Identification and Validation of Quantitative Trait Loci (QTL) for Canine Hip Dysplasia (CHD) in German Shepherd Dogs

Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA) 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20-32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL) and a novel QTL for CHD in German Shepherd Dogs.