02936: Validating Genetic Variants Underlying Canine Idiopathic Epilepsy and Exploring Their Functional Roles in the Belgian Sheepdog and Tervuren

Abstract

Canine epilepsy is a debilitating condition and, unfortunately, an all too common neurological disease with impact on a dog’s health and well-being, and a significant emotional toll on owners. Epilepsy is known to be inherited, and therefore characterizing the causal genetic alterations is important to assist in breeding decisions as well as reveal pathways that could be useful targets for therapeutic intervention to mitigate the seizures themselves. Although fairly widespread among all dogs, the prevalence of idiopathic epilepsy (IE) is considered elevated and a recognized health concern in the Belgian Sheepdog (BS) and Belgian Tervuren (BT) relative to other dog breeds, making them good candidate breeds for genetic studies on IE. In addition, it was through research on these breeds that an IE risk variant in the ADAM23 gene was initially discovered and then found to be a common risk variant across many breeds although the ADAM23 variant fails to completely explain disease expression in any of the breeds indicating the need for further exploration of causal variants contributing to disease expression in dogs. Investigators recently identified a novel genomic region on canine chromosome 14 (CFA14) associated with increased risk for IE in BS and BT dogs. When combined with the ADAM23 region, the risk for IE was further increased. The present research, while focusing on the BS and BT breeds, aims to validate the involvement of the risk region on CFA14 in these and other breeds, investigate the functional changes associated with the variants while discovering additional genetic variants underlying IE susceptibility, and provide insight into the regulatory components of this disorder pertinent to many breeds.

Publication(s)

Cayabyab, D.D., Belanger, J.M., Xu, C. et al. Cellular localization of a variant RAPGEF5 protein associated with idiopathic epilepsy risk in the Belgian shepherd. Canine Med Genet 11, 4 (2024). https://doi.org/10.1186/s40575-024-00138-3

Kinsey N, Belanger JM, Mandigers PJJ, et al. Idiopathic Epilepsy Risk Allele Trends in Belgian Tervuren: A Longitudinal Genetic Analysis. Genes. 2024;15(1):114. doi:10.3390/genes15010114

Belanger, J. M., Heinonen, T., Famula, T. R., Mandigers, P. J. J., Leegwater, P. A., Hytönen, M. K., Lohi, H., & Oberbauer, A. M. (2022). Validation of a Chromosome 14 Risk Haplotype for Idiopathic Epilepsy in the Belgian Shepherd Dog Found to Be Associated with an Insertion in the RAPGEF5 Gene. Genes, 13(7), 1124. https://doi.org/10.3390/genes13071124