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A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
Authors:Nerea Bartolomé  Sergi Segarra  Marta Artieda  Olga Francino  Elisenda Sánchez  Magdalena Szczypiorska  Joaquim Casellas  Diego Tejedor  Joaquín Cerdeira  Antonio Martínez  Alfonso Velasco  Armand Sánchez
Institution:1. Progenika Biopharma SA, a Grifols Company, Derio, Bizkaia, Spain.; 2. Bioibérica SA, Barcelona, Spain.; 3. Servei Veterinari de Genètica Molecular, Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona, Barcelona, Spain.; 4. Centro Veterinario Aluche Las Águilas, Madrid, Spain.; Tor Vergata University of Rome, ITALY,
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.
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