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A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches

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 mi...

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Autores principales: Bartolomé, Nerea, Segarra, Sergi, Artieda, Marta, Francino, Olga, Sánchez, Elisenda, Szczypiorska, Magdalena, Casellas, Joaquim, Tejedor, Diego, Cerdeira, Joaquín, Martínez, Antonio, Velasco, Alfonso, Sánchez, Armand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395148/
https://www.ncbi.nlm.nih.gov/pubmed/25874693
http://dx.doi.org/10.1371/journal.pone.0122558
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author Bartolomé, Nerea
Segarra, Sergi
Artieda, Marta
Francino, Olga
Sánchez, Elisenda
Szczypiorska, Magdalena
Casellas, Joaquim
Tejedor, Diego
Cerdeira, Joaquín
Martínez, Antonio
Velasco, Alfonso
Sánchez, Armand
author_facet Bartolomé, Nerea
Segarra, Sergi
Artieda, Marta
Francino, Olga
Sánchez, Elisenda
Szczypiorska, Magdalena
Casellas, Joaquim
Tejedor, Diego
Cerdeira, Joaquín
Martínez, Antonio
Velasco, Alfonso
Sánchez, Armand
author_sort Bartolomé, Nerea
collection PubMed
description 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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spelling pubmed-43951482015-04-21 A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches Bartolomé, Nerea Segarra, Sergi Artieda, Marta Francino, Olga Sánchez, Elisenda Szczypiorska, Magdalena Casellas, Joaquim Tejedor, Diego Cerdeira, Joaquín Martínez, Antonio Velasco, Alfonso Sánchez, Armand PLoS One Research Article 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. Public Library of Science 2015-04-13 /pmc/articles/PMC4395148/ /pubmed/25874693 http://dx.doi.org/10.1371/journal.pone.0122558 Text en © 2015 Bartolomé et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bartolomé, Nerea
Segarra, Sergi
Artieda, Marta
Francino, Olga
Sánchez, Elisenda
Szczypiorska, Magdalena
Casellas, Joaquim
Tejedor, Diego
Cerdeira, Joaquín
Martínez, Antonio
Velasco, Alfonso
Sánchez, Armand
A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title_full A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title_fullStr A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title_full_unstemmed A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title_short A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches
title_sort genetic predictive model for canine hip dysplasia: integration of genome wide association study (gwas) and candidate gene approaches
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395148/
https://www.ncbi.nlm.nih.gov/pubmed/25874693
http://dx.doi.org/10.1371/journal.pone.0122558
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