This application for International Research Scientist Development Award is aimed to study the genetic susceptibility associated with Type 2 Diabetes (Type 2D) in an endogamous community from North India utilizing the opportunity to gain access to a unique population. Applicant's ultimate goal is to perform genome-wide scan on extended family pedigrees of diabetic sib-pairs to detect linkage of diabetes to putative genomic regions not previously identified. Once the linkage is found, to perform direct search for molecular variation in positional candidate genes, and to test for linkage and association using family-based methods. However due to the budgetary limitation of the present award, proposing a genome-wide scan is beyond the scope of this award. Therefore, the applicant is proposing pilot study to collect family material of 500 sib-pairs with following aims: 1) recruitment of 500 extended families with affected sib-pairs; 2) to perform dense mapping around some selected chromosomal regions, and 3) statistical analysis. With the help of this award, candidate will be able to build up resources and to initiate a large budgetary program to achieve the ultimate goal. The strategies used in US population studies suffer from the basic flaw of presence of heterogeneity in sample and require replication in genetically homogenous populations and India offers unique advantage due to the presence of small endogamous caste groups with intact families. It is an exciting and rare opportunity to study this population where diabetes have reached to epidemic scale and information on genetic epidemiological aspects hardly exists. Feasibility of conducting genetic research in India at the proposed site has already been established by the successful completion of previous Fogarty award and presently on-going Indo-US studies and testifies the adequacy and the environment to support this project. This training award will substantially contribute to the scientific development of the candidate to ultimately achieve an independent and productive international research career. It also fulfills Fogarty's mission to reduce health disparities between developed and developing countries. Identifying the susceptibility loci in a population with high diabetic/CHD risk may be important beyond Indians and will increase our understanding of the disease in other groups.
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