Studies on Canine Hip Dysplasia

Hip dysplasia (HD) is a non-congenital and multifactorial disorder that affects several canine breeds. HD is chronic and often painful, and can significantly lower the quality of life. It usually develops during rapid growth in juvenile dogs. The increased laxity destabilizes the joint leading to a progressive complex phenotype. Different sub-traits include, e.g., joint incongruency, shallowness of the acetabulum, deformation of the femoral head, varying degrees of subluxation, erosion of the articular cartilage, sclerosis in the subchondral bone and formation of osteophytes. HD is evaluated by aggregating several sub-traits from hip-extended ventrodorsal radiographs. The clinical signs vary from occasional stiffness to severe chronic pain and impaired mobility of the joint.

The breed-specific frequency of HD varies from 0 to 71% [The Orthopedic Foundation for Animals]. Differences in growth rate, obesity, exercise habits and muscle condition, and in biomechanical, nutritional and hormonal factors have been suggested to contribute to the risk of developing HD. Heritability (h2) estimates vary typically between 0.15 and 0.80 indicating a significant genetic component. Individual loci have a rather limited contribution to the overall genetic risk. Further, there have been great difficulties to validate the observed associations using independent cohorts.

We conducted a case-control study using a cohort of 769 German Shepherds. We found significantly associating SNP-markers in chromosomes 1, 9 and 28 with genes such as NOX3, ARID1B, NOG and NANOS residing nearby. We also found deletion variants upstream NOG and showed that they affect reporter gene expression in vitro. Using a 1572 dog cohort from ten breeds we validated the association of 23 previously identified markers across 21 loci in 14 autosomes. Proteins involved in the neddylation protein modification pathway were overrepresented among the >250 protein coding genes residing within one megabase of the 23 markers.