This study will identify the loci involved in the expression of idiopathic generalized epilepsy (IGE) and investigate their interactions. In the previous grant period, we: 1) Completed a genome scan for loci of IGE; 2) Discovered at least 4 locations of genes for IGE; 3) Demonstrated and partly resolved heterogeneity in Juvenile Myoclonic Epilepsy (JME); 4) Narrowed the number of candidate loci for EJM1 to seven; 5) Found evidence that JME may be different in Caucasians and non-Caucasians. Pursuing these findings, we have the following aims: 1. Ascertain families with adolescent-onset forms of IGE. 2. Test for linkage heterogeneity at the loci on chromosomes 5, 8, and 18. 3. Test for further evidence of linkage at loci with promising but less significant lod scores on chromosomes 6q and 1. 4. Determine the relationship between genotype and seizure expression, correlating the linkage signal with the seizure types in the families. 5. Test whether non-EJM1 forms of JME map to chromosome 6q. 6. Test whether the frequency of JME due to EJM1 in non-Caucasians is the same as in Caucasians. 7. Determine which of 7 candidate loci is EJM1. 8. Fine-mapping on the candidate regions on chromosomes 5, 8, and 18. The exciting previous results suggest we may now have located many of the genes for adolescent-onset IGE. We will use the linkage and population studies to determine how interactions between the loci influence seizure type and, by eventually determining the actual disease loci, delineate how these loci produce seizures.
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