title: Efficient mapping of mendelian traits in dogs through genome-wide association.
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.
authors: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. elinor@broad.mit.edu
authors: Elinor K
authors: EK
authors: Karlsson
authors: Izabella
authors: I
authors: Baranowska
authors: Claire M
authors: CM
authors: Wade
authors: Nicolette H C
authors: NH
authors: Salmon Hillbertz
authors: Michael C
authors: MC
authors: Zody
authors: Nathan
authors: N
authors: Anderson
authors: Tara M
authors: TM
authors: Biagi
authors: Nick
authors: N
authors: Patterson
authors: Gerli Rosengren
authors: GR
authors: Pielberg
authors: Edward J
authors: EJ
authors: Kulbokas
authors: Kenine E
authors: KE
authors: Comstock
authors: Evan T
authors: ET
authors: Keller
authors: Jill P
authors: JP
authors: Mesirov
authors: Henrik
authors: H
authors: von Euler
authors: Olle
authors: O
authors: Kämpe
authors: Ake
authors: A
authors: Hedhammar
authors: Eric S
authors: ES
authors: Lander
authors: Göran
authors: G
authors: Andersson
authors: Leif
authors: L
authors: Andersson
authors: Kerstin
authors: K
authors: Lindblad-Toh
mesh_terms: D000818:Animals; D001947:Breeding; D002874:Chromosome Mapping; D004285:Dogs / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D006200:Hair Color / Q000235:genetics*; D006239:Haplotypes; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D051739:Microphthalmia-Associated Transcription Factor