Several genes involved in hip dysplasia in dogs

Canine hip dysplasia has a multifactorial origin. Numerous genes are involved in the development of the disease. However, the results of genetic studies are often biased and difficult to replicate. One study sought to confirm previous findings and validate the hereditary factors involved in dysplasia.   Canine hip dysplasia is a common condition that develops as the dog grows. This “developmental abnormality” affects an average of 15% of dogs and up to 77% in certain high-risk dog breeds. It leads to instability in the hip joint. This joint laxity is responsible for clinical signs such as pain, a swaying gait, varying degrees of lameness, and stiffness that develops gradually. Although it is fairly common in dogs, the disease is still poorly characterized. In fact, hip dysplasia is multifactorial. While it is largely hereditary, certain environmental factors are also involved in the onset of this condition. Rapid growth or weight gain, intense physical activity, or a diet that is too high in calories can notably increase the risk. Conversely, some genetically predisposed dogs will never develop the disease. Identifying the multiple genetic causes of hip dysplasia in dogs remains one of the greatest challenges in veterinary medicine in recent decades. Significant efforts have been made to identify the risk loci and the variants involved. To date, about a hundred genes have been suspected. However, validating the results of many studies, as well as replicating them, has proven difficult. This is due to sample sizes that are too small for highly complex and poorly characterized phenotypes, not to mention significant genetic variability among different breeds, which is sometimes highly specific. Researchers therefore sought to shed light on past studies by validating previously established associations. The goal was to better understand the role of each gene, as well as the overall genetic heterogeneity of the condition in dogs. Scientists at the University of Helsinki focused on 52 single-nucleotide polymorphisms (SNPs SNPs) identified through interspecific and intraspecific replication studies in nearly 1,600 pedigree dogs of ten different breeds. They were thus able to replicate the findings for twenty-one genes located on fourteen chromosomes, validating their usefulness in screening for canine dysplasia. Among these genes, only one is generally considered a genetic marker for dysplasia in dogs, while the other twenty are more specific to certain breeds. Among the latter, many genes are involved in the neddylation pathway, which contributes to numerous cellular functions, including inflammation. Although redundant, verifying previous advances appears crucial, particularly for a disease with such a complex and multifactorial genetic architecture. The identification and in-depth characterization of the genes involved and the loci variants associated with hip dysplasia in dogs remain a significant challenge. This would not only lead to a better understanding of the disease’s molecular pathogenesis by revealing the metabolic pathways involved, but also enable the characterization of different phenotypes, with a view to improving treatment and diagnostic options. Better characterization also means better prevention of this debilitating condition in dogs. And as with any hereditary disease, once the cause(s) are identified, genetic selection of breeding animals would eventually eliminate the defect. Although this solution may seem complex for dysplasia, given the various loci involved, there is hope that some of them can be eliminated.