Overcoming Genetic Heterogeneity in the Epilepsies

克服癫痫的遗传异质性

基本信息

批准号：
7236037
负责人：
JOCELYN F BAUTISTA
金额：
$ 13.5万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7236037
关键词：
Address Affect Age of Onset Biomedical Engineering Blood specimen Chromosome Mapping Chronic Classification Clinical Clinical Investigator Complex Data Analyses Data Collection Defect Development Development Plans Diagnosis Disease Electroencephalography Epilepsy Epileptogenesis Extended Family Familiarity Family Family history of Frequencies Genes Genetic Genetic Heterogeneity Genome Goals Heterogeneity Human Individual Knowledge Lead Measures Mentored Patient-Oriented Research Career Development Award Mentorship Methods Modeling Molecular Genetics Nature Neurologist Nuclear Family Numbers Phenotype Predisposition Prevention Prevention approach Process Recording of previous events Recurrence Relative (related person)Research Research Personnel Risk Role Seizures Severities Susceptibility Gene Syndrome Techniques Training Work base career design expectation experience genetic analysis genetic epidemiology genetic linkage analysis genetic pedigree improved innovation instrument medical specialties member multidisciplinary nervous system disorder neurophysiology novel novel strategies programs tool trait

项目摘要

DESCRIPTION (provided by applicant): In recent years genes for several rare, monogenic epilepsy syndromes have been discovered, but identifying genes involved in the more common, complex human epilepsies has been more difficult. Linkage studies performed to date have focused on homogeneous families with affected status based on syndromic classification. Less is known about how to analyze the overlap between epilepsy syndromes or how to address the phenotypic heterogeneity seen within an individual family. Evidence suggests that epilepsy involves susceptibility genes that influence overall risk for recurrent seizures, as well as modifier genes that influence the phenotypic features of epilepsy, such as seizure type, age of onset, seizure frequency and seizure severity. Understanding the inheritance of individual components of the epilepsy phenotype is a key step to understanding heterogeneity in the human epilepsies, and to identifying novel disease genes in the presence of such heterogeneity. The objective of this Mentored Patient-Oriented Research Career Development Award is to use novel methods of linkage analysis and epilepsy phenotyping to overcome genetic heterogeneity in gene mapping efforts. The parallel objective is to develop the applicant into an independent clinical investigator in the genetic epidemiology of epilepsy through experience in the design, data collection and data analysis of family-based genetic studies. The applicant will pursue the following Specific Aims: 1) To determine the familiarity of phenotypic features of epilepsy, 2) To evaluate electrophysiological traits as markers of epilepsy, and 3) To identify genetic loci underlying phenotypic features of epilepsy. The applicant, who is trained as a clinical neurologist with specialty training in epilepsy and clinical neurophysiology, will pursue further training in genetic epidemiology and statistical genetics as part of the career development plan. The work proposed will be significant in that it will introduce new tools in the search for epilepsy disease loci in the common, complex epilepsies. Drs. Elston, Wang, Luders, Burgess, lyengar and Ottman will provide mentorship and guidance of a multidisciplinary nature encompassing clinical epilepsy, clinical neurophysiology, biomedical engineering, genetic epidemiology, statistical genetics and molecular genetics.

描述（由申请人提供）：近年来，已经发现了几种罕见的单基因癫痫综合征的基因，但是鉴定涉及更常见，复杂的人类癫痫涉及的基因更加困难。迄今为止进行的连锁研究集中于基于综合征分类的均质家庭。关于如何分析癫痫综合征之间的重叠或如何解决单个家庭中看到的表型异质性的重叠知之甚少。有证据表明，癫痫涉及影响复发性癫痫发作的总体风险的易感基因，以及影响癫痫表型特征的修饰基因，例如癫痫发作类型，发作年龄，发作频率和癫痫发作严重程度。了解癫痫表型的单个成分的遗传是理解人癫痫中异质性的关键步骤，并在存在这种异质性的情况下鉴定新的疾病基因。这个受过指导的注重患者的研究职业发展奖的目的是使用新颖的链接分析方法和癫痫表型来克服基因映射工作中的遗传异质性。平行目标是通过在基于家庭的遗传研究的设计，数据收集和数据分析方面的经验，将申请人发展为癫痫遗传病学的独立临床研究者。申请人将追求以下特定目的：1）确定癫痫的表型特征的熟悉程度，2）评估电生理特征作为癫痫的标志物，以及3）识别癫痫病的基因型基因座的遗传位点。申请人接受了癫痫和临床神经生理学专业培训的临床神经科医生，将作为职业发展计划的一部分进行进一步的遗传流行病学和统计遗传学培训。提出的工作将很重要，因为它将引入新的工具，以寻找常见的复杂癫痫病中的癫痫疾病基因座。博士。 Elston，Wang，Luders，Burgess，Lyengar和Ottman将提供涵盖临床癫痫，临床神经生理学，生物医学工程，遗传流行病学，统计遗传学和分子遗传学的多学科性质的指导和指导。