Identification of Novel Genetic Risk Factors for AD and*
AD 的新遗传风险因素的鉴定和*
基本信息
- 批准号:7118073
- 负责人:
- 金额:$ 44.05万
- 依托单位:
- 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:
- 关键词:African AmericanAlzheimer&aposs diseaseChineseHispanic Americansbiotechnologycaucasian Americanclinical researchdata collection methodology /evaluationdementiafrontal lobe /cortexgene expressiongene mutationgenetic registry /resource /referral centergenetic screeninggenetic susceptibilityhigh throughput technologyhuman genetic material taghuman subjectmedically underserved populationmicroarray technologyneural degenerationnucleic acid sequenceracial /ethnic differencesingle nucleotide polymorphismtau proteinstemporal lobe /cortex disorder
项目摘要
DESCRIPTION (provided by applicant): The identification of the genetic bases of dementias remains an important goal of research whose aims are to improve our understanding and develop new therapeutics for these diseases. The discovery of tau mutations in inherited cases of frontotemporal dementia (FTD) demonstrated that tau dysregulation can cause neurodegenerative disease. But, tau mutations have not been described in AD, and tau mutations account for about 15% of familial FTD cases. An evolving body of work from many groups suggests that genes involved in modifying tau, especially those that modulate tau phosphorylation are enticing candidates for contributing to the genetic risk for these AD and FTD. In cases where tau abnormalities have not been identified on a pathological or genetic basis, dysregulation in key machinery involved in protein processing
and folding apparatus may provide additional genetic risk elements. The goal of this proposal is to identify and confirm these novel genetic risk factors in Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD) using a novel re-sequencing approach that allows massively parallel, cost-effective gene re-sequencing in patients recruited by a multi-center collaborative group of NIA funded ADCs, fully consistent with the stated RFA goals. This approach will allow a tour de force assessment of the hypothesis that these pathways that have been implicated in neurodegenerative disease, and for whom there is a strong underlying biological and pathophysiological rationale are involved, rather than simply testing one gene at a time. Some of these studies will be completed in understudied ethnic minorities, providing important data on sequence variants in populations that have not been studied in this detail and for whom such data is typically not yet available in public or commercial databases. The biomaterials and clinical data from these patients, along with the genetic data obtained will be deposited with the NACC and NCRAD, thus providing an invaluable genetic resource. This data will be integrated with other potential SNPs in a larger set of cases and controls, so as to make maximum use of haplotype information. Association studies will be performed to identify disease-associated variants in FTD and in each ethnic cohort of AD subjects, so as to identify any population specific risk variants that can provide important data that will serve as the foundation for future studies in these groups.
描述(由申请人提供):痴呆症遗传基础的鉴定仍然是研究的一个重要目标,其目的是提高我们对这些疾病的理解并开发新的治疗方法。在遗传性额颞叶痴呆 (FTD) 病例中发现 tau 突变,表明 tau 失调可导致神经退行性疾病。但是,tau 突变在 AD 中尚未被描述,并且 tau 突变约占家族性 FTD 病例的 15%。许多团体的不断发展的工作表明,参与修饰 tau 的基因,尤其是那些调节 tau 磷酸化的基因,是导致这些 AD 和 FTD 遗传风险的诱人候选者。如果在病理或遗传基础上尚未发现 tau 蛋白异常,则涉及蛋白质加工的关键机制出现失调
折叠装置可以提供额外的遗传风险因素。该提案的目标是使用一种新的重测序方法来识别和确认额颞叶痴呆 (FTD) 和阿尔茨海默病 (AD) 中的这些新的遗传风险因素,该方法允许对由 NIA 资助的 ADC 多中心协作小组招募的患者进行大规模并行、经济高效的基因重测序,完全符合既定的 RFA 目标。这种方法将允许对以下假设进行有力的评估:这些通路与神经退行性疾病有关,并且对这些通路有很强的潜在生物学和病理生理学原理的参与,而不是简单地一次测试一个基因。其中一些研究将在未充分研究的少数民族中完成,提供有关尚未进行如此详细研究的人群中序列变异的重要数据,并且这些数据通常尚未在公共或商业数据库中获得。这些患者的生物材料和临床数据以及获得的遗传数据将保存在 NACC 和 NCRAD 中,从而提供宝贵的遗传资源。该数据将与更多病例和对照中的其他潜在 SNP 整合,以便最大限度地利用单倍型信息。将进行关联研究,以确定 FTD 和 AD 受试者的每个种族队列中与疾病相关的变异,从而确定任何人群特定的风险变异,这些变异可以提供重要的数据,为这些群体的未来研究奠定基础。
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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DANIEL H GESCHWIND其他文献
DANIEL H GESCHWIND的其他文献
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{{ truncateString('DANIEL H GESCHWIND', 18)}}的其他基金
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项目 2:H1/H2 单倍型对 FTD 引起的 MAPT 突变驱动的细胞疾病相关表型的影响
- 批准号:
10834336 - 财政年份:2023
- 资助金额:
$ 44.05万 - 项目类别:
UCLA High-Throughput Neuropsychiatric Disorder Phenotyping Center (UCLA HT-NPC)
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- 批准号:
10643541 - 财政年份:2023
- 资助金额:
$ 44.05万 - 项目类别:
Uncovering the Genetic Mechanisms of the Chromosome 17q21.31 Tau Haplotype on Neurodegeneration Risk in FTD and PSP
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- 批准号:
10789246 - 财政年份:2023
- 资助金额:
$ 44.05万 - 项目类别:
Project 2: Impact of H1/H2 haplotypes on cellular disease-associated phenotypes driven by FTD-causing MAPT mutations
项目 2:H1/H2 单倍型对 FTD 引起的 MAPT 突变驱动的细胞疾病相关表型的影响
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10295518 - 财政年份:2021
- 资助金额:
$ 44.05万 - 项目类别:
Uncovering the genetic mechanisms of the Chromosome 17q21.31 Tau haplotype on neurodegeneration risk in FTD and PSP
揭示染色体 17q21.31 Tau 单倍型对 FTD 和 PSP 神经变性风险的遗传机制
- 批准号:
10902613 - 财政年份:2021
- 资助金额:
$ 44.05万 - 项目类别:
Uncovering the genetic mechanisms of the Chromosome 17q21.31 Tau haplotype on neurodegeneration risk in FTD and PSP
揭示染色体 17q21.31 Tau 单倍型对 FTD 和 PSP 神经变性风险的遗传机制
- 批准号:
10295512 - 财政年份:2021
- 资助金额:
$ 44.05万 - 项目类别:
High-throughput Modeling of Autism Risk Genes using Zebrafish - DIVERSITY SUPPLEMENT
使用斑马鱼对自闭症风险基因进行高通量建模 - 多样性补充
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10818861 - 财政年份:2020
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$ 44.05万 - 项目类别:
High-throughput modeling of autism risk genes using zebrafish
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- 批准号:
10478187 - 财政年份:2020
- 资助金额:
$ 44.05万 - 项目类别:
High-throughput modeling of autism risk genes using zebrafish
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- 批准号:
10121604 - 财政年份:2020
- 资助金额:
$ 44.05万 - 项目类别:
High-throughput modeling of autism risk genes using zebrafish
使用斑马鱼进行自闭症风险基因的高通量建模
- 批准号:
10264069 - 财政年份:2020
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$ 44.05万 - 项目类别: