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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)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the radiographic methods that best predict the development of osteoarthritis in the hip joints of a cohort of dogs with hip dysplasia and unaffected dogs.

Animals—205 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbred dogs.

Procedure—Pelvic radiography was performed when the dogs were 8 months old. Ventrodorsal extendedhip, distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral subluxation score, and Norberg angle were derived from examination of radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs ≥ 8 months of age on the basis of detection of articular cartilage lesions. Multiple logistic regression was used to determine the radiographic technique or techniques that best predicted development of osteoarthritis.

Results—A combination of 2 radiographic methods was better than any single method in predicting a cartilage lesion or a normal joint, but adding a third radiographic method did not improve that prediction. A combination of the DLS score and Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip joint. All models that excluded the DLS score were inferior to those that included it.

Conclusions and Clinical Relevance—A combination of the DLS score and Norberg angle was the best predictor of radiographic measures in 8-month-old dogs to determine whether a dog would have normal or osteoarthritic hip joints. (Am J Vet Res 2003;64:1472–1478)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the genetic influence on expression of traits associated with canine hip dysplasia.

Animals—193 dogs from an experimental canine pedigree.

Procedure—An experimental canine pedigree was developed for linkage analysis of hip dysplasia by mating dysplastic Labrador Retrievers with nondysplastic Greyhounds. A statistical model was designed to test the effects of Labrador Retriever and Greyhound alleles on age at detection of femoral capital epiphyseal ossification, 8-month distraction index, and 8-month dorsolateral subluxation score.

Results—The additive effect was significant for age at detection of femoral capital epiphyseal ossification. Restricted maximum likelihood estimates (± SD) for this trait were 6.4 ± 1.95, 10.2 ± 2.0, 10.8 ± 3.1, 11.4 ± 2.1, and 13.6 ± 4.6 days of age for Greyhounds, Greyhound backcross dogs, F1 dogs, Labrador Retriever backcross dogs, and Labrador Retrievers, respectively. The additive effect was also significant for the distraction index. Estimates for this trait were 0.21 ± 0.07, 0.29 ± 0.15, 0.44 ± 0.12, 0.52 ± 0.18, and 0.6 ± 0.17 for the same groups, respectively. For the dorsolateral subluxation score, additive and dominance effects were significant. Estimates for this trait were 73.5 ± 4.1, 71.3 ± 6.5, 69.1 ± 6.0, 50.6 ± 12.9, and 48.4 ± 7.7%, respectively, for the same groups.

Conclusions—In this canine pedigree, traits associated with canine hip dysplasia are heritable. Phenotypic differences exist among founder dogs of each breed and their crosses. This pedigree should be useful for identification of quantitative trait loci underlying the dysplastic phenotype. (Am J Vet Res 2002;63: 1029–1035)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs.

Animals—-1,551 dogs.

Procedures—Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever–Greyhound crossbreeds.

Results—The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage.

Conclusions and Clinical Relevance—The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

Full access
in American Journal of Veterinary Research