Genomics Core

基因组学核心

基本信息

批准号：
10663890
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
项目类别：
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/10663890
关键词：
Acceleration Advisory Committees African American population Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos 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 Library DNA Methylation DNA-Binding Proteins Data Databases Dedications Dementia 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 protein TDP-43 recruit resilience segregation statistics tau Proteins trait

项目摘要

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者：Vivianna M. Van Deerlin，医学博士、博士核心联合领导者：Corey T. McMillan，博士；宾夕法尼亚大学 (Penn) 阿尔茨海默病研究中心 (ADRC) 的重点是对阿尔茨海默病（AD）及相关疾病仍在不断发展的复杂性形成机制理解痴呆症（ADRD），通过研究从最早发病到进展阶段的疾病谱除了导致家族性 AD 的罕见且高度外显的突变之外，一些遗传因素对 AD/ADRD 风险也起着关键作用，表观遗传标记在整个过程中都会发生变化。寿命，并可能通过潜在地提供对病理或恢复的抵抗力来促进 AD 异质性遗传学核心于 2017 年首次获得资助，以满足宾夕法尼亚大学 ADRC 不断增长的需求。增加 Penn ADRC 队列的遗传特征，在这里我们建议从基因组学核心将创新性地将遗传学与基因组学相结合。生物信息学专业知识，目标是通过提供资源来支持宾夕法尼亚州 ADRC 的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 (2) 进行基因分型并产生多基因风险 (3) 测量DNA甲基化并生成表观遗传总结评分，如“表观遗传时钟”；(4) 筛查遗传性疾病并为其提供咨询； (5) 增强 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。通过生物标记和神经病理学 DNA 库接收临床核心受试者的 DNA。宾夕法尼亚大学老龄化大脑队列 (ABC) 研究中的努力对象的多样性将增强这一点为非裔美国人和致力于多样性的老龄化大脑队列 (ABCD2) 进行了丰富的研究。我们将与数据管理和统计（DMS）核心密切合作，将结果数据存入综合神经退行性疾病数据库将实现宾夕法尼亚大学 ADRC 核心的合作，以及通过数据共享计划与其他内部和外部研究人员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研究，目的是提高我们对 AD/ADRD 的复杂性和异质性，并确定新疗法的候选机制。通过这些活动，我们还将为研究和教育部分（REC）做出贡献：培训早期职业科学家，包括研究员和初级教师。