Efficient mapping of mendelian traits in dogs through genome-wide association.
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.
Karlsson
Elinor K
EK
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. elinor@broad.mit.edu
Baranowska
Izabella
I
Wade
Claire M
CM
Salmon Hillbertz
Nicolette H C
NH
Zody
Michael C
MC
Anderson
Nathan
N
Biagi
Tara M
TM
Patterson
Nick
N
Pielberg
Gerli Rosengren
GR
Kulbokas
Edward J
EJ
Comstock
Kenine E
KE
Keller
Evan T
ET
Mesirov
Jill P
JP
von Euler
Henrik
H
Kämpe
Olle
O
Hedhammar
Ake
A
Lander
Eric S
ES
Andersson
Göran
G
Andersson
Leif
L
Lindblad-Toh
Kerstin
K
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
D051739:Microphthalmia-Associated Transcription Factor