Analysis of allele fidelity, polymorphic information content, and density of microsatellites in a genome-wide screening for hip dysplasia in a crossbreed pedigree.

Recent advances in genomics resources and tools are facilitating quantitative trait locus mapping. We developed a crossbreed pedigree for mapping quantitative trait loci for hip dysplasia in dogs by crossing dysplastic Labrador Retrievers and normal Greyhounds. We show that one advantage to using a crossbreed pedigree is the increased marker informativeness in the backcross/F2 population relative to the founder populations. We also discuss three factors that affect the detection power in the context of this crossbreed pedigree: being able to detect and correct genotyping errors, increasing marker density for chromosomes with a sparse coverage, and adding individuals to the mapping population as soon as they become available.

Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree.

An outcrossed canine pedigree was developed for quantitative trait locus (QTL) mapping of hip dysplasia by breeding dysplastic Labrador retrievers to trait-free greyhounds. Measured susceptibility traits included age at onset of femoral capital chondroepiphyseal ossification (OSS), maximum hip distraction (laxity) index (DI), and the dorsolateral subluxation (DLS) score. The pedigrees consisted of 147 dogs representing four generations. For 59 dogs genotyped with 65 microsatellites, the median heterozygosity and polymorphic information content (PIC) values of the F(1) generation were 0.82 and 0.68, respectively. Seventy-seven percent of microsatellites had a PIC greater than 0.59 in the F(1)s. Ninety-six percent of alleles showed Mendelian inheritance. Based on marker informativeness, approximately 350 randomly selected markers would be required for genome-wide screening to obtain an average interval between informative markers of 10 cM. Heritability was estimated as 0.43, 0.5, and 0.61 for OSS, DI, and the DLS score, respectively. Biometric estimates of the mean (+/- variance) effective number of segregating QTLs was 1.2 (+/- 0.05), 0.8 (+/- 0.02), and 1.0 (+/- 0.03) for OSS, DI, and the DLS score, respectively. The distributions of simulated backcross trait data suggested that the loci controlling these traits acted additively and that the DI may be controlled by a major locus. When combined with previous power and quantitative genetic analyses, these estimates indicate that this pedigree is informative for QTL mapping of hip dysplasia traits.

Repeatability of dorsolateral subluxation scores in dogs and correlation with macroscopic appearance of hip osteoarthritis.

OBJECTIVE: To determine whether dorsolateral subluxation (DLS) scores in young dogs could be used to reliably predict which dogs would develop evidence of hip osteoarthritis and whether DLS scores measured at various ages correlated with each other. ANIMALS: 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. PROCEDURES: DLS scores were measured on radiographs taken at 4, 8, and 12 months of age and at necropsy (8 to 36 months of age). At necropsy, the hip joints were examined macroscopically and a score assigned for degree of cartilage degeneration. RESULTS: DLS scores at 4 (n = 35, r(s) = -0.62), 8 (n = 106, r(s) = -0.54), and 12 (n = 15, r(s) = -0.87) months of age were significantly correlated with cartilage degeneration scores, and DLS scores at 8 months of age were significantly correlated with scores obtained at the time of necropsy (n = 39, r(s) = 0.87). The DLS scores at 4 months of age were significantly different from scores at 8 months of age, but scores did not differ significantly thereafter. Likelihood ratios for cartilage lesions for low (< 45%), intermediate (> or = 45 but < or = 55%), and high (> 55%) DLS scores at 8 months of age were 8.0, 2.6, and 0.2, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that DLS score at 8 months of age was a reasonable, albeit imperfect, predictor of the condition of the hip joint cartilage at necropsy. Thus, the DLS method might be useful for early identification of dogs with hip dysplasia.

Comparison of three radiographic methods for diagnosis of hip dysplasia in eight-month-old dogs.

OBJECTIVE: To compare the accuracy of the extended-hip radiographic (EHR) score, the distraction index (DI), and the dorsolateral subluxation (DLS) score for identifying hip dysplasia in dogs at 8 months of age. DESIGN: Cohort study ANIMALS: 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. PROCEDURE: Radiography was performed when dogs were 8 months of age. Dogs were euthanatized at 8 to 36 months of age; hip dysplasia was diagnosed at the time of necropsy on the basis of results of a gross examination of the articular cartilage of the hip joints for signs of osteoarthritis. RESULTS: The EHR score, DI, and DLS score at 8 months of age were all significantly correlated with degree of cartilage degeneration at necropsy. Sensitivity and specificity of using EHR score at 8 months of age to diagnose hip dysplasia (scores > 3 were considered abnormal) were 38 and 96%, respectively; sensitivity and specificity of using DI (values > 0.7 were considered abnormal) were 50 and 89%; and sensitivity and specificity of using DLS score (scores < 55% were considered abnormal) were 83 and 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that specificities of the 3 methods for diagnosing hip dysplasia in dogs at 8 months of age were similar. However, the DLS score had higher sensitivity, indicating that there were fewer false-negative results.