Within the past year, we have obtained the genotypic results from the Affymetrix Mapping 100k SNP chip for a Genome-Wide Association study in Pima Indians. SNPs were analyzed for associations with T2DM and predictors of T2DM. My lab has validated the genotyping of this chip technology by re-genotyping several hundred samples by the method of SNPplex. We are currently following up the strongest signals from the GWA and, to date, have genotyped more than 2741 SNPs for fine-mapping in several genomic regions. We are also testing the population-level significance of the best SNPs and, to date, have genotyped more than 1004 SNPs in a population-based sample of 3500 full-heritage Pima Indians. We have identified variants in the FOXO1A gene that are associated with type 2 diabetes, insulin action and insulin secretion and have shown that a novel Asp/Asn missense variant reduces the ability of the protein to activate transcription from a reporter gene. In addition, our fine-mapping efforts to date suggest PLZF on chromosome 11, MAP3K8 on chromosome 10, Y5R on chromosome 4, SH3GL2 on chromosome 9, and a region of high LD encompassing CASP, COP1 and Iceberg on chromosome 11 will be some of the genes that will be studied much more intensely.
Muller, Yunhua L; Thearle, Marie S; Piaggi, Paolo et al. (2014) Common genetic variation in and near the melanocortin 4 receptor gene (MC4R) is associated with body mass index in American Indian adults and children. Hum Genet 133:1431-41 |
Hanson, Robert L; Bogardus, Clifton; Duggan, David et al. (2007) A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array. Diabetes 56:3045-52 |