Npgrj_ng_2007-10 1..8

نویسندگان

  • Elinor K Karlsson
  • 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
  • Kenine E Comstock
  • Evan T Keller
  • Jill P Mesirov
  • Henrik von Euler
  • Olle Kämpe
  • Åke Hedhammar
  • Eric S Lander
  • Göran Andersson
  • Leif Andersson
  • Kerstin Lindblad-Toh
چکیده

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 B27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only B20 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 o1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of B100 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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تاریخ انتشار 2007