A MULTICENTER STUDY OF IDIOPATHIC GENERALIZED EPILEPSY
特发性全身性癫痫的多中心研究
基本信息
- 批准号:7145743
- 负责人:
- 金额:$ 48.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1990
- 资助国家:美国
- 起止时间:1990-01-01 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:adolescence (12-20)blood chemistryclinical researchcooperative studydisease /disorder classificationdisease /disorder onsetelectroencephalographyfamily geneticsgene expressiongene frequencygene interactiongeneralized seizuresgenetic markersgenetic polymorphismgenotypehuman genetic material taghuman subjectlinkage mappingmyoclonus epilepsynervous system disorder epidemiologyneurogeneticspolymerase chain reactionracial /ethnic difference
项目摘要
DESCRIPTION (provided by applicant): We made notable progress in finding the genetic causes of adolescent-onset idiopathic generalized epilepsy (IGE). During the last grant period, we: 1) Found 5 IGE-linked loci on chrs. 5p, 5q, 6, 8, & 18. 2) Identified the chr. 18 gene as malic enzyme 2 (ME2), conferring susceptibility to several forms of IGE. 3) Identified case-control sequence differences in intron 1 of ME2. 4) Showed that inhibiting ME2 in brain increases neuroexcitability. 5) Identified the HLA-linked JME chr. 6 locus (EJM1) as the BRD2 gene. 6) Found maternal inheritance of EJM1 in linkage data and population data. 7) Showed BRD2 contains unusual intronic sequences with GC-rich regions seen in other imprinted genes. 8) Development of a BRD2 knockout mouse. 9) Showed BRD2 is highly expressed in brain during development using in-situ hybridization. 10) Found a childhood absence-specific association on chr. 5p in both case-control and family based data. We will exploit these findings to accomplish the following new aims: 1) Categorize SNPs in intron 1 of ME2 to identify susceptibility genotypes; 2) Analyze mRNA processing in ME2 to test the intron 1 finding. 3) Study the enzymatic activity of ME2 derived from IGE patients and compare to activity from control subjects. 3) Test for ME2 expression variants in brain. 4) Test for interaction between the identified genes using SNP and haplotype data. 5) Identify genes on chromosomes 5 and 8. 6) Test if identified genes are IGE susceptibility loci in non-European ethnic groups by looking for association in African-American and Central/South American-origin IGE patients. 7) Determine whether ME2 increases susceptibility to other forms of idiopathic epilepsy (e.g. Rolandic, childhood absence, etc.). The identification of two, and soon a third (the 5p gene), IGE susceptibility genes suggests that we can, in the next grant period, come closer than ever before to understanding some causes of IGE. The ME2 locus findings especially may suggest new directions for epilepsy drug development.
描述(由申请人提供):我们在发现复发性特发性全身性癫痫(IGE)的遗传原因方面取得了显著进展。在上一个研究期间,我们:1)在chrs上发现了5个与IgE连锁的位点。5 p,5 q,6,8和18。2)鉴定出chr.18基因为苹果酸酶2(ME 2),赋予对几种形式IGE的易感性。3)确定ME 2内含子1中的病例对照序列差异。4)显示抑制脑中的ME 2增加神经兴奋性。5)将HLA连锁的JME chr.6位点(EJM 1)鉴定为BRD 2基因。6)在连锁数据和群体数据中发现了EJM 1的母系遗传。7)显示BRD 2包含不寻常的内含子序列,在其他印记基因中看到富含GC的区域。8)BRD 2敲除小鼠的开发。9)原位杂交显示BRD 2在发育过程中在大脑中高度表达。10)在病例对照和基于家庭的数据中发现了chr. 5 p与儿童期缺失的特异性关联。我们将利用这些发现来实现以下新的目标:1)对ME 2内含子1中的SNP进行分类以鉴定易感基因型; 2)分析ME 2中的mRNA加工以检验内含子1的发现。3)研究来自IGE患者的ME 2的酶活性,并与来自对照受试者的活性进行比较。3)测试脑中的ME 2表达变体。4)使用SNP和单倍型数据测试所识别的基因之间的相互作用。5)识别染色体5和8上的基因。6)通过在非裔美国人和中/南美洲起源的IGE患者中寻找相关性,测试所识别的基因是否是非欧洲种族人群中的IGE易感基因座。7)确定ME 2是否会增加对其他形式的特发性癫痫(例如Rolandic,童年缺失等)的易感性。两个IGE易感基因的鉴定,以及第三个IGE易感基因(5 p基因)的鉴定表明,在下一个资助期,我们可以比以往任何时候都更接近了解IGE的一些原因。ME 2位点的发现尤其可能为癫痫药物开发提供新的方向。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DAVID A. GREENBERG其他文献
DAVID A. GREENBERG的其他文献
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{{ truncateString('DAVID A. GREENBERG', 18)}}的其他基金
Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
青少年肌阵挛性癫痫遗传性癫痫易感性机制
- 批准号:
8109724 - 财政年份:2009
- 资助金额:
$ 48.18万 - 项目类别:
Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
青少年肌阵挛性癫痫遗传性癫痫易感性机制
- 批准号:
8286827 - 财政年份:2009
- 资助金额:
$ 48.18万 - 项目类别:
Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
青少年肌阵挛性癫痫遗传性癫痫易感性机制
- 批准号:
7886503 - 财政年份:2009
- 资助金额:
$ 48.18万 - 项目类别:
Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
青少年肌阵挛性癫痫遗传性癫痫易感性机制
- 批准号:
7737552 - 财政年份:2009
- 资助金额:
$ 48.18万 - 项目类别:
Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
青少年肌阵挛性癫痫遗传性癫痫易感性机制
- 批准号:
8099781 - 财政年份:2009
- 资助金额:
$ 48.18万 - 项目类别:
RESOLVING HETEROGENEITY IN EPILEPSY USING GENETIC MARKERS
使用遗传标记解决癫痫的异质性
- 批准号:
6246217 - 财政年份:1997
- 资助金额:
$ 48.18万 - 项目类别:
A MULTICENTER STUDY OF IDIOPATHIC GENERALIZED EPILEPSY
特发性全身性癫痫的多中心研究
- 批准号:
2266672 - 财政年份:1995
- 资助金额:
$ 48.18万 - 项目类别:
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