The Epilepsy Phenome/ Genome Project (EPGP)

癫痫表型组/基因组计划 (EPGP)

基本信息

批准号：
7197009
负责人：
DANIEL H LOWENSTEIN
金额：
$ 400.13万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7197009
关键词：
Address Affect Age Alleles Antiepileptic Agents Arts Benchmarking Biological Biological Assay Brain Candidate Disease Gene Cell Line Cerebrum Clinical Cognitive deficits Commit Computing Methodologies Consent Copy Number Polymorphism Cortical Malformation Country Craniocerebral Trauma Cryptogenic Epilepsies Custom DNA DNA Sequence Rearrangement Data Data Collection Databases Development Diagnosis Disease Enrollment Epilepsy Epileptogenesis Ethnic Origin Family Frequencies Funding Future Gastaut syndrome Gender Generalized Epilepsy Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Genome Genomics Genotype Germ Lines Grant Human Genetics Individual Infantile spasms Infection Inherited Institutes Institution Investigation Knowledge Link Lymphocyte Medical Methodology Mutation Neurodevelopmental Impairment Nucleotides Numbers Operative Surgical Procedures Parents Partial Epilepsies Pathway interactions Patients Pattern Pharmaceutical Preparations Phase Phenotype Point Mutation Population Protocols documentation Quality of life Race Range Recruitment Activity Refractory Relative Risks Research Research Design Research Infrastructure Research Personnel Research Project Grants Resources Risk Role Sampling Scientist Screening procedure Seizures Siblings Single Nucleotide Polymorphism Specific qualifier value Statistically Significant Stroke Study Subject Technology Testing Therapeutic Unbalanced Translocation United States Variant Work acquired factor analytical method base comparative genomic hybridization density design early onset follow-up genetic pedigree genetic variant genome wide association study genome-wide linkage imprint improved nervous system disorder neuronal excitability novel outcome forecast repository response social

项目摘要

DESCRIPTION (provided by applicant): Epilepsy is one of the most common neurological disorders and has enormous impact, both medical and social, for the individual as well as for the family. Treatments developed for epilepsy have largely been empirical rather than derived from knowledge of basic mechanisms, because the mechanisms underlying seizure occurrence and epileptogenesis are poorly understood. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, national, multi-institutional, collaborative research project aimed at advancing our understanding of the genetic basis of the most common forms of idiopathic and cryptogenic epilepsies and a subset of symptomatic epilepsy; i.e. epilepsies that are probably related to genetic predispositions or developmental anomalies rather than endogenous, acquired factors such as CNS infection, head trauma or stroke. The overall strategy of EPGP is to collect detailed, high quality phenotypic information on 3,750 epilepsy patients and 3,000 controls, and to use state-of-the-art genomic and computational methods to identify the contribution of genetic variation to: 1) the epilepsy phenotype, 2) developmental anomalies of the brain, and 3) the varied therapeutic response of patients treated with AEDs. The EPGP Consortium was formed 3 years ago and is comprised of 15 U.S. academic institutions and organized into administrative and scientific cores. Through funding from a planning grant, the Consortium has already planned enrollment protocols, data collection methods, analytical approaches, and much of the infrastructure necessary for carrying out the proposed studies. The application of powerful high-throughput methodologies will permit us to efficiently perform the large- scale genotyping and other analyses described in this application. These studies will allow us to address critical unresolved questions concerning the underlying genomic mechanisms behind the most common forms of epilepsy, which are poorly understood, and to advance our understanding of the genetics of variable drug response. Timely data-sharing and the establishment of patient cell lines through the NINDS Human Genetics Repository will greatly facilitate the work of other epilepsy investigators throughout the country. Importantly, EPGP directly matches one of the high-priority, strategic objectives of NINDS as specified in Benchmark B2 of the Benchmarks for Epilepsy Research: "Organize a national group of scientists to work together in search of genes that might contribute to epilepsy by doing a large screening project that links people with epilepsy to particular gene patterns."

描述（由申请人提供）：癫痫是最常见的神经系统疾病之一，对个人和家庭都具有巨大的医学和社会影响。用于癫痫的治疗方法在很大程度上是经验的，而不是源于基本机制的知识，因为癫痫发作的发生和癫痫发生的机制知之甚少。癫痫现象/基因组项目（EPGP）是一个大规模的，民族的，多机构的协作研究项目，旨在促进我们对最常见的特发性和隐态性癫痫的遗传基础的理解和症状性癫痫的子集；即可能与遗传易感性或发育异常有关的癫痫病，而不是内源性的，可获得的因素，例如中枢神经系统感染，头部外伤或中风。 EPGP的总体策略是收集有关3,750名癫痫患者和3,000例对照的详细的高质量表型信息，并使用最先进的基因组和计算方法来确定遗传变异对：1）癫痫表型的贡献，2）大脑的发育异常，以及3）用AED治疗的患者的各种治疗反应。 EPGP财团由3年前组成，由15个美国学术机构组成，并组织成行政和科学核心。通过计划赠款的资助，该财团已经计划了入学方案，数据收集方法，分析方法以及进行拟议研究所需的许多基础设施。强大的高通量方法的应用将使我们能够有效执行本应用程序中描述的大规模基因分型和其他分析。这些研究将使我们能够解决有关最常见的癫痫形式背后的基本基因组机制的关键问题，这些癫痫的理解很少，并促进了我们对可变药物反应遗传学的理解。及时的数据共享和通过Ninds人类遗传学存储库建立患者细胞系将极大地促进全国其他癫痫研究人员的工作。重要的是，EPGP与癫痫研究基准B2中指定的NIND的高优先级，战略目标之一直接与癫痫研究的高优先级，战略目标匹配：大型筛查项目将癫痫患者与特定基因模式联系起来。”