Efficient mapping of mendelian traits in dogs through genome-wide association - PubMed (original) (raw)

. 2007 Nov;39(11):1321-8.

doi: 10.1038/ng.2007.10. Epub 2007 Sep 30.

Izabella Baranowska, Claire M Wade, Nicolette H C Salmon Hillbertz, Michael C Zody, Nathan Anderson, Tara M Biagi, Nick Patterson, Gerli Rosengren Pielberg, Edward J Kulbokas 3rd, Kenine E Comstock, Evan T Keller, Jill P Mesirov, Henrik von Euler, Olle Kämpe, Ake Hedhammar, Eric S Lander, Göran Andersson, Leif Andersson, Kerstin Lindblad-Toh

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Efficient mapping of mendelian traits in dogs through genome-wide association

Elinor K Karlsson et al. Nat Genet. 2007 Nov.

Abstract

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 approximately 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only approximately 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 approximately 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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