Canine Hip Dysplasia: Identification of Involved Genes

While the genetic cause of hip dysplasia in dogs has long been established, the genes involved remain elusive. A new study provides insights that could be useful for better characterizing and preventing this debilitating disease in dogs.   Hip dysplasia and osteoarthritis continue to be recurring problems in both veterinary medicine and human medicine. Canine hip dysplasia (CHD) is particularly problematic. It affects a large number of large-breed dogs and can lead to a severe decline in quality of life. This complex, hereditary, and multifactorial disease has puzzled many dog owners, as well as breeders, veterinarians, and researchers, for many decades. While the genetic cause has long been established, the precise identification of genes that could objectively characterize the disease is still lacking. To provide greater clarity, a standardized classification system, based on physiological observations, has been developed in the member countries of the Fédération Cynologique Internationale (FCI). The FCI score classifies HD from normal to severe (A to E) based on various hip characteristics: joint congruity, Norberg angle (NoA), degree of joint subluxation, shape and depth of the acetabulum, and whether or not there are visible signs of osteoarthritis (OA) in the joint. However, these various subclinical features may eventually lead to painful osteoarthritis regardless of the outcome. It is therefore difficult to differentiate between the two conditions. The development of osteoarthritis itself is already a complex process, involving changes in many different tissues, including bone, cartilage, the synovial membrane, and ligaments. It is therefore not surprising that genetic findings related to HD have remained rare. To address this and shed light on the genetic etiology behind the various subtypes that define dysplasia, researchers conducted a successful genome-wide association study (GWAS) on 750 well-phenotyped German Shepherds. They identified three loci implicated at the genomics level. A locus on chromosome 1 is associated with osteoarthritis and the FCI hip score, and loci on chromosomes 9 and 28 are associated with the central position of the femoral head relative to the dorsal acetabular rim (FHCDAE), which measures the misalignment of the hip joint. In addition to the three genomics-wide significant loci, two suggestive loci on chromosomes 9 and 25 were identified for comparisons of hip scores (OA, NoA, and FCI). To identify these significant genetic associations, large sample sizes were required to account for the complexity and polygenic nature of the sub-traits. It is possible that even larger cohorts may reveal additional loci with weaker effects. The identification of these pathways is an important step toward understanding the pathophysiology of CHD. It highlights the clear complexity of canine hip dysplasia phenotypes. In particular, it indicates the potential involvement of specific and partially distinct loci, genes, or pathways in the development of incongruity, mild dysplasia, moderate-to-severe dysplasia, and osteoarthritis of the canine hip joints. Further studies should help unravel the unique and common mechanisms underlying the various subtypes of hip dysplasia in dogs.