Abstract
BackgroundCanine hip dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants.ResultsWe execute a validation study of 46 genetic markers in a cohort of nearly 1600 dogs from ten different breeds. We categorize the dogs into cases and controls according to the hip scoring system defined by the Fédération Cynologique Internationale (FCI). We validate 21 different loci associated on fourteen chromosomes. Twenty of these associated with CHD in specific breeds, whereas one locus is unique to the across-breed study. We show that genes involved in the neddylation pathway are enriched among the genes in the validated loci. Neddylation contributes to many cellular functions including inflammation.ConclusionsOur study successfully replicates many loci and highlights the complex genetic architecture of CHD. Further characterisation of the associated loci could reveal CHD-relevant genes and pathways for improved understanding of the disease pathogenesis.
Highlights
Canine hip dysplasia (CHD) is a common disease, with a complex genetic background
In USA and Canada, where dogs scored within the American Veterinary Medical Association system, the extreme values vary from a zero disease prevalence in Italian Greyhounds to a high prevalence of 77.7% in the Bulldogs [1]
We genotyped 52 SNPs that have previously been associated with CHD (Additional files 1 and 2), and carried out various case-control association analyses of CHD
Summary
Canine hip dysplasia (CHD) is a common disease, with a complex genetic background. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. The independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants. Revealing the genetic background of canine hip dysplasia (CHD) has remained one of the biggest veterinary conundrums in the past few decades. Validation of breed-specific loci is a tedious effort, since one needs to collect a robustly phenotyped independent cohort of each breed. It is usually easier to collect a large multi-breed cohort that can be used to define which CHD associated loci are shared between breeds.
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