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

Show simple item record Mikkola, Lea Holopainen, Saila Pessa-Morikawa, Tiina Lappalainen, Anu K. Hytönen, Marjo K. Lohi, Hannes Iivanainen, Antti 2020-01-09T12:10:25Z 2020-01-09T12:10:25Z 2019-12-27
dc.identifier.citation 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 .
dc.identifier.other PURE: 129755008
dc.identifier.other PURE UUID: 61af0638-f8e3-4053-9eba-7238b51a2c91
dc.identifier.other WOS: 000504727300007
dc.identifier.other ORCID: /0000-0001-5992-8442/work/67132791
dc.identifier.other ORCID: /0000-0003-1976-5874/work/80222230
dc.description.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. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof BMC Genomics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Hip dysplasia
dc.subject Osteoarthritis
dc.subject Dog
dc.subject German shepherd
dc.subject Genome-wide association study
dc.subject FEMORAL-HEAD
dc.subject NOGGIN
dc.subject JOINT
dc.subject DOGS
dc.subject ASSOCIATION
dc.subject INVASION
dc.subject 413 Veterinary science
dc.subject 1184 Genetics, developmental biology, physiology
dc.title Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci en
dc.type Article
dc.contributor.organization Helsinki One Health (HOH)
dc.contributor.organization Developmental interactions
dc.contributor.organization Veterinary Biosciences
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Small Animal Hospital
dc.contributor.organization Hannes Tapani Lohi / Principal Investigator
dc.contributor.organization Equine and Small Animal Medicine
dc.contributor.organization Antti Iivanainen / Principal Investigator
dc.contributor.organization Veterinary Anatomy and Developmental Biology
dc.contributor.organization Departments of Faculty of Veterinary Medicine
dc.contributor.organization Doctoral Programme in Clinical Veterinary Medicine
dc.contributor.organization Veterinary Genetics
dc.contributor.organization Petbone – ortopedia, fysioterapia, kivunlievitys
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1471-2164
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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