5 of 7 Epi4K: Multiplex Families & Pairs Project

描述(申请人提供)：无墙Epi4K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。这种改善将以更好的诊断、治疗和治愈的形式出现。为了实现这一目标，Epi4K旨在分析来自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族的基因组。本项目采用的策略是通过研究包含多个个体的家系来丰富遗传对癫痫的影响的研究样本。被研究的家系包括1500对受影响的一级亲属和300个家庭，其中300个家庭包含先前收集并详细表型的三个或三个以上的受影响个体。我们建议定义可能具有不同遗传机制的新的家族性癫痫综合征，对影响癫痫风险的基因组变异进行全面分析，并评估特定临床定义亚组的已识别风险升高变异的影响的特异性。该项目拥有四名PI，他们拥有临床癫痫学、高级表型、癫痫临床和分子遗传学、遗传流行病学和统计遗传学方面的技能、经验和跟踪记录：墨尔本大学的Sam Berkovic博士(联系PI)、哥伦比亚大学的Ruth Ottman博士、Emory大学的Michael Epstein博士和蒙特利尔大学医院的Patrick Cossette对大量样本进行的全面基因组分析，丰富了对癫痫的遗传影响，可能会改变人们对导致这种复杂和异质疾病的路径的理解。 与公共卫生相关：癫痫是最常见的神经系统疾病之一，影响多达4%的人口。尽管遗传因素明显影响癫痫的风险，但人们对涉及的具体基因知之甚少。Epi4K项目将识别导致癫痫的新基因和遗传途径，并将通过改进诊断、治疗和治愈直接造福癫痫患者及其家人。 免责声明：请注意，以下批评是由评审员在研究小组会议之前准备的，基本上是以未经编辑的形式提供的。虽然审查员有机会根据小组的讨论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别批评意见。因此，这些评论可能不能完全反映评审员在小组讨论结束时的最终意见或小组的最终多数意见。因此，讨论纪要和总结是审查员在会议上实际上认为至关重要的最后结论。

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.