GENETIC EPIDEMIOLOGY OF FAMILIAL EPILEPSY

家族性癫痫的遗传流行病学

• 批准号: 6187706
• 负责人: RUTH OTTMAN
• 金额: $ 87.19万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-09 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187706
• 关键词: alleles; clinical research; disease /disorder onset; epilepsy; family genetics; genetic markers; genome; genotype; human subject; linkage mapping; nervous system disorder epidemiology

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).

我们建议继续长期研究基因的作用 癫痫的遗传连锁分析。我们之前的分析 这表明，在大多数家庭中， 癫痫的遗传方式是不确定的。因此，在拟议的 研究，我们将使用分析方法，不需要假设 关于继承方式。 大约195个家庭，其中有2人或2人以上居住在 年龄前发作的特发性/隐源性癫痫患者 25个家庭将被纳入研究（23个家庭已经从我们的 原始数据库，22个额外的家庭包含受影响的兄弟姐妹 从我们的原始数据库中，150个家庭被确定， 我们医疗中心的患者资源）。家族成员的基因型 将在大约400个微卫星标记处确定， 在整个基因组中平均间隔10厘摩分析 的标记等位基因共享相同的血统（IBD）在受影响的亲属 将用于识别可能的基因组区域， 不太可能含有增加特发性/隐源性风险的基因 25岁以前发作的癫痫。在基因组区域， 对于连锁证据，我们将使用多点连锁分析关联 分析，以进一步评估证据。如果有证据表明 获得，我们将探索最有可能导致的表型， 通过分析等位基因共享效应定位易感基因 当表型限于特定的临床亚组时（例如， 全身性癫痫、定位相关性癫痫）。