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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

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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.

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Acknowledgments

We gratefully acknowledge the Intramural Program of the National Human Genome Research Institute. We thank the many owners and participants who provided DNA samples and information regarding their dogs.

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Authors and Affiliations

  1. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Building 50, Room 5351, Bethesda, MD, 20892, USA

    Heather J. Huson, Maud Rimbault, Alexandra M. Byers, Heidi G. Parker & Elaine A. Ostrander

  2. Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, 99775, USA

    Heather J. Huson & Jonathan A. Runstadler

  3. Ecology & Evolutionary Biology, University of California Irvine, Irvine, CA, 92697, USA

    Bridgett M. vonHoldt

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  1. Heather J. Huson
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  2. Bridgett M. vonHoldt
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Correspondence to Elaine A. Ostrander.

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Huson, H.J., vonHoldt, B.M., Rimbault, M. et al. 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. Mamm Genome 23, 178–194 (2012). https://doi.org/10.1007/s00335-011-9374-y

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