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

路易体痴呆和额颞叶痴呆的基因组测序：阿尔茨海默病和相关痴呆研究的公共资源

• 批准号: 10005769
• 负责人: Bryan Traynor
• 金额: $ 5.41万
• 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/10005769
• 关键词: 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; Lead; Learning; Lewy Body Dementia; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurosciences; Onset of illness; Parkinson Disease; Patients; Personal Satisfaction; Phenotype; Process; Research; Research Personnel; Resources; Risk; Services; Syndrome; Technology; Testing; Time; United States National Institutes of Health; Universities; Work; aging brain; cohort; computing resources; cost; cost effective; drug development; drug discovery; effective intervention; frontotemporal lobar dementia-amyotrophic lateral sclerosis; gene discovery; genetic analysis; genome sequencing; genomic data; improved; insight; model design; nervous system disorder; neurogenetics; online resource; risk variant; sequencing platform; targeted treatment; therapeutic target

The Intramural Research Program is the ideal environment to undertake a project of this magnitude. The Laboratory of Neurogenetics has demonstrated expertise in handling large genomic datasets and has an exemplary track record of gene discovery. It is also remarkably cost effective to undertake this project within the Intramural Research Program. This project will place the Intramural Research Program at the forefront of dementia research and will greatly accelerate the pace of genetic discovery within the field. Specific Aim 1: We will perform genome sequencing of 3,000 LBD cases, 3,000 FTD cases and 2,500 neurologically normal control subjects. The Uniformed Services University will perform the sequencing using the Illumina X10 Sequencing platform. Specific Aim 2: We will analyze the genome sequence data generated from specific aim 1. The purpose of these analyses is to identify genetic loci that alter risk of developing disease and age at disease onset (i.e. genetic modifiers of phenotype). Specific Aim 3: We will make the genome sequence data generated from specific aim 1 publicly available. No embargo will be placed on access to the genome sequence data. These data will be 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 disease (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 is to establish a public resource that will accelerate high quality research within the field, and that will grow over time (Goal G and H).

壁内研究计划是进行此类项目的理想环境。神经遗传学实验室在处理大型基因组数据集方面具有专业知识，并且具有基因发现的典范记录。在壁内研究计划中进行该项目也非常有效。该项目将使壁内研究计划处于痴呆症研究的最前沿，并将大大加快该领域的遗传发现速度。 具体目标1：我们将对3,000例LBD病例，3,000例FTD病例和2,500名神经系统正常对照受试者进行基因组测序。统一的服务大学将使用Illumina X10测序平台进行测序。 特定目的2：我们将分析从特定目的1产生的基因组序列数据。这些分析的目的是确定改变疾病发作时疾病和年龄风险的遗传基因座（即表型的遗传修饰符）。 特定目的3：我们将使从特定目标1公开可用的基因组序列数据产生。对基因组序列数据的访问不会放禁止禁运。这些数据将是一种新的在线资源的基石，研究人员可以访问，分析和结合自己的数据，以增加其检测新遗传基因座的能力。这样，这个独特的数据库将随着时间的推移而增强，并将大大加速该领域的遗传发现速度。 我们的基因组测序项目与NIA的战略目标一致。它旨在通过揭示痴呆症的复杂生物学（目标A）来了解衰老过程的动态。通过提高我们对衰老大脑，阿尔茨海默氏病和其他神经退行性疾病（目标D）来改善我们对成年人年龄的了解，从而阐明了痴呆症的生物学将改善成年人随着年龄的增长的健康，福祉和独立性（目标D）。我们还希望学习痴呆症基础的遗传学将为药物发现提供治疗靶标，并最终导致有效的干预措施的发展（目标C）。该项目的目的是建立一种将在该领域加速高质量研究的公共资源，并随着时间的推移而增长（目标G和H）。