GENOME-WIDE FINE-MAPPNG OF DIABETIC TRAITS

2 diabetes results from both genes and the environment. Mapping genetic loci in animal models can help identify genes that are involved in type 2 diabetes to better understand the disease. Heterogeneous stock (HS) rats are derived from eight inbred founder strains and maintained in a breeding strategy that minimizes inbreeding. HS rats have a highly recombinant genome, which allows for rapid fine-mapping of complex traits genome-wide. However, this results in a complicated set of relationships between animals that is non-existent in traditional genetic mapping methods. To fine-map traits involved in type 2 diabetes, multiple diabetic phenotypes were collected in 1,038 HS male rats and these animals were genotyped using the Affymetrix 10K SNP array. Following ancestral haplotype reconstruction, a mixed modeling approach was used to identify genetic loci involved in two phenotypes suggestive of diabetes: fasting glucose and glucose area under the curve after a glucose tolerance test. Sibship was used as a random effect in the model to account for the complex family relationships. A genome-wide significant marker interval was detected on chromosome 11 for fasting glucose with a 95% confidence interval of 5.75 Mb. Genome-wide significant marker intervals were also detected on chromosomes 1,3, 10, and 13 for glucose area under the curve, with the average 95 % confidenc