Genome-wide Association Mapping in Dogs--A Powerful Approach to Gene Discovery
The domesticated dog encompasses hundreds of genetically isolated breeds and offers exceptional power for mapping genes. Due to small founder populations, specific breeds suffer increased rates of diseases including cancer, epilepsy and diabetes. This population history created long linkage disequilibrium within breeds, but across breeds LD is short, suggesting a two-stage mapping strategy. An associated region is first identified by genome-wide mapping within a breed, and subsequently refined by fine-mapping across multiple breeds.
We have mapped two traits with Mendelian inheritance, white coat color (Boxers) and dermoid sinus (Rhodesian Ridgebacks), using an ~27,000 SNP array designed in collaboration with Affymetrix. For each trait, with ~10 cases and ~10 controls we identified a single associated haplotype of <1Mb containing strong candidate gene(s). For coat color, subsequent fine-mapping in two breeds narrowed the association to just 100kb containing the melanocyte-specific promoter of the gene MITF.
The real challenge lies in mapping complex traits. Promising preliminary data for osteosarcoma and hemangiosarcoma identify several loci for each using only several hundred samples. The relatively easy identification of common canine disease genes should provide insights into human health.