MEXICAN-AMERICAN ADMIXTURE MAPPING DEVELOPMENT AND APPLICATION TO NIDDM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Admixture mapping is a developing method for examining complex genetic diseases that complements linkage analysis and association methods. For any disease, a recently admixed population can be used to define critical chromosomal regions if there is a different distribution of susceptibility genes in parental populations contributing to the admixed population. This is predicated on the ability to define the ancestry of the chromosomal segments in the admixed population. Recent studies indicate that Ancestry Informative Markers (AIMs) can be readily identified for major ancestral groups including European, East Asian, African and Amerindian (AI). For admixture studies in African Americans, > 2000 AIMs have been identified largely based on primary screens of more than 150,000 single nucleotide polymorphisms (SNPs). For studies of Mexican American (MA) populations, currently <500 AIMs are available to enable powerful admixture mapping studies. Current power estimations suggest that 3000-4000 evenly distributed AIMs are necessary for MA admixture studies given the estimated number of generations since admixture and simulations using hidden Markov model (HMM) algorithms to define ancestry transitions along chromosomes. The current proposal is designed to remedy the availability of AIMs that distinguish European American (EA) and AI ancestry and to demonstrate the potential of admixture mapping in the context of type 2 diabetes (DM2) [also known as non-insulin dependent diabetes (NIDDM)] and diabetic nephropathy. This study will take advantage and extend the current efforts of the FIND MA Admixture Mapping project. In addition, the current study will utilize a control group of MA subjects without diabetes to provide further support for any potential DM2 loci.