GENOME SCAN FOR NIDDM SUSCEPTIBILITY GENES AMONG SAMOANS

非胰岛素依赖型糖尿病（NIDDM）是一种复杂的， 以高血糖、高胰岛素血症为特征异质性疾病 和外周胰岛素抵抗。 这是一个重大的公共卫生问题 影响了世界上大约5%的人口。 而 有大量证据表明，有一个主要的遗传 成分对NIDDM易感性的影响， 普通型NIDDM的易感基因尚待研究。 完成了最近发表的研究表明， 存在易感基因座，并且 这些基因座上的易感等位基因在种群中各不相同。 在这 研究，我们建议进行全基因组搜索NIDDM 西太平洋萨摩亚人的易感基因位点。的 NIDDM在这一人群中的患病率相对较高， 发病率约为20%。 由于其独特的 导致遗传多样性减少的种群历史， 他们最近接触到现代化，有人怀疑， 特定基因座的等位基因对NIDDM易感性的贡献是 可能与其他人群不同。 这 将通过三个具体目标实现这一目标。 首先，300个同胞- 将确定受NIDDM影响的对。 第二，全基因组 将使用高密度微卫星面板进行扫描 多态性分布在整个基因组中，分辨率为 约10厘米。三、NIDDM易感基因位点的定位 将通过使用受影响的同胞对血统鉴定来确定 方法. 全基因组搜索将克服过去的缺点 候选基因的方法，其中积极的发现还没有 在人群中复制。 受影响最大的是同胞配对法 寻找NIDDM易感基因座的合适方法， 因为它不需要假设 疾病的遗传。 该项目的最终目标是 确定有助于个体易感性的特定基因 NIDDM。 通过10 cM扫描确定的重要联系区域将 进行高密度标测（约1.0 cM），以确认 联系的证据。这将是随后的立场候选人 基因分析，以确定负责增加的特定基因 易患NIDDM。

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.