Dataset Information

An across-breed validation study of 46 genetic markers in canine hip dysplasia.

ABSTRACT:

Background

Canine hip dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants.

Results

We execute a validation study of 46 genetic markers in a cohort of nearly 1600 dogs from ten different breeds. We categorize the dogs into cases and controls according to the hip scoring system defined by the Fédération Cynologique Internationale (FCI). We validate 21 different loci associated on fourteen chromosomes. Twenty of these associated with CHD in specific breeds, whereas one locus is unique to the across-breed study. We show that genes involved in the neddylation pathway are enriched among the genes in the validated loci. Neddylation contributes to many cellular functions including inflammation.

Conclusions

Our study successfully replicates many loci and highlights the complex genetic architecture of CHD. Further characterisation of the associated loci could reveal CHD-relevant genes and pathways for improved understanding of the disease pathogenesis.

SUBMITTER: Mikkola L

PROVIDER: S-EPMC7818755 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

An across-breed validation study of 46 genetic markers in canine hip dysplasia.

Mikkola Lea L Kyöstilä Kaisa K Donner Jonas J Lappalainen Anu K AK Hytönen Marjo K MK Lohi Hannes H Iivanainen Antti A

BMC genomics 20210121 1

<h4>Background</h4>Canine hip dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sa ...[more]

PMID: 33478395

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Project description: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.

Project description:Hip and elbow dysplasia are common disorders in larger dog breeds and crosses, and a known contributory factor to osteoarthritis, lameness and reduced mobility. Screening schemes evaluating the severity of hip and elbow dysplasia in the UK are administered by the British Veterinary Association (BVA) and the Kennel Club (KC). The BVA/KC Hip Dysplasia scoring scheme is over 50 years old, having originated in 1965, and has operated in its current form since 1983. The BVA/KC Elbow Dysplasia grading scheme commenced more recently in 1998 and is based on the International Elbow Working Group guidelines. Hip score and elbow grade data on a considerable number of dogs in the UK have been generated from these two screening schemes. This study analyses data from dogs of six breeds scored from 1990 to present, to establish any determinable trends in hip score and elbow grade parameters, and to examine whether the implementation of such schemes has had a positive influence on hip and elbow health. A range of criteria, including the rate of participation in the screening schemes, hip score and elbow grade parameters (e.g., median, mean, standard deviation), and estimated breeding values (EBVs) were analyzed, both in the overall population and also among breeding animals. The results show a general decline in hip score parameters (median, mean, standard deviation, and 75th percentile), revealing a reduction in the prevalence and severity of hip dysplasia. There was a more modest decline in mean elbow grade within breeds. The proportion of sires and dams (of dogs born per year) with no hip score or elbow grade fell substantially over time, demonstrating good participation in the screening schemes. In most breeds, the scores of sires and dams are demonstrably improving. There is a declining genetic trend as ascertained by EBVs for both hip scores and elbow grades in most breeds, implying that the improvement observed is due in part to selection for improvement in hip and elbow health as described by the respective screening schemes.

Dataset Information

An across-breed validation study of 46 genetic markers in canine hip dysplasia.

Background

Results

Conclusions

Publications

An across-breed validation study of 46 genetic markers in canine hip dysplasia.

Similar Datasets

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