Genome-wide Association Mapping in Dogs--A Powerful Approach to Gene Discovery
Tufts' Canine and Feline Breeding and Genetics Conference, 2007
Noriko Tonomura1,2; Elinor K. Karlsson2; Claire M. Wade2; Nicolette Salmon-Hillbertz3; Izabella Baranowska3; Evan Mauceli2; Nathan Anderson2; Tara Biagi2; Sarah Fryc2; Michael Zody2; Nick Patterson2; Jill Mesirov2; Eric S. Lander2; Göran Andersson3; Leif Andersson3,4; Kerstin Lindblad-Toh2
1Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA; 2Broad Institute of Harvard and MIT, Cambridge, MA, USA; 3Swedish University of Agricultural Sciences, Uppsala, Sweden; 4Uppsala University, Sweden

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.

Speaker Information
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Noriko Tonomura
Broad Institute of Harvard and MIT
Tufts Cummings School of Veterinary Medicine
North Grafton, MA

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