Candidate genes for idiopathic epilepsy in four dog breeds

Abstract

BackgroundIdiopathic epilepsy (IE) is a naturally occurring and significant seizure disorder affecting all dog breeds. Because dog breeds are genetically isolated populations, it is possible that IE is attributable to common founders and is genetically homogenous within breeds. In humans, a number of mutations, the majority of which are genes encoding ion channels, neurotransmitters, or their regulatory subunits, have been discovered to cause rare, specific types of IE. It was hypothesized that there are simple genetic bases for IE in some purebred dog breeds, specifically in Vizslas, English Springer Spaniels (ESS), Greater Swiss Mountain Dogs (GSMD), and Beagles, and that the gene(s) responsible may, in some cases, be the same as those already discovered in humans.ResultsCandidate 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.ConclusionsMost 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.

International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs

“…Pedigree analysis and results of segregation analysis of the US study were consistent with a partially penetrant autosomal recessive or polygenic inheritance [ 74 ]. The identification of a causative gene mutation has not yet reported [ 76 ]. Potential breed-specific diseases that may mimic idiopathic epilepsy: Fucosidosis is a lysosomal storage disease, which affects humans and English Springer Spaniels.…”

“…Pedigree analysis revealed that all affected dogs could be traced back to a common sire. The identification of a causative gene mutation has not yet reported [ 76 , 87 ].…”

“…Particularly for the Beagle, it should be mentioned that most of the earlier published data are based mainly on laboratory dog populations [ 117 ]. However, one recent epidemiological investigation and one genetic investigation support an increased risk for idiopathic epilepsy in Beagles at present [ 22 , 76 ]. In Beagles, Dachshunds (miniature wirehaired) and Basset Hounds it is important to consider the occurrence of progressive myoclonus epilepsy (Lafora disease), as the latter is considered a neurodegenerative disorder and structural-metabolic epilepsy rather than idiopathic epilepsy [ 121 – 123 ].…”

Identification of a Novel Idiopathic Epilepsy Locus in Belgian Shepherd Dogs

“…Despite efforts using either candidate gene [34] or low-resolution genome wide approaches [35], [36], the genetic background of many focal and generalized epilepsies remains largely unknown.…”

Disease Progression and Treatment Response of Idiopathic Epilepsy inAustralianShepherd Dogs

“…Recent epilepsy research in dogs mainly focuses on the identification of epilepsy genes, but interest in mechanisms of pharmacoresistance and the characterization of the clinical course are increasing . It is generally stated that pharmacoresistance can develop in up to 30% of dogs with epilepsy .…”