Genome sequencing of Lewy Body Dementia and Frontotemporal Dementia: a public resource for the study of Alzheimer's disease and related dementias

路易体痴呆和额颞叶痴呆的基因组测序：研究阿尔茨海默病和相关痴呆的公共资源

• 批准号: 10913165
• 负责人: Bryan Traynor
• 金额: $ 27.27万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10913165
• 关键词: Acceleration; Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Biology; Complex; Congresses; Data; Databases; Defect; Dementia; Development; Diagnosis; Disease; Disease model; Drug Targeting; Environment; Etiology; Evolution; Frontotemporal Dementia; Genes; Genetic; Genetic Research; Genetic Risk; Genome; Goals; Health; Human Genome; Intramural Research Program; Knowledge; Laboratories; Learning; Lewy Body Dementia; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurosciences; Onset of illness; Paper; Parkinson Disease; Pathogenesis; Patients; Personal Satisfaction; Phenotype; Process; Publishing; Research; Research Personnel; Resources; Risk; Role; Syndrome; Technology; Testing; Time; United States National Institutes of Health; Variant; Work; aging brain; cohort; computing resources; cost; database of Genotypes and Phenotypes; design; drug development; drug discovery; effective intervention; frontotemporal lobar dementia amyotrophic lateral sclerosis; genome sequencing; genomic locus; improved; insight; nervous system disorder; neurogenetics; novel; online resource; risk variant; sequencing platform; targeted treatment; therapeutic target; web portal

The Intramural Research Program is the ideal environment to undertake a project of this magnitude. This project places the Intramural Research Program at the forefront of dementia research and will greatly accelerate the pace of genetic discovery within the field. We performed genome sequencing of 3,000 LBD cases, 3,000 FTD cases and 2,500 neurologically normal control subjects using the Illumina X10 Sequencing platform. We analyzed the genome sequence data to identify genetic loci that alter the risk of developing disease and age at disease onset (i.e. genetic modifiers of phenotype). We have made the genome sequence data generated from this project publicly available on the dbGaP and AMP-PD web portals. These data act as the cornerstone of a new online resource that researchers can access, analyze, and combine with their own data to increase their power to detect new genetic loci. In this way, this unique database will be augmented over time and will greatly accelerate the pace of genetic discovery within the field. Our genome sequencing project is consistent with the strategic goals of the NIA. It aims to understand the dynamics of the aging process by unraveling the complex biology of dementia (Goal A). Unraveling the biology underlying dementia will improve the health, well-being and independence of adults as they age by improving our understanding of the aging brain, Alzheimer's disease, and other neurodegenerative diseases (Goal D). We also hope that learning the genetics underlying dementia will provide therapeutic targets for drug discovery and ultimately lead to the development of effective interventions (Goal C). The intent of this project was to establish a public resource that will accelerate high-quality research within the field, and that will grow over time (Goal G and H). The work on this project is ongoing and is being extended.

校内研究计划是开展如此规模的项目的理想环境。该项目将校内研究计划置于痴呆症研究的前沿，并将大大加快该领域基因发现的步伐。我们使用 Illumina X10 测序平台对 3,000 个 LBD 病例、3,000 个 FTD 病例和 2,500 个神经系统正常对照受试者进行了基因组测序。我们分析了基因组序列数据，以确定改变患病风险和发病年龄的基因位点（即表型的遗传修饰因子）。我们已在 dbGaP 和 AMP-PD 门户网站上公开提供该项目生成的基因组序列数据。这些数据是新在线资源的基石，研究人员可以访问、分析并与自己的数据相结合，以增强检测新基因位点的能力。通过这种方式，这个独特的数据库将随着时间的推移而不断扩大，并将大大加快该领域基因发现的步伐。 我们的基因组测序项目与 NIA 的战略目标是一致的。它旨在通过揭示痴呆症的复杂生物学原理来了解衰老过程的动态（目标 A）。揭示痴呆症背后的生物学原理将通过提高我们对大脑老化、阿尔茨海默病和其他神经退行性疾病的了解来改善成年人的健康、福祉和独立性（目标 D）。我们还希望了解痴呆症的遗传学将为药物发现提供治疗靶点，并最终导致有效干预措施的开发（目标C）。该项目的目的是建立一个公共资源，以加速该领域的高质量研究，并随着时间的推移而不断发展（目标 G 和 H）。 该项目的工作正在进行中并正在扩展。