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Epilepsy is the most common chronic neurological disorder in dogs – affecting somewhere between 0.5 and 5.7 percent of dogs, depending on their breed. It is also a significant problem for humans, and in recent years scientists have wondered whether canine epilepsy might be a good animal model for developing treatments for both canine and human disease. The seizures experienced by dogs and humans are extremely similar, but whether the heritable forms of the diseases have similar genetic causes is unknown.
That was the question that Dr. James R Mickelson and his colleagues from theUniversityofMinnesotarecently set out to answer, with the support of the AKC Canine Health Foundation. While some causes of epilepsy have been identified, a large proportion of cases in both humans and dogs are idiopathic – of unknown origin. Research has suggested that many cases of idiopathic epilepsy are inherited, but at least in humans, the specific genes that are associated with the condition seem to vary by family. To date, more than 20 candidate genes have been tentatively linked to familial epilepsy in humans, most of which code for ion channels or neurotransmitter receptors.
In their study published in BMC Genetics, Dr. Mickelson and his colleagues investigated whether any of the genes that had tentatively been linked to epilepsy in either humans or mice, as well as a number of other genes that coded for related ion channels, might be associated with idiopathic epilepsy in dogs as well. The scientists looked for links between 52 different candidate genes and epilepsy in four breeds of dogs – Vizslas, English Springer Spaniels, Greater Swiss Mountain Dogs, and Beagles. They assumed that the specific genes responsible for epilepsy would vary between breeds, and they hoped that investigating the causes of epilepsy in multiple breeds would allow them to identify a greater number of genes that were linked to both human and canine disease.
Interestingly, an association between canine epilepsy and most of the genes that had been previously linked to human epilepsy could be clearly ruled out. Although a potential link between canine epilepsy and a few specific genes – namely CACNB1 in the Vizsla, CHRNB2 in the Greater Swiss Mountain Dog, and KCNQ3 and LGI1 in the Beagle – could not be eliminated, neither could any of those genes clearly be identified as causal. It is possible that this might imply that canine epilepsy is caused by multiple genes, and that any linkages were too small to detect in this study, or it could be that idiopathic canine epilepsy is linked to genes other than the ones that were tested.
Either way, this research underscores the difficulty in doing research on epilepsy – a disease where similar symptoms may be caused by any of a number of genetic and non-heritable factors. Fortunately, the scientists intend to continue their search. Identifying the genetic components involved in hereditary canine epilepsy could improve the lives of humans and dogs alike.
This work was funded by AKC Canine Health Foundation Grant 598.
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