Poster 20
Presenter: Brittany Baur
Thursday, 4:00 – 6:00pm
Brittany Baur1, Katie Holl1, William Valdar2 and Leah Solberg Woods1 1Medical College of Wisconsin and 2University of North Carolina - Chapel Hill
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. We collected multiple diabetic phenotypes in 1,038 HS male rats and genotyped these animals using the Affymetrix 10K SNP array. Following ancestral haplotype reconstruction, a mixed modeling approach with sibship as a random effect was used to identify genetic loci. We report results for glucose area under the curve after a glucose tolerance test, the first of several diabetic traits that will be analyzed. Genome-wide significant marker intervals were detected on rat chromosomes 1, 3, 10 and 13, with the average 95% confidence interval for these loci being only 3.15 Mb. Most of these loci fall within regions previously identified for glucose tolerance using traditional mapping methods (e.g., F2 intercross studies) . A multilocus modeling technique involving resample model averaging is currently underway and will be used to determine how frequently each locus is detected when resampling a portion of the original data-set, thus reducing potential false positives. Follow-up studies using gene expression and sequence variation will be used to narrow candidate genes within these loci. These data demonstrate the utility of HS rats for detecting genetic loci for diabetic traits genome-wide.