Efficient mapping of mendelian traits in dogs through genome-wide association |
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Authors: | Karlsson Elinor K Baranowska Izabella Wade Claire M Salmon Hillbertz Nicolette H C Zody Michael C Anderson Nathan Biagi Tara M Patterson Nick Pielberg Gerli Rosengren Kulbokas Edward J Comstock Kenine E Keller Evan T Mesirov Jill P von Euler Henrik Kämpe Olle Hedhammar Ake Lander Eric S Andersson Göran Andersson Leif Lindblad-Toh Kerstin |
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Institution: | Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. elinor@broad.mit.edu |
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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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