LARGE-SCALE COLLECTION OF PANCREATIC ISLET ESTS AND CHROMOSOMAL MAPPING

大规模采集胰岛 ESTS 和染色体作图

• 批准号: 09044257
• 负责人: TAKEDA Jun
• 金额: $ 1.6万
• 依托单位: GUNMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044257/
• 关键词: GENOME; DATABASE; POSITIONAL CLONING; GENE EXPRESSION; CHROMOSOMAL MAPPING

Diabetes mellitus is characterized by elevated plasma glucose levels due to an absolute or relative deficiency of insulin. The genetic linkage studies looking for diabetes susceptibility genes are well underway in many labs, but this "positional cloning" is still a laborious work. Because of the central role of the pancreatic islets in the regulation of glucose homeostasis, we focused on this tissue as a primary site of expression of the major diabetogenic genes and created a database of genes expressed in this tissue as expressed sequence tags (ESTs). The analysis of 6,055 ESTs by database searches idicated that approximately 50% of the cDNAs so far isolated represented unknown human genes. Of these, 2,731 and 402 ESTs shoewed exact match with and significant similarty to known genes, respectively. 2,390 ESTs showed homology with other ESTs. 408 ESTs had no database match. Approximately half of these genes have been assigned to the chromosome by dbSTS search, RH mapping and/or FISH.The characterization of the tissue distribution and chromosomal localization of novel ESTs will facilitate the "positional candidate" approach. The pancreatic islet ESTs obtained in this project will provide a unique key source of new candidate genes for genetic studies of diabetes.

糖尿病的特征是由于绝对或相对缺乏胰岛素而导致血糖水平升高。寻找糖尿病易感基因的遗传连锁研究在许多实验室进行得很好，但这种“定位克隆”仍然是一项繁重的工作。由于胰岛在调节葡萄糖动态平衡中的中心作用，我们将该组织作为主要促糖尿病基因的主要表达部位，并建立了在该组织中表达的基因数据库，作为表达序列标签(EST)。通过数据库搜索对6,055个EST进行的分析表明，到目前为止分离的大约50%的cDNA代表未知的人类基因。在这些EST中，分别有2731个和402个EST与已知基因完全匹配和显著相似。2390个EST与其他EST同源。408个EST没有数据库匹配。通过数据库STS搜索、RH作图和/或FISH，这些基因中大约有一半被分配到染色体上。新EST的组织分布和染色体定位的特征将为“位置候选”方法提供便利。在该项目中获得的胰岛EST将为糖尿病遗传学研究提供一个独特的关键新候选基因来源。

项目成果

S. Yamada et al.: "Mutations in the hepatocyte nuclear factor-1α gene (MODY3) are not a major cause of late-onset NIDDM in Japanese." Diabetes. 46. 1512-1513 (1997)

S. Yamada 等人：“肝细胞核因子 1α 基因 (MODY3) 突变不是日本迟发性 NIDDM 的主要原因。”46. 1512-1513 (1997)。

S.Yamada et al.: "Mutations in the hepatocyte nuclear factor-lalpha gene (MODY3) are not a major cause of late-onset NIDDM in Japanese." Diabetes. 46. 1512-1513 (1997)

S.Yamada 等人：“肝细胞核因子-lalpha 基因 (MODY3) 突变并不是日本人迟发性 NIDDM 的主要原因。”

D. Wasserman et al.: "Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption." J. Clin. Invest.98. 2398-2402 (1996)

D. Wasserman 等人：“分离果糖吸收不良中果糖转运蛋白基因 (GLUT5) 的分子分析。”

K.Yamagata et al.: "Mutaions in the hepatocycte nuclear factor 1 alpha gene in maturity-onset diabetes of the young(MODY3)" Nature. 384. 455-458 (1996)

K.Yamagata 等人：“青少年发病型糖尿病中肝细胞核因子 1 α 基因的突变 (MODY3)”Nature。

D.Wasserman et al.: "Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption." J.Clin.Invest.98. 2398-2402 (1996)

D.Wasserman 等人：“分离果糖吸收不良中果糖转运蛋白基因 (GLUT5) 的分子分析。”