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.

TitleBreed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs.
Publication TypeJournal Article
Year of Publication2012
AuthorsHuson HJ, vonHoldt BM, Rimbault M, Byers AM, Runstadler JA, Parker HG, Ostrander EA
JournalMamm Genome
Volume23
Issue1-2
Pagination178-94
Date Published2012 Feb
ISSN1432-1777
KeywordsAlaska, Animals, Body Temperature Regulation, Breeding, Chromosome Mapping, Dogs, Genome, Genome-Wide Association Study, Genotype, Hot Temperature, Linkage Disequilibrium, Myosin Heavy Chains, Nerve Tissue Proteins, Physical Conditioning, Animal, Physical Endurance, Polymorphism, Single Nucleotide, Principal Component Analysis, Promoter Regions, Genetic, Selection, Genetic
Abstract

<p>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.</p>

DOI10.1007/s00335-011-9374-y
Alternate JournalMamm. Genome
PubMed ID22105876
PubMed Central IDPMC3320045
Grant ListZ99 HG999999 / / Intramural NIH HHS / United States
ZIA HG200325-07 / / Intramural NIH HHS / United States