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

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.

published proceedings

  • Nat Genet

altmetric score

  • 35.246

author list (cited authors)

  • Karlsson, E. K., Baranowska, I., Wade, C. M., Salmon Hillbertz, N., Zody, M. C., Anderson, N., ... Lindblad-Toh, K.

citation count

  • 431

complete list of authors

  • Karlsson, Elinor K||Baranowska, Izabella||Wade, Claire M||Salmon Hillbertz, Nicolette HC||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

publication date

  • November 2007