KR20110036557A - Composition for diagnosing colorectal cancer and use thereof - Google Patents

Composition for diagnosing colorectal cancer and use thereof Download PDF

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KR20110036557A
KR20110036557A KR1020110023855A KR20110023855A KR20110036557A KR 20110036557 A KR20110036557 A KR 20110036557A KR 1020110023855 A KR1020110023855 A KR 1020110023855A KR 20110023855 A KR20110023855 A KR 20110023855A KR 20110036557 A KR20110036557 A KR 20110036557A
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gene
protein
colorectal cancer
colon cancer
sense
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KR101115443B1 (en
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정경숙
원미선
안지원
염영일
이희구
송은영
김남순
양석진
김영호
전호경
강창모
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한국생명공학연구원
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    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57419Specifically defined cancers of colon
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854Immunoglobulins
    • G01N33/6857Antibody fragments
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Abstract

PURPOSE: A C13ORF3 gene for diagnosing colon cancer is provided to diagnose colon cancer and to enable drug screening. CONSTITUTION: A composition for diagnosing colon cancer contains C13ORF3(chromosome 13 open reading frame 3, GeneBank accession No. NM_145061.4) gene, a sense and antisense primer pair, a protein expressed from the gene, or antibody for the protein. The primer pair has sequence numbers 18 and 19. The composition contains a C13ORF18(chromosome 13 open reading frame 18, GeneBank accession No. NM_025113) gene; ASPM((asp(abnormal spindle)-like, microcephaly associated, GeneBank accession No. NM_018136.3) gene, IQGAP3(IQ motif containing GT pase activating protein 3, GeneBank accession No. NM_178229.4) gene, or ARID3A(AT rich interactive domain 3A), GeneBank accession No. NM_005224.2). A kit for diagnosing colon cancer contains the C13ORF3 gene, sense and antisense primer pair, protein, or antibody.

Description

대장암 진단용 조성물 및 그 용도{Composition for diagnosing colorectal cancer and use thereof}Composition for diagnosing colorectal cancer and use thereof TECHNICAL FIELD

본 발명은 대장암 진단용 조성물 및 그를 이용한 진단키트, 대장암 치료용 조성물, 및 대장암 치료제 스크리닝용 조성물 및 스크리닝 방법에 관한 것이다.The present invention relates to a composition for diagnosing colon cancer and a diagnostic kit using the same, a composition for treating colon cancer, and a composition for screening a therapeutic agent for colon cancer and a screening method.

대장암은 일반적으로 소득수준이 높은 집단에서 발생률이 높아 일반적으로 '선진국형 암'으로 인식되어지고 있으며 서양의 경우 암 사망에 있어서 제2위를 차지하는 암으로 전체 암의 약 15% 정도를 차지하고 있다. 미국의 경우 연간 약 56,000명이 대장암으로 사망하고 130,000명의 새로운 대장암 환자가 발생한다고 보고되고 있으며 우리나라에서 대장암은 사망률에서 전체 암에서 차지하는 비율이 위암, 간암, 폐암에 이어 제4위를 차지하는 암이다. 1980년에 전체암의 5.8%를 차지하던 것이 1985년에는 6.1%, 1995년에는 8.2%, 가장 최근 자료인 2002년에는 11.2%로 지속적인 증가 추세를 보이고 있으며, 1991년도 자료와 비교해 볼 때 위암, 간암, 자궁경부암의 사망률이 감소한 데 비해 대장암에 의한 사망률은 인구 10만 명당 4.7명에서 11.4명으로 2배 이상 증가하였다. 이와 같은 추세가 계속된다면 2010년경에는 우리나라에서의 대장암 발생빈도가 서양의 수준에 도달할 것으로 예측되며 2006년 대장암 발병률은 2위에 해당한다.Colorectal cancer is generally recognized as a'advanced country type cancer' due to its high incidence in high-income groups. In Western cases, it is a cancer that ranks second in cancer deaths, accounting for about 15% of all cancers. . In the US, it is reported that about 56,000 people die of colorectal cancer per year and 130,000 new colorectal cancer patients occur. In Korea, colorectal cancer accounts for the fourth largest mortality rate after gastric cancer, liver cancer, and lung cancer. to be. In 1980, 5.8% of all cancers were accounted for, 6.1% in 1985, 8.2% in 1995, and 11.2% in 2002, the most recent data. The mortality rate from liver and cervical cancer decreased, while the mortality rate from colon cancer increased more than double from 4.7 to 11.4 per 100,000 population. If this trend continues, it is predicted that the incidence of colon cancer in Korea will reach Western levels by 2010, and the incidence of colon cancer in 2006 is the second largest.

대장암 환자의 생존률을 높이기 위한 많은 노력이 진행되고 있으나 기존 치료법을 통하여 생존률을 향상시키기는 어려운 상태이다. 대장암 환자의 생존률을 높이기 위해서는 무엇보다도 조기진단과 새로운 대장암 맞춤타겟의 발굴이 시급하다. 대부분의 대장암은 선종에서 발생하며, 암으로의 변화에 약 10년이 소요되므로 조기진단을 통하여 전암성 병변인선종이나 조기암을 제거할 기회가 많다. 현재 사용되는 선별 검사로는 1) 대변 잠혈 검사, 2) 에스결장경 검사, 3) 대장 내시경 검사, 4) 대장 조영술이 사용되고 있는데 잠혈 검사는 조기진단용으로는 유용성이 떨어지며, 대장 조영술은 진단의 정확도가 떨어져 1cm 이하의 경우 20-50%, 1cm 이상일 때는 10-30%, 조기 대장암의 경우 15-45% 정도의 정확도를 보인다. 따라서 좀 더 정확하고 조기진단이 될 수 있는 진단시스템이 필요하며, 이는 대장암 관련 마커유전자의 발굴이 필요로 되어지는 부분이다. 또한 대장암이 발병했을 경우 예후를 예측하고 적절한 치료방침을 정하는데 대장암 마커가 적절히 활용될 수 있을 것으로 사료된다.Much efforts are being made to increase the survival rate of colon cancer patients, but it is difficult to improve the survival rate through existing treatments. In order to increase the survival rate of colon cancer patients, it is urgent to find an early diagnosis and new targets for colorectal cancer above all else. Most colorectal cancers occur from adenomas, and since it takes about 10 years to change to cancer, there are many opportunities to remove precancerous lesions such as adenoma or early cancer through early diagnosis. Currently used screening tests include 1) fecal occult blood test, 2) S colonoscopy, 3) colonoscopy, and 4) colonography, but occult blood test is less useful for early diagnosis, and colonography is less accurate in diagnosis. It shows an accuracy of 20-50% for less than 1cm apart, 10-30% for more than 1cm, and 15-45% for early colorectal cancer. Therefore, a more accurate and early diagnosis system is needed, which is a part that requires the discovery of marker genes related to colon cancer. In addition, it is believed that colon cancer markers can be appropriately utilized in predicting the prognosis and setting an appropriate treatment policy in case of colon cancer.

대장암의 발생과정에는 여러종류의 암 유전자, 종양 억제유전자등 다양한 유전자 변화가 관여하는 것으로 알려져 있다. 실제 대장암은 발암과정에서 일어나는 유전적 변화가 가장 많이 밝혀진 암이다. 대장암은 한 개의 암 유전자 또는 종양억제 유전자의 변화가 단독으로 암을 유발시킬 수 있는 것이 아니고 정상 대장 점막세포가 선종의 단계를 거쳐 대장암으로 진행되기 위해서는 수년에 걸친 긴 세월을 통해 여러 개의 암 관련 유전자의 변화가 축적되어야 하는데 이를 대장암 발생에 있어서 유전자의 다단계적 변화라고 한다. 여기서 중요한 것은 각 단계에서의 유전자 변화 순서가 아니라 궁극적으로 누적되는 유전자들의 변화의 총합이다. 대장암 발생과정에 관여하는 유전적 변화로는 K-ras, APC, MCC 유전자, 18번 염색체의 DCC유전자, 17번 염색체의 p53 유전자, 그리고 DNA methylation의 이상 등이 있으며, hMSH2, hMSH1, hPMS1, hPMS2 등의 돌연변이도 관계된다.It is known that various gene changes, such as various types of cancer genes and tumor suppressor genes, are involved in the development of colorectal cancer. In fact, colorectal cancer is a cancer with the most genetic changes that occur during the carcinogenesis process. In colorectal cancer, a change in a single cancer gene or tumor suppressor gene alone can not cause cancer. In order for normal colonic mucosal cells to progress to colorectal cancer through the stage of adenoma, several cancers over a long period of time. Changes in related genes must be accumulated, which is called multi-step change in genes in the occurrence of colorectal cancer. What is important here is not the sequence of changes in the genes at each stage, but the sum of changes in the genes that ultimately accumulate. Genetic changes involved in colon cancer development include K-ras, APC, MCC genes, DCC gene on chromosome 18, p53 gene on chromosome 17, and abnormal DNA methylation, hMSH2, hMSH1, hPMS1, Mutations such as hPMS2 are also involved.

이와 같이,암의 형성은 다양한 유전자들과 이들 유전자들의 발현및 조절 기작이 복합적으로 연관되어 진행되므로 최근 들어 다량의 유전자를 사용하는 올리고 칩을 이용한 암 관련 유전자들의 발현률을 비교하여 암의 새로운 진단이나 치료의 마커를 발굴하기 위한 연구들이 이루어지고 있다. 암세포에서 발현이 증가하거나 감소하는 유전자들은 세포분열, 세포신호전달, 세포 골격, 세포 운동, 세포 방어, 유전자및 단백질의 발현 그리고 세포내 물질대사등 여러부분에 관여하는 것으로 환자 조직들에 따라 동일한 발현변화를 보이는 유전자가 있는 반면 다른 발현 변화를 보이는 유전자들이 많다. 이것은 각각 환자들이 특이성 때문일 가능성이 크므로 연구하는 대상의 환자 조직들의 정확한 병리학적 소견과 분류에 따라야 하며 정확한 유전자를 이용한 진단에는 보다 많은 새로운 유전자들의 검색과 확인이 필요하다.As described above, the formation of cancer proceeds in a complex connection between various genes and expression and regulation mechanisms of these genes, so in recent years, the expression rates of cancer-related genes using an oligo chip that uses a large amount of genes are compared to find a new diagnosis of cancer. Research is being conducted to discover therapeutic markers. Genes whose expression increases or decreases in cancer cells are involved in various areas such as cell division, cell signaling, cytoskeleton, cell movement, cell defense, expression of genes and proteins, and intracellular metabolism. While some genes show changes, many genes show other changes in expression. This is likely due to the specificity of each patient, so it is necessary to follow the exact pathological findings and classification of the patient's tissues to be studied, and more new genes need to be searched and confirmed for diagnosis using accurate genes.

특정 세포내에서 특정 유전자의 발현 빈도를 조사함으로서 대장암 관련된 유전자의 발굴이 가능하며, 이를 통하여 대장암 진행의 분자적 메카니즘을 이해하게 되고, 나아가 대장암 진단 및 치료 타겟으로의 사용이 가능하게 될 것이다.By investigating the expression frequency of a specific gene in a specific cell, it is possible to discover a gene related to colon cancer. Through this, it is possible to understand the molecular mechanism of the progression of colon cancer, and furthermore, it will be possible to use it as a target for diagnosis and treatment of colon cancer. will be.

현재 C13ORF18 C13ORF3는 유전자의 기능에 대해서 전혀 보고된 바가 없으며, ASPM는 유사분열시 방추체를 조절하는 역할을 하며 주로 신경분화와 관련되어 보고되어 있다 [Nousiainen 등, PNAS, 2006]. 또한, ARID3A는 RB1 단백질과 E2F1 전사인자 신호전달과정의 또 다른 전사인자로서 세포주기조절에 관여하며, B 세포 분화에 관계한다고 보고 되어 있고[Ma 등, Mol Cancer Res, 2003], C2ORF15는 콜라겐 축적의 negative 조절자로서의 역할이 알려져 있다[Pyagay 등, Circ Res. 200]. 그리고, IQGAP3는 GTPase activating 단백질로서 Rac1 과 Cdc42의 새로운 타겟으로 신경돌기의 성장에 관계되어 보고되어 졌으며[Wang 등 J Cell Sci, 567-577, 2007], LOC644773는 ARP3 actin-related protein 3 homolog B로서 정의 되고 pseudogene일 가능성이 있으며 유전자의 기능에 대해서 전혀 보고된 바가 없으며, LOC144501는 keratin 의 새로운 멤버로서 기능이 알려져 있지는 않다 [Rogers 등, J. Invest Dermatol 536-544, 2005].Now with C13ORF18 C13ORF3 has not been reported on the function of the gene at all, and ASPM plays a role in regulating the spindle during mitosis and has been reported mainly related to neuronal differentiation [Nousiainen et al., PNAS, 2006]. In addition, ARID3A is another transcription factor in the signaling process of RB1 protein and E2F1 transcription factor, and is involved in cell cycle regulation and is reported to be involved in B cell differentiation [Ma et al., Mol Cancer Res, 2003]. C2ORF15 is known to play a role as a negative regulator of collagen accumulation [Pyagay et al., Circ Res. 200]. In addition, IQGAP3 is a GTPase activating protein and has been reported as a new target for Rac1 and Cdc42 related to neurite growth [Wang et al. J Cell Sci, 567-577, 2007], and LOC644773 is ARP3 actin-related protein 3 homolog B. It is defined and likely to be a pseudogene, and there are no reports on the function of the gene. LOC144501 is a new member of keratin, and its function is not known [Rogers et al., J. Invest Dermatol 536-544, 2005].

FLJ22655는 hypothetical 단백질을 암호화하고 있으나, 그 기능은 알려져 있지 않은 유전자이며, ZG16는 zymogen granule protein 16으로 간암에서 현저히 줄어드는 것으로 알려져 있고 [Zhou YB등 BBRC 2007], VMD2L2 는 칼슘민감성 chloride 채널을 형성하는 단백질로서 알려져 있을 뿐 암과의 관련성은 보고된 바 없다[Tsunenari 등, J Biol Chem 41114-41125, 2003]. 또한, MS4A12는 막 단백질로서 복합 수용체의 구성원 중의 하나이고 세포신호전달에 관여한다고 보고되어 있고[Liang등, Genomics, 119-127, 2001], KIAA1644는 그 기능이 아직 알려진 바 없다. FLJ22655 encodes a hypothetical protein, but its function is unknown. ZG16 is a zymogen granule protein 16, which is known to be significantly reduced in liver cancer [BBRC 2007 such as Zhou YB], and VMD2L2 is a protein that forms a calcium-sensitive chloride channel. It is known as, but no association with cancer has been reported [Tsunenari et al., J Biol Chem 41114-41125, 2003]. In addition, MS4A12 is a membrane protein, one of the members of the complex receptor and has been reported to be involved in cell signaling [Liang et al., Genomics, 119-127, 2001], and KIAA1644 has not yet known its function.

본 발명자들은 상기 유전자들이 대장암관련성이 있음을 발견하여 본 발명을 완성하였다.The present inventors have completed the present invention by discovering that the genes are related to colon cancer.

본 발명은 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644 유전자의 신규한 용도를 제공하는 것을 목적으로 한다.The present invention aims to provide a novel use of the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes.

보다 구체적으로, 본 발명은 상기 유전자로부터 발현된 단백질을 포함하는 대장암 진단용 또는 대장암치료제 스크리닝용 조성물, 상기 유전자의 억제제 또는 상기 유전자로부터 발현된 단백질의 억제제 및 약제학적으로 허용되는 담체를 포함하는 대장암 치료용 조성물, 및 대장암 진단용 키트를 제공하고자 한다. More specifically, the present invention comprises a composition for diagnosing colorectal cancer or screening a colorectal cancer therapeutic agent comprising a protein expressed from the gene, an inhibitor of the gene or an inhibitor of the protein expressed from the gene, and a pharmaceutically acceptable carrier. To provide a composition for treating colon cancer, and a kit for diagnosing colon cancer.

본 발명은 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자를 포함하는 대장암 진단용 조성물을 제공한다.The present invention provides a composition for colorectal cancer diagnosis comprising at least one gene selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644.

본 발명의 'C13ORF18', 'C13ORF3', 'ASPM', 'ARID3A', 'C2ORF15', 'IQGAP3', 'LOC644773', 'LOC144501', 'FLJ22655', 'ZG16', 'VMD2L2', 또는 'MS4A12'의 '유전자'라 함은 이들 유전자의 DNA 또는 mRNA를 말하며, DNA 또는 mRNA의 전부 또는 일부를 모두 포함하는 개념이다.'C13ORF18','C13ORF3','ASPM','ARID3A','C2ORF15','IQGAP3','LOC644773','LOC144501','FLJ22655','ZG16','VMD2L2', or'MS4A12' of the present invention 'Gene' refers to the DNA or mRNA of these genes, and includes all or part of the DNA or mRNA.

본 발명의 대장암 진단용 조성물은 상기 유전자 외에도 핵산의 구조를 안정하게 유지시키는 증류수 또는 완충액을 포함할 수 있다.The composition for diagnosing colorectal cancer of the present invention may include distilled water or a buffer solution for stably maintaining the structure of a nucleic acid in addition to the gene.

상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501 유전자는 대장암세포에서 특이적으로 발현이 증가하며, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644 유전자는 대장암세포에서 특이적으로 발현이 감소한다. 따라서 상기 유전자의 발현정도를 조사하면 대장암을 진단할 수 있다.The C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 genes are specifically expressed in colorectal cancer cells, and the FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes are specifically expressed in colorectal cancer cells. Decreases. Therefore, by examining the expression level of the gene, colon cancer can be diagnosed.

상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644유전자의 서열정보는 표 1에 나타낸 바와 같다.The sequence information of the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes are as shown in Table 1.

Figure pat00001
Figure pat00001

본 발명은 또한 상기 유전자들의 대장암 진단 용도 및 상기 조성물과 대상체로부터 얻은 시료 간의 반응을 확인하여 대장암을 진단하는 방법을 제공한다.The present invention also provides a method for diagnosing colorectal cancer by confirming the use of the genes for diagnosing colorectal cancer and the reaction between the composition and a sample obtained from a subject.

본 발명의 진단 방법에서 상기 유전자를 포함하는 조성물과 시료 간의 반응의 확인은 DNA-DNA, DNA-RNA, DNA-단백질 간의 반응 여부를 확인하는데 사용되는 통상적인 방법들, 예컨대 DNA 칩, 단백질 칩, 중합효소 연쇄반응 (PCR), 노던 블롯팅, 서던 블롯팅, ELISA(Enzyme Linked Immunosorbent assay), 효모 이중 혼성법(yeast two-hybrid), 2-D 겔 분석 및 시험관 내 결합 에세이 (in vitro binding assay) 등을 이용할 수 있다. 예컨대 상기 유전자의 전부 또는 일부를 프로브로 사용하여 대상자의 체액으로부터 분리한 핵산과 하이브리드화한 후 당분야에 공지된 다양한 방법, 예컨대 역전사 중합효소 연쇄반응(reverse transcription polymerases chain reaction), 써던블로팅(southern blotting), 노던 블롯팅(Northern blooting) 등으로 이를 검출함으로써 대상자에서 상기 유전자가 고발현된 상태인지 또는 저발현된 상태인지 조사하면 대장암의 발생 여부를 판단할 수 있다. 상기 프로브를 방사선 동위원소 또는 효소 등으로 표지하면 용이하게 유전자의 존재를 확인할 수 있다. 상기 프로브의 염기서열은 상기 유전자의 염기서열과 70% 이상의 유사성이 있으면 족하다. 상기 프로브는 본 발명의 센스 및 안티센스 프라이머를 이용한 유전자 증폭법에 의해 제조할 수 있다.In the diagnostic method of the present invention, confirmation of the reaction between the composition containing the gene and the sample is conventional methods used to determine whether a reaction between DNA-DNA, DNA-RNA, and DNA-protein, such as a DNA chip, a protein chip, Polymerase chain reaction (PCR), Northern blotting, Southern blotting, ELISA (Enzyme Linked Immunosorbent assay), yeast two-hybrid, 2-D gel analysis, and in vitro binding assay ), etc. can be used. For example, after hybridizing with a nucleic acid isolated from a subject's body fluid using all or part of the gene as a probe, various methods known in the art, such as reverse transcription polymerases chain reaction, southern blotting ( Southern blotting), Northern blotting, etc., by detecting this, and whether the gene is in a high-expression state or a low-expression state in a subject, it is possible to determine whether the occurrence of colorectal cancer. When the probe is labeled with a radioisotope or an enzyme, the presence of the gene can be easily confirmed. The nucleotide sequence of the probe is sufficient if it has a similarity of 70% or more with the nucleotide sequence of the gene. The probe can be prepared by a gene amplification method using the sense and antisense primers of the present invention.

또한, 본 발명은 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자의 센스 및 안티센스 프라이머쌍을 포함하는 대장암 진단용 조성물을 제공한다.In addition, the present invention comprises a sense and antisense primer pair of one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644. It provides a composition for diagnosis.

상기 센스 및 안티센스 프라이머쌍은 상기 유전자에 대한 상보적인 염기서열을 갖는 서열번호 3~28의 프라이머쌍일 수 있다. 상기 프라이머쌍은 다음의 표 2에 정리하였다. 본 발명에서 '상보적'이란 프라이머의 염기서열에서 완전히 상보적인 것과 80% 이상의 상동성이 있는 것을 포함하는 개념이다.The sense and antisense primer pair may be a primer pair of SEQ ID NOs: 3 to 28 having a base sequence complementary to the gene. The primer pairs are summarized in Table 2 below. In the present invention, the term'complementary' is a concept including those that are completely complementary in the nucleotide sequence of the primer and have 80% or more homology.

Figure pat00002
Figure pat00002

상기 센스 프라이머 및 안티센스 프라이머를 이용한 공지의 방법으로 상기 13종의 유전자의 발현양을 측정할 수 있다. 예를 들면, RT-PCR방법 등으로 측정할 수 있다.Expression levels of the 13 kinds of genes can be measured by a known method using the sense primers and antisense primers. For example, it can be measured by the RT-PCR method or the like.

본 발명은 또한 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자로부터 발현된 단백질을 포함하는 대장암 진단용 조성물을 제공한다.The present invention also provides a composition for diagnosis of colon cancer comprising a protein expressed from one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644. to provide.

본 발명의 조성물은 상기 단백질 외에도 단백질의 구조를 안정하게 유지시키는 증류수 또는 완충액을 포함할 수 있다.In addition to the protein, the composition of the present invention may contain distilled water or a buffer solution that stably maintains the structure of the protein.

앞서 언급한 바와 같이, 상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501 유전자는 대장암세포에서 특이적으로 발현이 증가하며, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644 유전자는 대장암세포에서 특이적으로 발현이 감소하므로 상기 유전자들로부터 발현된 단백질을 이용하여 상기 유전자 또는 단백질의 과발현 또는 저발현 여부를 조사하면 대장암을 진단할 수 있다.As mentioned above, the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 genes are specifically increased in colon cancer cells, and the FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes are colon cancer cells. Since expression is specifically reduced in, colorectal cancer can be diagnosed by examining whether the gene or protein is overexpressed or underexpressed using proteins expressed from the genes.

본 발명은 또한 상기 단백질의 대장암 진단 용도 및 상기 조성물과 대상체로부터 얻은 시료 간의 반응을 확인하여 대장암을 진단하는 방법을 제공한다.The present invention also provides a method for diagnosing colorectal cancer by confirming the use of the protein for diagnosing colorectal cancer and the reaction between the composition and a sample obtained from a subject.

본 발명의 진단 방법에서 상기 단백질을 포함하는 조성물과 시료 간의 반응의 확인은 DNA-단백질, RNA-단백질, 단백질-단백질 간의 반응 여부를 확인하는데 사용되는 통상적인 방법들, 예컨대 DNA 칩, 단백질 칩, 중합효소 연쇄반응 (PCR), 노던 블롯팅, 서던 블롯팅, 웨스턴 블롯팅, ELISA(Enzyme Linked Immunosorbent assay), 특이적 면역염색(histoimmunostaining), 효모 이중 혼성법(yeast two-hybrid), 2-D 겔 분석 및 시험관 내 결합 에세이 (in vitro binding assay) 등을 이용할 수 있다. 예컨대 상기 유전자들로부터 발현된 단백질의 전부 또는 일부를 프로브로 사용하여 대상자의 체액으로부터 분리한 핵산 또는 단백질과 하이브리드화한 후 당분야에 공지된 다양한 방법, 예컨대 역전사 중합효소 연쇄반응(reverse transcription polymerases chain reaction), 웨스턴 블로팅(western blotting) 등으로 이를 검출함으로써 대상자에서 상기 유전자가 고발현된 상태인지 조사하면 대장암의 발생 여부를 판단할 수 있다. 상기 프로브를 방사선 동위원소 또는 효소 등으로 표지하면 용이하게 유전자의 존재를 확인할 수 있다.In the diagnostic method of the present invention, the confirmation of the reaction between the composition containing the protein and the sample is conventional methods used to confirm the reaction between DNA-protein, RNA-protein, protein-protein, such as a DNA chip, a protein chip, Polymerase chain reaction (PCR), Northern blotting, Southern blotting, Western blotting, ELISA (Enzyme Linked Immunosorbent assay), specific immunostaining, yeast two-hybrid, 2-D Gel analysis and in vitro binding assay can be used. For example, after hybridizing with a nucleic acid or protein isolated from a subject's body fluid using all or part of the protein expressed from the genes as a probe, various methods known in the art, such as reverse transcription polymerase chain reactions reaction), western blotting, etc., by detecting whether the gene is highly expressed in the subject, it is possible to determine whether colon cancer has occurred. When the probe is labeled with a radioisotope or an enzyme, the presence of the gene can be easily confirmed.

또한 본 발명의 조성물은 상기 단백질 대신 상기 단백질에 대한 특이적 항체를 포함할 수 있다. C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 또는 LOC144501 유전자는 대장암세포에서 특이적으로 발현이 증가하여 상기 유전자로부터 발현된 단백질의 양 또한 증가하게 되며, FLJ22655, ZG16, VMD2L2, MS4A12, 또는 KIAA1644 유전자는 대장암세포에서 특이적으로 발현이 감소하여 상기 유전자로부터 발현된 단백질의 양 또한 감소하게 된다. 따라서 상기 유전자로부터 발현된 단백질에 대한 항체를 이용하는 경우, 항원-항체 반응을 통해 상기 단백질을 검출해 내어 대장암을 진단할 수 있다.In addition, the composition of the present invention may include a specific antibody against the protein instead of the protein. C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, or LOC144501 genes are specifically expressed in colon cancer cells to increase the amount of protein expressed from the gene, FLJ22655, ZG16, VMD2L2, MS4A12, or The KIAA1644 gene is specifically reduced in expression in colon cancer cells, and thus the amount of the protein expressed from the gene is also reduced. Therefore, when an antibody against a protein expressed from the gene is used, the protein can be detected through an antigen-antibody reaction to diagnose colorectal cancer.

상기 단백질에 대한 모노클로날 항체는 당업계에 통상적인 모노클로날 항체 제작 방법을 통해 제작되어 사용될 수도 있고, 시판되는 것을 사용할 수 있다. 상기 단백질에 대한 모노클로날 항체는 일반적으로 알칼라인 포스파타아제(alkaline phosphatase, AP) 또는 호올스래디쉬 퍼록시다제(horseradish peroxidase, HRP) 등의 효소가 컨쥬게이션된 2차 항체 및 이들의 기질을 사용하여 발색반응시킴으로써 정량분석할 수도 있고, 아니면 직접 상기 단백질에 대한 모노클로날 항체에 AP 또는 HRP 효소 등이 컨쥬게이션된 것을 사용하여 정량분석할 수도 있다. 또한, 모노클로날 항체 대신에 상기 단백질을 인식하는 폴리클로날 항체를 사용할 수도 있고 이는 당업계에 통상적인 항혈청 제작 방법을 통해 제작되어 사용될 수도 있으며, 항원결합성을 갖는 것이면 모노클로날 항체 또는 폴리클로날 항체의 일부도 본 발명의 항체에 포함되고, 모든 면역 글로불린 항체가 포함된다. 나아가, 본 발명의 항체에는 인간화 항체 등의 특수항체도 포함된다.The monoclonal antibody against the protein may be prepared and used through a method for producing a monoclonal antibody conventional in the art, or a commercially available one may be used. Monoclonal antibodies to the protein are generally used as secondary antibodies conjugated with enzymes such as alkaline phosphatase (AP) or horseradish peroxidase (HRP), and their substrates. Then, it may be quantitatively analyzed by performing a color reaction, or it may be quantitatively analyzed using a monoclonal antibody directly conjugated to the protein, such as AP or HRP enzyme. In addition, instead of a monoclonal antibody, a polyclonal antibody that recognizes the protein may be used, which may be prepared and used through an antisera production method conventional in the art. If it has antigen-binding properties, a monoclonal antibody or polyclonal antibody may be used. Some of the clonal antibodies are also included in the antibodies of the present invention, and all immunoglobulin antibodies are included. Furthermore, the antibody of the present invention also includes special antibodies such as humanized antibodies.

상기 항체는 본 발명의 13종의 각 유전자를 통상적인 방법에 따라 발현벡터에 클로닝하여 상기 유전자에 의해 코딩된 단백질을 얻고, 얻어진 단백질로부터 통상적인 방법에 의해 제조될 수 있다. 여기에는 13종의 단백질의 부분 펩타이드도 포함하며, 본 발명의 부분펩타이드로는 최소한 7개 이상, 바람직하게는 12개 이상의 아미노산을 포함한다.The antibody can be prepared by cloning each of the 13 genes of the present invention into an expression vector according to a conventional method to obtain a protein encoded by the gene, and from the obtained protein by a conventional method. This includes partial peptides of 13 kinds of proteins, and the partial peptides of the present invention include at least 7 or more, preferably 12 or more amino acids.

또한 본 발명은 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 포함하는 대장암 진단용 키트를 제공한다.In addition, the present invention is one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644, sense and antisense primer pairs of the genes, the gene It provides a diagnostic kit for colon cancer comprising a protein expressed from, or an antibody against the protein.

상기 대장암 진단용 키트는 지지체, 적당한 완충용액, 발색 효소 또는 형광물질로 표지된 2차 항체, 발색 기질액, 또는 1,6-N-아세틸글루코사민 당쇄가지 변화를 측정하기 위한 L4-PHA, 폴리(A) RNA 분리시약 등을 더 포함할 수 있다.The colorectal cancer diagnostic kit includes a support, a suitable buffer solution, a secondary antibody labeled with a color developing enzyme or a fluorescent substance, a color developing matrix solution, or L4-PHA for measuring changes in sugar chain branches of 1,6-N-acetylglucosamine, poly( A) RNA isolation reagents, etc. may further be included.

상기 지지체는 니트로셀룰로오즈막, 폴리비닐수지로 합성된 96웰플레이트(96 well plate), 폴리스티렌수지로 합성된 96웰플레이트, 또는 유리로 된 슬라이드글라스 등일 수 있고, 상기 발색효소는 퍼옥시다아제(peroxidase), 또는 알칼라인 포스파타아제(alkaline phosphatase) 등일 수 있으며, 상기 형광물질은 FITC, 또는 RITC 등일 수 있고, 상기 발색 기질액은 ABTS(2,2'-Azino-bis(3-ethylbenzenzothiazoline-6-sulfonic acid)), OPD(o-Phenylenediamine), 또는 TMB(Tetramethyl Benzidine) 등일 수 있다.The support may be a nitrocellulose membrane, a 96 well plate synthesized from polyvinyl resin, a 96 well plate synthesized from polystyrene resin, or a slide glass made of glass, and the color developing enzyme is peroxidase. , Or alkaline phosphatase, and the like, and the fluorescent material may be FITC or RITC, and the color developing substrate solution is ABTS(2,2'-Azino-bis(3-ethylbenzenzothiazoline-6-sulfonic acid). )), OPD (o-Phenylenediamine), or TMB (Tetramethyl Benzidine).

본 발명은 또한 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자를 포함하는 대장암 치료제 스크리닝용 조성물을 제공한다. 또한 본 발명은 상기 조성물의 대장암치료제 스크리닝용 용도 및 상기 조성물을 표적물질로 이용하여 시험대상물질을 접촉시키고, 표적물질과 시험대상물질 간의 반응을 확인하여, 시험대상물질이 상기 유전자의 발현을 증진시키는 활성 또는 억제하는 활성을 나타내는지를 결정하는 단계를 포함하는 대장암치료제 스크리닝 방법을 제공한다.The present invention also provides a composition for colorectal cancer treatment screening comprising at least one gene selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644. . In addition, the present invention uses the composition for screening for colorectal cancer treatment and uses the composition as a target substance to contact a test substance, and confirms the reaction between the target substance and the test substance, so that the test substance controls the expression of the gene. It provides a method for screening a colon cancer treatment agent comprising the step of determining whether it exhibits an enhancing activity or an inhibitory activity.

본 발명의 스크리닝 방법에서 상기 유전자를 포함하는 조성물과 시험대상물질 간의 반응 확인은, DNA-DNA, DNA-RNA, DNA-단백질, DNA-화합물 간의 반응 여부를 확인하는데 사용되는 통상적인 방법들을 사용할 수 있다. 예를 들면, 생체 외부에서(in vitro) 상기 유전자와 시험대상물질 사이의 결합 여부를 확인하기 위한 혼성화 시험, 포유류세포와 시험대상물질을 반응시킨 후 노던 분석, 정량적 PCR, 정량적 실시간 PCR 등을 통한 상기 유전자의 발현율 측정 방법, 또는 상기 유전자에 리포터 유전자를 연결시켜 세포 내로 도입한 후 시험대상물질과 반응시키고 리포터 단백질의 발현율을 측정하는 방법 등을 사용할 수 있다. 이러한 경우 본 발명의 조성물은 상기 유전자 외에도, 핵산의 구조를 안정하게 유지시키는 증류수 또는 완충액을 포함할 수 있다.In the screening method of the present invention, the reaction between the composition containing the gene and the test substance can be confirmed by conventional methods used to confirm the reaction between DNA-DNA, DNA-RNA, DNA-protein, and DNA-compound. have. For example, a hybridization test to confirm the binding between the gene and the test substance in vitro, Northern analysis, quantitative PCR, quantitative real-time PCR, etc. after reacting a mammalian cell with a test substance. A method of measuring the expression rate of the gene, or a method of linking a reporter gene to the gene and introducing it into a cell, reacting with a test substance, and measuring the expression rate of the reporter protein, may be used. In this case, the composition of the present invention may contain, in addition to the gene, distilled water or a buffer solution for stably maintaining the structure of the nucleic acid.

또한, 본 발명은 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자로부터 발현된 단백질을 포함하는 대장암치료제 스크리닝용 조성물을 제공한다. 본 발명은 또한 상기 조성물의 대장암치료제 스크리닝용 용도 및 상기 조성물을 표적물질로 이용하여 시험대상물질을 접촉시키고, 표적물질과 시험대상물질 간의 반응을 확인하여, 시험대상물질이 상기 단백질의 기능을 증진시키는 활성 또는 억제하는 활성을 나타내는지를 결정하는 단계를 포함하는 대장암치료제 스크리닝 방법을 제공한다.In addition, the present invention screening for colon cancer treatment comprising a protein expressed from one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 It provides a composition for use. The present invention also uses the composition for screening for colorectal cancer treatment and by using the composition as a target substance to contact a test substance, and by confirming the reaction between the target substance and the test substance, the test substance performs the function of the protein. It provides a method for screening a colon cancer treatment agent comprising the step of determining whether it exhibits an enhancing activity or an inhibitory activity.

본 발명의 스크리닝 방법에서 상기 단백질을 포함하는 조성물과 시험대상물질 간의 반응 확인은, 단백질-단백질, 단백질-화합물 간의 반응 여부를 확인하는데 사용되는 통상적인 방법들을 사용할 수 있다. 예를 들면, 상기 단백질과 시험대상물질을 반응시킨 후 활성을 측정하는 방법, 효모 이중 혼성법(yeast two-hybrid), 상기 단백질에 결합하는 파지 디스플레이 펩티드 클론(phage-displayed peptide clone)의 검색, 천연물 및 화학물질 라이브러리(chemical library) 등을 이용한 HTS(high throughput screening), 드럭 히트 HTS(drug hit HTS), 세포 기반 스크리닝(cell-based screening), 또는 DNA 어레이(DNA array)를 이용하는 스크리닝법 등을 사용할 수 있다. 이러한 경우 본 발명의 조성물은 상기 단백질 외에도, 단백질의 구조 또는 생리 활성을 안정하게 유지시키는 완충액 또는 반응액을 포함할 수 있다. 또한 본 발명의 조성물은 생체 내(in vivo) 실험을 위해, 상기 단백질을 발현하는 세포, 또는 전사율을 조절할 수 있는 프로모터 하에 상기 단백질을 발현하는 플라스미드를 함유하는 세포 등을 포함할 수 있다.In the screening method of the present invention, for confirming the reaction between the composition containing the protein and the test substance, conventional methods used to check whether a reaction between a protein-protein or a protein-compound can be used can be used. For example, a method of measuring activity after reacting the protein with a test substance, yeast two-hybrid, search for a phage-displayed peptide clone that binds to the protein, High throughput screening (HTS) using natural products and chemical libraries, drug hit HTS (drug hit HTS), cell-based screening, or screening using DNA arrays, etc. Can be used. In this case, the composition of the present invention may include, in addition to the protein, a buffer solution or a reaction solution that stably maintains the structure or physiological activity of the protein. In addition, the composition of the present invention may include cells expressing the protein for in vivo experiments, or cells containing a plasmid expressing the protein under a promoter capable of controlling the transcription rate.

본 발명의 스크리닝 방법에서, 시험대상물질은 통상적인 선정방식에 따라 대장암전이 억제제로서의 가능성을 지닌 것으로 추정되거나 또는 무작위적으로 선정된 개별적인 핵산, 단백질, 기타 추출물 또는 천연물, 화합물 등이 될 수 있다.In the screening method of the present invention, the test substance may be an individual nucleic acid, protein, other extract, natural product, compound, etc., which is estimated to have the potential as a colon cancer metastasis inhibitor according to a conventional selection method or randomly selected. .

본 발명의 스크리닝 방법을 통해 얻은, 대장암 고발현 유전자의 발현을 증진시키거나 단백질의 기능을 증진시키는 활성을 나타내는 시험대상물질 및 반대로 대장암 고발현 유전자의 발현을 억제시키거나 단백질의 기능을 억제시키는 활성을 나타내는 시험대상물질은, 전자의 경우, 시험대상물질에 대한 억제제를 개발함으로써 대장암치료제 후보물질이 될 수 있고, 후자의 경우는 대장암치료제 후보물질이 될 수 있다. 또한, 대장암 저발현 유전자의 발현을 증진시키거나 단백질의 기능을 증진시키는 활성을 나타내는 시험대상물질 및 반대로 대장암 저발현 유전자의 발현을 억제시키거나 단백질의 기능을 억제시키는 활성을 나타내는 시험대상 물질은, 전자의 경우, 대장암치료제 후보물질이 될 수 있고, 후자의 경우, 시험대상물질에 대한 억제제를 개발함으로써 대장암치료제 후보물질이 될 수 있다. 이와 같은 대장암치료제 후보물질은 이후의 대장암치료제 개발과정에서 선도물질(leading compound)로서 작용하게 되며, 선도물질이 상기 유전자 또는 그로부터 발현되는 단백질의 기능 억제효과를 나타낼 수 있도록 그 구조를 변형시키고 최적화함으로써, 새로운 대장암치료제를 개발할 수 있다.A test substance that exhibits the activity of enhancing the expression of a high-expressing colon cancer gene or enhancing the function of a protein obtained through the screening method of the present invention, and conversely, inhibiting the expression of a high-expressing colon cancer gene or inhibiting the function of a protein. In the former case, a test substance exhibiting an activity to be tested can be a candidate substance for colorectal cancer treatment by developing an inhibitor for the substance to be tested, and in the latter case, it may be a candidate substance for colorectal cancer treatment. In addition, a test substance exhibiting the activity of enhancing the expression of a low-expression gene for colon cancer or enhancing the function of a protein, and conversely, a test substance exhibiting an activity of inhibiting the expression of a low-expressing colon cancer gene or inhibiting the function of a protein. Silver, in the former case, can be a candidate for colorectal cancer treatment, and in the latter case, it can be a candidate for colorectal cancer treatment by developing an inhibitor for the test substance. Such a candidate for colorectal cancer treatment will act as a leading compound in the development of a subsequent colorectal cancer treatment, and its structure is modified so that the leading substance can exhibit the effect of inhibiting the function of the gene or protein expressed therefrom. By optimizing, new colorectal cancer treatments can be developed.

본 발명은 또한 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자의 siRNA를 제공한다.The present invention also provides siRNA of one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644.

상기 siRNA의 염기서열은 상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자(mRNA)의 염기서열 중 각각의 서열에서 연속된 19~23개의 염기서열일 수 있다.The nucleotide sequence of the siRNA is each of the nucleotide sequences of one or more genes (mRNA) selected from the group consisting of the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644. It may be a sequence of 19 to 23 consecutive nucleotides in the sequence.

상기 siRNA의 서열은 편의상 정방향 서열(sense strand)을 나타낸 것으로, 실제 유전자 억제효과를 나타내는 역방향 서열(antisense strand)과 함께 이중리보핵산쇄를 구성하게 된다.For convenience, the siRNA sequence represents a forward sequence (sense strand), and constitutes a double ribonucleic acid chain together with an antisense strand representing an actual gene suppression effect.

본 발명의 siRNA는 짧은 19-23개의 이중 리보핵산쇄로 세포내에 도입하면 비특이적 저해(non-specific inhibition)없이 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644로 이루어진 군에서 선택된 하나 이상의 유전자 발현만을 억제하는 효과를 나타내므로, 대장암 관련 유전자 기능연구에 이용할 수 있다. 또한, 상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자 발현을 억제하여 대장암세포를 죽이는 효과도 나타낼 수 있다.The siRNA of the present invention is introduced into cells with short 19-23 double ribonucleic acid chains without non-specific inhibition C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, Since it exhibits an effect of suppressing the expression of only one or more genes selected from the group consisting of MS4A12 and KIAA1644, it can be used for gene function studies related to colon cancer. In addition, the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and by inhibiting the expression of one or more genes selected from the group consisting of LOC144501 can also exhibit the effect of killing colon cancer cells.

본 발명은 또한 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자에 대한 억제제를 포함하는 대장암 치료용 조성물을 제공한다.The present invention also provides a composition for treating colon cancer comprising an inhibitor for one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501.

상기 조성물은 약제학적으로 허용되는 담체를 추가로 포함할 수 있다.The composition may further include a pharmaceutically acceptable carrier.

본 발명의 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자는 대장암 세포에서 다량 발현되므로, 상기 유전자의 억제제를 투여하여 상기 유전자의 발현을 저해시키면 대장암을 억제할 수 있다.Since at least one gene selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 of the present invention is expressed in large quantities in colon cancer cells, administration of an inhibitor of the gene to inhibit the expression of the gene It can inhibit colon cancer.

따라서 본 발명은 또한 상기 유전자의 억제제의 대장암 치료 용도 및 유효량의 상기 유전자의 억제제를 환자에게 투여하는 단계를 포함하는 대장암 치료방법을 제공한다. 본 발명에 있어서 대장암 치료는 대장암의 예방 및 억제를 포함한다.Accordingly, the present invention also provides a use of the gene inhibitor for the treatment of colorectal cancer and a method for treating colorectal cancer comprising administering an effective amount of the gene inhibitor to a patient. In the present invention, the treatment of colon cancer includes the prevention and inhibition of colon cancer.

본 발명에 있어서, C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자에 대한 억제제는 상기 유전자의 mRNA에 대한 안티센스 올리고뉴클레오타이드일 수 있다.In the present invention, the inhibitor for one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 may be an antisense oligonucleotide for the mRNA of the gene.

안티센스 올리고뉴클레오타이드는 생체 내 뿐만 아니라 생체 외에서도 유전자-특이적 억제를 달성하기 위해 성공적으로 사용되어 왔다. 안티센스 뉴클레오타이드는 특정 DNA 또는 RNA 타겟에 대해 안티센스(또는 상보)인 짧은 길이의 DNA 합성 가닥(또는 DNA 아날로그)이다. 안티센스 올리고뉴클레오타이드는 타겟에 결합하고 전사, 번역 또는 스플라이싱의 단계에서 발현을 멈추게 함으로써 DNA 또는 RNA 타겟에 의해 인코드된 단백질의 발현을 막기 위해 제안되었다. 안티센스 올리고뉴클레오타이드는 세포 배양 및 질병의 동물 모델에서도 성공적으로 이용되어 왔다(Hogrefe, 1999). 올리고뉴클레오타이드가 분해되지 않도록 더욱 안정하고 저항적이 되게 하기 위한 안티센스 올리고뉴클레오타이드의 또 다른 변형이 당업자에게 알려져 있고 이해된다. 여기서 사용된 안티센스 올리고뉴클레오타이드는 이중나선 또는 단일나선 DNA, 이중나선 또는 단일나선 RNA, DNA/RNA 하이브리드, DNA 및 RNA 아날로그 및 염기, 당 또는 백본 변형을 지닌 올리고뉴클레오타이드를 포함한다. 올리고뉴클레오타이드는 안정성을 증가시키고, 뉴클레아제 분해에 대한 저항성을 증가시키기 위해 당분야에 알려진 방법에 의해 변형된다. 이들 변형은 당분야에 알려져 있는 올리고뉴클레오타이드 백본의 변형, 당 모이어티의 변형 또는 염기의 변형을 포함하나 이에 한정적인 것은 아니다.Antisense oligonucleotides have been used successfully to achieve gene-specific inhibition in vivo as well as ex vivo. Antisense nucleotides are short-length DNA synthetic strands (or DNA analogues) that are antisense (or complementary) to a specific DNA or RNA target. Antisense oligonucleotides have been proposed to prevent the expression of proteins encoded by DNA or RNA targets by binding to the target and stopping expression at the stage of transcription, translation or splicing. Antisense oligonucleotides have also been successfully used in cell culture and in animal models of disease (Hogrefe, 1999). Other modifications of antisense oligonucleotides to make them more stable and resistant so that the oligonucleotides do not degrade are known and understood by those of skill in the art. Antisense oligonucleotides as used herein include double-stranded or single-stranded DNA, double-stranded or single-stranded RNA, DNA/RNA hybrids, DNA and RNA analogues and oligonucleotides with base, sugar or backbone modifications. Oligonucleotides are modified by methods known in the art to increase stability and increase resistance to nuclease degradation. These modifications include, but are not limited to, modifications of the oligonucleotide backbone, modifications of sugar moieties, or modifications of bases known in the art.

또한, C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자에 대한 억제제는 상기 유전자의 siRNA(Small Interfering RNA)일 수 있다.In addition, the inhibitor for one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 may be siRNA (Small Interfering RNA) of the gene.

즉, 상기 siRNA의 염기서열은 상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자(mRNA)의 염기서열 중 각각의 서열에서 연속된 19~23개의 연속된 염기서열일 수 있다.That is, the nucleotide sequence of the siRNA is 19 to 23 consecutive in each of the nucleotide sequences of one or more genes (mRNA) selected from the group consisting of the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501. It may be a continuous nucleotide sequence.

상기 siRNA의 서열은 편의상 정방향 서열(sense strand)을 나타낸 것으로, 실제 유전자 억제효과를 나타내는 역방향 서열(antisense strand)과 함께 이중리보핵산쇄를 구성하게 된다.For convenience, the siRNA sequence represents a forward sequence (sense strand), and constitutes a double ribonucleic acid chain together with an antisense strand representing an actual gene suppression effect.

siRNA는 세포 배양 및 생체 내에서 오래 지속되는 효과, 생체 내에서 세포를 트랜스펙션시키는 능력 및 혈청 내 분해에 대한 저항력의 측면에서 생체 내에서 특정한 유전자의 발현의 저해에 대해 매우 강한 약물이 되는 잠재력을 지닌다(Bertrand et al., 2002). siRNA의 전달 및 siRNA를 포함한 발현 컨스트럭트/벡터는 당업자에게 알려져 있다. 예를 들어, 미국 출원 제2004/106567 및 2004/0086884는 바이러스성 벡터, 비바이러스성 벡터, 리포솜 전달 운반체, 플라스미드 주입 시스템, 인공 바이러스 엔벨로프 및 폴리라이신 컨쥬게이트를 포함한 전달 메커니즘뿐만 아니라 많은 발현 컨스트럭트/벡터를 제공하고 있다.siRNA has the potential to be a very strong drug against inhibition of the expression of specific genes in vivo in terms of its long-lasting effect in cell culture and in vivo, ability to transfect cells in vivo, and resistance to degradation in serum. (Bertrand et al., 2002). Delivery of siRNA and expression constructs/vectors including siRNA are known to those of skill in the art. For example, U.S. applications 2004/106567 and 2004/0086884 describe many expression constructs as well as delivery mechanisms including viral vectors, non-viral vectors, liposome delivery vehicles, plasmid injection systems, artificial viral envelopes and polylysine conjugates. T/vector is provided.

siRNA는 상대적으로 낮은 농도로도 안티센스 올리고뉴클레오타이드에 의해 얻을 수 있는 효과와 동등하거나 높은 효과를 얻을 수 있기 때문에 안티센스 올리고뉴클레오타이드의 대안으로 제시되고 있다(Thompson, 2002). siRNA의 이용은 질병의 동물 모델에 있어서 유전자 발현을 저해하는 데 대중성을 나타내고 있다. 당업자는 당해 기술 분야에 공지된 방법을 이용하여 원하는 방식대로 상기 안티센스 올리고뉴클레오타이드 및 siRNA를 합성하고 변형시킬 수 있다(예를 들어, Andreas Henschel, Frank Buchholz1 and Bianca Habermann (2004) DEQOR: a web-based tool for the design and quality control of siRNAs. Nucleic Acids Research 32(Web Server Issue):W113-W120. 참조). 또한 당업자는 안티센스 올리고뉴클레오타이드 또는 siRNA를 지닌 발현 컨스트럭트/벡터에 유용한 조절 서열(예컨대, 구성적 프로모터, 유도성 프로모터, 조직-특이적 프로모터 또는 그의 결합)을 잘 이해하고 있다.siRNA has been suggested as an alternative to antisense oligonucleotides because it can obtain an effect equal to or higher than that obtained by antisense oligonucleotides even at a relatively low concentration (Thompson, 2002). The use of siRNA has shown popularity in inhibiting gene expression in animal models of disease. Those skilled in the art can synthesize and modify the antisense oligonucleotides and siRNAs in a desired manner using methods known in the art (e.g., Andreas Henschel, Frank Buchholz1 and Bianca Habermann (2004) DEQOR: a web-based tool for the design and quality control of siRNAs.Nucleic Acids Research 32 (Web Server Issue):W113-W120. Reference). In addition, those skilled in the art are well aware of regulatory sequences useful for expression constructs/vectors with antisense oligonucleotides or siRNAs (eg, constitutive promoters, inducible promoters, tissue-specific promoters or combinations thereof).

대장암 치료를 위해 사용되는 본 발명의 안티센스 올리고뉴클레오타이드 또는 siRNA는 약제학적으로 허용되는 담체를 추가적으로 포함한 조성물의 형태로 투여될 수 있다. 적당한 약제학적으로 허용되는 담체는 예를 들어 하나 이상의 물, 식염수, 인산 완충 식염수, 덱스트린, 글리세롤, 에탄올뿐만 아니라 이들의 조합을 포함한다. 이러한 조성물은 투여 후 활성 성분의 빠른 방출, 또는 지속적이거나 지연된 방출을 제공하도록 제제화될 수 있다.The antisense oligonucleotide or siRNA of the present invention used for the treatment of colorectal cancer may be administered in the form of a composition additionally comprising a pharmaceutically acceptable carrier. Suitable pharmaceutically acceptable carriers include, for example, one or more of water, saline, phosphate buffered saline, dextrin, glycerol, ethanol, as well as combinations thereof. Such compositions may be formulated to provide rapid release, or sustained or delayed release of the active ingredient after administration.

상기 유전자의 저해제는 안티센스 올리고뉴클레오타이드 또는 siRNA 외에도 상기 유전자의 발현을 억제하는 물질이면 어떤 것이든 가능하다. 따라서 종래 당해 기술 분야에서 상기 유전자의 저해제로 알려진 화합물 또한 이용가능하다.In addition to the antisense oligonucleotide or siRNA, the inhibitor of the gene may be any substance that inhibits the expression of the gene. Therefore, conventionally known compounds as inhibitors of the gene in the art can also be used.

본 발명은 또한 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501로 이루어진 군에서 선택된 하나 이상의 유전자로부터 발현된 단백질에 대한 억제제를 포함하는 대장암 치료용 조성물을 제공한다.The present invention also provides a composition for treating colorectal cancer comprising an inhibitor for a protein expressed from one or more genes selected from the group consisting of C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501.

본 발명의 유전자를 억제하면 그에 따른 단백질의 발현이 억제되어 대장암이 억제되는 것이므로, 상기 유전자의 단백질을 저해하면 대장암을 억제할 수 있다.Inhibiting the gene of the present invention suppresses the expression of the corresponding protein, thereby suppressing colorectal cancer, and inhibiting the protein of the gene may suppress colorectal cancer.

따라서 본 발명은 상기 단백질에 대한 억제제의 대장암 치료 용도 및 유효량의 상기 단백질의 억제제를 환자에게 투여하는 단계를 포함하는 대장암 치료방법을 제공한다. 본 발명에 있어서 대장암 치료는 대장암의 예방 및 억제를 포함한다.Accordingly, the present invention provides a method for treating colorectal cancer, including the use of the inhibitor for the protein for the treatment of colorectal cancer and administering an effective amount of the inhibitor for the protein to a patient. In the present invention, the treatment of colon cancer includes the prevention and inhibition of colon cancer.

상기 단백질에 대한 억제제는 본 발명의 유전자로부터 발현된 단백질에 대한 항체일 수 있다. 상기 단백질에 대한 모노클로날 항체는 당업계에 통상적인 모노클로날 항체 제작 방법을 통해 제작되어 사용될 수도 있고, 시판되는 것을 사용할 수 있다. 또한, 모노클로날 항체 대신에 상기 단백질을 인식하는 폴리클로날 항체를 사용할 수도 있고 이는 당업계에 통상적인 항혈청 제작 방법을 통해 제작되어 사용될 수도 있다.The inhibitor against the protein may be an antibody against a protein expressed from the gene of the present invention. The monoclonal antibody against the protein may be prepared and used through a method for producing a monoclonal antibody conventional in the art, or a commercially available one may be used. In addition, instead of a monoclonal antibody, a polyclonal antibody that recognizes the protein may be used, and it may be produced and used through a conventional antisera production method in the art.

본 발명의 대장암 치료용 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용되는 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다. 본 발명의 단백질에 대한 억제제가 항체일 경우 약제학적으로 허용되는 담체는 결합 단백질의 저장 수명 또는 유효성을 증가시키는 습윤제 또는 유화제, 방부제 또는 완충액과 같은 최소량의 보조 물질로 구성될 수 있다.The composition for treatment of colorectal cancer of the present invention may be preferably formulated as a pharmaceutical composition, including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration. When the inhibitor against the protein of the present invention is an antibody, the pharmaceutically acceptable carrier may be composed of a minimum amount of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers that increase the shelf life or effectiveness of the binding protein.

또한 본 발명의 대장암 치료용 조성물은 하나 또는 그 이상의 대장암치료제와 함께 사용될 수 있다. 본 발명의 대장암 치료용 조성물은 예를 들어 당업자에게 잘 알려진 화학요법약제(chemotherapeutic agent), 예컨대, 사이클로포스파마이드, 아지리딘, 알킬알콘설포네이트, 나이트로소우레아, 다카르바진, 카르보플라틴, 시스플라틴 등과 같은 알킬화제(alkylating agent), 마이토마이신 C, 안트라사이클린, 독소루비신(아드리아마이신) 등과 같은 항생제, 메토트렉세이트, 5-플루오로우라신, 시타라빈 등과 같은 항대사제(antimetabolitic agent), 빈카 알칼로이드와 같은 식물유래 약제 및 호르몬 등을 추가로 포함할 수 있다.In addition, the composition for treating colorectal cancer of the present invention may be used together with one or more colorectal cancer treatment agents. The composition for treating colorectal cancer of the present invention is, for example, chemotherapeutic agents well known to those skilled in the art, such as cyclophosphamide, aziridine, alkylalconsulfonate, nitrosourea, dacarbazine, carboplatin. , Alkylating agents such as cisplatin, antibiotics such as mitomycin C, anthracycline, doxorubicin (adriamycin), etc., antimetabolitic agents such as methotrexate, 5-fluorouracin, cytarabine, etc., such as vinca alkaloids. It may further include plant-derived drugs and hormones.

본 발명의 대장암 치료용 조성물은 상기 유효 성분 외에도 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 포함할 수 있으며, 이러한 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제, 또는 가용화제 등이 있다.The composition for treating colorectal cancer of the present invention may include a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and such adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, Lubricants, or solubilizing agents.

또한 본 발명의 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용되는 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.In addition, the composition of the present invention can be preferably formulated into a pharmaceutical composition, including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients for administration.

액상 용액으로 제제화되는 조성물에 있어서 허용되는 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Acceptable pharmaceutical carriers for compositions formulated as liquid solutions are sterilized and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as needed. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injection formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets. Further, it can be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

본 발명의 대장암 치료용 조성물의 약제 제제 형태는 과립제, 산제, 피복정, 정제, 캡슐제, 좌제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 및 활성 화합물의 서방출형 제제 등이 될 수 있다.The pharmaceutical formulation form of the composition for treating colorectal cancer of the present invention is granules, powders, coated tablets, tablets, capsules, suppositories, syrups, juices, suspensions, emulsions, drops or injectable liquids and sustained-release formulations of active compounds. Can be, etc.

본 발명의 대장암 치료용 조성물은 정맥내, 동맥내, 복강내, 근육내, 동맥내, 복강내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다.The composition for treatment of colorectal cancer of the present invention is through intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, nasal, inhalation, topical, rectal, oral, intraocular or intradermal routes. It can be administered in a conventional manner.

본 발명의 치료 방법에 있어서, "유효량"은 대장암을 억제하는 효과를 이루는데 요구되는 양을 의미한다. 따라서, 본 발명의 유효 성분의 "유효량"은 질환의 종류, 질환의 중증도, 조성물에 함유된 유효 성분 및 다른 성분의 종류 및 함량, 제형의 종류 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료 기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 성인의 경우, 상기 유전자 또는 단백질의 억제제를 1일 1회 내지 수회 투여시, siRNA일 경우 0.01ng/kg~10㎎/kg, 상기 유전자의 mRNA에 대한 안티센스 올리고뉴클레오타이드인 경우 0.01ng/kg~10㎎/kg, 화합물일 경우 0.1ng/kg~10㎎/kg, 상기 단백질에 대한 모노클로날 항체일 경우 0.1ng/kg~10㎎/kg의 용량으로 투여하는 것이 바람직하다.In the treatment method of the present invention, "effective amount" means an amount required to achieve an effect of inhibiting colon cancer. Accordingly, the "effective amount" of the active ingredient of the present invention is the type of disease, the severity of the disease, the type and content of the active ingredient and other ingredients contained in the composition, the type of formulation and the age, weight, general health condition, sex, and It can be adjusted according to a variety of factors, including diet, administration time, route of administration and rate of secretion of the composition, duration of treatment, and drugs used concurrently. In the case of adults, when the gene or protein inhibitor is administered once to several times a day, for siRNA 0.01 ng/kg to 10 mg/kg, for antisense oligonucleotides for the mRNA of the gene 0.01 ng/kg to 10 In the case of mg/kg, the compound is preferably administered at a dose of 0.1 ng/kg to 10 mg/kg, and in the case of a monoclonal antibody against the protein, 0.1 ng/kg to 10 mg/kg.

본 발명에 있어서, 상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644 유전자는 표 1의 염기서열 또는 상기 염기서열 중 하나 이상의 염기가 결실, 치환 또는 삽입된 염기서열일 수 있다.In the present invention, the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes have a nucleotide sequence of Table 1 or one or more of the nucleotide sequences deleted, It may be a substituted or inserted nucleotide sequence.

상기 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 및 상기 유전자의 siRNA 서열은 예시일 뿐 이에 한정되는 것이 아님은 당업자에게 자명하다. 상기 서열들에 대해 실질적인 서열 동일성 또는 실질적인 서열 상동성을 지닌 서열 또한 본 발명의 범주에 포함된다. 여기서 사용된 "실질적인 서열 동일성" 또는 "실질적인 서열 상동성"이라는 용어는 서열이 또 다른 서열과의 실질적인 구조적 또는 기능적 동일성을 나타냄을 표현하기 위해 사용된다. 이러한 차이는 예를 들어 다른 종 간의 코돈 용법의 고유의 변이에 기인한다. 2 이상의 다른 서열 사이의 유의적인 양의 서열 중복 또는 유사성이 있는 경우 이들 서열의 길이 또는 구조가 다르더라도 유사한 물리적 특성을 지니는 경우 구조적 차이는 무시할만한 정도가 된다.The C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 genes, the sense and antisense primer pairs of the gene, and the siRNA sequence of the gene are only examples. It is obvious to a person skilled in the art that it is not possible. Sequences having substantial sequence identity or substantial sequence homology to the above sequences are also included in the scope of the present invention. As used herein, the terms “substantial sequence identity” or “substantial sequence homology” are used to express that a sequence exhibits substantial structural or functional identity with another sequence. These differences are due to, for example, inherent variations in codon usage between different species. If there is a significant amount of sequence overlap or similarity between two or more different sequences, even if the lengths or structures of these sequences are different, if they have similar physical properties, the structural difference is negligible.

본 발명에서 유전공학적 기술과 관련된 사항은 샘브룩 등의 문헌(Sambrook, et al. Molecular Cloning, A Laboratory Manual, Cold Spring Harbor laboratory Press, Cold Spring Harbor, N. Y. (2001)) 및 프레드릭 등의 문헌 (Frederick M. Ausubel et al., Current protocols in molecular biology volume 1, 2, 3, John Wiley & Sons, Inc. (1994))에 개시되어 있는 내용에 의해 보다 명확하게 된다.In the present invention, matters related to genetic engineering techniques are described in Sambrook et al. Molecular Cloning, A Laboratory Manual, Cold Spring Harbor laboratory Press, Cold Spring Harbor, NY (2001) and Frederick et al. M. Ausubel et al., Current protocols in molecular biology volume 1, 2, 3, John Wiley & Sons, Inc. (1994)).

C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 또는 KIAA1644 유전자는 대장암과 높은 관련성을 가지므로, 상기 유전자의 발현량을 확인함으로써 대장암의 진단, 약물스크리닝 등이 가능하고, 본 발명의 유전자를 대장암 치료타겟으로 할 수 있다.C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, or KIAA1644 genes are highly related to colon cancer. Drug screening and the like are possible, and the gene of the present invention can be used as a treatment target for colorectal cancer.

도 1은 대장암 유전자의 마이크로어레이 결과를 나타낸 사진이다.
도 2는 임상조직에서 대장암 고발현 유전자의 발현량을 나타낸 RT-PCR결과 사진이다.
도 3은 임상조직에서 대장암 저발현 유전자의 발현량을 나타낸 RT-PCR결과 사진과 KIAA1644유전자의 발현비를 나타낸 그래프이다.
도 4는 대장암세포주에서 대장암 고발현 유전자의 발현비(대장암세포주/정상조직)를 나타낸 그래프이다.
도 5는 대장암세포주에서 대장암 저발현 유전자의 발현비(대장암세포주/정상조직)를 나타낸 그래프이다.
1 is a photograph showing a microarray result of a colon cancer gene.
2 is a picture of RT-PCR results showing the expression level of a high-expression gene for colon cancer in clinical tissues.
Figure 3 is a graph showing the expression ratio of the KIAA1644 gene and a picture of the RT-PCR result showing the expression level of the low-expression gene for colon cancer in clinical tissues.
4 is a graph showing the expression ratio (colorectal cancer cell line/normal tissue) of a high-expressing colon cancer gene in a colorectal cancer cell line.
5 is a graph showing the expression ratio (colorectal cancer cell line/normal tissue) of a colon cancer low-expression gene in a colorectal cancer cell line.

본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 상세하게 후술되어 있는 실시예들을 참조하면 명확해질 것이다. 그러나 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하고, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.
Advantages and features of the present invention, and a method of achieving them will become apparent with reference to the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in a variety of different forms, only the present embodiments are intended to complete the disclosure of the present invention, and the general knowledge in the technical field to which the present invention pertains. It is provided to completely inform the scope of the invention to the possessor, and the invention is only defined by the scope of the claims.

<실시예 1> 대장암진단용 유전자 확인<Example 1> Confirmation of the gene for colon cancer diagnosis

1-1. 대장암 임상조직과 정상조직, 6개의 대장암 세포주에서 총 RNA 분리1-1. Total RNA isolation from clinical and normal tissues for colon cancer and 6 colon cancer cell lines

(1) 대장암 임상조직의 준비(1) Preparation of clinical tissue for colon cancer

66쌍의 환자의 대장암 조직과 정상 조직은 삼성의료원으로부터 공급 받았다. 임상조직은 환자로부터 외과적으로 제거된 후, 분석때 까지 이를 액체질소에 보관하였다.Colon cancer tissues and normal tissues of 66 pairs of patients were supplied by Samsung Medical Center. After the clinical tissue was surgically removed from the patient, it was stored in liquid nitrogen until analysis.

(2) 대장암 세포주의 준비(2) Preparation of colorectal cancer cell line

10% 소혈청(Fetal Bovine Serum, GIBCO사), 페니실린 (10000U/ml)과 스트렙토마이신(10mg/ml) 을 첨가한 RPMI1640 (GIBCO) 배양액을 10mm 디쉬에 10ml씩 분주한 후 대장암 세포주인 HT29, SW480, DLD1, HCT116, SW620, Colo205(각각의 입수처 기재바랍니다.) 를 디쉬당 세포수가 1X106 이 되도록 접종하고 이를 37℃, 5% CO2 가 존재하는 배양기에서 배양하였다.10% of RPMI1640 (GIBCO) culture solution containing 10% bovine serum (Fetal Bovine Serum, GIBCO), penicillin (10000U/ml) and streptomycin (10mg/ml) was dispensed into a 10mm dish each 10ml, and then colon cancer cell line HT29, SW480, DLD1, HCT116, SW620, Colo205 (please describe each source) were inoculated so that the number of cells per dish was 1×10 6 and cultured in an incubator with 37° C. and 5% CO 2.

(3) 총 RNA 분리(3) total RNA isolation

총 RNA는 QIAGEN 킷트 (RNeasy Maxi kit: cat #75162)를 사용하여 분리하였고, Experion RNA StdSens(Bio-Rad사) 칩을 이용하여 정량하였다. 우선 상기 대장암 임상조직과 정상조직을 적절한 크기로 자른 후 150ul 의 베타 멀캅토 에탄올을 첨가한 15ml의 키트 내 분해 완충액에 용해시켰다. 여기에 15ml의 70% 에탄올을 넣어 잘 섞은 후, 3000g에서 5분간 원심분리하여 총 RNA를 막에 부착시켰다. 두 차례의 세척을 항 후 1.2ml의 RNase가 없는 물을 첨가하여 총 RNA를 분리하였다. 부착된 세포주의 경우는 트립신, EDTA를 이용하여 회수한 후 키트 내 분해 완충액 RLN (50mM TrisCl, pH 8.0, 140mM NaCl, 1.5mM MgCl2, 0.5% NP-40) 1ml에 베타 멀캅토 에탄올 10ul 를 첨가하여 용해시켰다. 여기에 1ml의 70% 에탄올을 넣어 잘 섞은 후, 3000g에서 5분간 원심분리하여 총 RNA를 막에 부착시켰다. 두 차례의 세척을 한 후 100ul의 RNase가 없는 물을 첨가하여 총 RNA를 분리하였다.Total RNA was isolated using a QIAGEN kit (RNeasy Maxi kit: cat #75162), and quantified using an Experion RNA StdSens (Bio-Rad) chip. First, the colon cancer clinical tissues and normal tissues were cut into appropriate sizes, and then dissolved in 15 ml of a digestion buffer in a kit to which 150 ul of beta mercapto ethanol was added. 15 ml of 70% ethanol was added thereto, mixed well, and then centrifuged at 3000 g for 5 minutes to attach total RNA to the membrane. After two washings, 1.2 ml of RNase-free water was added to isolate total RNA. In the case of the attached cell line, after recovering using trypsin or EDTA, 10ul of beta mercapto ethanol was added to 1 ml of the digestion buffer RLN (50mM TrisCl, pH 8.0, 140mM NaCl, 1.5mM MgCl2, 0.5% NP-40) in the kit. Dissolved. 1 ml of 70% ethanol was added thereto, mixed well, and then centrifuged at 3000 g for 5 minutes to attach total RNA to the membrane. After washing twice, 100ul of RNase-free water was added to isolate total RNA.

1-2. 총 RNA를 이용한 마이크로어레이 실시 및 대장암 진단용 유전자 확인1-2. Microarray using total RNA and identification of genes for colon cancer diagnosis

(1) 마이크로어레이 실시(1) Microarray implementation

하이브리드화를 위해 실시예 1-1에서 추출된 총 RNA를 Illumina TotalPrep RNA Amplification Kit (Ambion사)을 이용하였다. T7 Oligo(dT) primer를 이용하여 cDNA를 합성하고, biotin-UTP를 이용하여 in vitro transcription을 실시하여 biotin-labeled cRNA를 제조하였다. 제조된 cRNA는 NanoDrop(Nanodrop사, ND-1000)을 이용하여 정량하였다. 정상 대장 상피세포 및 대장암 세포에서 제조된 cRNA를 Human-6 V2 (Illumina사) 칩에 하이브리드화 하였다. 하이브리드화 후 비특이적 하이브리드화를 제거하기 위하여 Illumina Gene Expression System 세척액 (Illumina사)을 이용하여 Illumina Human-6 V2칩을 세척하였고, 세척된 Illumina Human-6 V2칩은 streptavidin-Cy3(Amersham사) 형광 염색약으로 표지하였다. 형광 표지된 DNA 칩은 공촛점(confocal) 레이저 스캐너 (Illumina사)를 이용하여 스캐닝하여 각 스팟에 존재하는 형광의 데이터를 얻어서 TIFF 형태의 이미지 파일로 저장하였다. TIFF 이미지 파일을 BeadStudio version 3(Illumina사)으로 정량하여 각 스팟의 형광값을 정량하였다. 정량된 결과는 Avadis Prophetic version 3.3(Strand Genomics사) 프로그램으로 ‘quantile’ 기능을 이용하여 보정하였다.For hybridization, the total RNA extracted in Example 1-1 was used using the Illumina TotalPrep RNA Amplification Kit (Ambion). CDNA was synthesized using T7 Oligo(dT) primer, and in In vitro transcription was performed to prepare biotin-labeled cRNA. The prepared cRNA was quantified using NanoDrop (Nanodrop, ND-1000). The cRNA prepared from normal colon epithelial cells and colon cancer cells was hybridized to a Human-6 V2 (Illumina) chip. After hybridization, to remove non-specific hybridization, the Illumina Human-6 V2 chip was washed with an Illumina Gene Expression System washing solution (Illumina), and the washed Illumina Human-6 V2 chip was streptavidin-Cy3 (Amersham) fluorescent dye. Labeled with. The fluorescence-labeled DNA chip was scanned using a confocal laser scanner (Illumina) to obtain fluorescence data present in each spot, and stored as a TIFF image file. The TIFF image file was quantified with BeadStudio version 3 (Illumina) to quantify the fluorescence value of each spot. The quantified results were corrected using the'quantile' function with the Avadis Prophetic version 3.3 (Strand Genomics) program.

(2) 대장암 진단용 유전자 확인(2) Confirmation of genes for colon cancer diagnosis

상기의 과정으로 얻어진 1,601개의 유전자 발현 정도 분석을 통하여 정상 대장 상피세포와 대장암 세포의 유전자 발현 양상을 비교 분석하여, 대장암 진단용 유전자를 확인하였다. 군집화 분석(hierarchical clustering analysis)를 이용하여 유전자 발현양상을 분석하였으며, 그 결과, 정상 대장 상피세포와 대장암 세포는 크게 두 개의 군집으로 나누어지는 것을 알 수 있었다 (정상과 대장암조직). 또한, 정상 대장 상피세포와 대장암 세포를 비교하여 60% 이상의 환자에서 2배 이상의 발현차이를 나타내는 유전자들을 발견할 수 있었으며, 이중 고발현과 저발현이 각각 281개 및 605개였고, 현재 대장암에서 유전자 발현량의 변화가 보고되지 않은 대장암 마커 유전자 후보를 선발할 수 있었다.Through the analysis of the expression level of 1,601 genes obtained by the above process, the gene expression patterns of normal colon epithelial cells and colon cancer cells were compared and analyzed to confirm the gene for colon cancer diagnosis. The gene expression patterns were analyzed using hierarchical clustering analysis, and as a result, it was found that normal colon epithelial cells and colon cancer cells are largely divided into two clusters (normal and colon cancer tissues). In addition, by comparing normal colon epithelial cells and colorectal cancer cells, genes showing a two-fold or more difference in expression were found in more than 60% of patients, of which 281 and 605 high and low expressions were respectively. Colorectal cancer marker gene candidates for which no change in expression level was reported could be selected.

정상조직을 대조군으로 한 대장암 조직에서의 각 유전자의 발현량을 고발현되는 유전자의 경우 붉은색으로, 저발현되는 유전자의 경우 초록색으로 나타내었다 (도 1). 도 1에 나타난 바와 같이, 고발현 유전자로 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 및 LOC144501을 확인하였고, 저발현 유전자로 FLJ22655, ZG16, VMD2L2, MS4A12, 및 KIAA1644를 확인하였다.The expression level of each gene in colon cancer tissues with normal tissues as a control is shown in red for high-expressing genes and green for low-expressing genes (FIG. 1). As shown in FIG. 1, as high-expression genes, C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501 were identified, and as low-expression genes, FLJ22655, ZG16, VMD2L2, MS4A12, and KIAA1644 were identified.

또한, 상기 각각의 유전자에 대해 마이크로어레이 상의 구체적인 변화율과 유의성(P값), 2배이상 변화한 시료의 수, 그리고 유전자의 정의 및 알려진 기능을 표 3에 나타내었다. 표 3에 나타난 바와 같이 고발현 유전자와 저발현 유전자는 정상 대장 상피세포와 비교하여 발현차이를 크게 나타내므로, 대장암 진단, 약물 스크리닝, 또는 치료타겟 등으로 사용할 수 있음을 알 수 있다.In addition, for each gene, the specific rate of change and significance (P value) on the microarray, the number of samples that changed more than twice, and the definition and known function of the gene are shown in Table 3. As shown in Table 3, since the high-expression gene and the low-expression gene show a large difference in expression compared to normal colon epithelial cells, it can be seen that it can be used as a colon cancer diagnosis, drug screening, or treatment target.

Figure pat00003
Figure pat00003

<실시예 2> 임상시료에서 대장암진단용 유전자 발현 확인<Example 2> Confirmation of gene expression for colon cancer diagnosis in clinical samples

17쌍의 임상환자 샘플(실시예 1의 66쌍의 대장암 환자로부터 채취한 대장암조직(T1~T66)과 정상조직(N1~N66) 중 임상2기에 해당하는 환자조직 17쌍(T1~T17, N1~N17))을 이용하였으며, 실시예 1에서 확인된 8종의 대장암 고발현 유전자와 5종의 대방암 저발현 유전자의 발현량을 RT-PCR 방법을 통하여 분석하였다.17 pairs of clinical patient samples (from the colon cancer tissues (T1 to T66) and normal tissues (N1 to N66) collected from 66 pairs of colorectal cancer patients in Example 1, 17 pairs of patient tissues corresponding to the second clinical stage (T1 to T17) , N1 to N17)) were used, and the expression levels of 8 kinds of high-expression genes for colon cancer and 5 kinds of low-expression genes for large breast cancer identified in Example 1 were analyzed through RT-PCR method.

2-1. 역전사 효소 반응에 의한 cDNA 합성2-1. CDNA synthesis by reverse transcriptase reaction

17쌍의 임상환자 샘플(실시예 1의 66쌍의 대장암 환자로부터 채취한 대장암조직(T1~T66)과 정상조직(N1~N66) 중 임상2기에 해당하는 환자조직 17쌍(T1~T17, N1~N17))의 RNA 를 이용하여 cDNA를 합성하였다. 시료 각각의 총 RNA 5ug, 프라이머인 50uM Olgo(dT)20 1ul와 10mM dNTP 2.5ul,를 넣고 RNase 저해제인 DEPC 가 들어 있는 멸균수로 전체가 25ul 가 되도록 하여 RNA/primer 혼합용액을 만들었다. 17 pairs of clinical patient samples (from the colon cancer tissues (T1 to T66) and normal tissues (N1 to N66) collected from 66 pairs of colorectal cancer patients in Example 1, 17 pairs of patient tissues corresponding to the second clinical stage (T1 to T17) , N1 ~ N17)) of cDNA was synthesized using RNA. 5 ug of total RNA of each sample, 1 ul of 50uM Olgo(dT)20 and 2.5 ul of 10mM dNTP, were added to each sample, and the total was 25 ul with sterile water containing DEPC, an RNase inhibitor, to prepare an RNA/primer mixed solution.

65℃에서 5분간 반응시킨 후 55℃로 옮겨 보관하였다. 다음 10X RT buffer 5ul, 25mM MgCl2 10ul, 0.1M DTT 5ul, RNase inhibitor 1ul, SuperScriptIII RT 효소를 1ul 넣고 전체가 25ul 가 되도록 한 후 55℃에서 보관 중인 RNA/primer 혼합용액과 섞어준 후, 55℃에서 50분간 반응시켰다. 그 후 85℃에서 5분간 반응시켜 RT 효소를 불활성화 한후 얼음에 넣어 반응을 종결시켰다. PCR 을 하기 전에 cDNA sample에 RNase 1ul 를 처리하여 37℃에서 20분간 반응 시켜 RNA 를 제거한 후 PCR 반응을 하였다.After reacting at 65° C. for 5 minutes, it was transferred to 55° C. and stored. Next, add 5ul of 10X RT buffer, 5ul of 25mM MgCl 2 , 5ul of 0.1M DTT, 1ul of RNase inhibitor, and 1ul of SuperScriptIII RT enzyme, make the total volume to 25ul, and mix it with the RNA/primer mixture solution stored at 55℃. Reacted for 50 minutes. Thereafter, the reaction was performed at 85° C. for 5 minutes to inactivate the RT enzyme, and then put in ice to terminate the reaction. Before PCR, cDNA sample was treated with 1ul of RNase and reacted at 37°C for 20 minutes to remove RNA, followed by PCR reaction.

2-2. PCR 을 통한 cDNA 증폭과 발현량 확인2-2. Confirmation of cDNA amplification and expression level through PCR

(1) 주형의 농도 보정(1) Correction of the concentration of the mold

마커유전자를 정량하기 위한 표준 유전자로서 GAPDH를 사용하였다. 표준 유전자의 프라이머를 이용하여 PCR 반응을 수행하고 표준 유전자 GAPDH의 발현량이 동일해지도록 cDNA의 농도를 보정하였다.GAPDH was used as a standard gene for quantifying the marker gene. PCR reaction was performed using the primers of the standard gene, and the concentration of cDNA was corrected so that the expression level of the standard gene GAPDH was the same.

우선 각각의 cDNA를 20배 희석한 후 희석된 샘플 2ul를 이용하여 PCR 반응을 수행하였다. PCR은 2X PCR premix (바이오니아사) 15ul, 2ul의 GAPDH 5' 프라이머(20pmole), 2ul 의 3' 프라이머(20pmole), 11ul 의 증류수를 넣어 사용하였고 20 cycle, 23cycle, 25cycle 을 수행하였다. 이 때 PCR 반응 조건은 94℃ 30초, 50℃ 30초, 72℃ 1분으로 수행하였으며, 산물의 크기는 457bp 이다.First, each cDNA was diluted 20 times, and a PCR reaction was performed using 2ul of the diluted sample. PCR was used by adding 15ul of 2X PCR premix (Bionia), 2ul of GAPDH 5'primer (20pmole), 2ul of 3'primer (20pmole), and 11ul of distilled water, and 20 cycles, 23 cycles, and 25 cycles were performed. At this time, PCR reaction conditions were carried out at 94°C for 30 seconds, 50°C for 30 seconds, and 72°C for 1 minute, and the size of the product is 457bp.

PCR 산물을 2% 아가로스 젤에 로딩하여 전기영동한 후 젤 사진을 찍고, 이미지를 TotalLab v1.0 프로그램[Nonlinear Dynamix사] 으로 정량 한 후, 다시 보정하여 PCR을 수행하여 정량하는 방식으로 각 시료의 농도를 동일하게 보정하였다.The PCR product is loaded on a 2% agarose gel, subjected to electrophoresis, and then a gel photo is taken, and the image is quantified with the TotalLab v1.0 program [Nonlinear Dynamix], and then re-calibrated to perform PCR to quantify each sample. The concentration of was equally corrected.

(2) PCR 에 의한 대장암 마커 유전자 증폭(2) Amplification of colon cancer marker gene by PCR

상기 (1)에서 보정된 시료를 20배 희석한 cDNA 를 각 유전자의 센스 및 안티센스 프라이머를 이용하여 PCR 하였다. PCR반응은 94도 1분, 54도 30초, 72도 1분으로 하였으며 cycle 수는 각 유전자의 샘플내의 농도에 따라 보정하면서 실시하였다. 적게는 25cycle을 수행하였으며 많게는 38cycle을 수행하였다. PCR 반응용액 조성은 표 4와 같고, 사용된 프라이머는 표 5와 같다.The cDNA obtained by diluting the sample corrected in (1) by 20 times was PCR using the sense and antisense primers of each gene. The PCR reaction was performed at 94 degrees 1 minute, 54 degrees 30 seconds, 72 degrees 1 minute, and the number of cycles was corrected according to the concentration in the sample of each gene. Less than 25 cycles were performed, and as many as 38 cycles. The composition of the PCR reaction solution is shown in Table 4, and the primers used are shown in Table 5.

Figure pat00004
Figure pat00004

Figure pat00005
Figure pat00005

대장암 관련 8종의 고발현 유전자인 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501 과 저발현 유전자 5종 FLJ22655, ZG16, VMD2L2, MS4A12, KIAA1644 의 프라이머는 단백질 코딩 내부에서 디자인 하였으며 각 프라이머의 길이는 20mer 이고 Tm 값은 55도 근처이다.The primers for 8 high-expression genes related to colon cancer, C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, and LOC144501, and 5 low-expression genes FLJ22655, ZG16, VMD2L2, MS4A12, KIAA1644 were designed inside the protein coding. The length of the primer is 20mer and the Tm value is around 55 degrees.

(3) 발현량 확인(3) Confirmation of expression level

PCR 산물을 확인하기 위하여 2% 아가로스 젤을 이용하여 전기영동하고 이미지 장비를 이용하여 분석하였다.To confirm the PCR product, electrophoresis was performed using 2% agarose gel and analyzed using an imaging device.

그 결과를 도 2 및 도 3에 나타내었으며, 도 2는 임상조직에서 대장암 고발현 유전자의 발현량을 나타낸 RT-PCR 결과사진이고, 도 3은 임상조직에서 대장암 저발현 유전자의 발현량을 나타낸 RT-PCR 결과사진과 KIAA1644의 발현량 그래프이다. 사진에서 N은 정상조직(nontumer 조직)을 의미하며, T는 그에 해당하는 대장암 조직을 의미한다. 확연한 차를 보이는 유전자에 대해서는 아가로스젤 이미지 사진으로 나타내었고, 발현량의 차이가 적은 KIAA1644의 경우는 이미지 사진을 TotalLab v1.0 프로그램[Nonlinear Dynamix사]으로 정량 한 후 GAPDH로 보정하고 그래프로 다시 나타내었다. 상기 그래프의 X축은 임상시료를 나타낸 것이며 Y축은 발현비(대장암조직/정상조직)를 나타낸다. 상기 발현비는 대장암 조직에서 발현되는 양(각각의 마커유전자의 발현량을 표준유전자인 GAPDH의 발현량으로 보정하여 준 값)을 각각의 셋트의 정상 대장 조직에서 발현되는 발현량으로 나누어 준 값이다.The results are shown in FIGS. 2 and 3, and FIG. 2 is a picture of RT-PCR results showing the expression level of a high-expressing colon cancer gene in a clinical tissue, and FIG. 3 is a photograph showing the expression level of a low-expressing colon cancer gene in a clinical tissue. This is a graph of the RT-PCR result and the expression level of KIAA1644. In the picture, N means normal tissue (nontumer tissue), and T means the corresponding colon cancer tissue. Genes showing obvious differences were shown in agarose gel images, and in the case of KIAA1644 with a small difference in expression levels, the images were quantified with TotalLab v1.0 program [Nonlinear Dynamix], corrected with GAPDH, and then again as a graph. Indicated. The X-axis of the graph represents the clinical sample, and the Y-axis represents the expression ratio (colorectal cancer tissue/normal tissue). The expression ratio is a value obtained by dividing the amount expressed in colon cancer tissues (a value obtained by correcting the expression level of each marker gene by the expression level of the standard gene GAPDH) by the expression level expressed in each set of normal colon tissues. to be.

그 결과 13종의 유전자들은 확연히 대장암 시료에서 고발현되거나 저발현됨을 확인하였고, 고발현되는 대장암 마커 유전자 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 또는 LOC144501는 대장암의 진단, 또는 약물스크리닝 등을 위한 대장암마커, 또는 치료타겟 등으로 사용할 수 있고, 저발현되는 유전자 FLJ22655, ZG16, VMD2L2, MS4A12 또는 KIAA1644는 대장암의 진단, 또는 약물스크리닝 등을 위한 대장암억제 마커로 사용가능할 것으로 보인다.
As a result, it was confirmed that 13 kinds of genes are clearly expressed high or low in colorectal cancer samples, and high-expressing colorectal cancer marker genes C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, or LOC144501 are the diagnosis of colorectal cancer, Alternatively, the genes FLJ22655, ZG16, VMD2L2, MS4A12, or KIAA1644 can be used as a colon cancer marker for drug screening, or as a therapeutic target, and are used as colon cancer inhibitory markers for diagnosis of colon cancer or drug screening. It seems to be possible.

<실시예 3> 대장암세포주에서의 대장암 진단용 유전자의 발현량 확인<Example 3> Confirmation of the expression level of a colon cancer diagnostic gene in a colon cancer cell line

실시예 2에서 발현량의 변화가 확인된 유전자에 대해서 대장암 세포주를 이용하여 그 발현량을 조사하였다. 실시예2와 동일하게 추출한 RNA를 이용하여 cDNA를 만들고 RT-PCR로 발현량을 조사하였다.For the gene whose expression level was confirmed in Example 2, the expression level was investigated using a colon cancer cell line. Using RNA extracted in the same manner as in Example 2, cDNA was prepared and the expression level was investigated by RT-PCR.

3-1. cDNA 합성3-1. cDNA synthesis

실시예 1의 6개의 대장암 세포주( HT29, SW480, DLD1, HCT116, SW620, Colo205) 각각의 총 RNA를 사용한 것을 제외하고는 실시예 2와 동일하게 수행하였다.Example 2 was performed in the same manner as in Example 2, except that total RNA of each of the six colorectal cancer cell lines (HT29, SW480, DLD1, HCT116, SW620, Colo205) was used.

3-2. PCR 을 통한 cDNA 증폭과 발현량 확인3-2. Confirmation of cDNA amplification and expression level through PCR

실시예 2와 동일하게 주형의 농도 보정, PCR 에 의한 유전자 증폭, 및 발현량 확인을 하였다.
In the same manner as in Example 2, the concentration of the template was corrected, gene amplification by PCR, and expression level were confirmed.

그 결과를 도 4와 도 5에 나타냈으며, 도 4는 대장암세포주에서 대장암 고발현 유전자의 발현량을 나타낸 그래프이고, 도 5는 대장암세포주에서 대장암 저발현 유전자의 발현량을 나타낸 그래프이다. 도 4 및 도 5의 y축에는 표준 유전자인 GAPDH로 보정한 PCR 산물의 량을 실시예 2의 정상 대장조직에서의 발현량의 평균값으로 나누어 준 값을 나타낸 것이며, x축은 대장암세포주를 나타낸 것이다.The results are shown in FIGS. 4 and 5, and FIG. 4 is a graph showing the expression level of a colon cancer high-expression gene in a colon cancer cell line, and FIG. 5 is a graph showing the expression level of a colon cancer low-expression gene in a colon cancer cell line. to be. The y-axis of FIGS. 4 and 5 represents a value obtained by dividing the amount of the PCR product corrected with the standard gene GAPDH by the average value of expression in the normal colon tissue of Example 2, and the x-axis represents the colon cancer cell line. .

그 결과 8종의 대장암 고발현 유전자 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, 또는 LOC144501의 발현량은 대장암 세포주에서 대체적으로 높게 나타났으며, 저발현유전자 FLJ22655, ZG16, VMD2L2, MS4A12 또는 KIAA1644의 발현량은 대장암 세포주에서 대체적으로 낮게 나타났다.As a result, the expression levels of 8 high-expression genes C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, or LOC144501 were generally high in colon cancer cell lines, and low-expression genes FLJ22655, ZG16, VMD2L2, The expression level of MS4A12 or KIAA1644 was generally low in colorectal cancer cell lines.

이와 같은 결과는 C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, 또는 KIAA1644 유전자와 대장암의 관련성을 재확인해 주는 것으로써, 상기 유전자의 발현량을 확인함으로써 대장암의 진단, 약물스크리닝 등이 가능하고, 상기 유전자를 대장암 치료타겟으로 할 수 있음을 나타내는 것으로 보인다.Such a result confirms the relationship between the C13ORF18, C13ORF3, ASPM, ARID3A, C2ORF15, IQGAP3, LOC644773, LOC144501, FLJ22655, ZG16, VMD2L2, MS4A12, or KIAA1644 gene and colorectal cancer, thereby confirming the expression level of the gene. By doing so, it seems that it is possible to diagnose colorectal cancer, screening drugs, and the like, and that the gene can be used as a treatment target for colorectal cancer.

<110> Korea Research Institute of Bioscience and Biotechnology <120> Composition for diagnosing colorectal cancer and use thereof <130> P07-062-KRI-DA2 <160> 41 <170> KopatentIn 1.71 <210> 1 <211> 3993 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(3993) <223> Homo sapiens chromosome 13 open reading frame 18 (C13orf18), mRNA. <400> 1 ggatttctag gaggaccggc agaggcgcgc ataggtgcgt ggtgctgggc ccgggcgccg 60 cggcaccggt gtaggagcgc gcatctccag agtttcttcc atctgggcga cgtctcggtg 120 cctgcggcgg gaacggcgct ttgcttccct gaggagcttc tagagagcta cggtggcccc 180 cgtgtgggag gcggggggcg tggcggcgtc ggggcgtcgc tgtcccctcc tcggtagctc 240 tcctccctcc cctttctgct gttaccggga gcgcggtggc cacggaacgc tgcccggagc 300 cgcgcgaggg aggacccgac gcgcggcgtt tacccagcgc agcgttccac cgctcgggtt 360 tggctggata aaataaaaaa tggggatatt gacctcctgt cactactgca tggactttga 420 tggtttccaa tcattacttt ctcctctgtg tcaatctgcc tcttcgagaa attcatactc 480 ctgaatagct ctccagaccc ccagctggcc atgtggtgag ttcagggccc aaatcaagta 540 gtaccagcaa tcagggaact cctatctgtt ttgaatggat tcacaccagc cacaagcctg 600 gaaagatggt gtcacaatct acagtcaggc aggattctcc tgtggagccc tgggaaggga 660 tcagcgatca ctctggcatt attgatggtt cgcccagact cctgaacact gaccatcctc 720 cttgccaatt agacatcagg ctcatgaggc acaaagctgt ctggattaac ccccaggatg 780 tgcagcaaca gccgcaggac ttgcaatctc aggtgccagc agcagggaac agtgggaccc 840 attttgtgac agatgctgcc tctccctcag gcccttcacc ttcgtgcctc ggggactccc 900 tggcagagac aacgttgtct gaggatacca cagactccgt tggcagcgct tctccccatg 960 gctcgagtga aaagagtagc agcttctctc tgtcctcaac agaggtacac atggtccgcc 1020 caggatactc tcatcgggtg tctctgccca caagccctgg gattttggcc acctccccat 1080 atcctgagac tgacagtgct ttttttgagc cttcccatct gacatctgct gctgatgaag 1140 gtgctgttca agtcagtaga agaaccattt cttcgaattc cttctcacca gaggtatttg 1200 tgctgcctgt tgatgtagaa aaggaaaatg cccactttta tgttgcagat atgattatat 1260 cagcaatgga gaaaatgaag tgtaacattc tgagtcaaca gcagacagag agctggagta 1320 aagaagtcag tgggttactt gggagtgatc agcctgactc tgaaatgact tttgatacca 1380 acataaagca agagtctggg tcttctactt cttcatacag tggctatgaa ggttgtgctg 1440 tgttacaggt cagcccagtg actgaaacac gtacttacca tgatgtgaaa gagatttgca 1500 aatgcgatgt tgatgaattt gttattttag agcttggaga ttttaatgat atcacagaaa 1560 cctgtagctg ttcctgcagc tcctctaaga gtgtcactta tgagccagac ttcaattctg 1620 cagaactatt agccaaagag ctgtaccgcg tgttccagaa gtgctggata ctgtcagtag 1680 ttaattctca gctggcaggt tccctgagtg cagctggctc gatagtcgta aatgaagagt 1740 gtgtccgaaa agactttgaa tccagtatga atgtagtaca ggaaattaaa tttaagtcta 1800 ggatcagagg gactgaagac tgggctcctc ctagatttca aatcatattt aatattcatc 1860 caccactcaa gagggacctt gtggtggcag cccagaattt tttctgtgcc ggctgtggaa 1920 ctccagtaga gcctaagttt gtgaagcggc tccggtactg cgaataccta gggaagtatt 1980 tctgtgactg ctgccactca tatgcagagt cgtgcatccc tgcccgaatc ctgatgatgt 2040 gggacttcaa gaagtactac gtcagcaatt tctccaaaca gctgctcgac agcatatggc 2100 accagcccat tttcaatttg ctgagcatcg gccaaagcct gtatgcgaaa gccaaggagc 2160 tggacagagt gaaggaaatt caggagcagc tcttccatat caagaagctg ttgaagacct 2220 gtaggtttgc taacagtgca ttaaaggagt tcgagcaggt gccgggacac ttgactgatg 2280 agctccacct gttctccctt gaggacctgg tcaggatcaa gaaagggctg ctggcaccct 2340 tactcaagga cattctgaaa gcttcccttg cacatgtggc tggctgtgag ctgtgtcaag 2400 gaaagggctt tatttgtgaa ttttgccaga atacgactgt catcttccca tttcagacag 2460 caacatgtag aagatgttca gcgtgcaggg cttgctttca caaacagtgc ttccagtcct 2520 ccgagtgccc ccggtgtgcg aggatcacag cgaggagaaa acttctggaa agtgtggcct 2580 ctgcagcaac atgatgcccc tgagtactgt gaaaaagact gttcaacatg ccttatgata 2640 acaccgattt gtgtctatta ttggtgacat tgttttagat attgggtatt gtatattaag 2700 gaaaaagatg gtctatattc tctttattgc atatacttaa tgtttcaaaa gaatgcagat 2760 tctgtgttta agcacagggc tgatagttgt ggttttgttt acaaatgttc tgttttggct 2820 gctattggtt ttttaaagag gttttttata cttttgtatt tgaatagtta tgtttcactg 2880 atgctgagcc agtttgtatg tgtgtgcata tatgtgaact gtaactgaca agatgaatta 2940 ctcagtttct ctttctctaa agcttgtttg atgaaactgg ttggtccttt cagtgaacaa 3000 aaatatgacc ccaaatctgt ttgctctggc ttttatttct tcaggaagca gacttccact 3060 taaatgccat tttgtgattg tgtcaatcat acacatttta tttacttcag agtttgaata 3120 gagagtacac atttcttctg cagatttatt tcatgatgag tttgagttgc ttagcagggc 3180 gtgtgggtcc cgttgaagtg cagtttgaag caactgcttc tagatggcac tctttcaggt 3240 ggcacaaatt gaacctgtat ttgtcatctc tgttccacac actgcaatgt caagggatgc 3300 agaagtgagt agaattccat ccctgccctt gaggatcttg ctttaacaga tgtaaaactg 3360 aacataaggt atttgcagat ttaaacgaac tgggggaaat aatgaacagt gtgattctag 3420 taataacatt aaaatcatag acattgacta ataaggttaa atgaatcaca aaacctttat 3480 gaatttcttt tttctaatag ttcttatatg ttttcctgaa acatgtgagc ctattctttt 3540 ttcttctact ttctatatac tttctcccac ttgagaaagg ggccttgagg ctgggtccct 3600 tcatggtata cctttagact gaacggtttg caacctaggg cttgggcatt acattccctg 3660 ggattcacat gccctaacta aacctacctt gattttctca gacagcacag gcaggcaata 3720 aagcgtcaca gattgtcccc taaccccatc cagccatgtg tatgagtgtg ttttattcaa 3780 tgggatagta ctgagcacat gaaagaaatg aatgacttct gtcaatctct tttcattcag 3840 tcttctcatt ctgtcaattg ttttctcatc cgcagtgcct ctgccagaac tgtgctcaca 3900 tccattattt aagccagatc ttttctaagt attatagaag tgtagaggca catagaataa 3960 ataaaaccag acttcaaaaa aaaaaaaaaa aaa 3993 <210> 2 <211> 2888 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2888) <223> Homo sapiens chromosome 13 open reading frame 3 (C13orf3), mRNA. <400> 2 gcgtccggcg ccgagattca aactagtggc gggaggctgt gagctgagcg gtggggtctg 60 cgtacgcctg gagtccttcc ccgctgtgct cagcatggac cctatccgga gcttctgcgg 120 gaagctgcgg tctctggcca gcacgctgga ctgcgagacg gcccggctgc agcgagcgct 180 ggacggagag gaaagcgact ttgaagatta tccaatgaga attttatatg accttcattc 240 agaagttcag actctaaagg atgatattaa tattcttctt gataaagcaa gattggaaaa 300 tcaagaaggc attgatttca taaaggcaac aaaagtacta atggaaaaaa attcaatgga 360 tattatgaaa ataagagagt atttccagaa gtatggatat agtccacgtg tcaagaaaaa 420 ttcagtacac gagcaagaag ccattaactc tgacccagag ttgtctaatt gtgaaaattt 480 tcagaagact gatgtgaaag atgatctgtc tgatcctcct gttgcaagca gttgtatttc 540 tgagaagtct ccacgtagtc cacaactttc agattttgga cttgagcggt acatcgtatc 600 ccaagttcta ccaaaccctc cacaggcagt gaacaactat aaggaagagc ccgtaattgt 660 aaccccacct accaaacaat cactagtaaa agtactaaaa actccaaaat gtgcactaaa 720 aatggatgat tttgagtgtg taactcctaa attagaacac tttggtatct ctgaatatac 780 tatgtgttta aatgaagatt acacaatggg acttaaaaat gcgaggaata ataaaagtga 840 ggaggccata gatacagaat ccaggctcaa tgataatgtt tttgccactc ccagccccat 900 catccagcag ttggaaaaaa gtgatgccga atataccaac tctcctttgg tacctacatt 960 ctgtactcct ggtttgaaaa ttccatctac aaagaacagc atagctttgg tatccacaaa 1020 ttacccatta tcaaaaacaa atagttcatc aaatgatttg gaagttgaag atcgtacttc 1080 gttggtttta aattcagaca catgctttga gaatttaaca gatccctctt cacctacgat 1140 ttcttcttat gagaatctgc tcagaacacc tacacctccg gaagtaacta aaattccaga 1200 agatattctc cagcttttat caaaatacaa ctcaaaccta gctactccaa tagcaattaa 1260 agcagtgcca cccagtaaaa ggttccttaa acatggacag aacatccgag atgtcagcaa 1320 caaagaaaac tgaaattcca gtggatctat ccaacacaga aactgaacaa aatgagatga 1380 aagccgagct ggaccgattt taacattcac attgccctgc ctctgtcccc ctttaaacgt 1440 tgacccattt taaagacaaa catgaacatt aacatcataa tatgcttttt atgaagtttc 1500 aataaggttt aaccttagtc ttgttgacat gtagcccagt cattcactct ttaaggatta 1560 ttagtgtttc attgatacta aattacccag cttaatcaac agaatggttt aagtagtacc 1620 aggaagtagg acaagtaatt tcaaaaatat aaaggtgttt gctactcaga tgaggccgcc 1680 cctgaccttc tggccagaga gacattgctg ccagccagct ctgccttccc atcatctcct 1740 ttcaggaccg tcccacacct tttacttgct cagtgctgtc tgaagatgca gttgctgttt 1800 gcaaacaaca ggaacaccag ttaaactaat taggaaaaga gggagatttc caggcctggg 1860 taactatata ctgtgaccat tggaggtaga gacaggtctc aacagttgga accaggaact 1920 ctgctgtcag gttgagagtt ttgtttctct tccagctttt cactgtgtgg gggtcttttc 1980 tcttatgtca gctctttcta tcacatggca gctgacctct cacgctccac tctgcagctt 2040 ggacacccag tagaccctga atttcactct ctctaaaagg ttctgagggc tcatcctggg 2100 ccaggggccc tcctgtgcac tgttagctat ggccacggga gcctccagag ctgcctggta 2160 gcttcaggtt gacctgctta tcaggcctac gatccttctg atttaagtac agctggaaag 2220 tattatctaa ttaagttcat gatagtgctt ttggagaact tgtcaaatta cagccaatga 2280 gaaaataagg acctagcata ctgtggagaa ccattaaaaa tttgagaaga aacaacaagt 2340 attatgtcaa cttacttcaa aggcgtagtt ttgggaattt gatgcagtaa agattaccct 2400 gttttatgat tgttccttga aagtcaaatg ggggacctgt ccattgtgct ctattaatct 2460 tgtcagaaaa ctgtcaccaa aacaaaactt gagtttgtcc ttgttctagg agttactggg 2520 tagttgtaag tattattttt attaaatata atgtaaaata aaatgttaag atacttagtt 2580 ttgtttttca aagtaaagct gtagtcagcc ttatgtatgc cattgactct gaaatgtata 2640 ccagcctttc actgtgtacc gtgtgtatat aaatccacag aaccggatga gctgcttagg 2700 gagggaatat attcaaagtg taccaaggac caaatcctgg agttctccca actttagagg 2760 atggaaaggg gcagagtaat ctagcaaagg agactgaggc cagtgaagta ggaagaaagt 2820 atttcaagga gagtgatgat tctgtgaata ttgctgagaa ttcaaataaa aagaggactg 2880 agaactga 2888 <210> 3 <211> 10611 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(10611) <223> Homo sapiens asp (abnormal spindle) homolog, microcephaly associated (Drosophila) (ASPM), mRNA. <400> 3 cctgagggga agcggtcagc gtaagtcccg gatccccgct ccggagccgc ctcgtgggag 60 cggggcaagg agatccagga ggggtctcga atctgccatg gcgaaccggc gagtggggcg 120 aggctgctgg gaagtgagcc cgaccgagcg gaggccgccc gcggggctgc ggggccccgc 180 ggccgaggag gaggcgtctt ccccgccggt cctgtctctc agccacttct gcaggtctcc 240 tttcctttgc ttcggggacg ttctcctggg agcctcacgg acgctgtctc tggccctaga 300 caaccctaac gaggaggtgg cagaagtgaa gatctcccac ttcccggccg cggacctggg 360 cttcagtgtg tcgcagcgct gtttcgtgtt gcagcctaaa gagaaaattg ttatttctgt 420 taactggaca ccactcaaag aaggccgagt aagagagatt atgacatttc ttgtaaatga 480 tgttctgaaa caccaagcta tattactagg aaatgcagaa gagcagaaaa agaaaaagag 540 gagtctttgg gataccatta aaaagaagaa aatttcagcc tctacaagtc acaacagaag 600 ggtttcaaat attcagaatg ttaataaaac atttagtgtt tcccaaaaag ttgacagagt 660 taggagccca ctacaagctt gtgaaaactt ggctatgaat gaaggcggtc ccccaacaga 720 aaacaattct ttaatacttg aagaaaataa aatacccata tcacctatta gccctgcttt 780 caatgaatgc catggtgcaa cttgcttgcc actctctgta cgtcgatcta ctacctactc 840 atctcttcat gcatcagaaa atagggaact attaaatgta cacagtgcca acgtttcaaa 900 agtttctttt aatgagaaag ctgtaactga aacttccttt aattccgtaa atgttaatgg 960 ccaaagagga gagaatagta aacttagtct tacccccaac tgttcttcaa ctttgaacat 1020 tacacaaagc caaatacatt ttctaagtcc agattctttt gtaaataata gtcatggagc 1080 taataatgaa ctagaattag taacatgtct ttcatcagat atgtttatga aagataattc 1140 acagcctgtg catttggaat caacaattgc acatgaaatt tatcagaaaa ttttaagtcc 1200 agattctttc ataaaagata attatggact aaatcaggat ctagaatcag agtcagttaa 1260 tcctatttta tcccctaatc aatttttaaa agataacatg gcatatatgt gtacatctca 1320 gcaaacatgt aaagtaccat tatcaaatga aaattctcaa gtcccacagt ctcctgaaga 1380 ttggagaaaa agtgaagttt cgccacgtat tcctgaatgt cagggttcaa aatctcccaa 1440 agctattttt gaagaactag tagaaatgaa gtcaaattac tacagtttta taaaacaaaa 1500 taatcctaaa ttttctgcag ttcaggatat ttctagtcat agccacaata aacaacctaa 1560 gagacgtcca atactttctg ccactgttac taaaaggaag gccacctgta ccagagaaaa 1620 ccaaactgag attaataaac caaaagcaaa aagatgtctc aacagtgcag tgggtgaaca 1680 tgaaaaagta ataaataatc aaaaggaaaa agaagatttt cattcttatc ttccaattat 1740 agatccaata ttaagtaaat ctaagagtta taaaaacgag gtaacaccct cttcgacaac 1800 agcttcagtt gctcggaaaa gaaagagcga tggaagcatg gaagatgcaa atgtgagagt 1860 tgcaattaca gaacatacag aagtgcgaga aatcaaaaga atccattttt ctccctcaga 1920 gcctaaaaca tcagctgtta agaaaacaaa aaatgtgaca acacccatct caaaacgtat 1980 tagcaacaga gagaaattaa acctgaagaa gaaaactgat ttatcaatat tcagaactcc 2040 aatttctaaa acaaacaaaa ggacaaaacc cattatcgct gtggcacagt ccagtttgac 2100 cttcataaaa ccattaaaaa cagatattcc cagacacccg atgccatttg ctgcaaaaaa 2160 catgttttat gatgaacgct ggaaggaaaa gcaggaacag ggcttcactt ggtggttaaa 2220 ttttatatta acccctgatg acttcactgt aaaaacaaat atttctgaag taaatgctgc 2280 tactcttctt ttgggaatag agaatcaaca taaaataagt gttcctagag cacctacaaa 2340 agaggaaatg tctctcagag cttatactgc tcggtgtagg ttaaacagac tacgtcgtgc 2400 agcatgccgt ttgtttactt ctgaaaaaat ggttaaagct attaaaaagc ttgaaattga 2460 aattgaagct aggcggttaa ttgttcgaaa agatagacac ctatggaaag atgtgggaga 2520 acgtcagaaa gtcctgaatt ggctgttgtc ctacaatcct ttgtggcttc gaattggtct 2580 agagacaact tatggagaac tcatatcttt ggaagataac agtgatgtca cagggttggc 2640 tatgtttatt ctgaatcgcc tactttggaa tcctgatata gcagctgagt atagacaccc 2700 cactgttcct cacctgtata gagatggtca tgaagaagct ttgtccaagt ttacattgaa 2760 aaagttattg ttgttggtct gttttcttga ttatgctaaa atttccagac tcattgatca 2820 tgatccttgt ctcttctgta aagatgccga attcaaggct agtaaagaaa tccttttggc 2880 tttttcacga gatttcctaa gtggtgaagg tgacctttcc cgtcaccttg gcttattggg 2940 attacctgtt aaccatgttc agacaccatt tgatgaattt gattttgccg ttacaaatct 3000 tgccgtagac ttgcaatgtg gagtgcgcct tgtgcgaacc atggaacttc tcacacagaa 3060 ctgggacctc tcaaagaaac tcaggattcc ggcaataagt cgtcttcaaa agatgcacaa 3120 tgttgacatt gttcttcaag ttcttaaatc acgaggaatt gaattaagtg atgagcatgg 3180 aaatacaatt ctatctaagg atattgtgga taggcacaga gaaaaaactc tcaggttgct 3240 ttggaaaata gcgtttgctt ttcaggtgga tatttccctt aacttagatc aattaaagga 3300 agaaattgcc tttctaaaac acacaaagag tataaagaaa acaatatctc tactatcatg 3360 ccattctgat gatcttatta ataagaaaaa aggcaaaagg gatagtggtt cctttgaaca 3420 atatagtgaa aacataaagt tattgatgga ttgggtaaat gctgtttgtg ccttctataa 3480 taaaaaggtg gagaatttta cagtgtcttt ctcagacggc cgtgtgttat gttacctgat 3540 ccaccattac catccttgct atgtgccatt tgacgctata tgtcagcgta ctactcaaac 3600 tgtggaatgt acgcaaactg gttcagtggt attaaattca tcatctgaat ctgatgacag 3660 ttctctggat atgtctctta aagcatttga tcatgaaaat acttcagagc tatacaaaga 3720 gctcctagaa aatgaaaaga aaaattttca cttggttagg tctgcagtta gagaccttgg 3780 tggaatacct gctatgatta atcattcaga tatgtcaaat acaattccag atgaaaaggt 3840 ggttattacc tatttgtcat ttctttgtgc aaggcttttg gatcttcgta aagaaataag 3900 agctgctcga ctcatacaaa caacatggag aaaatataaa ctaaaaacag atctcaaacg 3960 ccatcaggag agagagaaag ctgcaagaat tattcaattg gctgtaatca attttctagc 4020 aaaacaaaga ttgagaaaaa gagttaatgc agcactcgtc attcagaaat attggcgaag 4080 agtcttagca cagagaaaat tattaatgtt aaaaaaggaa aagctggaaa aagttcaaaa 4140 taaagcagca tcacttattc agggatattg gagaagatat tccactagac aaagatttct 4200 gaaattgaaa tattattcaa tcatcctgca atctaggata agaatgataa ttgctgttac 4260 atcttataaa cgatatcttt gggctacagt tacaattcag aggcattggc gtgcttattt 4320 aagaagaaaa caagatcaac aaagatatga aatgctaaaa tcatcaactc ttataatcca 4380 atctatgttc agaaaatgga agcaacgtaa aatgcaatca caagtaaaag ctacagtaat 4440 attgcaaaga gcttttagag aatggcattt aagaaaacaa gctaaagaag aaaattctgc 4500 tattatcata caatcatggt atagaatgca taaagaatta cggaaatata tttatattag 4560 atcttgtgtt gttatcattc agaaaagatt tcggtgcttt caagcccaaa agttatataa 4620 aagaagaaaa gagtccatac taaccatcca gaagtactac aaagcatatc tgaaaggaaa 4680 gattgagcgc accaactatt tgcagaaacg agctgcagcc attcaattac aagctgcttt 4740 taggagactg aaagctcata atttatgtag acaaattaga gctgcttgtg ttattcagtc 4800 atactggaga atgagacaag acagagttcg atttttaaac cttaagaaga ctattatcaa 4860 atttcaggca catgtaagaa aacatcaaca acgacagaaa tataagaaga tgaagaaagc 4920 agctgttata attcagactc atttccgagc ttatattttt gccatgaaag ttctagcatc 4980 ttaccagaaa acacgctctg ctgtcattgt gctgcagtct gcatatagag ggatgcaagc 5040 caggaaaatg tatattcaca tcctcacatc tgttataaag attcaatcat attatcgtgc 5100 ttatgtttct aaaaaggaat ttttgagcct aaaaaatgct acaataaaat tgcagtcaac 5160 tgttaagatg aaacaaacac gtaaacaata tttgcattta agagcagctg cactatttat 5220 ccagcaatgt taccgttcca aaaaaatagc tgcacaaaag agagaagagt atatgcagat 5280 gcgggaatct tgtatcaaac tgcaagcatt tgttagagga taccttgtcc gaaagcagat 5340 gaggttacaa agaaaagctg ttatttcact acagtcttat ttcagaatga gaaaggctcg 5400 gcagtattat ctgaaaatgt ataaagcaat tattgtcatt cagaattact atcatgcata 5460 caaagcacag gtcaatcaga ggaagaactt cttgcaagtc aaaaaagcag ctacttgctt 5520 gcaagcagct tacagaggtt ataaagtacg ccagctaatc aaacaacaat ctatagctgc 5580 tcttaaaatt cagtctgctt ttagaggcta taataaaagg gtaaaatatc aatctgtgct 5640 tcaatctata ataaagattc agagatggta cagggcgtac aagactcttc atgatacaag 5700 aacacatttt ttgaagacaa aggcagctgt gatttccctc cagtctgctt atcgtggctg 5760 gaaggttcgg aaacagatta gaagggaaca tcaagctgcc ttgaagattc agtctgcttt 5820 tagaatggcc aaggcccaga aacagtttag attgtttaaa acagcagcat tagtcatcca 5880 gcaaaatttc agagcatgga ctgcaggaag gaagcaatgt atggagtata ttgaactccg 5940 tcatgcggta ctggtgcttc aatctatgtg gaagggaaaa acactgagaa gacagcttca 6000 aaggcaacat aaatgtgcta tcatcataca gtcatactat agaatgcatg tgcaacaaaa 6060 gaagtggaaa atcatgaaaa aagctgctct tctgattcaa aagtattata gggcttacag 6120 tattggaaga gaacagaatc atttatattt gaaaacaaaa gcagctgtag taactttaca 6180 gtcagcttat cgtggtatga aagtgagaaa aagaataaag gattgcaaca aagcagcagt 6240 cactatacag tctaaataca gagcttacaa aaccaaaaag aaatatgcaa cctatagagc 6300 ttcagctatt ataattcaga gatggtatcg aggtattaaa attacaaacc atcagcataa 6360 ggagtatctt aatttgaaga agacagcaat taaaatccaa tctgtttata gaggtattag 6420 agttagaaga catattcaac acatgcacag ggcagccact tttattaaag ccatgtttaa 6480 aatgcatcag tcaagaataa gttaccatac aatgagaaaa gcagctattg ttattcaagt 6540 aagatgtaga gcatattatc aaggtaaaat gcagcgtgaa aagtacctga caattttgaa 6600 agctgttaaa gtccttcagg caagttttag aggagtaaga gttagacgga ctcttagaaa 6660 gatgcagact gcagcaacac tcattcagtc aaactacaga agatacagac agcaaacata 6720 ctttaataag ttaaagaaaa taacaaaaac agtacagcaa agatactggg caatgaaaga 6780 aagaaacata caatttcaaa ggtataacaa actgaggcat tctgtaatat acattcaggc 6840 tatttttagg ggaaagaaag ctagaagaca tttaaaaatg atgcatatag ccgcaactct 6900 cattcagagg agatttagaa ctctaatgat gagaagaaga ttcctctctc tcaagaaaac 6960 tgctattttg attcagagaa aatatcgggc acatctttgt acaaagcatc acttacagtt 7020 ccttcaggta caaaatgcag ttattaaaat ccagtcatca tacagaagat ggatgataag 7080 gaaaaggatg cgagagatgc acagggctgc tactttcatc cagtctactt tcagaatgca 7140 cagattacat atgagatatc aggctttgaa acaggcctcc gttgtgatcc aacagcaata 7200 ccaagcaaat agagctgcaa aactgcagag gcagcattat ctcagacaaa gacactctgc 7260 tgtgatcctt caggctgcat tcaggggtat gaaaactaga agacatttga agagtatgca 7320 ttcctctgca acccttattc agagtaggtt tagatcatta ctggtgagga gaagattcat 7380 ttccctcaaa aaagctacta tttttgttca gaggaaatat cgagccacca tttgtgccaa 7440 acataaattg taccaattct tgcacttaag aaaggcagcc attacaatac agtcatctta 7500 cagaagactg atggtaaaga agaagttaca agaaatgcaa agggctgcag ttctcattca 7560 ggctactttc aggatgtaca gaacatatat tacatttcag acttggaaac atgcttcaat 7620 tctaattcag caacattatc gaacatatag agctgcaaaa ttacaaagag aaaattatat 7680 cagacaatgg cattctgctg tggttattca ggctgcatat aaaggaatga aagcaagaca 7740 acttttaagg gaaaaacaca aagcttctat cgtaatacaa agcacctaca gaatgtatag 7800 gcagtattgt ttctaccaaa agcttcagtg ggctacaaaa atcatacaag aaaaatatag 7860 agcaaataaa aagaaacaga aagtatttca acacaatgaa cttaagaaag agacttgtgt 7920 tcaggcaggt tttcaggaca tgaacataaa aaaacagatt caggaacagc accaggctgc 7980 cattattatt cagaagcatt gtaaagcctt taaaataagg aagcattatc tccaccttag 8040 agcaacagta gtttctattc aaagaagata cagaaaacta actgcagtgc gtacccaagc 8100 agttatttgt atacagtctt attacagagg ctttaaagta cgaaaggata ttcaaaatat 8160 gcaccgggct gccacactaa ttcagtcatt ctatcgaatg cacagggcca aagttgatta 8220 tgaaacaaag aaaactgcaa ttgtggttat acagaattat tataggttgt atgttagagt 8280 aaaaacagaa agaaaaaact ttttagcagt tcagaaatct gtacgaacta ttcaggctgc 8340 ttttagaggc atgaaagtta gacaaaaatt gaaaaatgta tcagaggaaa agatggcagc 8400 cattgttaac caatctgcac tctgctgtta cagaagtaaa actcagtatg aagctgttca 8460 aagtgaaggt gttatgattc aagagtggta taaagcttct ggccttgctt gttcacagga 8520 agcagagtat cattctcaaa gtagggctgc agtaacaatt caaaaagctt tttgtagaat 8580 ggtcacaaga aaactggaaa cacagaaatg tgctgcccta cggattcagt tcttccttca 8640 gatggctgtg tatcggagaa gatttgttca gcagaaaaga gctgctatca ctttacagca 8700 ttattttagg acgtggcaaa ccagaaaaca gtttttacta tatagaaaag cagcagtggt 8760 tttacaaaat cactacagag catttctgtc tgcaaaacat caaagacaag tctatttaca 8820 gatcagaagc agtgttatca ttattcaagc tagaagtaaa ggatttatac agaaacggaa 8880 gtttcaggaa attaaaaata gcaccataaa aattcaggct atgtggagga gatatagagc 8940 caagaaatat ttatgtaaag tgaaagctgc ctgcaagatt caagcctggt atagatgttg 9000 gagagcacac aaagaatatc tagctatatt aaaagctgtt aaaattattc aaggttgctt 9060 ctataccaaa ctagagagaa cacggttttt gaatgtgaga gcatcagcaa ttatcattca 9120 gagaaaatgg agagctatac ttcctgcaaa gatagctcat gaacacttct taatgataaa 9180 aagacatcga gctgcttgtt tgatccaagc acattataga ggatataaag gaaggcaggt 9240 ctttcttcgg cagaaatctg ctgctttgat catacaaaaa tatatacgag ccagggaggc 9300 tggaaagcat gaaaggataa aatatattga atttaaaaaa tctacagtta tcctacaagc 9360 actggtgcgt ggttggctag tacgaaaaag atttttagaa cagagagcca aaattcgact 9420 tcttcacttc actgcagctg catattatca cctgaatgct gttagaattc aaagagccta 9480 taaactttac ctggctgtga agaatgctaa caagcaggtt aattcagtca tctgtattca 9540 gagatggttt cgagcaagat tacaagaaaa gagatttatt cagaaatatc atagcatcaa 9600 aaagattgag catgaaggtc aagaatgtct gagccagcga aatagggctg catcagtaat 9660 acagaaagca gtgcgccatt ttctcctccg taaaaagcag gaaaaattca ctagtggaat 9720 cattaaaatt caggcattat ggagaggcta ttcttggagg aagaaaaatg attgtacaaa 9780 aattaaagct atacgactaa gtcttcaagt tgttaatagg gagattcgag aagaaaacaa 9840 actctacaaa agaactgcac ttgcacttca ttaccttttg acatataagc acctttctgc 9900 cattcttgag gccttaaaac acctagaggt agttactaga ttgtctccac tttgttgtga 9960 gaacatggcc cagagtggag caatttctaa aatatttgtt ttgatccgaa gttgtaatcg 10020 cagtattcct tgtatggaag tcatcagata tgctgtgcaa gtcttgctta atgtatctaa 10080 gtatgagaaa actacttcag cagtttatga tgtagaaaat tgtatagata tactattgga 10140 gcttttgcag atataccgag aaaagcctgg taataaagtt gcagacaaag gcggaagcat 10200 ttttacaaaa acttgttgtt tgttggctat tttactgaag acaacaaata gagcctctga 10260 tgtacgaagt aggtccaaag ttgttgaccg tatttacagt ctctacaaac ttacagctca 10320 taaacataaa atgaatactg aaagaatact ttacaagcaa aagaagaatt cttctataag 10380 cattcctttt atcccagaaa cacctgtaag gaccagaata gtttcaagac ttaagccaga 10440 ttgggttttg agaagagata acatggaaga aatcacaaat cccctgcaag ctattcaaat 10500 ggtgatggat acgcttggca ttccttatta gtaaatgtaa acattttcag tatgtatagt 10560 gtaaagaaat attaaagcca atcatgagta cgtaaagtga tttttgctct c 10611 <210> 4 <211> 2823 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2823) <223> Homo sapiens AT rich interactive domain 3A (BRIGHT-like) (ARID3A), mRNA. <400> 4 acgcggacgc ggctggcggc tcggtttctg caaatgcgtg aatgagccgg atgccagcct 60 ctgtcccctg gagcccagcg tgaggaagag gcatgcccca tcagccttca gcttgagccc 120 ggcggccccc gcccccgccc cctgccaccc tgcactgccc cggctccccc gcggccccca 180 cgctgcagtg cggccgggcc ccctccccgc aggggccgcc cccgccgccc acccctagcg 240 cccgtggtgg tggtggtggt ggtggtggtg gtggcccggg ccgcagggcc atgaaactac 300 aggccgtgat ggagacgctg ttgcagcggc agcagcgggc gcgccaggag ctggaggccc 360 ggcagcagct gccccccgat ccccctgctg caccccccgg ccgggcccgg gctgcccccg 420 acgaggacag agagcccgag agtgcccgga tgcagcgggc tcagatggcc gcactggcag 480 ccatgcgggc tgcagctgcg ggcctgggac acccagccag ccccggcggc tctgaggatg 540 ggcccccagg ctcggaggag gaggacgcgg cccgggaggg gacaccgggc tcacccgggc 600 gaggcagaga agggccagga gaggagcact ttgaggacat ggcctccgac gaggacatga 660 agcccaaatg ggaggaggag gagatggagg aagacctcgg ggaggatgag gaggaggagg 720 aggaggatta cgaggatgag gaggaggagg aggacgagga ggggctgggc cccccaggcc 780 ctgccagctt gggcaccacg gcactgttcc cccgaaaggc ccagccaccc caggccttcc 840 gcggcgatgg cgttcccagg gtgctggggg gccaggagcg gccggggcct ggccctgccc 900 accccggagg ggccgcccac gtagccccgc agctgcagcc gcctgaccac ggcgactgga 960 cttacgagga gcagtttaag cagctctacg aactcgacgg ggaccccaag aggaaggaat 1020 tcctggatga cttgttcagc ttcatgcaga agcgagggac acctgtgaac cgcatcccca 1080 tcatggccaa acaggtcctt gacctgttca tgctgtacgt gctggtgacg gagaagggcg 1140 gcctcgtgga ggtcatcaac aagaagctgt ggcgtgagat caccaagggc ctcaacctgc 1200 ccacgtccat caccagtgca gccttcaccc tgcggaccca atacatgaag tacctgtacc 1260 cctacgagtg tgagaagcgg ggcctcagta accccaatga gctccaggca gccatagaca 1320 gcaaccgacg ggagggccgg cgccagagct ttggtggctc cctctttgcc tactcgccag 1380 gcggggcaca cggcatgctc tcctcaccca agctacccgt gtcctccctg ggcctggccg 1440 caagcaccaa tggcagctcc atcacccccg cccctaagat caagaaagag gaggactcag 1500 ccatccccat cacagtccct ggccgcctgc ctgtgtccct ggcgggccac cctgtggtgg 1560 cagcccaggc agcagctgtg caagcagcag ccgcccaagc agctgtggcc gcacaggcag 1620 ctgccctgga acagctgcgg gagaagctgg agtctgcaga gcctccggag aagaagatgg 1680 ccctggtggc cgatgagcag caacggctga tgcaacgtgc actccagcag aacttcctgg 1740 ccatggcggc ccagctgccc atgagcattc ggatcaacag ccaagcctcc gaaagccgcc 1800 aggactctgc tgtgaacctg acgggcacca acggcagcaa cagcatcagc atgtcggtgg 1860 agatcaacgg catcatgtac acaggagttc tgtttgctca gccgccggcc cccacgccaa 1920 cctctgctcc caacaaagga ggcggcggcg gcggcggcag cagcagcaac gcaggcggcc 1980 ggggaggaaa caccggaacc agcggcggcc aggctgggcc agcggggctg tccacaccct 2040 ccacatctac ctcaaataac tcgttgcctt aaccgcatca ctccccaccc gccacccacc 2100 ctggagcccg ccggcctggg cagggggtcc aggtgggcca cacaggggcc aggatggcgg 2160 aagatacggg tggggaggga agatatccag aaaggagcca cagctgacgc caaaaagaaa 2220 agaaaaaaga tatatatata tatatatata tatacacgta tatatataaa gagaatttaa 2280 taaaacaggg gaaaaccaag gaacacttga atttctcagg ttttggacat tcagagagat 2340 gaattgtgag aacagcaaag aaatccatca gaaaaacaga aagaggcaga cgtttcccag 2400 ggcgttcagg cagccctgat ggaccgaagg ctctggtgtc tggtttggcc ccacagcagt 2460 gtgggccgat cctgtttacc tcatacatcc ctgcactgtg tgttttcatt tttgtctgct 2520 ttagttctct tttattttct attcaccaca cactcaccac tcccagcttc tcgtgtccag 2580 tgaaacccct gaaccaagat cactgaattt ttgttttttt cttgttgctt tgggaaattt 2640 ttttttctct gtagggtttt taagaggttt cgggggtttt gttgtgtaaa tattctattt 2700 tattcttggg gggatcaaac cttaggaaaa ggatatctat atatctatat agctatatat 2760 ttgtgttcct tcagggaaac tggtcttgaa aaagcaagaa aaaaaagcaa aaaaaaaaaa 2820 aaa 2823 <210> 5 <211> 1430 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1430) <223> Homo sapiens chromosome 2 open reading frame 15(C2ORF15),mRNA. <400> 5 cttccctcag cttgaaacac ctgctgcttc gcggcggtgg ctttgtgcca cttttcccag 60 ggcttgggca tcattctgga cccatgttcg gtgaaccggt tactctcaga gctgctttcg 120 ggcgcagctc ctgctgcagc cagggcccgt tttaagagag gcttccaggt ccagccctcc 180 cgctgcagcc tgcagggagc gagccggcct gtcccgatga catagacact aggtttttac 240 agcaattctc tgatgacctt gatatggtag aacgctgtgt atttcaagag taagctctcg 300 tttgaggaga ctaacaattc ctgttttcgc cagatttctt cttgaatggc aacctaaatg 360 ccagtccaaa gaggccccca atagacttgt tcacccttca tgtcctcaac tctggggaag 420 ttaagtaatc aagttgaaga aacacttcca ctacttaaaa aggtacctgc aaattacttt 480 cacatttgtt cagctatcct aatgggattt tcacttagta aatctgctac tcaggtatct 540 gctatacata tggattcaaa agtggatgat cacttaatac gagggactga aaaaagcagg 600 ttggaaccag cgactcagtt atttcaaaac accaagaaaa taagattaga agacacaaat 660 caagaaaact ttacaaggat tgaagggact ggcacaggat ctctttctgg gaaagccttg 720 ggttcagtgg tatatgtcaa agaaagtgat ggactagaaa tgacagatgt ggaatgaagc 780 aatttgtacg tattaccaaa gaaaccaaaa actgcctttg actaaggggg gtgttgaaag 840 agaacttaac cttattagga aaccctgaca aaatgatgga agactattgc cttattttgc 900 actatttgtg aatcatctta cactgcattt ttttatgatg cttattcaaa aggcagttgc 960 tttagggtga aaaagccttc caagattcaa agcagatttc tctggtatta tattatatcc 1020 ttcttaaaaa ccagagtttt taagtaacag tatttgaatg gcatcaaaac attttcattt 1080 taatgtattt ctttaacaag tggttaaaaa aagtgtccaa gcagccgggc gcagtggctc 1140 acacctgtaa tcccagcact ttgggaggcc aaggcgggtc aatcacctga ggtcaggagt 1200 tcgcaaccag cctggccaat atggtgagac cccatctcta ctaaaaatgc aaaaagttag 1260 ccaggcatgg tggtgggcac ctgtgatccc agctacctgg gaggctgagg aaggagaatc 1320 gcttgaagcc tggaggcgga ggctgcactg agctgaggtc atgccattgt actccagcct 1380 gggcaacaag agcaaaactc cgtctcaaaa aaaaaaaaaa aaaaaaaaaa 1430 <210> 6 <211> 6069 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(6069) <223> Homo sapiens IQ motif containing GTPase activating protein 3(IQGAP3), mRNA. <400> 6 gtcctgtctg gcggtgccga cggtgagggg cggtggccca acggcgggag attcaaacct 60 ggaagaagga ggaacatgga gaggagagca gcgggcccag gctgggcagc ctatgaacgc 120 ctcacagctg aggagatgga tgagcagagg cggcagaatg ttgcctatca gtacctgtgc 180 cggctggagg aggccaagcg ctggatggag gcctgcctga aggaggagct tccttccccg 240 gtggagctgg aggagagcct tcggaatgga gtgctgctgg ccaagctagg ccactgtttt 300 gcaccctccg tggttccctt gaagaagatc tacgatgtgg agcagctgcg gtaccaggca 360 actggcttac atttccgtca cacagacaac atcaactttt ggctatctgc aatagcccac 420 atcggtctgc cttcgacctt cttcccagag accacggaca tctatgacaa aaagaacatg 480 ccccgggtag tctactgcat ccatgctctc agtctcttcc tcttccggct gggattggcc 540 cctcagatac atgatctata cgggaaagtg aaattcacag ctgaggaact cagcaacatg 600 gcgtccgaac tggccaaata tggcctccag ctgcctgcct tcagcaagat cgggggcatc 660 ttggccaatg agctctcggt ggatgaggct gcagtccatg cagctgttct tgccatcaat 720 gaagcagtgg agcgaggggt ggtggaggac accctggctg ccttgcagaa tcccagtgct 780 cttctggaga atctccgaga gcctctggca gccgtctacc aagagatgct ggcccaggcc 840 aagatggaga aggcagccaa tgccaggaac catgatgaca gagaaagcca ggacatctat 900 gaccactacc taactcaggc tgaaatccag ggcaatatca accatgtcaa cgtccatggg 960 gctctagaag ttgttgatga tgccctggaa agacagagcc ctgaagcctt gctcaaggcc 1020 cttcaagacc ctgccctggc cctgcgaggg gtgaggagag actttgctga ctggtacctg 1080 gagcagctga actcagacag agagcagaag gcacaggagc tgggcctggt ggagcttctg 1140 gaaaaggagg aagtccaggc tggtgtggct gcagccaaca caaagggtga tcaggaacaa 1200 gccatgctcc acgctgtgca gcggatcaac aaagccatcc ggaggggagt ggcggctgac 1260 actgtgaagg agctgatgtg ccctgaggcc cagctgcctc cagtgtaccc tgttgcatcg 1320 tctatgtacc agctggagct ggcagtgctc cagcagcagc agggggagct tggccaggag 1380 gagctcttcg tggctgtgga gatgctctca gctgtggtcc tgattaaccg ggccctggag 1440 gcccgggatg ccagtggctt ctggagcagc ctggtgaacc ctgccacagg cctggctgag 1500 gtggaaggag aaaatgccca gcgttacttc gatgccctgc tgaaattgcg acaggagcgt 1560 gggatgggtg aggacttcct gagctggaat gacctgcagg ccaccgtgag ccaggtcaat 1620 gcacagaccc aggaagagac tgaccgggtc cttgcagtca gcctcatcaa tgaggctctg 1680 gacaaaggca gccctgagaa gactctgtct gccctactgc ttcctgcagc tggcctagat 1740 gatgtcagcc tccctgtcgc ccctcggtac catctcctcc ttgtggcagc caaaaggcag 1800 aaggcccagg tgacagggga tcctggagct gtgctgtggc ttgaggagat ccgccaggga 1860 gtggtcagag ccaaccagga cactaataca gctcagagaa tggctcttgg tgtggctgcc 1920 atcaatcaag ccatcaagga gggcaaggca gcccagactg agcgggtgtt gaggaacccc 1980 gcagtggccc ttcgaggggt agttcccgac tgtgccaacg gctaccagcg agccctggaa 2040 agtgccatgg caaagaaaca gcgtccagca gacacagctt tctgggttca acatgacatg 2100 aaggatggca ctgcctacta cttccatctg cagaccttcc aggggatctg ggagcaacct 2160 cctggctgcc ccctcaacac ctctcacctg acccgggagg agatccagtc agctgtcacc 2220 aaggtcactg ctgcctatga ccgccaacag ctctggaaag ccaacgtcgg ctttgttatc 2280 cagctccagg cccgcctccg tggcttccta gttcggcaga agtttgctga gcattcccac 2340 tttctgagga cctggctccc agcagtcatc aagatccagg ctcattggcg gggttatagg 2400 cagcggaaga tttacctgga gtggttgcag tattttaaag caaacctgga tgccataatc 2460 aagatccagg cctgggcccg gatgtgggca gctcggaggc aatacctgag gcgtctgcac 2520 tacttccaga agaatgttaa ctccattgtg aagatccagg catttttccg agccaggaaa 2580 gcccaagatg actacaggat attagtgcat gcaccccacc ctcctctcag tgtggtacgc 2640 agatttgccc atctcttgaa tcaaagccag caagacttct tggctgaggc agagctgctg 2700 aagctccagg aagaggtagt taggaagatc cgatccaatc agcagctgga gcaggacctc 2760 aacatcatgg acatcaagat tggcctgctg gtgaagaacc ggatcactct gcaggaagtg 2820 gtctcccact gcaagaagct gaccaagagg aataaggaac agctgtcaga tatgatggtt 2880 ctggacaagc agaagggttt aaagtcgctg agcaaagaga aacggcagaa actagaagca 2940 taccaacacc tcttctacct gctccagact cagcccatct acctggccaa gctgatcttt 3000 cagatgccac agaacaaaac caccaagttc atggaggcag tgattttcag cctgtacaac 3060 tatgcctcca gccgccgaga ggcctatctc ctgctccagc tgttcaagac agcactccag 3120 gaggaaatca agtcaaaggt ggagcagccc caggacgtgg tgacaggcaa cccaacagtg 3180 gtgaggctgg tggtgagatt ctaccgtaat gggcggggac agagtgccct gcaggagatt 3240 ctgggcaagg ttatccagga tgtgctagaa gacaaagtgc tcagcgtcca cacagaccct 3300 gtccacctct ataagaactg gatcaaccag actgaggccc agacagggca gcgcagccat 3360 ctcccatatg atgtcacccc ggagcaggcc ttgagccacc ccgaggtcca gagacgactg 3420 gacatcgccc tacgcaacct cctcgccatg actgataagt tccttttagc catcacctca 3480 tctgtggacc aaattccgta tgggatgcga tatgtggcca aagtcctgaa ggcaactctg 3540 gcagagaaat tccctgacgc cacagacagc gaggtctata aggtggtcgg gaacctcctg 3600 tactaccgct tcctgaaccc agctgtggtg gctcctgacg ccttcgacat tgtggccatg 3660 gcagctggtg gagccctggc tgccccccag cgccatgccc tgggggctgt ggctcagctc 3720 ctacagcacg ctgcggctgg caaggccttc tctgggcaga gccagcacct acgggtcctg 3780 aatgactatc tggaggaaac acacctcaag ttcaggaagt tcatccatag agcctgccag 3840 gtgccagagc cagaggagcg ttttgcagtg gacgagtact cagacatggt ggctgtggcc 3900 aaacccatgg tgtacatcac cgtgggggag ctggtcaaca cgcacaggct gttgctggag 3960 caccaggact gcattgcccc tgatcaccaa gaccccctgc atgagctcct ggaggatctt 4020 ggggagctgc ccaccatccc tgaccttatt ggtgagagca tcgctgcaga tgggcacacg 4080 gacctgagca agctagaagt gtccctgacg ctgaccaaca agtttgaagg actagaggca 4140 gatgctgatg actccaacac ccgtagcctg cttctgagca ccaagcagct gttggccgat 4200 atcatacagt tccatcctgg ggacaccctc aaggagatcc tgtccctctc ggcttccaga 4260 gagcaagaag cagcccacaa gcagctgatg agccgacgcc aggcctgtac agcccagaca 4320 ccggagccac tgcgacgaca ccgctcactg acagctcact ccctcctgcc actggcagag 4380 aagcagcggc gcgtcctgcg gaacctacgc cgacttgaag ccctggggtt ggtcagcgcc 4440 agaaatggct accaggggct agtggacgag ctggccaagg acatccgcaa ccagcacaga 4500 cacaggcaca ggcggaaggc agagctggtg aagctgcagg ccacattaca gggcctgagc 4560 actaagacca ccttctatga ggagcagggt gactactaca gccagtacat ccgggcctgc 4620 ctggaccacc tggcccccga ctccaagagt tctgggaagg ggaagaagca gccttctctt 4680 cattacactg ctgctcagct cctggaaaag ggtgtcttgg tggaaattga agatcttccc 4740 gcctctcact tcagaaacgt catctttgac atcacgccgg gagatgaggc aggaaagttt 4800 gaagtaaatg ccaagttcct gggtgtggac atggagcgat ttcagcttca ctatcaggat 4860 ctcctgcagc tccagtatga gggtgtggct gtcatgaaac tcttcaacaa ggccaaagtc 4920 aatgtcaacc ttctcatctt cctcctcaac aagaagtttt tgcggaagtg acagaggcaa 4980 agggtgctac ccaagcccct cttacctctc tggatgcttt ctttaacact aactcaccac 5040 tgtgcttccc tgcagacacc cagagctcag gactgggcaa ggcccaggga ttctcacccc 5100 ttccccagct gggaggagct tgcctgcctg gccacagaca gtgtatcttc taattggcta 5160 aagtgggcct tgcccagagt ccagctgtgt ggcttttatc atgcatgaca aacccctggc 5220 tttcctgcca gatggtagga catggacctt gacctgggaa agccattact cttgtgtctg 5280 ctactgccct cccacagtca ccccaatatt acaagcactg ccccagcggc ttgatttccc 5340 ctctgccttc cttctctctg cactcccaca aagccagggc caggctcccc atccctacct 5400 cccactgcat cagcagtggg tgttcctgcc cttcctgagt ctaggcagct ctgctgctgt 5460 gatctgcaca ccctccaacc tgggcaggga ctggggggat gcagtgtgtg ttagtgccca 5520 tgtggcattg tggcactgtt gccccccatg gcggcatggg caagatgacc ttccattagc 5580 ttcaagtctt gttctcttgt ctgtggtctg tttaatatgt gggtcactag ggtatttatt 5640 ctttctccca tccttacact ctggatcatt gtgcagactt aatcagggtt ttaacgcttt 5700 catttttttt tttttttttt tttttttgag ctcaaagaga gttctcattt tccctattca 5760 aactaatacc catgccgtgt tttttacctt ggatttaaag tcaccttagg ttggggcaac 5820 agattctcac tcatgtttaa gatcttgtta tttcagcttc ataagatcaa agaggagtct 5880 ttcccttttc tcttttaccc tcaggattct catcccttac agctgactct tccaggcaat 5940 ttccatagat ctgcagtcct gcctctgcca cagtctctct gttgtcccca catctaccca 6000 acttcctgta ctgttgccct tctgatgtta ataaaagcag ctgttactcc caaaaaaaaa 6060 aaaaaaaaa 6069 <210> 7 <211> 1338 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1338) <223> Homo sapiens similar to ARP3 actin-related protein 3 homolog B (LOC644773), mRNA. <400> 7 cagaacttcc actgaataca ctagaaaata cagagcattt ttgcagaaat tatgtttgaa 60 ttatttaatg taccaggatt ctacattgca gttcaggagg tactagcctt ggaagtatct 120 tggacatctc aacaagtggg tgaatatatg ttaatgagta tagtcattga caaaggagat 180 ggagtcaccc ttgttctccc agttgtagaa ggttatgtaa ttgggagctg catcaatcac 240 atcctgattg taggtgatac tgtgtatttc attcaacagc tgctaaggga gagggaggta 300 ggaatccctc ttgagcagtc actggagaac acaaaagcca ttaaggagaa atactgttac 360 atttgccctg atatagtcaa ggaatttgct aagtatgatg tggatccctg gaagtggatc 420 aaacagtaca caggtatcaa tgtgatcaac caggagaagt tcataataga cgttggttac 480 aaaaggttcc tgcaacctga aatatttttt tacccagagt ttgccaaccc agactttatg 540 gaatccatct tgaatgttgt tgatgaatac aaaactgtcc cattgatgcg cattgtccac 600 tgtataagaa tgttgttctt tcaaggggtt tgaccatatt cagggatttg aatctcaact 660 acagagagat ttgaagagtg gtacatgcca gattaaaact caataaggag ctcagtggca 720 ggagaatcaa acctaagctt acaaaggttc gggtggtaat caatcacatg cagcactatg 780 ccttatggtt tggaagctta atgctagcct caactctgga gttatttcag gtctgtcaca 840 ccaagaagga ctataaagaa tatggcccca gcgtctgcca ccagagcctt ctctttggaa 900 taatgtctta gtgtctgcct tgaaagcatc atttaatagt gtcatgttgg ggaacaagtg 960 tccttcagaa cccagagaag actaccattt ctaaatgaca tttggtgttg atgtctgagc 1020 agcatgcttg caccacctag tgcatgaggc acagggcaga gtcatttcag taaaagccat 1080 ttctttatgt gttgactgtt gtatgcccac tcctccttct ctcactccct ttcttcatgc 1140 ttccccagtt tccctcctcc ttttcacttg aacttttttg ttgacaaata ccattctgaa 1200 ggaattcaaa tgtgactctg aaaattgtta agaggaaaaa aaatttcaaa aatggcccaa 1260 aatagttctc ccccaggaaa gaatgcagtg gtataaatcc ttttccccca gcttattttt 1320 ataaataaaa tgttataa 1338 <210> 8 <211> 3859 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(3859) <223> Homo sapiens keratin 80 (KRT80), transcript variant 1, mRNA. <400> 8 cccagctgtg accagagcaa ccagagcctg ccacccgacg caaccccagg ctcactcgct 60 cacccccctg ggccctcctg cttccggccg ggggcaccat ggcctgccgc tcctgcgtgg 120 ttggcttcag cagcctcagc agctgtgagg tgaccccggt gggcagcccc cggcctggaa 180 cctcaggatg ggacagctgc agggcccccg ggccgggctt cagctcccgc agcctcacag 240 gctgctggtc ggctggcact atctccaagg tgactgtgaa ccccggcctg ctggtgcccc 300 tggatgtcaa gttggacccc gctgttcagc agctgaagaa ccaggagaag gaggagatga 360 aggccctcaa tgataaattt gcctccctaa ttggcaaggt gcaagccctg gaacagcgca 420 accagctgct ggagacacgc tggagcttcc tgcagggcca ggactcagcc atcttcgacc 480 tcgggcatct ctatgaggaa tatcagggcc ggctgcagga ggaactgcgc aaagtgagcc 540 aggagcgggg gcagctggag gccaacctgc tgcaggtgct ggagaaggtt gaggagtttc 600 gaatcaggta tgaggatgag atctccaagc gcacagacat ggagttcacc tttgttcagc 660 tgaagaagga cctggatgca gagtgtcttc atcggactga actggaaacc aagttaaaaa 720 gcctggagag cttcgtggag ttgatgaaaa ccatctatga gcaggagctg aaggacctgg 780 cagcacaggt gaaggatgtg tcggtgaccg tcggcatgga cagccgctgc cacatcgacc 840 tgagcggcat cgtggaggag gtgaaggccc agtatgacgc cgtcgcggct cgcagcctgg 900 aggaggccga ggcatactct cggagccagc tggaggagca ggccgcccgc tcggccgagt 960 atgggagcag cctccagagc agccgcagcg agatcgcgga tctcaatgtg cgcatccaga 1020 agctgcggtc ccagatcctc tctgtcaaga gccattgcct gaaactggag gagaacatca 1080 agacagctga ggagcagggt gagctggcct tccaggatgc caagaccaag ctggcccagc 1140 tggaggccgc cctgcagcag gccaagcagg acatggcgcg gcagctgcgc aagtaccagg 1200 agctgatgaa cgtcaagctg gccctggaca tcgagatcgc cacctacagg aagctggtgg 1260 agggcgagga gggcaggatg gactcgccct cagccactgt ggtcagcgct gtgcagtcca 1320 ggtgcaaaac cgctgcctcc agatcaggcc tctccaaggc cccctcccga aagaagaagg 1380 gcagcaaagg ccccgtgatc aaaatcaccg aaatgtcaga gaagtacttc tcgcaggagt 1440 cggaggtctc agagtaaggc ggctggaccc caggaacccc agggcactcc actgcagcag 1500 gagggactta agctagactc aagaaagcag cttggagcct ctaggttgag aagagaggca 1560 aaacctgata ttgaactgag agaggggttc aaaactgact gtgttttgtg ggctgccagg 1620 gtgggagagg agcatcacca gctcctcaga gccactccgc tccatatcag tatctcacag 1680 tcccatcctt ccaaccttct ggccagaggt tttcctgatg ggtgagtcgg aattaggggt 1740 cagttttgtc tccacctcct cgctcctctg aggctcctcc tccagcatca ggctctgcca 1800 aggcccctct gactcttgcc caatccttga ccttgactcc tatctcaagc cttgccttgt 1860 ctctgcctcg gaactgggac tgggactggc tcatccacct atgtgcggga gccgaggagg 1920 acggcgtggg ccctgtcctg tatctggaat tcctgggaag gctggctgct gaagaccctc 1980 ttggctttcc cgtgctcttt gggctcccca gagacctgac agtattaggg agtgaaggga 2040 ggaggggccc tggctatttg ggacctaagc ctaggcccca gagatcagcc cgaacacccg 2100 catcccttcc tcctcccatg ggtccctccc agtaggcagt agtcagaact ggatgggctg 2160 cccccagcca gctcccagca gcttctccgg aagctgctct tgccataatc aactccctgg 2220 gagtggaagc cagatggcag cttgagattg ggcaggagca ttcgatcttc ctttcacctc 2280 cctgccatgc tggggtccta cccagcctgg atctgagctc tgtgccccca gccgggttgt 2340 tcccagcctg agcaccgggc tttggtgcac caggccttgg agacccctgg tcccacccct 2400 gccgtgaagc cccaggccca cttcccaaga atctcacttc tcagggcctc tgttctcctc 2460 tccactgggc caaatagcct ggccctcccc tccttggcat tcatggggga gcccaggaac 2520 cccccacacc tatggggtta gagctcctcc tttcttctca ctccttcccc ttcctccctc 2580 catgcccact ccccctgcct ccagcaggcc aggaagaagg cacagtccag gcaagtctgg 2640 gagcttccaa gcccttgagg tccagctgtg gggcccaaat gacagcctta caagggttct 2700 accagagagg aaaattccac atcccaccag aagacagggg tgttggcagg catactccta 2760 tctcctcctc ttggctctca atgctgaggc ttgcagaggc atcccagcgg caccagcctc 2820 ccactgcaca gcttccttcc ctccttcact ctcctctccc ctccctgccc cttgcctcac 2880 ctcctcttct agactgcatt agattcattc atctcatttg ccaggacatg ttggccagag 2940 gtctgggccc atcccaggcc tcaaggccct ccaggcctgt ggggagcact ggagggttac 3000 tgactctctg gccatgggaa ctcagagatt ctcatcccca aagtcccaaa agagggtgct 3060 gattggtgct tttcctcagg ctcttcattg gtttccaagg gagcaaatcc tcagtgggga 3120 tacaagacat ataaagtata tattattttt tcataactta tgtggctttt aacttattgc 3180 ttcccttcct gtttctgcat gatcagtctg tatgtactat ctggaaagat aacacatact 3240 ccagccacct cacctgattg gctatcttgg ggccatgtcc ccttcttgct gccacaggat 3300 gaataaagtg ttgagatttg tctatggaga aagctgtgtg tctgttttta tctcccctct 3360 caggaccagt cagccactgg tcaatcaggc tgatcatgga acattaggaa ttctccaatt 3420 aagggagaaa aagtccaggg acttagttat atcttcagac cagtgcagct ggtacacaca 3480 aagttctcct gtctcaccat ctgatatggt ttggatgctc gtcccctcca aatctcatgt 3540 tgaaatgtaa ttcccagtgt tggaagtgga gcctggtggg aagtatttgg atcatgagag 3600 aggatccttc atgaatggct cagcaccatc tccttggtga tgagtgagtt ctcactcaat 3660 tcacatagat atggttgttt aaaagagtct gagacctctc ccctctttct cgccatgtga 3720 tatgcctgct cccccttcac cttccgcctt tactgtaagc ttcctgaggc cctcaccaga 3780 agctgagcaa atgttggtgc catgccagta cagcctgcag aattgtgagc caaaataaat 3840 gtcttttctt tataaatta 3859 <210> 9 <211> 1182 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1182) <223> Homo sapiens hypothetical protein FLJ22655 (FLJ22655), mRNA. <400> 9 gttccagaaa ataggactga ccaagaagca gaaaagcaag atgaatgatg tgaagcttgc 60 tgtcttgggt ggtgaaggaa caggcaaatc tggtccctac atccttaaat aactgcaaat 120 acttggtagt gtctttgtga ctattacaca tagtaccttg aagccagact gagtttgaca 180 gagaaaataa acagatgtca aacttcttgc atctcaaata taatgagaaa tctgtttctg 240 ttacaaaagc ccttacagtg aggtttctta ctaagcgatt cattggagaa tatgcttcta 300 attttgaatc tatctataag aagcacttgt gtttggaaag gaaacaacta aatctagaaa 360 tatatgaccc ttgttctcaa acacagaaag caaaattctc cctcacaagt gagcttcact 420 gggcagatgg gtttgttatt gtgtatgaca tcagtgatag gtcttcattt gcttttgcaa 480 aagcgctgat ctacagaatc cgggagccac aaactagtca ttgtaaaaga gctgtggaat 540 cagcagtgtt tttggttggc aacaaacgag atctttgtca tgtgcgagag gttggctggg 600 aagaagggca aaagctggca ctggaaaacc gatgccaatt ctgtgaactg tctgcagcag 660 agcagtctct ggaggtggaa atgatgttta tcagaattat caaggacatc ctgataaact 720 tcaaactcaa agaaaagaga cgtcccagtg gatctaaatc aatggccaaa ttgatcaata 780 atgtatttgg aaagagaagg aaatctgttt agtagacagg taatcctggg agatttccta 840 tatcagagag tttcaaacat tcacatgata attaaactaa cctttgtatg caattttttt 900 ttggtaaaaa gaattctctt ggagatatga aatgattgag tatgaaccac agctgtgttt 960 tcaaatatgt agtttgcctt tttggttgtt gtaccctgct cactctcctt cacacagaac 1020 ctttcattta ttgtacaaca tcacactcac cctaacctac tggcggacag cgatcccagt 1080 ttgccttgcc aaataaactc tgtttatgtg aatttattaa acgaccatgc cataaaaaaa 1140 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1182 <210> 10 <211> 632 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(632) <223> Homo sapiens zymogen granule protein 16 (ZG16), mRNA. <400> 10 cccagaatgt tgacagtcgc tctcctagcc cttctctgtg cctcagcctc tggcaatgcc 60 attcaggcca ggtcttcctc ctatagtgga gagtatggaa gtggtggtgg aaagcgattc 120 tctcattctg gcaaccagtt ggacggcccc atcaccgccc tccgggtccg agtcaacaca 180 tactacatcg taggtcttca ggtgcgctat ggcaaggtgt ggagcgacta tgtgggtggt 240 cgcaacggag acctggagga gatctttctg caccctgggg aatcagtgat ccaggtttct 300 gggaagtaca agtggtacct gaagaagctg gtatttgtga cagacaaggg ccgctatctg 360 tcttttggga aagacagtgg cacaagtttc aatgccgtcc ccttgcaccc caacaccgtg 420 ctccgcttca tcagtggccg gtctggttct ctcatcgatg ccattggcct gcactgggat 480 gtttacccca ctagctgcag cagatgctga gcctcctctc cttggcaggg gcactgtgat 540 gaggagtaag aactccctta tcactaaccc ccatccaaat ggctcaataa aaaaatatgg 600 ttaaggctaa aaaaaaaaaa aaaaaaaaaa aa 632 <210> 11 <211> 2096 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2096) <223> Homo sapiens bestrophin 4 (BEST4), mRNA. <400> 11 cagccctggg ggcaactctt gtgacctcct gccccaggct cccagcacca tgacggtttc 60 atacactctc aaagtggcgg aggcccgctt cggaggtttc tctggcctgc ttctccgctg 120 gaggggaagc atctacaagc tcctctacaa ggaattcctc ctctttgggg ccttgtacgc 180 tgtgcttagc atcacctacc ggctgctgct gacccaggag cagaggtacg tgtatgctca 240 ggtggcccgg tactgcaacc gctcagcaga cctcattccc ttgtcctttg tattgggttt 300 ctatgtgact ctcgtggtga accgctggtg gtcccagtac acaagcatcc cgctgccaga 360 ccagctgatg tgcgtcatct cggctagcgt gcacggcgtg gaccagcggg gccgcctgct 420 gcgccgcacc ctcatccgct acgcgaacct ggcgtccgtg ctggtgctgc gctcggtcag 480 cacccgcgtg cttaagcgct tccccaccat ggagcacgtg gtggacgcag gtttcatgtc 540 ccaggaagag aggaaaaagt ttgagagcct gaaatccgac ttcaacaagt actgggtccc 600 ctgcgtctgg ttcaccaacc tggcggccca ggcccggagg gacgggcgaa tacgtgacga 660 tatcgctctc tgtctacttt tggaagagct gaacaagtac cgagccaagt gcagcatgct 720 attccactat gactggatca gcatccccct cgtctacacc caagtggtga ccatagccgt 780 ctactctttc tttgccctct ccctggttgg ccgccagttt gtggagccag aggcaggggc 840 tgccaaacct cagaagcttc tgaagccagg ccaggagcca gccccagccc tgggagaccc 900 ggacatgtac gtgcctctca ccactctgct gcagttcttc ttctatgctg gctggctcaa 960 ggtggctgaa cagatcatca acccatttgg tgaggatgat gacgactttg agacaaatca 1020 gctcatagac cgcaacttgc aggtgtccct gctatccgtg gacgaaatgt accagaacct 1080 tccccccgct gagaaggacc agtactggga tgaggaccag ccgcagccac cctacactgt 1140 ggccacggcg gccgagtctc tgcggccctc attcctgggc tccaccttca acctgcgcat 1200 gagcgacgac cctgagcaga gcctgcaggt ggaggcgtcc cccggatctg gtcggcccgc 1260 gcccgccgcg cagaccccgt tgctcggccg cttcctgggc gtaggggcgc cctccccggc 1320 catcagcctc cggaacttcg gccgcgtgcg aggcaccccc cgccccccgc atctgctgcg 1380 cttccgggcg gaggagggcg gcgaccccga ggccgcagcc cgcatcgagg aggaatcggc 1440 ggagtccggg gacgaggccc tggagccctg aggtctcgcc tgcccccgcc cggtttcccc 1500 cacccactgc cctccttccc tcccgtgccc ggtcctgcca gccagctcta ttagagcagc 1560 ttttcctgtg tgccttgaag gccagagcat ttagggacag aacttgaaag agaagatggc 1620 gaaaagggcc tgagccaggg ctgggaatgt gtccactttg gtgggagaga aggtcggttg 1680 cttgggggac gtgaagctag aaaaataaat gagcccaggc atagaggact agagcccagg 1740 tgcacggtta gcttcacagc aacagggagc taggccattg gttctcaaac ttaaggaagg 1800 atcagcatca cggaaggtct tgtcaaaaga gtgctgggca ccactcccag catttctggc 1860 acgttagatt tgggatggcg cccaataact tgcatttcta acaagttccc aggtgatgct 1920 gtgctgcttg tccaggaaac acaatttgag agtcatgtga aacgtgcttg aaggggtata 1980 ccttaccctg gtaaccttac tcaaaagaag ggtcagtgtg tgctggggga cttttgcctt 2040 gtttgtaatg ttaaagtttt tgtttacatt gagaatatat tcaagttttt gtttaa 2096 <210> 12 <211> 1182 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1182) <223> Homo sapiens membrane-spanning 4-domains, subfamily A, member 12(MS4A12), mRNA. <400> 12 acacaggttg gagcagagaa agaggaaaca tagaggtgcc aaaggaacaa agacataatg 60 atgtcatcca agccaacaag ccatgctgaa gtaaatgaaa ccatacccaa cccttaccca 120 ccaggcagct ttatggctcc tggatttcaa cagcctctgg gttcaatcaa cttagaaaac 180 caagctcagg gtgctcagcg tgctcagccc tacggcatca catctccggg aatctttgct 240 agcagtcaac cgggtcaagg aaatatacaa atgataaatc caagtgtggg aacagcagta 300 atgaacttta aagaagaagc aaaggcacta ggggtgatcc agatcatggt tggattgatg 360 cacattggtt ttggaattgt tttgtgttta atatccttct cttttagaga agtattaggt 420 tttgcctcta ctgctgttat tggtggatac ccattctggg gtggcctttc ttttattatc 480 tctggctctc tctctgtgtc agcatccaag gagctttccc gttgtctggt gaaaggcagc 540 ctgggaatga acattgttag ttctatcttg gccttcattg gagtgattct gctgctggtg 600 gatatgtgca tcaatggggt agctggccaa gactactggg ccgtgctttc tggaaaaggc 660 atttcagcca cgctgatgat cttctccctc ttggagttct tcgtagcttg tgccacagcc 720 cattttgcca accaagcaaa caccacaacc aatatgtctg tcctggttat tccaaatatg 780 tatgaaagca accctgtgac accagcgtct tcttcagctc ctcccagatg caacaactac 840 tcagctaatg cccctaaata gtaaaagaaa aaggggtatc agtctaatct catggagaaa 900 aactacttgc aaaaacttct taagaagatg tcttttattg tctacaatga tttctagtct 960 ttaaaaactg tgtttgagat ttgtttttag gttggtcgct aatgatggct gtatctccct 1020 tcactgtctc ttcctacatt accactacta catgctggca aaggtgaagg atcagaggac 1080 tgaaaaatga ttctgcaact ctcttaaagt tagaaatgtt tctgttcata ttactttttc 1140 cttaataaaa tgtcattaga aacaaaaaaa aaaaaaaaaa aa 1182 <210> 13 <211> 6741 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(6741) <223> Predicted: Homo sapiens KIAA1644 protein (KIAA1644), mRNA. <400> 13 aaggttggtg gcaaccagga gccggggaag aggccagcag ctgcagggag accgcagcca 60 gcggaggggg cttctgatcc ctcagtcaca gggctcggca ggcagctctg gacggatcaa 120 tgcaagccag acgatgacca gttgtggcca gcagtccttg aacgtgctcg ccgtcctctt 180 ctcattgctg ttttctgcag tcttgtctgc acatttccgg gtctgtgaac catacacaga 240 ccacaaaggc cgctaccact ttggcttcca ctgcccccgg ctctcggaca acaagacctt 300 catcctctgt tgtcaccata acaacacggt cttcaaatac tgctgcaacg agacggagtt 360 ccaggcggtg atgcaggcga acctcacggc cagctccgag ggttacatgc acaacaatta 420 caccgccttg ttgggagtgt ggatctatgg atttttcgtg ttgatgctgc tggttctgga 480 ccttttgtat tactcggcaa tgaactacga catctgcaag gtctacctgg cacggtgggg 540 catccaagga cgatggatga aacaggaccc ccggcggtgg gggaaccccg ctcgggcccc 600 tcggccgggt cagcgggccc cacagccgca gcctccccca ggcccgctgc cacaagcccc 660 acaggccgtg cacacattgc ggggagatgc tcacagccca ccgctgatga ccttccagag 720 ttcgtctgcc tgaaaacgct tttgctgtgc ctcaggatgg gggagatgag atctgaagca 780 cccggtgcag cctccgagaa gaacaacttc tacagagatg ccagggacag ccgaggtagc 840 ggcggtggca caggaggaaa tgctgcctgt gcccaaagcc cccttccgcg gacttctaag 900 attaggagca aactcagggg taggggctgg gggtgcaggg gaggggattc tgagccacct 960 gtccgcaagc aatagtccta ttttgggctg gtggcttctg agaggtgact cattgtggac 1020 tcaggatgac caagacaaag caactctggc tgattccagc caggaggatt gaggcctgtg 1080 agttatacct gtggttgaaa accgaagctt cccttgcccc tgctccctcc agtagtggcc 1140 ccttggggct atttgtgtca gaatattgaa tgtgcgtgtg tgtgtgcgtg tgtgtgattt 1200 ggggtgttct ttttgtttgc ttggttggtt ggtttttatt ggggcttccc ccctcaagtt 1260 ctctgatggg catgagtcac cctccggctg ggggttctca tccgtgtcaa tgtccgagcc 1320 gcaagcttat tgctaagcac agggtacggc ccctctgtgt ctcggggagc actggggatt 1380 tgaaaatgcc agtcagggtt gtttcttaca gaattcgttc ctgtaacaat agtaatacta 1440 agggctgcat ctcaggctga ccacagggca ggtgccaagt taagtgtttt catgcactcc 1500 ctctctcacc acctgggagg caggtatgat taaccccctg cagaaaaact cacagtgggg 1560 aagcggtgcc ggaacccaaa gtccaggctc caactccctg gacgtgacat gctcgccagc 1620 cggggtacac cctgcacaat gctgggagca tctccttgat gcctccacca tcaccgcctg 1680 gagcgctgat ccactcagca cattctggct aagcatctgc tgtgtgccag gccccgtgct 1740 gggcagtgat gggaatgaaa gatgagttag atctcatctc tgcccccggg gagcctccca 1800 tctggtggga gacacagaca cgtggatctt tgctggaaag ggtaacaagg ccatggaaac 1860 ccaggcagga gcgttctaga aatccatcca ctttcaagta ggacttccat gcccgtaaca 1920 tccacccacc gagctaatca cccccactcc tgccccgctg ccctgggaca cctatgagat 1980 ggcatcacct aaatcatcac aaacatctcc aaaggccatg ctgccagtgt agacacactc 2040 attccatggg tgttagtgat accaaatctc ccccagctct tagctcggga ggccctgctt 2100 gatcaatgtg tgtgtcctct gacgcagttt cctcatttca tcagacctag tgttctcaca 2160 ctgaccaccc atccattcac cagacacgac agtgagcaag gcaggtccct gctcactgtg 2220 ctagctttct agctggggca ggaagacagt gaagaaggaa ggtggcgaag gcagtgagtg 2280 ctctgccggg aactcagtgc caggaactca gttcgaggga cacgtgagtg agacccttgt 2340 ggacctgggg tggtctggga aggccgcctt gagcagatga ttgaagccca gatttgaatg 2400 acacacagga gccagtaatg ggcgttaaag ataggaaaag agcattccag gcagaaggaa 2460 cggctagtgc aaagatcctg cggcagccac aggcttggtg gtttcaagga agcacaagaa 2520 agccaggtgg cacaagaaag ccaggtggct ggggacccag agggaaggca gaaggagatg 2580 agggtgatag tgcccagctc tgggctctgc tgtgagtcaa gctgtgcaaa cacaatgtcc 2640 tgcctttgga aaagcagaac aaacttgcta gggtataaag catcctccat tctgcctggc 2700 tgtccatcct ctcaacagcc ccatgaagaa ggggctctcc ccattttatg gacaagaaga 2760 cagactcagc tgggtcaagt ggcttgccca ggatcacaca ggtcagctgt ggaagaccca 2820 ggcccctggc ttcagtcttt gggtccagct gtctcctcca ggcagtgctg ccagtgtcca 2880 ggcatatggc ttggcaaagt gggagaacct ctgcttgggg tctcgattgg agaaaggaat 2940 ggcttcctct cccctgatgt gagccgtccc agggccatgt tgccgtaagg gggtgcacag 3000 cctgtccact agcccagctg cggaagccac agctgtgtcc cacgtgcagt gcctcagaag 3060 gcagaggaag ccttgaggtg ggggcccaag acccagattc tgacatcagc tctgccactg 3120 agaacagcgt gacctcaggc aaggtctgtt acctcagttt ccccatcggt aagaggaagg 3180 agtcagatgg gtatttaagg agtttgcaac cctcgtgtcc tgctgtcctg gacaatgctc 3240 tgtaggtgct tcctctgcca aaaaggaact ggtggccttg cctccctctc ctggacacct 3300 ggggtcaaag gtcactgcca aatagacagc tagaactggg gttcacctaa gcatcccttg 3360 agatgtacaa ccttctagga ggacattcct cctgcctgcc cccctccccg caagaggtct 3420 tttcaggaat aactgaaaaa cccatggggt ttgtggtcct gctgctctgc caagtccctc 3480 ttgggcagct gggctgagga ctggaacatt ctgtggcaag caggaggcct cagcagagat 3540 caccaagacc cagcacacct ggtgcagaca gccacggcat cctccttcct gcaggtcacc 3600 cccacgagcc acttaacctc tcagagcctc tgcttctcac ctgtcaagtg tgtgaggtag 3660 ggtaccagtt agtcacggta cttgctgtct cacagaggag ccgacaggtg agaacagtgt 3720 gcatgtgggt gtgaacactc agtgtggaaa gcaggtgtgt gtgtattcaa tcccccaatg 3780 gtgtcaaggg ctcctcaaaa tgccatgggt ccccaggtca ttgtgataaa cactgtcccc 3840 atcctgctgt ggttgtggct ggaaggtccc tcaaggagta gactgtccct gagaacaaga 3900 tggatgcagg gtagtgacga gttcaagcat agctagagtt actgtttttt agcaactcaa 3960 cctgattttt taagctgcct acttttactt tttactgtga gcttctgtcc atcaccatgt 4020 aatttgtaat aataataata caaaaagaaa aacgagagag agaagaggac aagatgtcca 4080 cagaggaatc tgcattcgag gctgtttgca gaactaccgc gtttgtaagg actgtttccc 4140 actgggaact gtgtgtaatt aatgagcagt tttatgcttt ccctctcgtc tgtgtacggt 4200 gtgattgttg tgtgtttcag aatctctatt cagaaccaat agctggtaat gcctgctggc 4260 tcgctgccct caagttagcc tctgaacgtg ccctgcacct agagaagcag ccttctcacc 4320 cgcctcacct ggctgctcca gcggccaggc cagccacctg accatgacca ttgctgatgt 4380 gcaacaggcc ttaattgaaa aaacacacaa gtacatacat gcacatgcgc gcacacacac 4440 aggtgatttc acaggtagat ctggtccctc ttgctgtctc caatgctcta gaaagcagca 4500 agtaggcagc tgacagtgtt cccagggtga gtggcatctc ccctcatcat cagaaagatt 4560 cagtcaaatt ttggcccaga gctgaagagg aggacttggg aatgtcaggg aaaacatgac 4620 agggctaggg gttaacaggc ttctttggcc aggagatggt ttccagttca ccgtcaaccc 4680 aaaagctctc ttcaggtcat ggcaaacaga ccagggctgt gggtgtggct gtgcttggca 4740 ctgactcccc cacaggccgc tgtccaggtt ggctcaggat tccagctgcc atccccaggc 4800 aggcccctcc gctggctcgg ctgctttcac aatcaccatg tctgtctatt agagactgtg 4860 ccattcaagg agacggggtc cccgggggtg cagacttgta aaatttttta atttttcaac 4920 ttggctgaac tggtccccat caacaggaaa agccttcgga agtgaattta cagatttctc 4980 ccatgtttga aattaacata acatgaaccc agaaggcaga gcttgcagtg agctgagatc 5040 gcaccagtgc actccagcct gggcaacaga gtgagactct gtctaggtag gtaggtaaga 5100 aggaaggaag gaagaacaga cctggatgga gttattggga acatgtctta tcaatgttga 5160 agggccccct atcactgtag ggagacatcc acgtgggttg ttttcgtctg ctgtgaaaat 5220 ctagggttgg aatcatggaa gcaaactgca ggaattctta atcatcctgc tcacgtggtg 5280 ggcatcagag ggtgtctgct tggcccccac agcactggga cagtcagaga ggccatgagt 5340 ggatgacgcc ctgatcactg ccctttgcag tccaggaata cctcactggg ctggggccat 5400 accctgtgcc ctctggaaga caagcctgcg cacttactat gtgccagatg ccatgcacag 5460 tgccctagtt ccttgctgta gcaccaacac gtcccacgct ggtgcttaaa tgcacgcaaa 5520 caactttggt ggttgtggcc cgaaaagctc aaatgttaaa gttaagcagt caggcaagct 5580 agaagaggtg aggagcctcc tagaaaactc attcgatgac acgcgcttcc ctcacctatt 5640 cagatacttg ccgagtgcct gccacttgcc tggccctgta cccagggccc atctgggagc 5700 cattcctgct atagctggga ccacttgtga aacggctagt tgtgcctaac agacatgctc 5760 agattcacaa aatgaattca gaacacttac ctgtcccacc cgtgaaagtg accttggagg 5820 tgtcattgcc ccccaccacc ccagtttcta gtccaagcca acagctggtg ctagatagat 5880 gcttgatgaa tgagcagatt tgactgttag ttactctgta cctaaaactc ctatctttac 5940 atcaaagccc tgacagattt gcccttgaca gactgaaatc cggggctgct gcagggttca 6000 cctccaggag gcaccattca cgacactgtc ccataaatgg taatgggctc ccagggatac 6060 tgtttacata gactgcactg agaacggtga cccttaggtt tgtacaatga ggtaccctgt 6120 tgaatgaccc taaaccagcc tccaaaatgt gcaggatccc acattggtca gcgccaaccc 6180 tgagcacagg atctaaaact atagatgata tggccaccct ggccacagct ggaaccaagc 6240 tggtggccca agagagagcc tcttcttgga attgcatgtc agtttctcat acgcagtttc 6300 ttcctatttt tcccatttcc cgttttaaag ctagtggcat acctcacagt caaataacca 6360 agtggtcagt gtctcgacaa tgtgcagtaa cgaggtgggg gctgcaaggg tgaggggctc 6420 agtcacctta acaaggcagg agacctccca caaaaggctg atgtgtcgtc cccagggcca 6480 gctggacaag ggcatgcagc gcaggggtag ggggatggaa atattttctc tcccgtaaac 6540 tctgacttca tgtgagcagg catggggtct ccctgagagc tgataaccgg gaaaaccaaa 6600 accaataata ttcctaataa taatactaga atgtaagaat aatcatgtgt ttttcactga 6660 ccgctgttgc tctgcttttg tctttatata cagtagtttt tataacaatg tccctaggtt 6720 ttaataaagg agtgtcatgt c 6741 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying GAPDH <400> 14 tcatgaccac agtccatgcc 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying GAPDH <400> 15 tccaccaccc tgttgctgta 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13orf18 <400> 16 gctgctgatg aaggtgctgt 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13orf18 <400> 17 ctatcgagcc agctgcactc 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13ORF3 <400> 18 cagattttgg acttgagcgg 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13ORF3 <400> 19 ttccaactgc tggatgatgg 20 <210> 20 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ASPM <400> 20 tcgagctgct tgtttgat 18 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ASPM <400> 21 tttcgctggc tcagacattc 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ARID3A <400> 22 gtggctccct ctttgcctac 20 <210> 23 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ARID3A <400> 23 ttgatctcca ccgacatgct 20 <210> 24 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C2ORF15 <400> 24 tgtcctcaac tctggggaag t 21 <210> 25 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C2ORF15 <400> 25 agagatcctg tgccagtccc 20 <210> 26 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying IQGAP3 <400> 26 tacaactatg cctccagccg 20 <210> 27 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying IQGAP3 <400> 27 tagacctcgc tgtctgtggc 20 <210> 28 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644773 <400> 28 attgggagct gcatcaatca 20 <210> 29 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644773 <400> 29 agtggacaat gcgcatcaat 20 <210> 30 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC144501 <400> 30 aaaaagcctg gagagcttcg 20 <210> 31 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC144501 <400> 31 agcttcctgt aggtggcgat 20 <210> 32 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying FLJ22655 <400> 32 gcacttgtgt ttggaaagga a 21 <210> 33 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying FLJ22655 <400> 33 gttcacagaa ttggcatcgg 20 <210> 34 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ZG16 <400> 34 tcgctctcct agcccttctc 20 <210> 35 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ZG16 <400> 35 agatagcggc ccttgtctgt 20 <210> 36 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying VMD2L2 <400> 36 gctgaacaag taccgagcca 20 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying VMD2L2 <400> 37 ctggtacatt tcgtccacgg 20 <210> 38 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying MS4A12 <400> 38 tttcccgttg tctggtgaaa 20 <210> 39 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying MS4A12 <400> 39 tggtgtcaca gggttgcttt 20 <210> 40 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying KIAA1644 <400> 40 acaaaggccg ctaccacttt 20 <210> 41 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying KIAA1644 <400> 41 ggggtcctgt ttcatccatc 20 <110> Korea Research Institute of Bioscience and Biotechnology <120> Composition for diagnosing colorectal cancer and use thereof <130> P07-062-KRI-DA2 <160> 41 <170> KopatentIn 1.71 <210> 1 <211> 3993 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(3993) <223> Homo sapiens chromosome 13 open reading frame 18 (C13orf18), mRNA. <400> 1 ggatttctag gaggaccggc agaggcgcgc ataggtgcgt ggtgctgggc ccgggcgccg 60 cggcaccggt gtaggagcgc gcatctccag agtttcttcc atctgggcga cgtctcggtg 120 cctgcggcgg gaacggcgct ttgcttccct gaggagcttc tagagagcta cggtggcccc 180 cgtgtgggag gcggggggcg tggcggcgtc ggggcgtcgc tgtcccctcc tcggtagctc 240 tcctccctcc cctttctgct gttaccggga gcgcggtggc cacggaacgc tgcccggagc 300 cgcgcgaggg aggacccgac gcgcggcgtt tacccagcgc agcgttccac cgctcgggtt 360 tggctggata aaataaaaaa tggggatatt gacctcctgt cactactgca tggactttga 420 tggtttccaa tcattacttt ctcctctgtg tcaatctgcc tcttcgagaa attcatactc 480 ctgaatagct ctccagaccc ccagctggcc atgtggtgag ttcagggccc aaatcaagta 540 gtaccagcaa tcagggaact cctatctgtt ttgaatggat tcacaccagc cacaagcctg 600 gaaagatggt gtcacaatct acagtcaggc aggattctcc tgtggagccc tgggaaggga 660 tcagcgatca ctctggcatt attgatggtt cgcccagact cctgaacact gaccatcctc 720 cttgccaatt agacatcagg ctcatgaggc acaaagctgt ctggattaac ccccaggatg 780 tgcagcaaca gccgcaggac ttgcaatctc aggtgccagc agcagggaac agtgggaccc 840 attttgtgac agatgctgcc tctccctcag gcccttcacc ttcgtgcctc ggggactccc 900 tggcagagac aacgttgtct gaggatacca cagactccgt tggcagcgct tctccccatg 960 gctcgagtga aaagagtagc agcttctctc tgtcctcaac agaggtacac atggtccgcc 1020 caggatactc tcatcgggtg tctctgccca caagccctgg gattttggcc acctccccat 1080 atcctgagac tgacagtgct ttttttgagc cttcccatct gacatctgct gctgatgaag 1140 gtgctgttca agtcagtaga agaaccattt cttcgaattc cttctcacca gaggtatttg 1200 tgctgcctgt tgatgtagaa aaggaaaatg cccactttta tgttgcagat atgattatat 1260 cagcaatgga gaaaatgaag tgtaacattc tgagtcaaca gcagacagag agctggagta 1320 aagaagtcag tgggttactt gggagtgatc agcctgactc tgaaatgact tttgatacca 1380 acataaagca agagtctggg tcttctactt cttcatacag tggctatgaa ggttgtgctg 1440 tgttacaggt cagcccagtg actgaaacac gtacttacca tgatgtgaaa gagatttgca 1500 aatgcgatgt tgatgaattt gttattttag agcttggaga ttttaatgat atcacagaaa 1560 cctgtagctg ttcctgcagc tcctctaaga gtgtcactta tgagccagac ttcaattctg 1620 cagaactatt agccaaagag ctgtaccgcg tgttccagaa gtgctggata ctgtcagtag 1680 ttaattctca gctggcaggt tccctgagtg cagctggctc gatagtcgta aatgaagagt 1740 gtgtccgaaa agactttgaa tccagtatga atgtagtaca ggaaattaaa tttaagtcta 1800 ggatcagagg gactgaagac tgggctcctc ctagatttca aatcatattt aatattcatc 1860 caccactcaa gagggacctt gtggtggcag cccagaattt tttctgtgcc ggctgtggaa 1920 ctccagtaga gcctaagttt gtgaagcggc tccggtactg cgaataccta gggaagtatt 1980 tctgtgactg ctgccactca tatgcagagt cgtgcatccc tgcccgaatc ctgatgatgt 2040 gggacttcaa gaagtactac gtcagcaatt tctccaaaca gctgctcgac agcatatggc 2100 accagcccat tttcaatttg ctgagcatcg gccaaagcct gtatgcgaaa gccaaggagc 2160 tggacagagt gaaggaaatt caggagcagc tcttccatat caagaagctg ttgaagacct 2220 gtaggtttgc taacagtgca ttaaaggagt tcgagcaggt gccgggacac ttgactgatg 2280 agctccacct gttctccctt gaggacctgg tcaggatcaa gaaagggctg ctggcaccct 2340 tactcaagga cattctgaaa gcttcccttg cacatgtggc tggctgtgag ctgtgtcaag 2400 gaaagggctt tatttgtgaa ttttgccaga atacgactgt catcttccca tttcagacag 2460 caacatgtag aagatgttca gcgtgcaggg cttgctttca caaacagtgc ttccagtcct 2520 ccgagtgccc ccggtgtgcg aggatcacag cgaggagaaa acttctggaa agtgtggcct 2580 ctgcagcaac atgatgcccc tgagtactgt gaaaaagact gttcaacatg ccttatgata 2640 acaccgattt gtgtctatta ttggtgacat tgttttagat attgggtatt gtatattaag 2700 gaaaaagatg gtctatattc tctttattgc atatacttaa tgtttcaaaa gaatgcagat 2760 tctgtgttta agcacagggc tgatagttgt ggttttgttt acaaatgttc tgttttggct 2820 gctattggtt ttttaaagag gttttttata cttttgtatt tgaatagtta tgtttcactg 2880 atgctgagcc agtttgtatg tgtgtgcata tatgtgaact gtaactgaca agatgaatta 2940 ctcagtttct ctttctctaa agcttgtttg atgaaactgg ttggtccttt cagtgaacaa 3000 aaatatgacc ccaaatctgt ttgctctggc ttttatttct tcaggaagca gacttccact 3060 taaatgccat tttgtgattg tgtcaatcat acacatttta tttacttcag agtttgaata 3120 gagagtacac atttcttctg cagatttatt tcatgatgag tttgagttgc ttagcagggc 3180 gtgtgggtcc cgttgaagtg cagtttgaag caactgcttc tagatggcac tctttcaggt 3240 ggcacaaatt gaacctgtat ttgtcatctc tgttccacac actgcaatgt caagggatgc 3300 agaagtgagt agaattccat ccctgccctt gaggatcttg ctttaacaga tgtaaaactg 3360 aacataaggt atttgcagat ttaaacgaac tgggggaaat aatgaacagt gtgattctag 3420 taataacatt aaaatcatag acattgacta ataaggttaa atgaatcaca aaacctttat 3480 gaatttcttt tttctaatag ttcttatatg ttttcctgaa acatgtgagc ctattctttt 3540 ttcttctact ttctatatac tttctcccac ttgagaaagg ggccttgagg ctgggtccct 3600 tcatggtata cctttagact gaacggtttg caacctaggg cttgggcatt acattccctg 3660 ggattcacat gccctaacta aacctacctt gattttctca gacagcacag gcaggcaata 3720 aagcgtcaca gattgtcccc taaccccatc cagccatgtg tatgagtgtg ttttattcaa 3780 tgggatagta ctgagcacat gaaagaaatg aatgacttct gtcaatctct tttcattcag 3840 tcttctcatt ctgtcaattg ttttctcatc cgcagtgcct ctgccagaac tgtgctcaca 3900 tccattattt aagccagatc ttttctaagt attatagaag tgtagaggca catagaataa 3960 ataaaaccag acttcaaaaa aaaaaaaaaa aaa 3993 <210> 2 <211> 2888 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2888) <223> Homo sapiens chromosome 13 open reading frame 3 (C13orf3), mRNA. <400> 2 gcgtccggcg ccgagattca aactagtggc gggaggctgt gagctgagcg gtggggtctg 60 cgtacgcctg gagtccttcc ccgctgtgct cagcatggac cctatccgga gcttctgcgg 120 gaagctgcgg tctctggcca gcacgctgga ctgcgagacg gcccggctgc agcgagcgct 180 ggacggagag gaaagcgact ttgaagatta tccaatgaga attttatatg accttcattc 240 agaagttcag actctaaagg atgatattaa tattcttctt gataaagcaa gattggaaaa 300 tcaagaaggc attgatttca taaaggcaac aaaagtacta atggaaaaaa attcaatgga 360 tattatgaaa ataagagagt atttccagaa gtatggatat agtccacgtg tcaagaaaaa 420 ttcagtacac gagcaagaag ccattaactc tgacccagag ttgtctaatt gtgaaaattt 480 tcagaagact gatgtgaaag atgatctgtc tgatcctcct gttgcaagca gttgtatttc 540 tgagaagtct ccacgtagtc cacaactttc agattttgga cttgagcggt acatcgtatc 600 ccaagttcta ccaaaccctc cacaggcagt gaacaactat aaggaagagc ccgtaattgt 660 aaccccacct accaaacaat cactagtaaa agtactaaaa actccaaaat gtgcactaaa 720 aatggatgat tttgagtgtg taactcctaa attagaacac tttggtatct ctgaatatac 780 tatgtgttta aatgaagatt acacaatggg acttaaaaat gcgaggaata ataaaagtga 840 ggaggccata gatacagaat ccaggctcaa tgataatgtt tttgccactc ccagccccat 900 catccagcag ttggaaaaaa gtgatgccga atataccaac tctcctttgg tacctacatt 960 ctgtactcct ggtttgaaaa ttccatctac aaagaacagc atagctttgg tatccacaaa 1020 ttacccatta tcaaaaacaa atagttcatc aaatgatttg gaagttgaag atcgtacttc 1080 gttggtttta aattcagaca catgctttga gaatttaaca gatccctctt cacctacgat 1140 ttcttcttat gagaatctgc tcagaacacc tacacctccg gaagtaacta aaattccaga 1200 agatattctc cagcttttat caaaatacaa ctcaaaccta gctactccaa tagcaattaa 1260 agcagtgcca cccagtaaaa ggttccttaa acatggacag aacatccgag atgtcagcaa 1320 caaagaaaac tgaaattcca gtggatctat ccaacacaga aactgaacaa aatgagatga 1380 aagccgagct ggaccgattt taacattcac attgccctgc ctctgtcccc ctttaaacgt 1440 tgacccattt taaagacaaa catgaacatt aacatcataa tatgcttttt atgaagtttc 1500 aataaggttt aaccttagtc ttgttgacat gtagcccagt cattcactct ttaaggatta 1560 ttagtgtttc attgatacta aattacccag cttaatcaac agaatggttt aagtagtacc 1620 aggaagtagg acaagtaatt tcaaaaatat aaaggtgttt gctactcaga tgaggccgcc 1680 cctgaccttc tggccagaga gacattgctg ccagccagct ctgccttccc atcatctcct 1740 ttcaggaccg tcccacacct tttacttgct cagtgctgtc tgaagatgca gttgctgttt 1800 gcaaacaaca ggaacaccag ttaaactaat taggaaaaga gggagatttc caggcctggg 1860 taactatata ctgtgaccat tggaggtaga gacaggtctc aacagttgga accaggaact 1920 ctgctgtcag gttgagagtt ttgtttctct tccagctttt cactgtgtgg gggtcttttc 1980 tcttatgtca gctctttcta tcacatggca gctgacctct cacgctccac tctgcagctt 2040 ggacacccag tagaccctga atttcactct ctctaaaagg ttctgagggc tcatcctggg 2100 ccaggggccc tcctgtgcac tgttagctat ggccacggga gcctccagag ctgcctggta 2160 gcttcaggtt gacctgctta tcaggcctac gatccttctg atttaagtac agctggaaag 2220 tattatctaa ttaagttcat gatagtgctt ttggagaact tgtcaaatta cagccaatga 2280 gaaaataagg acctagcata ctgtggagaa ccattaaaaa tttgagaaga aacaacaagt 2340 attatgtcaa cttacttcaa aggcgtagtt ttgggaattt gatgcagtaa agattaccct 2400 gttttatgat tgttccttga aagtcaaatg ggggacctgt ccattgtgct ctattaatct 2460 tgtcagaaaa ctgtcaccaa aacaaaactt gagtttgtcc ttgttctagg agttactggg 2520 tagttgtaag tattattttt attaaatata atgtaaaata aaatgttaag atacttagtt 2580 ttgtttttca aagtaaagct gtagtcagcc ttatgtatgc cattgactct gaaatgtata 2640 ccagcctttc actgtgtacc gtgtgtatat aaatccacag aaccggatga gctgcttagg 2700 gagggaatat attcaaagtg taccaaggac caaatcctgg agttctccca actttagagg 2760 atggaaaggg gcagagtaat ctagcaaagg agactgaggc cagtgaagta ggaagaaagt 2820 atttcaagga gagtgatgat tctgtgaata ttgctgagaa ttcaaataaa aagaggactg 2880 agaactga 2888 <210> 3 <211> 10611 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(10611) <223> Homo sapiens asp (abnormal spindle) homolog, microcephaly associated (Drosophila) (ASPM), mRNA. <400> 3 cctgagggga agcggtcagc gtaagtcccg gatccccgct ccggagccgc ctcgtgggag 60 cggggcaagg agatccagga ggggtctcga atctgccatg gcgaaccggc gagtggggcg 120 aggctgctgg gaagtgagcc cgaccgagcg gaggccgccc gcggggctgc ggggccccgc 180 ggccgaggag gaggcgtctt ccccgccggt cctgtctctc agccacttct gcaggtctcc 240 tttcctttgc ttcggggacg ttctcctggg agcctcacgg acgctgtctc tggccctaga 300 caaccctaac gaggaggtgg cagaagtgaa gatctcccac ttcccggccg cggacctggg 360 cttcagtgtg tcgcagcgct gtttcgtgtt gcagcctaaa gagaaaattg ttatttctgt 420 taactggaca ccactcaaag aaggccgagt aagagagatt atgacatttc ttgtaaatga 480 tgttctgaaa caccaagcta tattactagg aaatgcagaa gagcagaaaa agaaaaagag 540 gagtctttgg gataccatta aaaagaagaa aatttcagcc tctacaagtc acaacagaag 600 ggtttcaaat attcagaatg ttaataaaac atttagtgtt tcccaaaaag ttgacagagt 660 taggagccca ctacaagctt gtgaaaactt ggctatgaat gaaggcggtc ccccaacaga 720 aaacaattct ttaatacttg aagaaaataa aatacccata tcacctatta gccctgcttt 780 caatgaatgc catggtgcaa cttgcttgcc actctctgta cgtcgatcta ctacctactc 840 atctcttcat gcatcagaaa atagggaact attaaatgta cacagtgcca acgtttcaaa 900 agtttctttt aatgagaaag ctgtaactga aacttccttt aattccgtaa atgttaatgg 960 ccaaagagga gagaatagta aacttagtct tacccccaac tgttcttcaa ctttgaacat 1020 tacacaaagc caaatacatt ttctaagtcc agattctttt gtaaataata gtcatggagc 1080 taataatgaa ctagaattag taacatgtct ttcatcagat atgtttatga aagataattc 1140 acagcctgtg catttggaat caacaattgc acatgaaatt tatcagaaaa ttttaagtcc 1200 agattctttc ataaaagata attatggact aaatcaggat ctagaatcag agtcagttaa 1260 tcctatttta tcccctaatc aatttttaaa agataacatg gcatatatgt gtacatctca 1320 gcaaacatgt aaagtaccat tatcaaatga aaattctcaa gtcccacagt ctcctgaaga 1380 ttggagaaaa agtgaagttt cgccacgtat tcctgaatgt cagggttcaa aatctcccaa 1440 agctattttt gaagaactag tagaaatgaa gtcaaattac tacagtttta taaaacaaaa 1500 taatcctaaa ttttctgcag ttcaggatat ttctagtcat agccacaata aacaacctaa 1560 gagacgtcca atactttctg ccactgttac taaaaggaag gccacctgta ccagagaaaa 1620 ccaaactgag attaataaac caaaagcaaa aagatgtctc aacagtgcag tgggtgaaca 1680 tgaaaaagta ataaataatc aaaaggaaaa agaagatttt cattcttatc ttccaattat 1740 agatccaata ttaagtaaat ctaagagtta taaaaacgag gtaacaccct cttcgacaac 1800 agcttcagtt gctcggaaaa gaaagagcga tggaagcatg gaagatgcaa atgtgagagt 1860 tgcaattaca gaacatacag aagtgcgaga aatcaaaaga atccattttt ctccctcaga 1920 gcctaaaaca tcagctgtta agaaaacaaa aaatgtgaca acacccatct caaaacgtat 1980 tagcaacaga gagaaattaa acctgaagaa gaaaactgat ttatcaatat tcagaactcc 2040 aatttctaaa acaaacaaaa ggacaaaacc cattatcgct gtggcacagt ccagtttgac 2100 cttcataaaa ccattaaaaa cagatattcc cagacacccg atgccatttg ctgcaaaaaa 2160 catgttttat gatgaacgct ggaaggaaaa gcaggaacag ggcttcactt ggtggttaaa 2220 ttttatatta acccctgatg acttcactgt aaaaacaaat atttctgaag taaatgctgc 2280 tactcttctt ttgggaatag agaatcaaca taaaataagt gttcctagag cacctacaaa 2340 agaggaaatg tctctcagag cttatactgc tcggtgtagg ttaaacagac tacgtcgtgc 2400 agcatgccgt ttgtttactt ctgaaaaaat ggttaaagct attaaaaagc ttgaaattga 2460 aattgaagct aggcggttaa ttgttcgaaa agatagacac ctatggaaag atgtgggaga 2520 acgtcagaaa gtcctgaatt ggctgttgtc ctacaatcct ttgtggcttc gaattggtct 2580 agagacaact tatggagaac tcatatcttt ggaagataac agtgatgtca cagggttggc 2640 tatgtttatt ctgaatcgcc tactttggaa tcctgatata gcagctgagt atagacaccc 2700 cactgttcct cacctgtata gagatggtca tgaagaagct ttgtccaagt ttacattgaa 2760 aaagttattg ttgttggtct gttttcttga ttatgctaaa atttccagac tcattgatca 2820 tgatccttgt ctcttctgta aagatgccga attcaaggct agtaaagaaa tccttttggc 2880 tttttcacga gatttcctaa gtggtgaagg tgacctttcc cgtcaccttg gcttattggg 2940 attacctgtt aaccatgttc agacaccatt tgatgaattt gattttgccg ttacaaatct 3000 tgccgtagac ttgcaatgtg gagtgcgcct tgtgcgaacc atggaacttc tcacacagaa 3060 ctgggacctc tcaaagaaac tcaggattcc ggcaataagt cgtcttcaaa agatgcacaa 3120 tgttgacatt gttcttcaag ttcttaaatc acgaggaatt gaattaagtg atgagcatgg 3180 aaatacaatt ctatctaagg atattgtgga taggcacaga gaaaaaactc tcaggttgct 3240 ttggaaaata gcgtttgctt ttcaggtgga tatttccctt aacttagatc aattaaagga 3300 agaaattgcc tttctaaaac acacaaagag tataaagaaa acaatatctc tactatcatg 3360 ccattctgat gatcttatta ataagaaaaa aggcaaaagg gatagtggtt cctttgaaca 3420 atatagtgaa aacataaagt tattgatgga ttgggtaaat gctgtttgtg ccttctataa 3480 taaaaaggtg gagaatttta cagtgtcttt ctcagacggc cgtgtgttat gttacctgat 3540 ccaccattac catccttgct atgtgccatt tgacgctata tgtcagcgta ctactcaaac 3600 tgtggaatgt acgcaaactg gttcagtggt attaaattca tcatctgaat ctgatgacag 3660 ttctctggat atgtctctta aagcatttga tcatgaaaat acttcagagc tatacaaaga 3720 gctcctagaa aatgaaaaga aaaattttca cttggttagg tctgcagtta gagaccttgg 3780 tggaatacct gctatgatta atcattcaga tatgtcaaat acaattccag atgaaaaggt 3840 ggttattacc tatttgtcat ttctttgtgc aaggcttttg gatcttcgta aagaaataag 3900 agctgctcga ctcatacaaa caacatggag aaaatataaa ctaaaaacag atctcaaacg 3960 ccatcaggag agagagaaag ctgcaagaat tattcaattg gctgtaatca attttctagc 4020 aaaacaaaga ttgagaaaaa gagttaatgc agcactcgtc attcagaaat attggcgaag 4080 agtcttagca cagagaaaat tattaatgtt aaaaaaggaa aagctggaaa aagttcaaaa 4140 taaagcagca tcacttattc agggatattg gagaagatat tccactagac aaagatttct 4200 gaaattgaaa tattattcaa tcatcctgca atctaggata agaatgataa ttgctgttac 4260 atcttataaa cgatatcttt gggctacagt tacaattcag aggcattggc gtgcttattt 4320 aagaagaaaa caagatcaac aaagatatga aatgctaaaa tcatcaactc ttataatcca 4380 atctatgttc agaaaatgga agcaacgtaa aatgcaatca caagtaaaag ctacagtaat 4440 attgcaaaga gcttttagag aatggcattt aagaaaacaa gctaaagaag aaaattctgc 4500 tattatcata caatcatggt atagaatgca taaagaatta cggaaatata tttatattag 4560 atcttgtgtt gttatcattc agaaaagatt tcggtgcttt caagcccaaa agttatataa 4620 aagaagaaaa gagtccatac taaccatcca gaagtactac aaagcatatc tgaaaggaaa 4680 gattgagcgc accaactatt tgcagaaacg agctgcagcc attcaattac aagctgcttt 4740 taggagactg aaagctcata atttatgtag acaaattaga gctgcttgtg ttattcagtc 4800 atactggaga atgagacaag acagagttcg atttttaaac cttaagaaga ctattatcaa 4860 atttcaggca catgtaagaa aacatcaaca acgacagaaa tataagaaga tgaagaaagc 4920 agctgttata attcagactc atttccgagc ttatattttt gccatgaaag ttctagcatc 4980 ttaccagaaa acacgctctg ctgtcattgt gctgcagtct gcatatagag ggatgcaagc 5040 caggaaaatg tatattcaca tcctcacatc tgttataaag attcaatcat attatcgtgc 5100 ttatgtttct aaaaaggaat ttttgagcct aaaaaatgct acaataaaat tgcagtcaac 5160 tgttaagatg aaacaaacac gtaaacaata tttgcattta agagcagctg cactatttat 5220 ccagcaatgt taccgttcca aaaaaatagc tgcacaaaag agagaagagt atatgcagat 5280 gcgggaatct tgtatcaaac tgcaagcatt tgttagagga taccttgtcc gaaagcagat 5340 gaggttacaa agaaaagctg ttatttcact acagtcttat ttcagaatga gaaaggctcg 5400 gcagtattat ctgaaaatgt ataaagcaat tattgtcatt cagaattact atcatgcata 5460 caaagcacag gtcaatcaga ggaagaactt cttgcaagtc aaaaaagcag ctacttgctt 5520 gcaagcagct tacagaggtt ataaagtacg ccagctaatc aaacaacaat ctatagctgc 5580 tcttaaaatt cagtctgctt ttagaggcta taataaaagg gtaaaatatc aatctgtgct 5640 tcaatctata ataaagattc agagatggta cagggcgtac aagactcttc atgatacaag 5700 aacacatttt ttgaagacaa aggcagctgt gatttccctc cagtctgctt atcgtggctg 5760 gaaggttcgg aaacagatta gaagggaaca tcaagctgcc ttgaagattc agtctgcttt 5820 tagaatggcc aaggcccaga aacagtttag attgtttaaa acagcagcat tagtcatcca 5880 gcaaaatttc agagcatgga ctgcaggaag gaagcaatgt atggagtata ttgaactccg 5940 tcatgcggta ctggtgcttc aatctatgtg gaagggaaaa acactgagaa gacagcttca 6000 aaggcaacat aaatgtgcta tcatcataca gtcatactat agaatgcatg tgcaacaaaa 6060 gaagtggaaa atcatgaaaa aagctgctct tctgattcaa aagtattata gggcttacag 6120 tattggaaga gaacagaatc atttatattt gaaaacaaaa gcagctgtag taactttaca 6180 gtcagcttat cgtggtatga aagtgagaaa aagaataaag gattgcaaca aagcagcagt 6240 cactatacag tctaaataca gagcttacaa aaccaaaaag aaatatgcaa cctatagagc 6300 ttcagctatt ataattcaga gatggtatcg aggtattaaa attacaaacc atcagcataa 6360 ggagtatctt aatttgaaga agacagcaat taaaatccaa tctgtttata gaggtattag 6420 agttagaaga catattcaac acatgcacag ggcagccact tttattaaag ccatgtttaa 6480 aatgcatcag tcaagaataa gttaccatac aatgagaaaa gcagctattg ttattcaagt 6540 aagatgtaga gcatattatc aaggtaaaat gcagcgtgaa aagtacctga caattttgaa 6600 agctgttaaa gtccttcagg caagttttag aggagtaaga gttagacgga ctcttagaaa 6660 gatgcagact gcagcaacac tcattcagtc aaactacaga agatacagac agcaaacata 6720 ctttaataag ttaaagaaaa taacaaaaac agtacagcaa agatactggg caatgaaaga 6780 aagaaacata caatttcaaa ggtataacaa actgaggcat tctgtaatat acattcaggc 6840 tatttttagg ggaaagaaag ctagaagaca tttaaaaatg atgcatatag ccgcaactct 6900 cattcagagg agatttagaa ctctaatgat gagaagaaga ttcctctctc tcaagaaaac 6960 tgctattttg attcagagaa aatatcgggc acatctttgt acaaagcatc acttacagtt 7020 ccttcaggta caaaatgcag ttattaaaat ccagtcatca tacagaagat ggatgataag 7080 gaaaaggatg cgagagatgc acagggctgc tactttcatc cagtctactt tcagaatgca 7140 cagattacat atgagatatc aggctttgaa acaggcctcc gttgtgatcc aacagcaata 7200 ccaagcaaat agagctgcaa aactgcagag gcagcattat ctcagacaaa gacactctgc 7260 tgtgatcctt caggctgcat tcaggggtat gaaaactaga agacatttga agagtatgca 7320 ttcctctgca acccttattc agagtaggtt tagatcatta ctggtgagga gaagattcat 7380 ttccctcaaa aaagctacta tttttgttca gaggaaatat cgagccacca tttgtgccaa 7440 acataaattg taccaattct tgcacttaag aaaggcagcc attacaatac agtcatctta 7500 cagaagactg atggtaaaga agaagttaca agaaatgcaa agggctgcag ttctcattca 7560 ggctactttc aggatgtaca gaacatatat tacatttcag acttggaaac atgcttcaat 7620 tctaattcag caacattatc gaacatatag agctgcaaaa ttacaaagag aaaattatat 7680 cagacaatgg cattctgctg tggttattca ggctgcatat aaaggaatga aagcaagaca 7740 acttttaagg gaaaaacaca aagcttctat cgtaatacaa agcacctaca gaatgtatag 7800 gcagtattgt ttctaccaaa agcttcagtg ggctacaaaa atcatacaag aaaaatatag 7860 agcaaataaa aagaaacaga aagtatttca acacaatgaa cttaagaaag agacttgtgt 7920 tcaggcaggt tttcaggaca tgaacataaa aaaacagatt caggaacagc accaggctgc 7980 cattattatt cagaagcatt gtaaagcctt taaaataagg aagcattatc tccaccttag 8040 agcaacagta gtttctattc aaagaagata cagaaaacta actgcagtgc gtacccaagc 8100 agttatttgt atacagtctt attacagagg ctttaaagta cgaaaggata ttcaaaatat 8160 gcaccgggct gccacactaa ttcagtcatt ctatcgaatg cacagggcca aagttgatta 8220 tgaaacaaag aaaactgcaa ttgtggttat acagaattat tataggttgt atgttagagt 8280 aaaaacagaa agaaaaaact ttttagcagt tcagaaatct gtacgaacta ttcaggctgc 8340 ttttagaggc atgaaagtta gacaaaaatt gaaaaatgta tcagaggaaa agatggcagc 8400 cattgttaac caatctgcac tctgctgtta cagaagtaaa actcagtatg aagctgttca 8460 aagtgaaggt gttatgattc aagagtggta taaagcttct ggccttgctt gttcacagga 8520 agcagagtat cattctcaaa gtagggctgc agtaacaatt caaaaagctt tttgtagaat 8580 ggtcacaaga aaactggaaa cacagaaatg tgctgcccta cggattcagt tcttccttca 8640 gatggctgtg tatcggagaa gatttgttca gcagaaaaga gctgctatca ctttacagca 8700 ttattttagg acgtggcaaa ccagaaaaca gtttttacta tatagaaaag cagcagtggt 8760 tttacaaaat cactacagag catttctgtc tgcaaaacat caaagacaag tctatttaca 8820 gatcagaagc agtgttatca ttattcaagc tagaagtaaa ggatttatac agaaacggaa 8880 gtttcaggaa attaaaaata gcaccataaa aattcaggct atgtggagga gatatagagc 8940 caagaaatat ttatgtaaag tgaaagctgc ctgcaagatt caagcctggt atagatgttg 9000 gagagcacac aaagaatatc tagctatatt aaaagctgtt aaaattattc aaggttgctt 9060 ctataccaaa ctagagagaa cacggttttt gaatgtgaga gcatcagcaa ttatcattca 9120 gagaaaatgg agagctatac ttcctgcaaa gatagctcat gaacacttct taatgataaa 9180 aagacatcga gctgcttgtt tgatccaagc acattataga ggatataaag gaaggcaggt 9240 ctttcttcgg cagaaatctg ctgctttgat catacaaaaa tatatacgag ccagggaggc 9300 tggaaagcat gaaaggataa aatatattga atttaaaaaa tctacagtta tcctacaagc 9360 actggtgcgt ggttggctag tacgaaaaag atttttagaa cagagagcca aaattcgact 9420 tcttcacttc actgcagctg catattatca cctgaatgct gttagaattc aaagagccta 9480 taaactttac ctggctgtga agaatgctaa caagcaggtt aattcagtca tctgtattca 9540 gagatggttt cgagcaagat tacaagaaaa gagatttatt cagaaatatc atagcatcaa 9600 aaagattgag catgaaggtc aagaatgtct gagccagcga aatagggctg catcagtaat 9660 acagaaagca gtgcgccatt ttctcctccg taaaaagcag gaaaaattca ctagtggaat 9720 cattaaaatt caggcattat ggagaggcta ttcttggagg aagaaaaatg attgtacaaa 9780 aattaaagct atacgactaa gtcttcaagt tgttaatagg gagattcgag aagaaaacaa 9840 actctacaaa agaactgcac ttgcacttca ttaccttttg acatataagc acctttctgc 9900 cattcttgag gccttaaaac acctagaggt agttactaga ttgtctccac tttgttgtga 9960 gaacatggcc cagagtggag caatttctaa aatatttgtt ttgatccgaa gttgtaatcg 10020 cagtattcct tgtatggaag tcatcagata tgctgtgcaa gtcttgctta atgtatctaa 10080 gtatgagaaa actacttcag cagtttatga tgtagaaaat tgtatagata tactattgga 10140 gcttttgcag atataccgag aaaagcctgg taataaagtt gcagacaaag gcggaagcat 10200 ttttacaaaa acttgttgtt tgttggctat tttactgaag acaacaaata gagcctctga 10260 tgtacgaagt aggtccaaag ttgttgaccg tatttacagt ctctacaaac ttacagctca 10320 taaacataaa atgaatactg aaagaatact ttacaagcaa aagaagaatt cttctataag 10380 cattcctttt atcccagaaa cacctgtaag gaccagaata gtttcaagac ttaagccaga 10440 ttgggttttg agaagagata acatggaaga aatcacaaat cccctgcaag ctattcaaat 10500 ggtgatggat acgcttggca ttccttatta gtaaatgtaa acattttcag tatgtatagt 10560 gtaaagaaat attaaagcca atcatgagta cgtaaagtga tttttgctct c 10611 <210> 4 <211> 2823 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2823) <223> Homo sapiens AT rich interactive domain 3A (BRIGHT-like) (ARID3A), mRNA. <400> 4 acgcggacgc ggctggcggc tcggtttctg caaatgcgtg aatgagccgg atgccagcct 60 ctgtcccctg gagcccagcg tgaggaagag gcatgcccca tcagccttca gcttgagccc 120 ggcggccccc gcccccgccc cctgccaccc tgcactgccc cggctccccc gcggccccca 180 cgctgcagtg cggccgggcc ccctccccgc aggggccgcc cccgccgccc acccctagcg 240 cccgtggtgg tggtggtggt ggtggtggtg gtggcccggg ccgcagggcc atgaaactac 300 aggccgtgat ggagacgctg ttgcagcggc agcagcgggc gcgccaggag ctggaggccc 360 ggcagcagct gccccccgat ccccctgctg caccccccgg ccgggcccgg gctgcccccg 420 acgaggacag agagcccgag agtgcccgga tgcagcgggc tcagatggcc gcactggcag 480 ccatgcgggc tgcagctgcg ggcctgggac acccagccag ccccggcggc tctgaggatg 540 ggcccccagg ctcggaggag gaggacgcgg cccgggaggg gacaccgggc tcacccgggc 600 gaggcagaga agggccagga gaggagcact ttgaggacat ggcctccgac gaggacatga 660 agcccaaatg ggaggaggag gagatggagg aagacctcgg ggaggatgag gaggaggagg 720 aggaggatta cgaggatgag gaggaggagg aggacgagga ggggctgggc cccccaggcc 780 ctgccagctt gggcaccacg gcactgttcc cccgaaaggc ccagccaccc caggccttcc 840 gcggcgatgg cgttcccagg gtgctggggg gccaggagcg gccggggcct ggccctgccc 900 accccggagg ggccgcccac gtagccccgc agctgcagcc gcctgaccac ggcgactgga 960 cttacgagga gcagtttaag cagctctacg aactcgacgg ggaccccaag aggaaggaat 1020 tcctggatga cttgttcagc ttcatgcaga agcgagggac acctgtgaac cgcatcccca 1080 tcatggccaa acaggtcctt gacctgttca tgctgtacgt gctggtgacg gagaagggcg 1140 gcctcgtgga ggtcatcaac aagaagctgt ggcgtgagat caccaagggc ctcaacctgc 1200 ccacgtccat caccagtgca gccttcaccc tgcggaccca atacatgaag tacctgtacc 1260 cctacgagtg tgagaagcgg ggcctcagta accccaatga gctccaggca gccatagaca 1320 gcaaccgacg ggagggccgg cgccagagct ttggtggctc cctctttgcc tactcgccag 1380 gcggggcaca cggcatgctc tcctcaccca agctacccgt gtcctccctg ggcctggccg 1440 caagcaccaa tggcagctcc atcacccccg cccctaagat caagaaagag gaggactcag 1500 ccatccccat cacagtccct ggccgcctgc ctgtgtccct ggcgggccac cctgtggtgg 1560 cagcccaggc agcagctgtg caagcagcag ccgcccaagc agctgtggcc gcacaggcag 1620 ctgccctgga acagctgcgg gagaagctgg agtctgcaga gcctccggag aagaagatgg 1680 ccctggtggc cgatgagcag caacggctga tgcaacgtgc actccagcag aacttcctgg 1740 ccatggcggc ccagctgccc atgagcattc ggatcaacag ccaagcctcc gaaagccgcc 1800 aggactctgc tgtgaacctg acgggcacca acggcagcaa cagcatcagc atgtcggtgg 1860 agatcaacgg catcatgtac acaggagttc tgtttgctca gccgccggcc cccacgccaa 1920 cctctgctcc caacaaagga ggcggcggcg gcggcggcag cagcagcaac gcaggcggcc 1980 ggggaggaaa caccggaacc agcggcggcc aggctgggcc agcggggctg tccacaccct 2040 ccacatctac ctcaaataac tcgttgcctt aaccgcatca ctccccaccc gccacccacc 2100 ctggagcccg ccggcctggg cagggggtcc aggtgggcca cacaggggcc aggatggcgg 2160 aagatacggg tggggaggga agatatccag aaaggagcca cagctgacgc caaaaagaaa 2220 agaaaaaaga tatatatata tatatatata tatacacgta tatatataaa gagaatttaa 2280 taaaacaggg gaaaaccaag gaacacttga atttctcagg ttttggacat tcagagagat 2340 gaattgtgag aacagcaaag aaatccatca gaaaaacaga aagaggcaga cgtttcccag 2400 ggcgttcagg cagccctgat ggaccgaagg ctctggtgtc tggtttggcc ccacagcagt 2460 gtgggccgat cctgtttacc tcatacatcc ctgcactgtg tgttttcatt tttgtctgct 2520 ttagttctct tttattttct attcaccaca cactcaccac tcccagcttc tcgtgtccag 2580 tgaaacccct gaaccaagat cactgaattt ttgttttttt cttgttgctt tgggaaattt 2640 ttttttctct gtagggtttt taagaggttt cgggggtttt gttgtgtaaa tattctattt 2700 tattcttggg gggatcaaac cttaggaaaa ggatatctat atatctatat agctatatat 2760 ttgtgttcct tcagggaaac tggtcttgaa aaagcaagaa aaaaaagcaa aaaaaaaaaa 2820 aaa 2823 <210> 5 <211> 1430 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1430) <223> Homo sapiens chromosome 2 open reading frame 15 (C2ORF15), mRNA. <400> 5 cttccctcag cttgaaacac ctgctgcttc gcggcggtgg ctttgtgcca cttttcccag 60 ggcttgggca tcattctgga cccatgttcg gtgaaccggt tactctcaga gctgctttcg 120 ggcgcagctc ctgctgcagc cagggcccgt tttaagagag gcttccaggt ccagccctcc 180 cgctgcagcc tgcagggagc gagccggcct gtcccgatga catagacact aggtttttac 240 agcaattctc tgatgacctt gatatggtag aacgctgtgt atttcaagag taagctctcg 300 tttgaggaga ctaacaattc ctgttttcgc cagatttctt cttgaatggc aacctaaatg 360 ccagtccaaa gaggccccca atagacttgt tcacccttca tgtcctcaac tctggggaag 420 ttaagtaatc aagttgaaga aacacttcca ctacttaaaa aggtacctgc aaattacttt 480 cacatttgtt cagctatcct aatgggattt tcacttagta aatctgctac tcaggtatct 540 gctatacata tggattcaaa agtggatgat cacttaatac gagggactga aaaaagcagg 600 ttggaaccag cgactcagtt atttcaaaac accaagaaaa taagattaga agacacaaat 660 caagaaaact ttacaaggat tgaagggact ggcacaggat ctctttctgg gaaagccttg 720 ggttcagtgg tatatgtcaa agaaagtgat ggactagaaa tgacagatgt ggaatgaagc 780 aatttgtacg tattaccaaa gaaaccaaaa actgcctttg actaaggggg gtgttgaaag 840 agaacttaac cttattagga aaccctgaca aaatgatgga agactattgc cttattttgc 900 actatttgtg aatcatctta cactgcattt ttttatgatg cttattcaaa aggcagttgc 960 tttagggtga aaaagccttc caagattcaa agcagatttc tctggtatta tattatatcc 1020 ttcttaaaaa ccagagtttt taagtaacag tatttgaatg gcatcaaaac attttcattt 1080 taatgtattt ctttaacaag tggttaaaaa aagtgtccaa gcagccgggc gcagtggctc 1140 acacctgtaa tcccagcact ttgggaggcc aaggcgggtc aatcacctga ggtcaggagt 1200 tcgcaaccag cctggccaat atggtgagac cccatctcta ctaaaaatgc aaaaagttag 1260 ccaggcatgg tggtgggcac ctgtgatccc agctacctgg gaggctgagg aaggagaatc 1320 gcttgaagcc tggaggcgga ggctgcactg agctgaggtc atgccattgt actccagcct 1380 gggcaacaag agcaaaactc cgtctcaaaa aaaaaaaaaa aaaaaaaaaa 1430 <210> 6 <211> 6069 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(6069) <223> Homo sapiens IQ motif containing GTPase activating protein 3 (IQGAP3), mRNA. <400> 6 gtcctgtctg gcggtgccga cggtgagggg cggtggccca acggcgggag attcaaacct 60 ggaagaagga ggaacatgga gaggagagca gcgggcccag gctgggcagc ctatgaacgc 120 ctcacagctg aggagatgga tgagcagagg cggcagaatg ttgcctatca gtacctgtgc 180 cggctggagg aggccaagcg ctggatggag gcctgcctga aggaggagct tccttccccg 240 gtggagctgg aggagagcct tcggaatgga gtgctgctgg ccaagctagg ccactgtttt 300 gcaccctccg tggttccctt gaagaagatc tacgatgtgg agcagctgcg gtaccaggca 360 actggcttac atttccgtca cacagacaac atcaactttt ggctatctgc aatagcccac 420 atcggtctgc cttcgacctt cttcccagag accacggaca tctatgacaa aaagaacatg 480 ccccgggtag tctactgcat ccatgctctc agtctcttcc tcttccggct gggattggcc 540 cctcagatac atgatctata cgggaaagtg aaattcacag ctgaggaact cagcaacatg 600 gcgtccgaac tggccaaata tggcctccag ctgcctgcct tcagcaagat cgggggcatc 660 ttggccaatg agctctcggt ggatgaggct gcagtccatg cagctgttct tgccatcaat 720 gaagcagtgg agcgaggggt ggtggaggac accctggctg ccttgcagaa tcccagtgct 780 cttctggaga atctccgaga gcctctggca gccgtctacc aagagatgct ggcccaggcc 840 aagatggaga aggcagccaa tgccaggaac catgatgaca gagaaagcca ggacatctat 900 gaccactacc taactcaggc tgaaatccag ggcaatatca accatgtcaa cgtccatggg 960 gctctagaag ttgttgatga tgccctggaa agacagagcc ctgaagcctt gctcaaggcc 1020 cttcaagacc ctgccctggc cctgcgaggg gtgaggagag actttgctga ctggtacctg 1080 gagcagctga actcagacag agagcagaag gcacaggagc tgggcctggt ggagcttctg 1140 gaaaaggagg aagtccaggc tggtgtggct gcagccaaca caaagggtga tcaggaacaa 1200 gccatgctcc acgctgtgca gcggatcaac aaagccatcc ggaggggagt ggcggctgac 1260 actgtgaagg agctgatgtg ccctgaggcc cagctgcctc cagtgtaccc tgttgcatcg 1320 tctatgtacc agctggagct ggcagtgctc cagcagcagc agggggagct tggccaggag 1380 gagctcttcg tggctgtgga gatgctctca gctgtggtcc tgattaaccg ggccctggag 1440 gcccgggatg ccagtggctt ctggagcagc ctggtgaacc ctgccacagg cctggctgag 1500 gtggaaggag aaaatgccca gcgttacttc gatgccctgc tgaaattgcg acaggagcgt 1560 gggatgggtg aggacttcct gagctggaat gacctgcagg ccaccgtgag ccaggtcaat 1620 gcacagaccc aggaagagac tgaccgggtc cttgcagtca gcctcatcaa tgaggctctg 1680 gacaaaggca gccctgagaa gactctgtct gccctactgc ttcctgcagc tggcctagat 1740 gatgtcagcc tccctgtcgc ccctcggtac catctcctcc ttgtggcagc caaaaggcag 1800 aaggcccagg tgacagggga tcctggagct gtgctgtggc ttgaggagat ccgccaggga 1860 gtggtcagag ccaaccagga cactaataca gctcagagaa tggctcttgg tgtggctgcc 1920 atcaatcaag ccatcaagga gggcaaggca gcccagactg agcgggtgtt gaggaacccc 1980 gcagtggccc ttcgaggggt agttcccgac tgtgccaacg gctaccagcg agccctggaa 2040 agtgccatgg caaagaaaca gcgtccagca gacacagctt tctgggttca acatgacatg 2100 aaggatggca ctgcctacta cttccatctg cagaccttcc aggggatctg ggagcaacct 2160 cctggctgcc ccctcaacac ctctcacctg acccgggagg agatccagtc agctgtcacc 2220 aaggtcactg ctgcctatga ccgccaacag ctctggaaag ccaacgtcgg ctttgttatc 2280 cagctccagg cccgcctccg tggcttccta gttcggcaga agtttgctga gcattcccac 2340 tttctgagga cctggctccc agcagtcatc aagatccagg ctcattggcg gggttatagg 2400 cagcggaaga tttacctgga gtggttgcag tattttaaag caaacctgga tgccataatc 2460 aagatccagg cctgggcccg gatgtgggca gctcggaggc aatacctgag gcgtctgcac 2520 tacttccaga agaatgttaa ctccattgtg aagatccagg catttttccg agccaggaaa 2580 gcccaagatg actacaggat attagtgcat gcaccccacc ctcctctcag tgtggtacgc 2640 agatttgccc atctcttgaa tcaaagccag caagacttct tggctgaggc agagctgctg 2700 aagctccagg aagaggtagt taggaagatc cgatccaatc agcagctgga gcaggacctc 2760 aacatcatgg acatcaagat tggcctgctg gtgaagaacc ggatcactct gcaggaagtg 2820 gtctcccact gcaagaagct gaccaagagg aataaggaac agctgtcaga tatgatggtt 2880 ctggacaagc agaagggttt aaagtcgctg agcaaagaga aacggcagaa actagaagca 2940 taccaacacc tcttctacct gctccagact cagcccatct acctggccaa gctgatcttt 3000 cagatgccac agaacaaaac caccaagttc atggaggcag tgattttcag cctgtacaac 3060 tatgcctcca gccgccgaga ggcctatctc ctgctccagc tgttcaagac agcactccag 3120 gaggaaatca agtcaaaggt ggagcagccc caggacgtgg tgacaggcaa cccaacagtg 3180 gtgaggctgg tggtgagatt ctaccgtaat gggcggggac agagtgccct gcaggagatt 3240 ctgggcaagg ttatccagga tgtgctagaa gacaaagtgc tcagcgtcca cacagaccct 3300 gtccacctct ataagaactg gatcaaccag actgaggccc agacagggca gcgcagccat 3360 ctcccatatg atgtcacccc ggagcaggcc ttgagccacc ccgaggtcca gagacgactg 3420 gacatcgccc tacgcaacct cctcgccatg actgataagt tccttttagc catcacctca 3480 tctgtggacc aaattccgta tgggatgcga tatgtggcca aagtcctgaa ggcaactctg 3540 gcagagaaat tccctgacgc cacagacagc gaggtctata aggtggtcgg gaacctcctg 3600 tactaccgct tcctgaaccc agctgtggtg gctcctgacg ccttcgacat tgtggccatg 3660 gcagctggtg gagccctggc tgccccccag cgccatgccc tgggggctgt ggctcagctc 3720 ctacagcacg ctgcggctgg caaggccttc tctgggcaga gccagcacct acgggtcctg 3780 aatgactatc tggaggaaac acacctcaag ttcaggaagt tcatccatag agcctgccag 3840 gtgccagagc cagaggagcg ttttgcagtg gacgagtact cagacatggt ggctgtggcc 3900 aaacccatgg tgtacatcac cgtgggggag ctggtcaaca cgcacaggct gttgctggag 3960 caccaggact gcattgcccc tgatcaccaa gaccccctgc atgagctcct ggaggatctt 4020 ggggagctgc ccaccatccc tgaccttatt ggtgagagca tcgctgcaga tgggcacacg 4080 gacctgagca agctagaagt gtccctgacg ctgaccaaca agtttgaagg actagaggca 4140 gatgctgatg actccaacac ccgtagcctg cttctgagca ccaagcagct gttggccgat 4200 atcatacagt tccatcctgg ggacaccctc aaggagatcc tgtccctctc ggcttccaga 4260 gagcaagaag cagcccacaa gcagctgatg agccgacgcc aggcctgtac agcccagaca 4320 ccggagccac tgcgacgaca ccgctcactg acagctcact ccctcctgcc actggcagag 4380 aagcagcggc gcgtcctgcg gaacctacgc cgacttgaag ccctggggtt ggtcagcgcc 4440 agaaatggct accaggggct agtggacgag ctggccaagg acatccgcaa ccagcacaga 4500 cacaggcaca ggcggaaggc agagctggtg aagctgcagg ccacattaca gggcctgagc 4560 actaagacca ccttctatga ggagcagggt gactactaca gccagtacat ccgggcctgc 4620 ctggaccacc tggcccccga ctccaagagt tctgggaagg ggaagaagca gccttctctt 4680 cattacactg ctgctcagct cctggaaaag ggtgtcttgg tggaaattga agatcttccc 4740 gcctctcact tcagaaacgt catctttgac atcacgccgg gagatgaggc aggaaagttt 4800 gaagtaaatg ccaagttcct gggtgtggac atggagcgat ttcagcttca ctatcaggat 4860 ctcctgcagc tccagtatga gggtgtggct gtcatgaaac tcttcaacaa ggccaaagtc 4920 aatgtcaacc ttctcatctt cctcctcaac aagaagtttt tgcggaagtg acagaggcaa 4980 agggtgctac ccaagcccct cttacctctc tggatgcttt ctttaacact aactcaccac 5040 tgtgcttccc tgcagacacc cagagctcag gactgggcaa ggcccaggga ttctcacccc 5100 ttccccagct gggaggagct tgcctgcctg gccacagaca gtgtatcttc taattggcta 5160 aagtgggcct tgcccagagt ccagctgtgt ggcttttatc atgcatgaca aacccctggc 5220 tttcctgcca gatggtagga catggacctt gacctgggaa agccattact cttgtgtctg 5280 ctactgccct cccacagtca ccccaatatt acaagcactg ccccagcggc ttgatttccc 5340 ctctgccttc cttctctctg cactcccaca aagccagggc caggctcccc atccctacct 5400 cccactgcat cagcagtggg tgttcctgcc cttcctgagt ctaggcagct ctgctgctgt 5460 gatctgcaca ccctccaacc tgggcaggga ctggggggat gcagtgtgtg ttagtgccca 5520 tgtggcattg tggcactgtt gccccccatg gcggcatggg caagatgacc ttccattagc 5580 ttcaagtctt gttctcttgt ctgtggtctg tttaatatgt gggtcactag ggtatttatt 5640 ctttctccca tccttacact ctggatcatt gtgcagactt aatcagggtt ttaacgcttt 5700 catttttttt tttttttttt tttttttgag ctcaaagaga gttctcattt tccctattca 5760 aactaatacc catgccgtgt tttttacctt ggatttaaag tcaccttagg ttggggcaac 5820 agattctcac tcatgtttaa gatcttgtta tttcagcttc ataagatcaa agaggagtct 5880 ttcccttttc tcttttaccc tcaggattct catcccttac agctgactct tccaggcaat 5940 ttccatagat ctgcagtcct gcctctgcca cagtctctct gttgtcccca catctaccca 6000 acttcctgta ctgttgccct tctgatgtta ataaaagcag ctgttactcc caaaaaaaaa 6060 aaaaaaaaa 6069 <210> 7 <211> 1338 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1338) <223> Homo sapiens similar to ARP3 actin-related protein 3 homolog B (LOC644773), mRNA. <400> 7 cagaacttcc actgaataca ctagaaaata cagagcattt ttgcagaaat tatgtttgaa 60 ttatttaatg taccaggatt ctacattgca gttcaggagg tactagcctt ggaagtatct 120 tggacatctc aacaagtggg tgaatatatg ttaatgagta tagtcattga caaaggagat 180 ggagtcaccc ttgttctccc agttgtagaa ggttatgtaa ttgggagctg catcaatcac 240 atcctgattg taggtgatac tgtgtatttc attcaacagc tgctaaggga gagggaggta 300 ggaatccctc ttgagcagtc actggagaac acaaaagcca ttaaggagaa atactgttac 360 atttgccctg atatagtcaa ggaatttgct aagtatgatg tggatccctg gaagtggatc 420 aaacagtaca caggtatcaa tgtgatcaac caggagaagt tcataataga cgttggttac 480 aaaaggttcc tgcaacctga aatatttttt tacccagagt ttgccaaccc agactttatg 540 gaatccatct tgaatgttgt tgatgaatac aaaactgtcc cattgatgcg cattgtccac 600 tgtataagaa tgttgttctt tcaaggggtt tgaccatatt cagggatttg aatctcaact 660 acagagagat ttgaagagtg gtacatgcca gattaaaact caataaggag ctcagtggca 720 ggagaatcaa acctaagctt acaaaggttc gggtggtaat caatcacatg cagcactatg 780 ccttatggtt tggaagctta atgctagcct caactctgga gttatttcag gtctgtcaca 840 ccaagaagga ctataaagaa tatggcccca gcgtctgcca ccagagcctt ctctttggaa 900 taatgtctta gtgtctgcct tgaaagcatc atttaatagt gtcatgttgg ggaacaagtg 960 tccttcagaa cccagagaag actaccattt ctaaatgaca tttggtgttg atgtctgagc 1020 agcatgcttg caccacctag tgcatgaggc acagggcaga gtcatttcag taaaagccat 1080 ttctttatgt gttgactgtt gtatgcccac tcctccttct ctcactccct ttcttcatgc 1140 ttccccagtt tccctcctcc ttttcacttg aacttttttg ttgacaaata ccattctgaa 1200 ggaattcaaa tgtgactctg aaaattgtta agaggaaaaa aaatttcaaa aatggcccaa 1260 aatagttctc ccccaggaaa gaatgcagtg gtataaatcc ttttccccca gcttattttt 1320 ataaataaaa tgttataa 1338 <210> 8 <211> 3859 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(3859) <223> Homo sapiens keratin 80 (KRT80), transcript variant 1, mRNA. <400> 8 cccagctgtg accagagcaa ccagagcctg ccacccgacg caaccccagg ctcactcgct 60 cacccccctg ggccctcctg cttccggccg ggggcaccat ggcctgccgc tcctgcgtgg 120 ttggcttcag cagcctcagc agctgtgagg tgaccccggt gggcagcccc cggcctggaa 180 cctcaggatg ggacagctgc agggcccccg ggccgggctt cagctcccgc agcctcacag 240 gctgctggtc ggctggcact atctccaagg tgactgtgaa ccccggcctg ctggtgcccc 300 tggatgtcaa gttggacccc gctgttcagc agctgaagaa ccaggagaag gaggagatga 360 aggccctcaa tgataaattt gcctccctaa ttggcaaggt gcaagccctg gaacagcgca 420 accagctgct ggagacacgc tggagcttcc tgcagggcca ggactcagcc atcttcgacc 480 tcgggcatct ctatgaggaa tatcagggcc ggctgcagga ggaactgcgc aaagtgagcc 540 aggagcgggg gcagctggag gccaacctgc tgcaggtgct ggagaaggtt gaggagtttc 600 gaatcaggta tgaggatgag atctccaagc gcacagacat ggagttcacc tttgttcagc 660 tgaagaagga cctggatgca gagtgtcttc atcggactga actggaaacc aagttaaaaa 720 gcctggagag cttcgtggag ttgatgaaaa ccatctatga gcaggagctg aaggacctgg 780 cagcacaggt gaaggatgtg tcggtgaccg tcggcatgga cagccgctgc cacatcgacc 840 tgagcggcat cgtggaggag gtgaaggccc agtatgacgc cgtcgcggct cgcagcctgg 900 aggaggccga ggcatactct cggagccagc tggaggagca ggccgcccgc tcggccgagt 960 atgggagcag cctccagagc agccgcagcg agatcgcgga tctcaatgtg cgcatccaga 1020 agctgcggtc ccagatcctc tctgtcaaga gccattgcct gaaactggag gagaacatca 1080 agacagctga ggagcagggt gagctggcct tccaggatgc caagaccaag ctggcccagc 1140 tggaggccgc cctgcagcag gccaagcagg acatggcgcg gcagctgcgc aagtaccagg 1200 agctgatgaa cgtcaagctg gccctggaca tcgagatcgc cacctacagg aagctggtgg 1260 agggcgagga gggcaggatg gactcgccct cagccactgt ggtcagcgct gtgcagtcca 1320 ggtgcaaaac cgctgcctcc agatcaggcc tctccaaggc cccctcccga aagaagaagg 1380 gcagcaaagg ccccgtgatc aaaatcaccg aaatgtcaga gaagtacttc tcgcaggagt 1440 cggaggtctc agagtaaggc ggctggaccc caggaacccc agggcactcc actgcagcag 1500 gagggactta agctagactc aagaaagcag cttggagcct ctaggttgag aagagaggca 1560 aaacctgata ttgaactgag agaggggttc aaaactgact gtgttttgtg ggctgccagg 1620 gtgggagagg agcatcacca gctcctcaga gccactccgc tccatatcag tatctcacag 1680 tcccatcctt ccaaccttct ggccagaggt tttcctgatg ggtgagtcgg aattaggggt 1740 cagttttgtc tccacctcct cgctcctctg aggctcctcc tccagcatca ggctctgcca 1800 aggcccctct gactcttgcc caatccttga ccttgactcc tatctcaagc cttgccttgt 1860 ctctgcctcg gaactgggac tgggactggc tcatccacct atgtgcggga gccgaggagg 1920 acggcgtggg ccctgtcctg tatctggaat tcctgggaag gctggctgct gaagaccctc 1980 ttggctttcc cgtgctcttt gggctcccca gagacctgac agtattaggg agtgaaggga 2040 ggaggggccc tggctatttg ggacctaagc ctaggcccca gagatcagcc cgaacacccg 2100 catcccttcc tcctcccatg ggtccctccc agtaggcagt agtcagaact ggatgggctg 2160 cccccagcca gctcccagca gcttctccgg aagctgctct tgccataatc aactccctgg 2220 gagtggaagc cagatggcag cttgagattg ggcaggagca ttcgatcttc ctttcacctc 2280 cctgccatgc tggggtccta cccagcctgg atctgagctc tgtgccccca gccgggttgt 2340 tcccagcctg agcaccgggc tttggtgcac caggccttgg agacccctgg tcccacccct 2400 gccgtgaagc cccaggccca cttcccaaga atctcacttc tcagggcctc tgttctcctc 2460 tccactgggc caaatagcct ggccctcccc tccttggcat tcatggggga gcccaggaac 2520 cccccacacc tatggggtta gagctcctcc tttcttctca ctccttcccc ttcctccctc 2580 catgcccact ccccctgcct ccagcaggcc aggaagaagg cacagtccag gcaagtctgg 2640 gagcttccaa gcccttgagg tccagctgtg gggcccaaat gacagcctta caagggttct 2700 accagagagg aaaattccac atcccaccag aagacagggg tgttggcagg catactccta 2760 tctcctcctc ttggctctca atgctgaggc ttgcagaggc atcccagcgg caccagcctc 2820 ccactgcaca gcttccttcc ctccttcact ctcctctccc ctccctgccc cttgcctcac 2880 ctcctcttct agactgcatt agattcattc atctcatttg ccaggacatg ttggccagag 2940 gtctgggccc atcccaggcc tcaaggccct ccaggcctgt ggggagcact ggagggttac 3000 tgactctctg gccatgggaa ctcagagatt ctcatcccca aagtcccaaa agagggtgct 3060 gattggtgct tttcctcagg ctcttcattg gtttccaagg gagcaaatcc tcagtgggga 3120 tacaagacat ataaagtata tattattttt tcataactta tgtggctttt aacttattgc 3180 ttcccttcct gtttctgcat gatcagtctg tatgtactat ctggaaagat aacacatact 3240 ccagccacct cacctgattg gctatcttgg ggccatgtcc ccttcttgct gccacaggat 3300 gaataaagtg ttgagatttg tctatggaga aagctgtgtg tctgttttta tctcccctct 3360 caggaccagt cagccactgg tcaatcaggc tgatcatgga acattaggaa ttctccaatt 3420 aagggagaaa aagtccaggg acttagttat atcttcagac cagtgcagct ggtacacaca 3480 aagttctcct gtctcaccat ctgatatggt ttggatgctc gtcccctcca aatctcatgt 3540 tgaaatgtaa ttcccagtgt tggaagtgga gcctggtggg aagtatttgg atcatgagag 3600 aggatccttc atgaatggct cagcaccatc tccttggtga tgagtgagtt ctcactcaat 3660 tcacatagat atggttgttt aaaagagtct gagacctctc ccctctttct cgccatgtga 3720 tatgcctgct cccccttcac cttccgcctt tactgtaagc ttcctgaggc cctcaccaga 3780 agctgagcaa atgttggtgc catgccagta cagcctgcag aattgtgagc caaaataaat 3840 gtcttttctt tataaatta 3859 <210> 9 <211> 1182 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1182) <223> Homo sapiens hypothetical protein FLJ22655 (FLJ22655), mRNA. <400> 9 gttccagaaa ataggactga ccaagaagca gaaaagcaag atgaatgatg tgaagcttgc 60 tgtcttgggt ggtgaaggaa caggcaaatc tggtccctac atccttaaat aactgcaaat 120 acttggtagt gtctttgtga ctattacaca tagtaccttg aagccagact gagtttgaca 180 gagaaaataa acagatgtca aacttcttgc atctcaaata taatgagaaa tctgtttctg 240 ttacaaaagc ccttacagtg aggtttctta ctaagcgatt cattggagaa tatgcttcta 300 attttgaatc tatctataag aagcacttgt gtttggaaag gaaacaacta aatctagaaa 360 tatatgaccc ttgttctcaa acacagaaag caaaattctc cctcacaagt gagcttcact 420 gggcagatgg gtttgttatt gtgtatgaca tcagtgatag gtcttcattt gcttttgcaa 480 aagcgctgat ctacagaatc cgggagccac aaactagtca ttgtaaaaga gctgtggaat 540 cagcagtgtt tttggttggc aacaaacgag atctttgtca tgtgcgagag gttggctggg 600 aagaagggca aaagctggca ctggaaaacc gatgccaatt ctgtgaactg tctgcagcag 660 agcagtctct ggaggtggaa atgatgttta tcagaattat caaggacatc ctgataaact 720 tcaaactcaa agaaaagaga cgtcccagtg gatctaaatc aatggccaaa ttgatcaata 780 atgtatttgg aaagagaagg aaatctgttt agtagacagg taatcctggg agatttccta 840 tatcagagag tttcaaacat tcacatgata attaaactaa cctttgtatg caattttttt 900 ttggtaaaaa gaattctctt ggagatatga aatgattgag tatgaaccac agctgtgttt 960 tcaaatatgt agtttgcctt tttggttgtt gtaccctgct cactctcctt cacacagaac 1020 ctttcattta ttgtacaaca tcacactcac cctaacctac tggcggacag cgatcccagt 1080 ttgccttgcc aaataaactc tgtttatgtg aatttattaa acgaccatgc cataaaaaaa 1140 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1182 <210> 10 <211> 632 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(632) <223> Homo sapiens zymogen granule protein 16 (ZG16), mRNA. <400> 10 cccagaatgt tgacagtcgc tctcctagcc cttctctgtg cctcagcctc tggcaatgcc 60 attcaggcca ggtcttcctc ctatagtgga gagtatggaa gtggtggtgg aaagcgattc 120 tctcattctg gcaaccagtt ggacggcccc atcaccgccc tccgggtccg agtcaacaca 180 tactacatcg taggtcttca ggtgcgctat ggcaaggtgt ggagcgacta tgtgggtggt 240 cgcaacggag acctggagga gatctttctg caccctgggg aatcagtgat ccaggtttct 300 gggaagtaca agtggtacct gaagaagctg gtatttgtga cagacaaggg ccgctatctg 360 tcttttggga aagacagtgg cacaagtttc aatgccgtcc ccttgcaccc caacaccgtg 420 ctccgcttca tcagtggccg gtctggttct ctcatcgatg ccattggcct gcactgggat 480 gtttacccca ctagctgcag cagatgctga gcctcctctc cttggcaggg gcactgtgat 540 gaggagtaag aactccctta tcactaaccc ccatccaaat ggctcaataa aaaaatatgg 600 ttaaggctaa aaaaaaaaaa aaaaaaaaaa aa 632 <210> 11 <211> 2096 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2096) <223> Homo sapiens bestrophin 4 (BEST4), mRNA. <400> 11 cagccctggg ggcaactctt gtgacctcct gccccaggct cccagcacca tgacggtttc 60 atacactctc aaagtggcgg aggcccgctt cggaggtttc tctggcctgc ttctccgctg 120 gaggggaagc atctacaagc tcctctacaa ggaattcctc ctctttgggg ccttgtacgc 180 tgtgcttagc atcacctacc ggctgctgct gacccaggag cagaggtacg tgtatgctca 240 ggtggcccgg tactgcaacc gctcagcaga cctcattccc ttgtcctttg tattgggttt 300 ctatgtgact ctcgtggtga accgctggtg gtcccagtac acaagcatcc cgctgccaga 360 ccagctgatg tgcgtcatct cggctagcgt gcacggcgtg gaccagcggg gccgcctgct 420 gcgccgcacc ctcatccgct acgcgaacct ggcgtccgtg ctggtgctgc gctcggtcag 480 cacccgcgtg cttaagcgct tccccaccat ggagcacgtg gtggacgcag gtttcatgtc 540 ccaggaagag aggaaaaagt ttgagagcct gaaatccgac ttcaacaagt actgggtccc 600 ctgcgtctgg ttcaccaacc tggcggccca ggcccggagg gacgggcgaa tacgtgacga 660 tatcgctctc tgtctacttt tggaagagct gaacaagtac cgagccaagt gcagcatgct 720 attccactat gactggatca gcatccccct cgtctacacc caagtggtga ccatagccgt 780 ctactctttc tttgccctct ccctggttgg ccgccagttt gtggagccag aggcaggggc 840 tgccaaacct cagaagcttc tgaagccagg ccaggagcca gccccagccc tgggagaccc 900 ggacatgtac gtgcctctca ccactctgct gcagttcttc ttctatgctg gctggctcaa 960 ggtggctgaa cagatcatca acccatttgg tgaggatgat gacgactttg agacaaatca 1020 gctcatagac cgcaacttgc aggtgtccct gctatccgtg gacgaaatgt accagaacct 1080 tccccccgct gagaaggacc agtactggga tgaggaccag ccgcagccac cctacactgt 1140 ggccacggcg gccgagtctc tgcggccctc attcctgggc tccaccttca acctgcgcat 1200 gagcgacgac cctgagcaga gcctgcaggt ggaggcgtcc cccggatctg gtcggcccgc 1260 gcccgccgcg cagaccccgt tgctcggccg cttcctgggc gtaggggcgc cctccccggc 1320 catcagcctc cggaacttcg gccgcgtgcg aggcaccccc cgccccccgc atctgctgcg 1380 cttccgggcg gaggagggcg gcgaccccga ggccgcagcc cgcatcgagg aggaatcggc 1440 ggagtccggg gacgaggccc tggagccctg aggtctcgcc tgcccccgcc cggtttcccc 1500 cacccactgc cctccttccc tcccgtgccc ggtcctgcca gccagctcta ttagagcagc 1560 ttttcctgtg tgccttgaag gccagagcat ttagggacag aacttgaaag agaagatggc 1620 gaaaagggcc tgagccaggg ctgggaatgt gtccactttg gtgggagaga aggtcggttg 1680 cttgggggac gtgaagctag aaaaataaat gagcccaggc atagaggact agagcccagg 1740 tgcacggtta gcttcacagc aacagggagc taggccattg gttctcaaac ttaaggaagg 1800 atcagcatca cggaaggtct tgtcaaaaga gtgctgggca ccactcccag catttctggc 1860 acgttagatt tgggatggcg cccaataact tgcatttcta acaagttccc aggtgatgct 1920 gtgctgcttg tccaggaaac acaatttgag agtcatgtga aacgtgcttg aaggggtata 1980 ccttaccctg gtaaccttac tcaaaagaag ggtcagtgtg tgctggggga cttttgcctt 2040 gtttgtaatg ttaaagtttt tgtttacatt gagaatatat tcaagttttt gtttaa 2096 <210> 12 <211> 1182 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1182) <223> Homo sapiens membrane-spanning 4-domains, subfamily A, member 12 (MS4A12), mRNA. <400> 12 acacaggttg gagcagagaa agaggaaaca tagaggtgcc aaaggaacaa agacataatg 60 atgtcatcca agccaacaag ccatgctgaa gtaaatgaaa ccatacccaa cccttaccca 120 ccaggcagct ttatggctcc tggatttcaa cagcctctgg gttcaatcaa cttagaaaac 180 caagctcagg gtgctcagcg tgctcagccc tacggcatca catctccggg aatctttgct 240 agcagtcaac cgggtcaagg aaatatacaa atgataaatc caagtgtggg aacagcagta 300 atgaacttta aagaagaagc aaaggcacta ggggtgatcc agatcatggt tggattgatg 360 cacattggtt ttggaattgt tttgtgttta atatccttct cttttagaga agtattaggt 420 tttgcctcta ctgctgttat tggtggatac ccattctggg gtggcctttc ttttattatc 480 tctggctctc tctctgtgtc agcatccaag gagctttccc gttgtctggt gaaaggcagc 540 ctgggaatga acattgttag ttctatcttg gccttcattg gagtgattct gctgctggtg 600 gatatgtgca tcaatggggt agctggccaa gactactggg ccgtgctttc tggaaaaggc 660 atttcagcca cgctgatgat cttctccctc ttggagttct tcgtagcttg tgccacagcc 720 cattttgcca accaagcaaa caccacaacc aatatgtctg tcctggttat tccaaatatg 780 tatgaaagca accctgtgac accagcgtct tcttcagctc ctcccagatg caacaactac 840 tcagctaatg cccctaaata gtaaaagaaa aaggggtatc agtctaatct catggagaaa 900 aactacttgc aaaaacttct taagaagatg tcttttattg tctacaatga tttctagtct 960 ttaaaaactg tgtttgagat ttgtttttag gttggtcgct aatgatggct gtatctccct 1020 tcactgtctc ttcctacatt accactacta catgctggca aaggtgaagg atcagaggac 1080 tgaaaaatga ttctgcaact ctcttaaagt tagaaatgtt tctgttcata ttactttttc 1140 cttaataaaa tgtcattaga aacaaaaaaa aaaaaaaaaa aa 1182 <210> 13 <211> 6741 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(6741) <223> Predicted: Homo sapiens KIAA1644 protein (KIAA1644), mRNA. <400> 13 aaggttggtg gcaaccagga gccggggaag aggccagcag ctgcagggag accgcagcca 60 gcggaggggg cttctgatcc ctcagtcaca gggctcggca ggcagctctg gacggatcaa 120 tgcaagccag acgatgacca gttgtggcca gcagtccttg aacgtgctcg ccgtcctctt 180 ctcattgctg ttttctgcag tcttgtctgc acatttccgg gtctgtgaac catacacaga 240 ccacaaaggc cgctaccact ttggcttcca ctgcccccgg ctctcggaca acaagacctt 300 catcctctgt tgtcaccata acaacacggt cttcaaatac tgctgcaacg agacggagtt 360 ccaggcggtg atgcaggcga acctcacggc cagctccgag ggttacatgc acaacaatta 420 caccgccttg ttgggagtgt ggatctatgg atttttcgtg ttgatgctgc tggttctgga 480 ccttttgtat tactcggcaa tgaactacga catctgcaag gtctacctgg cacggtgggg 540 catccaagga cgatggatga aacaggaccc ccggcggtgg gggaaccccg ctcgggcccc 600 tcggccgggt cagcgggccc cacagccgca gcctccccca ggcccgctgc cacaagcccc 660 acaggccgtg cacacattgc ggggagatgc tcacagccca ccgctgatga ccttccagag 720 ttcgtctgcc tgaaaacgct tttgctgtgc ctcaggatgg gggagatgag atctgaagca 780 cccggtgcag cctccgagaa gaacaacttc tacagagatg ccagggacag ccgaggtagc 840 ggcggtggca caggaggaaa tgctgcctgt gcccaaagcc cccttccgcg gacttctaag 900 attaggagca aactcagggg taggggctgg gggtgcaggg gaggggattc tgagccacct 960 gtccgcaagc aatagtccta ttttgggctg gtggcttctg agaggtgact cattgtggac 1020 tcaggatgac caagacaaag caactctggc tgattccagc caggaggatt gaggcctgtg 1080 agttatacct gtggttgaaa accgaagctt cccttgcccc tgctccctcc agtagtggcc 1140 ccttggggct atttgtgtca gaatattgaa tgtgcgtgtg tgtgtgcgtg tgtgtgattt 1200 ggggtgttct ttttgtttgc ttggttggtt ggtttttatt ggggcttccc ccctcaagtt 1260 ctctgatggg catgagtcac cctccggctg ggggttctca tccgtgtcaa tgtccgagcc 1320 gcaagcttat tgctaagcac agggtacggc ccctctgtgt ctcggggagc actggggatt 1380 tgaaaatgcc agtcagggtt gtttcttaca gaattcgttc ctgtaacaat agtaatacta 1440 agggctgcat ctcaggctga ccacagggca ggtgccaagt taagtgtttt catgcactcc 1500 ctctctcacc acctgggagg caggtatgat taaccccctg cagaaaaact cacagtgggg 1560 aagcggtgcc ggaacccaaa gtccaggctc caactccctg gacgtgacat gctcgccagc 1620 cggggtacac cctgcacaat gctgggagca tctccttgat gcctccacca tcaccgcctg 1680 gagcgctgat ccactcagca cattctggct aagcatctgc tgtgtgccag gccccgtgct 1740 gggcagtgat gggaatgaaa gatgagttag atctcatctc tgcccccggg gagcctccca 1800 tctggtggga gacacagaca cgtggatctt tgctggaaag ggtaacaagg ccatggaaac 1860 ccaggcagga gcgttctaga aatccatcca ctttcaagta ggacttccat gcccgtaaca 1920 tccacccacc gagctaatca cccccactcc tgccccgctg ccctgggaca cctatgagat 1980 ggcatcacct aaatcatcac aaacatctcc aaaggccatg ctgccagtgt agacacactc 2040 attccatggg tgttagtgat accaaatctc ccccagctct tagctcggga ggccctgctt 2100 gatcaatgtg tgtgtcctct gacgcagttt cctcatttca tcagacctag tgttctcaca 2160 ctgaccaccc atccattcac cagacacgac agtgagcaag gcaggtccct gctcactgtg 2220 ctagctttct agctggggca ggaagacagt gaagaaggaa ggtggcgaag gcagtgagtg 2280 ctctgccggg aactcagtgc caggaactca gttcgaggga cacgtgagtg agacccttgt 2340 ggacctgggg tggtctggga aggccgcctt gagcagatga ttgaagccca gatttgaatg 2400 acacacagga gccagtaatg ggcgttaaag ataggaaaag agcattccag gcagaaggaa 2460 cggctagtgc aaagatcctg cggcagccac aggcttggtg gtttcaagga agcacaagaa 2520 agccaggtgg cacaagaaag ccaggtggct ggggacccag agggaaggca gaaggagatg 2580 agggtgatag tgcccagctc tgggctctgc tgtgagtcaa gctgtgcaaa cacaatgtcc 2640 tgcctttgga aaagcagaac aaacttgcta gggtataaag catcctccat tctgcctggc 2700 tgtccatcct ctcaacagcc ccatgaagaa ggggctctcc ccattttatg gacaagaaga 2760 cagactcagc tgggtcaagt ggcttgccca ggatcacaca ggtcagctgt ggaagaccca 2820 ggcccctggc ttcagtcttt gggtccagct gtctcctcca ggcagtgctg ccagtgtcca 2880 ggcatatggc ttggcaaagt gggagaacct ctgcttgggg tctcgattgg agaaaggaat 2940 ggcttcctct cccctgatgt gagccgtccc agggccatgt tgccgtaagg gggtgcacag 3000 cctgtccact agcccagctg cggaagccac agctgtgtcc cacgtgcagt gcctcagaag 3060 gcagaggaag ccttgaggtg ggggcccaag acccagattc tgacatcagc tctgccactg 3120 agaacagcgt gacctcaggc aaggtctgtt acctcagttt ccccatcggt aagaggaagg 3180 agtcagatgg gtatttaagg agtttgcaac cctcgtgtcc tgctgtcctg gacaatgctc 3240 tgtaggtgct tcctctgcca aaaaggaact ggtggccttg cctccctctc ctggacacct 3300 ggggtcaaag gtcactgcca aatagacagc tagaactggg gttcacctaa gcatcccttg 3360 agatgtacaa ccttctagga ggacattcct cctgcctgcc cccctccccg caagaggtct 3420 tttcaggaat aactgaaaaa cccatggggt ttgtggtcct gctgctctgc caagtccctc 3480 ttgggcagct gggctgagga ctggaacatt ctgtggcaag caggaggcct cagcagagat 3540 caccaagacc cagcacacct ggtgcagaca gccacggcat cctccttcct gcaggtcacc 3600 cccacgagcc acttaacctc tcagagcctc tgcttctcac ctgtcaagtg tgtgaggtag 3660 ggtaccagtt agtcacggta cttgctgtct cacagaggag ccgacaggtg agaacagtgt 3720 gcatgtgggt gtgaacactc agtgtggaaa gcaggtgtgt gtgtattcaa tcccccaatg 3780 gtgtcaaggg ctcctcaaaa tgccatgggt ccccaggtca ttgtgataaa cactgtcccc 3840 atcctgctgt ggttgtggct ggaaggtccc tcaaggagta gactgtccct gagaacaaga 3900 tggatgcagg gtagtgacga gttcaagcat agctagagtt actgtttttt agcaactcaa 3960 cctgattttt taagctgcct acttttactt tttactgtga gcttctgtcc atcaccatgt 4020 aatttgtaat aataataata caaaaagaaa aacgagagag agaagaggac aagatgtcca 4080 cagaggaatc tgcattcgag gctgtttgca gaactaccgc gtttgtaagg actgtttccc 4140 actgggaact gtgtgtaatt aatgagcagt tttatgcttt ccctctcgtc tgtgtacggt 4200 gtgattgttg tgtgtttcag aatctctatt cagaaccaat agctggtaat gcctgctggc 4260 tcgctgccct caagttagcc tctgaacgtg ccctgcacct agagaagcag ccttctcacc 4320 cgcctcacct ggctgctcca gcggccaggc cagccacctg accatgacca ttgctgatgt 4380 gcaacaggcc ttaattgaaa aaacacacaa gtacatacat gcacatgcgc gcacacacac 4440 aggtgatttc acaggtagat ctggtccctc ttgctgtctc caatgctcta gaaagcagca 4500 agtaggcagc tgacagtgtt cccagggtga gtggcatctc ccctcatcat cagaaagatt 4560 cagtcaaatt ttggcccaga gctgaagagg aggacttggg aatgtcaggg aaaacatgac 4620 agggctaggg gttaacaggc ttctttggcc aggagatggt ttccagttca ccgtcaaccc 4680 aaaagctctc ttcaggtcat ggcaaacaga ccagggctgt gggtgtggct gtgcttggca 4740 ctgactcccc cacaggccgc tgtccaggtt ggctcaggat tccagctgcc atccccaggc 4800 aggcccctcc gctggctcgg ctgctttcac aatcaccatg tctgtctatt agagactgtg 4860 ccattcaagg agacggggtc cccgggggtg cagacttgta aaatttttta atttttcaac 4920 ttggctgaac tggtccccat caacaggaaa agccttcgga agtgaattta cagatttctc 4980 ccatgtttga aattaacata acatgaaccc agaaggcaga gcttgcagtg agctgagatc 5040 gcaccagtgc actccagcct gggcaacaga gtgagactct gtctaggtag gtaggtaaga 5100 aggaaggaag gaagaacaga cctggatgga gttattggga acatgtctta tcaatgttga 5160 agggccccct atcactgtag ggagacatcc acgtgggttg ttttcgtctg ctgtgaaaat 5220 ctagggttgg aatcatggaa gcaaactgca ggaattctta atcatcctgc tcacgtggtg 5280 ggcatcagag ggtgtctgct tggcccccac agcactggga cagtcagaga ggccatgagt 5340 ggatgacgcc ctgatcactg ccctttgcag tccaggaata cctcactggg ctggggccat 5400 accctgtgcc ctctggaaga caagcctgcg cacttactat gtgccagatg ccatgcacag 5460 tgccctagtt ccttgctgta gcaccaacac gtcccacgct ggtgcttaaa tgcacgcaaa 5520 caactttggt ggttgtggcc cgaaaagctc aaatgttaaa gttaagcagt caggcaagct 5580 agaagaggtg aggagcctcc tagaaaactc attcgatgac acgcgcttcc ctcacctatt 5640 cagatacttg ccgagtgcct gccacttgcc tggccctgta cccagggccc atctgggagc 5700 cattcctgct atagctggga ccacttgtga aacggctagt tgtgcctaac agacatgctc 5760 agattcacaa aatgaattca gaacacttac ctgtcccacc cgtgaaagtg accttggagg 5820 tgtcattgcc ccccaccacc ccagtttcta gtccaagcca acagctggtg ctagatagat 5880 gcttgatgaa tgagcagatt tgactgttag ttactctgta cctaaaactc ctatctttac 5940 atcaaagccc tgacagattt gcccttgaca gactgaaatc cggggctgct gcagggttca 6000 cctccaggag gcaccattca cgacactgtc ccataaatgg taatgggctc ccagggatac 6060 tgtttacata gactgcactg agaacggtga cccttaggtt tgtacaatga ggtaccctgt 6120 tgaatgaccc taaaccagcc tccaaaatgt gcaggatccc acattggtca gcgccaaccc 6180 tgagcacagg atctaaaact atagatgata tggccaccct ggccacagct ggaaccaagc 6240 tggtggccca agagagagcc tcttcttgga attgcatgtc agtttctcat acgcagtttc 6300 ttcctatttt tcccatttcc cgttttaaag ctagtggcat acctcacagt caaataacca 6360 agtggtcagt gtctcgacaa tgtgcagtaa cgaggtgggg gctgcaaggg tgaggggctc 6420 agtcacctta acaaggcagg agacctccca caaaaggctg atgtgtcgtc cccagggcca 6480 gctggacaag ggcatgcagc gcaggggtag ggggatggaa atattttctc tcccgtaaac 6540 tctgacttca tgtgagcagg catggggtct ccctgagagc tgataaccgg gaaaaccaaa 6600 accaataata ttcctaataa taatactaga atgtaagaat aatcatgtgt ttttcactga 6660 ccgctgttgc tctgcttttg tctttatata cagtagtttt tataacaatg tccctaggtt 6720 ttaataaagg agtgtcatgt c 6741 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying GAPDH <400> 14 tcatgaccac agtccatgcc 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying GAPDH <400> 15 tccaccaccc tgttgctgta 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13orf18 <400> 16 gctgctgatg aaggtgctgt 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13orf18 <400> 17 ctatcgagcc agctgcactc 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13ORF3 <400> 18 cagattttgg acttgagcgg 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13ORF3 <400> 19 ttccaactgc tggatgatgg 20 <210> 20 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ASPM <400> 20 tcgagctgct tgtttgat 18 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ASPM <400> 21 tttcgctggc tcagacattc 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ARID3A <400> 22 gtggctccct ctttgcctac 20 <210> 23 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ARID3A <400> 23 ttgatctcca ccgacatgct 20 <210> 24 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C2ORF15 <400> 24 tgtcctcaac tctggggaag t 21 <210> 25 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C2ORF15 <400> 25 agagatcctg tgccagtccc 20 <210> 26 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying IQGAP3 <400> 26 tacaactatg cctccagccg 20 <210> 27 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying IQGAP3 <400> 27 tagacctcgc tgtctgtggc 20 <210> 28 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644773 <400> 28 attgggagct gcatcaatca 20 <210> 29 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644773 <400> 29 agtggacaat gcgcatcaat 20 <210> 30 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC144501 <400> 30 aaaaagcctg gagagcttcg 20 <210> 31 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC144501 <400> 31 agcttcctgt aggtggcgat 20 <210> 32 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying FLJ22655 <400> 32 gcacttgtgt ttggaaagga a 21 <210> 33 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying FLJ22655 <400> 33 gttcacagaa ttggcatcgg 20 <210> 34 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying ZG16 <400> 34 tcgctctcct agcccttctc 20 <210> 35 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying ZG16 <400> 35 agatagcggc ccttgtctgt 20 <210> 36 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying VMD2L2 <400> 36 gctgaacaag taccgagcca 20 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying VMD2L2 <400> 37 ctggtacatt tcgtccacgg 20 <210> 38 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying MS4A12 <400> 38 tttcccgttg tctggtgaaa 20 <210> 39 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying MS4A12 <400> 39 tggtgtcaca gggttgcttt 20 <210> 40 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying KIAA1644 <400> 40 acaaaggccg ctaccacttt 20 <210> 41 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying KIAA1644 <400> 41 ggggtcctgt ttcatccatc 20

Claims (6)

C13ORF3(chromosome 13 open reading frame 3, GeneBank accession No.NM_145061.4) 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 포함하는 대장암 진단용 조성물.A composition for diagnosing colorectal cancer comprising a C13ORF3 (chromosome 13 open reading frame 3, GeneBank accession No. NM_145061.4) gene, a sense and antisense primer pair of the gene, a protein expressed from the gene, or an antibody against the protein. 제1항에 있어서, 상기 센스 및 안티센스 프라이머쌍은 서열번호 18 및 19인 대장암 진단용 조성물.The composition for diagnosing colorectal cancer according to claim 1, wherein the sense and antisense primer pairs are SEQ ID NOs: 18 and 19. 3. 제1항에 있어서, 상기 조성물은 C13ORF18(chromosome 13 open reading frame 18, GeneBank accession No.NM_025113), ASPM(asp(abnormal spindle)-like, microcephaly associated, GeneBank accession No.NM_018136.3), IQGAP3(IQ motif containing GT pase activating protein 3, GeneBank accession No.NM_178229.4) 및 ARID3A(AT rich interactive domain 3A, GeneBank accession No.NM_005224.2)로 이루어진 군에서 선택된 하나 이상의 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 추가로 포함하는 대장암 진단용 조성물.The composition of claim 1, wherein the composition is C13ORF18 (chromosome 13 open reading frame 18, GeneBank accession No.NM_025113), ASPM (abnormal spindle) -like, microcephaly associated, GeneBank accession No.NM_018136.3), IQGAP3 (IQ motif containing GT pase activating protein 3, GeneBank accession No.NM_178229.4) and ARID3A (AT rich interactive domain 3A, GeneBank accession No.NM_005224.2), one or more genes selected from the group consisting of the sense and antisense primer pairs of the gene , Colorectal cancer diagnostic composition further comprising a protein expressed from the gene, or an antibody against the protein. 제3항에 있어서, 상기 유전자의 센스 및 안티센스 프라이머쌍중 C13ORF18 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 16 및 17인 센스 및 안티센스 프라어머쌍, ASPM 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 20 및 21인 센스 및 안티센스 프라어머쌍, IQGAP3 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 26 및 27인 센스 및 안티센스 프라이머쌍, ARID3A 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 22 및 23인 센스 및 안티센스 프라이머쌍인 대장암 진단용 조성물.The method of claim 3, wherein the sense and antisense primer pair of the C13ORF18 gene of the sense and antisense primer pair of the gene is SEQ ID NO: 16 and 17, the sense and antisense primer pair of the ASPM gene is SEQ ID NO: 20 and 21 sense and antisense primer pairs, the sense and antisense primer pairs of the IQGAP3 gene, SEQ ID NO: 26 and 27 sense and antisense primer pairs, sense and antisense primer pairs of the ARID3A gene are the sense and antisense primer pairs SEQ ID NOs: 22 and 23 Phosphorus colorectal cancer diagnostic composition. C13ORF3(chromosome 13 open reading frame 3, GeneBank accession No.NM_145061.4) 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 포함하는 대장암 진단용 키트.A kit for diagnosing colorectal cancer comprising a C13ORF3 (chromosome 13 open reading frame 3, GeneBank accession No. NM_145061.4) gene, a sense and antisense primer pair of the gene, a protein expressed from the gene, or an antibody against the protein. 제5항에 있어서, 상기 키트는 C13ORF18(chromosome 13 open reading frame 18, GeneBank accession No.NM_025113), ASPM(asp(abnormal spindle)-like, microcephaly associated, GeneBank accession No.NM_018136.3), IQGAP3(IQ motif containing GT pase activating protein 3, GeneBank accession No.NM_178229.4) 및 ARID3A(AT rich interactive domain 3A, GeneBank accession No.NM_005224.2)로 이루어진 군에서 선택된 하나 이상의 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 추가로 포함하는 대장암 진단용 키트.The kit of claim 5, wherein the kit is C13ORF18 (chromosome 13 open reading frame 18, GeneBank accession No.NM_025113), ASPM (abnormal spindle) -like, microcephaly associated, GeneBank accession No.NM_018136.3), IQGAP3 (IQ motif containing GT pase activating protein 3, GeneBank accession No.NM_178229.4) and ARID3A (AT rich interactive domain 3A, GeneBank accession No.NM_005224.2), one or more genes selected from the group consisting of the sense and antisense primer pairs of the gene , Colorectal cancer diagnostic kit further comprising a protein expressed from the gene, or an antibody against the protein.
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