A multidisciplinary approach is being taken utilizing the expertise of clinicians, geneticists, and molecular biologists for this translational research. This project proposes to collect blood samples from patients with common forms of epilepsy (1500 persons) and their parents (3000 persons) over the course of five years. DNA will be extracted from these blood samples and specific genes will be studied for evidence of mutation related to seizure susceptibility. Results from these linkage data demonstrate that an epilepsy susceptibility gene is located on mouse chromosome 1 (Chr.1), and by conserved synteny, human Chr. 1. We identified a variation in a potassium ion channel gene that may represent the seizure susceptibility locus in our animal model. Preliminary data in humans confirms the existence of a variation in the same gene that is associated with seizure disorder. Further genetic analyses will be used to characterize the extent of association between specific gene variation and illness. This will be accomplished by measuring the passage of variations from parents to ill children and searching for those that are inherited by ill children more often than predicted statistically based on classical genetics. We have the ability to identify, ascertain ana analyze DNA samples from hundreds of individuals for these proposed studies. At minimum the identification of epilepsy susceptibility genes will focus further research on distinct mechanisms of seizure initiation and/or propagation. Additionally, identified gene variations will provide molecular markers for use in combination with EEG data for more accurate diagnosis in epilepsy patients. Finally, identification of seizure susceptibility alleles will provide molecular targets for new anticonvulsant drug design.