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Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis

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  • 1 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 2 College of Veterinary Medicine, and Biometrics Unit, College of Agricultural and Life Sciences, Cornell University, Ithaca NY 14853.
  • | 3 Present address is Department of Statistics, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611.
  • | 4 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 5 James A. Baker Institute for Animal Health, Cornell University, Ithaca NY 14853.
  • | 6 James A. Baker Institute for Animal Health, Cornell University, Ithaca NY 14853.
  • | 7 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 8 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 9 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 10 Department of Clinical Sciences, Cornell University, Ithaca NY 14853.
  • | 11 James A. Baker Institute for Animal Health, Cornell University, Ithaca NY 14853.
  • | 12 Genetics Section, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.
  • | 13 James A. Baker Institute for Animal Health, Cornell University, Ithaca NY 14853.

Abstract

Objective—To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree.

Animals—147 Labrador Retrievers, Greyhounds, and their crossbreed offspring.

Procedure—Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined.

Results—For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7.

Conclusions and Clinical Significance—Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs. (Am J Vet Res 2003;222:418–424)

Abstract

Objective—To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree.

Animals—147 Labrador Retrievers, Greyhounds, and their crossbreed offspring.

Procedure—Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined.

Results—For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7.

Conclusions and Clinical Significance—Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs. (Am J Vet Res 2003;222:418–424)