aaagcctctt ctgtttccaa tggggttttt ggcgcattct


 


301
cacagactta gatgaaactg tgatggccac cgcagggggc aggtgctgac atcgtcccca


 


361
gccctgtggc tgttcatccg gacatcattt ccaacctcaa tatctaaatg ccacagtgct


 


421
cttggagcaa gttgggctgg ggaccactgt tgccttttaa gaccataaaa ccatgggaaa


 


481
cgcagaaagt caacatgtag agcacgagtt ttatggagaa aagcatgcca gcctggggcg


 


541
caagcacact tcccgctccc tgcgcctctc gcacaagacg cggaggacca ggcacgcttc


 


601
ctcggggaag gtgatccaca ggaactccga agtgagcacc cgatccagca gcacccccag


 


661
catcccccag tccctggctg aaaatggcct ggagcccttc tcccaagatg gtaccctaga


 


721
agacttcggg agccccatct gggtggaccg agtggacatg ggcttgagac ctgtgtctta


 


781
cactgactct tctgtcactc ccagcgtaga cagcagcatc gtcctcacag cagcctctgt


 


841
gcagagcatg ccagacactg aggagagcag gctttacggg gatgacgcta catatttggc


 


901
tgagggaggc aggaggcagc attcctatac atccaatggg cccactttca tggagacggc


 


961
gagctttaag aagaaacgct ccaaatctgc agacatctgg cgggaggaca gcctggaatt


 


1021
ctcactctct gatctgagcc aagaacattt aacaagcaac gaagaaatct tgggttccgc


 


1081
cgaagagaag gactgcgagg aggctcgggg gatggaaacg cgggcgagtc cgcggcagct


 


1141
cagcacctgt cagagagcca attccttggg tgacttgtat gctcagaaaa actctggagt


 


1201
gacagcaaac ggggggccgg ggagcaaatt tgcaggctac tgtcggaatt tggtgtctga


 


1261
tattcccaat cttgcaaacc ataagatgcc accagctgct gctgaagaga ctcctccgta


 


1321
cagtaattat aacacacttc cctgtaggaa atctcactgt ctctctgaag gtgccaccaa


 


1381
cccacaaatt agccatagca acagcatgca aggcagaaga gctaaaacaa ctcaggatgt


 


1441
taatgcaggc gagggcagtg agtttgcaga cagtgggatt gaaggggcca ctaccgacac


 


1501
ggacctcctg tccaggcgat ctaatgccac caactccagc tactcaccca ccacaggccg


 


1561
ggcctttgtg ggcagcgaca gcggcagcag ctccaccggg gatgcggctc gtcagggggt


 


1621
gtacgagaac ttccggcggg agctggagat gagcaccacc aacagcgaga gcctggagga


 


1681
ggccggctcg gcgcacagcg atgagcagag cagcggcacc ctgagctctc cgggccagtc


 


1741
ggacatcctg ctgaccgccg cacagggcac ggtgcgcaag gccggcgccc tggccgtcaa


 


1801
gaacttcctg gtgcacaaga agaacaagaa ggtggagtca gccacccgga ggaagtggaa


 


1861
gcactactgg gtgtccctga aaggatgcac gctatttttc tacgagagcg acggcaggtc


 


1921
tgggatagac cacaacagca tccccaaaca cgccgtctgg gtggagaaca gcattgtgca


 


1981
ggcggtgcct gagcacccca agaaggactt tgtcttctgc ctcagcaatt ccctgggtga


 


2041
tgccttcctt tttcagacca ctagccagac ggagcttgaa aactggatca ccgccatcca


 


2101
ctctgcctgc gccactgcgg tcgcgaggca ccaccacaag gaagacacgc tccgactcct


 


2161
gaaatcagag atcaaaaaac tggaacagaa gattgacatg gatgaaaaga tgaagaaaat


 


2221
gggtgaaatg cagctgtctt cagtcactga ctcaaagaaa aagaaaacaa tattagatca


 


2281
gatctttgtc tgggagcaaa atctcgagca gttccaaatg gacctgtttc gtttccgctg


 


2341
ttatttagcc agccttcagg gtggggagct gccaaacccc aaaaggcttc tcgcttttgc


 


2401
aagtcgacca acgaaagtgg ccatgggccg ccttggaatc ttttcggtat catcgtttca


 


2461
tgccctggtg gcagcacgca ctggtgaaac tggagtgaga agacgtactc aggccatgtc


 


2521
cagatccgcg agcaagcgaa ggagcaggtt ttcttctctg tggggtctgg atactacctc


 


2581
caaaaagaag cagggacggc caagcatcaa tcaggtgttt ggagagggaa ccgaagctgt


 


2641
aaagaaatct ttagagggaa tatttgatga cattgttcca gatggcaaga gggagaaaga


 


2701
agtggtctta cctaacgttc accagcacaa ccctgactgc gacatttggg tccacgagta


 


2761
tttcactcca tcctggttct gtctgcccaa taatcagcct gccctgacgg tcgtccggcc


 


2821
aggcgacact gcacgggaca ccctggagct gatttgcaag acacatcaac tggatcattc


 


2881
tgctcattac ctgcgcctga aatttctaat agaaaacaaa atgcagctct atgttccaca


 


2941
gcccgaggaa gacatctatg agctgctgta caaagaaatt gaaatctgtc caaaagtcac


 


3001
tcagagcatc cacattgaga agtcagatac agctgctgat acttacgggt tttcactttc


 


3061
ttctgtggaa gaagatggta ttcgaaggct gtacgtgaat agtgtgaagg aaaccggttt


 


3121
agcttccaag aaaggcctga aagcaggaga tgagattctt gagatcaata atcgtgctgc


 


3181
tgacgccctg aactcttcta tgctcaaaga tttcctctca cagccctcgc tgggcctcct


 


3241
ggtgaggacc taccccgagc tggaggaagg agtggagctg ctggaaagcc cgccccaccg


 


3301
agtggacggc cctgccgacc ttggcgagag ccccctcgcc tttctcacca gcaacccagg


 


3361
gcacagcctt tgcagcgagc agggcagcag tgctgagacc gctccagagg agaccgaggg


 


3421
gccagacttg gaatcctcag atgagactga tcacagcagc aagagtacag aacaggtggc


 


3481
cgcattttgc cgcagtttgc atgagatgaa cccctctgac cagagcccat ctcctcagga


 


3541
ctccacgggg cctcagctgg cgaccatgag acaactctcg gatgcagata agctgcgcaa


 


3601
ggtgatctgc gagctcctgg agacggagcg cacctacgtg aaggatttaa actgtcttat


 


3661
ggagagatac ctaaagcctc ttcaaaaaga aacttttctc acccaggatg agcttgacgt


 


3721
gctttttgga aatttaacgg aaatggtaga gtttcaagta gaattcctta aaactctaga


 


3781
agatggagtg agactggtac ctgatttgga aaagcttgag aaggttgatc aatttaagaa


 


3841
agtgctgttc tctctggggg gatcattcct gtattatgct gaccgcttca agctctacag


 


3901
tgccttctgc gccagccaca caaaagttcc caaggtcctg gtgaaagcca agacagacac


 


3961
ggctttcaag gcattcttgg atgcccagaa cccgaagcag cagcactcat ccacgctgga


 


4021
gtcgtacctc atcaagccca tccagaggat cctcaagtac ccacttctgc tcagggagct


 


4081
gttcgccctg accgatgcgg agagcgagga gcactaccac ctggacgtgg ccatcaagac


 


4141
catgaacaag gttgccagtc acatcaatga gatgcagaaa atccatgaag agtttggggc


 


4201
tgtgtttgac cagctgattg ctgaacagac tggtgagaaa aaagaggttg cagatctgag


 


4261
catgggagac ctgcttttgc acactaccgt gatctggctg aacccgccgg cctcgctggg


 


4321
caagtggaaa aaggaaccag agttggcagc attcgtcttc aaaactgctg tggtccttgt


 


4381
gtataaagat ggttccaaac agaagaagaa acttgtagga tctcacaggc tttccattta


 


4441
tgaggactgg gaccccttca gatttcgaca catgatcccc acggaagcgc tgcaggttcg


 


4501
agctttggcg agtgcagatg cagaggcaaa tgccgtgtgt gaaattgtcc atgtaaaatc


 


4561
cgagtctgaa gggaggccgg agagggtctt tcacttgtgc tgcagctccc cagagagccg


 


4621
aaaggatttc ctaaaggctg tgcattcaat cctgcgtgat aagcacagaa gacagctcct


 


4681
caaaaccgag agccttccct catcccagca atatgtccct tttggaggca aaagattgtg


 


4741
tgcactgaag ggggccaggc cggccatgag cagggcagtg tctgccccaa gcaagtctct


 


4801
tgggaggagg aggcggcggc tggctcgaaa caggtttacc attgattctg atgccgtctc


 


4861
cgcaagcagc ccggagaaag agtcccagca gccccccggt ggtggggaca ctgaccgatg


 


4921
ggtagaggag cagtttgatc ttgctcagta tgaggagcaa gatgacatca aggagacaga


 


4981
catcctcagt gacgatgatg agttctgtga gtccgtgaag ggtgcctcag tggacagaga


 


5041
cctgcaggag cggcttcagg ccacctccat cagtcagcgg gaaagaggcc ggaaaaccct


 


5101
ggatagtcac gcgtcccgca tggcacagct caagaagcaa gctgccctgt cggggatcaa


 


5161
tggaggcctg gagagcgcaa gcgaggaagt catttgggtt aggcgtgaag actttgcccc


 


5221
ctccaggaaa ctgaacactg agatctgact gcgtcacctg ccccgtagag aatgtgtgta


 


5281
gatacttcct gccctaactc tgcccaccct cctgtaccgt cgacaagaat gtccccttag


 


5341
gtcgcgctct tgcacacacg gttttggcag ctgacttggt tctgaagcca tgtagccacc


 


5401
caactttgtc attttcaaca acatcagaaa gaattgatca gaatcccaaa taagcttgag


 


5461
tcctatcttc tgtatattac taagggcttt tatttattct caataaatca gggcctgaac


 


5521
aattaaaaga aaaaagattc tatagcactg gaaagcaaat caccccagga gttaacggat


 


5581
gtacaacaga ttaatttaag ggatagtagc acacacacga tccttctatc tgaaatcagt


 


5641
ctcctagctg gggaaacctc tttcacacac aaaatgaaat gtgtacagct tgccgtgttc


 


5701
tgactgtacc cttccctctt ccatgtctga gaatctccgt gtattttaag aatgtgtgag


 


5761
gagagggtgg cgattcatgt ttcaatgagc ctcttttttt ttttccttcc tgttttggtc


 


5821
tatggctggt cttactctgt gtccatgttc ggaagctcta gttttgcata gaattataga


 


5881
gatgccaaac tctttgaaaa gagatccaaa tttatcgctt gagagaaaga aaagaaacac


 


5941
tattttttgt attttacctg agatacaggg gcacaaatag atgagaattt tacagtgtta


 


6001
gtgtatgtat ccctgagcct aaaaaatgag gatataacct tttacagaga gagtgaggcg


 


6061
tggtggtttt atatttatat atgaaaggcc agcaagctca tgcgaaggat atacttttct


 


6121
tccaaaaagc ggattttttt tttttaatgt ttgaatctat atttgagatg ggagtttggt


 


6181
tggattaaac atgacacccc ggtgggcggt gtgtgtgtct gttgcacatg gcagggaggg


 


6241
gagcctcctt ctcatggggt tgccatggtg atcattggtt tttccatcaa aattgcatct


 


6301
tcatccatag attaccttcc ccttccctga cagtccataa ccaaaccttt aaacagaaca


 


6361
acctctttaa aaacttctct tgtgtttaac actttcttca tgccaacgaa acagggtaaa


 


6421
catgctcaaa acattaacag tctaaacaga tatccaaata ctaagaagaa aaacaagtta


 


6481
tagcactttc aatttttttt ttttttttaa aaaaaggttt atagcttttt cttttcccat


 


6541
gtcacaatgt ccacttccta agaagggttt aaaatactat gaaaactttc tttttgggga


 


6601
aaatatctat ttggtgtttg acacatcagt aggtacttta aagacctgaa ttttatagta


 


6661
gctttaggag ttatatttta taaaaatcag ttatgacttt atatttccag acaatagaga


 


6721
gttcagtaca tcatgctctt gtgcctctgc ctgcttttcc tgcgttccca ccctgtattc


 


6781
cccccgcctt tcgggtttcc agggcttcga gcttgatctt ttgaaagttt tattctatta


 


6841
aatttttgct atatcttctg gttttctgaa aaagctttag aatggtttct ataccctttg


 


6901
tatcactgca tttttccata tcatctccgg ttcgatcgcg tccagatgga aaacggaagc


 


6961
agaggcttct aatcgtcgca tttactggct ccagtgcaac acatccatct gaaaacactc


 


7021
ggaagtctgg tgcttggaga gggtgccatt gtctcttgta cataaggtca tgacgtgtct


 


7081
atgtcaaaag ttcttatata tttcttttat aagctgaaag aaggtctatt tttatgtttt


 


7141
taggtctatg aatggaacgt tgtaaatgct tgtcaaacaa taaaaataac gaaaagtgaa


 


7201
aaaaaaaaaa aaaaaaaa






One example of a nucleic acid sequence for human TIMP1 is available as NCBI accession number NM_003254 (gi: 73858576). This sequence is recited below for easy reference as SEQ ID NO:168.









1
tttcgtcggc ccgccccttg gcttctgcac tgatggtggg tggatgagta atgcatccag



 


61
gaagcctgga ggcctgtggt ttccgcaccc gctgccaccc ccgcccctag cgtggacatt


 


121
tatcctctag cgctcaggcc ctgccgccat cgccgcagat ccagcgccca gagagacacc


 


181
agagaaccca ccatggcccc ctttgagccc ctggcttctg gcatcctgtt gttgctgtgg


 


241
ctgatagccc ccagcagggc ctgcacctgt gtcccacccc acccacagac ggccttctgc


 


301
aattccgacc tcgtcatcag ggccaagttc gtggggacac cagaagtcaa ccagaccacc


 


361
ttataccagc gttatgagat caagatgacc aagatgtata aagggttcca agccttaggg


 


421
gatgccgctg acatccggtt cgtctacacc cccgccatgg agagtgtctg cggatacttc


 


481
cacaggtccc acaaccgcag cgaggagttt ctcattgctg gaaaactgca ggatggactc


 


541
ttgcacatca ctacctgcag ttttgtggct ccctggaaca gcctgagctt agctcagcgc


 


601
cggggcttca ccaagaccta cactgttggc tgtgaggaat gcacagtgtt tccctgttta


 


661
tccatcccct gcaaactgca gagtggcact cattgcttgt ggacggacca gctcctccaa


 


721
ggctctgaaa agggcttcca gtcccgtcac cttgcctgcc tgcctcggga gccagggctg


 


781
tgcacctggc agtccctgcg gtcccagata gcctgaatcc tgcccggagt ggaagctgaa


 


841
gcctgcacag tgtccaccct gttcccactc ccatctttct tccggacaat gaaataaaga


 


901
gttaccaccc agcagaaaaa aaaaaaaaaa a






One example of a nucleic acid sequence for human TNS3 is available as NCBI accession number NM_022748 (gi: 134152712). This sequence is recited below for easy reference as SEQ ID NO:169.









1
agaatgggaa actgccttgg gagaagcccc aagtgagccc aagggcgcag agcagaagga



 


61
ccctggagtg taagagccta gattgcaagc ctggcaggag gagccggaag aattaacctc


 


121
gagtctgcac gcttttaaga acaaggcctt taaaaaatcc aaagtgtgtg gagtttgcaa


 


181
acaaattatt gacggtcaag gtatttcatg ccgagcctgc aagtattcct gccacaagaa


 


241
atgtgaagcc aaggtggtga ttccctgcgg tgtgcaagtc cgactggaac aggctccagg


 


301
gagttccacg ctgtccagtt ctctctgccg tgataaacct ctgcggcccg tcatcctgag


 


361
tcccaccatg gaggagggcc atgggctgga cctcacttac atcacggagc gcatcatcgc


 


421
tgtgtccttc cctgccggct gctctgagga gtcctacctg cacaacctac aggaggtcac


 


481
gcgcatgctc aagtccaagc acggggacaa ctacctggta ttaaaccttt cagaaaagag


 


541
atatgacctt acgaagctta acccaaagat catggatgtg ggctggccag agctccacgc


 


601
accgcccctg gataagatgt gtaccatatg caaggcgcag gagtcctggc tgaacagcaa


 


661
cctccagcat gtggtcgtca ttcactgcag gggcgggaaa ggacgcatag gagtggtcat


 


721
atcatcctac atgcatttca ccaacgtctc agccagcgcc gaccaggccc ttgacaggtt


 


781
tgcaatgaag aagttttatg atgacaaagt ttcagcttta atgcagcctt cccaaaaacg


 


841
gtatgttcag ttcctcagtg ggctcctgtc cggatcggtg aaaatgaatg cctctcccct


 


901
gttcctgcat tttgtcatcc tccacggcac ccccaacttc gacacaggtg gagtgtgccg


 


961
gccctttctg aagctctacc aagccatgca gcctgtgtac acctccggga tctacaacgt


 


1021
tggcccagaa aaccccagca ggatctgcat cgtcatcgag ccggcccagc ttctgaaggg


 


1081
agatgtcatg gtgaaatgct accacaagaa ataccgctcg gccacccgtg acgtcatttt


 


1141
ccgcctgcag tttcacactg gggctgtgca gggctacggg ctggtgtttg ggaaggagga


 


1201
tctggacaat gccagcaaag atgaccgttt tcctgactat gggaaggttg aattagtctt


 


1261
ctctgccacg cctgagaaga ttcaagggtc cgaacacttg tacaacgacc acggtgtgat


 


1321
tgtggactac aacacaacag acccactgat acgctgggac tcgtacgaga acctcagtgc


 


1381
agatggagaa gtgctacaca cgcagggccc tgtcgatggc agcctttacg cgaaggtgag


 


1441
gaagaaaagc tcctcggatc ctggcatccc aggtggcccc caggcaatcc cggccaccaa


 


1501
cagcccagac cacagtgacc acaccttgtc tgtcagcagt gactccggcc actctacagc


 


1561
ctctgccagg acggataaga cggaagagcg cctggcccca ggaaccagga ggggcctgag


 


1621
tgcccaggag aaggcagagt tggaccagct gctcagtggc tttggcctgg aagatcctgg


 


1681
aagctccctc aaggaaatga ctgatgctcg aagcaagtac agtgggaccc gccacgtggt


 


1741
gccagcccag gttcacgtga atggagacgc tgctctgaag gatcgggaga cagacattct


 


1801
ggatgacgag atgccccacc acgacctgca cagtgtggac agccttggga ccctgtcctc


 


1861
ctcggaaggg cctcagtcgg cccacctggg tcccttcacc tgccacaaga gcagccagaa


 


1921
ctcactccta tctgacggtt ttggcagcaa cgttggtgaa gatccgcagg gcaccctcgt


 


1981
tccggacctg ggccttggca tggacggccc ctatgagcgg gagcggactt ttgggagtcg


 


2041
agagcccaag cagccccagc ccctgctgag aaagccctca gtgtccgccc agatgcaggc


 


2101
ctatgggcag agcagctact ccacacagac ctgggtgcgc cagcagcaga tggttgtagc


 


2161
tcaccagtat agcttcgccc cagatgggga ggcccggctg gtgagccgct gccctgcaga


 


2221
caatcctggc ctcgtccagg cccagcccag agtgccactc acccccaccc gagggaccag


 


2281
cagtagggtg gctgtccaga ggggtgtagg cagtgggcca catccccctg acacacagca


 


2341
gccctctccc agcaaagcgt tcaaacccag gtttccagga gaccaggttg tgaatggagc


 


2401
cggcccagag ctgagcacag gcccctcccc aggctcgccc accctggaca tcgaccagtc


 


2461
catcgagcag ctcaacaggc tgatcctgga gctggatccc accttcgagc ccatccctac


 


2521
ccacatgaac gccctcggta gccaggccaa tggctctgtg tctccagaca gcgtgggagg


 


2581
tgggctccgg gcaagcagca ggctgcctga cacaggagag ggccccagca gggccaccgg


 


2641
gcggcaaggc tcctctgctg aacagcccct gggcgggaga ctcaggaagc tgagcctggg


 


2701
gcagtacgac aacgatgctg gggggcagct gcccttctcc aaatgtgcat ggggaaaggc


 


2761
tggtgtggac tatgccccaa acctgccgcc attcccctca ccagcggacg tcaaagagac


 


2821
gatgacccct ggctatcccc aggacctcga tattatcgat ggcagaattt taagtagcaa


 


2881
ggagtccatg tgttcaactc cagcatttcc tgtgtctcca gagacaccgt atgtgaaaac


 


2941
agcgctgcgc catcctccgt tcagcccacc tgagcccccg ctgagcagcc cagccagtca


 


3001
gcacaaagga ggacgtgaac cacgaagctg ccctgagacg ctcactcacg ctgtggggat


 


3061
gtcagagagc cccatcggac ccaaatccac gatgctccgg gctgatgcgt cctcgacgcc


 


3121
ctcctttcag caggcttttg cttcttcctg caccatttcc agcaacggcc ctgggcagag


 


3181
gagagagagc tcctcttctg cagaacgcca gtgggtggag agcagcccca agcccatggt


 


3241
ttccctgctg gggagcggcc ggcccaccgg aagtcccctc agcgctgagt tctccggtac


 


3301
caggaaggac tccccagtgc tgtcctgctt cccgccgtca gagctccagg ctcctttcca


 


3361
cagccatgag ctgtccctag cagagccacc ggactccctg gcgcctccca gcagccaggc


 


3421
cttcctgggc ttcggcaccg ccccagtggg aagtggcctt ccgcccgagg aggacctggg


 


3481
ggccttgctg gccaattctc atggagcgtc accgaccccc agcatcccgc tgacagcgac


 


3541
aggggctgcc gacaatggct tcctgtccca caactttctc acggtggcgc ctggacacag


 


3601
cagccaccac agtccaggcc tgcagggcca gggtgtgacc ctgcccgggc agccacccct


 


3661
ccctgagaag aagcgggcct cggaggggga tcgttctttg ggctcagtct ctccctcctc


 


3721
cagtggcttc tccagcccgc acagcgggag caccatcagt atccccttcc caaatgtcct


 


3781
tcccgacttt tccaaggctt cagaagcggc ctcacctctg ccagatagtc caggtgataa


 


3841
acttgtgatc gtgaaatttg ttcaagacac ttccaagttc tggtacaagg cggatatttc


 


3901
aagagaacaa gccatcgcca tgttgaagga caaggagccg ggctcattca ttgttcgaga


 


3961
cagccattcc ttccgagggg cctatggcct ggccatgaag gtggccacgc ccccaccttc


 


4021
agtcctgcag ctgaacaaga aagctggaga tttggccaat gaactcgtcc ggcacttttt


 


4081
gatcgagtgt accccgaagg gagtgcggtt gaaagggtgc tcgaatgaac catatttcgg


 


4141
gagcctgacg gccttggtgt gccagcattc catcacgccc ttggccttgc cgtgcaagct


 


4201
gcttatccca gagagagatc cattggagga aatagcagaa agttctcccc agacggcagc


 


4261
caattcagca gctgagctgt tgaagcaggg ggcagcctgc aatgtgtggt acttgaactc


 


4321
tgtggagatg gagtccctca ccggccacca ggcgatccag aaggccctga gcatcaccct


 


4381
ggtccaggag cctccacctg tgtccacagt tgtgcacttc aaggtgtcag cccagggcat


 


4441
caccctgaca gacaatcaga ggaagctctt cttccggagg cattaccccg tgaacagtgt


 


4501
gattttctgt gccttggacc cacaagacag gaagtggatc aaagatggcc cttcctcaaa


 


4561
agtctttgga tttgtggccc ggaagcaggg cagtgccacg gataatgtgt gccacctgtt


 


4621
tgcagagcat gaccctgagc agcctgccag tgccattgtc aacttcgtat caaaggtcat


 


4681
gattggttcc ccaaagaagg tctgagaact cccctccctc cctggaccca ccgatgcctc


 


4741
tcgaagccct ggagacagcc gttgggtgag ggtggggccc ccacttttta ccaaactagt


 


4801
aaacctgaca ttccaggccc atgaggggaa agaggatctt ccagctctgc aaaaacaaga


 


4861
acaaacaaca tcaccgtgaa ttggcctttc ctgaaagtga cttatctgac acatctctgt


 


4921
agccacatgc tttttgggta gaagaagctg ggcatgggtg caccccaccc cctagggtcc


 


4981
ccatgggaaa gggacatgca aggaaacagc acagaacacg aggtggtccc catgtccctg


 


5041
gcacactagc attccggggg atgaggaatc cccagccctt gaggcagagg tgccgagtga


 


5101
ctgccatgct tcgcccgtcc gcatgggcgc ttctgtccag ctgcacccga ggccgggggt


 


5161
ttccctcacc tcggtcttcc caagatggag atgctaacga aactgagaag ggggcgtatg


 


5221
tttgacgaag gtttgtgcaa gtcaggccct tctggaacac agcagggcct acaacgaggg


 


5281
gcctttgcga tgggctgtga ggatgggggt ggtgggaaga attggccacg ttggagaccc


 


5341
catgccaccc caccatggtg agtgctctgt gcctcctgct cacctgtggt gagctgggcg


 


5401
agctgggcga gctgggcgag ctgggctggg gagagcctgt gaggaccgag aggagaaatg


 


5461
agaagaagga acaaaaatat tatttctatg taatttatat tttacttatg ccaaattatt


 


5521
tatgataatt tgccattgct atactgtacc agtgtcaaat gctgcagcct gccaagctgt


 


5581
gattttgtga ggcttgtccc tatgtaggat gcaccgcagg cccctggcca ctgaaagagt


 


5641
gtgcagtgga ctgtgggtct cccatatgcg gtgccgccca aaggtggctt tgcctcaagc


 


5701
aacctaccct gatgttttac tcattggaat gtttttcccc gattgtggat gacttctttt


 


5761
ctgatggaga gagtccagga gggatggaaa actcctggat ttaagctcag catcccccac


 


5821
atgggctttt cgatcatctt caggcctgaa gctgcacgac ctgaagttcg cctgcattta


 


5881
tcagccctct ttgtgctgct ccttgccacc ttggggttcc tgctggggac catgtgtggt


 


5941
tgtggcatgt gtgagcagaa gggaggatga ggaaaaagag aagaaacccc ggtactgaca


 


6001
agctgttttt gagtgccact gtttgccatc atctaagcca ctgaatcaag tgtatttcag


 


6061
gcttatttca acattccaat gccctggttt tcctgcttga atctgttcgt ggtcaaaggt


 


6121
ttgggggaat ttgtgaccct ggaacatccc cagagtgaaa gatggagctg ggccacatca


 


6181
gaataaggcc ttggccccat cctctcacag cctaggtgct ctgcaggcat gctgactgtc


 


6241
ctgattgcga tccagcccga aattccctcc tctgctttca aaagtcaaat cccccattct


 


6301
taggccacac tggtgtcaca agctcctgtc agggagctgg ggtttgggaa tgtgctttgt


 


6361
gaactctgct ttaaagtgag gggccgagga aaacttagaa acaggcagag ttggaagcag


 


6421
ccaaatcaca gtgggtgttg tgtgtgtgtg cgtgtgtgca tgcgtgcgtg tatgcgtgtg


 


6481
tgaaagcagg tggaccattc cactttttag ctcctattga tgcaccaaac caagtgcctc


 


6541
atttctgtgc caaatgtttg ccttggtcgt tgtggacctc cttctctaac ttgcggtggc


 


6601
atgactgtca ggaggtgctg gcattttcag cagatcctca tgtgttgacc ctgatgtctt


 


6661
tagcagaggc ctctagcatc tcggtttttc atccactgca ggaatgtggc cacagggagc


 


6721
agaggtttgt actttcccca agaggtcctc atcctgagac ggtctctacc catgtttaac


 


6781
ccaaagagtg caggccaggt tccttatcct tctgatgaag gatgagagag ctcatttaga


 


6841
agtcagagca aactagggtc tcagtattga gaaacgcagc ctgccaggga atcacagaga


 


6901
catcggggtg cccgcgatgg ccctcatgaa gccatgcctc gacggcattc aggaagccct


 


6961
gcaaacgtgc tttttgaact cattggccag gtgtgatttt tacacaaggt aaacgtggtc


 


7021
aagggcatcg gggaatttgc tccaagcaga tagctccctc tgaggaacca aaggaagcaa


 


7081
gtttccacga tttctgaaga gctggtatag gaagtttctt tcttcctttt gtgttacatg


 


7141
tgcattaaac agaacaagct gtgtgtcatc acagattgta ctgtgggctc agaaaccgtg


 


7201
agagagcccc caccgtggac accggctcta gggccacagg aaaaggaacg tttccaggca


 


7261
ttttgtctcc agggctcccg ctggacaggc acgtactgcc ctggggagta aatgcggaga


 


7321
gttcacgaac tgtgcccaac gcatgttata gccagggtcc tactaactac tcagtaaaag


 


7381
aacgtattgt tgtattcctc cagtgttaag ctatagccat gttaaaagtc actgtgcatt


 


7441
tattctcagc atcaaatacc ttgtaacgtc ttctctgcct tgttagtgca tatttttact


 


7501
tttctgatac tgtaaagaat atatccagta tgtaaatgaa tgttctataa atcttttgta


 


7561
tagtcatttt ctctgctcct taaatatcat ctctattcag agtataataa aattatgaac


 


7621
ttggtaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa


 


7681
aaaaaaaaaa aaaaaaa






One example of a nucleic acid sequence for human TSPAN12 is available as NCBI accession number NM_012338 (gi: 48255911). This sequence is recited below for easy reference as SEQ ID NO:170.









1
ggccctggct gccgccgctg cctcgtccgg actcggagag gacttgggag ggacagcggc



 


61
gctgggaggt ggcttagcag agactttcca gcaactgctg cccaggactt tttttttttt


 


121
ttttcttttt cccaggaggc ggcgacggcg gcggcggggg gagaggaaga gaaagaagcg


 


181
tctccagctg aagccaatgc agccctccgg ctctccgcga agaagttccc tgccccgatg


 


241
agcccccgcc gtgcgtcccc gactatcccc aggcgggcgt ggggcaccgg gcccagcgcc


 


301
gacgatcgct gccgttttgc ccttgggagt aggatgtggt gaaaggatgg ggcttctccc


 


361
ttacggggct cacaatggcc agagaagatt ccgtgaagtg tctgcgctgc ctgctctacg


 


421
ccctcaatct gctcttttgg ttaatgtcca tcagtgtgtt ggcagtttct gcttggatga


 


481
gggactacct aaataatgtt ctcactttaa ctgcagaaac gagggtagag gaagcagtca


 


541
ttttgactta ctttcctgtg gttcatccgg tcatgattgc tgtttgctgt ttccttatca


 


601
ttgtggggat gttaggatat tgtggaacgg tgaaaagaaa tctgttgctt cttgcatggt


 


661
actttggaag tttgcttgtc attttctgtg tagaactggc ttgtggcgtt tggacatatg


 


721
aacaggaact tatggttcca gtacaatggt cagatatggt cactttgaaa gccaggatga


 


781
caaattatgg attacctaga tatcggtggc ttactcatgc ttggaatttt tttcagagag


 


841
agtttaagtg ctgtggagta gtatatttca ctgactggtt ggaaatgaca gagatggact


 


901
ggcccccaga ttcctgctgt gttagagaat tcccaggatg ttccaaacag gcccaccagg


 


961
aagatctcag tgacctttat caagagggtt gtgggaagaa aatgtattcc tttttgagag


 


1021
gaaccaaaca actgcaggtg ctgaggtttc tgggaatctc cattggggtg acacaaatcc


 


1081
tggccatgat tctcaccatt actctgctct gggctctgta ttatgataga agggagccgg


 


1141
ggacagacca aatgatgtcc ttgaagaatg acaactctca gcacctgtca tgtccctcag


 


1201
tagaactgtt gaaaccaagc ctgtcaagaa tctttgaaca cacatccatg gcaaacagct


 


1261
ttaatacaca ctttgagatg gaggagttat aaaaagaaat gtcacagaag aaaaccacaa


 


1321
acttgtttta ctggacttgt gaatttttga gtacatacta tgtgtttcag aaatatgtag


 


1381
aaataaaaat gttgccataa aataacacct aagcatatac tattctatgc tttaaaatga


 


1441
ggatggaaaa gtttcatgtc ataagtcacc acctggacaa taattgatgc ccttaaaatg


 


1501
ctgaagacag atgtcatacc cactgtgtag cctgtgtatg acttttactg aacacagtta


 


1561
tgttttgagg cagcatggtt tgattagcat ttccgcatcc atgcaaacga gtcacatatg


 


1621
gtgggactgg agccatagta aaggttgatt tacttctacc aactagtata taaagtacta


 


1681
attaaatgct aacataggaa gttagaaaat actaataact tttattactc agcgatctat


 


1741
tcttctgatg ctaaataaat tatatatcag aaaactttca atattggtga ctacctaaat


 


1801
gtgatttttg ctggttacta aaatattctt accacttaaa agagcaagct aacacattgt


 


1861
cttaagctga tcagggattt tttgtatata agtctgtgtt aaatctgtat aattcagtcg


 


1921
atttcagttc tgataatgtt aagaataacc attatgaaaa ggaaaatttg tcctgtatag


 


1981
catcattatt tttagccttt cctgttaata aagctttact attctgtcct gggcttatat


 


2041
tacacatata actgttattt aaatacttaa ccactaattt tgaaaattac cagtgtgata


 


2101
cataggaatc attattcaga atgtagtctg gtctttagga agtattaata agaaaatttg


 


2161
cacataactt agttgattca gaaaggactt gtatgctgtt tttctcccaa atgaagactc


 


2221
tttttgacac taaacacttt ttaaaaagct tatctttgcc ttctccaaac aagaagcaat


 


2281
agtctccaag tcaatataaa ttctacagaa aatagtgttc tttttctcca gaaaaatgct


 


2341
tgtgagaatc attaaaacat gtgacaattt agagattctt tgttttattt cactgattaa


 


2401
tatactgtgg caaattacac agattattaa atttttttac aagagtatag tatatttatt


 


2461
tgaaatggga aaagtgcatt ttactgtatt ttgtgtattt tgtttatttc tcagaatatg


 


2521
gaaagaaaat taaaatgtgt caataaatat tttctagaga gtaaaaaaaa aaaaaaaaa






One example of a nucleic acid sequence for human UPP1 is available as NCBI accession number NM_003364 (gi: 31742506). This sequence is recited below for easy reference as SEQ ID NO:171.









1
ggtcagctga gttcgccggc ccagggcagg cggggcccga gcctagcggt aacccccggg



 


61
cagggcgggg ccgctcgcag actccatatg agattcacct cgcaggtggt tccctcattc


 


121
gagtgctccg gcgcacagac ccgcgccccg ccgtctgcga gcctcccgag agccgtccct


 


181
tcgtccggcc ctggagcatt gcgtttgtcg ccggtgtcgc agtgcgagga tggcgccgcg


 


241
ggtgtagcgg ctctctgcgc aggccgagtg ggcccagaga agcgaggaac tccgcagctc


 


301
gtcgacacgt ctcgtctcct gtcccaattc agggcttggt gaggtgactc gcggtcgcgg


 


361
gtgactcgcc ggcaggacac tgcctggaac gcctggagcg cctcccactg cagacgtctg


 


421
tccgcctcca gccgctctcc tctgacgggt cctgcctcag ttggcggaat ggcggccacg


 


481
ggagccaatg cagagaaagc tgaaagtcac aatgattgcc ccgtcagact tttaaatcca


 


541
aacatagcaa aaatgaaaga agatattctc tatcatttca atctcaccac tagcagacac


 


601
aatttcccag ccttgtttgg agatgtgaag tttgtgtgtg ttggtggaag cccctcccgg


 


661
atgaaagcct tcatcaggtg cgttggtgca gagctgggcc ttgactgccc aggtagagac


 


721
tatcccaaca tctgtgcggg aactgaccgc tatgccatgt ataaagtagg accggtgctg


 


781
tctgtcagtc atggtatggg cattccttct atctcaatca tgttgcatga gctcataaag


 


841
ctgctgtact atgcccggtg ctccaacgtc actatcatcc gcattggcac ttctggtggg


 


901
ataggtctgg agcccggcac tgtggtcata acagagcagg cagtggatac ctgcttcaag


 


961
gcagagtttg agcagattgt cctggggaag cgggtcatcc ggaaaacgga ccttaacaag


 


1021
aagctggtgc aggagctgtt gctgtgttct gcagagctga gcgagttcac cacagtggtg


 


1081
gggaacacca tgtgcacctt ggacttctat gaagggcaag gccgtctgga tggggctctc


 


1141
tgctcctaca cggagaagga caagcaggcg tatctggagg cagcctatgc agccggcgtc


 


1201
cgcaatatcg agatggagtc ctcggtgttt gccgccatgt gcagcgcctg cggcctccaa


 


1261
gcggccgtgg tgtgtgtcac cctcctgaac cgcctggaag gggaccagat cagcagccct


 


1321
cgcaatgtgc tcagcgagta ccagcagagg ccgcagcggc tggtgagcta cttcatcaag


 


1381
aagaaactga gcaaggcctg agcgctgccc tgcacctccg cagacctgct gtgatgactt


 


1441
gccattaaaa gcattgtcca aaatcccctg ttgtgtggac tttgagcaca ctttacacaa


 


1501
gaatctagaa aatcagatcg cgattaagag acagagaatc ttggattaac cgcatgggag


 


1561
atgttcttcc ttttgaagtt tcattggagc attttcaatg atgttagcct gatttggggt


 


1621
ttcttcaaga acattctacc aaatttttgt actatttcta gggaaatttt tcagacttta


 


1681
aaattctaat ggtagtcaga tttcatgtca ctaaacaaga aatctgacaa tagtgccagg


 


1741
aaactaattt cctgatacat taaaaaaatt ccatgcaaaa aaaaaaaaaa aaaaaa






One example of a nucleic acid sequence for human NAUK2 is available as NCBI accession number NM_030952 (gi: 13569921). This sequence is recited below for easy reference as SEQ ID NO:172.









1
gtgctttact gcgcgctctg gtactgctgt ggctccccgt cctggtgcgg gacctgtgcc



 


61
ccgcgcttca gccctccccg cacagcctac tgattcccct gccgcccttg ctcacctcct


 


121
gctcgccatg gagtcgctgg ttttcgcgcg gcgctccggc cccactccct cggccgcaga


 


181
gctagcccgg ccgctggcgg aagggctgat caagtcgccc aagcccctaa tgaagaagca


 


241
ggcggtgaag cggcaccacc acaagcacaa cctgcggcac cgctacgagt tcctggagac


 


301
cctgggcaaa ggcacctacg ggaaggtgaa gaaggcgcgg gagagctcgg ggcgcctggt


 


361
ggccatcaag tcaatccgga aggacaaaat caaagatgag caagatctga tgcacatacg


 


421
gagggagatt gagatcatgt catcactcaa ccaccctcac atcattgcca tccatgaagt


 


481
gtttgagaac agcagcaaga tcgtgatcgt catggagtat gccagccggg gcgaccttta


 


541
tgactacatc agcgagcggc agcagctcag tgagcgcgaa gctaggcatt tcttccggca


 


601
gatcgtctct gccgtgcact attgccatca gaacagagtt gtccaccgag atctcaagct


 


661
ggagaacatc ctcttggatg ccaatgggaa tatcaagatt gctgacttcg gcctctccaa


 


721
cctctaccat caaggcaagt tcctgcagac attctgtggg agccccctct atgcctcgcc


 


781
agagattgtc aatgggaagc cctacacagg cccagaggtg gacagctggt ccctgggtgt


 


841
tctcctctac atcctggtgc atggcaccat gccctttgat gggcatgacc ataagatcct


 


901
agtgaaacag atcagcaacg gggcctaccg ggagccacct aaaccctctg atgcctgtgg


 


961
cctgatccgg tggctgttga tggtgaaccc cacccgccgg gccaccctgg aggatgtggc


 


1021
cagtcactgg tgggtcaact ggggctacgc cacccgagtg ggagagcagg aggctccgca


 


1081
tgagggtggg caccctggca gtgactctgc ccgcgcctcc atggctgact ggctccggcg


 


1141
ttcctcccgc cccctcctgg agaatggggc caaggtgtgc agcttcttca agcagcatgc


 


1201
acctggtggg ggaagcacca cccctggcct ggagcgccag cattcgctca agaagtcccg


 


1261
caaggagaat gacatggccc agtctctcca cagtgacacg gctgatgaca ctgcccatcg


 


1321
ccctggcaag agcaacctca agctgccaaa gggcattctc aagaagaagg tgtcagcctc


 


1381
tgcagaaggg gtacaggagg accctccgga gctcagccca atccctgcga gcccagggca


 


1441
ggctgccccg ctgctcccca agaagggcat tctcaagaag ccccgacagc gcgagtctgg


 


1501
ctactactcc tctcccgagc ccagtgaatc tggggagctc ttggacgcag gcgacgtgtt


 


1561
tgtgagtggg gatcccaagg agcagaagcc tccgcaagct tcagggctgc tcctccatcg


 


1621
caaaggcatc ctcaaactca atggcaagtt ctcccagaca gccttggagc tcgcggcccc


 


1681
caccaccttc ggctccctgg atgaactcgc cccacctcgc cccctggccc gggccagccg


 


1741
accctcaggg gctgtgagcg aggacagcat cctgtcctct gagtcctttg accagctgga


 


1801
cttgcctgaa cggctcccag agcccccact gcggggctgt gtgtctgtgg acaacctcac


 


1861
ggggcttgag gagcccccct cagagggccc tggaagctgc ctgaggcgct ggcggcagga


 


1921
tcctttgggg gacagctgct tttccctgac agactgccag gaggtgacag cgacctaccg


 


1981
acaggcactg agggtctgct caaagctcac ctgagtggag taggcattgc cccagcccgg


 


2041
tcaggctctc agatgcagct ggttgcaccc cgaggggaga tgccttctcc cccacctccc


 


2101
aggacctgca tcccagctca gaaggctgag agggtttgca gtggagccct gagcagggct


 


2161
ggatatggga agtaggcaaa tgaaatgcgc caagggttca gtgtctgtct tcagccctgc


 


2221
tgaacgaaga ggatactaaa gagaggggaa cgggaatgcc cgcgacagag tccacattgc


 


2281
ctgtttcttg tgtacatggg ggggccacag agacctggaa agagaactct cccagggccc


 


2341
atctcctgca tcccatgaat actctgtaca catggtgcct tctaaggaca gctccttccc


 


2401
tactcattcc ctgcccaagt ggggccagac ctctttacac acacattccc gttcctacca


 


2461
accaccagaa ctggatggtg gcacccctaa tgtgcatgag gcatcctggg aatggtctgg


 


2521
agtaacgctt cgttattttt atttttattt ttatttattt atttattttt ttgagacgga


 


2581
gtttcgctct tggtgcccag gctagagtgc aatggcgcga tctcagctca cctcaacctc


 


2641
cgcctcccgg gttcaagcga ttctcctgcc tcagcctccc tagtagctgg gattacaggc


 


2701
gcccgccacc atgcccggct aattttgtat ttttagtaga gacagggttt ctccatgttg


 


2761
gtcaggctgg tctcaaactc ccgacctcag gtgatccacc cacctcggcc tcccaaagtg


 


2821
ctgggattac aggcgtgagc caccgcgccc cacctaaccc ttccttattt agcctaggag


 


2881
taagagaaca caatctctgt ttcttcaatg gttctcttcc cttttccatc ctccaaacct


 


2941
ggcctgagcc tcctgaagtt gctgctgtga atctgaaaga cttgaaaagc ctccgcctgc


 


3001
tgtgtggact tcatctcaag gggcccagcc tcctctggac tccaccttgg acctcagtga


 


3061
ctcagaactt ctgcctctaa gctgctctaa agtccagact atggatgtgt tctctaggcc


 


3121
ttcaggactc tagaatgtcc atatttattt ttatgttctt ggctttgtgt tttaggaaaa


 


3181
gtgaatcttg ctgttttcaa taatgtgaat gctatgttct gggaaaatcc actatgacat


 


3241
ctaagttttg tgtacagaga gatatttttg caactatttc cacctcctcc cacaaccccc


 


3301
cacactccac tccacactct tgagtctctt tacctaatgg tctctaccta atggacctcc


 


3361
gtggccaaaa agtaccatta aaaccagaaa ggtgattgga aaaaaaaaaa aaaaaaaaaa


 


3421
aaaaaaaaaa aaaaaaaaaa aaa






REFERENCES


    1. Mazzaferri E L. Solitary thyroid nodule. 2. Selective approach to management. Postgrad Med. 1981; 70:107-109, 112, 116.
    2. Davies L. Welch H G. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006; 295:2164-2167.
    3. Arora N, Scognamiglio T, Zhu B, Fahey T J 3rd. Do benign thyroid nodules have malignant potential? An evidence-based review. World J Surg. 2008; 32:1237-1246.
    4. Chan J K. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002; 117:16-18.
    5. Franc B, de la Salmoniere P, Lange F, et al. Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Hum Pathol, 2003; 34:1092-1100.
    6. Lloyd R V, Erickson L A, Casey M B, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004; 28:1336-1340.
    7. Saxen E, Franssila K, Bjarnason O, Normann T, Ringertz N. Observer variation in histologic classification of thyroid cancer. Acta Pathol Microbiol Scand [A]. 1978; 86A:483-486.
    8. Hirokawa M, Carney J A, Goellner J R, et al. Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol. 2002; 26:1508-1514.
    9, Williams E D. Guest editorial: two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol. 2000; 8:181-183.
    10. Miettinen M, Karkkainen P. Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours, Virchows Arch. 1996; 429(4-5):213-21.9.
    11. Cheung C C, Ezzat S, Freeman J L, Rosen I B, Asa S L. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol, 2001; 14:338-342.
    12. Choi Y L, Kim M K, Suh J W, et al. Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci. 2005; 20:853-859,
    13. de Matos P S, Ferreira A P, de Oliveira Facuri F, Assumpcao L V, Metze K, Ward L S, Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology. 2005; 47:391-401.
    14. Papotti M, Rodriguez J, De Pompa R, Bartolazzi A, Rosai J. Galectin-3 and HBME-1 expression in well differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol. 2005; 18:541-546.
    15. Prasad M L, Pellegata N S, Huang Y. Nagaraja H N, de la Chapelle A, Kloos R T. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors, Mod Pathol. 2005; 18:48-57.
    16. Scognamiglio T, Hyjek E, Kao J, Chen Y T. Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol. 2006; 126:700-708.
    17, Fusco A, Chiappetta G, Hui P. et al. Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer. Am J Pathol. 2002; 160:2157-2167.
    18. Chevillard S, Ugolin N, Vieth P. et al. Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications. Clin Cancer Res. 2004; 10:6586-6597.
    19. Finley D J, Thu B, Barden C B, Fahey T J 3rd. Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg. 2004; 240:425-436; discussion 436-437.
    20. Huang Y, Prasad M, Lemon W J, et al. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA. 2001; 98:15044-15049.
    21. Mazzanti C, Zeiger M A, Costouros N G; et al. Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res. 2004; 64:2898-2903.
    22. Lubitz C C, Ugras S K, Kazam J J, et al. Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions. J Mol Diagn. 2006; 8:490-498; quiz 528.
    23. Jarzab B, Wiench M, Fujarewicz K, et al. Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. Cancer Res. 2005; 65:1587-1597.
    24. Nikiforova M N, Kimura E T, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003; 88:5399-5404.
    25. Fontaine J F, Mirebeau-Prunier D, Franc B, et al. Microarray analysis refines classification of non-medullary thyroid tumours of uncertain malignancy. Oncogene. 2008; 27:2228-2236.
    26. Frasca F, Nucera C, Pellegriti C, et al. BRAF(V600E) mutation and the biology of papillary thyroid cancer. Endocr. Relat. Cancer. 2008; 15:191-205.
    27. Kebebew E, Weng J, Bauer J, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann. Surg. 2007; 246:466-470; discussion 470-471.
    28. Trovisco V. Vieira de Castro I, Soares P, et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004; 202:247-251.
    29. Zhu X L, Zhou X Y, Zhu X Z, [BRAFV599E mutation and RET/PTC rearrangements in papillary thyroid carcinoma]. Zhonghua Bing Li Xue Za Zhi. 2005; 34:270-274.
    30. Pennelli N, Pennelli G, Merante Boschin I, Pelizzo M R. Thyroid intrafollicular neoplasia (TIN) as a precursor of papillary microcarcinoma. Ann Ital Chir. 2005; 76:219-224.
    31. Vasko V V, Gaudart J, Allasia C, et al. Thyroid follicular adenomas may display features of follicular carcinoma and follicular variant of papillary carcinoma. Eur J Endocrinol. 2004; 1.51:779-786.
    32. Prasad M L, Huang Y, Pellegata N S, de la Chapelle A, Kloos R T. Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC. Histopathology. 2004; 45:39-46.
    33. Arif S, Blanes A, Diaz-Cano S J. Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma. Histopathology. 2002; 41:357-362.
    34. Nikiforov Y E. RET/PTC rearrangement—a link between Hashimoto's thyroiditis and thyroid cancer . . . or not. J Clin Endocrinol Metab. 2006; 91:2040-2042.
    35. Rhoden K J, Unger K, Salvatore G, et al. RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma, J. Clin Endocrinol Metab. 2006; 91:2414-2423.
    36. Rosai J. Handling of thyroid follicular patterned lesions, Endocr Pathol. 2005; 16:279-283.
    37. Liu J, Singh B, Tallini G, et al. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer. 2006; 1.07:1255-1264.
    38. Vickery A L Jr, Thyroid papillary carcinoma. Pathological and philosophical controversies. Am J Surg Pathol. 1983; 7: 797-807.
    39. Evans H L. Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years. Am J Surg Pathol. 1987; 11:592-597.


All patents and publications referenced or mentioned herein are indicative of the levels of skill of those skilled in the art to which the invention pertains, and each such referenced patent or publication is hereby incorporated by reference to the same extent as if it had been incorporated by reference in its entirety individually or set forth herein in its entirety. Applicants reserve the right to physically incorporate into this specification any and all materials and information from any such cited patents or publications.
The specific methods and compositions described herein are representative of preferred embodiments and are exemplary and not intended as limitations on the scope of the invention. Other objects, aspects, and embodiments will occur to those skilled in the art upon consideration of this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, or limitation or limitations, which is not specifically disclosed herein as essential. The methods and processes illustratively described herein suitably may be practiced in differing orders of steps, and that they are not necessarily restricted to the orders of steps indicated herein or in the claims. As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a host cell” includes a plurality (for example, a culture or population) of such host cells, and so forth. Under no circumstances may the patent be interpreted to be limited to the specific examples or embodiments or methods specifically disclosed herein. Under no circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation expressly adopted in a responsive writing by Applicants.
The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intent in the use of such terms and expressions to exclude any equivalent of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as claimed. Thus, it will be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.
Other embodiments are within the following claims. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

## Claims

1. A method comprising:
measuring levels of RNA expression of genes consisting of DPP4, SERPINA1, MATN2, and PROS1 in a test tissue or cell sample from a subject by microarray analysis and/or quantitative polymerase chain reaction using primers or probes, wherein at least one of the primers or probes is SEQ ID NO: 18, 33, 42, or 50; and
treating the subject for thyroid cancer when thyroid cancer cells in the test tissue or cell sample have at least a 50% increase in the measured levels of RNA expression of genes consisting of DPP4, SERPINA1, and PROS1 and at least a 50% decrease in the measured level of MATN2 RNA expression compared to RNA expression levels of genes consisting of DPP4, SERPINA1, MATN2, and PROS1 in a benign thyroid standard sample.

2. The method of claim 1, further comprising performing fine needle aspiration to obtain the test tissue or cell sample.

3. The method of claim 1, wherein the test tissue sample or cell sample is an unclassified tumor sample.

4. The method of claim 1, wherein the test tissue or cell sample is a formalin fixed test tissue or cell sample.

5. The method of claim 1, wherein the method detects thyroid cancer cells in the test tissue or cell sample with greater than 80% specificity.

6. The method of claim 1, wherein thyroid cancer cells are detected in the test tissue or cell sample when the RNA expression of DPP4, SERPINA1, MATN2, and PROS1 is at least 2.4 fold different as compared to the RNA expression of DPP4, SERPINA1, MATN2, and PROS1 in the benign thyroid standard sample.

7. A method comprising:
obtaining a test thyroid tissue sample from a subject by fine needle aspirate;
measuring levels of RNA expression of genes consisting of DPP4, SERPINA1, MATN2, and PROS1 in the test thyroid tissue sample using primers or probes, wherein at least one of the primers or probes is SEQ ID NO: 18, 33, 42, or 50; and
treating the subject for thyroid cancer when at least a 50% increase in the measured levels of RNA expression of genes consisting of DPP4, SERPINA1, and PROS1 and at least a 50% decrease in the measured level of MATN2 RNA expression are detected in the thyroid tissue sample compared to RNA expression levels of genes consisting of DPP4, SERPINA1, MATN2, and PROS1 in a benign thyroid standard sample.

8. The method of claim 7, wherein thyroid cancer cells are detected in the test thyroid tissue sample when the RNA expression of DPP4, SERPINA1, MATN2, and PROS1 is at least 2.4 fold different as compared to the RNA expression of genes consisting of DPP4, SERPINA1, MATN2, and PROS1 in the benign thyroid standard sample.

9. The method of claim 7, wherein the test tissue sample is an unclassified tumor sample.

10. The method of claim 1, further comprising performing reverse transcription polymerase chain reaction, and/or real time polymerase chain reaction, before or in conjunction with microarray analysis and/or quantitative polymerase chain reaction.