02257: Identification of Genetic Risk Factors for Canine Epilepsy
Grant Status: Closed
Epilepsy is one of the most common neurologic diseases of dogs and a top concern of dog breeders. Despite strong evidence that genetics is important in determining the risk of idiopathic epilepsy, numerous gene mapping studies have failed to identify a locus that accounts for that risk in either dogs or humans. Seizures occur when excessive activity goes beyond the normal threshold for brain function, many factors contribute to that level of activity, and therefore, mutations in numerous genes may collectively contribute to increased activity until that threshold is exceeded, resulting in epilepsy. Any one of these mutations may be present in non-epileptic dogs, but because it only partially alters activity, it would not produce seizures. Therefore, traditional gene mapping studies might overlook that mutation. Using a novel whole genome sequencing approach the investigators hope to identify DNA variations in epileptic dogs that could affect the function of genes such as ion channels and neurotransmitter receptors that have been shown to alter the seizure threshold in humans or rodents. The frequency of such variations in populations of epileptic and non-epileptic dogs will be directly compared rather than the indirect markers used in traditional mapping studies. The increased power provided by looking for specific gene candidate variations rather than linked markers will aid the identification of epilepsy risk factors, perhaps leading to the development of DNA tests to enable breeders to select against such risk factors.
Kolicheski, A., Johnson, G. S., Villani, N. A., O’Brien, D. P., Mhlanga-Mutangadura, T., Wenger, D. A., … Katz, M. L. (2017). GM2 Gangliosidosis in Shiba Inu Dogs with an In-Frame Deletion in HEXB. Journal of Veterinary Internal Medicine, 31(5), 1520–1526. https://doi.org/10.1111/jvim.14794
Kolicheski, A., Barnes Heller, H. L., Arnold, S., Schnabel, R. D., Taylor, J. F., Knox, C. A., … Katz, M. L. (2017). Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis. Journal of Veterinary Internal Medicine, 31(1), 149–157. https://doi.org/10.1111/jvim.14632
Villani, N. A., Bullock, G., Michaels, J. R., Yamato, O., O’Brien, D. P., Mhlanga Mutangadura, T., … Katz, M. L. (2019). A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in border collies and Australian cattle dogs. Molecular Genetics and Metabolism. https://doi.org/10.1016/j.ymgme.2019.04.003
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