Novel protective and risk loci in hip dysplasia in German Shepherds.
Animals
Carrier Proteins
/ genetics
Case-Control Studies
Chromosome Mapping
Chromosomes, Mammalian
/ genetics
Dogs
Enhancer Elements, Genetic
Genetic Testing
/ veterinary
Genome-Wide Association Study
/ veterinary
Hip Dysplasia, Canine
/ genetics
Sequence Analysis, DNA
/ veterinary
Sequence Deletion
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
01
05
2018
accepted:
14
05
2019
revised:
31
07
2019
pubmed:
20
7
2019
medline:
18
12
2019
entrez:
20
7
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31323019
doi: 10.1371/journal.pgen.1008197
pii: PGENETICS-D-18-00893
pmc: PMC6668854
doi:
Substances chimiques
Carrier Proteins
0
noggin protein
148294-77-3
Banques de données
figshare
['10.6084/m9.figshare.8231456']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008197Déclaration de conflit d'intérêts
I have read the journal's policy and the authors of this manuscript have the following competing interests: HL provides consultancy to Genoscoper Laboratories Oy, a canine DNA diagnostics company, he used to partially own during the study (till 12/2017). There are no other competing interests.
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