Our prior genomic scan in Pima Indians indicated an obesity susceptibility locus on chromosome 11q23-24 (LOD=3.6). There was also evidence that the same genomic region contained a susceptibility locus for type 2 diabetes mellitus (T2DM)(LOD=1.7) and a bivariate linkage analysis for the combined phenotype ?diabesity? gave the strongest evidence for a susceptibility locus (LOD= 5.2). Our current goal is to positionally clone the gene(s) responsible for the linkages. Positional candidate genes across the region of linkage are being sequenced for variants, and to date, 29 genes have been analyzed. In addition, linkage disequilibrium (LD) mapping is being used to narrow the susceptibility region. For LD mapping, single nucleotide polymorphisms (SNPs) are being systematically identified and genotyped at 50 kB intervals across the region of linkage. To date, approximately 200 SNPs have been individually genotyped and tested for association with either body mass index (BMI) or T2DM in 1229 Pimas. Three distinct, narrow regions have been preliminarily identified that contain multiple SNPs significantly associated with BMI. A single region has been identified that contains a cluster of SNPs significantly associated with diabetes.
