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

Autor: Saila Holopainen, Tiina Pessa-Morikawa, Lea Mikkola, Hannes Lohi, Marjo K. Hytönen, Antti Iivanainen, Anu K. Lappalainen
Přispěvatelé: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Mild Dysplasia
Candidate gene
INVASION
Osteoarthritis
413 Veterinary science
Bioinformatics
Hip dysplasia (canine)
Joint laxity
0403 veterinary science
Dog
Hip Dysplasia
Canine
Dog Diseases
2. Zero hunger
0303 health sciences
JOINT
1184 Genetics
developmental biology
physiology
Chromosome Mapping
ASSOCIATION
04 agricultural and veterinary sciences
Hip dysplasia
3. Good health
German shepherd
medicine.anatomical_structure
Phenotype
GENOMIC PREDICTION
Biotechnology
Research Article
musculoskeletal diseases
Genome-wide association study
lcsh:QH426-470
040301 veterinary sciences
lcsh:Biotechnology
Quantitative Trait Loci
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
Femoral head
SYNOVIAL-FLUID
Dogs
lcsh:TP248.13-248.65
Genetics
medicine
Animals
Genetic Predisposition to Disease
Alleles
Genetic Association Studies
030304 developmental biology
Subluxation
IDENTIFICATION
NOGGIN
medicine.disease
lcsh:Genetics
Dysplasia
FEMORAL-HEAD
Zdroj: BMC Genomics, Vol 20, Iss 1, Pp 1-13 (2019)
BMC Genomics
ISSN: 1471-2164
Popis: 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 Fédération 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.
Databáze: OpenAIRE
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