21 QTL Mapping Using Crossbreed Pedigrees: Strategies for Canine Hip Dysplasia

Abstract

Canine hip dysplasia (CHD) is a common inherited trait in dogs and the secondary debilitating hip osteoarthritis (OA) results in pain, lameness, and physical disability. Because CHD is a complex trait, the genotype of a dog cannot be judged from its phenotype. Furthermore, dysplastic dogs also have abnormalities in other joints (Olsewski et al. 1983; Kealy et al. 1992, 1997, 2000; Farquhar et al. 1997; Morgan et al. 1999), indicating that the primary defect is systemic, rather than restricted to the hip. We developed an informative crossbreed pedigree for mapping the quantitative trait loci (QTL) contributing to CHD expression. In the context of this unique pedigree, we review here recent advances in CHD and our first attempts in defining the molecular genetic basis of this common complex disease trait, although the trigger event for CHD remains elusive. The dysplastic dog presents itself as an important natural large animal model of a complex human trait. BREED PREVALENCE Hip dysplasia occurs in any pure or mixed breed dog but more commonly affects large breed dogs (Hedhammar et al. 1974; Leighton et al. 1977; Cardinet et al. 1983; Willis 1989; Kaneene et al. 1997; Breur et al. 2002). Breed prevalence, as estimated by the Orthopedic Foundation for Animals (OFA), varies from 1% to 75% (http://www.offa.org/hipstatbreed.html). Phenotype Traditional Mature dogs are positioned in dorsal recumbency with the hips extended, and a ventrodorsal radiograph is taken (Fig. 1). In North America, radiographs are scored based on the degree of subluxation and secondary OA according to...