KR102115941B1 - Single nucleotide polymorphism for predicting the risk factor of metabolic syndrome and the use thereof - Google Patents

Abstract

The present invention relates to a single nucleotide polymorphism (SNP) for predicting a risk factor of metabolic syndrome and a use thereof, particularly comprising the steps of: organizing and preparing a next generation sequence (NGS) gene panel for a group of metabolic syndrome, a group of metabolic syndrome accompanied by non-alcoholic fatty liver disease, and a normal control group without any of the diseases; preparing an NGS library by using the NGS gene panel; generating NGS data for the prepared NGS library by using an NGS analysis instrument; and selecting SNP deemed to be clinically significant based on a bioinformatical analysis, thereby confirming an SNP which is not detected from the normal control group, but is significantly detected from the group of metabolic syndrome and the group of metabolic syndrome accompanied by non-alcoholic fatty liver disease. Accordingly, the SNP can be useful in early diagnosing and predicting metabolic syndrome and a risk factor closely related thereto.

Description

Single nucleotide polymorphism for predicting the risk factor of metabolic syndrome and the use thereof

The present invention relates to a single nucleotide polymorphisml (SNP) for predicting risk factors of metabolic syndrome and a use thereof.

Metabolic syndrome refers to a condition that has three or more of the five risk factors for abdominal obesity, high blood pressure, hypertriglyceridemia, low high density (HDL) cholesterol, and hyperglycemia. If the metabolic syndrome condition persists without proper personal management, it can lead to serious disease conditions such as various cardiovascular diseases, type 2 diabetes, and non-alcoholic steatohepatitis. It is known as a disease of modern people that requires early prediction, diagnosis, treatment, and systematic management. Recently, in Korea, the obese population has exploded due to westernization of dietary habits and changes in lifestyle, and accordingly, the prevalence of metabolic syndrome is rapidly increasing.

On the other hand, in Western cases, ^{high obesity with a BMI of more than 30 kg/m 2} accounts for about 33.8% of the total population, and it is known that the prevalence of metabolic syndrome with non-alcoholic steatosis has a prevalence of about 30%. However, it is known that the prevalence of non-alcoholic steatosis, including metabolic syndrome, is almost similar, although only 5% of cases in the East, including Korea, have a BMI ^{of more than 30 kg/m 2 compared to the West.} In addition, European, North American, and Latino races show a much higher total calorie intake than Asians, but the prevalence of nonalcoholic steatosis is not significantly different from that of Koreans. This suggests that there is a link to the susceptibility of non-alcoholic steatosis.

Gene biomarkers can be widely used in molecular diagnosis and treatment areas, such as gene expression, gene diversity, and their interactions, so they are used to predict and diagnose the onset of metabolic syndrome and risky diseases closely related to Koreans early. For example, the existing domestic and international research on metabolic syndrome is called a genome-wide association study (GWAS), a number of single nucleotide polymorphisms scattered throughout the human genome that are related to the human phenotype. polymorphism, SNP).

However, since the GWAS technology is a method of analyzing SNPs for human phenotypes, it is limited to analysis of SNPs (universal SNPs) commonly possessed by the general public. For this reason, since most of the SNPs related to metabolic syndrome and related diseases (including non-alcoholic steatosis, etc.) found in existing GWAS studies are SNPs that are also found in normal people without the disease, the entire metabolic syndrome and related diseases It is possible to explain only about 20 to 30% of them as the cause of the outbreak.

Therefore, in order to explain the exact cause of the onset of metabolic syndrome and related risk diseases, the influence of the rare mutant gene biomarker, which is not commonly present in individuals or the general public, must be considered, and detection and selection methods for this This is very important.

In other words, in addition to the microarray technology that analyzes only universal SNPs such as the existing GWAS, we have developed a technology to find genetic biomarkers of individuals who show metabolic syndrome and risk factors closely related to metabolic syndrome by analyzing the entire nucleotide sequence of each gene. It is necessary to apply.

Accordingly, the present inventors have tried to develop a genetic biomarker with improved accuracy in early diagnosis and prediction of metabolic syndrome and risk factors closely related thereto. As a result, the metabolic syndrome group and the disease are accompanied by the metabolic syndrome group and non-alcoholic steatosis. A newly designed NGS (next generation sequencing) gene panel test was applied to the normal control group with no symptoms, and through this test, it was not detected in the normal control group, and the metabolic syndrome group and non-alcoholic steatohepatic disease were combined. Since SNPs that are significantly detected only in the accompanying metabolic syndrome group have been identified, the SNP can be usefully used for early diagnosis and prediction of metabolic syndrome and risk factors closely related thereto.

US Patent Publication No. 2009-0186347

Genome-Wide Association Study of Metabolic Syndrome in Koreans, SW Jeong, et al. Genomics & Informatics 2014; 12(4): 187-194. Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population, J Yang, et al. PLoS One. 2014; 9(6): e100548.

An object of the present invention is to provide a single nucleotide polymorphisml (SNP) for predicting risk factors for metabolic syndrome and a method for predicting risk factors for metabolic syndrome using the same.

In order to achieve the above object, the present invention is a single nucleotide polymorphism in which the base at the 796th position in the ABCA1 gene consisting of SEQ ID NO: 1 is changed from G to A (c.796G>A), and the base at the 1631th position is at G Single nucleotide polymorphism changed to A (c.1631G>A), single nucleotide polymorphism in which the base at 6608 is changed from T to A (c.6608T>A), and the base at 4995 is changed from G to T Polymorphism (c.4995G>T) or single nucleotide polymorphism in which the base at the 2940th position is changed from G to T (c.2940G>T), the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 is in G Single nucleotide polymorphism changed to T (c.452G>T), single nucleotide polymorphism in which the base at position 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), located at 814 Monobasic polymorphism in which the base is changed from A to T (c.814A>T), monobasic polymorphism in which the base at 571 is changed from C to A (c.571C>A), and the base at 1045 is changed from C to C. Single nucleotide polymorphism changed to A (c.1045C>A), single nucleotide polymorphism in which the base at position 769 changed from C to T (c.769C>T), single base at position 197 changed from T to A Polymorphism (c.197T>A) or single nucleotide polymorphism in which the base at the 196th is changed from G to T (c.196G>T), and the base at the 745th in the SCARB1 gene consisting of SEQ ID NO:27 is G Including any one or more monobasic polymorphisms selected from the group consisting of monobasic polymorphism changed from to T (c.745G>T) or monobasic polymorphism changed from G to A in the fourth position (c.4G>A) And, as a risk factor for metabolic syndrome, including a gene panel for early diagnosis or prediction of low HDL cholesterol and a probe polynucleotide complementary to the gene of the gene panel, as a risk factor for metabolic syndrome, early diagnosis of low HDL cholesterol or Provides a prediction kit.

In addition, the present invention is a single base polymorphism in which the base at the 796th position in the ABCA1 gene consisting of SEQ ID NO: 1 is changed from G to A (c.796G>A), the single base at which the base at the 1631th is changed from G to A Polymorphism (c.1631G>A), monobasic polymorphism in which the base at position 6608 is changed from T to A (c.6608T>A), monobasic polymorphism in which the base at position 4995 is changed from G to T (c. 4995G>T) or a single nucleotide polymorphism in which the base at the 2940th position was changed from G to T (c.2940G>T), a single base in which the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 was changed from G to T Polymorphism (c.452G>T), single nucleotide polymorphism in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), the base at 814 is from A to T Single base polymorphism changed to (c.814A>T), single base polymorphism in which the base at the 571th was changed from C to A (c.571C>A), and the base at the 1045th was changed from C to A Polymorphism (c.1045C>A), monobasic polymorphism in which the base at position 769 is changed from C to T (c.769C>T), monobasic polymorphism in which the base at position 197 is changed from T to A (c. 197T>A) or single nucleotide polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T Any one or more single nucleotide polymorphisms selected from the group consisting of polymorphism (c.745G>T) or monopolymorphism in which the base at the fourth position is changed from G to A (c.4G>A) can be detected at the nucleic acid level. It provides a composition for early diagnosis or prediction of hypoHDL cholesterolemia as a risk factor for metabolic syndrome, including reagents that are present.

In addition, the present invention

1) separating the nucleic acid from the biological sample isolated from the subject; And

2) Single nucleotide polymorphism in which the base at the 796 position of the ABCA1 gene composed of SEQ ID NO: 1 is changed from G to A (c.796G>A) from the nucleic acid, and the single base at which the base at the 1631 position is changed from G to A Polymorphism (c.1631G>A), monobasic polymorphism in which the base at position 6608 is changed from T to A (c.6608T>A), monobasic polymorphism in which the base at position 4995 is changed from G to T (c. 4995G>T) or a single nucleotide polymorphism in which the base at the 2940th position was changed from G to T (c.2940G>T), a single base in which the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 was changed from G to T Polymorphism (c.452G>T), single nucleotide polymorphism in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), the base at 814 is from A to T Single base polymorphism changed to (c.814A>T), single base polymorphism in which the base at the 571th was changed from C to A (c.571C>A), and the base at the 1045th was changed from C to A Polymorphism (c.1045C>A), monobasic polymorphism in which the base at position 769 is changed from C to T (c.769C>T), monobasic polymorphism in which the base at position 197 is changed from T to A (c. 197T>A) or single nucleotide polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T Identifying one or more single nucleotide polymorphism sequences selected from the group consisting of polymorphism (c.745G>T) or monobasic polymorphism (c.4G>A) in which the base at the fourth position is changed from G to A. It provides a method of providing information necessary for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, including.

In addition, the present invention changes the amino acid glycine (G) at the 266th from the N-terminus to arginine (R) from the biological sample isolated from the subject (c.796G>A), and the amino acid glycine (G) at the 544th This aspartic acid (D) changes (c.1631G>A), the amino acid isoleucine (I) at the 2203th changes to lysine (K) (c.6608T>A), the amino acid methionine at the 1665th (M ) Changed to isoleucine (I) (c.4995G>T) or the amino acid glutamine (Q) at the 980th changed to histidine (H) (c.2940G>T), an ABCA1 protein mutation, 151 from the N-terminus CETP protein mutation in which the amino acid glycine (G) is changed to valine (V) (c.452G>T) in the first, and aspartic acid (D), the amino acid in the 589th from the N-terminus, is changed to asparagine (N) ( c.1765G>A), the amino acid asparagine (N) at the 272th changed to tyrosine (Y) (c.814A>T), the amino acid at the 191th glutamine (Q) changed to lysine (K) (c. 571C>A), the amino acid glutamine (Q) at position 349 changes to lysine (K) (c.1045C>A), the amino acid arginine (R) at position 257 changes to tryptophan (W) (c.769C> T), the amino acid valine (V) at the 66th is changed to aspartic acid (D) (c.197T>A) or the amino acid at the 66th is valine (V) is changed to phenylalanine (F) (c.196G> T) mutation of the LDLR protein, and aspartic acid (D), an amino acid at the 249th from the N-terminus, changes to tyrosine (Y) (c.745G>T), or glycine (G), an amino acid at the second, serine ( It is necessary for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, comprising the step of identifying any one or more protein mutations selected from the group consisting of S) changed (c.4G>A) SCARB1 protein mutations. Provides a way to present information.

In the present invention, the steps of constructing and preparing a NGS (next generation sequence) gene panel for the metabolic syndrome group and the metabolic syndrome group accompanied by non-alcoholic steatosis and the normal control group without the disease at all; Preparing an NGS library using the NGS gene panel; Generating NGS data from the prepared NGS library using an NGS analysis device; And bioinformatics analysis based on the step of selecting SNPs that are judged to have clinical significance in the metabolic syndrome, which were not detected in the normal control group, and only in the metabolic syndrome group accompanied by the metabolic syndrome group and non-alcoholic steatosis. Since the SNPs that are significantly detected have been identified, the SNPs can be usefully used for early diagnosis and prediction of metabolic syndrome and risk factors closely related thereto.

1 is a diagram schematically illustrating a process of selecting single nucleotid polymorphism (SNP) related to metabolic syndrome and risk factors closely related thereto.

Hereinafter, the present invention will be described in detail.

The present invention is a single nucleotide polymorphism in which the base at the 796 position of the ABCA1 gene consisting of SEQ ID NO: 1 is changed from G to A (c.796G>A), and the single nucleotide polymorphism at the base at the 1631 position is changed from G to A ( c.1631G>A), monobasic polymorphism in which the base at the 6608th was changed from T to A (c.6608T>A), monobasic polymorphism in which the base at the 4995th was changed from G to T (c.4995G> T) or a single nucleotide polymorphism in which the base at the 2940 position was changed from G to T (c.2940G>T), a single nucleotide polymorphism in which the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 was changed from G to T ( c.452G>T), single nucleotide polymorphism in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 was changed from G to A (c.1765G>A), the base at the 814 was changed from A to T Monobasic polymorphism (c.814A>T), monobasic polymorphism in which the base at the 571th was changed from C to A (c.571C>A), monobasic polymorphism in which the base at the 1045th was changed from C to A ( c.1045C>A), monobasic polymorphism in which the base at position 769 changed from C to T (c.769C>T), monobasic polymorphism in which the base at position 197 changed from T to A (c.197T> A) or single nucleotide polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T (c.745G>T) or any one or more monobasic polymorphisms selected from the group consisting of a monobasic polymorphism in which the base at the fourth position is changed from G to A (c.4G>A), and a risk factor for metabolic syndrome As a result, a gene panel for early diagnosis or prediction of hypoHDL cholesterol is provided.

In addition, the present invention provides a kit for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, comprising a probe polynucleotide complementary to the gene of the gene panel.

In the present invention, the gene panel may be a next generation sequencing (NGS) gene panel.

In the present invention, the gene panel, more specifically, the NGS gene panel includes a probe polynucleotide complementary to the gene for prediction and diagnosis of metabolic syndrome and risk factors thereof. A method of preparing an NGS gene panel using the probe polynucleotide is well known in the art. The constitution "probe polynucleotide" constituting the NGS panel refers to a polynucleotide capable of hybridizing, and refers to an oligonucleotide capable of sequence-specifically binding to a complementary strand of a nucleic acid. The probe polynucleotide may be manufactured in the form of an oligonucleotide probe, a single strand DNA probe, a double strand DNA probe, an RNA probe, or the like. Each probe polynucleotide may consist of 10 or more, more specifically 100 to 150 consecutive bases. The probe polynucleotides are 5'-biotinylated or 3'-biotinylated polynucleotides composed of DNA or RNA capable of hybridizing and binding sequence-specifically to the complementary strand of the CDS (Coding DNA Sequence) of the target gene. It can hybridize to a specific portion of the entire CDS region of the target gene. In addition, the probe polynucleotides may be configured to share a hybridization region with probe polynucleotides that hybridize adjacently in order to reduce the hybridization missing region.

In addition, the present invention is a single base polymorphism in which the base at the 796th position in the ABCA1 gene consisting of SEQ ID NO: 1 is changed from G to A (c.796G>A), the single base at which the base at the 1631th is changed from G to A Polymorphism (c.1631G>A), monobasic polymorphism in which the base at position 6608 is changed from T to A (c.6608T>A), monobasic polymorphism in which the base at position 4995 is changed from G to T (c. 4995G>T) or a single nucleotide polymorphism in which the base at the 2940th position was changed from G to T (c.2940G>T), a single base in which the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 was changed from G to T Polymorphism (c.452G>T), single nucleotide polymorphism in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), the base at 814 is from A to T Single base polymorphism changed to (c.814A>T), single base polymorphism in which the base at the 571th was changed from C to A (c.571C>A), and the base at the 1045th was changed from C to A Polymorphism (c.1045C>A), monobasic polymorphism in which the base at position 769 is changed from C to T (c.769C>T), monobasic polymorphism in which the base at position 197 is changed from T to A (c. 197T>A) or single nucleotide polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T Any one or more single nucleotide polymorphisms selected from the group consisting of polymorphism (c.745G>T) or monopolymorphism in which the base at the fourth position is changed from G to A (c.4G>A) can be detected at the nucleic acid level. It provides a composition for early diagnosis or prediction of hypoHDL cholesterolemia as a risk factor for metabolic syndrome, including reagents that are present.

In the present invention, the composition is a single nucleotide polymorphism in which the base at the 796 position of the ABCA1 gene composed of SEQ ID NO: 1 is changed from G to A (c.796G>A), and the base at the 1631 position is G to A Single base polymorphism changed to (c.1631G>A), single base polymorphism in which the base at 6608 is changed from T to A (c.6608T>A), and the base at 4995 is changed from G to T Polymorphism (c.4995G>T) or single nucleotide polymorphism in which the base at the 2940th position was changed from G to T (c.2940G>T), the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 is from G to T Single nucleotide polymorphism changed to (c.452G>T), single nucleotide polymorphism (c.1765G>A) in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), base at 814 Is changed from A to T (c.814A>T), the base at the 571th is changed from C to A (c.571C>A), the base at the 1045th is changed from C to A Single base polymorphism changed to (c.1045C>A), single base polymorphism in which the base at the 769 position changed from C to T (c.769C>T), the base at the 197 position changed from T to A Polymorphism (c.197T>A) or single nucleotide polymorphism in which the base at 196 is changed from G to T (c.196G>T), or the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is in G A complementary probe or primer set capable of detecting mononucleotide polymorphism changed to T (c.745G>T) or mononucleotide polymorphism changed from G to A at the fourth position (c.4G>A) at the nucleic acid level , More specifically, 5'-biotinylated probes or primer sets may be included.

In addition, it may include a reagent necessary for the detection of the single nucleotide polymorphism of the probe, and for this purpose, a reagent required for amplification of a nucleic acid may be further included. In this case, the probe may be labeled with biotin for selection based on straptabine-biotin binding according to selective hybridization, but is not limited thereto.

In addition, the hybridization may further include any one or more selected from the group consisting of a buffer solution, streptavidin magnetic beads, dNTP, and a washing buffer solution, but is not limited thereto.

In addition, in the present specification, the term "probe" refers to a linear oligomer having a natural or modified monomer or bond including a deoxyribonucleotide and a ribonucleotide capable of hybridizing to a specific nucleotide sequence. Preferably, the probe is single stranded for maximum efficiency in hybridization. The probe is preferably a deoxyribonucleotide.

In addition, the probe may be configured to share a hybridization region of 1% or more with adjacent hybridization probes, and more specifically, may be configured to share a hybridization region within 50%, but is not limited thereto.

In addition, the primer may amplify the single nucleotide polymorphism, which is a target site, and the size and position of binding to the template are not limited, and those skilled in the art may design a primer using conventional primer promotion software.

In addition, a reaction reagent may be additionally included in the composition, and the reaction reagent is a buffer solution used for hybridization, a polymerase for amplification of nucleic acids, a primer set for binding to an NGS substrate, a washing buffer solution, etc. It may be configured, but is not limited thereto, and may include all reaction reagents required for hybridization reactions of the gene panel known to those skilled in the art, specifically, the NGS gene panel.

In addition, the present invention

1) separating the nucleic acid from the biological sample isolated from the subject; And

2) Single nucleotide polymorphism in which the base at the 796 position of the ABCA1 gene composed of SEQ ID NO: 1 is changed from G to A (c.796G>A) from the nucleic acid, and the single base at which the base at the 1631 position is changed from G to A Polymorphism (c.1631G>A), monobasic polymorphism in which the base at position 6608 is changed from T to A (c.6608T>A), monobasic polymorphism in which the base at position 4995 is changed from G to T (c. 4995G>T) or a single nucleotide polymorphism in which the base at the 2940th position was changed from G to T (c.2940G>T), a single base in which the base at the 452th position in the CETP gene consisting of SEQ ID NO:9 was changed from G to T Polymorphism (c.452G>T), single nucleotide polymorphism in which the base at 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), the base at 814 is from A to T Single base polymorphism changed to (c.814A>T), single base polymorphism in which the base at the 571th was changed from C to A (c.571C>A), and the base at the 1045th was changed from C to A Polymorphism (c.1045C>A), monobasic polymorphism in which the base at position 769 is changed from C to T (c.769C>T), monobasic polymorphism in which the base at position 197 is changed from T to A (c. 197T>A) or single nucleotide polymorphism in which the base at position 196 was changed from G to T (c.196G>T), and the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 was changed from G to T. The step of confirming any one or more single nucleotide polymorphism nucleotide sequences selected from the group consisting of polymorphism (c.745G>T) or monobasic polymorphism in which the base at the fourth position is changed from G to A (c.4G>A) It provides a method of providing information necessary for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, including.

In the method of the present invention, the step of extracting genomic DNA from the sample isolated from the subject in step 1) may be performed through a method known in the art. For example, when the DNA of interest is in the cell, in order to prepare pure DNA, a cell extract may be first prepared, and then differential precipitation, column chromatography, organic solvent extraction, etc. may be further performed, and the extract is the corresponding technology. It can be manufactured by standard technology in the field. DNA isolated from cells or tissues by the above method may be directly purified or may be achieved by specifically amplifying a specific region and isolating it using an amplification method such as PCR or RT-PCT (real time PCR), but is limited thereto. It doesn't work. The DNA includes not only DNA but also cDNA synthesized from mRNA. In addition, PCR or RT-PCR may be performed on the entire DNA sequence of an individual, but may be performed only around a site known as mononucleotide polymorphism.

In the above method of the present invention, confirmation of the nucleotide sequence of the isolated DNA may be performed by various methods known in the art.

For example, polymorphic sites by hybridizing a probe containing a sequence of a mononucleotide polymorphic site or a probe complementary thereto with the DNA and measuring the degree of hybridization obtained therefrom by confirming the nucleotide sequence of DNA directly by the dideoxy method. A method of confirming the nucleotide sequence of may be used. The degree of hybridization may be achieved by labeling a detectable label on the target DNA and specifically detecting only the hybridized target DNA, but other electrical signal detection methods may be used. Specifically, hybridization by NGS gene panel probe, hybridization by microarray, allele-specific hybridization, allele-specific amplification, and sequencing. , 5'nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis and single-stranded polymorphism conformation polymorphism), but is not limited thereto.

In addition, the present invention changes the amino acid glycine (G) at the 266th from the N-terminus to arginine (R) from the biological sample isolated from the subject (c.796G>A), and the amino acid glycine (G) at the 544th This aspartic acid (D) changes (c.1631G>A), the amino acid isoleucine (I) at the 2203th changes to lysine (K) (c.6608T>A), the amino acid methionine at the 1665th (M ) Changed to isoleucine (I) (c.4995G>T) or the amino acid glutamine (Q) at the 980th changed to histidine (H) (c.2940G>T), an ABCA1 protein mutation, 151 from the N-terminus CETP protein mutation in which the amino acid glycine (G) is changed to valine (V) (c.452G>T) in the first, and aspartic acid (D), the amino acid in the 589th from the N-terminus, is changed to asparagine (N) ( c.1765G>A), the amino acid asparagine (N) at the 272th changed to tyrosine (Y) (c.814A>T), the amino acid at the 191th glutamine (Q) changed to lysine (K) (c. 571C>A), the amino acid glutamine (Q) at position 349 changes to lysine (K) (c.1045C>A), the amino acid arginine (R) at position 257 changes to tryptophan (W) (c.769C> T), the amino acid valine (V) at the 66th is changed to aspartic acid (D) (c.197T>A) or the amino acid at the 66th is valine (V) is changed to phenylalanine (F) (c.196G> T) mutation of the LDLR protein, and aspartic acid (D), an amino acid at the 249th from the N-terminus, changes to tyrosine (Y) (c.745G>T), or glycine (G), an amino acid at the second, serine ( It is necessary for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, comprising the step of identifying any one or more protein mutations selected from the group consisting of S) changed (c.4G>A) SCARB1 protein mutations. Provides a way to present information.

In the method of the present invention, the protein mutation can be confirmed by calculating protein mutation information based on bioinformatics analysis from a biological sample isolated from a subject.

In the method of the present invention, the sample may be selected from the group consisting of hair, blood, tissue, cells, serum, plasma, saliva, sputum, and urine, but is not limited thereto.

Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

< Example 1> Selection of subjects for metabolic syndrome

Metabolic syndrome subjects and normal control subjects were selected as follows.

Specifically, metabolic syndrome subjects and normal control subjects were men and women aged 18 years or older residing in Korea. At this time, subjects who took two or more combination drugs due to a specific disease and who were taking special drugs such as chemotherapy or anticancer drugs were excluded. In addition, basic information such as drug consumption status, alcohol consumption, or smoking amount was obtained based on the results of a survey conducted on the study participants in advance.

For the study participants, a total of 48 subjects who met the diagnostic criteria of (1) were selected as subjects for metabolic syndrome. Among them, a total of 33 patients who met the diagnostic criteria in (2) below were selected as subjects for metabolic syndrome accompanied by non-alcoholic steatosis. In addition, a total of 48 subjects meeting the following diagnostic criteria (3) were selected as normal control subjects.

(1) Diagnosis criteria for metabolic syndrome

The diagnostic criteria for metabolic syndrome are the guidelines for clinical treatment published by the Korean Academy of Family Medicine in 2015 (Jeyong Shim et al., Prevention and treatment of metabolic syndrome in adults in Korea. Korean J. Fam. Pract. 2015;5(3):375-420.) According to the following (A) to (E), five were diagnosed, and specifically, subjects who met three or more of these criteria were selected as metabolic syndrome subjects.

(A) Abdominal obesity: When the waist circumference is 90 cm or more for men and 85 cm or more for women

(B) Hypertriglyceridemia: When the serum triglyceride concentration is 150 mg/dL or more, or when a drug is being administered to treat hypertriglyceridemia.

(C) HypoHDL cholesterol: When the serum HDL cholesterol concentration is less than 40 mg/dL in men, less than 50 mg/dL in women, or in a condition under medication to treat low HDL cholesterol

(D) Hypertension: If the systolic blood pressure is 130.85 mmHg or higher, the diastolic blood pressure is 85 mmHg or higher, or if the drug is being administered to treat hypertension.

(E) Hyperglycemia: When the concentration of fasting blood sugar is 100 mg/dL or more, or when a drug is being administered to control blood sugar.

(2) Non-alcoholic Diagnosis Criteria for Metabolic Syndrome with Fatty Liver Disease

Among the subjects selected as the diagnosis criteria in (1) above, the diagnosis criteria for subjects with non-alcoholic steatoeclampsia followed the guidelines for treatment of non-alcoholic steatosis published by the Korean Liver Association in 2013.

Specifically, among the subjects selected as the diagnostic criteria in (1), significant alcohol intake for the last two years did not exceed 210 g per week for men, 140 g per week for women, and did not take drugs that cause fatty liver disease. , If there was no liver disease due to other causes, and showed fat deposits in the liver through radiological examination (liver ultrasound), the subjects were selected as subjects for metabolic syndrome accompanied by non-alcoholic steatohepatic disease.

At this time, the above significant alcohol intake is a consensus recommendation from the United States (Sanyal AJ, et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis. et al. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease.A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee.Dig Liver Dis. 2010; 42: 272-282; Chalasani N, et al. al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.Hepatology 2012; 55: 2005-2023.) This is the standard we are doing.

(3) Normal control diagnosis criteria

Body mass index: <25 kg/m ² ;

Blood sugar: 70-100 mg/dL;

Blood pressure: systolic- 120-130 mmHg, diastolic- 70-84 mmHg;

Total cholesterol among lipid indicators: 100-200 mg/dL;

LDL-cholesterol among lipid indicators: 1-130 mg/dL;

HDL-cholesterol among lipid indicators: male-≥40 mg/dL, female-≥50 mg/dL;

Triglycerides among lipid indicators: <150 mg/dL;

Among the indicators of liver function, AST: 1~40 U/L;

Among the indicators of liver function, ALT: 1~40 U/L;

Γ-GTP among liver function indicators: 6-71 U/L;

Serum creatinine among renal function indicators: 0.7-1.2 mg/dL;

GFR among renal function indicators: 〉60 mL/min/1.73m ²

When all of the above ranges were satisfied, and there was no finding of fatty liver as a result of liver ultrasound, it was selected as a normal control group.

At this time, when one or two of the diagnostic criteria of (A) to (E) of (1) were included, it was excluded from the normal control group. In addition, the state of drug administration for the treatment of hypertriglyceridemia, the state of drug administration for the treatment of hypoHDL cholesterol, and the state of drug administration to control hypertension and blood sugar were also excluded from the normal control group. In addition, smokers were also excluded from the normal control group.

< Example 2> NGS (next Generation Sequencing) Gene panel construction and manufacturing

In order to select single nucleotid polymorphism (SNP) indicators related to metabolic syndrome and risk factors closely related thereto (obesity, hyperglycemia, hypoHLD cholesterolemia, hypertension, hypertriglyceridemia and non-alcoholic steatosis), the following As shown in Table 1, an NGS gene panel was constructed using genes related to metabolic diseases.

NGS Gene Panel ABCA1, ABCG5, ABCG8, ABO, ADD1, ADIPOQ, ADM, ADRB2, APOA1, APOA4, APOA5, APOB, APOC2, APOC3, APOE, CAV1, CETP,COL6A2, CREB3L3, FAM3A, FAM3B, GPITO, FAM3C, FAM3B, FAM3C IGF1, LDLR, LDLRAP1, LEP, LEPR, LMF1, LPA, LPL,MTHFR, MTTP, PCSK9, SCARB1, SIRT1, SLC2A2, SORT1, SPARC, SREBF2, ZHX3

< Example 3> NGS Library manufacturing

An NGS library was prepared using the gene panel prepared in <Example 2>.

Specifically, whole blood from metabolic syndrome subjects (including subjects with non-alcoholic steatosis) and normal control subjects selected in Example 1 were collected, and DNA was extracted therefrom. Then, in order to use NextSeq550, one of the NGS systems of Illumina, the NGS library was prepared from the extracted DNA through the steps of 1) to 6) below:

1) DNA fragmentation (DNA fragmentation) step: The extracted DNA was subjected to sonication and fractionated into nucleotide sequences having an average length of 180 to 200 bp.

2) End Repair Step: The lengths of both ends of the two single-stranded DNAs constituting the double-stranded DNA fractionated in step 1) were made equal to each other.

3) Adenosine conjugation (dA-Tailing) step: One of the bases, adenosine (A), was conjugated to the 3′-end of the double-stranded DNA subjected to terminal repair in step 2).

4) Adapter conjugation step: The adapter was conjugated to the double-stranded DNA fraction subjected to the adenosine conjugation of step 3) for one nucleotide sequence analysis using an NGS analyzer. In this case, the adapter was used as an adapter composed of a commonly required nucleotide sequence.

5) Target gene capture step using a gene panel: The DNA subjected to the adapter conjugation of step 4) was mixed with the target gene to be detected by hybridization using the gene panel prepared in Example 2 above. Captured.

6) Polymerase chain reaction (PCR) step: The DNA to be analyzed was amplified through PCR for the DNA captured in step 5). At this time, the platform-specific index primer of Illumina is inserted with an index sequence of 8bp (base pair) to distinguish different samples that are sequenced together in one lane of one sequencing substrate (flow cell). Index PCR was performed using (primer) to introduce and amplify the index sequence into the DNA to be analyzed.

< Example 4> NGS analysis

The NGS library prepared in Example 3 was subjected to sequencing using the NextSeq550 model, an NGS system manufactured by Illumina, to detect genes related to metabolic syndrome and risk factors closely related thereto.

Specifically, the <Example 3> was placed on a sequencing substrate (flow cell) of an NGS analyzer in which a primer base fragment having a base sequence complementary to an adapter base sequence included in the NGS library prepared in Example 3 was immobilized. The NGS library prepared in was injected, and the single-stranded NGS library was fixed on the sequencing substrate. Then, A, T, C, G bases and DNA polymerase were added to amplify the immobilized DNA strand as a template. After completing the amplification, a cluster for a specific DNA strand template was formed on the sequencing substrate.

After cluster formation, fluorescent substance-labeled A, T, C, G bases, primers, and DNA polymerase were added. In this case, the DNA strands that make up the cluster are used as a template, and the DNA sequences complementary to this are synthesized using fluorescent markers A, T, C, and G bases each showing different colors, and the emitted fluorescence is detected through a laser. Thus, it was confirmed which base sequence was formed of the template of each DNA strand.

< Example 5> SNP screening related to metabolic syndrome

As shown in the schematic diagram of FIG. 1, single nucleotide polymorphism (SNP) related to metabolic syndrome and risk factors closely related to metabolic syndrome was selected through bioinformatics analysis using the NGS data obtained in Example 4 above. .

Specifically, the NGS data were separated for each sample by using the 8bp index sequence used for each sample from the NGS integration file obtained by integrating the NGS data of the samples (S110).

Then, by comparing the nucleotide sequence included in the NGS data to be analyzed with a standard genomic nucleotide sequence (reference genomic nucleotide sequence), information on what nucleotide sequence the DNA of the analyzed target genes for each sample consists of was confirmed. The reference genome sequence used in the above process was hg19/GRCh37 of UCSC Genome browser (S120).

Then, in order to correct the nucleotide sequence comparison error due to the occurrence of an indel in which the nucleotide sequence is deleted or inserted in the above process, the estimated indel region was corrected through a recomparison process (S130).

Then, if the same nucleotide sequence is duplicated in the PCR process to create an error in sequencing, such an error in sequencing may affect the selection process of genetic biomarkers in the future, so the nucleotide sequence treated as a cloned nucleotide sequence is used with the Picard program. And removed (S140).

Then, the nucleotide sequence variation that appeared different from the standard genomic nucleotide sequence was confirmed for each specimen. In the above process, the Unified Genotyper program of GATK (genome analysis tool kit) was used. In addition, in order to extract nucleotide sequence mutation information, such as the nucleotide sequence mutations detected through the above process, the mutations found in which genes were extracted using the SNPeff or SNPsift program (S150).

Then, SNPs judged to be of clinical significance were first selected. The screening process is classified into five categories according to the guidelines of The American College of Medical Genetics and Genomics (ACMG), of which the remaining three are classified except those classified as positive gene markers (Benign and Likely Benign). SNPs included in the criteria (pathogenic, likely pathogenic, variant of uncertain significance) were selected. The above three classification criteria (pathogenic, likely pathogenic, variant of uncertain significance) are currently applied in the process of reading the results of a patient's genetic test in almost all laboratories conducting NGS-based genetic panel tests worldwide. In the screening process, SNPs related to metabolic syndrome and SNPs related to metabolic syndrome accompanied by non-alcoholic steatosis were classified and selected. Therefore, among the SNPs found in the metabolic syndrome group, SNP candidates related to metabolic syndrome were limited to SNPs that were not detected in the normal control group in which abdominal obesity, serum triglycerides, serum HDL-cholesterol, blood pressure, and fasting blood sugar were all in the normal category. In addition, among the SNPs found in subjects with metabolic syndrome and nonalcoholic steatosis, abdominal obesity, serum triglycerides, serum HDL-cholesterol, blood pressure, and fasting blood sugar are all normal categories. , Non-drinking and non-smokers were limited to SNPs that were not detected in the normal control group. In addition, the SNP included in the selection process was limited to cases that can directly affect the structure and function of the protein expressed by the gene. The criterion is a case where all conditions of discovery in exon and splicing region, causing amino acid change, sequencing depth of 20 or more, and allele frequency of 30% or more (S160).

Then, the SNP was classified based on the ACMG criteria. In silico used for the verification of PP3 and BP4 items of ACMG guidelines The protein damage score calculation algorithm ( in silico prediction algorithm) was SIFT, Polyphen2, and MutationTaster. This process is to predict how much each SNP candidate affects protein function, and how much this effect impairs the function of the protein. In addition, "1000 Genome Project" was used as a control population database used for verification of the PM2 and BA1 items of the ACMG guidelines. In the control population database, factor frequency information of East Asians was used together with factor frequency information for the entire population. In addition, for the verification of the PS1, PM5, PP5, BS3 and BP6 items of the ACMG guidelines, the Clinical Database is PubMed (https://www.ncbi.nlm.nih) along with data from HGMD, ClinVar, ClinGen, and SNP4Disease (https://www.ncbi.nlm.nih). .gov/pubmed/). In addition, the verification of the PM1 item of the ACMG guidelines was based on the gene database of the National Center for Biotechnology Information (NCBI) (S170).

SNPs that have gone through all the above-described screening processes are each effective SNP according to the presence or absence of association with metabolic syndrome and risk factors closely related to obesity, hypoHDL cholesterol, hypertriglyceridemia, hypertension, hyperglycemia, and nonalcoholic steatosis. Final selection was performed (S180), and the results are shown in Tables 2 to 8.

As shown in Tables 2 to 8, the SNP was not detected in the normal control group and detected in the metabolic syndrome group accompanied by metabolic syndrome and non-alcoholic fatty liver disease, thereby making the SNP early diagnosis and prediction of metabolic syndrome. It was confirmed that it can be used as a marker for use.

In addition, it was confirmed that the SNP can be used as a marker for early diagnosis and prediction of obesity, hyperglycemia, hypoHLD cholesterolemia, hypertension, hypertriglyceridemia, and nonalcoholic steatosis as a risk factor closely related to metabolic syndrome.

Phenotype gene SNP Amino acid mutation obesity COL6A2 NM_058174.2:c.2524G>T A842S NM_001849.3:c.272C>T A91V NM_001849.3:c.1327G>A E443K NM_001849.3:c.2927T>C L976S NM_001849.3:c.2944A>G M982V FTO NM_001080432.2:c.400G>A A134T SPARC NM_001309444.1:c.230G>T C77F NM_001309444.1:c.253C>A L85M NM_001309444.1:
c.1024_1025delTA Ter342fs MTHFR NM_005957.4:c.1498T>G W500G

Phenotype gene SNP Amino acid mutation Hyperglycemia



































APOB



































NM_000384.2:c.5816C>A A1939E NM_000384.2:c.11953G>A D3985N NM_000384.2:c.2992G>T D998Y NM_000384.2:c.13270G>T E4424* NM_000384.2:c.4364T>A F1455Y NM_000384.2:c.5091C>A F1697L NM_000384.2:c.3122G>T G1041V NM_000384.2:c.8266G>T G2756C NM_000384.2:c.12674G>T G4225V NM_000384.2:c.2459G>T G820V NM_000384.2:c.1462A>T I488F NM_000384.2:c.12853A>T K4285* NM_000384.2:c.13255A>T K4419* NM_000384.2:c.531G>T L177F NM_000384.2:c.5378T>A L1793Q NM_000384.2:c.5799G>T L1933F NM_000384.2:c.6894A>T L2298F NM_000384.2:c.7397T>A L2466* NM_000384.2:c.13055T>A L4352Q NM_000384.2:c.1461G>T L487F NM_000384.2:c.3700A>G M1234V NM_000384.2:c.5394C>A N1798K NM_000384.2:c.5967C>A N1989K NM_000384.2:c.2706C>A N902K NM_000384.2:c.4653A>T Q1551H NM_000384.2:c.6538C>A Q2180K NM_000384.2:c.6655C>T R2219C NM_000384.2:c.3683C>A S1228Y NM_000384.2:c.5054C>A T1685K NM_000384.2:c.562A>T T188S NM_000384.2:c.602C>T T201I NM_000384.2:c.10283C>A T3428N NM_000384.2:c.7138G>T V2380F NM_000384.2:c.11464G>T V3822L NM_000384.2:c.12704T>A V4235D NM_000384.2:c.12794T>A V4265E NM_000384.2:c.5409C>A Y1803*

Phenotype gene SNP Amino acid mutation Hyperglycemia












GCKR
NM_001486.3:c.169G>T D57Y NM_001486.3:c.249G>A M83I LPA









NM_005577.2:c.5221T>A C1741S NM_005577.2:c.5897A>G E1966G NM_005577.2:c.5690T>C F1897S NM_005577.2:c.6037G>T G2013C NM_005577.2:c.3806C>A P1269H NM_005577.2:c.2638C>G P880A NM_005577.2:c.3530G>A R1177Q NM_005577.2:c.4189C>T R1397* NM_005577.2:c.3053C>T S1018L NM_005577.2:c.4880C>A T1627K NM_005577.2:c.6068A>T Y2023F SLC2A2 NM_000340.1:c.1521C>A H507Q

Phenotype gene SNP Amino acid mutation Low HDL cholesterol













ABCA1



NM_005502.3:c.796G>A G266R NM_005502.3:c.1631G>A G544D NM_005502.3:c.6608T>A I2203K NM_005502.3:c.4995G>T M1665I NM_005502.3:c.2940G>T Q980H CETP NM_000078.2:c.452G>T G151V LDLR





NM_000527.4:c.1765G>A D589N NM_000527.4:c.814A>T N272Y NM_000527.4:c.571C>A Q191K NM_000527.4:c.1045C>A Q349K NM_000527.4:c.769C>T R257W NM_000527.4:c.197T>A V66D NM_000527.4:c.196G>T V66F SCARB1 NM_005505.4:c.745G>T D249Y NM_005505.4:c.4G>A G2S

Phenotype gene SNP Amino acid mutation High blood pressure ADD1 NM_014189.3:c.1003G>C A335P NM_014189.3:c.1051G>C A351P NM_014189.3:c.16C>T R6C

Phenotype gene SNP Amino acid mutation

Hypertriglyceridemia






APOA1 NM_000039.2:c.664G>T E222* NM_000039.2:c.76G>T E26* APOA4 NM_000482.3:c.23T>A L8Q APOC2 NM_000483.4:c.205G>T E69* NM_000483.4:c.214A>T R72W LMF1

NM_022773.2:c.1621G>A G541R NM_022773.2:c.668T>A L223Q NM_022773.2:c.1177A>T M393L NM_022773.2:c.1644C>A S548R NM_022773.2:c.1207G>T V403F

Phenotype gene SNP Amino acid mutation Non-alcoholic steatosis ABCG5 NM_022436.2:c.89C>A A30D NM_022436.2:c.254T>A L85Q ABCG8 NM_022437.2:c.900G>T M300I NM_022437.2:c.419C>A S140* NM_022437.2:c.562G>T V188L FAM3A NM_001282311.1:c.170G>T G57V NM_001282311.1:c.324G>T M108I NM_001282311.1:c.350G>T R117L NM_001171132.2:c.28G>T V10L FAM3B NM_058186.3:c.20G>T G7V FAM3C NM_001040020.1:c.418C>A Q140K LEPR NM_002303.5:c.403G>A G135R NM_002303.5:c.2348T>A I783K NM_002303.5:c.3183delG K1062fs NM_002303.5:c.398T>A L133Q NM_002303.5:c.722T>A L241* NM_002303.5:c.808C>A Q270K NM_002303.5:c.1025C>A T342K MTTP NM_001300785.1:c.766G>T A256S NM_001300785.1:c.2507C>A A836E NM_001300785.1:c.1633G>T D545Y NM_001300785.1:c.1628T>A I543K NM_001300785.1:c.2528C>A T843K PCSK9 NM_174936.3:c.1502A>T E501V NM_174936.3:c.253G>A E85K NM_174936.3:c.1151G>T G384V NM_174936.3:c.481A>T I161F NM_174936.3:c.479G>T R160L NM_174936.3:c.1406G>T R469L NM_174936.3:c.17C>T S6F SIRT1 NM_012238.4:c.1534G>A E512K NM_012238.4:c.618G>T L206F NM_012238.4:c.95C>G P32R SREBF2 NM_004599.3:c.2068G>A D690N NM_004599.3:c.2243G>T G748V NM_004599.3:c.3265C>T R1089C NM_004599.3:c.2704G>C V902L ZHX3 NM_015035.3:c.2291C>A P764Q

<110> SCL Healthcare <120> Single nucleotide polymorphism for predicting the risk factor of metabolic syndrome and the use thereof <130> PB2019-185 <150> KR 10-2019-0012632 <151> 2019-01-31 <160> 30 <170> PatentIn version 3.5 <210> 1 <211> 6786 <212> DNA <213> Homo sapiens <400> 1 atggcttgtt ggcctcagct gaggttgctg ctgtggaaga acctcacttt cagaagaaga 60 caaacatgtc agctgctgct ggaagtggcc tggcctctat ttatcttcct gatcctgatc 120 tctgttcggc tgagctaccc accctatgaa caacatgaat gccattttcc aaataaagcc 180 atgccctctg caggaacact tccttgggtt caggggatta tctgtaatgc caacaacccc 240 tgtttccgtt acccgactcc tggggaggct cccggagttg ttggaaactt taacaaatcc 300 attgtggctc gcctgttctc agatgctcgg aggcttcttt tatacagcca gaaagacacc 360 agcatgaagg acatgcgcaa agttctgaga acattacagc agatcaagaa atccagctca 420 aacttgaagc ttcaagattt cctggtggac aatgaaacct tctctgggtt cctgtatcac 480 aacctctctc tcccaaagtc tactgtggac aagatgctga gggctgatgt cattctccac 540 aaggtatttt tgcaaggcta ccagttacat ttgacaagtc tgtgcaatgg atcaaaatca 600 gaagagatga ttcaacttgg tgaccaagaa gtttctgagc tttgtggcct accaagggag 660 aaactggctg cagcagagcg agtacttcgt tccaacatgg acatcctgaa gccaatcctg 720 agaacactaa actctacatc tcccttcccg agcaaggagc tggctgaagc cacaaaaaca 780 ttgctgcata gtcttgggac tctggcccag gagctgttca gcatgagaag ctggagtgac 840 atgcgacagg aggtgatgtt tctgaccaat gtgaacagct ccagctcctc cacccaaatc 900 taccaggctg tgtctcgtat tgtctgcggg catcccgagg gaggggggct gaagatcaag 960 tctctcaact ggtatgagga caacaactac aaagccctct ttggaggcaa tggcactgag 1020 gaagatgctg aaaccttcta tgacaactct acaactcctt actgcaatga tttgatgaag 1080 aatttggagt ctagtcctct ttcccgcatt atctggaaag ctctgaagcc gctgctcgtt 1140 gggaagatcc tgtatacacc tgacactcca gccacaaggc aggtcatggc tgaggtgaac 1200 aagaccttcc aggaactggc tgtgttccat gatctggaag gcatgtggga ggaactcagc 1260 cccaagatct ggaccttcat ggagaacagc caagaaatgg accttgtccg gatgctgttg 1320 gacagcaggg acaatgacca cttttgggaa cagcagttgg atggcttaga ttggacagcc 1380 caagacatcg tggcgttttt ggccaagcac ccagaggatg tccagtccag taatggttct 1440 gtgtacacct ggagagaagc tttcaacgag actaaccagg caatccggac catatctcgc 1500 ttcatggagt gtgtcaacct gaacaagcta gaacccatag caacagaagt ctggctcatc 1560 aacaagtcca tggagctgct ggatgagagg aagttctggg ctggtattgt gttcactgga 1620 attactccag gcagcattga gctgccccat catgtcaagt acaagatccg aatggacatt 1680 gacaatgtgg agaggacaaa taaaatcaag gatgggtact gggaccctgg tcctcgagct 1740 gacccctttg aggacatgcg gtacgtctgg gggggcttcg cctacttgca ggatgtggtg 1800 gagcaggcaa tcatcagggt gctgacgggc accgagaaga aaactggtgt ctatatgcaa 1860 cagatgccct atccctgtta cgttgatgac atctttctgc gggtgatgag ccggtcaatg 1920 cccctcttca tgacgctggc ctggatttac tcagtggctg tgatcatcaa gggcatcgtg 1980 tatgagaagg aggcacggct gaaagagacc atgcggatca tgggcctgga caacagcatc 2040 ctctggttta gctggttcat tagtagcctc attcctcttc ttgtgagcgc tggcctgcta 2100 gtggtcatcc tgaagttagg aaacctgctg ccctacagtg atcccagcgt ggtgtttgtc 2160 ttcctgtccg tgtttgctgt ggtgacaatc ctgcagtgct tcctgattag cacactcttc 2220 tccagagcca acctggcagc agcctgtggg ggcatcatct acttcacgct gtacctgccc 2280 tacgtcctgt gtgtggcatg gcaggactac gtgggcttca cactcaagat cttcgctagc 2340 ctgctgtctc ctgtggcttt tgggtttggc tgtgagtact ttgccctttt tgaggagcag 2400 ggcattggag tgcagtggga caacctgttt gagagtcctg tggaggaaga tggcttcaat 2460 ctcaccactt cggtctccat gatgctgttt gacaccttcc tctatggggt gatgacctgg 2520 tacattgagg ctgtctttcc aggccagtac ggaattccca ggccctggta ttttccttgc 2580 accaagtcct actggtttgg cgaggaaagt gatgagaaga gccaccctgg ttccaaccag 2640 aagagaatat cagaaatctg catggaggag gaacccaccc acttgaagct gggcgtgtcc 2700 attcagaacc tggtaaaagt ctaccgagat gggatgaagg tggctgtcga tggcctggca 2760 ctgaattttt atgagggcca gatcacctcc ttcctgggcc acaatggagc ggggaagacg 2820 accaccatgt caatcctgac cgggttgttc cccccgacct cgggcaccgc ctacatcctg 2880 ggaaaagaca ttcgctctga gatgagcacc atccggcaga acctgggggt ctgtccccag 2940 cataacgtgc tgtttgacat gctgactgtc gaagaacaca tctggttcta tgcccgcttg 3000 aaagggctct ctgagaagca cgtgaaggcg gagatggagc agatggccct ggatgttggt 3060 ttgccatcaa gcaagctgaa aagcaaaaca agccagctgt caggtggaat gcagagaaag 3120 ctatctgtgg ccttggcctt tgtcggggga tctaaggttg tcattctgga tgaacccaca 3180 gctggtgtgg acccttactc ccgcagggga atatgggagc tgctgctgaa ataccgacaa 3240 ggccgcacca ttattctctc tacacaccac atggatgaag cggacgtcct gggggacagg 3300 attgccatca tctcccatgg gaagctgtgc tgtgtgggct cctccctgtt tctgaagaac 3360 cagctgggaa caggctacta cctgaccttg gtcaagaaag atgtggaatc ctccctcagt 3420 tcctgcagaa acagtagtag cactgtgtca tacctgaaaa aggaggacag tgtttctcag 3480 agcagttctg atgctggcct gggcagcgac catgagagtg acacgctgac catcgatgtc 3540 tctgctatct ccaacctcat caggaagcat gtgtctgaag cccggctggt ggaagacata 3600 gggcatgagc tgacctatgt gctgccatat gaagctgcta aggagggagc ctttgtggaa 3660 ctctttcatg agattgatga ccggctctca gacctgggca tttctagtta tggcatctca 3720 gagacgaccc tggaagaaat attcctcaag gtggccgaag agagtggggt ggatgctgag 3780 acctcagatg gtaccttgcc agcaagacga aacaggcggg ccttcgggga caagcagagc 3840 tgtcttcgcc cgttcactga agatgatgct gctgatccaa atgattctga catagaccca 3900 gaatccagag agacagactt gctcagtggg atggatggca aagggtccta ccaggtgaaa 3960 ggctggaaac ttacacagca acagtttgtg gcccttttgt ggaagagact gctaattgcc 4020 agacggagtc ggaaaggatt ttttgctcag attgtcttgc cagctgtgtt tgtctgcatt 4080 gcccttgtgt tcagcctgat cgtgccaccc tttggcaagt accccagcct ggaacttcag 4140 ccctggatgt acaacgaaca gtacacattt gtcagcaatg atgctcctga ggacacggga 4200 accctggaac tcttaaacgc cctcaccaaa gaccctggct tcgggacccg ctgtatggaa 4260 ggaaacccaa tcccagacac gccctgccag gcaggggagg aagagtggac cactgcccca 4320 gttccccaga ccatcatgga cctcttccag aatgggaact ggacaatgca gaacccttca 4380 cctgcatgcc agtgtagcag cgacaaaatc aagaagatgc tgcctgtgtg tcccccaggg 4440 gcaggggggc tgcctcctcc acaaagaaaa caaaacactg cagatatcct tcaggacctg 4500 acaggaagaa acatttcgga ttatctggtg aagacgtatg tgcagatcat agccaaaagc 4560 ttaaagaaca agatctgggt gaatgagttt aggtatggcg gcttttccct gggtgtcagt 4620 aatactcaag cacttcctcc gagtcaagaa gttaatgatg ccatcaaaca aatgaagaaa 4680 cacctaaagc tggccaagga cagttctgca gatcgatttc tcaacagctt gggaagattt 4740 atgacaggac tggacaccaa aaataatgtc aaggtgtggt tcaataacaa gggctggcat 4800 gcaatcagct ctttcctgaa tgtcatcaac aatgccattc tccgggccaa cctgcaaaag 4860 ggagagaacc ctagccatta tggaattact gctttcaatc atcccctgaa tctcaccaag 4920 cagcagctct cagaggtggc tctgatgacc acatcagtgg atgtccttgt gtccatctgt 4980 gtcatctttg caatgtcctt cgtcccagcc agctttgtcg tattcctgat ccaggagcgg 5040 gtcagcaaag caaaacacct gcagttcatc agtggagtga agcctgtcat ctactggctc 5100 tctaattttg tctgggatat gtgcaattac gttgtccctg ccacactggt cattatcatc 5160 ttcatctgct tccagcagaa gtcctatgtg tcctccacca atctgcctgt gctagccctt 5220 ctacttttgc tgtatgggtg gtcaatcaca cctctcatgt acccagcctc ctttgtgttc 5280 aagatcccca gcacagccta tgtggtgctc accagcgtga acctcttcat tggcattaat 5340 ggcagcgtgg ccacctttgt gctggagctg ttcaccgaca ataagctgaa taatatcaat 5400 gatatcctga agtccgtgtt cttgatcttc ccacattttt gcctgggacg agggctcatc 5460 gacatggtga aaaaccaggc aatggctgat gccctggaaa ggtttgggga gaatcgcttt 5520 gtgtcaccat tatcttggga cttggtggga cgaaacctct tcgccatggc cgtggaaggg 5580 gtggtgttct tcctcattac tgttctgatc cagtacagat tcttcatcag gcccagacct 5640 gtaaatgcaa agctatctcc tctgaatgat gaagatgaag atgtgaggcg ggaaagacag 5700 agaattcttg atggtggagg ccagaatgac atcttagaaa tcaaggagtt gacgaagata 5760 tatagaagga agcggaagcc tgctgttgac aggatttgcg tgggcattcc tcctggtgag 5820 tgctttgggc tcctgggagt taatggggct ggaaaatcat caactttcaa gatgttaaca 5880 ggagatacca ctgttaccag aggagatgct ttccttaaca aaaatagtat cttatcaaac 5940 atccatgaag tacatcagaa catgggctac tgccctcagt ttgatgccat cacagagctg 6000 ttgactggga gagaacacgt ggagttcttt gcccttttga gaggagtccc agagaaagaa 6060 gttggcaagg ttggtgagtg ggcgattcgg aaactgggcc tcgtgaagta tggagaaaaa 6120 tatgctggta actatagtgg aggcaacaaa cgcaagctct ctacagccat ggctttgatc 6180 ggcgggcctc ctgtggtgtt tctggatgaa cccaccacag gcatggatcc caaagcccgg 6240 cggttcttgt ggaattgtgc cctaagtgtt gtcaaggagg ggagatcagt agtgcttaca 6300 tctcatagta tggaagaatg tgaagctctt tgcactagga tggcaatcat ggtcaatgga 6360 aggttcaggt gccttggcag tgtccagcat ctaaaaaata ggtttggaga tggttataca 6420 atagttgtac gaatagcagg gtccaacccg gacctgaagc ctgtccagga tttctttgga 6480 cttgcatttc ctggaagtgt tctaaaagag aaacaccgga acatgctaca ataccagctt 6540 ccatcttcat tatcttctct ggccaggata ttcagcatcc tctcccagag caaaaagcga 6600 ctccacatag aagactactc tgtttctcag acaacacttg accaagtatt tgtgaacttt 6660 gccaaggacc aaagtgatga tgaccactta aaagacctct cattacacaa aaaccagaca 6720 gtagtggacg ttgcagttct cacatctttt ctacaggatg agaaagtgaa agaaagctat 6780 gtatga 6786 <210> 2 <211> 1956 <212> DNA <213> Homo sapiens <400> 2 atgggtgacc tctcatcttt gacccccgga gggtccatgg gtctccaagt aaacagaggc 60 tcccagagct ccctggaggg ggctcctgcc accgccccgg agcctcacag cctgggcatc 120 ctccatgcct cctacagcgt cagccaccgc gtgaggccct ggtgggacat cacatcttgc 180 cggcagcagt ggaccaggca gatcctcaaa gatgtctcct tgtacgtgga gagcgggcag 240 atcatgtgca tcctaggaag ctcaggctcc gggaaaacca cgctgctgga cgccatgtcc 300 gggaggctgg ggcgcgcggg gaccttcctg ggggaggtgt atgtgaacgg ccgggcgctg 360 cgccgggagc agttccagga ctgcttctcc tacgtcctgc agagcgacac cctgctgagc 420 agcctcaccg tgcgcgagac gctgcactac accgcgctgc tggccatccg ccgcggcaat 480 cccggctcct tccagaagaa ggtggaggcc gtcatggcag agctgagtct gagccatgtg 540 gcagaccgac tgattggcaa ctacagcttg gggggcattt ccacgggtga gcggcgccgg 600 gtctccatcg cagcccagct gctccaggat cctaaggtca tgctgtttga tgagccaacc 660 acaggcctgg actgcatgac tgctaatcag attgtcgtcc tcctggtgga actggctcgc 720 aggaaccgaa ttgtggttct caccattcac cagccccgtt ctgagctttt tcagctcttt 780 gacaaaattg ccatcctgag cttcggagag ctgattttct gtggcacgcc agcggaaatg 840 cttgatttct tcaatgactg cggttaccct tgtcctgaac attcaaaccc ttttgacttc 900 tatatggacc tgacgtcagt ggatacccaa agcaaggaac gggaaataga aacctccaag 960 agagtccaga tgatagaatc tgcctacaag aaatcagcaa tttgtcataa aactttgaag 1020 aatattgaaa gaatgaaaca cctgaaaacg ttaccaatgg ttcctttcaa aaccaaagat 1080 tctcctggag ttttctctaa actgggtgtt ctcctgagga gagtgacaag aaacttggtg 1140 agaaataagc tggcagtgat tacgcgtctc cttcagaatc tgatcatggg tttgttcctc 1200 cttttcttcg ttctgcgggt ccgaagcaat gtgctaaagg gtgctatcca ggaccgcgta 1260 ggtctccttt accagtttgt gggcgccacc ccgtacacag gcatgctgaa cgctgtgaat 1320 ctgtttcccg tgctgcgagc tgtcagcgac caggagagtc aggacggcct ctaccagaag 1380 tggcagatga tgctggccta tgcactgcac gtcctcccct tcagcgttgt tgccaccatg 1440 attttcagca gtgtgtgcta ctggacgctg ggcttacatc ctgaggttgc ccgatttgga 1500 tatttttctg ctgctctctt ggccccccac ttaattggtg aatttctaac tcttgtgcta 1560 cttggtatcg tccaaaatcc aaatatagtc aacagtgtag tggctctgct gtccattgcg 1620 ggggtgcttg ttggatctgg attcctcaga aacatacaag aaatgcccat tccttttaaa 1680 atcatcagtt attttacatt ccaaaaatat tgcagtgaga ttcttgtagt caatgagttc 1740 tacggactga atttcacttg tggcagctca aatgtttctg tgacaactaa tccaatgtgt 1800 gccttcactc aaggaattca attcattgag aaaacctgcc caggtgcaac atctagattc 1860 acaatgaact ttctgatttt gtattcattt attccagctc ttgtcatcct aggaatagtt 1920 gttttcaaaa taagggatca tctcattagc aggtag 1956 <210> 3 <211> 2022 <212> DNA <213> Homo sapiens <400> 3 atggccggga aggcggcaga ggagagaggg ctgccgaaag gggccactcc ccaggatacc 60 tcgggcctcc aggatagatt gttctcctct gaaagtgaca acagcctgta cttcacctac 120 agtggccagc ccaacaccct ggaggtcaga gacctcaact accaggtgga cctggcctct 180 caggtccctt ggtttgagca gctggctcag ttcaagatgc cctggacatc tcccagctgc 240 cagaattctt gtgagctggg catccagaac ctaagcttca aagtgagaag tgggcagatg 300 ctggccatca tagggagctc aggttgtggg agagcctcct tgctagatgt gatcactggc 360 cgaggtcacg gcggcaagat caagtcaggc cagatctgga tcaatgggca gcccagctcg 420 cctcagctgg tgaggaagtg tgtggcccac gtgcgccagc acaaccagct gctccccaac 480 ttgactgtgc gagagacctt ggccttcatt gcccagatgc ggctgcccag aaccttctcc 540 caggcccagc gtgacaaaag ggtggaggac gtgatcgcgg agctgcggct taggcagtgc 600 gctgacaccc gcgtgggcaa catgtacgtg cgggggttgt cggggggtga gcgcaggaga 660 gtcagcattg gggtgcagct cctgtggaac ccaggaatcc ttattctcga cgaacccacc 720 tctgggctcg acagcttcac agcccacaac ctggtgaaga ccttgtccag gctggccaaa 780 ggcaaccggc tggtgctcat ctccctccac cagcctcgct ctgacatctt caggctgttt 840 gatctggtcc tcctgatgac gtctggcacc cccatctact taggggcggc ccagcacatg 900 gtccagtatt tcacagccat cggctacccc tgtcctcgct acagcaatcc tgctgacttc 960 tatgtggacc tgaccagcat tgacaggcgc agcagagagc aggaattggc caccagggag 1020 aaggctcagt cactcgcagc cctgtttcta gaaaaagtgc gtgacttaga tgactttcta 1080 tggaaagcag agacgaagga tcttgacgag gacacctgtg tggaaagcag cgtgacccca 1140 ctagacacca actgcctccc gagtcctacg aagatgcctg gggcggtgca gcagtttacg 1200 acgctgatcc gtcgtcagat ttccaacgac ttccgagacc tgcccaccct cctcatccat 1260 ggggcggagg cctgtctgat gtcaatgacc atcggcttcc tctattttgg ccatgggagc 1320 atccagctct ccttcatgga tacagccgcc ctcttgttca tgatcggtgc tctcatccct 1380 ttcaacgtca ttctggatgt catctccaaa tgttactcag agagggcaat gctttactat 1440 gaactggaag acgggctgta caccactggt ccatatttct ttgccaagat cctcggggag 1500 cttccggagc actgtgccta catcatcatc tacgggatgc ccacctactg gctggccaac 1560 ctgaggccag gcctccagcc cttcctgctg cacttcctgc tggtgtggct ggtggtcttc 1620 tgttgcagga ttatggccct ggccgccgcg gccctgctcc ccaccttcca catggcctcc 1680 ttcttcagca atgccctcta caactccttc tacctcgccg ggggcttcat gataaacttg 1740 agcagcctgt ggacagtgcc cgcgtggatt tccaaagtgt ccttcctgcg gtggtgtttt 1800 gaagggctga tgaagattca gttcagcaga agaacttata aaatgcctct cgggaacctc 1860 accatcgcgg tctcaggaga taaaatcctc agtgtcatgg agctggactc gtaccctctc 1920 tacgccatct acctcatcgt cattggcctc agcggtggct tcatggtcct gtactacgtg 1980 tccttaaggt tcatcaaaca gaaaccaagt caagactggt ga 2022 <210> 4 <211> 2307 <212> DNA <213> Homo sapiens <400> 4 atgaatggtg attctcgtgc tgcggtggtg acctcaccac ccccgaccac agcccctcac 60 aaggagaggt acttcgaccg agtagatgag aacaacccag agtacttgag ggagaggaac 120 atggcaccag accttcgcca ggacttcaac atgatggagc aaaagaagag ggtgtccatg 180 attctgcaaa gccctgcttt ctgtgaagaa ttggaatcaa tgatacagga gcaatttaag 240 aaggggaaga accccacagg cctattggca ttacagcaga ttgcagattt tatgaccacg 300 aatgtaccaa atgtctaccc agcagctccg caaggaggga tggctgcctt aaacatgagt 360 cttggtatgg tgactcctgt gaacgatctt agaggatctg attctattgc gtatgacaaa 420 ggagagaagt tattacggtg taaattggca gcgttttata gactagcaga tctctttggg 480 tggtctcagc ttatctacaa tcatatcaca accagagtga actccgagca ggaacacttc 540 ctcattgtcc cttttgggct tctttacagt gaagtgactg catccagttt ggttaagatc 600 aatctacaag gagatatagt agatcgtgga agcactaatc tgggagtgaa tcaggccggc 660 ttcaccttac actctgcaat ttatgctgca cgcccggacg tgaagtgcgt cgtgcacatt 720 cacaccccag caggggctgc ggtctctgca atgaaatgtg gcctcttgcc aatctccccg 780 gaggcgcttt cccttggaga agtggcttat catgactacc atggcattct ggttgatgaa 840 gaggaaaaag ttttgattca gaaaaatctg gggcctaaaa gcaaggttct tattctccgg 900 aaccatgggc tcgtgtcagt tggagagagc gttgaggagg ccttctatta catccataac 960 cttgtggttg cctgtgagat ccaggttcga actctggcca gtgcaggagg accagacaac 1020 ttagtcctgc tgaatcctga gaagtacaaa gccaagtccc gttccccagg gtctccggta 1080 ggggaaggca ctggatcgcc tcccaagtgg cagattggtg agcaggaatt tgaagccctc 1140 atgcggatgc tcgataatct gggctacaga actggctacc cttatcgata ccctgctctg 1200 agagagaagt ctaaaaaata cagcgatgtg gaggttcctg ctagtgtcac aggttactcc 1260 tttgctagtg acggtgattc gggcacttgc tccccactca gacacagttt tcagaagcag 1320 cagcgggaga agacaagatg gctgaactct ggccggggcg acgaagcttc cgaggaaggg 1380 cagaatggaa gcagtcccaa gtcgaagact aaggtgtgga cgaacattac acacgatcac 1440 gtgaaaccct tgctgcagtc tctctcgtcc ggtgtctgcg tgccaagctg tattaccaac 1500 tgcttgtgga ctaaagagga tggacataga acttccacct ctgctgtccc taacctgttt 1560 gttccattga acactaaccc aaaagaggtc caggagatga ggaacaagat ccgagagcag 1620 aatttacagg acattaagac ggctggccct cagtcccagg ttttgtgtgg tgtagtgatg 1680 gacaggagcc tcgtccaggg agagctggtg acggcctcca aggccatcat tgaaaaggag 1740 taccagcccc acgtcattgt gagcaccacg ggccccaacc ccttcaccac actcacagac 1800 cgtgagctgg aggagtaccg cagggaggtg gagaggaagc agaagggctc tgaagagaat 1860 ctggacgagg ctagagaaca gaaagaaaag agtcctccag accagcctgc ggtcccccac 1920 ccgcctccca gcactcccat caagctggag gaagaccttg tgccggagcc gactactgga 1980 gatgacagtg atgctgccac ctttaagcca actctccccg atctgtcccc tgatgaacct 2040 tcagaagcac tcggcttccc aatgttagag aaggaggagg aagcccatag acccccaagc 2100 cccactgagg cccctactga ggccagcccc gagccagccc cagacccagc cccggtggct 2160 gaagaggctg ccccctcagc tgtcgaggag ggggccgccg cggaccctgg cagcgatggg 2220 tctccaggca agtccccgtc caaaaagaag aagaagttcc gtaccccgtc ctttctgaag 2280 aagagcaaga agaagagtga ctcctga 2307 <210> 5 <211> 804 <212> DNA <213> Homo sapiens <400> 5 atgaaagctg cggtgctgac cttggccgtg ctcttcctga cggggagcca ggctcggcat 60 ttctggcagc aagatgaacc cccccagagc ccctgggatc gagtgaagga cctggccact 120 gtgtacgtgg atgtgctcaa agacagcggc agagactatg tgtcccagtt tgaaggctcc 180 gccttgggaa aacagctaaa cctaaagctc cttgacaact gggacagcgt gacctccacc 240 ttcagcaagc tgcgcgaaca gctcggccct gtgacccagg agttctggga taacctggaa 300 aaggagacag agggcctgag gcaggagatg agcaaggatc tggaggaggt gaaggccaag 360 gtgcagccct acctggacga cttccagaag aagtggcagg aggagatgga gctctaccgc 420 cagaaggtgg agccgctgcg cgcagagctc caagagggcg cgcgccagaa gctgcacgag 480 ctgcaagaga agctgagccc actgggcgag gagatgcgcg accgcgcgcg cgcccatgtg 540 gacgcgctgc gcacgcatct ggccccctac agcgacgagc tgcgccagcg cttggccgcg 600 cgccttgagg ctctcaagga gaacggcggc gccagactgg ccgagtacca cgccaaggcc 660 accgagcatc tgagcacgct cagcgagaag gccaagcccg cgctcgagga cctccgccaa 720 ggcctgctgc ccgtgctgga gagcttcaag gtcagcttcc tgagcgctct cgaggagtac 780 actaagaagc tcaacaccca gtga 804 <210> 6 <211> 1191 <212> DNA <213> Homo sapiens <400> 6 atgttcctga aggccgtggt cctgaccctg gccctggtgg ctgtcgccgg agccagggct 60 gaggtcagtg ctgaccaggt ggccacggtg atgtgggact acttcagcca gctgagcaac 120 aatgccaagg aggccgtgga acatctccag aaatctgaac tcacccagca actcaatgcc 180 ctcttccagg acaaacttgg agaagtgaac acttacgcag gtgacctgca gaagaagctg 240 gtgccctttg ccaccgagct gcatgaacgc ctggccaagg actcggagaa actgaaggag 300 gagattggga aggagctgga ggagctgagg gcccggctgc tgccccatgc caatgaggtg 360 agccagaaga tcggggacaa cctgcgagag cttcagcagc gcctggagcc ctacgcggac 420 cagctgcgca cccaggtcag cacgcaggcc gagcagctgc ggcgccagct gaccccctac 480 gcacagcgca tggagagagt gctgcgggag aacgccgaca gcctgcaggc ctcgctgagg 540 ccccacgccg acgagctcaa ggccaagatc gaccagaacg tggaggagct caagggacgc 600 cttacgccct acgctgacga attcaaagtc aagattgacc agaccgtgga ggagctgcgc 660 cgcagcctgg ctccctatgc tcaggacacg caggagaagc tcaaccacca gcttgagggc 720 ctgaccttcc agatgaagaa gaacgccgag gagctcaagg ccaggatctc ggccagtgcc 780 gaggagctgc ggcagaggct ggcgcccttg gccgaggacg tgcgtggcaa cctgaggggc 840 aacaccgagg ggctgcagaa gtcactggca gagctgggtg ggcacctgga ccagcaggtg 900 gaggagttcc gacgccgggt ggagccctac ggggaaaact tcaacaaagc cctggtgcag 960 cagatggaac agctcaggca gaaactgggc ccccatgcgg gggacgtgga aggccacttg 1020 agcttcctgg agaaggacct gagggacaag gtcaactcct tcttcagcac cttcaaggag 1080 aaagagagcc aggacaagac tctctccctc cctgagctgg agcaacagca ggaacagcag 1140 caggagcagc agcaggagca ggtgcagatg ctggcccctt tggagagctg a 1191 <210> 7 <211> 13692 <212> DNA <213> Homo sapiens <400> 7 atggacccgc cgaggcccgc gctgctggcg ctgctggcgc tgcctgcgct gctgctgctg 60 ctgctggcgg gcgccagggc cgaagaggaa atgctggaaa atgtcagcct ggtctgtcca 120 aaagatgcga cccgattcaa gcacctccgg aagtacacat acaactatga ggctgagagt 180 tccagtggag tccctgggac tgctgattca agaagtgcca ccaggatcaa ctgcaaggtt 240 gagctggagg ttccccagct ctgcagcttc atcctgaaga ccagccagtg caccctgaaa 300 gaggtgtatg gcttcaaccc tgagggcaaa gccttgctga agaaaaccaa gaactctgag 360 gagtttgctg cagccatgtc caggtatgag ctcaagctgg ccattccaga agggaagcag 420 gttttccttt acccggagaa agatgaacct acttacatcc tgaacatcaa gaggggcatc 480 atttctgccc tcctggttcc cccagagaca gaagaagcca agcaagtgtt gtttctggat 540 accgtgtatg gaaactgctc cactcacttt accgtcaaga cgaggaaggg caatgtggca 600 acagaaatat ccactgaaag agacctgggg cagtgtgatc gcttcaagcc catccgcaca 660 ggcatcagcc cacttgctct catcaaaggc atgacccgcc ccttgtcaac tctgatcagc 720 agcagccagt cctgtcagta cacactggac gctaagagga agcatgtggc agaagccatc 780 tgcaaggagc aacacctctt cctgcctttc tcctacaaga ataagtatgg gatggtagca 840 caagtgacac agactttgaa acttgaagac acaccaaaga tcaacagccg cttctttggt 900 gaaggtacta agaagatggg cctcgcattt gagagcacca aatccacatc acctccaaag 960 caggccgaag ctgttttgaa gactctccag gaactgaaaa aactaaccat ctctgagcaa 1020 aatatccaga gagctaatct cttcaataag ctggttactg agctgagagg cctcagtgat 1080 gaagcagtca catctctctt gccacagctg attgaggtgt ccagccccat cactttacaa 1140 gccttggttc agtgtggaca gcctcagtgc tccactcaca tcctccagtg gctgaaacgt 1200 gtgcatgcca acccccttct gatagatgtg gtcacctacc tggtggccct gatccccgag 1260 ccctcagcac agcagctgcg agagatcttc aacatggcga gggatcagcg cagccgagcc 1320 accttgtatg cgctgagcca cgcggtcaac aactatcata agacaaaccc tacagggacc 1380 caggagctgc tggacattgc taattacctg atggaacaga ttcaagatga ctgcactggg 1440 gatgaagatt acacctattt gattctgcgg gtcattggaa atatgggcca aaccatggag 1500 cagttaactc cagaactcaa gtcttcaatc ctgaaatgtg tccaaagtac aaagccatca 1560 ctgatgatcc agaaagctgc catccaggct ctgcggaaaa tggagcctaa agacaaggac 1620 caggaggttc ttcttcagac tttccttgat gatgcttctc cgggagataa gcgactggct 1680 gcctatctta tgttgatgag gagtccttca caggcagata ttaacaaaat tgtccaaatt 1740 ctaccatggg aacagaatga gcaagtgaag aactttgtgg cttcccatat tgccaatatc 1800 ttgaactcag aagaattgga tatccaagat ctgaaaaagt tagtgaaaga agctctgaaa 1860 gaatctcaac ttccaactgt catggacttc agaaaattct ctcggaacta tcaactctac 1920 aaatctgttt ctcttccatc acttgaccca gcctcagcca aaatagaagg gaatcttata 1980 tttgatccaa ataactacct tcctaaagaa agcatgctga aaactaccct cactgccttt 2040 ggatttgctt cagctgacct catcgagatt ggcttggaag gaaaaggctt tgagccaaca 2100 ttggaagctc tttttgggaa gcaaggattt ttcccagaca gtgtcaacaa agctttgtac 2160 tgggttaatg gtcaagttcc tgatggtgtc tctaaggtct tagtggacca ctttggctat 2220 accaaagatg ataaacatga gcaggatatg gtaaatggaa taatgctcag tgttgagaag 2280 ctgattaaag atttgaaatc caaagaagtc ccggaagcca gagcctacct ccgcatcttg 2340 ggagaggagc ttggttttgc cagtctccat gacctccagc tcctgggaaa gctgcttctg 2400 atgggtgccc gcactctgca ggggatcccc cagatgattg gagaggtcat caggaagggc 2460 tcaaagaatg acttttttct tcactacatc ttcatggaga atgcctttga actccccact 2520 ggagctggat tacagttgca aatatcttca tctggagtca ttgctcccgg agccaaggct 2580 ggagtaaaac tggaagtagc caacatgcag gctgaactgg tggcaaaacc ctccgtgtct 2640 gtggagtttg tgacaaatat gggcatcatc attccggact tcgctaggag tggggtccag 2700 atgaacacca acttcttcca cgagtcgggt ctggaggctc atgttgccct aaaagctggg 2760 aagctgaagt ttatcattcc ttccccaaag agaccagtca agctgctcag tggaggcaac 2820 acattacatt tggtctctac caccaaaacg gaggtgatcc cacctctcat tgagaacagg 2880 cagtcctggt cagtttgcaa gcaagtcttt cctggcctga attactgcac ctcaggcgct 2940 tactccaacg ccagctccac agactccgcc tcctactatc cgctgaccgg ggacaccaga 3000 ttagagctgg aactgaggcc tacaggagag attgagcagt attctgtcag cgcaacctat 3060 gagctccaga gagaggacag agccttggtg gataccctga agtttgtaac tcaagcagaa 3120 ggtgcgaagc agactgaggc taccatgaca ttcaaatata atcggcagag tatgaccttg 3180 tccagtgaag tccaaattcc ggattttgat gttgacctcg gaacaatcct cagagttaat 3240 gatgaatcta ctgagggcaa aacgtcttac agactcaccc tggacattca gaacaagaaa 3300 attactgagg tcgccctcat gggccaccta agttgtgaca caaaggaaga aagaaaaatc 3360 aagggtgtta tttccatacc ccgtttgcaa gcagaagcca gaagtgagat cctcgcccac 3420 tggtcgcctg ccaaactgct tctccaaatg gactcatctg ctacagctta tggctccaca 3480 gtttccaaga gggtggcatg gcattatgat gaagagaaga ttgaatttga atggaacaca 3540 ggcaccaatg tagataccaa aaaaatgact tccaatttcc ctgtggatct ctccgattat 3600 cctaagagct tgcatatgta tgctaataga ctcctggatc acagagtccc tcaaacagac 3660 atgactttcc ggcacgtggg ttccaaatta atagttgcaa tgagctcatg gcttcagaag 3720 gcatctggga gtcttcctta tacccagact ttgcaagacc acctcaatag cctgaaggag 3780 ttcaacctcc agaacatggg attgccagac ttccacatcc cagaaaacct cttcttaaaa 3840 agcgatggcc gggtcaaata taccttgaac aagaacagtt tgaaaattga gattcctttg 3900 ccttttggtg gcaaatcctc cagagatcta aagatgttag agactgttag gacaccagcc 3960 ctccacttca agtctgtggg attccatctg ccatctcgag agttccaagt ccctactttt 4020 accattccca agttgtatca actgcaagtg cctctcctgg gtgttctaga cctctccacg 4080 aatgtctaca gcaacttgta caactggtcc gcctcctaca gtggtggcaa caccagcaca 4140 gaccatttca gccttcgggc tcgttaccac atgaaggctg actctgtggt tgacctgctt 4200 tcctacaatg tgcaaggatc tggagaaaca acatatgacc acaagaatac gttcacacta 4260 tcatgtgatg ggtctctacg ccacaaattt ctagattcga atatcaaatt cagtcatgta 4320 gaaaaacttg gaaacaaccc agtctcaaaa ggtttactaa tattcgatgc atctagttcc 4380 tggggaccac agatgtctgc ttcagttcat ttggactcca aaaagaaaca gcatttgttt 4440 gtcaaagaag tcaagattga tgggcagttc agagtctctt cgttctatgc taaaggcaca 4500 tatggcctgt cttgtcagag ggatcctaac actggccggc tcaatggaga gtccaacctg 4560 aggtttaact cctcctacct ccaaggcacc aaccagataa caggaagata tgaagatgga 4620 accctctccc tcacctccac ctctgatctg caaagtggca tcattaaaaa tactgcttcc 4680 ctaaagtatg agaactacga gctgacttta aaatctgaca ccaatgggaa gtataagaac 4740 tttgccactt ctaacaagat ggatatgacc ttctctaagc aaaatgcact gctgcgttct 4800 gaatatcagg ctgattacga gtcattgagg ttcttcagcc tgctttctgg atcactaaat 4860 tcccatggtc ttgagttaaa tgctgacatc ttaggcactg acaaaattaa tagtggtgct 4920 cacaaggcga cactaaggat tggccaagat ggaatatcta ccagtgcaac gaccaacttg 4980 aagtgtagtc tcctggtgct ggagaatgag ctgaatgcag agcttggcct ctctggggca 5040 tctatgaaat taacaacaaa tggccgcttc agggaacaca atgcaaaatt cagtctggat 5100 gggaaagccg ccctcacaga gctatcactg ggaagtgctt atcaggccat gattctgggt 5160 gtcgacagca aaaacatttt caacttcaag gtcagtcaag aaggacttaa gctctcaaat 5220 gacatgatgg gctcatatgc tgaaatgaaa tttgaccaca caaacagtct gaacattgca 5280 ggcttatcac tggacttctc ttcaaaactt gacaacattt acagctctga caagttttat 5340 aagcaaactg ttaatttaca gctacagccc tattctctgg taactacttt aaacagtgac 5400 ctgaaataca atgctctgga tctcaccaac aatgggaaac tacggctaga acccctgaag 5460 ctgcatgtgg ctggtaacct aaaaggagcc taccaaaata atgaaataaa acacatctat 5520 gccatctctt ctgctgcctt atcagcaagc tataaagcag acactgttgc taaggttcag 5580 ggtgtggagt ttagccatcg gctcaacaca gacatcgctg ggctggcttc agccattgac 5640 atgagcacaa actataattc agactcactg catttcagca atgtcttccg ttctgtaatg 5700 gccccgttta ccatgaccat cgatgcacat acaaatggca atgggaaact cgctctctgg 5760 ggagaacata ctgggcagct gtatagcaaa ttcctgttga aagcagaacc tctggcattt 5820 actttctctc atgattacaa aggctccaca agtcatcatc tcgtgtctag gaaaagcatc 5880 agtgcagctc ttgaacacaa agtcagtgcc ctgcttactc cagctgagca gacaggcacc 5940 tggaaactca agacccaatt taacaacaat gaatacagcc aggacttgga tgcttacaac 6000 actaaagata aaattggcgt ggagcttact ggacgaactc tggctgacct aactctacta 6060 gactccccaa ttaaagtgcc acttttactc agtgagccca tcaatatcat tgatgcttta 6120 gagatgagag atgccgttga gaagccccaa gaatttacaa ttgttgcttt tgtaaagtat 6180 gataaaaacc aagatgttca ctccattaac ctcccatttt ttgagacctt gcaagaatat 6240 tttgagagga atcgacaaac cattatagtt gtactggaaa acgtacagag aaacctgaag 6300 cacatcaata ttgatcaatt tgtaagaaaa tacagagcag ccctgggaaa actcccacag 6360 caagctaatg attatctgaa ttcattcaat tgggagagac aagtttcaca tgccaaggag 6420 aaactgactg ctctcacaaa aaagtataga attacagaaa atgatataca aattgcatta 6480 gatgatgcca aaatcaactt taatgaaaaa ctatctcaac tgcagacata tatgatacaa 6540 tttgatcagt atattaaaga tagttatgat ttacatgatt tgaaaatagc tattgctaat 6600 attattgatg aaatcattga aaaattaaaa agtcttgatg agcactatca tatccgtgta 6660 aatttagtaa aaacaatcca tgatctacat ttgtttattg aaaatattga ttttaacaaa 6720 agtggaagta gtactgcatc ctggattcaa aatgtggata ctaagtacca aatcagaatc 6780 cagatacaag aaaaactgca gcagcttaag agacacatac agaatataga catccagcac 6840 ctagctggaa agttaaaaca acacattgag gctattgatg ttagagtgct tttagatcaa 6900 ttgggaacta caatttcatt tgaaagaata aatgacattc ttgagcatgt caaacacttt 6960 gttataaatc ttattgggga ttttgaagta gctgagaaaa tcaatgcctt cagagccaaa 7020 gtccatgagt taatcgagag gtatgaagta gaccaacaaa tccaggtttt aatggataaa 7080 ttagtagagt tggcccacca atacaagttg aaggagacta ttcagaagct aagcaatgtc 7140 ctacaacaag ttaagataaa agattacttt gagaaattgg ttggatttat tgatgatgct 7200 gtcaagaagc ttaatgaatt atcttttaaa acattcattg aagatgttaa caaattcctt 7260 gacatgttga taaagaaatt aaagtcattt gattaccacc agtttgtaga tgaaaccaat 7320 gacaaaatcc gtgaggtgac tcagagactc aatggtgaaa ttcaggctct ggaactacca 7380 caaaaagctg aagcattaaa actgttttta gaggaaacca aggccacagt tgcagtgtat 7440 ctggaaagcc tacaggacac caaaataacc ttaatcatca attggttaca ggaggcttta 7500 agttcagcat ctttggctca catgaaggcc aaattccgag agaccctaga agatacacga 7560 gaccgaatgt atcaaatgga cattcagcag gaacttcaac gatacctgtc tctggtaggc 7620 caggtttata gcacacttgt cacctacatt tctgattggt ggactcttgc tgctaagaac 7680 cttactgact ttgcagagca atattctatc caagattggg ctaaacgtat gaaagcattg 7740 gtagagcaag ggttcactgt tcctgaaatc aagaccatcc ttgggaccat gcctgccttt 7800 gaagtcagtc ttcaggctct tcagaaagct accttccaga cacctgattt tatagtcccc 7860 ctaacagatt tgaggattcc atcagttcag ataaacttca aagacttaaa aaatataaaa 7920 atcccatcca ggttttccac accagaattt accatcctta acaccttcca cattccttcc 7980 tttacaattg actttgtaga aatgaaagta aagatcatca gaaccattga ccagatgctg 8040 aacagtgagc tgcagtggcc cgttccagat atatatctca gggatctgaa ggtggaggac 8100 attcctctag cgagaatcac cctgccagac ttccgtttac cagaaatcgc aattccagaa 8160 ttcataatcc caactctcaa ccttaatgat tttcaagttc ctgaccttca cataccagaa 8220 ttccagcttc cccacatctc acacacaatt gaagtaccta cttttggcaa gctatacagt 8280 attctgaaaa tccaatctcc tcttttcaca ttagatgcaa atgctgacat agggaatgga 8340 accacctcag caaacgaagc aggtatcgca gcttccatca ctgccaaagg agagtccaaa 8400 ttagaagttc tcaattttga ttttcaagca aatgcacaac tctcaaaccc taagattaat 8460 ccgctggctc tgaaggagtc agtgaagttc tccagcaagt acctgagaac ggagcatggg 8520 agtgaaatgc tgttttttgg aaatgctatt gagggaaaat caaacacagt ggcaagttta 8580 cacacagaaa aaaatacact ggagcttagt aatggagtga ttgtcaagat aaacaatcag 8640 cttaccctgg atagcaacac taaatacttc cacaaattga acatccccaa actggacttc 8700 tctagtcagg ctgacctgcg caacgagatc aagacactgt tgaaagctgg ccacatagca 8760 tggacttctt ctggaaaagg gtcatggaaa tgggcctgcc ccagattctc agatgaggga 8820 acacatgaat cacaaattag tttcaccata gaaggacccc tcacttcctt tggactgtcc 8880 aataagatca atagcaaaca cctaagagta aaccaaaact tggtttatga atctggctcc 8940 ctcaactttt ctaaacttga aattcaatca caagtcgatt cccagcatgt gggccacagt 9000 gttctaactg ctaaaggcat ggcactgttt ggagaaggga aggcagagtt tactgggagg 9060 catgatgctc atttaaatgg aaaggttatt ggaactttga aaaattctct tttcttttca 9120 gcccagccat ttgagatcac ggcatccaca aacaatgaag ggaatttgaa agttcgtttt 9180 ccattaaggt taacagggaa gatagacttc ctgaataact atgcactgtt tctgagtccc 9240 agtgcccagc aagcaagttg gcaagtaagt gctaggttca atcagtataa gtacaaccaa 9300 aatttctctg ctggaaacaa cgagaacatt atggaggccc atgtaggaat aaatggagaa 9360 gcaaatctgg atttcttaaa cattccttta acaattcctg aaatgcgtct accttacaca 9420 ataatcacaa ctcctccact gaaagatttc tctctatggg aaaaaacagg cttgaaggaa 9480 ttcttgaaaa cgacaaagca atcatttgat ttaagtgtaa aagctcagta taagaaaaac 9540 aaacacaggc attccatcac aaatcctttg gctgtgcttt gtgagtttat cagtcagagc 9600 atcaaatcct ttgacaggca ttttgaaaaa aacagaaaca atgcattaga ttttgtcacc 9660 aaatcctata atgaaacaaa aattaagttt gataagtaca aagctgaaaa atctcacgac 9720 gagctcccca ggacctttca aattcctgga tacactgttc cagttgtcaa tgttgaagtg 9780 tctccattca ccatagagat gtcggcattc ggctatgtgt tcccaaaagc agtcagcatg 9840 cctagtttct ccatcctagg ttctgacgtc cgtgtgcctt catacacatt aatcctgcca 9900 tcattagagc tgccagtcct tcatgtccct agaaatctca agctttctct tccagatttc 9960 aaggaattgt gtaccataag ccatattttt attcctgcca tgggcaatat tacctatgat 10020 ttctccttta aatcaagtgt catcacactg aataccaatg ctgaactttt taaccagtca 10080 gatattgttg ctcatctcct ttcttcatct tcatctgtca ttgatgcact gcagtacaaa 10140 ttagagggca ccacaagatt gacaagaaaa aggggattga agttagccac agctctgtct 10200 ctgagcaaca aatttgtgga gggtagtcat aacagtactg tgagcttaac cacgaaaaat 10260 atggaagtgt cagtggcaac aaccacaaaa gcccaaattc caattttgag aatgaatttc 10320 aagcaagaac ttaatggaaa taccaagtca aaacctactg tctcttcctc catggaattt 10380 aagtatgatt tcaattcttc aatgctgtac tctaccgcta aaggagcagt tgaccacaag 10440 cttagcttgg aaagcctcac ctcttacttt tccattgagt catctaccaa aggagatgtc 10500 aagggttcgg ttctttctcg ggaatattca ggaactattg ctagtgaggc caacacttac 10560 ttgaattcca agagcacacg gtcttcagtg aagctgcagg gcacttccaa aattgatgat 10620 atctggaacc ttgaagtaaa agaaaatttt gctggagaag ccacactcca acgcatatat 10680 tccctctggg agcacagtac gaaaaaccac ttacagctag agggcctctt tttcaccaac 10740 ggagaacata caagcaaagc caccctggaa ctctctccat ggcaaatgtc agctcttgtt 10800 caggtccatg caagtcagcc cagttccttc catgatttcc ctgaccttgg ccaggaagtg 10860 gccctgaatg ctaacactaa gaaccagaag atcagatgga aaaatgaagt ccggattcat 10920 tctgggtctt tccagagcca ggtcgagctt tccaatgacc aagaaaaggc acaccttgac 10980 attgcaggat ccttagaagg acacctaagg ttcctcaaaa atatcatcct accagtctat 11040 gacaagagct tatgggattt cctaaagctg gatgtaacca ccagcattgg taggagacag 11100 catcttcgtg tttcaactgc ctttgtgtac accaaaaacc ccaatggcta ttcattctcc 11160 atccctgtaa aagttttggc tgataaattc attattcctg ggctgaaact aaatgatcta 11220 aattcagttc ttgtcatgcc tacgttccat gtcccattta cagatcttca ggttccatcg 11280 tgcaaacttg acttcagaga aatacaaatc tataagaagc tgagaacttc atcatttgcc 11340 ctcaacctac caacactccc cgaggtaaaa ttccctgaag ttgatgtgtt aacaaaatat 11400 tctcaaccag aagactcctt gattcccttt tttgagataa ccgtgcctga atctcagtta 11460 actgtgtccc agttcacgct tccaaaaagt gtttcagatg gcattgctgc tttggatcta 11520 aatgcagtag ccaacaagat cgcagacttt gagttgccca ccatcatcgt gcctgagcag 11580 accattgaga ttccctccat taagttctct gtacctgctg gaattgtcat tccttccttt 11640 caagcactga ctgcacgctt tgaggtagac tctcccgtgt ataatgccac ttggagtgcc 11700 agtttgaaaa acaaagcaga ttatgttgaa acagtcctgg attccacatg cagctcaacc 11760 gtacagttcc tagaatatga actaaatgtt ttgggaacac acaaaatcga agatggtacg 11820 ttagcctcta agactaaagg aacatttgca caccgtgact tcagtgcaga atatgaagaa 11880 gatggcaaat atgaaggact tcaggaatgg gaaggaaaag cgcacctcaa tatcaaaagc 11940 ccagcgttca ccgatctcca tctgcgctac cagaaagaca agaaaggcat ctccacctca 12000 gcagcctccc cagccgtagg caccgtgggc atggatatgg atgaagatga cgacttttct 12060 aaatggaact tctactacag ccctcagtcc tctccagata aaaaactcac catattcaaa 12120 actgagttga gggtccggga atctgatgag gaaactcaga tcaaagttaa ttgggaagaa 12180 gaggcagctt ctggcttgct aacctctctg aaagacaacg tgcccaaggc cacaggggtc 12240 ctttatgatt atgtcaacaa gtaccactgg gaacacacag ggctcaccct gagagaagtg 12300 tcttcaaagc tgagaagaaa tctgcagaac aatgctgagt gggtttatca aggggccatt 12360 aggcaaattg atgatatcga cgtgaggttc cagaaagcag ccagtggcac cactgggacc 12420 taccaagagt ggaaggacaa ggcccagaat ctgtaccagg aactgttgac tcaggaaggc 12480 caagccagtt tccagggact caaggataac gtgtttgatg gcttggtacg agttactcaa 12540 gaattccata tgaaagtcaa gcatctgatt gactcactca ttgattttct gaacttcccc 12600 agattccagt ttccggggaa acctgggata tacactaggg aggaactttg cactatgttc 12660 ataagggagg tagggacggt actgtcccag gtatattcga aagtccataa tggttcagaa 12720 atactgtttt cctatttcca agacctagtg attacacttc ctttcgagtt aaggaaacat 12780 aaactaatag atgtaatctc gatgtatagg gaactgttga aagatttatc aaaagaagcc 12840 caagaggtat ttaaagccat tcagtctctc aagaccacag aggtgctacg taatcttcag 12900 gaccttttac aattcatttt ccaactaata gaagataaca ttaaacagct gaaagagatg 12960 aaatttactt atcttattaa ttatatccaa gatgagatca acacaatctt cagtgattat 13020 atcccatatg tttttaaatt gttgaaagaa aacctatgcc ttaatcttca taagttcaat 13080 gaatttattc aaaacgagct tcaggaagct tctcaagagt tacagcagat ccatcaatac 13140 attatggccc ttcgtgaaga atattttgat ccaagtatag ttggctggac agtgaaatat 13200 tatgaacttg aagaaaagat agtcagtctg atcaagaacc tgttagttgc tcttaaggac 13260 ttccattctg aatatattgt cagtgcctct aactttactt cccaactctc aagtcaagtt 13320 gagcaatttc tgcacagaaa tattcaggaa tatcttagca tccttaccga tccagatgga 13380 aaagggaaag agaagattgc agagctttct gccactgctc aggaaataat taaaagccag 13440 gccattgcga cgaagaaaat aatttctgat taccaccagc agtttagata taaactgcaa 13500 gatttttcag accaactctc tgattactat gaaaaattta ttgctgaatc caaaagattg 13560 attgacctgt ccattcaaaa ctaccacaca tttctgatat acatcacgga gttactgaaa 13620 aagctgcaat caaccacagt catgaacccc tacatgaagc ttgctccagg agaacttact 13680 atcatcctct aa 13692 <210> 8 <211> 306 <212> DNA <213> Homo sapiens <400> 8 atgggcacac gactcctccc agctctgttt cttgtcctcc tggtattggg atttgaggtc 60 caggggaccc aacagcccca gcaagatgag atgcctagcc cgaccttcct cacccaggtg 120 aaggaatctc tctccagtta ctgggagtca gcaaagacag ccgcccagaa cctgtacgag 180 aagacatacc tgcccgctgt agatgagaaa ctcagggact tgtacagcaa aagcacagca 240 gccatgagca cttacacagg catttttact gaccaagttc tttctgtgct gaagggagag 300 gagtaa 306 <210> 9 <211> 1482 <212> DNA <213> Homo sapiens <400> 9 atgctggctg ccacagtcct gaccctggcc ctgctgggca atgcccatgc ctgctccaaa 60 ggcacctcgc acgaggcagg catcgtgtgc cgcatcacca agcctgccct cctggtgttg 120 aaccacgaga ctgccaaggt gatccagacc gccttccagc gagccagcta cccagatatc 180 acgggcgaga aggccatgat gctccttggc caagtcaagt atgggttgca caacatccag 240 atcagccact tgtccatcgc cagcagccag gtggagctgg tggaagccaa gtccattgat 300 gtctccattc agaacgtgtc tgtggtcttc aaggggaccc tgaagtatgg ctacaccact 360 gcctggtggc tgggtattga tcagtccatt gacttcgaga tcgactctgc cattgacctc 420 cagatcaaca cacagctgac ctgtgactct ggtagagtgc ggaccgatgc ccctgactgc 480 tacctgtctt tccataagct gctcctgcat ctccaagggg agcgagagcc tgggtggatc 540 aagcagctgt tcacaaattt catctccttc accctgaagc tggtcctgaa gggacagatc 600 tgcaaagaga tcaacgtcat ctctaacatc atggccgatt ttgtccagac aagggctgcc 660 agcatccttt cagatggaga cattggggtg gacatttccc tgacaggtga tcccgtcatc 720 acagcctcct acctggagtc ccatcacaag ggtcatttca tctacaagaa tgtctcagag 780 gacctccccc tccccacctt ctcgcccaca ctgctggggg actcccgcat gctgtacttc 840 tggttctctg agcgagtctt ccactcgctg gccaaggtag ctttccagga tggccgcctc 900 atgctcagcc tgatgggaga cgagttcaag gcagtgctgg agacctgggg cttcaacacc 960 aaccaggaaa tcttccaaga ggttgtcggc ggcttcccca gccaggccca agtcaccgtc 1020 cactgcctca agatgcccaa gatctcctgc caaaacaagg gagtcgtggt caattcttca 1080 gtgatggtga aattcctctt tccacgccca gaccagcaac attctgtagc ttacacattt 1140 gaagaggata tcgtgactac cgtccaggcc tcctattcta agaaaaagct cttcttaagc 1200 ctcttggatt tccagattac accaaagact gtttccaact tgactgagag cagctccgag 1260 tccgtccaga gcttcctgca gtcaatgatc accgctgtgg gcatccctga ggtcatgtct 1320 cggctcgagg tagtgtttac agccctcatg aacagcaaag gcgtgagcct cttcgacatc 1380 atcaaccctg agattatcac tcgagatggc ttcctgctgc tgcagatgga ctttggcttc 1440 cctgagcacc tgctggtgga tttcctccag agcttgagct ag 1482 <210> 10 <211> 2757 <212> DNA <213> Homo sapiens <400> 10 atgctccagg gcacctgctc cgtgctcctg ctctggggaa tcctgggggc catccaggcc 60 cagcagcagg aggtcatctc gccggacact accgagagaa acaacaactg cccagagaag 120 accgactgcc ccatccacgt gtacttcgtg ctggacacct cggagagcgt caccatgcag 180 tcccccacgg acatcctgct cttccacatg aagcagttcg tgccgcagtt catcagccag 240 ctgcagaacg agttctacct ggaccaggtg gcgctgagct ggcgctacgg cggcctgcac 300 ttctctgacc aggtggaggt gttcagccca ccgggcagcg accgggcctc cttcatcaag 360 aacctgcagg gcatcagctc cttccgccgc ggcaccttca ccgactgcgc gctggccaac 420 atgacggagc agatccggca ggaccgcagc aagggcaccg tccacttcgc cgtggtcatc 480 accgacggcc acgtcaccgg cagcccctgc gggggcatca agctgcaggc cgagcgggcc 540 cgcgaggagg gcatccggct cttcgccgtg gcccccaacc agaacctgaa ggagcagggc 600 ctgcgggaca tcgccagcac gccgcacgag ctctaccgca acgactacgc caccatgctg 660 cccgactcca ccgagatcga ccaggacacc atcaaccgca tcatcaaggt catgaaacac 720 gaagcctacg gagagtgcta caaggtgagc tgcctggaaa tccctgggcc ctctggcccc 780 aagggctacc gtggacagaa gggtgccaag ggcaacatgg gtgagccggg agagcctggc 840 cagaagggaa gacagggaga cccgggcatc gaaggcccca ttggattccc aggacccaag 900 ggcgttcctg gcttcaaagg agagaagggt gaatttggag ccgacggtcg caagggggcc 960 cctggcctgg ctggcaagaa cgggaccgat ggacagaagg gcaagctggg gcgcatcgga 1020 cctcctggct gcaagggaga ccctggaaac cggggccccg acggttaccc gggggaagca 1080 gggagtccag gggagcgagg agaccaaggc ggcaaggggg accctggccg cccaggacgc 1140 agagggcccc cgggagaaat cggggccaag ggaagcaagg ggtatcaagg caacagtgga 1200 gccccaggaa gtcctggtgt gaaaggagcc aagggcgggc ctgggccccg cggacccaaa 1260 ggcgagccgg ggcgcagggg agaccccggc accaagggca gcccaggcag cgatggcccc 1320 aagggggaga agggggaccc tggccctgag gggccccgcg gcctggctgg agaggttggc 1380 aacaaaggag ccaagggaga ccgaggcttg cctggaccca gaggccccca gggagctctt 1440 ggggagcccg gaaagcaggg atctcgggga gaccccggtg atgcaggacc ccgtggagac 1500 tcaggacagc caggccccaa gggagacccc ggcaggcctg gattcagcta cccaggaccc 1560 cgaggagcac ccggagaaaa aggcgagccc ggcccacgcg gccccgaggg aggccgaggc 1620 gactttggct tgaaaggaga acctgggagg aaaggagaga aaggagagcc tgcggatcct 1680 ggtccccctg gtgagccagg ccctcggggg ccaagaggag tcccaggacc cgagggtgag 1740 cccggccccc ctggagaccc cggtctcacg gagtgtgacg tcatgaccta cgtgagggag 1800 acctgcgggt gctgcgactg tgagaagcgc tgtggcgccc tggacgtggt cttcgtcatc 1860 gacagctccg agagcattgg gtacaccaac ttcacactgg agaagaactt cgtcatcaac 1920 gtggtcaaca ggctgggtgc catcgctaag gaccccaagt ccgagacagg gacgcgtgtg 1980 ggcgtggtgc agtacagcca cgagggcacc tttgaggcca tccagctgga cgacgaacgt 2040 atcgactccc tgtcgagctt caaggaggct gtcaagaacc tcgagtggat tgcgggcggc 2100 acctggacac cctcagccct caagtttgcc tacgaccgcc tcatcaagga gagccggcgc 2160 cagaagacac gtgtgtttgc ggtggtcatc acggacgggc gccacgaccc tcgggacgat 2220 gacctcaact tgcgggcgct gtgcgaccgc gacgtcacag tgacggccat cggcatcggg 2280 gacatgttcc acgagaagca cgagagtgaa aacctctact ccatcgcctg cgacaagcca 2340 cagcaggtgc gcaacatgac gctgttctcc gacctggtcg ctgagaagtt catcgatgac 2400 atggaggacg tcctctgccc ggaccctcag atcgtgtgcc cagaccttcc ctgccaaaca 2460 gatgcaccgt ggcctggcgg cgagcccccg gtcaccttcc tccgcacgga agaggggccg 2520 gacgccacct tccccaggac cattcccctg atccaacagt tgctaaacgc cacggagctc 2580 acgcaggacc cggccgccta ctcccagctg gtggccgtgc tggtctacac cgccgagcgg 2640 gccaagttcg ccaccggggt agagcggcag gactggatgg agctgttcat tgacaccttt 2700 aagctggtgc acagggacat cgtgggggac cccgagaccg cgctggccct ctgctaa 2757 <210> 11 <211> 3060 <212> DNA <213> Homo sapiens <400> 11 atgctccagg gcacctgctc cgtgctcctg ctctggggaa tcctgggggc catccaggcc 60 cagcagcagg aggtcatctc gccggacact accgagagaa acaacaactg cccagagaag 120 accgactgcc ccatccacgt gtacttcgtg ctggacacct cggagagcgt caccatgcag 180 tcccccacgg acatcctgct cttccacatg aagcagttcg tgccgcagtt catcagccag 240 ctgcagaacg agttctacct ggaccaggtg gcgctgagct ggcgctacgg cggcctgcac 300 ttctctgacc aggtggaggt gttcagccca ccgggcagcg accgggcctc cttcatcaag 360 aacctgcagg gcatcagctc cttccgccgc ggcaccttca ccgactgcgc gctggccaac 420 atgacggagc agatccggca ggaccgcagc aagggcaccg tccacttcgc cgtggtcatc 480 accgacggcc acgtcaccgg cagcccctgc gggggcatca agctgcaggc cgagcgggcc 540 cgcgaggagg gcatccggct cttcgccgtg gcccccaacc agaacctgaa ggagcagggc 600 ctgcgggaca tcgccagcac gccgcacgag ctctaccgca acgactacgc caccatgctg 660 cccgactcca ccgagatcga ccaggacacc atcaaccgca tcatcaaggt catgaaacac 720 gaagcctacg gagagtgcta caaggtgagc tgcctggaaa tccctgggcc ctctggcccc 780 aagggctacc gtggacagaa gggtgccaag ggcaacatgg gtgagccggg agagcctggc 840 cagaagggaa gacagggaga cccgggcatc gaaggcccca ttggattccc aggacccaag 900 ggcgttcctg gcttcaaagg agagaagggt gaatttggag ccgacggtcg caagggggcc 960 cctggcctgg ctggcaagaa cgggaccgat ggacagaagg gcaagctggg gcgcatcgga 1020 cctcctggct gcaagggaga ccctggaaac cggggccccg acggttaccc gggggaagca 1080 gggagtccag gggagcgagg agaccaaggc ggcaaggggg accctggccg cccaggacgc 1140 agagggcccc cgggagaaat cggggccaag ggaagcaagg ggtatcaagg caacagtgga 1200 gccccaggaa gtcctggtgt gaaaggagcc aagggcgggc ctgggccccg cggacccaaa 1260 ggcgagccgg ggcgcagggg agaccccggc accaagggca gcccaggcag cgatggcccc 1320 aagggggaga agggggaccc tggccctgag gggccccgcg gcctggctgg agaggttggc 1380 aacaaaggag ccaagggaga ccgaggcttg cctggaccca gaggccccca gggagctctt 1440 ggggagcccg gaaagcaggg atctcgggga gaccccggtg atgcaggacc ccgtggagac 1500 tcaggacagc caggccccaa gggagacccc ggcaggcctg gattcagcta cccaggaccc 1560 cgaggagcac ccggagaaaa aggcgagccc ggcccacgcg gccccgaggg aggccgaggc 1620 gactttggct tgaaaggaga acctgggagg aaaggagaga aaggagagcc tgcggatcct 1680 ggtccccctg gtgagccagg ccctcggggg ccaagaggag tcccaggacc cgagggtgag 1740 cccggccccc ctggagaccc cggtctcacg gagtgtgacg tcatgaccta cgtgagggag 1800 acctgcgggt gctgcgactg tgagaagcgc tgtggcgccc tggacgtggt cttcgtcatc 1860 gacagctccg agagcattgg gtacaccaac ttcacactgg agaagaactt cgtcatcaac 1920 gtggtcaaca ggctgggtgc catcgctaag gaccccaagt ccgagacagg gacgcgtgtg 1980 ggcgtggtgc agtacagcca cgagggcacc tttgaggcca tccagctgga cgacgaacgt 2040 atcgactccc tgtcgagctt caaggaggct gtcaagaacc tcgagtggat tgcgggcggc 2100 acctggacac cctcagccct caagtttgcc tacgaccgcc tcatcaagga gagccggcgc 2160 cagaagacac gtgtgtttgc ggtggtcatc acggacgggc gccacgaccc tcgggacgat 2220 gacctcaact tgcgggcgct gtgcgaccgc gacgtcacag tgacggccat cggcatcggg 2280 gacatgttcc acgagaagca cgagagtgaa aacctctact ccatcgcctg cgacaagcca 2340 cagcaggtgc gcaacatgac gctgttctcc gacctggtcg ctgagaagtt catcgatgac 2400 atggaggacg tcctctgccc ggaccctcag atcgtgtgcc cagaccttcc ctgccaaaca 2460 gagctgtccg tggcacagtg cacgcagcgg cccgtggaca tcgtcttcct gctggacggc 2520 tccgagcggc tgggtgagca gaacttccac aaggcccggc gcttcgtgga gcaggtggcg 2580 cggcggctga cgctggcccg gagggacgac gaccctctca acgcacgcgt ggcgctgctg 2640 cagtttggtg gccccggcga gcagcaggtg gccttcccgc tgagccacaa cctcacggcc 2700 atccacgagg cgctggagac cacacaatac ctgaactcct tctcgcacgt gggcgcaggc 2760 gtggtgcacg ccatcaatgc catcgtgcgc agcccgcgtg gcggggcccg gaggcacgca 2820 gagctgtcct tcgtgttcct cacggacggc gtcacgggca acgacagtct gcacgagtcg 2880 gcgcactcca tgcgcaagca gaacgtggta cccaccgtgc tggccttggg cagcgacgtg 2940 gacatggacg tgctcaccac gctcagcctg ggtgaccgcg ccgccgtgtt ccacgagaag 3000 gactatgaca gcctggcgca acccggcttc ttcgaccgct tcatccgctg gatctgctag 3060 3060 <210> 12 <211> 3426 <212> DNA <213> Homo sapiens <400> 12 atggacgaca gcggcgagct gggtggtctg gagaccatgg agaccctcac ggagctgggc 60 gacgagctga ccctgggaga catcgacgag atgctgcaat ttgtcagtaa tcaagtggga 120 gagttccctg acttgttttc agaacagctg tgtagctcct ttcctggcag tggtggtagt 180 ggtagcagca gcggcagcag tggcagcagc agcagcagca gcaatggcag gggcagcagc 240 agcggagctg tggacccttc agtgcaacgg tcattcaccc aggtcacatt accttccttc 300 tctccctcgg cggcctcccc acaggctcca actctgcaag tcaaggtttc tcccacctca 360 gttcccacca cacccagggc aactcctatt cttcagcccc gcccccagcc ccagcctcaa 420 cctcaaactc agctgcaaca acagacggta atgatcacgc caacattcag caccactccg 480 cagacgagga tcatccagca gcctttgata taccagaatg cagctactag ctttcaagtc 540 cttcagcctc aagtccaaag cctggtgaca tcctcccagg tacagccggt caccattcag 600 cagcaggtgc agacagtaca ggcccagcgg gtgctgacac aaacggccaa tggcacgctg 660 cagacccttg ccccggctac ggtgcagaca gttgctgcgc cacaggtgca gcaggtcccg 720 gtcctggtcc agcctcagat catcaagaca gattcccttg ttttgaccac actgaagaca 780 gatggcagcc ctgttatggc tgcggtccag aacccggccc tcaccgccct caccacccct 840 atccagacgg ctgcccttca agtaccaacc ctggtgggca gcagtgggac cattctgacc 900 acaatgcctg taatgatggg gcaagagaaa gtgcccatta agcaggtacc tgggggagtc 960 aagcagcttg agccccccaa agaaggagaa aggcggacaa cccataatat cattgagaaa 1020 cgatatcgct cctccatcaa tgacaaaatc atcgaattga aagacctggt catggggaca 1080 gacgccaaga tgcacaagtc tggcgttctg aggaaggcca ttgattacat caaatacttg 1140 cagcaggtca atcataaact gcgccaggag aacatggtgc tgaagctggc aaatcaaaag 1200 aacaagcttc taaagggcat cgacctaggc agtctggtgg acaatgaggt ggacctgaag 1260 atcgaggact ttaatcagaa tgtccttctg atgtcccccc cagcctctga ctcagggtcc 1320 caggctggct tctctcccta ctccattgac tctgagccag gaagccctct attggatgat 1380 gcaaaggtca aagatgagcc agactctcct cctgtggcgc tgggcatggt agaccgctca 1440 cggattcttc tgtgtgtcct caccttcctg tgcctctcct ttaaccccct gacttccctg 1500 ctgcagtggg gaggggccca cgactctgac cagcacccac actcaggctc tggccgcagt 1560 gtcctgtcat tcgagtcagg ttctgggggc tggtttgact ggatgatgcc tactcttctc 1620 ttatggctgg taaatggtgt gattgtcctg agcgtctttg tgaagctgct ggttcatggg 1680 gagccagtga tccggccaca ctcgcgctcc tcggtcacct tctggaggca ccggaaacag 1740 gcagatctgg atctcgccag aggagatttt gcagctgctg ccggcaacct acaaacctgc 1800 ctggcagttt tgggccgggc actgcccacc tcccgcctgg acctggcctg cagcctctcc 1860 tggaacgtga tccgctacag cctgcagaag ctacgcctgg tgcgctggct gctcaagaaa 1920 gtcttccagt gccggcgggc cacgccagcc actgaggcag gctttgaaga cgaagctaag 1980 accagcgccc gggatgcggc tctggcctat caccggctgc accagctgca catcacaggg 2040 aagcttcctg caggatccgc ctgttccgat gtacacatgg cgttgtgtgc cgtgaacctg 2100 gctgaatgtg cagaggagaa gatcccaccg agcacactgg ttgagatcca tctgactgct 2160 gccatggggc tcaagacccg gtgtggaggc aagctgggct tcctggccag ctacttcctc 2220 agccgagccc agagcctgtg tggccccgag cacagtgctg ttcctgactc cctgcgctgg 2280 ctctgccacc ccctgggcca gaagtttttc atggagcgga gctggtctgt gaagtcagct 2340 gccaaggaga gtctatactg tgcccagagg aacccagctg accccattgc gcaggtccac 2400 caggccttct gcaagaacct gctggagcga gctatagagt ccttggtgaa acctcaggcc 2460 aagaagaagg ctggagacca ggaagaagag agctgtgaat tctccagtgc tctggagtac 2520 ttgaaattac ttcattcttt tgtggactct gtgggggtta tgagcccccc actctccagg 2580 agctccgtgc tcaagtccgc cctgggtcca gacatcatct gtcggtggtg gacgtctgca 2640 atcactgtgg ccatcagctg gctccaggga gacgatgcag ctgtgcgctc tcattttacc 2700 aaagtggaac gcatccccaa ggccctggaa gtgacagaga gccccctggt gaaggccatc 2760 ttccatgcct gcagagccat gcatgcctca ctccctggga aagcagatgg gcagcagagt 2820 tccttctgcc attgcgagag ggccagtggc cacctatgga gcagcctcaa cgtcagtggg 2880 gccacctctg accctgccct caaccacgtg gtccagctgc tcacctgtga cctgctactg 2940 tcgctacgga cagcgctctg gcaaaaacag gccagtgcca gccaggctgt gggggagacc 3000 taccacgcgt caggcgctga actggcgggc ttccaacggg acctgggcag cctgcgcagg 3060 ctggcacaca gcttccgccc agcataccgc aaggtgttcc tgcatgaagc caccgtgcgc 3120 ctgatggcag gagccagccc cacccgcacc caccagctgc tggaacacag cctgcggcgg 3180 cgcaccacgc agagcaccaa gcacggagag gtggatgcct ggcccggcca gcgagagcgg 3240 gccaccgcca tcctgctggc ctgccgccac ctgcccctct ccttcctctc ctccccgggc 3300 cagcgggcag tgctgctggc cgaagctgcc cgcaccctgg agaaggtggg cgaccggcgc 3360 tcctgcaacg actgccagca gatgattgtt aagctgggtg gtggcactgc cattgccgcc 3420 tcctga 3426 <210> 13 <211> 735 <212> DNA <213> Homo sapiens <400> 13 atggatcgtg gtcagcatcc tcctgggtgg gcctggcagt ggctttcctc gcatccagca 60 actcttcacc agctggagtg cagtggtgca atctcggttc actgcaacct ctacctcctg 120 ggttcaagcg attctagtgc cccagcctcc cgagtagctg agactacagg tccagagagc 180 tcggtgactg cagcgccacg ggccaggaag tacaagtgtg gcctgcccca gccgtgtcct 240 gaggagcacc tggccttccg cgtggtcagc ggggccgcca acgtcattgg gcccaagatc 300 tgcctcgagg acaagatgct gatgagcagc gtcaaggaca acgtgggccg cgggctgaac 360 atcgccctgg tgaacggggt cagcggcgag ctcatcgagg cccgggcctt tgacatgtgg 420 gccggagatg tcaacgacct gttgaagttt attcggccac tgcacgaagg caccctggtg 480 ttcgtggcat cctacgacga cccagccacc aagatgaatg aagagaccag aaagctcttc 540 agtgagctgg gcagcaggaa cgccaaggag ctggccttcc gggacagctg ggtgtttgtc 600 ggggccaagg gtgtgcagaa caagagcccc tttgagcagc acgtgaagaa cagtaagcac 660 agcaacaagt acgaaggctg gcccgaggcg ctggagatgg aaggctgtat cccgcggaga 720 agcacggcca gctag 735 <210> 14 <211> 693 <212> DNA <213> Homo sapiens <400> 14 atgaggttgg caggccctct ccgcattgtg gtcctagtcg tcagtgtggg tgtcacatgg 60 atcgtggtca gcatcctcct gggtgggcct ggcagtggct ttcctcgcat ccagcaactc 120 ttcaccagtc cagagagctc ggtgactgca gcgccacggg ccaggaagta caagtgtggc 180 ctgccccagc cgtgtcctga ggagcacctg gccttccgcg tggtcagcgg ggccgccaac 240 gtcattgggc ccaagatctg cctcgaggac aagatgctga tgagcagcgt caaggacaac 300 gtgggccgcg ggctgaacat cgccctggtg aacggggtca gcggcgagct catcgaggcc 360 cgggcctttg acatgtgggc cggagatgtc aacgacctgt tgaagtttat tcggccactg 420 cacgaaggca ccctggtgtt cgtggcatcc tacgacgacc cagccaccaa gatgaatgaa 480 gagaccagaa agctcttcag tgagctgggc agcaggaacg ccaaggagct ggccttccgg 540 gacagctggg tgtttgtcgg ggccaagggt gtgcagaaca agagcccctt tgagcagcac 600 gtgaagaaca gtaagcacag caacaagtac gaaggctggc ccgaggcgct ggagatggaa 660 ggctgtatcc cgcggagaag cacggccagc tag 693 <210> 15 <211> 708 <212> DNA <213> Homo sapiens <400> 15 atgcgcccat tggctggtgg cctgctcaag gtggtgttcg tggtcttcgc ctccttgtgt 60 gcctggtatt cggggtacct gctcgcagag ctcattccag atgcacccct gtccagtgct 120 gcctatagca tccgcagcat cggggagagg cctgtcctca aagctccagt ccccaaaagg 180 caaaaatgtg accactggac tccctgccca tctgacacct atgcctacag gttactcagc 240 ggaggtggca gaagcaagta cgccaaaatc tgctttgagg ataacctact tatgggagaa 300 cagctgggaa atgttgccag aggaataaac attgccattg tcaactatgt aactgggaat 360 gtgacagcaa cacgatgttt tgatatgtat gaaggtgata actctggacc gatgacaaag 420 tttattcaga gtgctgctcc aaaatccctg ctcttcatgg tgacctatga cgacggaagc 480 acaagactga ataacgatgc caagaatgcc atagaagcac ttggaagtaa agaaatcagg 540 aacatgaaat tcaggtctag ctgggtattt attgcagcaa aaggcttgga actcccttcc 600 gaaattcaga gagaaaagat caaccactct gatgctaaga acaacagata ttctggctgg 660 cctgcagaga tccagataga aggctgcata cccaaagaac gaagctga 708 <210> 16 <211> 684 <212> DNA <213> Homo sapiens <400> 16 atgagggtag caggtgctgc aaagttggtg gtagctgtgg cagtgttttt actgacattt 60 tatgttattt ctcaagtatt tgaaataaaa atggatgcaa gtttaggaaa tctatttgca 120 agatcagcat tggacacagc tgcacgttct acaaagcctc ccagatataa gtgtgggatc 180 tcaaaagctt gccctgagaa gcattttgct tttaaaatgg caagtggagc agccaacgtg 240 gtgggaccca aaatctgcct ggaagataat gttttaatga gtggtgttaa gaataatgtt 300 ggaagaggga tcaatgttgc cttggcaaat ggaaaaacag gagaagtatt agacactaaa 360 tattttgaca tgtggggagg agatgtggca ccatttattg agtttctgaa ggccatacaa 420 gatggaacaa tagttttaat gggaacatac gatgatggag caaccaaact caatgatgag 480 gcacggcggc tcattgctga tttggggagc acatctatta ctaatcttgg ttttagagac 540 aactgggtct tctgtggtgg gaagggcatt aagacaaaaa gcccttttga acagcacata 600 aagaacaata aggatacaaa caaatatgaa ggatggcctg aagttgtaga aatggaagga 660 tgcatccccc agaagcaaga ctaa 684 <210> 17 <211> 1518 <212> DNA <213> Homo sapiens <400> 17 atgaagcgca ccccgactgc cgaggaacga gagcgcgaag ctaagaaact gaggcttctt 60 gaagagcttg aagacacttg gctcccttat ctgaccccca aagatgatga attctatcag 120 cagtggcagc tgaaatatcc taaactaatt ctccgagaag ccagcagtgt atctgaggag 180 ctccataaag aggttcaaga agcctttctc acactgcaca agcatggctg cttatttcgg 240 gacctggtta ggatccaagg caaagatctg ctcactccgg tatctcgcat cctcattggt 300 aatccaggct gcacctacaa gtacctgaac accaggctct ttacggtccc ctggccagtg 360 aaagggtcta atataaaaca caccgaggct gaaatagccg ctgcttgtga gaccttcctc 420 aagctcaatg actacctgca gatagaaacc atccaggctt tggaagaact tgctgccaaa 480 gagaaggcta atgaggatgc tgtgccattg tgtatgtctg cagatttccc cagggttggg 540 atgggttcat cctacaacgg acaagatgaa gtggacatta agagcagagc agcatacaac 600 gtaactttgc tgaatttcat ggatcctcag aaaatgccat acctgaaaga ggaaccttat 660 tttggcatgg ggaaaatggc agtgagctgg catcatgatg aaaatctggt ggacaggtca 720 gcggtggcag tgtacagtta tagctgtgaa ggccctgaag aggaaagtga ggatgactct 780 catctcgaag gcagggatcc tgatatttgg catgttggtt ttaagatctc atgggacata 840 gagacacctg gtttggcgat accccttcac caaggagact gctatttcat gcttgatgat 900 ctcaatgcca cccaccaaca ctgtgttttg gccggttcac aacctcggtt tagttccacc 960 caccgagtgg cagagtgctc aacaggaacc ttggattata ttttacaacg ctgtcagttg 1020 gctctgcaga atgtctgtga cgatgtggac aatgatgatg tctctttgaa atcctttgag 1080 cctgcagttt tgaaacaagg agaagaaatt cataatgagg tcgagtttga gtggctgagg 1140 cagttttggt ttcaaggcaa tcgatacaga aagtgcactg actggtggtg tcaacccatg 1200 gctcaactgg aagcactgtg gaagaagatg gagggtgtga caaatgctgt gcttcatgaa 1260 gttaaaagag aggggctccc cgtggaacaa aggaatgaaa tcttgactgc catccttgcc 1320 tcgctcactg cacgccagaa cctgaggaga gaatggcatg ccaggtgcca gtcacgaatt 1380 gcccgaacat tacctgctga tcagaagcca gaatgtcggc catactggga aaaggatgat 1440 gcttcgatgc ctctgccgtt tgacctcaca gacatcgttt cagaactcag aggtcagctt 1500 ctggaagcaa aaccctag 1518 <210> 18 <211> 1878 <212> DNA <213> Homo sapiens <400> 18 atgccaggca caaaacggtt tcaacatgtc attgagaccc cggagcctgg caagtgggag 60 ttgtctgggt acgaggcagc tgtgccaatc acggagaagt caaacccact gacccaggat 120 ctagacaaag cagatgctga gaacattgtt cgactgctag ggcaatgtga tgctgagatc 180 ttccaggagg aggggcaagc cctgtccaca taccagagac tctacagcga atccattctg 240 accaccatgg tacaggtggc tgggaaagtt caggaagtgc tgaaggagcc agatgggggg 300 ctggttgtgc tgagtggagg gggcacctct ggccggatgg cattcctcat gtcggtgtcc 360 tttaatcagc tgatgaaagg tctgggacag aaacctcttt acacctacct cattgcaggt 420 ggtgacaggt ctgtggtggc ctctagggag gggacagaag atagtgcctt gcacgggatt 480 gaggaactga agaaggtggc tgccgggaag aagagagtga ttgtcattgg catttctgtg 540 ggactctctg ctccctttgt ggcaggccag atggactgct gcatgaacaa cacagctgtc 600 ttcttgccag tcctggttgg cttcaatcca gtgagcatgg ccagaaatga ccccattgaa 660 gactggagtt caacattccg acaagtagca gagcggatgc agaaaatgca ggagaaacag 720 aaagcttttg tgctcaatcc tgccatcggg cccgagggtc tcagcggctc ctcccggatg 780 aaaggtggaa gtgccaccaa gattctgctg gaaaccctgt tattagcagc ccataagact 840 gtggaccagg gcattgcagc atctcaaaga tgcctcctgg aaatcttgcg gacatttgag 900 cgagctcatc aggtgaccta cagccaaagc cccaagattg ccaccctgat gaagagtgtc 960 agcaccagtc tggagaagaa aggccacgtg tacctggttg gctggcagac cctgggcatc 1020 attgccatca tggatggagt agagtgcatc cacacctttg gtgctgattt ccgagatgtc 1080 cgtggctttc tcattggtga tcacagtgac atgtttaacc agaaggctga gctcaccaac 1140 cagggtcccc agttcacctt ctcccaggag gacttcctga cttccatcct tccctctctc 1200 acggaaatcg atactgtggt cttcattttc accctggatg acaacctcac ggaggtgcag 1260 actatagtgg agcaggtgaa agagaagacc aaccacatcc aggccctggc acacagcacc 1320 gtgggtcaga ccttgctgat ccctctgaag aagctctttc cctccatcat cagcatcaca 1380 tggccactgc ttttctttga atatgaaggg aacttcatcc agaagttcca gcgtgagcta 1440 agcaccaaat gggtgctgaa tacagtgagt acaggtgctc atgtgcttct tggtaagatc 1500 ctacaaaacc acatgttgga ccttcggatt agcaactcca agctcttctg gcgggcgctg 1560 gccatgctgc agcggttctc tggacagtcc aaggctcgat gcatcgagag cctcctccga 1620 gcgatccact ttccccagcc actgtcagat gatattcggg ctgctcccat ctcctgccat 1680 gtccaggttg cacatgagaa ggaacaggtg atacccatcg ccttgctgag cctcctattc 1740 cggtgctcga tcactgaggc tcaggcacac ctggctgcag ctccttctgt ctgtgaggct 1800 gtcaggagtg ctcttgctgg gccaggtcag aagcgcactg cggaccccct cgagatccta 1860 gagcctgacg ttcagtga 1878 <210> 19 <211> 2583 <212> DNA <213> Homo sapiens <400> 19 atggggccct ggggctggaa attgcgctgg accgtcgcct tgctcctcgc cgcggcgggg 60 actgcagtgg gcgacagatg cgaaagaaac gagttccagt gccaagacgg gaaatgcatc 120 tcctacaagt gggtctgcga tggcagcgct gagtgccagg atggctctga tgagtcccag 180 gagacgtgct tgtctgtcac ctgcaaatcc ggggacttca gctgtggggg ccgtgtcaac 240 cgctgcattc ctcagttctg gaggtgcgat ggccaagtgg actgcgacaa cggctcagac 300 gagcaaggct gtccccccaa gacgtgctcc caggacgagt ttcgctgcca cgatgggaag 360 tgcatctctc ggcagttcgt ctgtgactca gaccgggact gcttggacgg ctcagacgag 420 gcctcctgcc cggtgctcac ctgtggtccc gccagcttcc agtgcaacag ctccacctgc 480 atcccccagc tgtgggcctg cgacaacgac cccgactgcg aagatggctc ggatgagtgg 540 ccgcagcgct gtaggggtct ttacgtgttc caaggggaca gtagcccctg ctcggccttc 600 gagttccact gcctaagtgg cgagtgcatc cactccagct ggcgctgtga tggtggcccc 660 gactgcaagg acaaatctga cgaggaaaac tgcgctgtgg ccacctgtcg ccctgacgaa 720 ttccagtgct ctgatggaaa ctgcatccat ggcagccggc agtgtgaccg ggaatatgac 780 tgcaaggaca tgagcgatga agttggctgc gttaatgtga cactctgcga gggacccaac 840 aagttcaagt gtcacagcgg cgaatgcatc accctggaca aagtctgcaa catggctaga 900 gactgccggg actggtcaga tgaacccatc aaagagtgcg ggaccaacga atgcttggac 960 aacaacggcg gctgttccca cgtctgcaat gaccttaaga tcggctacga gtgcctgtgc 1020 cccgacggct tccagctggt ggcccagcga agatgcgaag atatcgatga gtgtcaggat 1080 cccgacacct gcagccagct ctgcgtgaac ctggagggtg gctacaagtg ccagtgtgag 1140 gaaggcttcc agctggaccc ccacacgaag gcctgcaagg ctgtgggctc catcgcctac 1200 ctcttcttca ccaaccggca cgaggtcagg aagatgacgc tggaccggag cgagtacacc 1260 agcctcatcc ccaacctgag gaacgtggtc gctctggaca cggaggtggc cagcaataga 1320 atctactggt ctgacctgtc ccagagaatg atctgcagca cccagcttga cagagcccac 1380 ggcgtctctt cctatgacac cgtcatcagc agagacatcc aggcccccga cgggctggct 1440 gtggactgga tccacagcaa catctactgg accgactctg tcctgggcac tgtctctgtt 1500 gcggatacca agggcgtgaa gaggaaaacg ttattcaggg agaacggctc caagccaagg 1560 gccatcgtgg tggatcctgt tcatggcttc atgtactgga ctgactgggg aactcccgcc 1620 aagatcaaga aagggggcct gaatggtgtg gacatctact cgctggtgac tgaaaacatt 1680 cagtggccca atggcatcac cctagatctc ctcagtggcc gcctctactg ggttgactcc 1740 aaacttcact ccatctcaag catcgatgtc aacgggggca accggaagac catcttggag 1800 gatgaaaaga ggctggccca ccccttctcc ttggccgtct ttgaggacaa agtattttgg 1860 acagatatca tcaacgaagc cattttcagt gccaaccgcc tcacaggttc cgatgtcaac 1920 ttgttggctg aaaacctact gtccccagag gatatggttc tcttccacaa cctcacccag 1980 ccaagaggag tgaactggtg tgagaggacc accctgagca atggcggctg ccagtatctg 2040 tgcctccctg ccccgcagat caacccccac tcgcccaagt ttacctgcgc ctgcccggac 2100 ggcatgctgc tggccaggga catgaggagc tgcctcacag aggctgaggc tgcagtggcc 2160 acccaggaga catccaccgt caggctaaag gtcagctcca cagccgtaag gacacagcac 2220 acaaccaccc gacctgttcc cgacacctcc cggctgcctg gggccacccc tgggctcacc 2280 acggtggaga tagtgacaat gtctcaccaa gctctgggcg acgttgctgg cagaggaaat 2340 gagaagaagc ccagtagcgt gagggctctg tccattgtcc tccccatcgt gctcctcgtc 2400 ttcctttgcc tgggggtctt ccttctatgg aagaactggc ggcttaagaa catcaacagc 2460 atcaactttg acaaccccgt ctatcagaag accacagagg atgaggtcca catttgccac 2520 aaccaggacg gctacagcta cccctcgaga cagatggtca gtctggagga tgacgtggcg 2580 tga 2583 <210> 20 <211> 2871 <212> DNA <213> Homo sapiens <400> 20 atggccagca agaggaaatc caccacacca tgcatgatcc cagtgaagac tgtggtgttg 60 caagatgcca gcatggaggc ccagcccgct gagaccttgc ctgaaggacc ccagcaggat 120 ctgcccccag aagcatctgc tgccagcagt gaggcagcac agaaccccag cagtactgat 180 ggctctacac tggccaatgg gcatcggagc actttagatg gctatttata ttcctgtaaa 240 tactgcgatt tcagatccca tgacatgacc caatttgtgg gacatatgaa ctcagagcac 300 acagacttta ataaagaccc aacctttgta tgcagtgggt gcagttttct ggcaaaaacc 360 cctgaggggc tttccttgca caatgccaca tgtcactccg gggaagccag ctttgtgtgg 420 aacgtggcca agccagacaa tcatgtggtt gtggagcaga gcatccctga gagcaccagc 480 actcctgacc tagcgggtga gcccagtgct gaaggggctg atggacaggc agaaatcatc 540 attaccaaaa ctccaatcat gaagataatg aaaggcaaag ctgaagccaa aaaaattcat 600 acactcaagg agaatgtccc tagccagcct gtgggtgagg ccttaccaaa gctgtcgact 660 ggagaaatgg aggtgagaga gggggaccat tccttcatca atggggcagt tccagtcagc 720 caggcatctg ccagctctgc aaaaaacccc catgccgcca acgggcccct gataggaaca 780 gtgccagttt tgccagctgg catagcacag ttcctctccc tccagcagca gcccccagtg 840 catgcccaac accatgtcca ccagccactg cccacggcca aggcccttcc caaagtgatg 900 atccccctga gcagcattcc aacgtacaat gcagccatgg actctaacag cttcctgaag 960 aactccttcc acaagttccc ctaccccacc aaagccgagc tctgctattt gactgtggtg 1020 accaagtatc cagaagaaca gctcaagatc tggttcacag cccaaaggct gaagcagggg 1080 atcagctggt cccctgagga gattgaggat gcccggaaaa agatgttcaa tacagtcatc 1140 cagtctgtgc ctcagcccac aattacggtt ctaaataccc cactcgtcgc cagtgctggc 1200 aatgtccagc atctcatcca ggccgctctt ccaggtcacg ttgtggggca gccagagggt 1260 acaggagggg gacttctggt cactcagcca ttgatggcca atgggttgca agcaacaagt 1320 tcccctctcc ccctcacggt gacatccgtc cccaagcagc caggtgtggc acccattaac 1380 actgtgtgtt caaatacaac gtcagctgtg aaggtggtca atgcggccca gtcgctcctc 1440 acggcctgcc ccagcataac ctcccaagcc ttccttgatg ctagcatcta caaaaataag 1500 aaatctcatg aacagctgtc agctctgaaa gggagcttct gtcggaacca gttcccaggg 1560 cagagcgaag ttgaacatct cacaaaagtg acgggcctca gtaccagaga ggtgcggaaa 1620 tggttcagtg atcgtagata ccactgccgg aacttgaagg gctccagagc gatgatacct 1680 ggagatcaca gttccatcat cattgactct gtgccagagg tgtccttctc cccatcgtcc 1740 aaggtccctg aggtaacctg cattccgaca acagccacac tagcaaccca cccttctgcc 1800 aaacgacaat cttggcacca gactcctgac ttcacaccaa ccaaatacaa ggagagagcc 1860 cctgagcagc tcagagccct ggagagcagt tttgcacaaa accctcttcc tcttgatgag 1920 gaactggacc gcctgagaag tgaaaccaaa atgacccgac gagaaattga tagctggttt 1980 tcagagagac ggaaaaaagt gaatgctgag gagaccaaga aggctgagga gaatgcctct 2040 caggaggaag aggaggctgc tgaggatgag ggtggagaag aggatttggc cagtgagcta 2100 agggtctctg gtgaaaatgg ctctctggaa atgcccagca gccatatctt ggcagagcgc 2160 aaagtcagcc ccattaaaat caacctgaag aacctgaggg tcactgaagc caatggcagg 2220 aacgagattc cagggctggg tgcctgtgac cctgaggatg atgagtcaaa caaactggca 2280 gagcagctcc caggcaaagt gagctgcaaa aagactgccc agcagcggca cttgctgcgg 2340 cagctctttg tccagacaca gtggccaagc aaccaggact atgactccat catggcccag 2400 acgggtctgc cacggccaga ggtggtgcgc tggtttggag atagcaggta cgcactgaag 2460 aacggccaac tcaaatggta cgaagactat aagcgaggca acttcccacc agggctactg 2520 gtcattgccc ctggcaaccg ggagctcctg caggactatt acatgacaca caagatgctg 2580 tatgaagagg acctgcagaa cctctgtgac aagacccaga tgagctccca gcaggtcaag 2640 cagtggtttg ctgagaaaat gggggaggag accagagccg tggcagacac aggcagtgag 2700 gaccagggcc ctggtactgg tgagctcaca gcagttcaca aagggatggg tgacacctat 2760 tcagaggtgt ctgagaacag tgagtcgtgg gagccccgtg tccctgaggc cagctcagag 2820 ccctttgaca catcgagtcc ccaggctgga cgtcagctcg aaacagactg a 2871 <210> 21 <211> 3498 <212> DNA <213> Homo sapiens <400> 21 atgatttgtc aaaaattctg tgtggttttg ttacattggg aatttattta tgtgataact 60 gcgtttaact tgtcatatcc aattactcct tggagattta agttgtcttg catgccacca 120 aattcaacct atgactactt ccttttgcct gctggactct caaagaatac ttcaaattcg 180 aatggacatt atgagacagc tgttgaacct aagtttaatt caagtggtac tcacttttct 240 aacttatcca aaacaacttt ccactgttgc tttcggagtg agcaagatag aaactgctcc 300 ttatgtgcag acaacattga aggaaagaca tttgtttcaa cagtaaattc tttagttttt 360 caacaaatag atgcaaactg gaacatacag tgctggctaa aaggagactt aaaattattc 420 atctgttatg tggagtcatt atttaagaat ctattcagga attataacta taaggtccat 480 cttttatatg ttctgcctga agtgttagaa gattcacctc tggttcccca aaaaggcagt 540 tttcagatgg ttcactgcaa ttgcagtgtt catgaatgtt gtgaatgtct tgtgcctgtg 600 ccaacagcca aactcaacga cactctcctt atgtgtttga aaatcacatc tggtggagta 660 attttccagt cacctctaat gtcagttcag cccataaata tggtgaagcc tgatccacca 720 ttaggtttgc atatggaaat cacagatgat ggtaatttaa agatttcttg gtccagccca 780 ccattggtac catttccact tcaatatcaa gtgaaatatt cagagaattc tacaacagtt 840 atcagagaag ctgacaagat tgtctcagct acatccctgc tagtagacag tatacttcct 900 gggtcttcgt atgaggttca ggtgaggggc aagagactgg atggcccagg aatctggagt 960 gactggagta ctcctcgtgt ctttaccaca caagatgtca tatactttcc acctaaaatt 1020 ctgacaagtg ttgggtctaa tgtttctttt cactgcatct ataagaagga aaacaagatt 1080 gttccctcaa aagagattgt ttggtggatg aatttagctg agaaaattcc tcaaagccag 1140 tatgatgttg tgagtgatca tgttagcaaa gttacttttt tcaatctgaa tgaaaccaaa 1200 cctcgaggaa agtttaccta tgatgcagtg tactgctgca atgaacatga atgccatcat 1260 cgctatgctg aattatatgt gattgatgtc aatatcaata tctcatgtga aactgatggg 1320 tacttaacta aaatgacttg cagatggtca accagtacaa tccagtcact tgcggaaagc 1380 actttgcaat tgaggtatca taggagcagc ctttactgtt ctgatattcc atctattcat 1440 cccatatctg agcccaaaga ttgctatttg cagagtgatg gtttttatga atgcattttc 1500 cagccaatct tcctattatc tggctacaca atgtggatta ggatcaatca ctctctaggt 1560 tcacttgact ctccaccaac atgtgtcctt cctgattctg tggtgaagcc actgcctcca 1620 tccagtgtga aagcagaaat tactataaac attggattat tgaaaatatc ttgggaaaag 1680 ccagtctttc cagagaataa ccttcaattc cagattcgct atggtttaag tggaaaagaa 1740 gtacaatgga agatgtatga ggtttatgat gcaaaatcaa aatctgtcag tctcccagtt 1800 ccagacttgt gtgcagtcta tgctgttcag gtgcgctgta agaggctaga tggactggga 1860 tattggagta attggagcaa tccagcctac acagttgtca tggatataaa agttcctatg 1920 agaggacctg aattttggag aataattaat ggagatacta tgaaaaagga gaaaaatgtc 1980 actttacttt ggaagcccct gatgaaaaat gactcattgt gcagtgttca gagatatgtg 2040 ataaaccatc atacttcctg caatggaaca tggtcagaag atgtgggaaa tcacacgaaa 2100 ttcactttcc tgtggacaga gcaagcacat actgttacgg ttctggccat caattcaatt 2160 ggtgcttctg ttgcaaattt taatttaacc ttttcatggc ctatgagcaa agtaaatatc 2220 gtgcagtcac tcagtgctta tcctttaaac agcagttgtg tgattgtttc ctggatacta 2280 tcacccagtg attacaagct aatgtatttt attattgagt ggaaaaatct taatgaagat 2340 ggtgaaataa aatggcttag aatctcttca tctgttaaga agtattatat ccatgatcat 2400 tttatcccca ttgagaagta ccagttcagt ctttacccaa tatttatgga aggagtggga 2460 aaaccaaaga taattaatag tttcactcaa gatgatattg aaaaacacca gagtgatgca 2520 ggtttatatg taattgtgcc agtaattatt tcctcttcca tcttattgct tggaacatta 2580 ttaatatcac accaaagaat gaaaaagcta ttttgggaag atgttccgaa ccccaagaat 2640 tgttcctggg cacaaggact taattttcag aagccagaaa cgtttgagca tctttttatc 2700 aagcatacag catcagtgac atgtggtcct cttcttttgg agcctgaaac aatttcagaa 2760 gatatcagtg ttgatacatc atggaaaaat aaagatgaga tgatgccaac aactgtggtc 2820 tctctacttt caacaacaga tcttgaaaag ggttctgttt gtattagtga ccagttcaac 2880 agtgttaact tctctgaggc tgagggtact gaggtaacct atgaggacga aagccagaga 2940 caaccctttg ttaaatacgc cacgctgatc agcaactcta aaccaagtga aactggtgaa 3000 gaacaagggc ttataaatag ttcagtcacc aagtgcttct ctagcaaaaa ttctccgttg 3060 aaggattctt tctctaatag ctcatgggag atagaggccc aggcattttt tatattatca 3120 gatcagcatc ccaacataat ttcaccacac ctcacattct cagaaggatt ggatgaactt 3180 ttgaaattgg agggaaattt ccctgaagaa aataatgata aaaagtctat ctattattta 3240 ggggtcacct caatcaaaaa gagagagagt ggtgtgcttt tgactgacaa gtcaagggta 3300 tcgtgcccat tcccagcccc ctgtttattc acggacatca gagttctcca ggacagttgc 3360 tcacactttg tagaaaataa tatcaactta ggaacttcta gtaagaagac ttttgcatct 3420 tacatgcctc aattccaaac ttgttctact cagactcata agatcatgga aaacaagatg 3480 tgtgacctaa ctgtgtaa 3498 <210> 22 <211> 1704 <212> DNA <213> Homo sapiens <400> 22 atgcgccctg acagcccaac aatggcggcg cccgcggagt cgctgaggag gcggaagact 60 gggtactcgg atccggagcc tgagtcgccg cccgcgccgg ggcgtggccc cgcaggctct 120 ccggcccatc tccacacggg caccttctgg ctgacccgga tcgtgctcct gaaggcccta 180 gccttcgtgt acttcgtggc attcctggtg gctttccatc agaacaagca gctcatcggt 240 gacagggggc tgcttccctg cagagtgttc ctgaagaact tccagcagta cttccaggac 300 aggacgagct gggaagtctt cagctacatg cccaccatcc tctggctgat ggactggtca 360 gacatgaact ccaacctgga cttgctggct cttctcggac tgggcatctc gtctttcgta 420 ctgatcacgg gctgcgccaa catgcttctc atggctgccc tgtggggcct ctacatgtcc 480 ctggttaatg tgggccatgt ctggtactct ttcggatggg agtcccagct tctggagacg 540 gggttcctgg ggatcttcct gtgccctctg tggacgctgt caaggctgcc ccagcatacc 600 cccacatccc ggattgtcct gtggggcttc cggtggctga tcttcaggat catgcttgga 660 gcaggcctga tcaagatccg gggggaccgg tgctggcgag acctcacctg catggacttc 720 cactatgaga cccagccgat gcccaatcct gtggcgtact acctgcacca ctcaccctgg 780 tggttccatc gcttcgagac gctcagcaac cacttcatcg agctcctggt gcccttcttc 840 ctcttcctcg gccggcgggc gtgcatcatc cacggggtgc tgcagatcct gttccaggcc 900 gtcctcatcg tcagcgggaa cctcagcttc ctgaactggc tgactatggt gcccagcctg 960 gcctgctttg atgacgccac cctgggattc ttgttcccct ctgggccagg cagcctgaag 1020 gaccgagttc tgcagatgca gagggacatc cgaggggccc ggcccgagcc cagattcggc 1080 tccgtggtgc ggcgtgcagc caacgtctcg ctgggcgtcc tgctggcctg gctcagcgtg 1140 cccgtggtcc tcaacttgct gagctccagg caggtcatga acacccactt caactctctt 1200 cacatcgtca acacttacgg ggccttcgga agcatcacca aggagcgggc ggaggtgatc 1260 ctgcagggca cagccagctc caacgccagc gcccccgatg ccatgtggga ggactacgag 1320 ttcaagtgca agccaggtga ccccagcaga cggccctgcc tcatctcccc gtaccactac 1380 cgcctggact ggctgatgtg gttcgcggcc ttccagacct acgagcacaa cgactggatc 1440 atccacctgg ctggcaagct cctggccagc gacgccgagg ccttgtccct gctggcacac 1500 aaccccttcg cgggcaggcc cccgcccagg tgggtccgag gagagcacta caggtacaag 1560 ttcagccgtc ctgggggcag gcacgccgcc gagggcaagt ggtgggtgcg gaagaggatc 1620 ggagcctact tccctccgct cagcctggag gagctgaggc cctacttcag ggaccgtggg 1680 tggcctctgc ccgggcccct ctag 1704 <210> 23 <211> 6123 <212> DNA <213> Homo sapiens <400> 23 atggaacata aggaagtggt tcttctactt cttttatttc tgaaatcagc agcacctgag 60 caaagccatg tggtccagga ttgctaccat ggtgatggac agagttatcg aggcacgtac 120 tccaccactg tcacaggaag gacctgccaa gcttggtcat ctatgacacc acatcaacat 180 aataggacca cagaaaacta cccaaatgct ggcttgatca tgaactactg caggaatcca 240 gatgctgtgg cagctcctta ttgttatacg agggatcccg gtgtcaggtg ggagtactgc 300 aacctgacgc aatgctcaga cgcagaaggg actgccgtcg cgcctccgac tgttaccccg 360 gttccaagcc tagaggctcc ttccgaacaa gcaccgactg agcaaaggcc tggggtgcag 420 gagtgctacc atggtaatgg acagagttat cgaggcacat actccaccac tgtcacagga 480 agaacctgcc aagcttggtc atctatgaca ccacactcgc atagtcggac cccagaatac 540 tacccaaatg ctggcttgat catgaactac tgcaggaatc cagatgctgt ggcagctcct 600 tattgttata cgagggatcc cggtgtcagg tgggagtact gcaacctgac gcaatgctca 660 gacgcagaag ggactgccgt cgcgcctccg actgttaccc cggttccaag cctagaggct 720 ccttccgaac aagcaccgac tgagcaaagg cctggggtgc aggagtgcta ccatggtaat 780 ggacagagtt atcgaggcac atactccacc actgtcacag gaagaacctg ccaagcttgg 840 tcatctatga caccacactc gcatagtcgg accccagaat actacccaaa tgctggcttg 900 atcatgaact actgcaggaa tccagatgct gtggcagctc cttattgtta tacgagggat 960 cccggtgtca ggtgggagta ctgcaacctg acgcaatgct cagacgcaga agggactgcc 1020 gtcgcgcctc cgactgttac cccggttcca agcctagagg ctccttccga acaagcaccg 1080 actgagcaga ggcctggggt gcaggagtgc taccacggta atggacagag ttatcgaggc 1140 acatactcca ccactgtcac tggaagaacc tgccaagctt ggtcatctat gacaccacac 1200 tcgcatagtc ggaccccaga atactaccca aatgctggct tgatcatgaa ctactgcagg 1260 aatccagatg ctgtggcagc tccttattgt tatacgaggg atcccggtgt caggtgggag 1320 tactgcaacc tgacgcaatg ctcagacgca gaagggactg ccgtcgcgcc tccgactgtt 1380 accccggttc caagcctaga ggctccttcc gaacaagcac cgactgagca aaggcctggg 1440 gtgcaggagt gctaccatgg taatggacag agttatcgag gcacatactc caccactgtc 1500 acaggaagaa cctgccaagc ttggtcatct atgacaccac actcgcatag tcggacccca 1560 gaatactacc caaatgctgg cttgatcatg aactactgca ggaatccaga tgctgtggca 1620 gctccttatt gttatacgag ggatcccggt gtcaggtggg agtactgcaa cctgacgcaa 1680 tgctcagacg cagaagggac tgccgtcgcg cctccgactg ttaccccggt tccaagccta 1740 gaggctcctt ccgaacaagc accgactgag caaaggcctg gggtgcagga gtgctaccat 1800 ggtaatggac agagttatcg aggcacatac tccaccactg tcacaggaag aacctgccaa 1860 gcttggtcat ctatgacacc acactcgcat agtcggaccc cagaatacta cccaaatgct 1920 ggcttgatca tgaactactg caggaatcca gatgctgtgg cagctcctta ttgttatacg 1980 agggatcccg gtgtcaggtg ggagtactgc aacctgacgc aatgctcaga cgcagaaggg 2040 actgccgtcg cgcctccgac tgttaccccg gttccaagcc tagaggctcc ttccgaacaa 2100 gcaccgactg agcaaaggcc tggggtgcag gagtgctacc atggtaatgg acagagttat 2160 cgaggcacat actccaccac tgtcacagga agaacctgcc aagcttggtc atctatgaca 2220 ccacactcgc atagtcggac cccagaatac tacccaaatg ctggcttgat catgaactac 2280 tgcaggaatc cagatgctgt ggcagctcct tattgttata cgagggatcc cggtgtcagg 2340 tgggagtact gcaacctgac gcaatgctca gacgcagaag ggactgccgt cgcgcctccg 2400 actgttaccc cggttccaag cctagaggct ccttccgaac aagcaccgac tgagcagagg 2460 cctggggtgc aggagtgcta ccacggtaat ggacagagtt atcgaggcac atactccacc 2520 actgtcactg gaagaacctg ccaagcttgg tcatctatga caccacactc gcatagtcgg 2580 accccagaat actacccaaa tgctggcttg atcatgaact actgcaggaa tccagatcct 2640 gtggcagccc cttattgtta tacgagggat cccagtgtca ggtgggagta ctgcaacctg 2700 acacaatgct cagacgcaga agggactgcc gtcgcgcctc caactattac cccgattcca 2760 agcctagagg ctccttctga acaagcacca actgagcaaa ggcctggggt gcaggagtgc 2820 taccacggaa atggacagag ttatcaaggc acatacttca ttactgtcac aggaagaacc 2880 tgccaagctt ggtcatctat gacaccacac tcgcatagtc ggaccccagc atactaccca 2940 aatgctggct tgatcaagaa ctactgccga aatccagatc ctgtggcagc cccttggtgt 3000 tatacaacag atcccagtgt caggtgggag tactgcaacc tgacacgatg ctcagatgca 3060 gaatggactg ccttcgtccc tccgaatgtt attctggctc caagcctaga ggcttttttt 3120 gaacaagcac tgactgagga aacccccggg gtacaggact gctactacca ttatggacag 3180 agttaccgag gcacatactc caccactgtc acaggaagaa cttgccaagc ttggtcatct 3240 atgacaccac accagcatag tcggacccca gaaaactacc caaatgctgg cctgaccagg 3300 aactactgca ggaatccaga tgctgagatt cgcccttggt gttacaccat ggatcccagt 3360 gtcaggtggg agtactgcaa cctgacacaa tgcctggtga cagaatcaag tgtccttgca 3420 actctcacgg tggtcccaga tccaagcaca gaggcttctt ctgaagaagc accaacggag 3480 caaagccccg gggtccagga ttgctaccat ggtgatggac agagttatcg aggctcattc 3540 tctaccactg tcacaggaag gacatgtcag tcttggtcct ctatgacacc acactggcat 3600 cagaggacaa cagaatatta tccaaatggt ggcctgacca ggaactactg caggaatcca 3660 gatgctgaga ttagtccttg gtgttatacc atggatccca atgtcagatg ggagtactgc 3720 aacctgacac aatgtccagt gacagaatca agtgtccttg cgacgtccac ggctgtttct 3780 gaacaagcac caacggagca aagccccaca gtccaggact gctaccatgg tgatggacag 3840 agttatcgag gctcattctc caccactgtt acaggaagga catgtcagtc ttggtcctct 3900 atgacaccac actggcatca gagaaccaca gaatactacc caaatggtgg cctgaccagg 3960 aactactgca ggaatccaga tgctgagatt cgcccttggt gttataccat ggatcccagt 4020 gtcagatggg agtactgcaa cctgacgcaa tgtccagtga tggaatcaac tctcctcaca 4080 actcccacgg tggtcccagt tccaagcaca gagcttcctt ctgaagaagc accaactgaa 4140 aacagcactg gggtccagga ctgctaccga ggtgatggac agagttatcg aggcacactc 4200 tccaccacta tcacaggaag aacatgtcag tcttggtcgt ctatgacacc acattggcat 4260 cggaggatcc cattatacta tccaaatgct ggcctgacca ggaactactg caggaatcca 4320 gatgctgaga ttcgcccttg gtgttacacc atggatccca gtgtcaggtg ggagtactgc 4380 aacctgacac gatgtccagt gacagaatcg agtgtcctca caactcccac agtggccccg 4440 gttccaagca cagaggctcc ttctgaacaa gcaccacctg agaaaagccc tgtggtccag 4500 gattgctacc atggtgatgg acggagttat cgaggcatat cctccaccac tgtcacagga 4560 aggacctgtc aatcttggtc atctatgata ccacactggc atcagaggac cccagaaaac 4620 tacccaaatg ctggcctgac cgagaactac tgcaggaatc cagattctgg gaaacaaccc 4680 tggtgttaca caaccgatcc gtgtgtgagg tgggagtact gcaatctgac acaatgctca 4740 gaaacagaat caggtgtcct agagactccc actgttgttc cagttccaag catggaggct 4800 cattctgaag cagcaccaac tgagcaaacc cctgtggtcc ggcagtgcta ccatggtaat 4860 ggccagagtt atcgaggcac attctccacc actgtcacag gaaggacatg tcaatcttgg 4920 tcatccatga caccacaccg gcatcagagg accccagaaa actacccaaa tgatggcctg 4980 acaatgaact actgcaggaa tccagatgcc gatacaggcc cttggtgttt taccatggac 5040 cccagcatca ggtgggagta ctgcaacctg acgcgatgct cagacacaga agggactgtg 5100 gtcgctcctc cgactgtcat ccaggttcca agcctagggc ctccttctga acaagactgt 5160 atgtttggga atgggaaagg ataccggggc aagaaggcaa ccactgttac tgggacgcca 5220 tgccaggaat gggctgccca ggagccccat agacacagca cgttcattcc agggacaaat 5280 aaatgggcag gtctggaaaa aaattactgc cgtaaccctg atggtgacat caatggtccc 5340 tggtgctaca caatgaatcc aagaaaactt tttgactact gtgatatccc tctctgtgca 5400 tcctcttcat ttgattgtgg gaagcctcaa gtggagccga agaaatgtcc tggaagcatt 5460 gtaggggggt gtgtggccca cccacattcc tggccctggc aagtcagtct cagaacaagg 5520 tttggaaagc acttctgtgg aggcacctta atatccccag agtgggtgct gactgctgct 5580 cactgcttga agaagtcctc aaggccttca tcctacaagg tcatcctggg tgcacaccaa 5640 gaagtgaacc tcgaatctca tgttcaggaa atagaagtgt ctaggctgtt cttggagccc 5700 acacaagcag atattgcctt gctaaagcta agcaggcctg ccgtcatcac tgacaaagta 5760 atgccagctt gtctgccatc cccagactac atggtcaccg ccaggactga atgttacatc 5820 actggctggg gagaaaccca aggtaccttt gggactggcc ttctcaagga agcccagctc 5880 cttgttattg agaatgaagt gtgcaatcac tataagtata tttgtgctga gcatttggcc 5940 agaggcactg acagttgcca gggtgacagt ggagggcctc tggtttgctt cgagaaggac 6000 aaatacattt tacaaggagt cacttcttgg ggtcttggct gtgcacgccc caataagcct 6060 ggtgtctatg ctcgtgtttc aaggtttgtt acttggattg agggaatgat gagaaataat 6120 taa 6123 <210> 24 <211> 1971 <212> DNA <213> Homo sapiens <400> 24 atggtgaacg aagccagagg aaacagcagc ctcaacccct gcttggaggg cagtgccagc 60 agtggcagtg agagctccaa agatagttcg agatgttcca ccccgggcct ggaccccgag 120 cggcatgaga gactccggga gaagatgagg cggcgattgg aatctggtga caagtggttc 180 tccctggaat tcttccctcc tcgaactgct gagggagctg tcaatctcat ctcaaggttt 240 gaccggatgg cagcaggtgg ccccctctac atagacgtga cctggcaccc agcaggtgac 300 cctggctcag acaaggagac ctcctccatg atgatcgcca gcaccgccgt gaactactgt 360 ggcctggaga ccatcctgca catgacctgc tgccgtcagc gcctggagga gatcacgggc 420 catctgcaca aagctaagca gctgggcctg aagaacatca tggcgctgcg gggagaccca 480 ataggtgacc agtgggaaga ggaggaggga ggcttcaact acgcagtgga cctggtgaag 540 cacatccgaa gtgagtttgg tgactacttt gacatctgtg tggcaggtta ccccaaaggc 600 caccccgaag cagggagctt tgaggctgac ctgaagcact tgaaggagaa ggtgtctgcg 660 ggagccgatt tcatcatcac gcagcttttc tttgaggctg acacattctt ccgctttgtg 720 aaggcatgca ccgacatggg catcacttgc cccatcgtcc ccgggatctt tcccatccag 780 ggctaccact cccttcggca gcttgtgaag ctgtccaagc tggaggtgcc acaggagatc 840 aaggacgtga ttgagccaat caaagacaac gatgctgcca tccgcaacta tggcatcgag 900 ctggccgtga gcctgtgcca ggagcttctg gccagtggct tggtgccagg cctccacttc 960 tacaccctca accgcgagat ggctaccaca gaggtgctga agcgcctggg gatgtggact 1020 gaggacccca ggcgtcccct accctgggct ctcagcgccc accccaagcg ccgagaggaa 1080 gatgtacgtc ccatcttctg ggcctccaga ccaaagagtt acatctaccg tacccaggag 1140 tgggacgagt tccctaacgg ccgctggggc aattcctctt cccctgcctt tggggagctg 1200 aaggactact acctcttcta cctgaagagc aagtccccca aggaggagct gctgaagatg 1260 tggggggagg agctgaccag tgaagaaagt gtctttgaag tcttcgttct ttacctctcg 1320 ggagaaccaa accggaatgg tcacaaagtg acttgcctgc cctggaacga tgagcccctg 1380 gcggctgaga ccagcctgct gaaggaggag ctgctgcggg tgaaccgcca gggcatcctc 1440 accatcaact cacagcccaa catcaacggg aagccgtcct ccgaccccat cgtgggctgg 1500 ggccccagcg ggggctatgt cttccagaag gcctacttag agtttttcac ttcccgcgag 1560 acagcggaag cacttctgca agtgctgaag aagtacgagc tccgggttaa ttaccacctt 1620 gtcaatgtga agggtgaaaa catcaccaat gcccctgaac tgcagccgaa tgctgtcact 1680 tggggcatct tccctgggcg agagatcatc cagcccaccg tagtggatcc cgtcagcttc 1740 atgttctgga aggacgaggc ctttgccctg tggattgagc ggtggggaaa gctgtatgag 1800 gaggagtccc cgtcccgcac catcatccag tacatccacg acaactactt cctggtcaac 1860 ctggtggaca atgacttccc actggacaac tgcctctggc aggtggtgga agacacattg 1920 gagcttctca acaggcccac ccagaatgcg agagaaacgg aggctccatg a 1971 <210> 25 <211> 2766 <212> DNA <213> Homo sapiens <400> 25 atggaagaaa ggggaggggt ttatgcgggg cggggtctgg agttagtgtt ttgggagtgg 60 gaggtagtta cagtgatgtc tgttttttcc cgttcaagaa ttaagtgtgt acctgcagac 120 gtgtattcat tcatatattc ttgtcacaca actggtctct cattaaataa tgaccggctg 180 tacaagctca cgtactccac tgaagttctt cttgatcggg gcaaaggaaa actgcaagac 240 agcgtgggct accgcatttc ctccaacgtg gatgtggcct tactatggag gaatcctgat 300 ggtgatgatg accagttgat ccaaataacg atgaaggatg taaatgttga aaatgtgaat 360 cagcagagag gagagaagag catcttcaaa ggaaaaagcc catctaaaat aatgggaaag 420 gaaaacttgg aagctctgca aagacctacg ctccttcatc taatccatgg aaaggtcaaa 480 gagttctact catatcaaaa tgaggcagtg gccatagaaa atatcaagag aggtctggct 540 agcctatttc agacacagtt aagctctgga accaccaatg aggtagatat ctctggaaat 600 tgtaaagtga cctaccaggc tcatcaagac aaagtgatca aaattaaggc cttggattca 660 tgcaaaatag cgaggtctgg atttacgacc ccaaatcagg tcttgggtgt cagttcaaaa 720 gctacatctg tcaccaccta taagatagaa gacagctttg ttatagctgt gcttgctgaa 780 gaaacacaca attttggact gaatttccta caaaccatta aggggaaaat agtatcgaag 840 cagaaattag agctgaagac aaccgaagca ggcccaagat tgatgtctgg aaagcaggct 900 gcagccataa tcaaagcagt tgattcaaag tacacggcca ttcccattgt ggggcaggtc 960 ttccagagcc actgtaaagg atgtccttct ctctcggagc tctggcggtc caccaggaaa 1020 tacctgcagc ctgacaacct ttccaaggct gaggctgtca gaaacttcct ggccttcatt 1080 cagcacctca ggactgcgaa gaaagaagag atccttcaaa tactaaagat ggaaaataag 1140 gaagtattac ctcagctggt ggatgctgtc acctctgctc agacctcaga ctcattagaa 1200 gccattttgg actttttgga tttcaaaagt gacagcagca ttatcctcca ggagaggttt 1260 ctctatgcct gtggatttgc ttctcatccc aatgaagaac tcctgagagc cctcattagt 1320 aagttcaaag gttctattgg tagcagtgac atcagagaaa ctgttatgat catcactggg 1380 acacttgtca gaaagttgtg tcagaatgaa ggctgcaaac tcaaagcagt agtggaagct 1440 aagaagttaa tcctgggagg acttgaaaaa gcagagaaaa aagaggacac caggatgtat 1500 ctgctggctt tgaagaatgc cctgcttcca gaaggcatcc caagtcttct gaagtatgca 1560 gaagcaggag aagggcccat cagccacctg gctaccactg ctctccagag atatgatctc 1620 cctttcataa ctgatgaggt gaagaagacc ttaaacagaa tataccacca aaaccgtaaa 1680 gttcatgaaa agactgtgcg cactgctgca gctgctatca ttttaaataa caatccatcc 1740 tacatggacg tcaagaacat cctgctgtct attggggagc ttccccaaga aatgaataaa 1800 tacatgctcg ccattgttca agacatccta cgttttgaaa tgcctgcaag caaaattgtc 1860 cgtcgagttc tgaaggaaat ggtcgctcac aattatgacc gtttctccag gagtggatct 1920 tcttctgcct acactggcta catagaacgt agtccccgtt cggcatctac ttacagccta 1980 gacattctct actcgggttc tggcattcta aggagaagta acctgaacat ctttcagtac 2040 attgggaagg ctggtcttca cggtagccag gtggttattg aagcccaagg actggaagcc 2100 ttaatcgcag ccacccctga cgagggggag gagaaccttg actcctatgc tggtatgtca 2160 gccatcctct ttgatgttca gctcagacct gtcacctttt tcaacggata cagtgatttg 2220 atgtccaaaa tgctgtcagc atctggcgac cctatcagtg tggtgaaagg acttattctg 2280 ctaatagatc attctcagga acttcagtta caatctggac taaaagccaa tatagaggtc 2340 cagggtggtc tagctattga tatttcaggt gcaatggagt ttagcttgtg gtatcgtgag 2400 tctaaaaccc gagtgaaaaa tagggtgact gtggtaataa ccactgacat cacagtggac 2460 tcctcttttg tgaaagctgg cctggaaacc agtacagaaa cagaagcagg cttggagttt 2520 atctccacag tgcagttttc tcagtaccca ttcttagttt gcatgcagat ggacaaggat 2580 gaagctccat tcaggcaatt tgagaaaaag tacgaaaggc tgtccacagg cagaggttat 2640 gtctctcaga aaagaaaaga aagcgtatta gcaggatgtg aattcccgct ccatcaagag 2700 aactcagaga tgtgcaaagt ggtgtttgcc cctcagccgg atagtacttc cagcggatgg 2760 ttttga 2766 <210> 26 <211> 2079 <212> DNA <213> Homo sapiens <400> 26 atgggcaccg tcagctccag gcggtcctgg tggccgctgc cactgctgct gctgctgctg 60 ctgctcctgg gtcccgcggg cgcccgtgcg caggaggacg aggacggcga ctacgaggag 120 ctggtgctag ccttgcgttc cgaggaggac ggcctggccg aagcacccga gcacggaacc 180 acagccacct tccaccgctg cgccaaggat ccgtggaggt tgcctggcac ctacgtggtg 240 gtgctgaagg aggagaccca cctctcgcag tcagagcgca ctgcccgccg cctgcaggcc 300 caggctgccc gccggggata cctcaccaag atcctgcatg tcttccatgg ccttcttcct 360 ggcttcctgg tgaagatgag tggcgacctg ctggagctgg ccttgaagtt gccccatgtc 420 gactacatcg aggaggactc ctctgtcttt gcccagagca tcccgtggaa cctggagcgg 480 attacccctc cacggtaccg ggcggatgaa taccagcccc ccgacggagg cagcctggtg 540 gaggtgtatc tcctagacac cagcatacag agtgaccacc gggaaatcga gggcagggtc 600 atggtcaccg acttcgagaa tgtgcccgag gaggacggga cccgcttcca cagacaggcc 660 agcaagtgtg acagtcatgg cacccacctg gcaggggtgg tcagcggccg ggatgccggc 720 gtggccaagg gtgccagcat gcgcagcctg cgcgtgctca actgccaagg gaagggcacg 780 gttagcggca ccctcatagg cctggagttt attcggaaaa gccagctggt ccagcctgtg 840 gggccactgg tggtgctgct gcccctggcg ggtgggtaca gccgcgtcct caacgccgcc 900 tgccagcgcc tggcgagggc tggggtcgtg ctggtcaccg ctgccggcaa cttccgggac 960 gatgcctgcc tctactcccc agcctcagct cccgaggtca tcacagttgg ggccaccaat 1020 gcccaagacc agccggtgac cctggggact ttggggacca actttggccg ctgtgtggac 1080 ctctttgccc caggggagga catcattggt gcctccagcg actgcagcac ctgctttgtg 1140 tcacagagtg ggacatcaca ggctgctgcc cacgtggctg gcattgcagc catgatgctg 1200 tctgccgagc cggagctcac cctggccgag ttgaggcaga gactgatcca cttctctgcc 1260 aaagatgtca tcaatgaggc ctggttccct gaggaccagc gggtactgac ccccaacctg 1320 gtggccgccc tgccccccag cacccatggg gcaggttggc agctgttttg caggactgta 1380 tggtcagcac actcggggcc tacacggatg gccacagccg tcgcccgctg cgccccagat 1440 gaggagctgc tgagctgctc cagtttctcc aggagtggga agcggcgggg cgagcgcatg 1500 gaggcccaag ggggcaagct ggtctgccgg gcccacaacg cttttggggg tgagggtgtc 1560 tacgccattg ccaggtgctg cctgctaccc caggccaact gcagcgtcca cacagctcca 1620 ccagctgagg ccagcatggg gacccgtgtc cactgccacc aacagggcca cgtcctcaca 1680 ggctgcagct cccactggga ggtggaggac cttggcaccc acaagccgcc tgtgctgagg 1740 ccacgaggtc agcccaacca gtgcgtgggc cacagggagg ccagcatcca cgcttcctgc 1800 tgccatgccc caggtctgga atgcaaagtc aaggagcatg gaatcccggc ccctcaggag 1860 caggtgaccg tggcctgcga ggagggctgg accctgactg gctgcagtgc cctccctggg 1920 acctcccacg tcctgggggc ctacgccgta gacaacacgt gtgtagtcag gagccgggac 1980 gtcagcacta caggcagcac cagcgaaggg gccgtgacag ccgttgccat ctgctgccgg 2040 agccggcacc tggcgcaggc ctcccaggag ctccagtga 2079 <210> 27 <211> 1530 <212> DNA <213> Homo sapiens <400> 27 atgggctgct ccgccaaagc gcgctgggct gccggggcgc tgggcgtcgc ggggctactg 60 tgcgctgtgc tgggcgctgt catgatcgtg atggtgccgt cgctcatcaa gcagcaggtc 120 cttaagaacg tgcgcatcga ccccagtagc ctgtccttca acatgtggaa ggagatccct 180 atccccttct atctctccgt ctacttcttt gacgtcatga accccagcga gatcctgaag 240 ggcgagaagc cgcaggtgcg ggagcgcggg ccctacgtgt acagggagtt caggcacaaa 300 agcaacatca ccttcaacaa caacgacacc gtgtccttcc tcgagtaccg caccttccag 360 ttccagccct ccaagtccca cggctcggag agcgactaca tcgtcatgcc caacatcctg 420 gtcttgggtg cggcggtgat gatggagaat aagcccatga ccctgaagct catcatgacc 480 ttggcattca ccaccctcgg cgaacgtgcc ttcatgaacc gcactgtggg tgagatcatg 540 tggggctaca aggaccccct tgtgaatctc atcaacaagt actttccagg catgttcccc 600 ttcaaggaca agttcggatt atttgctgag ctcaacaact ccgactctgg gctcttcacg 660 gtgttcacgg gggtccagaa catcagcagg atccacctcg tggacaagtg gaacgggctg 720 agcaaggttg acttctggca ttccgatcag tgcaacatga tcaatggaac ttctgggcaa 780 atgtggccgc ccttcatgac tcctgagtcc tcgctggagt tctacagccc ggaggcctgc 840 cgatccatga agctaatgta caaggagtca ggggtgtttg aaggcatccc cacctatcgc 900 ttcgtggctc ccaaaaccct gtttgccaac gggtccatct acccacccaa cgaaggcttc 960 tgcccgtgcc tggagtctgg aattcagaac gtcagcacct gcaggttcag tgcccccttg 1020 tttctctccc atcctcactt cctcaacgct gacccggttc tggcagaagc ggtgactggc 1080 ctgcacccta accaggaggc acactccttg ttcctggaca tccacccggt cacgggaatc 1140 cccatgaact gctctgtgaa actgcagctg agcctctaca tgaaatctgt cgcaggcatt 1200 ggacaaactg ggaagattga gcctgtggtc ctgccgctgc tctggtttgc agagagcggg 1260 gccatggagg gggagactct tcacacattc tacactcagc tggtgttgat gcccaaggtg 1320 atgcactatg cccagtacgt cctcctggcg ctgggctgcg tcctgctgct ggtccctgtc 1380 atctgccaaa tccggagcca agagaaatgc tatttatttt ggagtagtag taaaaagggc 1440 tcaaaggata aggaggccat tcaggcctat tctgaatccc tgatgacatc agctcccaag 1500 ggctctgtgc tgcaggaagc aaaactgtag 1530 <210> 28 <211> 2244 <212> DNA <213> Homo sapiens <400> 28 atggcggacg aggcggccct cgcccttcag cccggcggct ccccctcggc ggcgggggcc 60 gacagggagg ccgcgtcgtc ccccgccggg gagccgctcc gcaagaggcc gcggagagat 120 ggtcccggcc tcgagcggag cccgggcgag cccggtgggg cggccccaga gcgtgaggtg 180 ccggcggcgg ccaggggctg cccgggtgcg gcggcggcgg cgctgtggcg ggaggcggag 240 gcagaggcgg cggcggcagg cggggagcaa gaggcccagg cgactgcggc ggctggggaa 300 ggagacaatg ggccgggcct gcagggccca tctcgggagc caccgctggc cgacaacttg 360 tacgacgaag acgacgacga cgagggcgag gaggaggaag aggcggcggc ggcggcgatt 420 gggtaccgag ataaccttct gttcggtgat gaaattatca ctaatggttt tcattcctgt 480 gaaagtgatg aggaggatag agcctcacat gcaagctcta gtgactggac tccaaggcca 540 cggataggtc catatacttt tgttcagcaa catcttatga ttggcacaga tcctcgaaca 600 attcttaaag atttattgcc ggaaacaata cctccacctg agttggatga tatgacactg 660 tggcagattg ttattaatat cctttcagaa ccaccaaaaa ggaaaaaaag aaaagatatt 720 aatacaattg aagatgctgt gaaattactg caagagtgca aaaaaattat agttctaact 780 ggagctgggg tgtctgtttc atgtggaata cctgacttca ggtcaaggga tggtatttat 840 gctcgccttg ctgtagactt cccagatctt ccagatcctc aagcgatgtt tgatattgaa 900 tatttcagaa aagatccaag accattcttc aagtttgcaa aggaaatata tcctggacaa 960 ttccagccat ctctctgtca caaattcata gccttgtcag ataaggaagg aaaactactt 1020 cgcaactata cccagaacat agacacgctg gaacaggttg cgggaatcca aaggataatt 1080 cagtgtcatg gttcctttgc aacagcatct tgcctgattt gtaaatacaa agttgactgt 1140 gaagctgtac gaggagatat ttttaatcag gtagttcctc gatgtcctag gtgcccagct 1200 gatgaaccgc ttgctatcat gaaaccagag attgtgtttt ttggtgaaaa tttaccagaa 1260 cagtttcata gagccatgaa gtatgacaaa gatgaagttg acctcctcat tgttattggg 1320 tcttccctca aagtaagacc agtagcacta attccaagtt ccatacccca tgaagtgcct 1380 cagatattaa ttaatagaga acctttgcct catctgcatt ttgatgtaga gcttcttgga 1440 gactgtgatg tcataattaa tgaattgtgt cataggttag gtggtgaata tgccaaactt 1500 tgctgtaacc ctgtaaagct ttcagaaatt actgaaaaac ctccacgaac acaaaaagaa 1560 ttggcttatt tgtcagagtt gccacccaca cctcttcatg tttcagaaga ctcaagttca 1620 ccagaaagaa cttcaccacc agattcttca gtgattgtca cacttttaga ccaagcagct 1680 aagagtaatg atgatttaga tgtgtctgaa tcaaaaggtt gtatggaaga aaaaccacag 1740 gaagtacaaa cttctaggaa tgttgaaagt attgctgaac agatggaaaa tccggatttg 1800 aagaatgttg gttctagtac tggggagaaa aatgaaagaa cttcagtggc tggaacagtg 1860 agaaaatgct ggcctaatag agtggcaaag gagcagatta gtaggcggct tgatggtaat 1920 cagtatctgt ttttgccacc aaatcgttac attttccatg gcgctgaggt atattcagac 1980 tctgaagatg acgtcttatc ctctagttct tgtggcagta acagtgatag tgggacatgc 2040 cagagtccaa gtttagaaga acccatggag gatgaaagtg aaattgaaga attctacaat 2100 ggcttagaag atgagcctga tgttccagag agagctggag gagctggatt tgggactgat 2160 ggagatgatc aagaggcaat taatgaagct atatctgtga aacaggaagt aacagacatg 2220 aactatccat caaacaaatc atag 2244 <210> 29 <211> 1575 <212> DNA <213> Homo sapiens <400> 29 atgacagaag ataaggtcac tgggaccctg gttttcactg tcatcactgc tgtgctgggt 60 tccttccagt ttggatatga cattggtgtg atcaatgcac ctcaacaggt aataatatct 120 cactatagac atgttttggg tgttccactg gatgaccgaa aagctatcaa caactatgtt 180 atcaacagta cagatgaact gcccacaatc tcatactcaa tgaacccaaa accaacccct 240 tgggctgagg aagagactgt ggcagctgct caactaatca ccatgctctg gtccctgtct 300 gtatccagct ttgcagttgg tggaatgact gcatcattct ttggtgggtg gcttggggac 360 acacttggaa gaatcaaagc catgttagta gcaaacattc tgtcattagt tggagctctc 420 ttgatggggt tttcaaaatt gggaccatct catatactta taattgctgg aagaagcata 480 tcaggactat attgtgggct aatttcaggc ctggttccta tgtatatcgg tgaaattgct 540 ccaaccgctc tcaggggagc acttggcact tttcatcagc tggccatcgt cacgggcatt 600 cttattagtc agattattgg tcttgaattt atcttgggca attatgatct gtggcacatc 660 ctgcttggcc tgtctggtgt gcgagccatc cttcagtctc tgctactctt tttctgtcca 720 gaaagcccca gataccttta catcaagtta gatgaggaag tcaaagcaaa acaaagcttg 780 aaaagactca gaggatatga tgatgtcacc aaagatatta atgaaatgag aaaagaaaga 840 gaagaagcat cgagtgagca gaaagtctct ataattcagc tcttcaccaa ttccagctac 900 cgacagccta ttctagtggc actgatgctg catgtggctc agcaattttc cggaatcaat 960 ggcatttttt actactcaac cagcattttt cagacggctg gtatcagcaa acctgtttat 1020 gcaaccattg gagttggcgc tgtaaacatg gttttcactg ctgtctctgt attccttgtg 1080 gagaaggcag ggcgacgttc tctctttcta attggaatga gtgggatgtt tgtttgtgcc 1140 atcttcatgt cagtgggact tgtgctgctg aataagttct cttggatgag ttatgtgagc 1200 atgatagcca tcttcctctt tgtcagcttc tttgaaattg ggccaggccc gatcccctgg 1260 ttcatggtgg ctgagttttt cagtcaagga ccacgtcctg ctgctttagc aatagctgca 1320 ttcagcaatt ggacctgcaa tttcattgta gctctgtgtt tccagtacat tgcggacttc 1380 tgtggacctt atgtgttttt cctctttgct ggagtgctcc tggcctttac cctgttcaca 1440 ttttttaaag ttccagaaac caaaggaaag tcttttgagg aaattgctgc agaattccaa 1500 aagaagagtg gctcagccca caggccaaaa gctgctgtag aaatgaaatt cctaggagct 1560 acagagactg tgtaa 1575 <210> 30 <211> 3399 <212> DNA <213> Homo sapiens <400> 30 atgagggcct ggatcttctt tctcctttgc ctggccggga gggccttggc agcccctcag 60 caagaagccc tgcctgatga gacagaggtg gtggaagaaa ctgtggcaga ggtgactgag 120 gtatctgtgg gagctaatcc tgtccaggtg gaagtaggag aatttgatga tggtgcagag 180 gaaaccgaag aggaggtggt ggcggaaaat ccctgccaga accaccactg caaacacggc 240 aaggtgtgcg agctggatga gaacaacacc cccatgtgcg tgtgccagga ccccaccagc 300 tgcccagccc ccattggcga gtttgagaag gtgtgcagca atgacaacaa gaccttcgac 360 tcttcctgcc acttctttgc cacaaagtgc accctggagg gcaccaagaa gggccacaag 420 ctccacctgg actacatcgg gccttgcaaa tacatccccc cttgcctgga ctctgagctg 480 accgaattcc ccctgcgcat gcgggactgg ctcaagaacg tcctggtcac cctgtatgag 540 agggatgagg acaacaacct tctgactgag aagcagaagc tgcgggtgaa gaagatccat 600 gagaatgaga agcgcctgga ggcaggagac caccccgtgg agctgctggc ccgggacttc 660 gagaagaact ataacatgta catcttccct gtacactggc agttcggcca gctggaccag 720 caccccattg acgggtacct ctcccacacc gagctggctc cactgcgtgc tcccctcatc 780 cccatggagc attgcaccac ccgctttttc gagacctgtg acctggacaa tgacaagtac 840 atcgccctgg atgagtgggc cggctgcttc ggcatcaagc agagatatcg acaaggatct 900 tgtgatctaa atccactcct tccacagtac cggattctct ctttaaccct ccccttcgtg 960 tttcccccaa tgtttaaaat gtttggatgg tttgttgttc tgcctggaga caaggtgcta 1020 acatagattt aagtgaatac attaacggtg ctaaaaatga aaattctaac ccaagacatg 1080 acattcttag ctgtaactta actattaagg ccttttccac acgcattaat agtcccattt 1140 ttctcttgcc atttgtagct ttgcccattg tcttattggc acatgggtgg acacggatct 1200 gctgggctct gccttaaaca cacattgcag cttcaacttt tctctttagt gttctgtttg 1260 aaactaatac ttaccgagtc agactttgtg ttcatttcat ttcagggtct tggctgcctg 1320 tgggcttccc caggtggcct ggaggtgggc aaagggaagt aacagacaca cgatgttgtc 1380 aaggatggtt ttgggactag aggctcagtg gtgggagaga tccctgcaga acccaccaac 1440 cagaacgtgg tttgcctgag gctgtaactg agagaaagat tctggggctg tgttatgaaa 1500 atatagacat tctcacataa gcccagttca tcaccatttc ctcctttacc tttcagtgca 1560 gtttcttttc acattaggct gttggttcaa acttttggga gcacggactg tcagttctct 1620 gggaagtggt cagcgcatcc tgcagggctt ctcctcctct gtcttttgga gaaccagggc 1680 tcttctcagg ggctctaggg actgccaggc tgtttcagcc aggaaggcca aaatcaagag 1740 tgagatgtag aaagttgtaa aatagaaaaa gtggagttgg tgaatcggtt gttctttcct 1800 cacatttgga tgattgtcat aaggttttta gcatgttcct ccttttcttc accctcccct 1860 tttttcttct attaatcaag agaaacttca aagttaatgg gatggtcgga tctcacaggc 1920 tgagaactcg ttcacctcca agcatttcat gaaaaagctg cttcttatta atcatacaaa 1980 ctctcaccat gatgtgaaga gtttcacaaa tccttcaaaa taaaaagtaa tgacttagaa 2040 actgccttcc tgggtgattt gcatgtgtct tagtcttagt caccttatta tcctgacaca 2100 aaaacacatg agcatacatg tctacacatg actacacaaa tgcaaacctt tgcaaacaca 2160 ttatgctttt gcacacacac acctgtacac acacaccggc atgtttatac acagggagtg 2220 tatggttcct gtaagcacta agttagctgt tttcatttaa tgacctgtgg tttaaccctt 2280 ttgatcacta ccaccattat cagcaccaga ctgagcagct atatcctttt attaatcatg 2340 gtcattcatt cattcattca ttcacaaaat atttatgatg tatttactct gcaccaggtc 2400 ccatgccaag cactggggac acagttatgg caaagtagac aaagcatttg ttcatttgga 2460 gcttagagtc caggaggaat acattagata atgacacaat caaatataaa ttgcaagatg 2520 tcacaggtgt gatgaaggga gagtaggaga gaccatgagt atgtgtaaca ggaggacaca 2580 gcattattct agtgctgtac tgttccgtac ggcagccact acccacatgt aactttttaa 2640 gatttaaatt taaattagtt aacattcaaa acgcagctcc ccaatcacac tagcaacatt 2700 tcaagtgctt gagagccatg catgattagt ggttacccta ttgaataggt cagaagtaga 2760 atcttttcat catcacagaa agttctattg gacagtgctc ttctagatca tcataagact 2820 acagagcact tttcaaagct catgcatgtt catcatgtta gtgtcgtatt ttgagctggg 2880 gttttgagac tccccttaga gatagagaaa cagacccaag aaatgtgctc aattgcaatg 2940 ggccacatac ctagatctcc agatgtcatt tcccctctct tattttaagt tatgttaaga 3000 ttactaaaac aataaaagct cctaaaaaat caaactgtat tctggtgttc tcttctacac 3060 agtgggaggg cgagcagtag gagagattgg cccatttggt gctggccatt tgaggaatgc 3120 aagcccagca ctagtctcat aatctctagg aatctgtaga gagaggaatt gaagtaaatt 3180 tcagcattgg ctcattcagt cattcggcga cattcatcag gtacctgcaa tgtgttaggg 3240 gatcttatga gtaggcagcg tgcgtgatcc ttgctcccct ggagctttct aacattctag 3300 caggcagacc acacataaat ttgcaatact gtttctgata aaaacgtgct gtaaaggaaa 3360 taaagcagag aactatcatg gaaaaaaaaa aaaaaaaaa 3399

Claims (8)

Single base polymorphism in which the base located at position 796 in the ABCA1 gene consisting of SEQ ID NO: 1 was changed from G to A (c.796G>A), and single base polymorphism in which the base located at 1631 was changed from G to A (c.1631G) >A), single base polymorphism where the base at 6608 is changed from T to A (c.6608T>A), single base polymorphism at which the base at 4995 is changed from G to T (c.4995G>T), and Single base polymorphism in which the base at position 2940 is changed from G to T (c.2940G>T), single base polymorphism in which the base at position 452 in the CETP gene consisting of SEQ ID NO: 9 is changed from G to T (c.452G) >T), a single nucleotide polymorphism in which the base located at position 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), and a single nucleotide polymorphism in which the base at position 814 is changed from A to T (c.814A>T), single base polymorphism where the base at position 571 is changed from C to A (c.571C>A), and single base polymorphism at the base at position 1045 is changed from C to A (c.1045C) >A), single base polymorphism where the base at position 769 is changed from C to T (c.769C>T), single base polymorphism at which the base at position 197 is changed from T to A (c.197T>A), and The single base polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the single base polymorphism in which the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T (c. 745G>T) and a panel of genes for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, including a single nucleotide polymorphism (c.4G>A) in which the base at position 4 is changed from G to A.
The gene panel of claim 1, wherein the gene panel is a next generation sequencing (NGS) gene panel.
A kit for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, comprising a probe polynucleotide complementary to a gene of the gene panel of claim 1.
Single base polymorphism in which the base located at position 796 in the ABCA1 gene consisting of SEQ ID NO: 1 is changed from G to A (c.796G>A), and single base polymorphism in which the base located at 1631 is changed from G to A (c.1631G) >A), single base polymorphism where the base at 6608 is changed from T to A (c.6608T>A), single base polymorphism at which the base at 4995 is changed from G to T (c.4995G>T), and Single base polymorphism in which the base at position 2940 is changed from G to T (c.2940G>T), single base polymorphism in which the base at position 452 in the CETP gene consisting of SEQ ID NO: 9 is changed from G to T (c.452G) >T), a single nucleotide polymorphism in which the base located at position 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), and a single nucleotide polymorphism in which the base at position 814 is changed from A to T (c.814A>T), single base polymorphism where the base at position 571 is changed from C to A (c.571C>A), and single base polymorphism at the base at position 1045 is changed from C to A (c.1045C) >A), single base polymorphism where the base at position 769 is changed from C to T (c.769C>T), single base polymorphism at which the base at position 197 is changed from T to A (c.197T>A), and The single base polymorphism in which the base at position 196 is changed from G to T (c.196G>T), and the single base polymorphism in which the base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T (c. Hypocholesterolemia as a risk factor for metabolic syndrome, including reagents capable of detecting at the nucleic acid level a single base polymorphism (c.4G>A) where the base located at 745G>T) and the fourth position is changed from G to A Composition for early diagnosis or prediction of.
1) separating nucleic acids from biological samples separated from the subject; And
2) The single base polymorphism in which the base located at position 796 in the ABCA1 gene consisting of SEQ ID NO: 1 was changed from G to A (c.796G>A), and the base located at 1631 was changed from G to A Polymorphism (c.1631G>A), single base polymorphism where the base at 6608 is changed from T to A (c.6608T>A), single base polymorphism at which the base at 4995 is changed from G to T (c. 4995G>T) and the single base polymorphism in which the base at 2940 is changed from G to T (c.2940G>T), and the single base from the GTP to the 452th base in the CETP gene consisting of SEQ ID NO:9 Polymorphism (c.452G>T), single base polymorphism in which the base located at position 1765 in the LDLR gene consisting of SEQ ID NO: 19 is changed from G to A (c.1765G>A), and the base located at position 814 is from A to T Single base polymorphism changed to (c.814A>T), single base polymorphism at base 571 changed from C to A (c.571C>A), single base at base 1045 changed from C to A Polymorphism (c.1045C>A), single base polymorphism where base 769 is changed from C to T (c.769C>T), single base polymorphism at base 197 is changed from T to A (c. 197T>A) and the single base polymorphism (c.196G>T) in which the base at position 196 is changed from G to T (c.196G>T), and the single base base at position 745 in the SCARB1 gene consisting of SEQ ID NO: 27 is changed from G to T Baseline polymorphism (c.745G>T) and identifying the single base polymorphism (c.4G>A) sequence in which the base located at 4 is changed from G to A, has low HDL as a risk factor for metabolic syndrome. A method that provides information needed for early diagnosis or prediction of cholesterol.
From the biological sample isolated from the subject, the 266th amino acid glycine (G) is changed to arginine (R) from the N-terminus (c.796G>A), and the 544th amino acid glycine (G) is aspartic acid ( D) change (c.1631G>A), 2203th amino acid isoleucine (I) to lysine (K) (c.6608T>A), 1665th amino acid methionine (M) isoleucine ( I) changed to (c.4995G>T) and 980th amino acid glutamine (Q) changed to histidine (H) (c.2940G>T) ABCA1 protein mutation, 151th amino acid glycine (G) Changes to valine (V) (c.452G>T) CETP protein mutation, 589th amino acid aspartic acid (D) changed to asparagine (N) from the N-terminus (c.1765G>A ), asparagine (N), amino acid at 272th, changed to tyrosine (Y) (c.814A>T), glutamine (Q) amino acid at 191th, changed to lysine (K) (c.571C>A), 349th amino acid glutamine (Q) changed to lysine (K) (c.1045C>A), 257th amino acid arginine (R) changed to tryptophan (W) (c.769C>T), 66th LDLR protein with amino acid valine (V) changed to aspartic acid (D) (c.197T>A) and at 66th amino acid valine (V) changed to phenylalanine (F) (c.196G>T) Variation, and the 249th amino acid aspartic acid (D) changed to tyrosine (Y) from the N-terminus (c.745G>T) and the 2nd amino acid glycine (G) changed to serine (S) ( c.4G>A) A method of providing information necessary for early diagnosis or prediction of hypoHDL cholesterol as a risk factor for metabolic syndrome, comprising the step of identifying a variant of the SCARB1 protein.
The method of claim 6, wherein the protein mutation is characterized by calculating and confirming protein mutation information based on bioinformatics analysis from biological samples separated from the subject, an early diagnosis diagnosis of hypoHDL cholesterol as a risk factor for metabolic syndrome. Or how to provide the information needed for prediction.
The method of claim 6, wherein the sample is selected from the group consisting of hair, blood, tissue, cells, serum, plasma, saliva, sputum, and urine, early diagnosis of hypoHDL cholesterol as a risk factor for metabolic syndrome. How to provide information necessary for diagnosis or prediction.

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