Searching the genetic causes of canine epilepsy as a model for human epilepsy

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Authors Pascale QUIGNON (1), Catherine ESCRIOU (2), Stéphanie MOTTIER (1), Anna LETKO (3) and Catherine ANDRÉ (1)
Affiliations 1. Univ Rennes, CNRS, IGDR (Institute of Genetics and Developement of Rennes) – UMR6290, F-35000 Rennes, France 2. Département animaux de compagnie ; Vetagro Sup Campus vétérinaire de Lyon, 69280 Marcy l’étoile, France 3. Genetics Institute, Bern university, 3001 Bern, Suisse
Presentation Type Talk


In human, epilepsy is the most disabling neurological disease, with a large number of forms, each considered a rare disease. Interestingly, epilepsy is also widespread in the canine species, with 5% of dogs affected, each breed or breed group presenting a specific clinical form with a high prevalence underlying a breed-specific genetic origin. However, to date, despite the many canine breeds affected, current studies tend to conclude that the disease is multigenic, and few of the genes involved have been discovered. We therefore propose to study and compare four dog breeds particularly prone to generalized epilepsy and tonic-clonic seizures: Greater Swiss Mountain Dog, Bernese Mountain Dog, Cane Corso and Dogue de Bordeaux, for which we have collected DNA samples and clinical data from affected and unaffected dogs. We hypothesized that in Bernese Mountain Dogs and Greater Swiss Mountain Dogs, which share the same geographical and genetic origins, epilepsy would be due to common mutations; and we made the same assumption for Cane Corso and Dogue de Bordeaux, which belong to the same molossoid breed group.
So, to search for the genes and mutations involved, we have already sequenced the complete genomes of 2 affected and 3 healthy dogs in each of the 4 breeds of interest. The sequences were aligned with the CanFam4 reference genome, using the GATK pipeline. The sequences were then compared with the genomic sequences of over 300 healthy dogs with epilepsy, to identify genetic alterations in the 4 breeds and to find variations common to the different breeds, 2 by 2 (Bernese Mountain Dog / Greater Swiss Mountain Dog and Cane Corso / Dogue de Bordeaux). The effect of the variants thus identified was predicted using the snpEFF tool.
The preliminary analyses of these data are encouraging, with common variants annotated in functionally relevant candidate genes. These variants now need to be validated in a larger number of dogs of the breeds of interest, as well as in other breeds without genetic epilepsy. We very much hope that this approach will enable us to identify the genetic basis of epilepsy in these dog breeds, and bring new candidate genes to the corresponding human epilepsies, thus presenting diagnostic and therapeutic interest in human and veterinary medicine.