POSITIONAL CLONING OF GENES FOR NIDDM

1994年，据估计，超过1300万美国人 患有糖尿病，其中约95%患有非糖尿病。 胰岛素依赖型糖尿病（NIDDM）。糖尿病是 失明和非创伤性截肢的主要原因， 是其他疾病的危险因素， 高血压和心血管疾病，导致严重的 发病率和死亡率。 这一建议的具体假设是，存在一套 易患NIDDM的可定位基因， 疾病基因的鉴定应该是可能的， 使用受影响的同胞对策略进行定位克隆。测试 根据这一假设，提出统计遗传分析 表型和基因型数据收集自 芬兰-美国调查的500个同胞对家庭 NIDDM遗传学（FUSION），一项旨在确定 NIDDM的基因这项建议的具体目标是： 1.进行NIDDM相关定量的分离分析 性状传统的NIDDM相关的数量性状将是 测试沿着与替代性状，可能有更大的 歧视的力量。 2.执行链接分析。这些分析将包括风险- 基于比率的连锁分析，基于遗传模式的连锁 分析，以及。NIDDM相关定量连锁分析 性状

In 1994, it was estimated that more than 13 million Americans suffered from diabetes mellitus, with approximately 95% having non- insulin-dependent diabetes mellitus (NIDDM). Diabetes is the leading cause of blindness and non-trauma related amputations in the United States and is a risk factor for other disorders such as hypertension and cardiovascular disease, resulting in significant morbidity and mortality. The specific hypothesis of this proposal is that there exists a set of mappable genes that predispose to the development of NIDDM and identification of the disease genes should be possible through positional cloning using an affected sib-pair strategy. To test this hypothesis, it is proposed that statistical genetic analysis be performed on phenotypic and genotypic data collected from the 500 sib-pair families of the Finland-United States Investigation of NIDDM Genetics (FUSION), a multicenter study aimed at identifying genes for NIDDM. The specific aims of this proposal are: 1. Perform segregation analysis of NIDDM-related quantitative traits. Traditional NIDDM-related quantitative traits will be tested along with alternative traits which may have greater discriminatory power. 2. Perform linkage analysis. These analyses will include risk- ratio-based linkage analysis, mode-of-inheritance-based linkage analysis, and. linkage analysis of NIDDM-related quantitative traits.