The inheritance of type 2 diabetes and obesity is likely determined by multiple genes. Consequently, a single susceptibility gene with a small effect may remain obscured in family-based linkage studies, but could be detected in a genome-wide association scan. We have previously reported the application of the amplified fragment length polymorphism (AFLP) technique to search for markers that may be associated with diabetes or obesity in the Pima Indians. Furthermore, we also explored a modification of the AFLP procedure to isolate new markers from the 1q21-q23 genomic region linked with type 2 diabetes in Pimas (see project ZO1-DK69073). This approach is based on capture of AFLPs using large genomic clones spanning 1q21-q23, and analyzing such markers for differences between diabetic and non-diabetic Pimas. We performed a small-scale study using yeast artificial chromosome (YAC) clones for the capture that yielded three informative markers, thus indicating the feasibility of this strategy. Because a detailed bacterial artificial chromosome (BAC) clone coverage of 1q21-q23 is now available (see project ZO1-DK69073), we are exploring this resource to detect additional markers in the region of interest. This project is intended as a complementation of Z01-DK69073 to facilitate the identification of a diabetes susceptibility gene on Chromosome 1q.
