Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci

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Mikkola , L , Holopainen , S , Pessa-Morikawa , T , Lappalainen , A K , Hytönen , M K , Lohi , H & Iivanainen , A 2019 , ' Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci ' , BMC Genomics , vol. 20 , no. 1 , 1027 .

Title: Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci
Author: Mikkola, Lea; Holopainen, Saila; Pessa-Morikawa, Tiina; Lappalainen, Anu K.; Hytönen, Marjo K.; Lohi, Hannes; Iivanainen, Antti
Contributor organization: Helsinki One Health (HOH)
Developmental interactions
Veterinary Biosciences
Department of Medical and Clinical Genetics
Small Animal Hospital
Hannes Tapani Lohi / Principal Investigator
Equine and Small Animal Medicine
Antti Iivanainen / Principal Investigator
Veterinary Anatomy and Developmental Biology
Departments of Faculty of Veterinary Medicine
Doctoral Programme in Clinical Veterinary Medicine
Veterinary Genetics
Petbone – ortopedia, fysioterapia, kivunlievitys
Date: 2019-12-27
Language: eng
Number of pages: 13
Belongs to series: BMC Genomics
ISSN: 1471-2164
Abstract: Background Hip dysplasia and osteoarthritis continue to be prevalent problems in veterinary and human medicine. Canine hip dysplasia is particularly problematic as it massively affects several large-sized breeds and can cause a severe impairment of the quality of life. In Finland, the complex condition is categorized to five classes from normal to severe dysplasia, but the categorization includes several sub-traits: congruity of the joint, Norberg angle, subluxation degree of the joint, shape and depth of the acetabulum, and osteoarthritis. Hip dysplasia and osteoarthritis have been proposed to have separate genetic etiologies. Results Using Federation Cynologique Internationale -standardized ventrodorsal radiographs, German shepherds were rigorously phenotyped for osteoarthritis, and for joint incongruity by Norberg angle and femoral head center position in relation to dorsal acetabular edge. The affected dogs were categorized into mild, moderate and severe dysplastic phenotypes using official hip scores. Three different genome-wide significant loci were uncovered. The strongest candidate genes for hip joint incongruity were noggin (NOG), a bone and joint developmental gene on chromosome 9, and nanos C2HC-type zinc finger 1 (NANOS1), a regulator of matrix metalloproteinase 14 (MMP14) on chromosome 28. Osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3), an intriguing candidate for articular cartilage degradation, and AT-rich interactive domain 1B (ARID1B) that has been previously linked to joint laxity. Conclusions Our findings highlight the complexity of canine hip dysplasia phenotypes. In particular, the results of this study point to the potential involvement of specific and partially distinct loci and genes or pathways in the development of incongruity, mild dysplasia, moderate-to-severe dysplasia and osteoarthritis of canine hip joints. Further studies should unravel the unique and common mechanisms for the various sub-traits.
Subject: Hip dysplasia
German shepherd
Genome-wide association study
413 Veterinary science
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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