A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches

PLoS One. 2015 Apr 13;10(4):e0122558. doi: 10.1371/journal.pone.0122558. eCollection 2015.

Abstract

Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Dogs
  • Genetic Association Studies*
  • Genome-Wide Association Study*
  • Hip Dysplasia, Canine / genetics*
  • Hip Dysplasia, Canine / pathology
  • Polymorphism, Single Nucleotide / genetics

Grants and funding

This work has been supported by Grants IG-2011/0000745 and IG-2012/0000068 from the Basque Government and by the corporate sponsor Bioibérica SA. The funder Bioibérica SA provided support in the form of salaries and research materials for authors AV and SS, while Progenika Biopharma SA provided support in the form of salaries for authors NB, MA, MS, DT, and AM, but neither company had any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section.