Genetic Core H

宾夕法尼亚大学阿尔茨海默病核心中心 摘要：修订以创建新的遗传学核心(核心H) ADCC主任兼首席调查员：John Q.Trojanowski，医学博士 遗传学核心负责人：Vivianna Van Deerlin，医学博士；联合负责人：Gerard Schellenberg，博士 这是宾夕法尼亚大学(宾夕法尼亚大学)阿尔茨海默病核心中心的修订申请 (ADCC)建立一个独立的遗传学核心(核心H)。我们建议创建一个遗传学核心，它将 加强和扩大宾夕法尼亚大学ADCC的遗传学活动。宾夕法尼亚大学ADCC的重点是开发一种 对阿尔茨海默病(AD)和相关痴呆仍在发展中的复杂性的机械性理解 (ADRD)通过研究从最早的发病到疾病的进展阶段和 最终在尸检时。遗传因素在AD和相关痴呆(RD)的风险中起着关键作用 包括路易体痴呆和额颞部退行性变，它们都有共同的发病机制 阿尔茨海默病的神经退行性变。此外，许多患者具有不止一种临床或病理表型。 临床诊断为AD的患者中有20%-30%没有AD病理，而是表现为RD。 因此，拟议的遗传核心将支持宾夕法尼亚ADCC的使命，提供必要的 资源，包括Vivianna Van Deerlin和Gerard Schellenberg的领导力和遗传学专业知识， 与现有核心合作开展和支持ADRD的分子遗传学研究。对这件事 最后，Core H的具体目标是：1)作为从临床Core B收集的DNA的存储库 参与者和以神经病理核心D为特征的尸检大脑。收集的样本将接受 质量控制和血统措施，将供宾夕法尼亚大学调查人员和外部人员使用 合作者，包括向NCRAD发货；2)与ADRD相关的基因风险因子变体 在宾夕法尼亚大学研究中用作协变量的ADRD、MCI和对照受试者的临床核心B队列，包括 APOE和其他以前识别的危险因素基因座使用各种方法。此外，执行遗传操作 ADRD患者遗传性神经退行性疾病相关基因分析 与数据一起存储和处理遗传数据和样本数据的集中资源 管理、生物信息学和生物统计学核心C；4)为患者和社区教育工作作出贡献 通过向临床核心B提供遗传咨询服务，扩展和招聘核心E 参与者和研究教育核心F的培训活动，因为它们与遗传学和生物谱有关 收藏教育。总而言之，建议的Genetics核心H将与所有现有核心以及 最近提交的Biomarker Core G从而增强了遗传学活动并扩展了 宾夕法尼亚大学ADCC作为一个整体。

UNIVERSITY OF PENNSYLVANIA ALZHEIMER’S DISEASE CORE CENTER ABSTRACT: REVISION TO CREATE A NEW GENETICS CORE (CORE H) ADCC Director and Principal Investigator: John Q. Trojanowski, MD, PhD Genetics Core Leader: Vivianna Van Deerlin, MD, PhD; Co-Leader: Gerard Schellenberg, PhD This is an application for a revision of the University of Pennsylvania (Penn) Alzheimer Disease Core Center (ADCC) to establish an independent Genetics Core (Core H). We propose to create a Genetics Core which will enhance and expand the genetics activities of the Penn ADCC. The focus of the Penn ADCC 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. Genetic factors play a critical role in the risk for AD as well as related dementias (RD) including Lewy body dementia and frontotemporal degeneration, which share common mechanisms of neurodegeneration with AD. Furthermore, many patients have more than one clinical or pathologic phenotype and 20-30% of patients with a clinical diagnosis of AD do not have AD pathology, but instead represent a RD. Therefore, the proposed Genetics Core will support the mission of the Penn ADCC by providing the necessary resources, including the leadership and genetics expertise of Vivianna Van Deerlin and Gerard Schellenberg, to conduct and support molecular genetics research of ADRD in collaboration with the existing Cores. To this end, the Specific Aims of Core H are to: 1) Serve as a repository for DNA collected from Clinical Core B participants and autopsy brains characterized in Neuropathology Core D. Collected samples will undergo quality control and ancestry measures and will be available for use by Penn investigators and external collaborators, including shipment to NCRAD; 2) Genotype risk factor variants associated with ADRD in the Clinical Core B cohort of ADRD, MCI, and control subjects to use in Penn studies as covariates, including APOE and other previously identified risk factor loci using a variety of approaches. In addition, perform genetic analysis of genes associated with hereditary neurodegenerative diseases in ADRD subjects; 3) Serve as a centralized resource for storage and handling of genetic and sample data in conjunction with the Data Management, Bioinformatics and Biostatistics Core C; 4) Contribute to patient and community education efforts of the Outreach and Recruitment Core E by providing genetic counseling services to Clinical Core B participants and to training activities of Research Education Core F as they relate to genetics and biospecimen collection education. In summary, this proposed Genetics Core H will interact with all existing cores as well as the recently submitted Biomarker Core G thereby augmenting the genetics activities and extending the aims of the Penn ADCC as a whole.