With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with ∼27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only ∼20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of ∼100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health.
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We thank the Genetic Analysis Platform at the Broad Institute of MIT and Harvard for performing the SNP array genotyping, and L. Gaffney for assistance with figures. The work was supported by the AKC/Canine Health Foundation (grant 373), the Foundation for Strategic Research, and the Donald and Jo Ann Petersen Endowed Research Fund of the University of Michigan Comprehensive Cancer Center.
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Karlsson, E., Baranowska, I., Wade, C. et al. Efficient mapping of mendelian traits in dogs through genome-wide association. Nat Genet 39, 1321–1328 (2007). https://doi.org/10.1038/ng.2007.10
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