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

Nerea Bartolomé,Alfonso Velasco,Joaquim Casellas,Sergi Segarra,Marta Artieda,Armand Sánchez,Elisenda Sánchez,Diego Tejedor,Olga Francino,Antonio Martínez,Joaquín Cerdeira,Magdalena Szczypiorska

doi:10.1371/journal.pone.0122558

Nerea Bartolomé, Alfonso Velasco + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0122558

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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.

Highlights

Canine hip dysplasia (CHD) is one of the most prevalent developmental orthopedic diseases in dogs worldwide
Principal component analysis (PCA) plot of the 240 Labrador included at the development study and 80,116 SNPs revealed no stratification among the affected dogs and free of hip dysplasia dogs (Fig 1)
We found 250 SNPs significantly associated to CHD after False Discovery Rate (FDR) correction for multiple testing in the Genome Wide Association Study (GWAS) analysis (p1.96x10-5) and 33 SNPs in the candidate genes study (p5x10-3)

Summary

Introduction

Canine hip dysplasia (CHD) is one of the most prevalent developmental orthopedic diseases in dogs worldwide. It is characterized by an abnormal formation of the hip joint with different degrees of laxity and subluxation, which leads to secondary osteoarthritis (OA) and impaired animal welfare. The diagnosis of CHD is established through radiographic examination of the hip joint using different accepted scores. During the last decades a high number of selective breeding programs based on radiographies have been implemented for different breeds with the aim of reducing CHD incidence and improving animal’s welfare. An improvement was described in some cases [5,6], but a slow progress or no improvement was achieved in others [7,8,9]

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