Idiopathic epilepsy (IE) is a common condition in human patients as well as the domestic dog (Canis familiaris). In both species, genetic factors are believed to be a significant factor in conferring susceptibility to seizures. The most common forms of human IE are known to be polygenic, and consequently dissecting out individual epilepsy susceptibility genes has been difficult. Dogs have been strongly inbred over the last 100 years, and therefore many of their inherited diseases are caused by a "founder" effect similar to that found in isolated human populations. We hypothesize that idiopathic epilepsy in some dog breeds has a simple mode of inheritance (monogenic or oligogenic), and consequently it will be possible to efficiently map the genetic loci and eventually identify causative mutations. The causative mutation(s) could be used as candidate genes for IE's of human patients, and as a basis for experimental studies of neuronal hyperexcitability. The overall objective of this proposal is to locate chromosomal loci linked to idiopathic epilepsy in dogs, as a major step towards identifying susceptibility genes and developing a model for human idiopathic epilepsy. Dr. Edward (Ned) Patterson received his D.V.M. in 1996. He is nearing completion of his residency in small animal internal medicine with an emphasis in medical neurology, and is working towards a Ph.D. in the Veterinary Medicine Graduate Program at the University of Minnesota. He has chosen a thesis project and a research career in comparative neurogenetics using a canine model. During the initial two years of support for this award, Dr. Patterson will be working under the direct supervision of the sponsor, Dr. James Mickelson. He will have frequent meetings with the co-sponsors Drs. Laura Ranum and Yang Da. During this time, while he completes the Ph.D. thesis, 75% effort will be placed on the proposed research, and 25% on clinical and teaching duties. Dr. Mickelson has trained successful scientists in the past and is a well-known and respected scientist in the field of animal neuromuscular genetics. Dr. Ranum is a respected scientist in field of human neuroscience and genetics. Dr. Da is an accomplished statistical animal geneticist. Upon completion of his Ph.D, Dr. Patterson will be appointed to an Assistant Professorship. At this time, 75% effort will be placed on the proposed research, while other time will be utilized teaching and in clinical services. The advisory committee, composed of individuals who are all active in the areas of veterinary medicine and/or genetics, will meet quarterly to discuss research and future directions. Upon completion of the five-year plan, Dr. Patterson will have fully developed into an independent investigator who can bridge the gap from characterizing clinical inherited neuromuscular disorders to identifying the causative molecular pathobiology.
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