Dataset Information

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.

SUBMITTER: Huson HJ

PROVIDER: S-EPMC3320045 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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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.

Huson Heather J HJ vonHoldt Bridgett M BM Rimbault Maud M Byers Alexandra M AM Runstadler Jonathan A JA Parker Heidi G HG Ostrander Elaine A EA

Mammalian genome : official journal of the International Mammalian Genome Society 20111122 1-2

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 ...[more]

PMID: 22105876

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Project description:BackgroundThis study describes the presence and frequency of health traits among three populations of dogs traditionally used for sledding and explores their ancestry and breed composition as provided by the commercially available Embark dog DNA test. The three populations include the purebred Siberian Husky and the admixed populations of Alaskan sled dogs and Polar Huskies. While the Siberian Husky represents a well-established breed with extensive historical and health data, the Alaskan sled dog is less studied but has been the subject of nutritional, physiological, and genetic studies related to ancestry and performance. In contrast, the Polar Husky is a relatively obscure and rare group of dogs used for arctic exploration with very little-known information. The three populations were compared using Embark results, providing new insight into the health traits circulating within the populations and the potential ancestral linkage of the health traits between the sledding populations. Embark results are based upon 228,588 single-nucleotide polymorphisms (SNPs) spanning the canine genome, characterized using a custom-designed Illumina beadchip array.ResultsSpecifically, breed composition was summarized for the two admixed populations with most of the dogs being predominantly categorized as Alaskan husky- type dog or "Supermutt". Mitochondrial and Y chromosome haplogroups and haplotypes were found with Alaskan sled dogs carrying most of the haplogroups and types found in Siberian and Polar Huskies. Genomic principal component analysis reflected population structure corresponding to breed and substructure within the Alaskan sled dogs related to sprint or distance competition. Genetic markers associated with Alanine Aminotransferase activity, Alaskan Husky Encephalopathy, dilated cardiomyopathy, Collie eye anomaly, degenerative myelopathy, ichthyosis, and factor VII deficiency were identified in the populations of sledding breeds.ConclusionThese results provide a preliminary description of genetic characteristics found in sledding breeds, improving the understanding and care of working sled dogs.

Project description:Background: Muscle responses to exercise are complex, and potentially include acute responses to exercise-induced injury as well as longer-term adaptive training responses. Using Alaskan sled dogs as an experimental model, changes in muscle gene expression were analyzed to better understand the temporal changes that occur after severe exercise. Methods: Dogs were randomly assigned to undertake in a 160 km run (n=9), or to remain at rest (n=4). Biceps femoris muscle was obtained by needle biopsy from the unexercised dogs and two dogs at each of 2, 6 and 12 hours after the exercise and from 3 dogs 24 hours after exercise. RNA was extracted and microarray analysis used to define gene transcriptional changes. Results: Nine hundred sixty three transcripts exhibited statistically significant change over time after exercise as compared to the unexercised dogs. The changes in gene expression after exercise occurred in a clear temporal pattern and included transcripts with increased expression 2 hours after exercise with a return towards resting levels by 6 hours after exercise. Other transcripts demonstrated increased expression which peaked at six hours after exercise, while other transcripts showed sustained induction or repression over the 24 hours after exercise. Increases in a number of known transcriptional regulators, including PPAR-Î±, CERM and CEBPD, were observed 2-hours after exercise. Pathway analysis demonstrated coordinated changes in expression of genes with known functional relationships, including genes involved in muscle remodeling and growth, intermediary metabolism and immune regulation. Conclusion: Sustained endurance exercise by Alaskan sled dogs induces coordinated changes in gene expression with a clear temporal pattern. RNA expression profiling has the potential to identify novel regulatory mechanisms and responses to exercise stimuli. Subjects were 13 Alaskan sled dogs aged 4.5 + 2.5 years (mean + SD) and weighing 23.3 + 2.5 kg. Dogs were randomly assigned to two groups â one group of 9 dogs subsequently ran 160 km in 24 hours as 2 sessions of 80 km, separated by a 6 hour rest period. The second group consisted of four dogs housed in unheated kennels, their usual housing, for the duration of the experiment. All dogs were from the same kennel. Dogs were fed a commercial kibble (Eukanuba, Iams Company, Dayton, OH) supplemented with frozen meat during the 8 weeks preceding the study and throughout the study period. The dogâs diet was consistent before, during and after the exercise bout. All dogs had completed 1590 + 100 km of training runs in the 3 months before the study. The dogs had not exercised for 72 hors before the start of this study. Dogs in the exercise group ran as a team pulling a lightly laden sled and driver over packed snow. Ambient temperatures were -20o to -10o C with no wind. Dogs completed the two 80 km runs in 23 hours, including the 6 hour rest period. Blood samples were collected by jugular venepuncture from all dogs the day before exercise, and within a 10 minute window at 2, 6, 12, and 24 hours after completing the second run. Samples were collected into evacuated glass tubes containing a clot enhancer. Muscle samples were collected from each of two dogs within a 10 minute window at 2, 6 and 12 hours after completing exercise and from three dogs 24 hours after completing exercise. Muscle samples were collected from each of the four unexercised dogs within two hours of the other dogs initiating their exercise bout. Each dog had only one biopsy procedure performed. Muscle samples were collected from the biceps femoris muscle using a needle biopsy that yielded approximately 40-60 mg of muscle. The biopsy was performed after clipping and aseptic preparation of the skin overlying the biopsy site. The dog was anesthetized with propofol (6 mg/kg, IV, maintained as necessary with 2 mg/kg additional boluses), a cuffed orotracheal tube placed and the dog ventilated with a hand-held ventilation bag. When adequate anesthesia had been obtained a 5 mm incision was made in the skin. A sterile biopsy needle (12 g PGI EZ Core, Products group International, Inc. Lyons, CO) was then inserted through the incision and a sample of muscle collected. If necessary, repeated collections of muscle were made until a minimum of 40 mg of muscle has been collected from an individual dog. The skin incision was closed with tissue glue and an antibiotic ointment applied. The dog was monitored closely until recovery from anesthesia was complete. Carprofen (4.4 mg/kg, orally) was administered when the dog had recovered sufficiently from anesthesia to have a gag reflex.

Dataset Information

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.

Publications

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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