title: An outcrossed canine pedigree for linkage analysis of hip dysplasia.
abstract: Canine hip dysplasia (CHD) is a prevalent, debilitating, polygenic disease characterized by hip subluxation and laxity which results in osteoarthritis. We are developing an informative pedigree for linkage analysis of CHD. The seven greyhound founders had excellent hip conformation with high dorsolateral subluxation scores (percentage of femoral head covered by the dorsal acetabulum in a weight-bearing position) of 66 +/- 4% (mean +/- SD averaged over both hips) and low hip distraction (laxity) indices of 0.14 +/- 0.08. Nine greyhounds bred on site had radiographic evidence of ossification in the capital femoral chondroepiphysis at 7.7 +/- 0.9 days of age. At 8 months of age they had a mean distraction index of 0.24 +/- 0.08 and dorsolateral subluxation score of 76 +/- 1%. Of the four dysplastic Labrador retriever founders, three had mean age at onset of capital femoral chondroeplphyseal ossification of 20 +/- 7 days of age n = 3) and a mean distraction index of 0.46 +/- 0.1 accompanied by hip osteoarthritis. Thirty-four F1s had mean onset of capital femoral ossification (10.7 +/- 4.0 days of age) and mean dorsolateral subluxation scores (61 +/- 12%) similar to the greyhound founders, but distraction indices (0.42 +/- 0.2) more similar to the Labrador retriever founders. One F1 had CHD radiographically but none of 20 F1s had osteoarthritis at necropsy at 10 months of age. These data suggested that maximum passive laxity (as measured by the distraction index) and normal osseous conformation (as indicated by a high dorsolateral subluxation score) were both dominant traits and were controlled by separate quantitative trait loci (QTL). Forty-three back-crosses between F1s with the highest hip laxity and greyhound founders had mean onset of capital femoral ossification at 9.9 +/- 2.6 days of age. Of 10 dogs in the backcross generation that have reached 8 months of age, 2 had palpable subluxation without marked CHD radiographically. The mean distraction index of these dogs was 0.36 +/- 0.16 and the dorsolateral subluxation score was 65 +/- 5%. Although dogs in the backcross generation that were three-quarter greyhound had a broad range of hip laxity, a protective effect of the greyhound QTLs for good osseous conformation has mitigated thus far against subluxation and CHD.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. rjt2@cornell.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Todhunter
authors.forename: G M
authors.initials: GM
authors.lastname: Acland
authors.forename: M
authors.initials: M
authors.lastname: Olivier
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Vernier-Singer
authors.forename: N
authors.initials: N
authors.lastname: Burton-Wurster
authors.forename: J P
authors.initials: JP
authors.lastname: Farese
authors.forename: Y T
authors.initials: YT
authors.lastname: Gröhn
authors.forename: R O
authors.initials: RO
authors.lastname: Gilbert
authors.forename: N L
authors.initials: NL
authors.lastname: Dykes
authors.forename: G
authors.initials: G
authors.lastname: Lust
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D008040:Genetic Linkage; D006619:Hip Dysplasia, Canine / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D011859:Radiography