Canine models of human disease – hip dysplasia

 A genetic study of canine hip dysplasia reveals new loci and a regulatory variant of the NOG gene, which is essential to joint development. NOG mutations have also been found in human joint disorders.

Hip dysplasia is a hereditary disorder with a multifactorial background, and it is common both in dogs and humans. Hip dysplasia often leads to the development of osteoarthritis. The prevalence of hip dysplasia is high in many dog breeds such as the German shepherd.

A genetic study of canine hip dysplasia that included over 500 German shepherds revealed novel associated loci in canine chromosomes 1 and 9. Dogs from different disease categories (mild or moderate-to-severe) were compared with dogs with normal hip joints. The results indicated that mild hip dysplasia may have a partially different genetic etiology in comparison with the more severe disease forms. Further investigation revealed a regulatory variant for the NOG gene, which appeared to have a protective effect. NOG is essential for normal joint development, and NOG mutations have been reported to cause joint disorders in humans.

Because of the multifactorial and highly polygenic background of hip dysplasia, a small set of gene variants is not useful in disease diagnostics or as a breeding aid, but they bring about important new insights on the biological pathways that impact the disease development. Future studies need to untangle the gene networks and molecular pathways that play a role in hip dysplasia within and across species.

This study was enabled by active dog owners, a vast dog DNA biobank with robust phenotypes, and active cooperation between the investigators, the Finnish Kennel Club, and the University of Helsinki Veterinary Teaching Hospital. The results of this study highlight the complex nature of hip dysplasia.

Original Article:

Mikkola LI, Holopainen S, Lappalainen AK, Pessa-Morikawa T, Augustine TJP, Arumilli M, Hytönen MK, Hakosalo O, Lohi H*, Iivanainen A*. Protective regulatory NOG variants against hip dysplasia in German Shepherds. PLoS Genet 15: e1008197, 2019 (doi: 10.1371/journal.pgen.1008197).