5 of 7 Epi4K: Multiplex Families & Pairs Project

5 of 7 Epi4K：多重系列

• 批准号: 8241181
• 负责人: Samuel Frank Berkovic
• 金额: $ 33.6万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241181
• 关键词: Address; Affect; Age; Area; Clinical; Code; Complex; Critiques; Data Set; Development; Diagnosis; Diagnostic; Disease; Epilepsy; Evaluation; Family; Family Study; Family member; Febrile Convulsions; First Degree Relative; Focal Seizure; Functional RNA; Generalized Epilepsy; Genes; Genetic; Genetic Research; Genome; Genomics; Genotype; Goals; Human; Individual; Knowledge; Lead; Life; Medicine; Molecular Genetics; Neurology; Nucleotides; Parents; Partial Epilepsies; Pathway interactions; Patients; Personal Satisfaction; Phenotype; Population; Predisposition; Relative (related person); Research; Research Personnel; Risk; Sampling; Sampling Studies; Scientific Advances and Accomplishments; Seizures; Series; Siblings; Specificity; Study Section; Subgroup; Syndrome; Universities; Update; Variant; Work; Writing; base; clinical phenotype; effective therapy; experience; follow-up; genetic analysis; genetic epidemiology; genetic risk factor; genome sequencing; human disease; improved; insight; meetings; nervous system disorder; next generation; offspring; phenome; segregation; skills

DESCRIPTION (provided by applicant): The primary goal of the Epi4K Center Without Walls Is to Increase understanding of the genetic basis of human epilepsy in order to improve the well-being of patients and family members living with these disorders. This improvement will come in the form of better diagnostics, treatments and cures. To accomplish this goal, Epi4K aims to analyze the genomes of a large number of well-phenotyped epilepsy patients and families collected by investigators from several major research groups. The strategy used in this project (5 of 7 - Multiplex Families & Pairs) is to enrich the study sample for genetic influences on epilepsy by studying families containing multiple individuals. The families to be studied include 1500 pairs of affected first-degree relatives and 300 families containing three or more affected individuals previously collected and phenotyped in detail. We propose to define new familial epilepsy syndromes likely to have distinct genetic mechanisms, perform comprehensive analyses of genomic variation influencing risk for epilepsy, and assess the specificity of effect o identified risk-raising variants for specific clinically defined subsets. The project has four PIs ith skills, experience and track record in clinical epileptology, high level phenotyping, clinical and molecular genetics of epilepsy, genetic epidemiology and statistical genetics: Drs. Sam Berkovic of University of Melbourne (contact PI), Ruth Ottman of Columbia University, Michael Epstein of Emory University and Patrick Cossette of Centre Hospitaller de I'Universite de Montreal This comprehensive genomic analysis of a large sample enriched for genetic influences on epilepsy is likely to transform understanding of the pathways leading to this complex and heterogeneous disorder. PUBLIC HEALTH RELEVANCE: .Epilepsy is one of the most common neurologic disorders, affecting up to 4% of the population. Although inherited factors clearly influence risk for epileps, little is known about the specific genes Involved. The Epi4K project will Identify new genes and genetic pathways leading to epilepsy and will directly benefit individuals with epilepsy and their families through improved diagnosis, treatments, and cures. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.

Epi4K无墙中心的主要目标是增加对人类癫痫遗传基础的了解，以改善患有这些疾病的患者和家庭成员的福祉。这种改进将以更好的诊断、治疗和治愈的形式出现。为了实现这一目标，Epi4K旨在分析由几个主要研究小组的研究人员收集的大量表型良好的癫痫患者和家庭的基因组。本项目中使用的策略（7个多重家庭和配对中的5个）是通过研究包含多个个体的家庭来丰富癫痫遗传影响的研究样本。待研究的家庭包括1500对受影响的一级亲属和300个家庭包含三个或更多的受影响的个人以前收集和表型的详细。我们建议定义新的家族性癫痫综合征可能有不同的遗传机制，进行全面的基因组变异影响癫痫风险的分析，并评估特定的临床定义的子集的风险提高的变种的效果的特异性。该项目有四名PI，他们在临床癫痫学，高水平表型，癫痫的临床和分子遗传学，遗传流行病学和统计遗传学方面具有技能，经验和记录：墨尔本大学的萨姆·贝尔科维奇博士（联系PI），来自哥伦比亚大学的Ruth Wellman，埃默里大学的迈克尔·爱泼斯坦和蒙特利尔大学中心医院的帕特里克·科塞特对一个大的富含癫痫遗传影响的样本可能会改变对导致这种复杂和异质性疾病的途径的理解。 公共卫生相关性：癫痫是最常见的神经系统疾病之一，影响高达4%的人口。虽然遗传因素明显影响癫痫的风险，但对涉及的特定基因知之甚少。Epi4K项目将识别导致癫痫的新基因和遗传途径，并通过改进诊断，治疗和治愈直接使癫痫患者及其家人受益。 免责声明：请注意，以下评论是由审查员在研究部分会议之前准备的，并且以基本上未经编辑的形式提供。 虽然审查人员有机会根据小组讨论情况更新或修订其书面评价，但不能保证在会议讨论之后更新了个人评论。 因此，评论可能无法完全反映小组讨论结束时个人评论者的最终意见或小组的最终多数意见。因此，讨论的简历和摘要是评审员在会议上实际认为关键的最后一句话。