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

Nat Genet. 2007 Nov;39(11):1321-8. doi: 10.1038/ng.2007.10. Epub 2007 Sep 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Chromosome Mapping*
  • Dogs / genetics*
  • Female
  • Genetic Linkage*
  • Genome
  • Hair Color / genetics*
  • Haplotypes
  • Male
  • Melanocytes / cytology
  • Melanocytes / metabolism
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Mutation / genetics
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic

Substances

  • Microphthalmia-Associated Transcription Factor