POSITIONAL CLONING OF GENES FOR NIDDM

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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.