Novel protective and risk loci in hip dysplasia in German Shepherds

by Lea I. Mikkola, Saila Holopainen, Anu K. Lappalainen, Tiina Pessa-Morikawa, Thomas J. P. Augustine, Meharji Arumilli, Marjo K. Hyt önen, Osmo Hakosalo, Hannes Lohi, Antti Iivanainen Canine hip dysplasia is a common, non-congenital, complex and hereditary disorder. It can inflict severe pain via secondary osteoarthritis and lead to euthanasia. An analogous disorder exists in humans. The genetic background of hip dysplasia in both species has remained ambiguous despite rigorous studies. We aimed to investigate the genetic causes of this disorder in one of the high-risk breeds, the German Shepherd. We performed genetic analyses with carefully phenotyped case-control cohorts comprising 525 German Shepherds. In our genome-wide association studies we identified four suggestiv e loci on chromosomes 1 and 9. Targeted resequencing of the two loci on chromosome 9 from 24 affected and 24 control German Shepherds revealed deletions of variable sizes in a putative enhancer element of theNOG gene.NOG encodes for noggin, a well-described bone morphogenetic protein inhibitor affecting multiple developmental processes, including joint development. The deletion was associated with the healthy controls and mildly dysplastic dogs suggesting a protective role against canine hip dysplasia. Two enhancer variants displayed a decreased activity in a dual luciferase reporter assay. Our study identifies novel loci and candidate genes for canine hip dysplasia, with potential regulatory variants in ...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research