Novel protective and risk loci in hip dysplasia in German Shepherds

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http://hdl.handle.net/10138/305170

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Mikkola , L , Holopainen , S , Lappalainen , A , Pessa-Morikawa , T , Pulikotial Augustine , T , Arumilli , M , Hytönen , M K , Hakosalo , O T V , Lohi , H & Iivanainen , A 2019 , ' Novel protective and risk loci in hip dysplasia in German Shepherds ' , PLoS Genetics , vol. 15 , no. 7 , 1008197 . https://doi.org/10.1371/journal.pgen.1008197

Title: Novel protective and risk loci in hip dysplasia in German Shepherds
Author: Mikkola, Lea; Holopainen, Saila; Lappalainen, Anu; Pessa-Morikawa, Tiina; Pulikotial Augustine, Thomas; Arumilli, Meharji; Hytönen, Marjo Kristiina; Hakosalo, Osmo Topi Valtteri; Lohi, Hannes; Iivanainen, Antti
Contributor: University of Helsinki, Veterinary Biosciences
University of Helsinki, Veterinary Biosciences
University of Helsinki, Equine and Small Animal Medicine
University of Helsinki, Veterinary Biosciences
University of Helsinki, Veterinary Biosciences
University of Helsinki, Veterinary Biosciences
University of Helsinki, Veterinary Biosciences
University of Helsinki, Veterinary Biosciences
University of Helsinki, Hannes Tapani Lohi / Principal Investigator
University of Helsinki, Antti Iivanainen / Principal Investigator
Date: 2019-07-19
Language: eng
Number of pages: 30
Belongs to series: PLoS Genetics
ISSN: 1553-7404
URI: http://hdl.handle.net/10138/305170
Abstract: 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 suggestive 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 the NOG 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 the NOG gene. Further research is warranted to elucidate how the identified variants affect the expression of noggin in canine hips, and what the potential effects of the other identified loci are.
Subject: 1184 Genetics, developmental biology, physiology
Canine genetics
Veterinary genetics
Hip dysplasia
QUANTITATIVE TRAIT LOCI
NOGGIN
DOG
ASSOCIATION
GENE
HERITABILITY
CARTILAGE
PROTEIN
OSTEOARTHRITIS
RADIOGRAPHS
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