MULTICENTER STUDY OF IDIOPATHIC GENERALIZED EPILEPSY

描述(申请人摘要)：这项研究将确定涉及的基因座 特发性全身性癫痫(IGE)的表现及探讨 他们的互动。在之前的资助期间，我们：1)完成了基因组 扫描免疫球蛋白基因座；2)发现至少4个免疫球蛋白基因位置；3) 青少年肌阵挛癫痫患者表现出并部分解决了异质性 (JME)；4)将EJM1的候选基因座数量缩小到7个；5)发现 有证据表明JME在高加索人和非高加索人中可能是不同的。追求 在这些发现中，我们有以下目标： 1.确定患有青春期免疫球蛋白E的家庭。2.联动测试 5、8和18.3号染色体上的基因座的异质性。进一步的测试 有希望但不那么显著的Lod得分的基因座连锁的证据 染色体6q和1.4。确定基因和基因之间的关系 癫痫发作的表达，连锁信号与癫痫发作类型的相关性 这些家庭。5.检测JME的非EJM1类型是否定位于染色体6q。6. 检测非高加索人群中由EJM1引起的JME频率是否与 在高加索人。7.确定7个候选基因座中的哪一个是EJM1。8.精细制图 关于第5、8和18号染色体上的候选区域。令人兴奋的先前 结果表明，我们现在可能已经定位了许多青少年发病的基因 伊格。我们将使用链接和人口研究来确定如何 基因座之间的相互作用会影响癫痫发作类型，并最终 确定实际的疾病部位，描绘这些部位是如何产生癫痫的。

DESCRIPTION (Applicant's Abstract): 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.