Genome-wide association study of idiopathic epilepsy in the Italian Spinone dog breed.

Idiopathic epilepsy (IE) has a high prevalence and a severe clinical course in the Italian Spinone breed of dog. A genome-wide association study meta-analysis of 52 cases and 51 controls was conducted to identify genomic regions that may be involved with the development of IE. Subsequent to the meta-analysis, a set of 175 controls and an independent validation set of 23 cases and 23 controls were genotyped for SNPs showing suggestive association with IE to find variants exhibiting evidence of replicable association and to test the predictiveness of SNPs for IE status when combined in a weighted risk score. Although two regions showed statistically significant association with IE in the GWAS meta-analysis, and additional regions with suggestive association were identified, the findings were not emulated in the validation set. This is the first GWAS of IE in the Italian Spinone, and the findings suggest that IE in the breed is not monogenic and demonstrates the challenges when investigating a multigenic or complex inherited disease in a numerically small domesticated animal population.

Description

Acknowledgements: We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics for the generation and initial processing of the Axiom array data. We sincerely thank all owners and breeders for providing samples from their dogs for this study and the Italian Spinone Club of Great Britain for their support with sample collection. We thank Lotta Koskinen, Marjo Hytönen, Tiina Harmas and Sini Karjalainen for assistance with the Finnish samples. We thank Janine Lamb, University of Manchester, for critical review of the manuscript. We thank Ellen Schofield for bioinformatics assistance and David Sargan for laboratory support with the project.

Funder: Italian Spinone Club of Great Britain Health Fund and the Jane and Aatos Erkko Foundation (HL). CAJ, SLR and CSM were supported during this study by the Kennel Club Charitable Trust.

Keywords

Animals, Dogs, Breeding, Case-Control Studies, Dog Diseases, Epilepsy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Italy, Polymorphism, Single Nucleotide

Journal Title

PLoS One

Journal ISSN

1932-6203
1932-6203

Volume Title

20

Publisher

Public Library of Science (PLoS)

Publisher DOI

https://doi.org/10.1371/journal.pone.0315546

Rights and licensing

Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/

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