KR20110036560A - Composition for diagnosing colorectal cancer and use thereof - Google Patents

Composition for diagnosing colorectal cancer and use thereof Download PDF

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KR20110036560A
KR20110036560A KR1020110023977A KR20110023977A KR20110036560A KR 20110036560 A KR20110036560 A KR 20110036560A KR 1020110023977 A KR1020110023977 A KR 1020110023977A KR 20110023977 A KR20110023977 A KR 20110023977A KR 20110036560 A KR20110036560 A KR 20110036560A
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정경숙
원미선
최정해
염영일
이희구
송은영
김선영
김영호
전호경
강창모
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한국생명공학연구원
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Abstract

PURPOSE: A LMTK3 gene is provided to diagnose colon cancer by checking expression level of the gene and to enable drug screening. CONSTITUTION: A composition for diagnosing colon cancer contains LMTK3[lemur tyrosine kinase 3](GeneBank accession No. NM_001080434) gene, a sense and antisense primer pair of the gene, a protein expressed from the gene, or antibody for the protein. The primer pair has sequence numbers 15 and 16. A kit for diagnosing colon cancer contains the LMTK3 gene, 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 LMTK3는 기능적으로는 Tyrosine kinase 도메인을 가지고 있다는 것이 알려져 있을 뿐, 다른 기능에 대해서 전혀 보고된 바가 없으며, LOC644774는 Phosphoglycerate kinase 1 의 유사 단백질을 코딩하고 있으나 기능 연구는 되어 있지 않다. HS.389988는 염기서열만 알려져 있고 WDR72는 WD repeat 도메인을 가진 미지의 단백질이다. LOC440157, LOC643911, C13ORF23, 및 LOC644424 또한 전혀 기능이 알려져 있지 않다. FLJ21511는 기능이 알려져 있지 않고 C9ORF19 는 Glioma pathogenesis와 관련되어 보고되었으나 암관련 보고는 없으며, MGC15476 는 DACT3 로도 알려져 있고 DACT3 단백질은 마우스의 뇌 분화시 발현되는 단백질로 알려져 있으며, HS.388347 는 유전자 서열만이 알려져 있다. Currently, it is known that LMTK3 functionally has a Tyrosine kinase domain, but no other functions have been reported. LOC644774 encodes a protein similar to Phosphoglycerate kinase 1, but functional studies have not been conducted. HS.389988 is an unknown protein with a known nucleotide sequence and WDR72 is a WD repeat domain. LOC440157, LOC643911, C13ORF23, and LOC644424 Also, the function is not known at all. FLJ21511 has unknown function and C9ORF19 Has been reported related to Glioma pathogenesis, but no cancer-related reports. MGC15476 is also known as DACT3, DACT3 protein is known as a protein expressed during brain differentiation in mice, and HS.388347 has only known gene sequence.

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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381 유전자의 신규한 용도를 제공하는 것을 목적으로 한다.The present invention aims to provide a novel use of the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 이루어진 군에서 선택된 하나 이상의 유전자를 포함하는 대장암 진단용 조성물을 제공한다.
The present invention provides a composition for diagnosing colon cancer comprising at least one gene selected from the group consisting of LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381.

본 발명의 'LMTK3', 'LOC644774', 'HS.389988', 'WDR72', 'LOC440157‘, ’LOC643911', 'C13ORF23', 'LOC644424', 'FLJ21511', 'C9ORF19', 'MGC15476', 또는 'LOC143381'의 '유전자'라 함은 이들 유전자의 DNA 또는 mRNA를 말하며, DNA 또는 mRNA의 전부 또는 일부를 모두 포함하는 개념이다.'LMTK3','LOC644774','HS.389988','WDR72','LOC440157','LOC643911','C13ORF23','LOC644424','FLJ21511','C9ORF19','MGC15476', or The term'gene' in'LOC143381' 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23 및 LOC644424 유전자는 대장암세포에서 특이적으로 발현이 증가하며, FLJ21511, C9ORF19, MGC15476 및 LOC143381 유전자는 대장암세포에서 특이적으로 발현이 감소한다. 따라서 상기 유전자의 발현정도를 조사하면 대장암을 진단할 수 있다.The LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424 genes are specifically increased in expression in colon cancer cells, and the FLJ21511, C9ORF19, MGC15476 and LOC143381 genes are specifically reduced in expression in colon cancer cells. . Therefore, by examining the expression level of the gene, colon cancer can be diagnosed.

상기 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381유전자의 서열정보는 표 1에 나타낸 바와 같다.The sequence information of the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 이루어진 군에서 선택된 하나 이상의 유전자의 센스 및 안티센스 프라이머쌍을 포함하는 대장암 진단용 조성물을 제공한다.In addition, the present invention is for the diagnosis of colorectal cancer comprising sense and antisense primer pairs of one or more genes selected from the group consisting of LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 The composition is provided.

상기 센스 및 안티센스 프라이머쌍은 상기 유전자에 대한 상보적인 염기서열을 갖는 서열번호 15~38의 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: 15 to 38 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 12종의 유전자의 발현양을 측정할 수 있다. 예를 들면, RT-PCR방법 등으로 측정할 수 있다.The expression level of the 12 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 이루어진 군에서 선택된 하나 이상의 유전자로부터 발현된 단백질을 포함하는 대장암 진단용 조성물을 제공한다.The present invention also provides a composition for colon cancer diagnosis comprising a protein expressed from one or more genes selected from the group consisting of LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381. do.

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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23 또는 LOC644424 유전자는 대장암세포에서 특이적으로 발현이 증가하며, FLJ21511, C9ORF19, MGC15476 또는 LOC143381 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23 or LOC644424 genes are specifically increased in colorectal cancer cells, and the FLJ21511, C9ORF19, MGC15476 or LOC143381 genes are specific in colorectal cancer cells. Since expression is reduced, colon cancer can be diagnosed by investigating 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. LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23 또는 LOC644424 유전자는 대장암세포에서 특이적으로 발현이 증가하여 상기 유전자로부터 발현된 단백질의 양 또한 증가하게 되며, FLJ21511, C9ORF19, MGC15476, 또는 LOC143381 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. LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23 or LOC644424 genes specifically increase in colorectal cancer cells, resulting in an increase in the amount of protein expressed from the gene, FLJ21511, C9ORF19, MGC15476, or LOC143381 The expression of the gene is specifically reduced in colon cancer cells, so that the amount of the protein expressed from the gene is also decreased. 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 12종의 각 유전자를 통상적인 방법에 따라 발현벡터에 클로닝하여 상기 유전자에 의해 코딩된 단백질을 얻고, 얻어진 단백질로부터 통상적인 방법에 의해 제조될 수 있다. 여기에는 12종의 단백질의 부분 펩타이드도 포함하며, 본 발명의 부분펩타이드로는 최소한 7개 이상, 바람직하게는 12개 이상의 아미노산을 포함한다.The antibody is obtained by cloning each of the 12 genes of the present invention into an expression vector according to a conventional method to obtain a protein encoded by the gene, and can be prepared from the obtained protein by a conventional method. This includes partial peptides of 12 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381, sense and antisense primer pairs of the genes, from the gene It provides a kit for diagnosing colon cancer comprising the expressed protein 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381. 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 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 is for screening colorectal cancer treatments comprising proteins expressed from one or more genes selected from the group consisting of LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 The composition is provided. 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381.

상기 siRNA의 염기서열은 상기 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 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 sequence of one or more genes (mRNA) selected from the group consisting of the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381. It may be a continuous 19-23 base 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381로 이루어진 군에서 선택된 하나 이상의 유전자 발현만을 억제하는 효과를 나타내므로, 대장암 관련 유전자 기능연구에 이용할 수 있다. 또한, 상기 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, Since it exhibits an effect of suppressing the expression of only one or more genes selected from the group consisting of MGC15476 and LOC143381, it can be used for gene function studies related to colon cancer. In addition, the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and by inhibiting the expression of one or more genes selected from the group consisting of LOC644424 can also exhibit the effect of killing colon cancer cells.

본 발명은 또한 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424.

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

본 발명의 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424 of the present invention is highly expressed in colorectal cancer cells, administration of the gene inhibitor to express the gene When inhibited, colon cancer can be suppressed.

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, LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424 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, LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424 may be siRNA (Small Interfering RNA) of the gene.

즉, 상기 siRNA의 염기서열은 상기 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 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 consecutive in each of the nucleotide sequences of one or more genes (mRNA) selected from the group consisting of the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424. It may be a sequence of 23 consecutive bases.

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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424로 이루어진 군에서 선택된 하나 이상의 유전자로부터 발현된 단백질에 대한 억제제를 포함하는 대장암 치료용 조성물을 제공한다.The present invention also provides a composition for treating colon cancer comprising an inhibitor for a protein expressed from one or more genes selected from the group consisting of LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424.

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, 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 agents, emulsifiers, 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381 유전자는 표 1의 염기서열 또는 상기 염기서열 중 하나 이상의 염기가 결실, 치환 또는 삽입된 염기서열일 수 있다.In the present invention, the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 genes are the nucleotide sequence of Table 1 or one or more of the nucleotide sequences are deleted or substituted. Or it may be an inserted nucleotide sequence.

상기 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 및 LOC143381 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 and LOC143381 genes, the sense and antisense primer pairs of the gene, and the siRNA sequence of the gene are examples only, and are limited thereto. It is obvious to a person skilled in the art that it is not. 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)).

LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 또는 LOC143381 유전자는 대장암과 높은 관련성을 가지므로, 상기 유전자의 발현량을 확인함으로써 대장암의 진단, 약물스크리닝 등이 가능하고, 본 발명의 유전자를 대장암 치료타겟으로 할 수 있다.LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476 or LOC143381 genes are highly related to colon cancer. 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 사진(A)과 LOC440157 유전자와 LOC643911 유전자의 발현비를 나타낸 그래프(B)이다.
도 3은 임상조직에서 대장암 저발현 유전자의 발현량을 나타낸 RT-PCR결과 사진(A)과 MGC15476유전자의 발현비를 나타낸 그래프(B)이다.
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.
Figure 2 is a picture of the RT-PCR results showing the expression level of the high-expression gene for colon cancer in clinical tissues (A) and a graph (B) showing the expression ratio of the LOC440157 gene and the LOC643911 gene.
3 is a photo (A) of the RT-PCR result showing the expression level of the low-expression gene for colon cancer in clinical tissues and a graph (B) showing the expression ratio of the MGC15476 gene.
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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424을 확인하였고, 저발현 유전자로 FLJ21511, C9ORF19, MGC15476 및 LOC143381을 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, LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424 were identified as high-expression genes, and FLJ21511, C9ORF19, MGC15476 and LOC143381 were identified as low-expression genes.

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. 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.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. 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, 25cycle을 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 및 LOC644424 와 저발현 유전자인 FLJ21511, C9ORF19, MGC15476 및 LOC143381의 프라이머는 단백질 코딩 내부에서 디자인 하였으며 각 프라이머의 길이는 19~24mer 이고 Tm 값은 55도 근처이다.Primers for 8 high-expression genes related to colon cancer, LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, and LOC644424, and low-expression genes FLJ21511, C9ORF19, MGC15476 and LOC143381, were designed inside the protein coding. The length of the primer is 19~24mer 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(A, B) 및 도 3(A, B)에 나타내었으며, 도 2는 임상조직에서 대장암 고발현 유전자의 발현량을 나타낸 RT-PCR 결과사진(A)과 LOC440157과 LOC643911의 발현비를 나타낸 그래프(B)이다. 도 3은 임상조직에서 대장암 저발현 유전자의 발현량을 나타낸 RT-PCR 결과사진(A)과 MGC15476의 발현비를 나타낸 그래프(B)이다. 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 LOC440157과 LOC643911, 저발현유전자 MGC15476의 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 (A, B) and 3 (A, B), and Fig. 2 is a photo of RT-PCR results showing the expression levels of high-expressing colon cancer genes in clinical tissues (A) and LOC440157 and LOC643911. It is a graph (B) showing the expression ratio of. 3 is an RT-PCR result picture showing the expression level of a low-expression gene for colon cancer in clinical tissues (A) and a graph showing the expression ratio of MGC15476 (B). 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 LOC440157 and LOC643911, and the low-expression gene MGC15476, which showed little difference in expression levels, the images were quantified with the TotalLab v1.0 program [Nonlinear Dynamix Co., Ltd.]. Corrected with GAPDH and plotted again. 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 또는 LOC644424는 대장암의 진단, 또는 약물스크리닝 등을 위한 대장암마커, 또는 치료타겟 등으로 사용할 수 있고, 저발현되는 유전자 FLJ21511, C9ORF19, MGC15476, 또는 LOC143381는 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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, or LOC644424 are The genes FLJ21511, C9ORF19, MGC15476, or LOC143381, which can be used as a colon cancer marker for diagnosis or drug screening, or as a therapeutic target, are underexpressed as colon cancer inhibitory markers for diagnosis of colon cancer or drug screening, etc. It seems to be available.

<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 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, 또는 LOC644424의 발현량은 대장암 세포주에서 대체적으로 높게 나타났으며, 저발현유전자 FLJ21511, C9ORF19, MGC15476 또는 LOC143381의 발현량은 대장암 세포주에서 대체적으로 낮게 나타났다.As a result, the expression levels of 8 kinds of colon cancer high expression genes LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, or LOC644424 were generally high in colon cancer cell lines, and the low expression genes FLJ21511, C9ORF19, The expression level of MGC15476 or LOC143381 was generally low in colorectal cancer cell lines.

이와 같은 결과는 LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476, 또는 LOC143381 유전자와 대장암의 관련성을 재확인해 주는 것으로써, 상기 유전자의 발현량을 확인함으로써 대장암의 진단, 약물스크리닝 등이 가능하고, 상기 유전자를 대장암 치료타겟으로 할 수 있음을 나타내는 것이다.These results confirm the relationship between the LMTK3, LOC644774, HS.389988, WDR72, LOC440157, LOC643911, C13ORF23, LOC644424, FLJ21511, C9ORF19, MGC15476, or LOC143381 gene and colon cancer, thereby confirming the expression level of the gene. By doing so, it is possible to diagnose colorectal cancer, screening drugs, and the like, and indicate 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> P07-075-KRI-DA2 <160> 38 <170> KopatentIn 1.71 <210> 1 <211> 4972 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(4470) <223> PREDICTED: lemur tyrosine kinase 3(LMTK3), mRNA. <400> 1 atgaggcaag tgctgtggtt gtgtaatgtc tgcgtaaccg cacgggaaac ccgccaccac 60 ctccacctcc ctgccatcct cgacaagatg cctgcccccg gcgccctcat cctccttgcg 120 gccgtctccg cctccggctg cctggcgtcc ccggcccacc ccgatggatt cgccctgggc 180 cgggctcctc tggctcctcc ctacgctgtg gtcctcattt cctgctccgg cctgctggcc 240 ttcatcttcc tcctcctcac ctgtctgtgc tgcaaacggg gcgatgtcgg cttcaaggaa 300 tttgagaacc ctgaagggga ggactgctcc ggggagtaca ctccccctgc ggaggagacc 360 tcctcctcac agtcgctgcc tgatgtctac attctcccgc tggctgaggt ctccctgcca 420 atgcctgccc cgcagccttc acactcagac atgaccaccc ccctgggcct tagccggcag 480 cacctgagct acctgcagga gattgggagt ggctggtttg ggaaggtgat cctgggagag 540 attttctccg actacacccc cgcccaggtg gtggtgaagg agctccgagc cagcgcgggg 600 cccctggagc aacgcaagtt catctcggaa gcacagccgt acaggagcct gcagcacccc 660 aatgtcctcc agtgcctggg tctgtgcgtg gagacgctgc cgtttctgct gattatggag 720 ttctgtcaac tgggggacct gaagcgttac ctccgagccc agcggccccc cgagggcctg 780 tcccctgagc taccccctcg agacctgcgg acgctgcaga ggatgggcct ggagatcgcc 840 cgcgggctgg cgcacctgca ttcccacaac tacgtgcaca gcgacctggc cctgcgcaac 900 tgcctgctga cctctgacct gaccgtgcgc atcggagact acgggctggc ccacagcaac 960 tacaaggagg actactacct gaccccagag cgcctgtgga tcccactgcg ctgggcggcg 1020 cccgagctcc tcggggagct ccacgggacc ttcatggtgg tggaccagag ccgcgagagc 1080 aacatctggt ccctgggggt gaccctgtgg gagctgtttg agtttggggc ccagccctac 1140 cgccacctgt cagacgagga ggtcctcgcc ttcgtggtcc gccagcagca tgtgaagctg 1200 gcccggccga ggctcaagct gccttacgcg gactactggt atgacattct tcagtcctgc 1260 tggcggccac ctgcccagcg cccttcagcc tctgatctcc aattgcagct cacctacttg 1320 ctctccgagc ggcctccccg gcccccaccg ccgccacccc caccccgaga cggtcccttc 1380 ccctggccct ggccccctgc acacagtgcg ccccgcccgg ggaccctctc ctcaccgttc 1440 cccctactgg atggcttccc tggagccgac cccgacgatg tgctcacggt caccgagagt 1500 agccgcggcc tcaacctcga gtgcctgtgg gagaaggccc ggcgtggggc cggccggggt 1560 gggggggcac ctgcctggca gccggcgtcg gcccccccgg ccccccacgc caacccctcc 1620 aaccctttct acgaggcgct gtccacgccc agcgtgctgc ctgtcatcag cgcccgcagc 1680 ccctccgtga gcagcgagta ctacatccgc ttggaggagc acggctcccc tcctgagccc 1740 ctcttcccca acgactggga ccccctggac ccaggagtgc ccgcccctca ggccccccag 1800 gccccctccg aggtccccca gctggtgtcc gagacctggg cctcccccct cttccctgcg 1860 ccccggccct tcccagccca gtcctcagcg tcaggcagct tcctgctgag cggctgggac 1920 cccgagggcc ggggcgccgg ggagaccctg gcgggagacc ctgccgaggt cttgggggag 1980 cgggggaccg ccccgtgggt ggaagaagaa gaggaggagg aggagggcag ctccccaggg 2040 gaagacagca gcagccttgg aggtggccca agccgccggg gtcccctacc ctgtcccctg 2100 tgcagccgcg agggggcctg ctcctgcctg ccactggagc ggggggacgc cgtagcaggc 2160 tggggaggcc accctgctct tggctgcccc cacccccccg aggacgactc ctcgctgcgg 2220 gcagagcggg gctccctggc cgacttgccc atggcccccc ccgcctcggc cccccccgag 2280 tttctggacc ccctcatggg ggcggcggcg ccccagtacc ccgggcgggg gccacctccc 2340 gctccccccc ccccgccgcc acctcctcgg gcccccgcgg acccggccgc gtcccccgac 2400 cccccttcgg ccgtggccag tcccggttca ggcctctcgt cgccgggccc caagccgggg 2460 gacagcggct acgagaccga gacccctttt tccccagagg gagccttccc aggtgggggg 2520 gcggccgagg aggaaggggt ccctcggccg cgggctcccc ccgagccacc cgacccagga 2580 gcgccccggc cacctccaga cccgggtccg ctcccactcc cggggccccg ggagaagccg 2640 accttcgtgg ttcaagtgag cacggaacag ctgctgatgt ccctgcggga ggatgtgaca 2700 aggaacctcc tgggggagaa gggggcgaca gcccgggaga caggacccag gaaggcgggg 2760 agaggccccg ggaacagaga gaaagtcccg ggcctgaaca gggacccgac agtcctgggc 2820 aacgggaaac aagccccaag cctgagcctc ccagtgaacg gggtgacagt gctggagaac 2880 ggggaccaga gagccccagg catcgaggag aaggcggcgg agaatggggc cctggggtcc 2940 cccgagagag aagagaaagt gctggagaat ggggagctga cacccccaag gagggaggag 3000 aaagcgctgg agaatgggga gctgaggtcc ccagaggccg gggagaaggt gctggtgaat 3060 gggggcctga cacccccaaa gagcgaggac aaggtgtcag agaatggggg cctgagattc 3120 cccaggaaca cggagaggcc accagagact gggccttgga gagccccagg gccctgggag 3180 aagacgcccg agagttgggg tccagccccc acgatcgggg agccagcccc agagacctct 3240 ctggagagag cccctgcacc cagcgcagtg gtctcctccc ggaacggcgg ggagacagcc 3300 cctggccccc ttggcccagc ccccaagaac gggacgctgg aacccgggac cgagaggaga 3360 gcccccgaga ctgggggggc gccgagagcc ccaggggctg ggaggctgga cctcgggagt 3420 gggggccgag ccccagtggg cacggggacg gcccccggcg gcggccccgg aagcggcgtg 3480 gacgcaaagg ccggatgggt agacaacacg aggccgcagc caccgccgcc accgctgcca 3540 ccgccaccgg aggcacagcc gaggaggctg gagccagcgc ccccgagagc caggccggag 3600 gtggcccccg agggagagcc cggggcccca gacagcaggg ccggcggaga cacggcactc 3660 agcggagacg gggacccccc caagcccgag aggaagggcc ccgagatgcc acgactattc 3720 ttggacttgg gaccccctca ggggaacagc gagcagatca aagccaggct ctcccggctc 3780 tcgctggcgc tgccgccgct cacgctcacg ccattcccgg ggccgggccc gcggcggccc 3840 ccgtgggagg gcgcggacgc cggggcggct ggcggggagg ccggcggggc gggagcgccg 3900 gggccggcgg aggaggacgg ggaggacgag gacgaggacg aggaggagga cgaggaggcg 3960 gcggcgccgg gcgcggcggc ggggccgcgg ggccccggga gggcgcgagc agccccggtg 4020 cccgtcgtgg tgagcagcgc cgacgcggac gcggcccgcc cgctgcgggg gctgctcaag 4080 tctccgcgcg gggccgacga gccagaggac agcgagctgg agaggaagcg caagatggtc 4140 tccttccacg gggacgtgac cgtctacctc ttcgaccagg agacgccaac caacgagctg 4200 agcgtccagg ccccccccga gggggacacg gacccgtcaa cgcctccagc gcccccgaca 4260 cctccccacc ccgccacccc cggagatggg tttcccagca acgacagcgg ctttggaggc 4320 agtttcgagt gggcggagga tttccccctc ctcccccctc caggcccccc gctgtgcttc 4380 tcccgcttct ccgtctcgcc tgcgctggag accccggggc cacccgcccg ggcccccgac 4440 gcccggcccg caggccccgt ggagaattga ttccccgaag acccgacccc gctgcaccct 4500 cagaagaggg gttgagaatg gaatcctctg tggatgacgg cgccactgcc accaccgcag 4560 acgccgcctc tggggaggcc cccgaggctg ggccctcccc ctcccactcc cctaccatgt 4620 gccaaacggg aggccccggg cccccgcccc ccagcccccc agatggctcc cctgaccccc 4680 ctgaccccct cggagccaaa tgaggcagga atccccccgc ccctccatag agagccgcct 4740 ttctcggaac tgaactgaac tcttttgggc ctggagcccc tcgacacagc ggaggtccct 4800 cctcacccac tcctggccca agacaggggc cgcaggcttc ggggacccgg accccccatt 4860 tcgcgtctcc cctttccctc cccagcccgg cccctggagg ggcctctggt tcaaaccttc 4920 gcgtggcatt ttcacattat ttaaaaaaga caaaaacaac tttttggagg aa 4972 <210> 2 <211> 282 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(282) <223> PREDICTED: similar to Phosphoglycerate kinase 1(LOC644774), mRNA. <400> 2 atgatgcttt gggcactggt tcacagagcc cacagctcca tggtaggagt caatctgcca 60 cagaaggctg gtgggttttt gatgaagaag gagctgaact actttgcaaa ggccttggag 120 agcccagagc gacccttcct ggccatcctg ggcggagcta aagttgcaga caagatccag 180 ctcatcaata atatgctgga caaagtcaat gagatgatta ttggtggtgg aatggctttt 240 aagttcctta aggtgctcaa caacatggag gtaggaactt aa 282 <210> 3 <211> 488 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(488) <223> K-EST0184252 L9SNU354 cDNA clone L9SNU354-11G075, mRNA sequence <400> 3 cttattttct ctgaacgatc ctgattccag tcatcttgtt gaatacccta gttctaataa 60 ttgactcttg cttttctaga gaaatatttc caaatgatgc tagttttgtc tcttcctttc 120 aaagttgtat accacttctt tttcttgtca ttttgcattg cctgggacct ccagaataat 180 gtttcatgaa gtagcatgta tccatatctg gttcttgact ttttcatcat tataattgtt 240 ttctatgggt tacttatcag tttaagaatg cttaattcct agatgaacta agagtgttta 300 ttacatgttg agatttatgg tatgcttttt cttcctcaag ataatgcatt ttttgtatta 360 tctgttaatg tgataggtta tccatttgtg tattttcaat cattgaacaa cccttgattt 420 ttttggataa actctatttg gtcattatgc atcattctat aaaccctgct gaatttttca 480 tttgccaa 488 <210> 4 <211> 7326 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(7326) <223> WD repeat domain 72(WDR72), mRNA. <400> 4 cctctgccgc tcctccgccc cacggctcag gattcgccca aaatgaggac ttccctgcag 60 gcagtggcac tctggggaca gaaggcccct ccccacagca tcactgccat catgatcact 120 gatgaccagc gaacgattgt gactggaagt caagagggtc agctctgtct ctggaatctc 180 tcacatgaac taaagatttc agcgaaagaa ctcctatttg gtcattcagc ttcggtaaca 240 tgtttggcaa gagcaaggga cttctctaaa cagccctaca ttgttagtgc tgctgaaaat 300 ggggagatgt gtgtttggaa tgtcaccaat ggacagtgcg tggagaaggc tacacttcct 360 tacaggcaca ctgcaatctg ttattaccac tgctcattcc ggatgacagg agaaggctgg 420 cttctttgtt gtggagaata tcaagatgtc cttataattg atgccaaaac tttggctgtt 480 gttcacagtt ttagatcatc tcagtttcct gactggatca actgcatgtg cattgttcac 540 tccatgagaa ttcaagaaga ttctctcttg gtggtatcag tagctggtga gctcaaagta 600 tgggatcttt cctcatctat caacagcatt caggaaaagc aagatgtcta tgaaaaagaa 660 tccaagtttc ttgagtcctt gaactgccag acaattcgat tttgcacata tactgagaga 720 cttctattgg tggtattttc taaatgttgg aaggtttatg attattgtga tttttccctt 780 ctgctgactg aagttagtag aaatgggcag ttctttgctg gtggagaagt gattgctgct 840 cacagaatcc tcatctggac agaagatggt cacagttaca tctatcagct gctgaacagt 900 gggctttcaa aaagcatata ccctgctgat ggaagagtgc ttaaagagac catttatcct 960 catttactgt gctctacttc tgtgcaggaa aataaggaac agagccgtcc ctttgttatg 1020 ggctacatga atgaaaggaa agagcctttt tacaaggtac ttttctctgg agaagtctca 1080 ggaagaatta ctttgtggca catccctgat gttcctgtat ccaagtttga tggttctcct 1140 agagagatac cagtaactgc cacctggact cttcaagata attttgataa gcatgatact 1200 atgtcacaaa gtattattga ctatttctct gggcttaaag atggggcagg aactgctgta 1260 gtcacttcat cagagtatat tccaagtctt gataaactaa tatgtggctg tgaagatggg 1320 acaattatca ttacccaggc tttgaatgct gccaaagcaa gacttctgga aggtggttct 1380 ttagtaaaag attctccccc tcataaagtt cttaaaggcc accaccaaag tgtcacttca 1440 ttactctatc cacatggtct ctcttcgaaa ttagaccaaa gttggatgtt gtctggggac 1500 ctggactcat gtgtgatctt gtgggatatc tttactgaag aaattttgca taaattcttt 1560 ttggaagctg gtccagtaac aagtcttttg atgtcaccag agaagtttaa actaaggggt 1620 gagcagataa tttgctgtgt gtgcggtgac cattccgtgg ctctccttca ccttgaggga 1680 aagagttgcc tcctgcatgc ccggaagcac ctttttcctg tgaggatgat aaaatggcac 1740 ccggttgaga attttttaat tgttggatgt gcagatgact cagtttatat ctgggaaatt 1800 gaaacaggca ctttggaaag acatgagaca ggagaaagag cacgaattat tcttaattgt 1860 tgtgatgatt cacagcttgt gaagtctgta cttcccattg cctcagagac acttaagcac 1920 aaaagtatag aacagagatc ctccagcccc taccagcttg ggccattacc ttgccctggt 1980 ctgcaggtgg agtcttcatg taaggttact gatgccaaat tttgcccaag accttttaat 2040 gtcttgcctg tgaagacaaa atggagtaac gttggctttc atattcttct atttgatctg 2100 gaaaaccttg ttgaactttt gctaccaact ccactcagtg atgttgactc ttccagttca 2160 ttctatggtg gtgaggtcct gagaagagcc aagagcacag tggagaagaa gacactgaca 2220 ctgagaaaaa gtaaaactgc ctgtggtcct ctttcagcag aggcactagc caagcctatt 2280 actgaaagcc tggcccaagg agataatacc atcaaattct cagaagaaaa tgatggcatt 2340 aaaaggcaga agaaaatgaa gatctccaaa aaaatgcagc ctaagccatc aagaaaagta 2400 gatgccagtc tcacaataga cacagcaaaa ttgtttctgt cttgcctttt gccatgggga 2460 gtggataaag atttagatta tctttgcatt aagcacctca atattttaaa gcttcagggt 2520 cctatttctt tgggaatttc tttgaatgaa gataatttct cactgatgtt gccaggttgg 2580 gatttatgca atagtggaat gataaaagac tattcaggag taaatttatt ttccaggaaa 2640 gttttggact tgtcagataa atacacagcc actcttccaa atcaggttgg aattccaaga 2700 ggattggaaa ataattgtga ttctttgcga gagtcagata ctatagttta tttgttgagc 2760 agactatttt tagttaataa attagttaac atgcctttag aattggcatg tagagttggc 2820 agttctttca gaatggaaag tatacataat aagatgagag gtgctgggaa tgacatttta 2880 aatatgtcaa gcttctacag ttgcttacga aatggtaaga atgaatccca tgtacctgag 2940 gctgaccttt cacttttgaa gctaatttcc tgttggagag accagtctgt gcaggtaact 3000 gaagcaatac aagctgttct cttggcggaa gttcaacaac acatgaagag tttgggaaag 3060 atacccgtca atagtcaacc agtgtccatg gcagagaatg gtaactgtga gatgaagcag 3120 atgctgccaa agctggaatg gacagaagaa ctagagttac agtgtgttag aaacactttg 3180 cctctgcaaa ctccagtcag cccggtcaag catgacagca actcaaactc ggcaaacttc 3240 caagacgtgg aggacatgcc tgacagatgt gccttggaag agtctgagag tccaggtgag 3300 ccaaggcatc attcatggat agcaaaggtc tgcccctgca aggtgtctta aatggaatct 3360 catcagtagg agctgaattt ggacaaatta agaaatccaa aagatgccat ttgtttatta 3420 ctgtataaaa gcattgttgt tattggtcaa gttattaggc tgtagtggat ttgctaatac 3480 tttagccaac atgtattaaa gtgattttaa tacatgctga ttacaatgca atacatactg 3540 attgaaaata ttcatattca tctaatttta gaaaaatatt gcctagatca ttctctattc 3600 ctgtttctta ctttttctgt taatatttcc aacagggaat gccagtccac agacacaaat 3660 ttaatactgc tttaaatttt ctcctatcct tttagtccct gaattatata ataaacaatg 3720 ttaaaaccaa tgtagtacac aatacttact tacaaattta atactgcttc aaggtattta 3780 atctaaaatt ttaccaactt tgatttgtct ggttaggata ttttgtttta gtggatatgc 3840 tttaattcgg atcaattact gcagtaaatc tcatccctaa gcatgaaatg ttgtcaacaa 3900 atacccagtt ccatttagtt atcaattagc ccaaataaga gatacaaagt ataacagtga 3960 ccaaccttgt actgttgagt taatttgaac ttctaatgac attgaggcta atgtctttag 4020 ctcaaggttg atcttgttgg ccatatagat gtgaactagg gaaggggaat caacttacag 4080 catatcacaa ttgatcctta ttaagtataa actcttgtag gtcttttccc agaaagaagc 4140 ttgactagca ggaattctaa aactgaaata tatcaaacag cataaatagg aatagacata 4200 aagtgctctt ctattaaagc ctttggtgat ctatttacta tgatttatat tgtacagttc 4260 ctcgatttac agaaaatcat caaaattatt aatctacata tcttatgtat ataaatattg 4320 cctaatccat agaaaaaagg atataaagta ttaaatatgt gatatatagc tatatctatc 4380 tatctatgta tctaataggg aagtccaagt cacttcaatt gaagaaacat atctctgagc 4440 ataggagcag cctcaggtcc tatggtggga tgcagtggac aggagagggg gaaattagaa 4500 aagagaacta tataattgaa aaagggatat aaagcattaa atatatgata tatagctata 4560 tctatgtatg tatctaacag agaagttcaa gtcacttcaa ttaaagaaac atttttgagc 4620 atgggaccag cctcaggtct tatgctggga tgcagtagac aggagatggg gaaattagaa 4680 aagagaactg tgtaattgaa atgacgtggg ctgcaccctt aaggaactta taattaatga 4740 tgatctgaat aaacatacca ggataaagat gtcaaatgag tgtgactccc ttaaagtaga 4800 ttaaagtgtg cattctttgt ttcctaaaat atgattttac tgcttgaaat tacatttgag 4860 ttgaagttta gaaactaaca tagcattaat atgaataatc atggaaaatt attatccttt 4920 gaaaactgat tgataaatat attccccctc ctttagaaac agtcaaaagc cacttcaaac 4980 aagtttcaaa ataaaggaag gtagcaagtt aggcgatgga ttatattttc ttgcttgttg 5040 tataccagtt gtcaaggaca ttataaggac tcccaaaagc attttgaagg atggcaatat 5100 caaataagtg tatgtcctct caaatgaggc atttttaatt gttaaaatct atttggacgc 5160 tcaggttatg atatgtttat gaaaaataag cttcattatt tttatagcta catcctatta 5220 ttccctttta gaaacaagaa taacaatagg ttttaatagt tgccatactt agcatttatc 5280 agttctaatg aaaccaatat tgaatctctg ataaatattt tctgatgtta ctagctatgg 5340 gaaattagaa ctggcacaac cctgacatta ctaagtggaa atgttaggat ttttcggcat 5400 cgcatgttag aatctctaaa atttaaacat tcctgttaaa tgactaaggt ttgcttttat 5460 caatatgaat tctgaaggcc aatatcatac cattaactat gaaagctttt aattcctaaa 5520 aatagtttta gagatattca agcaatgctc tcctaatatc catacgcaag tgtgtttatg 5580 acacaaattc actagtctgt ttaaaaatga attctttata ttgactggtg ttccacatat 5640 ttcagtaatt tctgttatga gaggacttga aatagcaaat tgccacacag ttaactggat 5700 agaccacgta cgtggtgatc ataaccactt ggtactacac ccagaaactc aaaattgtct 5760 ttctcctgat gagatatggg tgtccttttg tacgtctagg cctaggtaac cagtggagtg 5820 attatattag caaatgtgtt tgtatccgga gtcttcctgt cattgtaata aaaaatttat 5880 ttaaaaattt tgtcttgtgt ttcttttttg gtaatcatct tggtgatatt tatgaatgta 5940 tttgtgtgtg tgtgtgtgtg tgtatacata catatatatg tgtgtatata tatacacaca 6000 tatatataca catatatatg tgtgtatata tatatatata tggcatatcc cccaaaggaa 6060 tatcatattt tcatttgcaa gccttgattc tttgacttgc tgttgagttt cacattggct 6120 ccattgtata ttgcaggaaa aagtacctgg aaagcctgga gggttaaaag cagaggctcc 6180 tcggcagcgt gtccaggccg tgtgtgcttg ctgtgcttgt cagagcctca ttccctcccc 6240 tgtgttggag agctttctca cagggctcat ccagaggtgc tagaaagcaa tgtgagcact 6300 attaaacact tcaaatataa ggaaaaatgt ataatgttag aaacacacag ttaaaaagta 6360 gccccaggta tcaaacattc tgttactatt ttagaaacta aattaaggct gctttgaaca 6420 tgatggtatt agaaaaatgg tagaatacag tttgttaaat attaatattc tatctttaga 6480 tgatagcatt tggtgacttt tatttctttt ctcatacatt ttttccagtg ttctgtattt 6540 ttaaaatcct ttcataatta ttataatgaa cactttagaa aagatactat ttctcttcca 6600 tccttagagg gcacattata ataattgagt attttaaaat taaattttat gccatgtatt 6660 taaaatgaaa gttcaggtta cattaattcc aactgatttt aaagccttat tttcacagag 6720 tggactcatt caatttttta aattttatat tcatacattt tgattgctca gttatataaa 6780 agcggtgtta tagactcctt tattctccac aaaatgttgt cttatatgta aagtgccaaa 6840 agttgtgttt aatttcctaa gaaagtcatt gctttgtaaa catttgcata atacttagtg 6900 ttttttgtaa ttttaaaaaa ttagcttaac caaaagagtt gcaaaattaa aacttacttg 6960 agtaggtatc tttcagacaa agctgcatgg cttcatgtac aatagtcccc agatcacctc 7020 gcactgtagt ttgctcaaga aggagcctac agatggcagg taggagaagg taaactggaa 7080 attaacaggt ctgtctgtaa gagcatgcca ctggaaacac ccatccaatt tgggacccct 7140 ggaagacagc atgtgtctaa tgggaggcct gtcctagtac aactccttta ctcttttcac 7200 cttcatcttg accttctcag ataccatctt tatgtaaaat gttgatgttg tggagttttt 7260 gcagtaattt aatttttata aatattgtat taaaatatat ttatcttgaa aaaaaaaaaa 7320 aaaaaa 7326 <210> 5 <211> 2779 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2779) <223> hypothetical gene supported by AK096951; BC066547(LOC440157), mRNA. <400> 5 cagcgatcag cttggctgcc cttgcttcgt agtgccacag tagaggctag gggagcaact 60 ggctttcctc cccaaaaggc gggcagggtt atccacactt tgcccaggtc cctgaagcct 120 gcggctgagc tcggggataa caggggccaa gtcaccggtc ccagacacct aggaactatt 180 agagacagga accagcatat gacacagggg ctgttaagta ggaggttgga gaacacacgt 240 ttttggtcta aaccgggggc ccctctcttt gcccactgag cccgcggcct gcgtggtgct 300 gagactgcct ctggccgcgt ccgcttggga caaggcctga gcggtggctg atcccacctg 360 gatgtcccgg gccggctccc acccgaagcc cgccatcccg ggacgcggtg gggagaagct 420 ggcactgctc cttgccatgc ttggcggccg ctgctgcccg gctgggggtc ccgagtcgca 480 cacgccctgc aagccctggc caccgatccg gagggaacgc cctgggctgc ggtccccgaa 540 gccaagagaa gaagcaggtc ccagggccga ctccaaagcc gcatctccag ctttgttcat 600 gggtccggga agcagaggcc gccgccggcc accgtcgtgg gcgagaagaa gggcacgagg 660 cggccggggc tcctgcccgg aaccacatgt gcgcgccggg ccccgcttct tcatcgcact 720 tgcggccccg gctgcccggg gcctgcgagt ttccagccag ggcccgggac tctggcgcgg 780 tccggccgcg aggaaggaag gcgtggcccg ggtgggggta gcggcaggcc tgcggctcag 840 gccatggggc aggggcagaa aaacgacccc ggcgctgtcc gggcatccag ctcggttccc 900 gctgcagcca ggagactccc gggagcgctc taggaaccac agagccctgg aactcacctg 960 gcagcctcgc ggcgctaaag ccggcggagc ctgagacagc gcgcggcgag gcggtcacgc 1020 tccacccccg cgtggcggca ggactcggat ttcgcccctg gttttaaaat tgtgccggtg 1080 gagcccggga cgctgggaag agcgttctgc gcccctccag tcgcggtctc cgccctaaac 1140 cgacttccag agccgcctct gctccctgga ggggcgcagt ggcggacacc ggcgtcccac 1200 gaagtcgcag gtcctcagtc tgagggctgc cccgcacgct cggaatgcag gagggtctcc 1260 gcctcgctgc gctgcccctg ggggcggagg cgtgcgctgc aggcgagaga ggcggcccgg 1320 tatcgatgga gaagcacaga gggctttgag gtcgcaacgt cccggttgct gagcggagtc 1380 aggagtcagg ttccaaaggg acagcgctca gggttgtaat caccacccgg cccaccgctt 1440 ccgcagctgc gagtctaggg cggagctgtt gggtggaccg agcaggcgag gcgcaggcag 1500 gcagcggctc cgcctcggaa tccgcctcga ccggggcaca ggtgcccgcc ccacctgtcc 1560 ctcggtcacc ccaaccctgt ttcctcgacc cccagcactc ctccaggcct agttcgcttc 1620 agaggcgcaa gacccggaaa acaaggaaga agcgagctca gcctcaatcc ccgtccccac 1680 cccactttcg ggaccgctaa gctggagaat tgaagggggc ggaccccgga ttaaagccgc 1740 tcccttccca gcctcgcccc gctttcctaa tgtccgtgat gatttcgtta ttggcaggga 1800 agagccagac tccctgcgct cccaagacgg ggcgattggg agggggttct ggagctcatg 1860 cctggggtcg gcccggcggg ggtgaccccg cgccctcgcc ggtgcaagga gaacagctgg 1920 ttcccgccgg ggcagggaag cgtggacggt gtgggctcag gcgcctggca ggcacacggg 1980 gcctctaaag cttggtcact gtcacagatc gtgtggttgt ttcttccgtc cccgccacgc 2040 cttcctcctg ggatggggat tcattcccta gcaggtgtcg gagaactggc gcccttgcag 2100 ggtaggcgcc ccggagcctg aggcgggaac tttaaaatca gacgcttggg ggccgggctg 2160 ggaaaaactg gcggaaaata ttataactga actctcaatg ccagctgttg tagaagctcc 2220 tgggacaagc ggtggaagtc ccctcaggag gcttccgcga tgtcctaggt ggctgctccg 2280 cccgccacgg tcatttccat tgactcacac gcgccgcctg gaggaggagg ctgcgctgga 2340 cacgccggtg gcgcctttgc ctgggggagc gcagcctgga gctctggcgg tagcgctggg 2400 agcggggcct cggaggctgg gcctggggac ccaaggttgg gcggggcgca ggaggtgggc 2460 tcagggttct ccagagaatc cccatgagct gacccgcagg gcggccgtgc cagtaggcac 2520 cgggcccccg cggtgacctg cggccccgaa gctggagcag ccactgcaaa tgctgcgctg 2580 accccaaatg ctgtgtcctt taaatgtttt aattaagaat aattaatagg tccgggtgtg 2640 gaggctcaag ccttaatccc cagcacctgg cgaggccgag gagggaggat cccttgagcc 2700 cagaggttcg agactagcct gggcaacaca gtcagactcc atccttccaa aacaaacaaa 2760 caaaaaaaaa aaaaaaaaa 2779 <210> 6 <211> 558 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(558) <223> PREDICTED: hypothetical protein LOC643911(LOC643911), mRNA. <400> 6 aggtgttaag tgtgatgctt ccataataca tttggatgct gtcagctaag ttcacttctg 60 aactaagggg ttcctccaaa tgttggctga aattcatccc aaggctggtc tgcaaagtct 120 gcaattcata atggagctac tgtactggct attggaagga ggagattctg aagataagga 180 ggatgccact ggaaatgttg aaatgaaaaa tattcagccg ttggtctttg aaatttcctg 240 tgatgtgttt caatctagat gcaaagaaca tggaaaaatc aaagtgctcg agtggtttaa 300 atatgttttg ggtattcctg tttatagact ataatacttt tccaattaaa atcctcagtt 360 gtcacgcaga agaaggttaa gctgtatttg attgccagtt ttactgaaaa tgcttagtat 420 tttacagtat caccaaatat attttgttta gccaaggtat aggaaaaata aaataaattg 480 tataggttga cttttttcta aaatgtcttt attggattga atgaatgttt atacctgaaa 540 aaaaaaggtt caaaaaaa 558 <210> 7 <211> 5228 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(5228) <223> chromosome 13 open reading frame 23(C13orf23), transcript variant 1, mRNA. <400> 7 acaccaggac cccacctctg gctttcagga aagaggggcc caagctggcg gcgcagtgtt 60 gagtttactt gggcgcgact ggctttattg taggtcccca tgagctggtg ggggctgtag 120 gggtaaccag gcagggcgtc tggcgctgtt ggggctgcgt ttttccggag tccccctatg 180 cgaggccgtg cccctcttcg cccggctcct ggtgctcccc agccgccggc ccgctcccgg 240 aagctgcagc agctggtaac aaagagcctg ccgggccgcc tgctgccggg gccgaggtat 300 ccaggagtcg ggcggagcgg ctggggatga gcgcgagccg gaccatgcgt ccgggttcgc 360 ggcggtgagg gtcgcggccg gcggccgagg cgcaggtgcg ggtcgagaga ccggcgcctc 420 cctccccgcc gcccgtggac tctgagcgca ggtgtttcta ctctgccggc cgctccacct 480 gggaaagcgc cttcaagagc tacctctggc ggcacctggc cctcagctgc agggaaaccg 540 cactcaaacc tgccgccgag cccgggtttt tctgcaaaac tcagaggacc tggctcttgc 600 ccgaggtgcc ctgaaccatt gtgtgaataa gctggggaag cctgactgga gtgttttttc 660 tttttaataa aaagagtttt tctgaatctc aatttttaga aatttttttt gcgaagtttg 720 caatactctc tacctcttcg catcctctct tgctcgtgga gtctttttcc tcctcagcta 780 taaatatttt ttactatcgg cggagcagac cagggatgaa cgtcttttaa ttgcaagtat 840 aactgttaaa accacgtcgg gatagtagtc aagatggata aaaagtcctt tgaaatggtg 900 ctggatgaaa ttagaaaggc tgttttgaca gaatacaaat taaaagcaat tgaatatgtg 960 catggatact tttctagtga acaggtggtt gatttgctga gatatttttc ctgggccgag 1020 ccccagttga aggcaatgaa agcattacag cataaaatgg tggctgtcca gccaacagaa 1080 gtggtcaata tactcaactg tttcactttc agtaaagaca aactagttgc tcttgaactg 1140 ttagcctcga acattattga tgcacagaat tctcgtccta ttgaagattt attcagggta 1200 aatatgtctg agaagaaacg gtgcaagaga atacttgaac aggctttcaa ggggggctgc 1260 aaagctcctc atgctatgat atcttcttgt ggaacaatcc caggaaatcc atatcccaaa 1320 ggaagaccta gccgcataaa tggaattttc ccaggaactc ctttgaaaaa agatggtgaa 1380 gaatgtacta acgaaggcaa aggaatagct gcacgaattc ttgggccatc caaaccacct 1440 ccttcaacat ataatccaca taaacctgtt ccttatccga tacctccatg ccgaccacat 1500 gcaactattg caccaagtgc ttataacaat gcaggtctgg taccattagc gaatgtcata 1560 gctccacctc cacctccata tactcctaat cctgtaggaa cagagaatga agacctttcg 1620 aatccgtcaa aacctataca gaatcaaaca ttttccaccc cagcaagtca actcttttct 1680 cctcatggtt ctaatccttc aacacctgct gcaactcctg ttcctactgc atccccagtc 1740 aaggcaatta atcatccatc agcatcagca gctgccaccg tttctggaat gaacctgctg 1800 aatactgtcc ttcctgtgtt cccagggcag gtctcctcag ccgttcacac acctcagcca 1860 tcaataccaa acccaacagt tatcagaacc ccttcattgc ccactgcacc tgttacatcc 1920 atccacagta caaccaccac tcctgttcct tccatttttt ctggcctagt gtcactgcca 1980 ggtccttctg ccactcctac cgcagccact cctaccccag gacctacacc acggtccact 2040 cttggttcca gtgaagcatt tgcttctact tctgcacctt tcactagcct ccccttttcc 2100 accagctctt ctgctgcttc taccagcaac ccaaattctg cttcattgtc atcagttttt 2160 gcagggctcc ctttgccctt accaccaaca tcccaaggcc tatccaaccc gactcctgta 2220 attgctggtg gctctactcc cagcgttgcc ggtccacttg gtgtgaacag tcctcttttg 2280 tctgcgttaa aaggttttct gacatccaat gacaccaatt taatcaactc ctctgcttta 2340 tcctctgctg tcacaagtgg gctggcttca ctatcttctc ttactcttca gaactctgac 2400 tcttctgctt cagcccctaa caagtgctat gccccatcag ccatccctac cccacagagg 2460 acttccactc cagggttggc cctgttccca ggcctgccgt ctcccgtggc taactcaact 2520 tccactcccc tgacattgcc tgtacagtct cctttagcca ctgctgcatc agcttccacg 2580 tcagtgccag ttagctgtgg ctcctcagcc tcccttttgc gtggccccca cccaggtacc 2640 tcagatctgc atatttcatc tacccctgct gcaacaactc ttcctgttat gatcaaaact 2700 gagcccacaa gtcctactcc ctcggccttc aaaggtccat ctcattctgg gaatccctct 2760 catggcactt taggtttgtc agggacattg ggccgtgcat atacttcaac atccgtgccc 2820 atcagtttat ctgcttgcct taatcctgca ttgtcaggtc tctccagctt gagtactcct 2880 ttaaatggtt caaatcctct ttcctctatt tcccttccac cacatggttc ctccactccc 2940 attgcaccag tattcactgc tcttccttct tttacttctt tgaccaacaa ttttccttta 3000 actggcaacc catctcttaa tccgtcagta tctctcccag ggtcattaat agccacctca 3060 tctaccgctg ccacctccac atctctccct catcctagct caacggcagc tgttctctca 3120 gggctttctg cttcagcacc agtctcagca gcacctttcc ccctcaacct gtccactgct 3180 gttccctcac ttttctctgt tactcaagga cctctgtcat cttcaaatcc ctcctatcca 3240 ggcttttctg tctctaatac cccaagcgtt acccctgctc ttccctcatt cccggggctg 3300 caggcgccct ctacagtcgc agctgtcaca ccactacctg tggctgccac agccccatcc 3360 ccagctccag tcctcccagg attcgcctca gcattcagtt ccaatttcaa ctccgctctt 3420 gttgcacaag ccggtttatc atctggactt caagctgcag gcagttctgt ttttccaggc 3480 cttttgtccc tcccgggtat ccctgggttt cctcagaatc cttcacaatc atccttgcaa 3540 gaattacagc ataatgcggc tgcgcagtca gcattgttac agcaggtcca ttcagcttcg 3600 gctctggaaa gctatccagc tcagcctgat gggtttccta gttatccttc agcgccagga 3660 acaccatttt ctttgcaacc aagcctgtcc cagagtgggt ggcagtgaat acttttaact 3720 tttattctcc ttcagagcaa catcagaatt gcctgagaac tgcaatgaac aatctgacaa 3780 atgtgaagct ggccaaaagt cggaaaatga gaatgagggt aatcctggag aaattgtgac 3840 aacaatttga aaattgtggt tgcattttaa agtgtgaaca ctcccctatg taaatatgct 3900 gacaataaat tgtatggaga atggtattta aaaagtgttt ggagactttt cacctgtcct 3960 ataaaatttt gaattgtgta tgtgatctac atagaaagaa tattaaagag taggttgaac 4020 tctttatagc cgaatacagc cttaaatatg cttgtatagc atccactggc agaagtaata 4080 gttgtgcctc agacttgggg gttgcatgtg gccctggggg agttactacc cttggtatgc 4140 atgagcggtt cctattagca tcagtgggaa ctcagtactc tgtatgtatc cacaaaaggg 4200 aacttgagac ccacagttat tcttaatttc tgatattaac aaccgtacat actgctgaat 4260 ttaactcaaa atatttcagg taagtgaaag tggtgcttaa tgtagactat agaatgactt 4320 tcaggtgttt tcaactgaaa gtatatatcc agaactgcat ccttatagaa atacaagtaa 4380 gacttaggat aatttgcctt caaaacagtt ttcctaatct cagcagtatc cagtgagtga 4440 agaacacttg actgactctt gggccacctc tgttacttac tgtactatgg aagctcctgg 4500 tgaatgttta caattatggg atgtagtatt tctatttgta ctttaagtca aatgcttata 4560 tgaaatatgt gacaacaaat agagaagact ggctctgtta gtaattatgc agtatgtact 4620 ctatttaagg atctgtggta gtataacatg agtgaatgtc attaattttg aagtaataac 4680 tgccacatgt gggaagtagg ggagtaagga gaatgaattc caatctgtga ttaaaagtgt 4740 aaactataga ctctactgta gtacatttca ggatctagaa gttttacttt tataaagatg 4800 gtgtccggaa gatgttgcta atgtatttta cttcaacata gggaacaaac tttttaagta 4860 tattaataaa cctgtatggt tagtttttaa cagtttttta aaataaacta tggatatgac 4920 aaatattctg tgttttacta agtgcttgga taggctttct aattttgtat acgtgctaga 4980 gttaattatt gaacattttt atccaaattt agttgtaact ctgtttatac tactgattgc 5040 tcattcgttt aaatgatatt ttaatgtaaa agtcataacc aacatatgaa cagacagatt 5100 tatgtcttta aacacagaat gtaagctata gtttaatctg ataccagttg ctggaagttg 5160 ccatttgttt ttcttaaatc tatacccata aaacttcttt taagattaaa aaaaaaaaaa 5220 aaaaaaaa 5228 <210> 8 <211> 1610 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1610) <223> PREDICTED: hypothetical protein LOC644424(LOC64424), mRNA. <400> 8 caaaaggcca aagtaaaaaa aaaaaaaaaa ggaaaaaatg aaaaagaagc cattgaatac 60 cctattgacc ataagaaaaa ggcagggaaa gttgttcaac ggcaacccag gcactgaagg 120 aaaaagaaca tggagaatga caaaagccca gagggaggag taaaaggaca caaacaccat 180 tctcagggac caggactggg cgctgttctc agggaccagg actgggcact aatcacagaa 240 ctgtaacagg cgccccatgg gaatgaccaa ctgttagatg gggcctgcag ggcagcacct 300 ccctcctgcc tcccaccaac agcttctaaa gggaaatgcc gactcttttc acaccagtcc 360 cctcactgcg gctgagtgtg tgggcgcaga tgataggtca caacaacctg attcagtcct 420 cactgcggct gagtgtgtcg ggtgcagatg acaggccacc acaacctgat tcagtcccca 480 ctgtggctgt gtgtgggggt gcagatgaca ggccaccaca acctgattca ggattcagtt 540 ggctaccagc cagtgccata aggaaaacca ttctggggct cttgagaggg gcaaagcata 600 atttgcatgt gggagaaatg ttaatagttt gtgaccagag gacaagctgt ggtttattaa 660 agactgctgc aggttcctac tatgcttctc atcaagaggc ggaatctaat caccttcccc 720 ccttgaatca tggctggtct cagtgatgag tacgactgga cagtgtggca ggagagatgc 780 tctgggactt ctgaggggcg atcatgagag gccttacagc ttctgcctgg gcctcttgga 840 cacacaccct gggagaagcc agacaaacct gactacctga cactgccaga ctgggaggaa 900 gtccatgctg gccacaaaga gagggctggg tgcctgctcc atgtccccag ccactagagt 960 ccttctgggt gcctgcttca cgtccccagc cactagagtc cttccagatg agaccaggga 1020 catcatgaag caaccaaccc acacagccct gtcctgtgtc ttgacccaga aaattgtgac 1080 atgtaaaaag aataaattcc tggtttaagc cagtaaggtt actggtacat tgttacatct 1140 cagataatta aaaccttgaa aaactcatga gagatcacaa gtagaacctt gatctgaaac 1200 atggcatgtg gcgatttata ttgagtatta ggttaaaaat gcaagaaggg agcatagtta 1260 atattttacg ttaaagctaa aactataatt gcctacttaa aattttcagt taattaggtt 1320 gtcacttttt gttcttaacg aagaaatcaa ctagttttat tccataaaca gttagaactg 1380 atgcacacat ccgtttctcc ttactcattt taaacagcta tctgaaatag gaagtgtaat 1440 ataattttta aagaatctga aaacatgaca gaaatgttta aactataaac atatattgta 1500 tatgttagca tattgtatac attgcatatt aacataagct agaatcattg acataaattt 1560 atataaacaa aaggtataaa ataaaaaaaa aaaaaaaaaa aaaaaaaaaa 1610 <210> 9 <211> 2486 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2486) <223> hypothetical protein FLJ21511(FLJ21511), mRNA. <400> 9 acactgcctc ggttcggcaa gtgggtcagt tggctggggc tcacttggca acgggacgcg 60 ggaacgaggg gcgcggacgc aggcccggga ggacgcggcg gcgggaacct gggggcgcag 120 ggctagggca gcgggcccga cccgcacggc tttcctggaa agcgctgccc ctcgccgcgg 180 cgatgccctc gctgtggaga gaaatcctct tggagtcgct gctgggatgt gtttcttggt 240 ctctctacca tgacctggga ccgatgatct attactttcc tttgcaaaca ctagaactca 300 ctgggcttga aggttttagt atagcatttc tttctccaat attcctaaca attactcctt 360 tctggaaatt ggttaacaag aagtggatgc taaccctgct gaggataatc actattggca 420 gcatagcctc cttccaggct ccaaatgcca aacttcgact gatggttctt gcgcttgggg 480 tgtcttcctc actgatagtg caagctgtga cttggtggtc aggaagtcat ttgcaaaggt 540 acctcagaat ttggggattc attttaggac agattgttct tgttgttcta cgcatatggt 600 atacttcact aaacccaatc tggagttatc agatgtccaa caaagtgata ctgacattaa 660 gtgccatagc cacacttgat cgtattggca cagatggtga ctgcagtaaa cctgaagaaa 720 agaagactgg tgaggtagcc acggggatgg cctctagacc caactggctg ctggcagggg 780 ctgcttttgg tagccttgtg ttcctcaccc actgggtttt tggagaagtc tctcttgttt 840 ccagatgggc agtgagtggg catccacatc cagggccaga tcctaaccca tttggaggtg 900 cagtactgct gtgcttggca agtggattga tgcttccatc ttgtttgtgg tttcgtggta 960 ctggtttgat ctggtgggtt acaggaacag cttcagctgc ggggctcctt tacctgcaca 1020 catgggcagc tgctgtgtct ggctgtgtct tcgccatctt tactgcatcc atgtggcccc 1080 aaacacttgg acaccttatt aactcaggga caaaccctgg gaaaaccatg accattgcca 1140 tgatatttta tcttctagaa atatttttct gtgcctggtg cacagctttt aagtttgtcc 1200 caggaggtgt ctacgctaga gaaagatcag atgtgctttt ggggacaatg atgttaatta 1260 tcgggctgaa tatgctattt ggtcctaaga aaaaccttga cttgcttctt caaacaaaaa 1320 acagttctaa agtgcttttc agaaagagtg aaaaatacat gaaacttttt ctgtggctgc 1380 ttgttggtgt gggattgttg ggattaggac tacggcataa agcctatgag agaaaactgg 1440 gcaaagtggc accaaccaaa gaggtctctg ctgccatctg gcctttcagg tttggatatg 1500 acaatgaagg gtggtctagt ctagaaagat cagctcacct gctcaatgaa acaggtgcag 1560 atttcataac aattttggag agtgatgctt ctaagcccta tatggggaac aatgacttaa 1620 ccatgtggct aggggaaaag ttgggtttct atacagactt tggtccaagc acaaggtatc 1680 acacttgggg gattatggct ttgtcaagat acccaattgt gaaatctgag catcaccttc 1740 ttccgtcacc agagggcgag atcgcaccag ccatcacatt gaccgttaac atttcgggca 1800 agctggtgga ttttgtcgtg acacactttg ggaaccacga agatgacctc gacaggaaac 1860 tgcaggctat tgctgtttca aaactactga aaagtagctc taatcaagtg atatttctgg 1920 gatatatcac ttcagcacct ggctccagag attatctaca gctcactgaa catggcaatg 1980 tgaaggatat cgacagcact gatcatgaca gatggtgtga atacattatg tatcgagggc 2040 tgatcaggtt gggttatgca agaatctccc atgctgaact gagtgattca gaaattcaga 2100 tggcaaaatt taggatccct gatgacccca ctaattatag agacaaccag aaagtggtca 2160 tagaccacag agaagtttct gagaaaattc attttaatcc cagatttgga tcctacaaag 2220 aaggacacaa ttatgaaaac aaccatcatt ttcatatgaa tactcccaaa tactttttat 2280 gaaacattta aaacaagaag ttattggctg ggaaaatcta agaaaaaaag tatgtaagat 2340 aaaaagaaga gattaatgaa agtgggaaaa tacacatgaa gaacctcaac ttaaaaaaca 2400 catggtatct atgcagtggg aaattacctc catttgtaaa ctatgttgct taataaaaac 2460 atttctctaa aaaaaaaaaa aaaaaa 2486 <210> 10 <211> 1900 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1900) <223> chromosome 9 open reading frame 19(C9orf19), mRNA. <400> 10 agccgcgggg agcgaggagc gcgcggagcc ggccatgggc aagtcagctt ccaaacagtt 60 tcataatgag gtcctgaagg cccacaatga gtaccggcag aagcacggcg tccccccact 120 gaagctctgc aagaacctca accgggaggc tcaacagtat tctgaggccc tggccagcac 180 gaggatcctc aagcacagcc cggagtccag ccgtggccag tgtggggaga accttgcatg 240 ggcatcctat gatcagacag gaaaggaggt ggctgataga tggtacagtg aaatcaagaa 300 ctataacttc cagcagcctg gcttcacctc ggggactgga cacttcacgg ccatggtatg 360 gaagaacacc aagaagatgg gcgtggggaa ggcgtccgca agtgacgggt cctcctttgt 420 ggtggccaga tacttcccag cggggaatgt tgtcaatgag ggcttcttcg aagaaaacgt 480 cctgccgccg aagaagtaac ttgttaaatg taatgggaag gtggcagact taagaacgtg 540 gatatgaagt gcctagaacc accacaacct ggctgtgcgt ctgtccctgt gggtgtatgt 600 gcttgtgtgt gtgatgcatg tgagcgtctc tggcacacac acttggacat acagttctgt 660 gtgcgctcat tcttattaca ggagtgagca aaggaagcat ttaccccgat ggttacctag 720 accacgatta tttggattgg ggggaggggg gatccgtttt ttttttttaa ttttttgtta 780 tttctaagca aacctctttt gtacttttct tacttctaat atccatccct ggactttttg 840 tattccaaat gtttgtgatg ctgagaagtg aagttcattt tatgtgatct tcatgcgtcg 900 taatctactt ttggtagata attaagatta ttaaaccctc atttaaatgt gacataaaat 960 acagctttaa gcacataaat ataaagcagc ttccatcagg aacatggagc aggcagggac 1020 tccattttac agaattactg agatttctca gttgtaaaac atgatgtcat cctgcatgcc 1080 tcctggaatt ctccaatggg gtcgccaaac aacaaatgga gaaaaaaagt tttacttcct 1140 tgcattcttc tacctttaaa tagcaaagta ccactaccac caccacctct tgcccccttc 1200 cctcttttct taaacttctg gcatttcaga gctcagcagg ctacccctgg tttctggaga 1260 gttgggctag gcctgaagct ccccctcccc cacctctgct aggcagccca ggcctggtct 1320 gggagacagc ccctcaccct gcctgggctc ttggccaagc ggccttggat ggatgaagtc 1380 agagaggtgg ggtgagggtg agcttactca gggcccccag aggaagccct cagcctctgc 1440 cctcccccca cacagggcgg gagcccaggc ctgttcctgg cagctgtggc tgcagctgtg 1500 ctcctgctcc ctcctggaat gtgcgacaag cccaaatgtt ccagggaggc ggccggggca 1560 gggggcttag aagtgctaat atggttctgt gttttgcctg aaacgatacc aggttcccct 1620 gaatagcaac tttacaaggt ccatgtggga gggaccaacc cagatgccct gctgagtgtc 1680 cctgaaacca tggcagctcc atctgtcaag atggcagggg ccggagtgag ggggctgctg 1740 gcttaacagc aggcatctgg gcaggccagt cctcaaagca gctcctgaag gtctgtgttg 1800 cactgtcacc agtctcaagc tatgcctcta atttcaccag ggatattgac taagaagaca 1860 ataaaatctt tttctttgtg taaaaaaaaa aaaaaaaaaa 1900 <210> 11 <211> 2544 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2544) <223> thymus expressed gene 3-like(MGC15476), mRNA. <400> 11 ctcactcaga cccatgaggc cctgcctggt ctcgtctggg acctgggaca gcagctggga 60 gacctgagcc tggagtctgg gggcctggaa caggagagcg ggcgtagctc gggcttctat 120 gaagatccca gctctacagg aggtccagat tcaccaccct caaccttctg tggggacagt 180 ggcttctctg gatccagctc ctatggtcgc ctgggtccct ctgagccccg gggcatctat 240 gccagtgaga ggcccaagtc cctaggagac gccagtccca gcgctccgga ggtggtgggc 300 gcgcgggcag cggtgccgcg gtccttctca gcgccctacc cgacggcagg tgggtcgccg 360 gcccggaggc ctgctcctcg gcggagcggc gggcccgcgc cgggcccttt ctgacgccca 420 gccccctgca cgccgtggcg atgcgcagcc cgcggccctg cggccgccct cccaccgact 480 cgcccgacgc ggggggcgca gggcggcccc tggacggcta catctcggcg ctcctgcgca 540 ggcgccgccg ccggggggcg ggccagcccc ggaccagtcc tgggggcgcg gacggcggcc 600 cgcggcgcca gaacagcgtg cgccagcggc cgcccgacgc gtctccgtcc cccggcagcg 660 cgcgacccgc gcgggagccc tcgttggagc gcgtcggggg ccaccccacc agccctgccg 720 ccttgagccg cgcctgggcg tcgtcgtggg agtcggaggc ggcacccgag cccgctgcgc 780 cgcccgccgc cccctcaccc cccgacagcc cggctgaggg ccgcttggtg aaggcgcagt 840 acatcccggg cgcgcaggcg gccacccgag gcctccctgg ccgcgccgcc cgccgcaaac 900 cgccgccact gacccgcggc cgcagcgtgg agcagtcacc accccgggag cgtccccggg 960 ccgccggccg ccgtggacgc atggccgagg cttcgggccg ccgcggctcg cccagggccc 1020 gcaaggcctc gcgctcccag tctgagacca gcctgctggg ccgcgcctcc gcggtccctt 1080 cggggccccc taagtacccc acggcggagc gggaagagcc tcggcctcca cggccacgcc 1140 gcggcccagc gcccacgctg gcggcccagg ccgcagggtc ctgccgtcgc tggcgctcca 1200 ctgcggagat cgacgctgcc gatgggcgcc gcgtgcggcc ccgagcccct gcggcgcgtg 1260 ttcccggccc cggcccgtcc ccgtcagctc cccagcgtcg tctgctttac ggctgcgcgg 1320 gcagcgactc cgagtgctcg gctgggcgcc tggggcccct gggacgccgg gggcctgcgg 1380 gaggcgtcgg cgggggttac ggggagagcg aatcgagcgc cagcgaggga gaatcgcctg 1440 ccttcagctc tgcctccagc gactcagacg gcagcggtgg cctcgtgtgg ccgcagcagc 1500 tggtggcggc caccgcggcc tctgggggtg gagcaggtgc aggggcgccc gcaggccccg 1560 ccaaagtctt cgtgaaaatc aaagcttccc acgcgctcaa gaaaaagata ctgcgtttcc 1620 gttcgggttc tctcaaggtc atgactacag tgtgagtttg gggatttgct tgggctcccc 1680 cttcatggcc tctgcacctc cacactccca accactgacc cttccacatc taccttccaa 1740 agaccatcgt tttctctgct tccaaagacc cccctcactc tccccactcc taacagtctt 1800 ggttgaaaag gctcccccac caccaccgag aggaatgggg aggagccctg tttgacccag 1860 ttcagcttct agcttggaag cccttgggca agacagttcc ccttctctgg gcgtcacttt 1920 cctcatctgt acagtaagtg tccatgtatg caaaaggggt aattcggttt gaatttcccc 1980 gttttagttt agaagcctag tctgtttgtt ccccttcacc gctctccctc tcattcctga 2040 tgagccctct cattcctcct ttccttgccc agctatggcc ccctctcatt cacaaagtgc 2100 cccctccatg tccctggacc cttaagatat ccccttggca ccctggtcag agactctgtg 2160 tctgactcag gtggtccctg cagagtgccc tgggaaggga aggagcactg atttgggggt 2220 tttgagggtc aagtaggggt tggtaacacc tggaaagaag gactctttca cttcgatccc 2280 tggacaatta tggaggattc ggaggtagaa gaggggaagg aagatggttt ctatctcatg 2340 acccccactc cctgtgagag ggaatggggg aagcctgatg accctcagct gttccaatct 2400 agtatttttt ttctttttta aaattactgt atttattatg acgatggtga ctccccagtg 2460 caaagggggg ccagattctg tgtgtttctc taacctcttt gtaaataaat gcacagtgta 2520 acataaaaaa aaaaaaaaaa aaaa 2544 <210> 12 <211> 4471 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(4471) <223> mRNA; cDNA DKFZp686J0156(from clone DKFZp686J0156) <400> 12 caattacata tttatttttc catacctgat ttttttcaag tctgtaataa aaaaagtata 60 agttgagatt aacataggtt atttttcatg aagtatagca aacgatctag aatgtgatag 120 gagtgtggtt tccatttctt tttttttttt tttaacagac ttttgtgctg tagtaagaat 180 gtcttagaag ttgtgtcttc gagttcctca aacaccggac agggctcccc cagagctgcc 240 tcagcctttg atttggtcca tattcagaca cttcctgtct tgcatacact ctgaggatgg 300 gccgcttcta gctgccgccc gtctccctct tgccttcttg tctctaaatc agacactccc 360 aagcactcca tctgctatac taggagagtg ggagagccaa agcattttgg agtccatgta 420 aagtgcctgg gaaaagagat gtaagagcag tgggagttta tataattagc gaattctttt 480 ctcagaattc agcggaaatg tatttctgtt gttattattt acaaaattgt ggcctcagag 540 gagctgtctt ttggaaaata agttttcatt catgcagtta gttagacatg cacgatgtac 600 ttgaatcaat aaactgtgga ccagaaaagg gctgcttaaa tgaattcacg tgttctaatt 660 ctctttcgag gctgttgatg acctcctgga ttcatacccc catgatctgt cttgctcttg 720 cctctgttct ttgataaagc acatcagact atgtgacacc catcttttca agaacgacct 780 aaaagcaatg acaacaggca ggagagaatt accactggcc tgggcacagt gacagcagaa 840 ggcccacctg agcttggaga gttggcgaga taaggcaaaa tcaaggtgca acagtgggcc 900 atgttccaag ggtgaatgga tctgagagtc cgctgatgtt ccttactgat cagaacaggg 960 accttctaac gaaacagcca gagttccttg aatcaggcag aagttcttta gagacaggaa 1020 gccagagcta ttgataatat ccgaacgaca gaggaaggaa tttcttatta gaaattctaa 1080 aataaaacaa gtggggattt ggttggatac ccttagaagc tacatttttc tctcatccct 1140 aagatagata tctcaagtgt atatctgaca cctcttggct ttgacacggc tctgcttctc 1200 aagtgaccat ttgttttaag tctgttgtct agaattcttt gtgggggctg gacctctgaa 1260 aaagattctc actgcagagg ctttaaatct gtgttttttt ccactccctc cgtcctggga 1320 tgtattcggt aggacatttc atttatatca ggatattggc tgattcagct ctctttcatc 1380 gttattattc aggcctccct ccaccacctt gttctttatt gcctaagtat tgccctcccc 1440 aattcttcat cgtaatagct ctaaatttag tttgacccaa attaattttt gttccaacag 1500 atatatttta agacagagaa gcctctctca ggagccagat gatctgaaga tgatgctaat 1560 ccccaaatac gaagttcctc cagctaactc tcctctgagc tccctcttct tagctttggg 1620 attggggatg gtctcatcct tgccaggaat ccctttgttg ctcccagtgt ctctgatgag 1680 cttctcctcc ctcccagaga caatgcaggg gtggttttca gcagaatgtg ccacctgcac 1740 ttctgattgt tctgagaccc agcccagagg ggtggagaag gcgcacaaac cctattccaa 1800 taaactgcct gcagagaacc acagcctgct aatagtcgtt gaggtctcag ccccctaagg 1860 tctccaagct catttgacca gcgcagctgc gacttcggct gtctgcctct ggcaggtgcc 1920 aatatcagca tcttgtccca ctgccatggg gagttaattt ttgctccagg gcagctgcca 1980 agcccagcac cggcatcaat agaaggtttt ctctgatttt cttctcttcc tctcaggcta 2040 ggctttctta ccaatcccca atttccttct gtagggcgcc aggagactgg ccagagatct 2100 ttagactctt acttagtttg aacatctctt gctgctcaca cccaggcttc ttcagcagaa 2160 agcatgaccc atagtaggta ctcagaaact ggttgaatga aaagccttga catttaaggg 2220 ctttattctg tcatacggtg gcaagaactg gcctattggc atcgtattcc tggcattgag 2280 ctgtattgac cctgaatgtg tcctcctgag gtttttgagg gtgacctagg agaaagggtc 2340 tgaaaaagca ctgggatcca agtgacttta aatctgcccg tggcatttcc tgctgagagg 2400 cgagaaacta gcatctctcc caacaggctc acatccgcca ggaaggacag agtccaaaac 2460 gggggtagac tttgtgggaa attcgccagt tagtccgctg agattttaat ctgcctcaag 2520 cacaggatgc tgacaagaaa ggtagaccac tcccccgatc ccagacaaac cccaggggtg 2580 acaacttctc catcagtatc ctgagaagca acatcaaatg cttaccaagt cagcacgttt 2640 actgagtgag tactctgacg gaataaacca gcatttggag ctgaacttga gaacacaggg 2700 ccctctgaca gcagcttagg gaaacaccca tcccttccag attggcagaa tccttccatt 2760 tcatgtcctt cggagacgct gtattctctt tacaaatcat tcatgaaact gagactcagt 2820 ctcccagggg taagtcctgg gccacgtgca aacaatggca aatccagctc ttccatgata 2880 gagaaggcaa acacacccac cttcatcctg agcctaaaag gccacctctg agcacttggg 2940 cagccactcc tctgggcctc agagggccat gagcttggcc aggtaggcac agcggcgggg 3000 aagtcacagc tgtcaggtac cggccatggt gcaggtggga ataggagatg ccagagctgc 3060 tttagctgag gaaagcaaac agtcagcagt gctcaaagga gcaaaacttc gaatgtgcac 3120 attgacccct gacacctgca agcataacac agatcctaag actagagtga agtaggaaga 3180 agaattagaa aatccagtgg atgtcctgag tatagggaac cagggccgtt gaaaatcagt 3240 aaaggttgat tacctggggc gagaccgggt gactgtggca gtgcaggtga aggtaccctg 3300 gaccttctca gttcgctggc acataaggct ccgccaataa agcgtggttc tctctgtcac 3360 acacacacac acacacacac acacacacac acaatgattg gagggctata tgatccagca 3420 ttagcttcct ggtgtgccaa gcatgcttga tcgggaattt ttttttatta ttattatttt 3480 ttagctgtag ctgaaggcat ttctcggatg tggagaggag aatggaaatc gcagaaccaa 3540 atcagtttgc cctgccatat ttggctgtgg tctgtcattg ggcatttctg atgtgctttt 3600 ctggattcag gaagagctga ttgtcctccg agggttgaaa aaaaaaaaac agtttcagaa 3660 acctgaatcc agggccttat agttctcctc attatcgatc ttcttctccc ttccctcgcc 3720 caagggagtg ggggaaacac ttttcactgc agagtttgct ttaaagtttt cccatcttgc 3780 gtgcattatc ccttgatatt aaaattattt tctcagttta atccaactcc tgctgagaag 3840 ctgtgtgaga tttaggctgt ggggtttttt tcttgtactc ttttggatgg tgttgcattt 3900 ttcactctta acccgagggt gtgtttcagc ttatgttcgt tctgtttcat gcaggtttat 3960 agcacggtag agtagaaggc ggcttctgat ttttagggta tttttagaat tcattcctga 4020 gtgtggggtt cagacaccca gtctcctcgg aacaggggtg aggggtcgac tgagctttgt 4080 tgagaagcct ccagttaggc ttcgggcggg tctccatgtt atattgtgtg tttactgagc 4140 ttcccactgg tagaagatga cacatttgtc catcgtcctg tgtatctgct ttccagagga 4200 caccggagca ttctcctggg gtcactccca catggctgcc tcacatagct gttttgcaac 4260 agcctttatt gccaacaccc ttggaagaac atctcctgta gaagtacaag ttttgcaata 4320 tggactttgg aagtggtttt gtgatgttcg aattttctgt tagcctattg ctcaagcact 4380 acagaatgta catagtccct ttggccatcc tctcacccca gaatatccta ataaacattg 4440 ttttcttttt taaaaaaaaa aaaaaaaaaa a 4471 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying GAPDH <400> 13 tcatgaccac agtccatgcc 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying GAPDH <400> 14 tccaccaccc tgttgctgta 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LMTK3 <400> 15 ggaacagcga gcagatcaaa 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LMTK3 <400> 16 aggagaccat cttgcgcttc 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644774 <400> 17 tcaatctgcc acagaaggct 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644774 <400> 18 ccaggatggc caggaagggt 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying Hs.389988 <400> 19 gcctgggacc tccagaataa 20 <210> 20 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying Hs.389988 <400> 20 tggcaaatga aaaattcagc a 21 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying WDR72 <400> 21 tcccatgtac ctgaggctga 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying WDR72 <400> 22 ttggaagttt gccgagtttg 20 <210> 23 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC440157 <400> 23 gagaagaagc aggtcccagg 20 <210> 24 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC440157 <400> 24 agttccaggg ctctgtggtt 20 <210> 25 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC643911 <400> 25 aattcatccc aaggctggtc 20 <210> 26 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC643911 <400> 26 cccaaaacat atttaaacca ctcg 24 <210> 27 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13ORF23 <400> 27 agcaccagtc tcagcagcac 20 <210> 28 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13ORF23 <400> 28 gaactgaatg ctgaggcgaa 20 <210> 29 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644424 <400> 29 attcagtcct cactgcggct 20 <210> 30 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644424 <400> 30 ttccgcctct tgatgagaag 20 <210> 31 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying FLJ21511 <400> 31 gtggctaggg gaaaagttgg 20 <210> 32 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying FLJ21511 <400> 32 aatctctgga gccaggtgct 20 <210> 33 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C9ORF19 <400> 33 accgggaggc tcaacagtat 20 <210> 34 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C9ORF19 <400> 34 tatctggcca ccacaaagga 20 <210> 35 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying MGC15476 <400> 35 cactgcggag atcgacgct 19 <210> 36 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying MGC15476 <400> 36 ttttcacgaa gactttggcg 20 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC143381 <400> 37 ggcggcttct gatttttagg 20 <210> 38 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC143381 <400> 38 tccaagggtg ttggcaataa 20 <110> Korea Research Institute of Bioscience and Biotechnology <120> Composition for diagnosing colorectal cancer and use thereof <130> P07-075-KRI-DA2 <160> 38 <170> KopatentIn 1.71 <210> 1 <211> 4972 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(4470) <223> PREDICTED: lemur tyrosine kinase 3 (LMTK3), mRNA. <400> 1 atgaggcaag tgctgtggtt gtgtaatgtc tgcgtaaccg cacgggaaac ccgccaccac 60 ctccacctcc ctgccatcct cgacaagatg cctgcccccg gcgccctcat cctccttgcg 120 gccgtctccg cctccggctg cctggcgtcc ccggcccacc ccgatggatt cgccctgggc 180 cgggctcctc tggctcctcc ctacgctgtg gtcctcattt cctgctccgg cctgctggcc 240 ttcatcttcc tcctcctcac ctgtctgtgc tgcaaacggg gcgatgtcgg cttcaaggaa 300 tttgagaacc ctgaagggga ggactgctcc ggggagtaca ctccccctgc ggaggagacc 360 tcctcctcac agtcgctgcc tgatgtctac attctcccgc tggctgaggt ctccctgcca 420 atgcctgccc cgcagccttc acactcagac atgaccaccc ccctgggcct tagccggcag 480 cacctgagct acctgcagga gattgggagt ggctggtttg ggaaggtgat cctgggagag 540 attttctccg actacacccc cgcccaggtg gtggtgaagg agctccgagc cagcgcgggg 600 cccctggagc aacgcaagtt catctcggaa gcacagccgt acaggagcct gcagcacccc 660 aatgtcctcc agtgcctggg tctgtgcgtg gagacgctgc cgtttctgct gattatggag 720 ttctgtcaac tgggggacct gaagcgttac ctccgagccc agcggccccc cgagggcctg 780 tcccctgagc taccccctcg agacctgcgg acgctgcaga ggatgggcct ggagatcgcc 840 cgcgggctgg cgcacctgca ttcccacaac tacgtgcaca gcgacctggc cctgcgcaac 900 tgcctgctga cctctgacct gaccgtgcgc atcggagact acgggctggc ccacagcaac 960 tacaaggagg actactacct gaccccagag cgcctgtgga tcccactgcg ctgggcggcg 1020 cccgagctcc tcggggagct ccacgggacc ttcatggtgg tggaccagag ccgcgagagc 1080 aacatctggt ccctgggggt gaccctgtgg gagctgtttg agtttggggc ccagccctac 1140 cgccacctgt cagacgagga ggtcctcgcc ttcgtggtcc gccagcagca tgtgaagctg 1200 gcccggccga ggctcaagct gccttacgcg gactactggt atgacattct tcagtcctgc 1260 tggcggccac ctgcccagcg cccttcagcc tctgatctcc aattgcagct cacctacttg 1320 ctctccgagc ggcctccccg gcccccaccg ccgccacccc caccccgaga cggtcccttc 1380 ccctggccct ggccccctgc acacagtgcg ccccgcccgg ggaccctctc ctcaccgttc 1440 cccctactgg atggcttccc tggagccgac cccgacgatg tgctcacggt caccgagagt 1500 agccgcggcc tcaacctcga gtgcctgtgg gagaaggccc ggcgtggggc cggccggggt 1560 gggggggcac ctgcctggca gccggcgtcg gcccccccgg ccccccacgc caacccctcc 1620 aaccctttct acgaggcgct gtccacgccc agcgtgctgc ctgtcatcag cgcccgcagc 1680 ccctccgtga gcagcgagta ctacatccgc ttggaggagc acggctcccc tcctgagccc 1740 ctcttcccca acgactggga ccccctggac ccaggagtgc ccgcccctca ggccccccag 1800 gccccctccg aggtccccca gctggtgtcc gagacctggg cctcccccct cttccctgcg 1860 ccccggccct tcccagccca gtcctcagcg tcaggcagct tcctgctgag cggctgggac 1920 cccgagggcc ggggcgccgg ggagaccctg gcgggagacc ctgccgaggt cttgggggag 1980 cgggggaccg ccccgtgggt ggaagaagaa gaggaggagg aggagggcag ctccccaggg 2040 gaagacagca gcagccttgg aggtggccca agccgccggg gtcccctacc ctgtcccctg 2100 tgcagccgcg agggggcctg ctcctgcctg ccactggagc ggggggacgc cgtagcaggc 2160 tggggaggcc accctgctct tggctgcccc cacccccccg aggacgactc ctcgctgcgg 2220 gcagagcggg gctccctggc cgacttgccc atggcccccc ccgcctcggc cccccccgag 2280 tttctggacc ccctcatggg ggcggcggcg ccccagtacc ccgggcgggg gccacctccc 2340 gctccccccc ccccgccgcc acctcctcgg gcccccgcgg acccggccgc gtcccccgac 2400 cccccttcgg ccgtggccag tcccggttca ggcctctcgt cgccgggccc caagccgggg 2460 gacagcggct acgagaccga gacccctttt tccccagagg gagccttccc aggtgggggg 2520 gcggccgagg aggaaggggt ccctcggccg cgggctcccc ccgagccacc cgacccagga 2580 gcgccccggc cacctccaga cccgggtccg ctcccactcc cggggccccg ggagaagccg 2640 accttcgtgg ttcaagtgag cacggaacag ctgctgatgt ccctgcggga ggatgtgaca 2700 aggaacctcc tgggggagaa gggggcgaca gcccgggaga caggacccag gaaggcgggg 2760 agaggccccg ggaacagaga gaaagtcccg ggcctgaaca gggacccgac agtcctgggc 2820 aacgggaaac aagccccaag cctgagcctc ccagtgaacg gggtgacagt gctggagaac 2880 ggggaccaga gagccccagg catcgaggag aaggcggcgg agaatggggc cctggggtcc 2940 cccgagagag aagagaaagt gctggagaat ggggagctga cacccccaag gagggaggag 3000 aaagcgctgg agaatgggga gctgaggtcc ccagaggccg gggagaaggt gctggtgaat 3060 gggggcctga cacccccaaa gagcgaggac aaggtgtcag agaatggggg cctgagattc 3120 cccaggaaca cggagaggcc accagagact gggccttgga gagccccagg gccctgggag 3180 aagacgcccg agagttgggg tccagccccc acgatcgggg agccagcccc agagacctct 3240 ctggagagag cccctgcacc cagcgcagtg gtctcctccc ggaacggcgg ggagacagcc 3300 cctggccccc ttggcccagc ccccaagaac gggacgctgg aacccgggac cgagaggaga 3360 gcccccgaga ctgggggggc gccgagagcc ccaggggctg ggaggctgga cctcgggagt 3420 gggggccgag ccccagtggg cacggggacg gcccccggcg gcggccccgg aagcggcgtg 3480 gacgcaaagg ccggatgggt agacaacacg aggccgcagc caccgccgcc accgctgcca 3540 ccgccaccgg aggcacagcc gaggaggctg gagccagcgc ccccgagagc caggccggag 3600 gtggcccccg agggagagcc cggggcccca gacagcaggg ccggcggaga cacggcactc 3660 agcggagacg gggacccccc caagcccgag aggaagggcc ccgagatgcc acgactattc 3720 ttggacttgg gaccccctca ggggaacagc gagcagatca aagccaggct ctcccggctc 3780 tcgctggcgc tgccgccgct cacgctcacg ccattcccgg ggccgggccc gcggcggccc 3840 ccgtgggagg gcgcggacgc cggggcggct ggcggggagg ccggcggggc gggagcgccg 3900 gggccggcgg aggaggacgg ggaggacgag gacgaggacg aggaggagga cgaggaggcg 3960 gcggcgccgg gcgcggcggc ggggccgcgg ggccccggga gggcgcgagc agccccggtg 4020 cccgtcgtgg tgagcagcgc cgacgcggac gcggcccgcc cgctgcgggg gctgctcaag 4080 tctccgcgcg gggccgacga gccagaggac agcgagctgg agaggaagcg caagatggtc 4140 tccttccacg gggacgtgac cgtctacctc ttcgaccagg agacgccaac caacgagctg 4200 agcgtccagg ccccccccga gggggacacg gacccgtcaa cgcctccagc gcccccgaca 4260 cctccccacc ccgccacccc cggagatggg tttcccagca acgacagcgg ctttggaggc 4320 agtttcgagt gggcggagga tttccccctc ctcccccctc caggcccccc gctgtgcttc 4380 tcccgcttct ccgtctcgcc tgcgctggag accccggggc cacccgcccg ggcccccgac 4440 gcccggcccg caggccccgt ggagaattga ttccccgaag acccgacccc gctgcaccct 4500 cagaagaggg gttgagaatg gaatcctctg tggatgacgg cgccactgcc accaccgcag 4560 acgccgcctc tggggaggcc cccgaggctg ggccctcccc ctcccactcc cctaccatgt 4620 gccaaacggg aggccccggg cccccgcccc ccagcccccc agatggctcc cctgaccccc 4680 ctgaccccct cggagccaaa tgaggcagga atccccccgc ccctccatag agagccgcct 4740 ttctcggaac tgaactgaac tcttttgggc ctggagcccc tcgacacagc ggaggtccct 4800 cctcacccac tcctggccca agacaggggc cgcaggcttc ggggacccgg accccccatt 4860 tcgcgtctcc cctttccctc cccagcccgg cccctggagg ggcctctggt tcaaaccttc 4920 gcgtggcatt ttcacattat ttaaaaaaga caaaaacaac tttttggagg aa 4972 <210> 2 <211> 282 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(282) <223> PREDICTED: similar to Phosphoglycerate kinase 1 (LOC644774), mRNA. <400> 2 atgatgcttt gggcactggt tcacagagcc cacagctcca tggtaggagt caatctgcca 60 cagaaggctg gtgggttttt gatgaagaag gagctgaact actttgcaaa ggccttggag 120 agcccagagc gacccttcct ggccatcctg ggcggagcta aagttgcaga caagatccag 180 ctcatcaata atatgctgga caaagtcaat gagatgatta ttggtggtgg aatggctttt 240 aagttcctta aggtgctcaa caacatggag gtaggaactt aa 282 <210> 3 <211> 488 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(488) <223> K-EST0184252 L9SNU354 cDNA clone L9SNU354-11G075, mRNA sequence <400> 3 cttattttct ctgaacgatc ctgattccag tcatcttgtt gaatacccta gttctaataa 60 ttgactcttg cttttctaga gaaatatttc caaatgatgc tagttttgtc tcttcctttc 120 aaagttgtat accacttctt tttcttgtca ttttgcattg cctgggacct ccagaataat 180 gtttcatgaa gtagcatgta tccatatctg gttcttgact ttttcatcat tataattgtt 240 ttctatgggt tacttatcag tttaagaatg cttaattcct agatgaacta agagtgttta 300 ttacatgttg agatttatgg tatgcttttt cttcctcaag ataatgcatt ttttgtatta 360 tctgttaatg tgataggtta tccatttgtg tattttcaat cattgaacaa cccttgattt 420 ttttggataa actctatttg gtcattatgc atcattctat aaaccctgct gaatttttca 480 tttgccaa 488 <210> 4 <211> 7326 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(7326) <223> WD repeat domain 72 (WDR72), mRNA. <400> 4 cctctgccgc tcctccgccc cacggctcag gattcgccca aaatgaggac ttccctgcag 60 gcagtggcac tctggggaca gaaggcccct ccccacagca tcactgccat catgatcact 120 gatgaccagc gaacgattgt gactggaagt caagagggtc agctctgtct ctggaatctc 180 tcacatgaac taaagatttc agcgaaagaa ctcctatttg gtcattcagc ttcggtaaca 240 tgtttggcaa gagcaaggga cttctctaaa cagccctaca ttgttagtgc tgctgaaaat 300 ggggagatgt gtgtttggaa tgtcaccaat ggacagtgcg tggagaaggc tacacttcct 360 tacaggcaca ctgcaatctg ttattaccac tgctcattcc ggatgacagg agaaggctgg 420 cttctttgtt gtggagaata tcaagatgtc cttataattg atgccaaaac tttggctgtt 480 gttcacagtt ttagatcatc tcagtttcct gactggatca actgcatgtg cattgttcac 540 tccatgagaa ttcaagaaga ttctctcttg gtggtatcag tagctggtga gctcaaagta 600 tgggatcttt cctcatctat caacagcatt caggaaaagc aagatgtcta tgaaaaagaa 660 tccaagtttc ttgagtcctt gaactgccag acaattcgat tttgcacata tactgagaga 720 cttctattgg tggtattttc taaatgttgg aaggtttatg attattgtga tttttccctt 780 ctgctgactg aagttagtag aaatgggcag ttctttgctg gtggagaagt gattgctgct 840 cacagaatcc tcatctggac agaagatggt cacagttaca tctatcagct gctgaacagt 900 gggctttcaa aaagcatata ccctgctgat ggaagagtgc ttaaagagac catttatcct 960 catttactgt gctctacttc tgtgcaggaa aataaggaac agagccgtcc ctttgttatg 1020 ggctacatga atgaaaggaa agagcctttt tacaaggtac ttttctctgg agaagtctca 1080 ggaagaatta ctttgtggca catccctgat gttcctgtat ccaagtttga tggttctcct 1140 agagagatac cagtaactgc cacctggact cttcaagata attttgataa gcatgatact 1200 atgtcacaaa gtattattga ctatttctct gggcttaaag atggggcagg aactgctgta 1260 gtcacttcat cagagtatat tccaagtctt gataaactaa tatgtggctg tgaagatggg 1320 acaattatca ttacccaggc tttgaatgct gccaaagcaa gacttctgga aggtggttct 1380 ttagtaaaag attctccccc tcataaagtt cttaaaggcc accaccaaag tgtcacttca 1440 ttactctatc cacatggtct ctcttcgaaa ttagaccaaa gttggatgtt gtctggggac 1500 ctggactcat gtgtgatctt gtgggatatc tttactgaag aaattttgca taaattcttt 1560 ttggaagctg gtccagtaac aagtcttttg atgtcaccag agaagtttaa actaaggggt 1620 gagcagataa tttgctgtgt gtgcggtgac cattccgtgg ctctccttca ccttgaggga 1680 aagagttgcc tcctgcatgc ccggaagcac ctttttcctg tgaggatgat aaaatggcac 1740 ccggttgaga attttttaat tgttggatgt gcagatgact cagtttatat ctgggaaatt 1800 gaaacaggca ctttggaaag acatgagaca ggagaaagag cacgaattat tcttaattgt 1860 tgtgatgatt cacagcttgt gaagtctgta cttcccattg cctcagagac acttaagcac 1920 aaaagtatag aacagagatc ctccagcccc taccagcttg ggccattacc ttgccctggt 1980 ctgcaggtgg agtcttcatg taaggttact gatgccaaat tttgcccaag accttttaat 2040 gtcttgcctg tgaagacaaa atggagtaac gttggctttc atattcttct atttgatctg 2100 gaaaaccttg ttgaactttt gctaccaact ccactcagtg atgttgactc ttccagttca 2160 ttctatggtg gtgaggtcct gagaagagcc aagagcacag tggagaagaa gacactgaca 2220 ctgagaaaaa gtaaaactgc ctgtggtcct ctttcagcag aggcactagc caagcctatt 2280 actgaaagcc tggcccaagg agataatacc atcaaattct cagaagaaaa tgatggcatt 2340 aaaaggcaga agaaaatgaa gatctccaaa aaaatgcagc ctaagccatc aagaaaagta 2400 gatgccagtc tcacaataga cacagcaaaa ttgtttctgt cttgcctttt gccatgggga 2460 gtggataaag atttagatta tctttgcatt aagcacctca atattttaaa gcttcagggt 2520 cctatttctt tgggaatttc tttgaatgaa gataatttct cactgatgtt gccaggttgg 2580 gatttatgca atagtggaat gataaaagac tattcaggag taaatttatt ttccaggaaa 2640 gttttggact tgtcagataa atacacagcc actcttccaa atcaggttgg aattccaaga 2700 ggattggaaa ataattgtga ttctttgcga gagtcagata ctatagttta tttgttgagc 2760 agactatttt tagttaataa attagttaac atgcctttag aattggcatg tagagttggc 2820 agttctttca gaatggaaag tatacataat aagatgagag gtgctgggaa tgacatttta 2880 aatatgtcaa gcttctacag ttgcttacga aatggtaaga atgaatccca tgtacctgag 2940 gctgaccttt cacttttgaa gctaatttcc tgttggagag accagtctgt gcaggtaact 3000 gaagcaatac aagctgttct cttggcggaa gttcaacaac acatgaagag tttgggaaag 3060 atacccgtca atagtcaacc agtgtccatg gcagagaatg gtaactgtga gatgaagcag 3120 atgctgccaa agctggaatg gacagaagaa ctagagttac agtgtgttag aaacactttg 3180 cctctgcaaa ctccagtcag cccggtcaag catgacagca actcaaactc ggcaaacttc 3240 caagacgtgg aggacatgcc tgacagatgt gccttggaag agtctgagag tccaggtgag 3300 ccaaggcatc attcatggat agcaaaggtc tgcccctgca aggtgtctta aatggaatct 3360 catcagtagg agctgaattt ggacaaatta agaaatccaa aagatgccat ttgtttatta 3420 ctgtataaaa gcattgttgt tattggtcaa gttattaggc tgtagtggat ttgctaatac 3480 tttagccaac atgtattaaa gtgattttaa tacatgctga ttacaatgca atacatactg 3540 attgaaaata ttcatattca tctaatttta gaaaaatatt gcctagatca ttctctattc 3600 ctgtttctta ctttttctgt taatatttcc aacagggaat gccagtccac agacacaaat 3660 ttaatactgc tttaaatttt ctcctatcct tttagtccct gaattatata ataaacaatg 3720 ttaaaaccaa tgtagtacac aatacttact tacaaattta atactgcttc aaggtattta 3780 atctaaaatt ttaccaactt tgatttgtct ggttaggata ttttgtttta gtggatatgc 3840 tttaattcgg atcaattact gcagtaaatc tcatccctaa gcatgaaatg ttgtcaacaa 3900 atacccagtt ccatttagtt atcaattagc ccaaataaga gatacaaagt ataacagtga 3960 ccaaccttgt actgttgagt taatttgaac ttctaatgac attgaggcta atgtctttag 4020 ctcaaggttg atcttgttgg ccatatagat gtgaactagg gaaggggaat caacttacag 4080 catatcacaa ttgatcctta ttaagtataa actcttgtag gtcttttccc agaaagaagc 4140 ttgactagca ggaattctaa aactgaaata tatcaaacag cataaatagg aatagacata 4200 aagtgctctt ctattaaagc ctttggtgat ctatttacta tgatttatat tgtacagttc 4260 ctcgatttac agaaaatcat caaaattatt aatctacata tcttatgtat ataaatattg 4320 cctaatccat agaaaaaagg atataaagta ttaaatatgt gatatatagc tatatctatc 4380 tatctatgta tctaataggg aagtccaagt cacttcaatt gaagaaacat atctctgagc 4440 ataggagcag cctcaggtcc tatggtggga tgcagtggac aggagagggg gaaattagaa 4500 aagagaacta tataattgaa aaagggatat aaagcattaa atatatgata tatagctata 4560 tctatgtatg tatctaacag agaagttcaa gtcacttcaa ttaaagaaac atttttgagc 4620 atgggaccag cctcaggtct tatgctggga tgcagtagac aggagatggg gaaattagaa 4680 aagagaactg tgtaattgaa atgacgtggg ctgcaccctt aaggaactta taattaatga 4740 tgatctgaat aaacatacca ggataaagat gtcaaatgag tgtgactccc ttaaagtaga 4800 ttaaagtgtg cattctttgt ttcctaaaat atgattttac tgcttgaaat tacatttgag 4860 ttgaagttta gaaactaaca tagcattaat atgaataatc atggaaaatt attatccttt 4920 gaaaactgat tgataaatat attccccctc ctttagaaac agtcaaaagc cacttcaaac 4980 aagtttcaaa ataaaggaag gtagcaagtt aggcgatgga ttatattttc ttgcttgttg 5040 tataccagtt gtcaaggaca ttataaggac tcccaaaagc attttgaagg atggcaatat 5100 caaataagtg tatgtcctct caaatgaggc atttttaatt gttaaaatct atttggacgc 5160 tcaggttatg atatgtttat gaaaaataag cttcattatt tttatagcta catcctatta 5220 ttccctttta gaaacaagaa taacaatagg ttttaatagt tgccatactt agcatttatc 5280 agttctaatg aaaccaatat tgaatctctg ataaatattt tctgatgtta ctagctatgg 5340 gaaattagaa ctggcacaac cctgacatta ctaagtggaa atgttaggat ttttcggcat 5400 cgcatgttag aatctctaaa atttaaacat tcctgttaaa tgactaaggt ttgcttttat 5460 caatatgaat tctgaaggcc aatatcatac cattaactat gaaagctttt aattcctaaa 5520 aatagtttta gagatattca agcaatgctc tcctaatatc catacgcaag tgtgtttatg 5580 acacaaattc actagtctgt ttaaaaatga attctttata ttgactggtg ttccacatat 5640 ttcagtaatt tctgttatga gaggacttga aatagcaaat tgccacacag ttaactggat 5700 agaccacgta cgtggtgatc ataaccactt ggtactacac ccagaaactc aaaattgtct 5760 ttctcctgat gagatatggg tgtccttttg tacgtctagg cctaggtaac cagtggagtg 5820 attatattag caaatgtgtt tgtatccgga gtcttcctgt cattgtaata aaaaatttat 5880 ttaaaaattt tgtcttgtgt ttcttttttg gtaatcatct tggtgatatt tatgaatgta 5940 tttgtgtgtg tgtgtgtgtg tgtatacata catatatatg tgtgtatata tatacacaca 6000 tatatataca catatatatg tgtgtatata tatatatata tggcatatcc cccaaaggaa 6060 tatcatattt tcatttgcaa gccttgattc tttgacttgc tgttgagttt cacattggct 6120 ccattgtata ttgcaggaaa aagtacctgg aaagcctgga gggttaaaag cagaggctcc 6180 tcggcagcgt gtccaggccg tgtgtgcttg ctgtgcttgt cagagcctca ttccctcccc 6240 tgtgttggag agctttctca cagggctcat ccagaggtgc tagaaagcaa tgtgagcact 6300 attaaacact tcaaatataa ggaaaaatgt ataatgttag aaacacacag ttaaaaagta 6360 gccccaggta tcaaacattc tgttactatt ttagaaacta aattaaggct gctttgaaca 6420 tgatggtatt agaaaaatgg tagaatacag tttgttaaat attaatattc tatctttaga 6480 tgatagcatt tggtgacttt tatttctttt ctcatacatt ttttccagtg ttctgtattt 6540 ttaaaatcct ttcataatta ttataatgaa cactttagaa aagatactat ttctcttcca 6600 tccttagagg gcacattata ataattgagt attttaaaat taaattttat gccatgtatt 6660 taaaatgaaa gttcaggtta cattaattcc aactgatttt aaagccttat tttcacagag 6720 tggactcatt caatttttta aattttatat tcatacattt tgattgctca gttatataaa 6780 agcggtgtta tagactcctt tattctccac aaaatgttgt cttatatgta aagtgccaaa 6840 agttgtgttt aatttcctaa gaaagtcatt gctttgtaaa catttgcata atacttagtg 6900 ttttttgtaa ttttaaaaaa ttagcttaac caaaagagtt gcaaaattaa aacttacttg 6960 agtaggtatc tttcagacaa agctgcatgg cttcatgtac aatagtcccc agatcacctc 7020 gcactgtagt ttgctcaaga aggagcctac agatggcagg taggagaagg taaactggaa 7080 attaacaggt ctgtctgtaa gagcatgcca ctggaaacac ccatccaatt tgggacccct 7140 ggaagacagc atgtgtctaa tgggaggcct gtcctagtac aactccttta ctcttttcac 7200 cttcatcttg accttctcag ataccatctt tatgtaaaat gttgatgttg tggagttttt 7260 gcagtaattt aatttttata aatattgtat taaaatatat ttatcttgaa aaaaaaaaaa 7320 aaaaaa 7326 <210> 5 <211> 2779 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2779) <223> hypothetical gene supported by AK096951; BC066547 (LOC440157), mRNA. <400> 5 cagcgatcag cttggctgcc cttgcttcgt agtgccacag tagaggctag gggagcaact 60 ggctttcctc cccaaaaggc gggcagggtt atccacactt tgcccaggtc cctgaagcct 120 gcggctgagc tcggggataa caggggccaa gtcaccggtc ccagacacct aggaactatt 180 agagacagga accagcatat gacacagggg ctgttaagta ggaggttgga gaacacacgt 240 ttttggtcta aaccgggggc ccctctcttt gcccactgag cccgcggcct gcgtggtgct 300 gagactgcct ctggccgcgt ccgcttggga caaggcctga gcggtggctg atcccacctg 360 gatgtcccgg gccggctccc acccgaagcc cgccatcccg ggacgcggtg gggagaagct 420 ggcactgctc cttgccatgc ttggcggccg ctgctgcccg gctgggggtc ccgagtcgca 480 cacgccctgc aagccctggc caccgatccg gagggaacgc cctgggctgc ggtccccgaa 540 gccaagagaa gaagcaggtc ccagggccga ctccaaagcc gcatctccag ctttgttcat 600 gggtccggga agcagaggcc gccgccggcc accgtcgtgg gcgagaagaa gggcacgagg 660 cggccggggc tcctgcccgg aaccacatgt gcgcgccggg ccccgcttct tcatcgcact 720 tgcggccccg gctgcccggg gcctgcgagt ttccagccag ggcccgggac tctggcgcgg 780 tccggccgcg aggaaggaag gcgtggcccg ggtgggggta gcggcaggcc tgcggctcag 840 gccatggggc aggggcagaa aaacgacccc ggcgctgtcc gggcatccag ctcggttccc 900 gctgcagcca ggagactccc gggagcgctc taggaaccac agagccctgg aactcacctg 960 gcagcctcgc ggcgctaaag ccggcggagc ctgagacagc gcgcggcgag gcggtcacgc 1020 tccacccccg cgtggcggca ggactcggat ttcgcccctg gttttaaaat tgtgccggtg 1080 gagcccggga cgctgggaag agcgttctgc gcccctccag tcgcggtctc cgccctaaac 1140 cgacttccag agccgcctct gctccctgga ggggcgcagt ggcggacacc ggcgtcccac 1200 gaagtcgcag gtcctcagtc tgagggctgc cccgcacgct cggaatgcag gagggtctcc 1260 gcctcgctgc gctgcccctg ggggcggagg cgtgcgctgc aggcgagaga ggcggcccgg 1320 tatcgatgga gaagcacaga gggctttgag gtcgcaacgt cccggttgct gagcggagtc 1380 aggagtcagg ttccaaaggg acagcgctca gggttgtaat caccacccgg cccaccgctt 1440 ccgcagctgc gagtctaggg cggagctgtt gggtggaccg agcaggcgag gcgcaggcag 1500 gcagcggctc cgcctcggaa tccgcctcga ccggggcaca ggtgcccgcc ccacctgtcc 1560 ctcggtcacc ccaaccctgt ttcctcgacc cccagcactc ctccaggcct agttcgcttc 1620 agaggcgcaa gacccggaaa acaaggaaga agcgagctca gcctcaatcc ccgtccccac 1680 cccactttcg ggaccgctaa gctggagaat tgaagggggc ggaccccgga ttaaagccgc 1740 tcccttccca gcctcgcccc gctttcctaa tgtccgtgat gatttcgtta ttggcaggga 1800 agagccagac tccctgcgct cccaagacgg ggcgattggg agggggttct ggagctcatg 1860 cctggggtcg gcccggcggg ggtgaccccg cgccctcgcc ggtgcaagga gaacagctgg 1920 ttcccgccgg ggcagggaag cgtggacggt gtgggctcag gcgcctggca ggcacacggg 1980 gcctctaaag cttggtcact gtcacagatc gtgtggttgt ttcttccgtc cccgccacgc 2040 cttcctcctg ggatggggat tcattcccta gcaggtgtcg gagaactggc gcccttgcag 2100 ggtaggcgcc ccggagcctg aggcgggaac tttaaaatca gacgcttggg ggccgggctg 2160 ggaaaaactg gcggaaaata ttataactga actctcaatg ccagctgttg tagaagctcc 2220 tgggacaagc ggtggaagtc ccctcaggag gcttccgcga tgtcctaggt ggctgctccg 2280 cccgccacgg tcatttccat tgactcacac gcgccgcctg gaggaggagg ctgcgctgga 2340 cacgccggtg gcgcctttgc ctgggggagc gcagcctgga gctctggcgg tagcgctggg 2400 agcggggcct cggaggctgg gcctggggac ccaaggttgg gcggggcgca ggaggtgggc 2460 tcagggttct ccagagaatc cccatgagct gacccgcagg gcggccgtgc cagtaggcac 2520 cgggcccccg cggtgacctg cggccccgaa gctggagcag ccactgcaaa tgctgcgctg 2580 accccaaatg ctgtgtcctt taaatgtttt aattaagaat aattaatagg tccgggtgtg 2640 gaggctcaag ccttaatccc cagcacctgg cgaggccgag gagggaggat cccttgagcc 2700 cagaggttcg agactagcct gggcaacaca gtcagactcc atccttccaa aacaaacaaa 2760 caaaaaaaaa aaaaaaaaa 2779 <210> 6 <211> 558 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(558) <223> PREDICTED: hypothetical protein LOC643911 (LOC643911), mRNA. <400> 6 aggtgttaag tgtgatgctt ccataataca tttggatgct gtcagctaag ttcacttctg 60 aactaagggg ttcctccaaa tgttggctga aattcatccc aaggctggtc tgcaaagtct 120 gcaattcata atggagctac tgtactggct attggaagga ggagattctg aagataagga 180 ggatgccact ggaaatgttg aaatgaaaaa tattcagccg ttggtctttg aaatttcctg 240 tgatgtgttt caatctagat gcaaagaaca tggaaaaatc aaagtgctcg agtggtttaa 300 atatgttttg ggtattcctg tttatagact ataatacttt tccaattaaa atcctcagtt 360 gtcacgcaga agaaggttaa gctgtatttg attgccagtt ttactgaaaa tgcttagtat 420 tttacagtat caccaaatat attttgttta gccaaggtat aggaaaaata aaataaattg 480 tataggttga cttttttcta aaatgtcttt attggattga atgaatgttt atacctgaaa 540 aaaaaaggtt caaaaaaa 558 <210> 7 <211> 5228 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(5228) <223> chromosome 13 open reading frame 23(C13orf23), transcript variant 1, mRNA. <400> 7 acaccaggac cccacctctg gctttcagga aagaggggcc caagctggcg gcgcagtgtt 60 gagtttactt gggcgcgact ggctttattg taggtcccca tgagctggtg ggggctgtag 120 gggtaaccag gcagggcgtc tggcgctgtt ggggctgcgt ttttccggag tccccctatg 180 cgaggccgtg cccctcttcg cccggctcct ggtgctcccc agccgccggc ccgctcccgg 240 aagctgcagc agctggtaac aaagagcctg ccgggccgcc tgctgccggg gccgaggtat 300 ccaggagtcg ggcggagcgg ctggggatga gcgcgagccg gaccatgcgt ccgggttcgc 360 ggcggtgagg gtcgcggccg gcggccgagg cgcaggtgcg ggtcgagaga ccggcgcctc 420 cctccccgcc gcccgtggac tctgagcgca ggtgtttcta ctctgccggc cgctccacct 480 gggaaagcgc cttcaagagc tacctctggc ggcacctggc cctcagctgc agggaaaccg 540 cactcaaacc tgccgccgag cccgggtttt tctgcaaaac tcagaggacc tggctcttgc 600 ccgaggtgcc ctgaaccatt gtgtgaataa gctggggaag cctgactgga gtgttttttc 660 tttttaataa aaagagtttt tctgaatctc aatttttaga aatttttttt gcgaagtttg 720 caatactctc tacctcttcg catcctctct tgctcgtgga gtctttttcc tcctcagcta 780 taaatatttt ttactatcgg cggagcagac cagggatgaa cgtcttttaa ttgcaagtat 840 aactgttaaa accacgtcgg gatagtagtc aagatggata aaaagtcctt tgaaatggtg 900 ctggatgaaa ttagaaaggc tgttttgaca gaatacaaat taaaagcaat tgaatatgtg 960 catggatact tttctagtga acaggtggtt gatttgctga gatatttttc ctgggccgag 1020 ccccagttga aggcaatgaa agcattacag cataaaatgg tggctgtcca gccaacagaa 1080 gtggtcaata tactcaactg tttcactttc agtaaagaca aactagttgc tcttgaactg 1140 ttagcctcga acattattga tgcacagaat tctcgtccta ttgaagattt attcagggta 1200 aatatgtctg agaagaaacg gtgcaagaga atacttgaac aggctttcaa ggggggctgc 1260 aaagctcctc atgctatgat atcttcttgt ggaacaatcc caggaaatcc atatcccaaa 1320 ggaagaccta gccgcataaa tggaattttc ccaggaactc ctttgaaaaa agatggtgaa 1380 gaatgtacta acgaaggcaa aggaatagct gcacgaattc ttgggccatc caaaccacct 1440 ccttcaacat ataatccaca taaacctgtt ccttatccga tacctccatg ccgaccacat 1500 gcaactattg caccaagtgc ttataacaat gcaggtctgg taccattagc gaatgtcata 1560 gctccacctc cacctccata tactcctaat cctgtaggaa cagagaatga agacctttcg 1620 aatccgtcaa aacctataca gaatcaaaca ttttccaccc cagcaagtca actcttttct 1680 cctcatggtt ctaatccttc aacacctgct gcaactcctg ttcctactgc atccccagtc 1740 aaggcaatta atcatccatc agcatcagca gctgccaccg tttctggaat gaacctgctg 1800 aatactgtcc ttcctgtgtt cccagggcag gtctcctcag ccgttcacac acctcagcca 1860 tcaataccaa acccaacagt tatcagaacc ccttcattgc ccactgcacc tgttacatcc 1920 atccacagta caaccaccac tcctgttcct tccatttttt ctggcctagt gtcactgcca 1980 ggtccttctg ccactcctac cgcagccact cctaccccag gacctacacc acggtccact 2040 cttggttcca gtgaagcatt tgcttctact tctgcacctt tcactagcct ccccttttcc 2100 accagctctt ctgctgcttc taccagcaac ccaaattctg cttcattgtc atcagttttt 2160 gcagggctcc ctttgccctt accaccaaca tcccaaggcc tatccaaccc gactcctgta 2220 attgctggtg gctctactcc cagcgttgcc ggtccacttg gtgtgaacag tcctcttttg 2280 tctgcgttaa aaggttttct gacatccaat gacaccaatt taatcaactc ctctgcttta 2340 tcctctgctg tcacaagtgg gctggcttca ctatcttctc ttactcttca gaactctgac 2400 tcttctgctt cagcccctaa caagtgctat gccccatcag ccatccctac cccacagagg 2460 acttccactc cagggttggc cctgttccca ggcctgccgt ctcccgtggc taactcaact 2520 tccactcccc tgacattgcc tgtacagtct cctttagcca ctgctgcatc agcttccacg 2580 tcagtgccag ttagctgtgg ctcctcagcc tcccttttgc gtggccccca cccaggtacc 2640 tcagatctgc atatttcatc tacccctgct gcaacaactc ttcctgttat gatcaaaact 2700 gagcccacaa gtcctactcc ctcggccttc aaaggtccat ctcattctgg gaatccctct 2760 catggcactt taggtttgtc agggacattg ggccgtgcat atacttcaac atccgtgccc 2820 atcagtttat ctgcttgcct taatcctgca ttgtcaggtc tctccagctt gagtactcct 2880 ttaaatggtt caaatcctct ttcctctatt tcccttccac cacatggttc ctccactccc 2940 attgcaccag tattcactgc tcttccttct tttacttctt tgaccaacaa ttttccttta 3000 actggcaacc catctcttaa tccgtcagta tctctcccag ggtcattaat agccacctca 3060 tctaccgctg ccacctccac atctctccct catcctagct caacggcagc tgttctctca 3120 gggctttctg cttcagcacc agtctcagca gcacctttcc ccctcaacct gtccactgct 3180 gttccctcac ttttctctgt tactcaagga cctctgtcat cttcaaatcc ctcctatcca 3240 ggcttttctg tctctaatac cccaagcgtt acccctgctc ttccctcatt cccggggctg 3300 caggcgccct ctacagtcgc agctgtcaca ccactacctg tggctgccac agccccatcc 3360 ccagctccag tcctcccagg attcgcctca gcattcagtt ccaatttcaa ctccgctctt 3420 gttgcacaag ccggtttatc atctggactt caagctgcag gcagttctgt ttttccaggc 3480 cttttgtccc tcccgggtat ccctgggttt cctcagaatc cttcacaatc atccttgcaa 3540 gaattacagc ataatgcggc tgcgcagtca gcattgttac agcaggtcca ttcagcttcg 3600 gctctggaaa gctatccagc tcagcctgat gggtttccta gttatccttc agcgccagga 3660 acaccatttt ctttgcaacc aagcctgtcc cagagtgggt ggcagtgaat acttttaact 3720 tttattctcc ttcagagcaa catcagaatt gcctgagaac tgcaatgaac aatctgacaa 3780 atgtgaagct ggccaaaagt cggaaaatga gaatgagggt aatcctggag aaattgtgac 3840 aacaatttga aaattgtggt tgcattttaa agtgtgaaca ctcccctatg taaatatgct 3900 gacaataaat tgtatggaga atggtattta aaaagtgttt ggagactttt cacctgtcct 3960 ataaaatttt gaattgtgta tgtgatctac atagaaagaa tattaaagag taggttgaac 4020 tctttatagc cgaatacagc cttaaatatg cttgtatagc atccactggc agaagtaata 4080 gttgtgcctc agacttgggg gttgcatgtg gccctggggg agttactacc cttggtatgc 4140 atgagcggtt cctattagca tcagtgggaa ctcagtactc tgtatgtatc cacaaaaggg 4200 aacttgagac ccacagttat tcttaatttc tgatattaac aaccgtacat actgctgaat 4260 ttaactcaaa atatttcagg taagtgaaag tggtgcttaa tgtagactat agaatgactt 4320 tcaggtgttt tcaactgaaa gtatatatcc agaactgcat ccttatagaa atacaagtaa 4380 gacttaggat aatttgcctt caaaacagtt ttcctaatct cagcagtatc cagtgagtga 4440 agaacacttg actgactctt gggccacctc tgttacttac tgtactatgg aagctcctgg 4500 tgaatgttta caattatggg atgtagtatt tctatttgta ctttaagtca aatgcttata 4560 tgaaatatgt gacaacaaat agagaagact ggctctgtta gtaattatgc agtatgtact 4620 ctatttaagg atctgtggta gtataacatg agtgaatgtc attaattttg aagtaataac 4680 tgccacatgt gggaagtagg ggagtaagga gaatgaattc caatctgtga ttaaaagtgt 4740 aaactataga ctctactgta gtacatttca ggatctagaa gttttacttt tataaagatg 4800 gtgtccggaa gatgttgcta atgtatttta cttcaacata gggaacaaac tttttaagta 4860 tattaataaa cctgtatggt tagtttttaa cagtttttta aaataaacta tggatatgac 4920 aaatattctg tgttttacta agtgcttgga taggctttct aattttgtat acgtgctaga 4980 gttaattatt gaacattttt atccaaattt agttgtaact ctgtttatac tactgattgc 5040 tcattcgttt aaatgatatt ttaatgtaaa agtcataacc aacatatgaa cagacagatt 5100 tatgtcttta aacacagaat gtaagctata gtttaatctg ataccagttg ctggaagttg 5160 ccatttgttt ttcttaaatc tatacccata aaacttcttt taagattaaa aaaaaaaaaa 5220 aaaaaaaa 5228 <210> 8 <211> 1610 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1610) <223> PREDICTED: hypothetical protein LOC644424 (LOC64424), mRNA. <400> 8 caaaaggcca aagtaaaaaa aaaaaaaaaa ggaaaaaatg aaaaagaagc cattgaatac 60 cctattgacc ataagaaaaa ggcagggaaa gttgttcaac ggcaacccag gcactgaagg 120 aaaaagaaca tggagaatga caaaagccca gagggaggag taaaaggaca caaacaccat 180 tctcagggac caggactggg cgctgttctc agggaccagg actgggcact aatcacagaa 240 ctgtaacagg cgccccatgg gaatgaccaa ctgttagatg gggcctgcag ggcagcacct 300 ccctcctgcc tcccaccaac agcttctaaa gggaaatgcc gactcttttc acaccagtcc 360 cctcactgcg gctgagtgtg tgggcgcaga tgataggtca caacaacctg attcagtcct 420 cactgcggct gagtgtgtcg ggtgcagatg acaggccacc acaacctgat tcagtcccca 480 ctgtggctgt gtgtgggggt gcagatgaca ggccaccaca acctgattca ggattcagtt 540 ggctaccagc cagtgccata aggaaaacca ttctggggct cttgagaggg gcaaagcata 600 atttgcatgt gggagaaatg ttaatagttt gtgaccagag gacaagctgt ggtttattaa 660 agactgctgc aggttcctac tatgcttctc atcaagaggc ggaatctaat caccttcccc 720 ccttgaatca tggctggtct cagtgatgag tacgactgga cagtgtggca ggagagatgc 780 tctgggactt ctgaggggcg atcatgagag gccttacagc ttctgcctgg gcctcttgga 840 cacacaccct gggagaagcc agacaaacct gactacctga cactgccaga ctgggaggaa 900 gtccatgctg gccacaaaga gagggctggg tgcctgctcc atgtccccag ccactagagt 960 ccttctgggt gcctgcttca cgtccccagc cactagagtc cttccagatg agaccaggga 1020 catcatgaag caaccaaccc acacagccct gtcctgtgtc ttgacccaga aaattgtgac 1080 atgtaaaaag aataaattcc tggtttaagc cagtaaggtt actggtacat tgttacatct 1140 cagataatta aaaccttgaa aaactcatga gagatcacaa gtagaacctt gatctgaaac 1200 atggcatgtg gcgatttata ttgagtatta ggttaaaaat gcaagaaggg agcatagtta 1260 atattttacg ttaaagctaa aactataatt gcctacttaa aattttcagt taattaggtt 1320 gtcacttttt gttcttaacg aagaaatcaa ctagttttat tccataaaca gttagaactg 1380 atgcacacat ccgtttctcc ttactcattt taaacagcta tctgaaatag gaagtgtaat 1440 ataattttta aagaatctga aaacatgaca gaaatgttta aactataaac atatattgta 1500 tatgttagca tattgtatac attgcatatt aacataagct agaatcattg acataaattt 1560 atataaacaa aaggtataaa ataaaaaaaa aaaaaaaaaa aaaaaaaaaa 1610 <210> 9 <211> 2486 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2486) <223> hypothetical protein FLJ21511 (FLJ21511), mRNA. <400> 9 acactgcctc ggttcggcaa gtgggtcagt tggctggggc tcacttggca acgggacgcg 60 ggaacgaggg gcgcggacgc aggcccggga ggacgcggcg gcgggaacct gggggcgcag 120 ggctagggca gcgggcccga cccgcacggc tttcctggaa agcgctgccc ctcgccgcgg 180 cgatgccctc gctgtggaga gaaatcctct tggagtcgct gctgggatgt gtttcttggt 240 ctctctacca tgacctggga ccgatgatct attactttcc tttgcaaaca ctagaactca 300 ctgggcttga aggttttagt atagcatttc tttctccaat attcctaaca attactcctt 360 tctggaaatt ggttaacaag aagtggatgc taaccctgct gaggataatc actattggca 420 gcatagcctc cttccaggct ccaaatgcca aacttcgact gatggttctt gcgcttgggg 480 tgtcttcctc actgatagtg caagctgtga cttggtggtc aggaagtcat ttgcaaaggt 540 acctcagaat ttggggattc attttaggac agattgttct tgttgttcta cgcatatggt 600 atacttcact aaacccaatc tggagttatc agatgtccaa caaagtgata ctgacattaa 660 gtgccatagc cacacttgat cgtattggca cagatggtga ctgcagtaaa cctgaagaaa 720 agaagactgg tgaggtagcc acggggatgg cctctagacc caactggctg ctggcagggg 780 ctgcttttgg tagccttgtg ttcctcaccc actgggtttt tggagaagtc tctcttgttt 840 ccagatgggc agtgagtggg catccacatc cagggccaga tcctaaccca tttggaggtg 900 cagtactgct gtgcttggca agtggattga tgcttccatc ttgtttgtgg tttcgtggta 960 ctggtttgat ctggtgggtt acaggaacag cttcagctgc ggggctcctt tacctgcaca 1020 catgggcagc tgctgtgtct ggctgtgtct tcgccatctt tactgcatcc atgtggcccc 1080 aaacacttgg acaccttatt aactcaggga caaaccctgg gaaaaccatg accattgcca 1140 tgatatttta tcttctagaa atatttttct gtgcctggtg cacagctttt aagtttgtcc 1200 caggaggtgt ctacgctaga gaaagatcag atgtgctttt ggggacaatg atgttaatta 1260 tcgggctgaa tatgctattt ggtcctaaga aaaaccttga cttgcttctt caaacaaaaa 1320 acagttctaa agtgcttttc agaaagagtg aaaaatacat gaaacttttt ctgtggctgc 1380 ttgttggtgt gggattgttg ggattaggac tacggcataa agcctatgag agaaaactgg 1440 gcaaagtggc accaaccaaa gaggtctctg ctgccatctg gcctttcagg tttggatatg 1500 acaatgaagg gtggtctagt ctagaaagat cagctcacct gctcaatgaa acaggtgcag 1560 atttcataac aattttggag agtgatgctt ctaagcccta tatggggaac aatgacttaa 1620 ccatgtggct aggggaaaag ttgggtttct atacagactt tggtccaagc acaaggtatc 1680 acacttgggg gattatggct ttgtcaagat acccaattgt gaaatctgag catcaccttc 1740 ttccgtcacc agagggcgag atcgcaccag ccatcacatt gaccgttaac atttcgggca 1800 agctggtgga ttttgtcgtg acacactttg ggaaccacga agatgacctc gacaggaaac 1860 tgcaggctat tgctgtttca aaactactga aaagtagctc taatcaagtg atatttctgg 1920 gatatatcac ttcagcacct ggctccagag attatctaca gctcactgaa catggcaatg 1980 tgaaggatat cgacagcact gatcatgaca gatggtgtga atacattatg tatcgagggc 2040 tgatcaggtt gggttatgca agaatctccc atgctgaact gagtgattca gaaattcaga 2100 tggcaaaatt taggatccct gatgacccca ctaattatag agacaaccag aaagtggtca 2160 tagaccacag agaagtttct gagaaaattc attttaatcc cagatttgga tcctacaaag 2220 aaggacacaa ttatgaaaac aaccatcatt ttcatatgaa tactcccaaa tactttttat 2280 gaaacattta aaacaagaag ttattggctg ggaaaatcta agaaaaaaag tatgtaagat 2340 aaaaagaaga gattaatgaa agtgggaaaa tacacatgaa gaacctcaac ttaaaaaaca 2400 catggtatct atgcagtggg aaattacctc catttgtaaa ctatgttgct taataaaaac 2460 atttctctaa aaaaaaaaaa aaaaaa 2486 <210> 10 <211> 1900 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(1900) <223> chromosome 9 open reading frame 19 (C9orf19), mRNA. <400> 10 agccgcgggg agcgaggagc gcgcggagcc ggccatgggc aagtcagctt ccaaacagtt 60 tcataatgag gtcctgaagg cccacaatga gtaccggcag aagcacggcg tccccccact 120 gaagctctgc aagaacctca accgggaggc tcaacagtat tctgaggccc tggccagcac 180 gaggatcctc aagcacagcc cggagtccag ccgtggccag tgtggggaga accttgcatg 240 ggcatcctat gatcagacag gaaaggaggt ggctgataga tggtacagtg aaatcaagaa 300 ctataacttc cagcagcctg gcttcacctc ggggactgga cacttcacgg ccatggtatg 360 gaagaacacc aagaagatgg gcgtggggaa ggcgtccgca agtgacgggt cctcctttgt 420 ggtggccaga tacttcccag cggggaatgt tgtcaatgag ggcttcttcg aagaaaacgt 480 cctgccgccg aagaagtaac ttgttaaatg taatgggaag gtggcagact taagaacgtg 540 gatatgaagt gcctagaacc accacaacct ggctgtgcgt ctgtccctgt gggtgtatgt 600 gcttgtgtgt gtgatgcatg tgagcgtctc tggcacacac acttggacat acagttctgt 660 gtgcgctcat tcttattaca ggagtgagca aaggaagcat ttaccccgat ggttacctag 720 accacgatta tttggattgg ggggaggggg gatccgtttt ttttttttaa ttttttgtta 780 tttctaagca aacctctttt gtacttttct tacttctaat atccatccct ggactttttg 840 tattccaaat gtttgtgatg ctgagaagtg aagttcattt tatgtgatct tcatgcgtcg 900 taatctactt ttggtagata attaagatta ttaaaccctc atttaaatgt gacataaaat 960 acagctttaa gcacataaat ataaagcagc ttccatcagg aacatggagc aggcagggac 1020 tccattttac agaattactg agatttctca gttgtaaaac atgatgtcat cctgcatgcc 1080 tcctggaatt ctccaatggg gtcgccaaac aacaaatgga gaaaaaaagt tttacttcct 1140 tgcattcttc tacctttaaa tagcaaagta ccactaccac caccacctct tgcccccttc 1200 cctcttttct taaacttctg gcatttcaga gctcagcagg ctacccctgg tttctggaga 1260 gttgggctag gcctgaagct ccccctcccc cacctctgct aggcagccca ggcctggtct 1320 gggagacagc ccctcaccct gcctgggctc ttggccaagc ggccttggat ggatgaagtc 1380 agagaggtgg ggtgagggtg agcttactca gggcccccag aggaagccct cagcctctgc 1440 cctcccccca cacagggcgg gagcccaggc ctgttcctgg cagctgtggc tgcagctgtg 1500 ctcctgctcc ctcctggaat gtgcgacaag cccaaatgtt ccagggaggc ggccggggca 1560 gggggcttag aagtgctaat atggttctgt gttttgcctg aaacgatacc aggttcccct 1620 gaatagcaac tttacaaggt ccatgtggga gggaccaacc cagatgccct gctgagtgtc 1680 cctgaaacca tggcagctcc atctgtcaag atggcagggg ccggagtgag ggggctgctg 1740 gcttaacagc aggcatctgg gcaggccagt cctcaaagca gctcctgaag gtctgtgttg 1800 cactgtcacc agtctcaagc tatgcctcta atttcaccag ggatattgac taagaagaca 1860 ataaaatctt tttctttgtg taaaaaaaaa aaaaaaaaaa 1900 <210> 11 <211> 2544 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(2544) <223> thymus expressed gene 3-like (MGC15476), mRNA. <400> 11 ctcactcaga cccatgaggc cctgcctggt ctcgtctggg acctgggaca gcagctggga 60 gacctgagcc tggagtctgg gggcctggaa caggagagcg ggcgtagctc gggcttctat 120 gaagatccca gctctacagg aggtccagat tcaccaccct caaccttctg tggggacagt 180 ggcttctctg gatccagctc ctatggtcgc ctgggtccct ctgagccccg gggcatctat 240 gccagtgaga ggcccaagtc cctaggagac gccagtccca gcgctccgga ggtggtgggc 300 gcgcgggcag cggtgccgcg gtccttctca gcgccctacc cgacggcagg tgggtcgccg 360 gcccggaggc ctgctcctcg gcggagcggc gggcccgcgc cgggcccttt ctgacgccca 420 gccccctgca cgccgtggcg atgcgcagcc cgcggccctg cggccgccct cccaccgact 480 cgcccgacgc ggggggcgca gggcggcccc tggacggcta catctcggcg ctcctgcgca 540 ggcgccgccg ccggggggcg ggccagcccc ggaccagtcc tgggggcgcg gacggcggcc 600 cgcggcgcca gaacagcgtg cgccagcggc cgcccgacgc gtctccgtcc cccggcagcg 660 cgcgacccgc gcgggagccc tcgttggagc gcgtcggggg ccaccccacc agccctgccg 720 ccttgagccg cgcctgggcg tcgtcgtggg agtcggaggc ggcacccgag cccgctgcgc 780 cgcccgccgc cccctcaccc cccgacagcc cggctgaggg ccgcttggtg aaggcgcagt 840 acatcccggg cgcgcaggcg gccacccgag gcctccctgg ccgcgccgcc cgccgcaaac 900 cgccgccact gacccgcggc cgcagcgtgg agcagtcacc accccgggag cgtccccggg 960 ccgccggccg ccgtggacgc atggccgagg cttcgggccg ccgcggctcg cccagggccc 1020 gcaaggcctc gcgctcccag tctgagacca gcctgctggg ccgcgcctcc gcggtccctt 1080 cggggccccc taagtacccc acggcggagc gggaagagcc tcggcctcca cggccacgcc 1140 gcggcccagc gcccacgctg gcggcccagg ccgcagggtc ctgccgtcgc tggcgctcca 1200 ctgcggagat cgacgctgcc gatgggcgcc gcgtgcggcc ccgagcccct gcggcgcgtg 1260 ttcccggccc cggcccgtcc ccgtcagctc cccagcgtcg tctgctttac ggctgcgcgg 1320 gcagcgactc cgagtgctcg gctgggcgcc tggggcccct gggacgccgg gggcctgcgg 1380 gaggcgtcgg cgggggttac ggggagagcg aatcgagcgc cagcgaggga gaatcgcctg 1440 ccttcagctc tgcctccagc gactcagacg gcagcggtgg cctcgtgtgg ccgcagcagc 1500 tggtggcggc caccgcggcc tctgggggtg gagcaggtgc aggggcgccc gcaggccccg 1560 ccaaagtctt cgtgaaaatc aaagcttccc acgcgctcaa gaaaaagata ctgcgtttcc 1620 gttcgggttc tctcaaggtc atgactacag tgtgagtttg gggatttgct tgggctcccc 1680 cttcatggcc tctgcacctc cacactccca accactgacc cttccacatc taccttccaa 1740 agaccatcgt tttctctgct tccaaagacc cccctcactc tccccactcc taacagtctt 1800 ggttgaaaag gctcccccac caccaccgag aggaatgggg aggagccctg tttgacccag 1860 ttcagcttct agcttggaag cccttgggca agacagttcc ccttctctgg gcgtcacttt 1920 cctcatctgt acagtaagtg tccatgtatg caaaaggggt aattcggttt gaatttcccc 1980 gttttagttt agaagcctag tctgtttgtt ccccttcacc gctctccctc tcattcctga 2040 tgagccctct cattcctcct ttccttgccc agctatggcc ccctctcatt cacaaagtgc 2100 cccctccatg tccctggacc cttaagatat ccccttggca ccctggtcag agactctgtg 2160 tctgactcag gtggtccctg cagagtgccc tgggaaggga aggagcactg atttgggggt 2220 tttgagggtc aagtaggggt tggtaacacc tggaaagaag gactctttca cttcgatccc 2280 tggacaatta tggaggattc ggaggtagaa gaggggaagg aagatggttt ctatctcatg 2340 acccccactc cctgtgagag ggaatggggg aagcctgatg accctcagct gttccaatct 2400 agtatttttt ttctttttta aaattactgt atttattatg acgatggtga ctccccagtg 2460 caaagggggg ccagattctg tgtgtttctc taacctcttt gtaaataaat gcacagtgta 2520 acataaaaaa aaaaaaaaaa aaaa 2544 <210> 12 <211> 4471 <212> DNA <213> Homo sapiens <220> <221> mRNA <222> (1)..(4471) <223> mRNA; cDNA DKFZp686J0156 (from clone DKFZp686J0156) <400> 12 caattacata tttatttttc catacctgat ttttttcaag tctgtaataa aaaaagtata 60 agttgagatt aacataggtt atttttcatg aagtatagca aacgatctag aatgtgatag 120 gagtgtggtt tccatttctt tttttttttt tttaacagac ttttgtgctg tagtaagaat 180 gtcttagaag ttgtgtcttc gagttcctca aacaccggac agggctcccc cagagctgcc 240 tcagcctttg atttggtcca tattcagaca cttcctgtct tgcatacact ctgaggatgg 300 gccgcttcta gctgccgccc gtctccctct tgccttcttg tctctaaatc agacactccc 360 aagcactcca tctgctatac taggagagtg ggagagccaa agcattttgg agtccatgta 420 aagtgcctgg gaaaagagat gtaagagcag tgggagttta tataattagc gaattctttt 480 ctcagaattc agcggaaatg tatttctgtt gttattattt acaaaattgt ggcctcagag 540 gagctgtctt ttggaaaata agttttcatt catgcagtta gttagacatg cacgatgtac 600 ttgaatcaat aaactgtgga ccagaaaagg gctgcttaaa tgaattcacg tgttctaatt 660 ctctttcgag gctgttgatg acctcctgga ttcatacccc catgatctgt cttgctcttg 720 cctctgttct ttgataaagc acatcagact atgtgacacc catcttttca agaacgacct 780 aaaagcaatg acaacaggca ggagagaatt accactggcc tgggcacagt gacagcagaa 840 ggcccacctg agcttggaga gttggcgaga taaggcaaaa tcaaggtgca acagtgggcc 900 atgttccaag ggtgaatgga tctgagagtc cgctgatgtt ccttactgat cagaacaggg 960 accttctaac gaaacagcca gagttccttg aatcaggcag aagttcttta gagacaggaa 1020 gccagagcta ttgataatat ccgaacgaca gaggaaggaa tttcttatta gaaattctaa 1080 aataaaacaa gtggggattt ggttggatac ccttagaagc tacatttttc tctcatccct 1140 aagatagata tctcaagtgt atatctgaca cctcttggct ttgacacggc tctgcttctc 1200 aagtgaccat ttgttttaag tctgttgtct agaattcttt gtgggggctg gacctctgaa 1260 aaagattctc actgcagagg ctttaaatct gtgttttttt ccactccctc cgtcctggga 1320 tgtattcggt aggacatttc atttatatca ggatattggc tgattcagct ctctttcatc 1380 gttattattc aggcctccct ccaccacctt gttctttatt gcctaagtat tgccctcccc 1440 aattcttcat cgtaatagct ctaaatttag tttgacccaa attaattttt gttccaacag 1500 atatatttta agacagagaa gcctctctca ggagccagat gatctgaaga tgatgctaat 1560 ccccaaatac gaagttcctc cagctaactc tcctctgagc tccctcttct tagctttggg 1620 attggggatg gtctcatcct tgccaggaat ccctttgttg ctcccagtgt ctctgatgag 1680 cttctcctcc ctcccagaga caatgcaggg gtggttttca gcagaatgtg ccacctgcac 1740 ttctgattgt tctgagaccc agcccagagg ggtggagaag gcgcacaaac cctattccaa 1800 taaactgcct gcagagaacc acagcctgct aatagtcgtt gaggtctcag ccccctaagg 1860 tctccaagct catttgacca gcgcagctgc gacttcggct gtctgcctct ggcaggtgcc 1920 aatatcagca tcttgtccca ctgccatggg gagttaattt ttgctccagg gcagctgcca 1980 agcccagcac cggcatcaat agaaggtttt ctctgatttt cttctcttcc tctcaggcta 2040 ggctttctta ccaatcccca atttccttct gtagggcgcc aggagactgg ccagagatct 2100 ttagactctt acttagtttg aacatctctt gctgctcaca cccaggcttc ttcagcagaa 2160 agcatgaccc atagtaggta ctcagaaact ggttgaatga aaagccttga catttaaggg 2220 ctttattctg tcatacggtg gcaagaactg gcctattggc atcgtattcc tggcattgag 2280 ctgtattgac cctgaatgtg tcctcctgag gtttttgagg gtgacctagg agaaagggtc 2340 tgaaaaagca ctgggatcca agtgacttta aatctgcccg tggcatttcc tgctgagagg 2400 cgagaaacta gcatctctcc caacaggctc acatccgcca ggaaggacag agtccaaaac 2460 gggggtagac tttgtgggaa attcgccagt tagtccgctg agattttaat ctgcctcaag 2520 cacaggatgc tgacaagaaa ggtagaccac tcccccgatc ccagacaaac cccaggggtg 2580 acaacttctc catcagtatc ctgagaagca acatcaaatg cttaccaagt cagcacgttt 2640 actgagtgag tactctgacg gaataaacca gcatttggag ctgaacttga gaacacaggg 2700 ccctctgaca gcagcttagg gaaacaccca tcccttccag attggcagaa tccttccatt 2760 tcatgtcctt cggagacgct gtattctctt tacaaatcat tcatgaaact gagactcagt 2820 ctcccagggg taagtcctgg gccacgtgca aacaatggca aatccagctc ttccatgata 2880 gagaaggcaa acacacccac cttcatcctg agcctaaaag gccacctctg agcacttggg 2940 cagccactcc tctgggcctc agagggccat gagcttggcc aggtaggcac agcggcgggg 3000 aagtcacagc tgtcaggtac cggccatggt gcaggtggga ataggagatg ccagagctgc 3060 tttagctgag gaaagcaaac agtcagcagt gctcaaagga gcaaaacttc gaatgtgcac 3120 attgacccct gacacctgca agcataacac agatcctaag actagagtga agtaggaaga 3180 agaattagaa aatccagtgg atgtcctgag tatagggaac cagggccgtt gaaaatcagt 3240 aaaggttgat tacctggggc gagaccgggt gactgtggca gtgcaggtga aggtaccctg 3300 gaccttctca gttcgctggc acataaggct ccgccaataa agcgtggttc tctctgtcac 3360 acacacacac acacacacac acacacacac acaatgattg gagggctata tgatccagca 3420 ttagcttcct ggtgtgccaa gcatgcttga tcgggaattt ttttttatta ttattatttt 3480 ttagctgtag ctgaaggcat ttctcggatg tggagaggag aatggaaatc gcagaaccaa 3540 atcagtttgc cctgccatat ttggctgtgg tctgtcattg ggcatttctg atgtgctttt 3600 ctggattcag gaagagctga ttgtcctccg agggttgaaa aaaaaaaaac agtttcagaa 3660 acctgaatcc agggccttat agttctcctc attatcgatc ttcttctccc ttccctcgcc 3720 caagggagtg ggggaaacac ttttcactgc agagtttgct ttaaagtttt cccatcttgc 3780 gtgcattatc ccttgatatt aaaattattt tctcagttta atccaactcc tgctgagaag 3840 ctgtgtgaga tttaggctgt ggggtttttt tcttgtactc ttttggatgg tgttgcattt 3900 ttcactctta acccgagggt gtgtttcagc ttatgttcgt tctgtttcat gcaggtttat 3960 agcacggtag agtagaaggc ggcttctgat ttttagggta tttttagaat tcattcctga 4020 gtgtggggtt cagacaccca gtctcctcgg aacaggggtg aggggtcgac tgagctttgt 4080 tgagaagcct ccagttaggc ttcgggcggg tctccatgtt atattgtgtg tttactgagc 4140 ttcccactgg tagaagatga cacatttgtc catcgtcctg tgtatctgct ttccagagga 4200 caccggagca ttctcctggg gtcactccca catggctgcc tcacatagct gttttgcaac 4260 agcctttatt gccaacaccc ttggaagaac atctcctgta gaagtacaag ttttgcaata 4320 tggactttgg aagtggtttt gtgatgttcg aattttctgt tagcctattg ctcaagcact 4380 acagaatgta catagtccct ttggccatcc tctcacccca gaatatccta ataaacattg 4440 ttttcttttt taaaaaaaaa aaaaaaaaaa a 4471 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying GAPDH <400> 13 tcatgaccac agtccatgcc 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying GAPDH <400> 14 tccaccaccc tgttgctgta 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LMTK3 <400> 15 ggaacagcga gcagatcaaa 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LMTK3 <400> 16 aggagaccat cttgcgcttc 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644774 <400> 17 tcaatctgcc acagaaggct 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644774 <400> 18 ccaggatggc caggaagggt 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying Hs.389988 <400> 19 gcctgggacc tccagaataa 20 <210> 20 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying Hs.389988 <400> 20 tggcaaatga aaaattcagc a 21 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying WDR72 <400> 21 tcccatgtac ctgaggctga 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying WDR72 <400> 22 ttggaagttt gccgagtttg 20 <210> 23 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC440157 <400> 23 gagaagaagc aggtcccagg 20 <210> 24 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC440157 <400> 24 agttccaggg ctctgtggtt 20 <210> 25 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC643911 <400> 25 aattcatccc aaggctggtc 20 <210> 26 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC643911 <400> 26 cccaaaacat atttaaacca ctcg 24 <210> 27 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C13ORF23 <400> 27 agcaccagtc tcagcagcac 20 <210> 28 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C13ORF23 <400> 28 gaactgaatg ctgaggcgaa 20 <210> 29 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC644424 <400> 29 attcagtcct cactgcggct 20 <210> 30 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC644424 <400> 30 ttccgcctct tgatgagaag 20 <210> 31 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying FLJ21511 <400> 31 gtggctaggg gaaaagttgg 20 <210> 32 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying FLJ21511 <400> 32 aatctctgga gccaggtgct 20 <210> 33 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying C9ORF19 <400> 33 accgggaggc tcaacagtat 20 <210> 34 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying C9ORF19 <400> 34 tatctggcca ccacaaagga 20 <210> 35 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying MGC15476 <400> 35 cactgcggag atcgacgct 19 <210> 36 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying MGC15476 <400> 36 ttttcacgaa gactttggcg 20 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as forward primer for amplifying LOC143381 <400> 37 ggcggcttct gatttttagg 20 <210> 38 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid used as reverse primer for amplifying LOC143381 <400> 38 tccaagggtg ttggcaataa 20

Claims (6)

LMTK3(lemur tyrosine kinase 3, GeneBank accession No.NM_001080434) 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 포함하는 대장암 진단용 조성물.LMTK3 (lemur tyrosine kinase 3, Gene Bank accession No. NM_001080434) gene, a composition for diagnosing colorectal cancer comprising a pair of sense and antisense primers of the gene, a protein expressed from the gene, or an antibody against the protein. 제2항에 있어서, 상기 센스 및 안티센스 프라이머쌍은 서열번호 15 및 16 인 대장암 진단용 조성물.The composition for diagnosing colorectal cancer according to claim 2, wherein the sense and antisense primer pairs are SEQ ID NOs: 15 and 16. 4. 제1항에 있어서, 상기 조성물은 LOC644774(similar to phosphoglycerate kinase 1, GeneBank accession No.XM_927868.1), WDR72(WD repeat domain 72, GeneBank accession No.NM_182758.2), LOC440157(hypothetical gene supported by AK096951; BC066547, GeneBank accession No.NM_001013701.1) 및 LOC643911(hypothetical protein LOC643911, GeneBank accession No.XM_931911.2)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.According to claim 1, wherein the composition is LOC644774 (similar to phosphoglycerate kinase 1, GeneBank accession No. XM_927868.1), WDR72 (WD repeat domain 72, GeneBank accession No. NM_182758.2), LOC440157 (hypothetical gene supported by AK096951; BC066547, GeneBank accession No.NM_001013701.1) and LOC643911 (hypothetical protein LOC643911, GeneBank accession No.XM_931911.2), one or more genes selected from the group, sense and antisense primer pairs of the genes, proteins expressed from the genes, Or a composition for diagnosing colorectal cancer further comprising an antibody to the protein. 제3항에 있어서, 상기 유전자의 센스 및 안티센스 프라이머쌍중 LOC644774 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 17 및 18인 센스 및 안티센스 프라어머쌍, WDR72 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 21 및 22인 센스 및 안티센스 프라어머쌍, LOC440157 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 23 및 24인 센스 및 안티센스 프라이머쌍, LOC643911 유전자의 센스 및 안티센스 프라이머쌍은 서열번호 25 및 26인 센스 및 안티센스 프라이머쌍인 대장암 진단용 조성물.The method of claim 3, wherein the sense and antisense primer pair of the LOC644774 gene of the sense and antisense primer pair of the gene is SEQ ID NO: 17 and 18, the sense and antisense primer pair of the WDR72 gene is SEQ ID NO: 21 and 22 sense and antisense primer pairs, sense and antisense primer pairs of the LOC440157 gene, SEQ ID NO: 23 and 24 sense and antisense primer pairs, sense and antisense primer pairs of the LOC643911 gene, sense and antisense primer pairs of SEQ ID NOs: 25 and 26 Phosphorus colorectal cancer diagnostic composition. LMTK3(lemur tyrosine kinase 3, GeneBank accession No.NM_001080434) 유전자, 상기 유전자의 센스 및 안티센스 프라이머쌍, 상기 유전자로부터 발현된 단백질, 또는 상기 단백질에 대한 항체를 포함하는 대장암 진단용 키트.LMTK3 (lemur tyrosine kinase 3, Gene Bank accession No. NM_001080434) gene, a sense and antisense primer pair of the gene, a protein expressed from the gene, or a kit for diagnosing colorectal cancer. 제5항에 있어서, 상기 키트는 LOC644774(similar to phosphoglycerate kinase 1, GeneBank accession No.XM_927868.1), WDR72(WD repeat domain 72, GeneBank accession No.NM_182758.2), LOC440157(hypothetical gene supported by AK096951; BC066547, GeneBank accession No.NM_001013701.1) 및 LOC643911(hypothetical protein LOC643911, GeneBank accession No.XM_931911.2)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 comprises LOC644774 (similar to phosphoglycerate kinase 1, GeneBank accession No. XM_927868.1), WDR72 (WD repeat domain 72, GeneBank accession No.NM_182758.2), LOC440157 (hypothetical gene supported by AK096951; BC066547, GeneBank accession No.NM_001013701.1) and LOC643911 (hypothetical protein LOC643911, GeneBank accession No.XM_931911.2), one or more genes selected from the group, sense and antisense primer pairs of the genes, proteins expressed from the genes, Or a kit for diagnosing colorectal cancer further comprising an antibody to the protein.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111936858A (en) * 2019-04-04 2020-11-13 清华大学 Gastric cancer very early cell marker and gastric precancerous lesion early cell marker and application thereof in diagnostic kit

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