Single nucleotide polymorphisms refine QTL intervals for hip joint laxity in dogs

Hip laxity is one characteristic of canine hip dysplasia (CHD), an inheritable disease that leads to hip osteoarthritis. Using a genome-wide screen with 250 microsatellites in a crossbreed pedigree of 159 dysplastic Labrador retrievers and unaffected greyhounds, we previously identified putative (P < 0.01) QTL on canine chromosomes 11 and 29 (CFA11 and CFA29). To refine these QTL locations, we have genotyped 257 dogs including 105 Labrador retrievers, seven greyhounds, four generations of their crossbreed offspring and three German shepherds for 111 and 171 SNPs on CFA11 and CFA29 respectively. The distraction index (DI, a measure of maximum hip laxity) was used as an intermediate phenotype that predicts whether a hip joint will or will not develop osteoarthritis. Using a multipoint linkage analysis, significant evidence (95% posterior probability) was found for QTL contributing to hip laxity in the 16.2-21 cM region on CFA11 that explained 15-18% of the total variance in DI. Evidence for an independent QTL on CFA29 was weaker than that on CFA11. Identification of the causative mutation(s) will lead to better understanding of biochemical pathways in both dogs and humans with hip laxity and dysplasia.