Genomics Core

基因组学核心

• 批准号: 10461089
• 负责人: VIVIANNA M VAN DEERLIN
• 金额: $ 27.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461089
• 关键词: Advisory Committees; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Autopsy; Bioinformatics; Biological; Biological Markers; Blood; Brain; C9ORF72; Cerebrovascular Disorders; Chronology; Clinical; Clinical Trials; Cohort Studies; Collaborations; Collection; Communities; Complex; Counseling; DNA; DNA Methylation; DNA-Binding Proteins; Data; Databases; Deposition; Disease; Doctor of Philosophy; Education; Ensure; Epigenetic Process; Faculty; Family; Family member; Funding; Genes; Genetic; Genetic Counseling; Genome; Genomics; Genotype; Goals; Hereditary Disease; Heterogeneity; Inherited; Longevity; Measurement; Measures; Mission; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Nucleic Acids; Onset of illness; Participant; Pathogenicity; Pathologic; Pathology; Patients; Pennsylvania; Play; Population; Population Heterogeneity; Process; Quality Control; Recording of previous events; Research; Research Personnel; Resistance; Resources; Risk; Role; Sampling; Scientist; Services; Severity of illness; Training; Trans-Omics for Precision Medicine; Universities; Variant; aging brain; alpha synuclein; biobank; brain tissue; career; cohort; data management; data sharing; disease heterogeneity; disorder risk; education research; epigenetic marker; exome; familial Alzheimer disease; genetic analysis; genetic association; genetic counselor; genetic variant; genome-wide; improved; innovation; member; neuroimaging; neuropathology; novel therapeutics; outreach; polygenic risk score; presenilin-1; recruit; resilience; segregation; tau Proteins; trait

GENOMICS CORE SUMMARY Core Leader: Vivianna M. Van Deerlin, MD, PhD; Core Co-leader: Corey T. McMillan, PhD The focus of the University of Pennsylvania (Penn) Alzheimer’s Disease Research Center (ADRC) is to develop a mechanistic understanding of the still evolving complexity of Alzheimer disease (AD) and related dementias (ADRD) by studying the spectrum of disease from earliest onset through progressive stages of disease and ultimately at autopsy. Aside from rare and highly penetrant mutations that cause familial AD, several genetic factors play a critical role for risk of AD/ADRD. Also, epigenetic markers change throughout the lifespan and may contribute to AD heterogeneity by potentially providing resistance to pathology or resilience to clinical progression. The Genetics Core was first funded in 2017 to meet the Penn ADRC’s growing needs of increasing the genetic characterization of the Penn ADRC Cohort and here we propose to transition from traditional genetics to a Genomics Core. The Genomics Core will innovatively incorporate genetics and bioinformatics expertise with the goal of supporting the Penn ADRC mission by providing resources to conduct and support genomics research in collaboration with the other cores through the following Aims: (1) Extract nucleic acid from biosamples for biobanking and sharing; (2) Perform genotyping and generate polygenic risk scores to relate to pathology and downstream processes of AD; (3) Measure DNA methylation and generate epigenetic summary scores like “epigenetic clock”; (4) Screen and counsel patients for hereditary disease; and (5) Enhance diversity in research and education of genetics of AD. We will accomplish these Aims by receiving DNA from Clinical Core subjects through the Biomarker and Neuropathology Cores. DNA banking efforts will be enhanced by the diversity of subjects in the Penn Aging Brain Cohort (ABC) Study that is enriched for African Americans and the collaborating Aging Brain Cohort Dedicated to Diversity (ABCD2). We will closely collaborate with the Data Management and Statistic (DMS) Core to deposit resulting data into the Integrated Neurodegenerative Disease Database. This will enable collaborating Penn ADRC Cores, and through data sharing initiatives other internal and external investigators, to perform genetic association studies of neuroimaging, biofluid biomarkers and clinical progression with the goal of improving our understanding of the complexities and heterogeneity of AD/ADRD and identifying mechanistic candidates for novel therapies. Through these activities we will additionally contribute to the Research and Education Component (REC) by training early career scientists including fellows and junior faculty.

基因组学核心摘要 核心领导人：Vivianna M.货车Deerlin，MD，PhD;核心共同负责人：Corey T. McMillan博士 宾夕法尼亚大学阿尔茨海默病研究中心（ADRC）的重点是 发展对阿尔茨海默病（AD）及其相关疾病仍在发展的复杂性的机械理解 痴呆症（ADRD）通过研究疾病谱从最早发病到进展阶段， 疾病，最后在解剖。除了导致家族性AD的罕见和高度渗透性突变外， 一些遗传因素对AD/ADRD的风险起着关键作用。此外，表观遗传标记在整个过程中发生变化， 寿命，并可能通过潜在地提供对病理学的抵抗力或恢复力而导致AD异质性 临床进展。遗传学核心于2017年首次获得资助，以满足宾夕法尼亚州ADRC日益增长的需求， 增加宾夕法尼亚州ADRC队列的遗传特征，在这里，我们建议从 从传统遗传学到基因组学核心基因组学核心将创新地将遗传学和 生物信息学专业知识，目标是通过提供资源进行支持宾夕法尼亚州ADRC使命 并通过以下目标与其他核心合作支持基因组学研究：（1）提取 用于生物库和共享的生物样本中的核酸;（2）进行基因分型并产生多基因风险 与AD的病理学和下游过程相关的评分;（3）测量DNA甲基化并产生 表观遗传综合评分，如“表观遗传时钟”;（4）筛查和咨询患者的遗传性疾病;以及 (5)加强AD遗传学研究和教育的多样性。我们将通过以下方式实现这些目标： 通过生物标志物和神经病理学核心接收来自临床核心受试者的DNA。DNA库 宾夕法尼亚大学老龄化大脑队列（ABC）研究中受试者的多样性将加强这方面的努力， 为非裔美国人和合作的老龄化大脑队列致力于多样性（ABCD 2）丰富。 我们将与数据管理和统计（DMS）核心密切合作，将结果数据存款 综合神经退行性疾病数据库这将使合作的Penn ADRC核心， 通过与其他内部和外部研究者的数据共享倡议，进行遗传关联研究 神经影像学，生物流体生物标志物和临床进展的目的是提高我们的理解， AD/ADRD的复杂性和异质性，并确定新疗法的机制候选者。 通过这些活动，我们还将通过以下方式为研究和教育部分（REC）做出贡献： 培训早期职业科学家，包括研究员和初级教员。