GENETIC EPIDEMIOLOGY OF FAMILIAL EPILEPSY

我们建议继续我们对遗传贡献的长期研究 通过进行遗传连锁分析来诊断癫痫。我们之前的分析 这表明，在大多数家庭中，包含多个具有 癫痫的遗传方式尚不确定。因此，在建议的 研究中，我们将使用不需要假设的分析方法 关于继承的方式。 大约195个家庭，有等于或超过2个生活费 在年龄之前发病的特发性/隐源性癫痫患者 25个将包括在研究中(23个家庭已经从我们的 原始数据库，包含受影响兄弟姐妹的另外22个家庭 来自我们原始数据库的配对和150个待确定的家庭 我们医疗中心的患者资源)。家系成员的基因分型 将在大约400个间隔为 整个基因组的平均间隔为10厘米。分析 在患病亲属中共有相同血统(IBD)的标记等位基因的比例 将用于识别可能的基因组区域，并排除区域 不太可能，包含增加特发性/隐匿性基因风险的基因 发病年龄在25岁之前的癫痫。在基因组区域有提示作用 对于连锁的证据，我们将使用多点连锁分析关联 分析，以进一步评估证据。如果存在关联的证据是 ，我们将探索最可能导致的表型 分析易感基因对等位基因共享的影响 当表型限于特定的临床亚组时(例如， 全身性癫痫、定位相关癫痫)。

We propose to continue our long-term study of the genetic contributions to epilepsy by performing genetic linkage analysis. Our previous analyses indicate that in most families containing multiple individuals with epilepsy, the mode of inheritance is uncertain. Thus in the proposed study, we shall use analytic approaches that do not require assumptions about mode of inheritance. Approximately 195 families containing equal to or greater than 2 living individuals with idiopathic/cryptogenic epilepsy with onset prior to age 25 will be included in the study (23 families already collected from our original database, 22 additional families containing affected sibling pairs from our original database, and 150 families to be ascertained from the patient resources at our medical center). Genotypes in family members will be determined at approximately 400 microsatellite markers spaced at an average of 10 centimorgan intervals throughout the genome. Analysis of marker alleles shared identical-by-descent (IBD) in affected relatives will be used to identify genomic regions likely, and exclude regions unlikely, to contain genes raising risk for idiopathic/cryptogenic epilepsy with onset prior to age 25. In genomic regions with suggestive evidence for linkage, we will use multipoint linkage analysis association analysis to assess the evidence further. If evidence for linkage is obtained, we will explore the phenotypes most likely to result from the mapped susceptibility genes by analysis of the effect on allele sharing when the phenotype is restricted to specific clinical subgroups (e.g., generalized epilepsy, localization-related epilepsy).