title: Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs.
abstract: Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.
authors: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Building 50, Room 5351, Bethesda, MD 20892, USA.
authors: Heather J
authors: HJ
authors: Huson
authors: Bridgett M
authors: BM
authors: vonHoldt
authors: Maud
authors: M
authors: Rimbault
authors: Alexandra M
authors: AM
authors: Byers
authors: Jonathan A
authors: JA
authors: Runstadler
authors: Heidi G
authors: HG
authors: Parker
authors: Elaine A
authors: EA
authors: Ostrander
mesh_terms: D000413:Alaska; D000818:Animals; D001833:Body Temperature Regulation; D001947:Breeding; D002874:Chromosome Mapping; D004285:Dogs / Q000235:genetics* / Q000502:physiology*; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006358:Hot Temperature; D015810:Linkage Disequilibrium; D018995:Myosin Heavy Chains / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010805:Physical Conditioning, Animal; D010807:Physical Endurance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic; D012641:Selection, Genetic
chemical_list: D009419:Nerve Tissue Proteins; D018995:Myosin Heavy Chains