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Identification of quantitative trait loci for osteoarthritis of hip joints in dogs

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  • 1 Department of Animal Science, College of Agricultural Sciences and Natural Resources, Oklahoma State University, Stillwater, OK 74078.
  • | 2 Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
  • | 4 Faculty of Veterinary Medicine, Kasetsart University, Nakhon-Pathom, 73140, Thailand.
  • | 5 Institute for Genomic Diversity, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853.
  • | 6 Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
  • | 7 Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 8 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Abstract

Objective—To identify quantitative trait loci (QTL) associated with osteoarthritis (OA) of hip joints of dogs by use of a whole-genome microsatellite scan.

Animals—116 founder, backcross, F1, and F2 dogs from a crossbred pedigree.

Procedures—Necropsy scores and an optimized set of 342 microsatellite markers were used for interval mapping by means of a combined backcross and F2 design module from an online statistical program. Breed and sex were included in the model as fixed effects. Age of dog at necropsy and body weight at 8 months of age were also included in the model as covariates. The chromosomal location at which the highest F score was obtained was considered the best estimate of a QTL position. Chromosome-wide significance thresholds were determined empirically from 10,000 permutations of marker genotypes.

Results—4 chromosomes contained putative QTL for OA of hip joints in dogs at the 5% chromosome-wide significance threshold: chromosomes 5, 18, 23, and 31.

Conclusions and Clinical Relevance—Osteoarthritis of canine hip joints is a complex disease to which many genes and environmental factors contribute. Identification of contributing QTL is a strategy to elucidate the genetic mechanisms that underlie this disease. Refinement of the putative QTL and subsequent candidate gene studies are needed to identify the genes involved in the disease process.

Abstract

Objective—To identify quantitative trait loci (QTL) associated with osteoarthritis (OA) of hip joints of dogs by use of a whole-genome microsatellite scan.

Animals—116 founder, backcross, F1, and F2 dogs from a crossbred pedigree.

Procedures—Necropsy scores and an optimized set of 342 microsatellite markers were used for interval mapping by means of a combined backcross and F2 design module from an online statistical program. Breed and sex were included in the model as fixed effects. Age of dog at necropsy and body weight at 8 months of age were also included in the model as covariates. The chromosomal location at which the highest F score was obtained was considered the best estimate of a QTL position. Chromosome-wide significance thresholds were determined empirically from 10,000 permutations of marker genotypes.

Results—4 chromosomes contained putative QTL for OA of hip joints in dogs at the 5% chromosome-wide significance threshold: chromosomes 5, 18, 23, and 31.

Conclusions and Clinical Relevance—Osteoarthritis of canine hip joints is a complex disease to which many genes and environmental factors contribute. Identification of contributing QTL is a strategy to elucidate the genetic mechanisms that underlie this disease. Refinement of the putative QTL and subsequent candidate gene studies are needed to identify the genes involved in the disease process.

Contributor Notes

The authors thank Alma Williams, Liz Corey, and Margaret Vernier-Singer for technical assistance.

Deceased.

Address correspondence to Dr. Todhunter.