Efficient mapping of mendelian traits in dogs through genome-wide association.
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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. |
Year of Publication | 2007
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Journal | Nat Genet
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Volume | 39
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Issue | 11
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Pages | 1321-8
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Date Published | 2007 Nov
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ISSN | 1546-1718
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URL | |
DOI | 10.1038/ng.2007.10
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PubMed ID | 17906626
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