Candidate genes for idiopathic epilepsy in four dog breeds

Candidate genes known to be involved in human epilepsy, along with selected additional genes in the same gene families that are involved in murine epilepsy or are expressed in neural tissue, were examined in populations of affected and unaffected dogs. Microsatellite markers in close proximity to each candidate gene were genotyped and subjected to two-point linkage in Vizslas, and association analysis in ESS, GSMD and Beagles.Most of these candidate genes were not significantly associated with IE in these four dog breeds, while a few genes remained inconclusive. Other genes not included in this study may still be causing monogenic IE in these breeds or, like many cases of human IE, the disease in dogs may be likewise polygenic.The prevalence of epilepsy in humans is reported to be in the range of 4 - 10/1000 in most study settings [1], with idiopathic epilepsy (IE) representing 15 - 20% of these cases [2]. It is now generally accepted that IE in humans is due to an underlying genetic origin [2], although causative mutations have been discovered in only a small subset of IEs, mostly in isolated populations. These identified epilepsy mutations are, for the most part, Mendelian or monogenic IEs [3-6], and are often termed "channelopathies" due to their occurrence in ion channel genes. In a recent review, 16 of 21 susceptibility genes for human epilepsy were ion channels or neurotransmitter receptors [7].Canine epilepsy is a naturally occurring, spontaneous condition. Canine seizures exhibit a remarkable resemblance to human seizures [8] and the usefulness of naturally occurring canine epilepsy as a translational model to explore potential treatments for human epilepsy was recently proposed by Leppik, et al. [9]. The prevalence of canine epilepsy is estimated to be between 0.5% and 5.7% and it is the most common chronic neurological disorder in dogs [10]. A diagnosis of IE in the canine indicates recurrent seizures for which no cause can be identified and implies a gene