Genetic Influences on human Epilepsy

遗传对人类癫痫的影响

• 批准号: 6333608
• 负责人: Russell J BUONO
• 金额: $ 51.55万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6333608
• 关键词: chromosomes; electroencephalography; epilepsy; family genetics; gene expression; genetic disorder; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; linkage disequilibriums; linkage mapping; magnetic resonance imaging; neuropsychological tests; northern blottings; nucleic acid sequence; patient oriented research; polymerase chain reaction; protein structure function; single strand conformation polymorphism; statistics /biometry

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.

利用临床医生，遗传学家和分子生物学家的专业知识，正在采用一种多学科的方法。 该项目建议在五年的时间内从具有常见形式的癫痫病（1500人）及其父母（3000人）的患者那里收集血液样本。 将从这些血液样本中提取DNA，并将研究特定基因以证明与癫痫发作相关的突变证据。 这些连锁数据的结果表明，癫痫敏感性基因位于小鼠染色体1（Chr.1）上，并通过保守的同义，人类Chr。 1。我们确定了钾离子通道基因的变异，该变异可能代表我们动物模型中的癫痫敏感性基因座。人类的初步数据证实了与癫痫发作障碍相关的同一基因中存在变异。 进一步的遗传分析将用于表征特定基因变异与疾病之间的关联程度。 这将通过衡量从父母到生病的孩子的变化通过，而不是基于经典遗传学的统计学上的预测，而搜索患病儿童遗传的变化的经历更频繁。 我们有能力识别，确定ANA分析来自数百个个体的DNA样本进行这些提出的研究。 至少鉴定癫痫敏感性基因将进一步研究癫痫发作和/或传播的不同机制。此外，鉴定的基因变异将提供分子标记物与脑电图数据结合使用，以在癫痫患者中更准确地诊断。 最后，鉴定癫痫敏感性等位基因将为新的抗惊厥药设计提供分子靶标。