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02-04-2012 | Veterinary medicine | Article

Genetic locus for epilepsy found in Belgian Shepherd dogs

Abstract

Free abstract

MedWire News: An international team of researchers has identified a new genetic locus for epilepsy in Belgian Shepherd dogs.

The identified region is on canine chromosome 37 and contains "excellent neurologic candidate genes" for epilepsy, say the researchers writing in PLoS One. The team is now working to identify the specific gene that causes epilepsy in the breed.

"There are only few genes in the identified region and I believe that the ongoing analyses will help us to discover the specific epilepsy gene," said Hannes Lohi (University of Helsinki, Finland), the study's lead author, in an accompanying press statement.

"This will give us a better understanding of the disease mechanisms and provide us with new diagnostic tools for the disease."

Epilepsy is the most common neurologic disorder in dogs, with an incidence of between 0.5% and 20.0% depending on the breed. Canine epilepsy is classified as either idiopathic (generic) or symptomatic (structural/metabolic), and the former subtype is known to have a strong genetic component.

To investigate further, Lohi and co-workers identified 159 German Shepherd dogs with idiopathic epilepsy and 148 dogs of the same breed without epilepsy. All dogs underwent clinical examination, including electroencephalography, and a subset of animals had blood taken for genome-wide association studies.

This revealed a candidate locus on chromosome 37, and 96 single nucleotide polymorphisms were subsequently mapped and sequenced. The locus contains 12 genes, report Lohi et al, of which two - ADAM23 and KLF7 - are known to have neuronal functions.

Of potential signficance, mutations in ADAM23 are known to interact with LGI1, a gene associated with familial epilepsy in humans, and with LGI2, which is the causative gene for benign focal epilepsy in dogs.

"ADAM23 represents an excellent candidate gene," the team remarks.

The team also tested whether the identified locus on chromosome 37 was associated with epilepsy in other dog breeds. There was no such association in Finnish Spitz and Schipperke dogs but a tentative association in Kromfohrländers and Whippets.

"These results in both breeds need to be confirmed in a larger sample cohort with additional markers before further conclusions," the authors write.

They conclude: "Our data suggests that the ADAM23 variant is a polymorphism and we have initiated a targeted re-sequencing study across the locus to identify the causative mutation.

"It would establish the affected breed as a novel therapeutic model, help to develop a DNA test for breeding purposes and introduce a novel candidate gene for human idiopathic epilepsies."

By Joanna Lyford