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的异质性疾病 外周胰岛素抵抗。这是一个重大的公共卫生问题。 影响了大约5%的世界人口。而当 已经提出了大量证据表明，有一种主要的基因 成分对NIDDM易感性的鉴定 常见形式的NIDDM的易感基因尚未确定 完成了。最近发表的研究表明，有几项 易感基因座存在，并且发生和/或频率 这些基因座的易感等位基因在不同的人群中存在差异。在这 研究中，我们建议对NIDDM进行全基因组搜索 西太平洋萨摩亚人的易感基因座。这个 NIDDM在这一人群中的患病率相对较高， 发病率约为20%。因为他们的独特之处 导致遗传多样性减少的种群历史 他们最近接触到的现代化，被怀疑是 特定基因座的等位基因对NIDDM易感性的贡献是 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来实现。首先，300 sib- 将确定受NIDDM影响的对。第二，全基因组 扫描将使用一块高密度微卫星板进行 多态分布在整个基因组中，分辨率为 大约10厘米。第三，NIDDM易感基因的定位 将通过使用受影响的兄弟姐妹对按血统标识来确定 方法：研究方法。全基因组搜索将克服过去的缺点 尚未发现阳性结果的候选基因方法 在人群中复制。受影响最大的是同胞配对方法 寻找NIDDM易感基因座的合适方法， 因为它不做任何假设，也不需要假设 疾病的遗传性。这个项目的最终目标是 确定导致个体易感性的特定基因 NIDDM。由10厘米扫描确定的显著连锁区将 接受高密度测绘(约1.0厘米)以确认 有关联的证据。紧随其后的是一位职位候选人 基因分析以确定导致基因增加的特定基因 对NIDDM的易感性。

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.