A fibrillin 2 mutation associated with canine hip dysplasia

Abstract

Hip joint laxity, instability, and osteoarthritis are features of developmental dysplasia of the canine hip. Previous genetic mapping narrowed a quantitative trait locus to18.5-21 cM (95% posterior probability interval) on Canis familaris (Cfa) 11, which explained about 15-18% of the total variance in hip laxity. In this study, among 100 Labrador retrievers a 10 base-pair haplotype in intron 30 of fibrillin (FBN) 2 at 20.3-20.5 Mb on Cfa11 was significantly (p=0.007) associated with a worsening of hip laxity (distraction index). Among 14 Labrador retriever/greyhound cross breeds, hip dysplasia was associated with a significant (p=0.04) decrease in FBN2 mRNA levels in hip capsule of the same joints. Among the same dogs, those with incipient hip osteoarthritis that resulted from hip dysplasia and who were also homozygous for the deletion haplotype had a 4-5 fold decrease in FBN2 mRNA levels in their hip joint capsules compared to those homozygous for the unaffected haplotype. Less FBN2 immunostaining was observed in hip capsules from osteoarthritic compared to unaffected hips. Conclusion: This is the first identified mutation associated with hip dysplasia and we posit FBN2 as a candidate gene for canine hip dysplasia.