GENOME SCAN FOR NIDDM SUSCEPTIBILITY GENES AMONG SAMOANS

萨摩亚人 NIDDM 易感性基因的基因组扫描

• 批准号: 6177420
• 负责人: Ranjan Deka
• 金额: $ 29.81万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-15 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177420
• 关键词: Asians; alleles; clinical research; computer assisted sequence analysis; family genetics; gene expression; gene frequency; genetic mapping; genetic markers; genetic polymorphism; genetic susceptibility; genome; genotype; glucose tolerance test; human genetic material tag; human population genetics; human subject; linkage mapping; metabolism disorder diagnosis; noninsulin dependent diabetes mellitus; polymerase chain reaction; radioimmunoassay; statistics /biometry

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex and heterogeneous disease characterized by hyperglycemia, hyperinsulinemia and peripheral insulin resistance. It is a major public health problem affecting approximately 5 percent of the world population. While substantial evidence has been presented that there is a major genetic component to NIDDM susceptibility, the identification of the major susceptibility genes for the common form of NIDDM is yet to be accomplished. Recently published studies suggest that several susceptibility loci exist, and that the occurrence and/or frequency of predisposing alleles at these loci varies among populations. In this study, we propose to conduct a genome-wide search for NIDDM susceptibility loci among the Samoans of the Western Pacific. The prevalence of NIDDM in this population is comparatively high with an incidence of approximately 20 percent. Because of their unique population history that has led to a reduction in genetic diversity and their recent exposure to modernization, it is suspected that the contribution of alleles at specific loci to NIDDM susceptibility is likely to be different in Samoans than in other populations. This objective will be achieved through three specific aims. First, 300 sib- pairs affected with NIDDM will be ascertained. Second, a genome-wide scan will be conducted using a panel of high density microsattelite polymorphisms spaced throughout the genome at a resolution of approximately 10 cM. Third, the location of NIDDM susceptibility loci will be determined by using affected-sib-pair identify-by-descent methods. The genome-wide search will overcome the shortcomings of past candidate gene approaches where positive findings have not been replicated across populations. The affected sib-pair method is the most appropriate approach for searching for NIDDM susceptibility loci, because it makes and requires no assumption about the mode of inheritance of the disease. The ultimate goal of this project is to identify specific genes that contribute to individual susceptibility to NIDDM. Areas of significant linkage identified by the 10 cM scan will be subjected to high density mapping (approximately 1.0 cM) to confirm evidence of linkage. This will be followed by a positional candidate gene analysis to identify the specific genes responsible for increased susceptibility to NIDDM.

非胰岛素依赖性糖尿病（NIDDM）是复杂的， 以高血糖，高胰岛素血症为特征的异质疾病 和周围胰岛素抵抗。 这是一个主要的公共卫生问题 影响大约5％的世界人口。 尽管 已经有大量证据表明有一个主要的遗传 NIDDM敏感性的组成部分，识别主要 NIDDM共同形式的敏感基因尚未 成就。最近发表的研究表明了一些 存在敏感性基因座，并且发生的发生和/或频率 这些基因座的易感等位基因在人群之间有所不同。 在这个 研究，我们建议对NIDDM进行全基因组搜索 西太平洋萨摩亚人的敏感性基因座。这 该人群中NIDDM的患病率相对较高， 大约20％的发病率。 因为他们的独特 人口历史导致遗传多样性降低和 他们最近接触现代化，怀疑 特定基因座对NIDDM易感性的等位基因的贡献为 萨摩亚人可能与其他人群不同。 这 目标将通过三个具体目标实现。 首先，300个sib- 将确定受NIDDM影响的对。 第二，全基因组 扫描将使用一组高密度微颗粒的面板进行 整个基因组间隔的多态性以分辨率 约10厘米。第三，NIDDM易感基因座的位置 将通过使用受影响的SIB-PAIR逐个识别来确定 方法。 全基因组搜索将克服过去的缺点 尚未有积极发现的候选基因方法 在人群中复制。 受影响的SIB-PAIR方法最多 搜索NIDDM易感位点的适当方法， 因为它使得它不需要假设 疾病的继承。 该项目的最终目标是 确定有助于个人敏感性的特定基因 NIDDM。 10厘米扫描确定的重大连锁区域将 进行高密度映射（约1.0厘米）以确认 联系的证据。接下来是职位候选人 基因分析以识别负责增加的特定基因 对NIDDM的敏感性。