GENETICS CORE

遗传学核心

基本信息

批准号：
8444443
负责人：
VIVIANNA M VAN DEERLIN
金额：
$ 17.13万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
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/8444443
关键词：
Autopsy Behavioral Biometry Brain Case Study Clinical Collaborations Consent Forms DNA DNA Library DNA Sequence Analysis DNA-Binding Proteins Data Databases Disease Education Etiology Family member Fostering Frontotemporal Dementia Frontotemporal Lobar Degenerations Functional disorder Gene Mutation Genes Genetic Genetic screening method Genotype Haplotypes Inborn Genetic Diseases Inclusion Bodies Individual Informed Consent LRRK2 gene Laboratories Language Disorders Lead Link Mutation Neurodegenerative Disorders Participant Pathologic Patients Pennsylvania Phenotype Professional counselor Program Research Project Grants Progranulin Proteins Protocols documentation Recontacts Research Risk Factors Sampling Spouses Testing Training Translations Universities University Hospitals Validation clinically relevant data management disease phenotype disorder risk genetic analysis genetic pedigree improved molecular pathology neuropathology novel presenilin-1 protein TDP-43 research clinical testing tau Proteins

项目摘要

PROJECT SUMMARY: Frontotemporal Lobar degeneration (FTLD) manifests clinically with progressive behavioral and/or language deficits. Subtypes of FTLD are classified neuropathologically by the protein composition of cellular inclusion bodies. The most common neuropathological correlates of FTLD have TAR DNA binding protein (TDP-43) inclusions (FTLD-TDP) or tau inclusions (FTLD-tau). FTLD is frequently familial and can occur as an autosomal dominantly inherited disorder. Genes with mutations causing FTLD include /W/APT (encodes tau) and GRN (encodes progranulin) among others, each of which is associated with a specific FTLD pathological subtype: GRN mutations with FTLD-TDP and MAPT mutations with FTLD-tau. Studying the genetics of FTLD can help elucidate its etiology and pathophysiology and provide targets for therapy as well as identify risk factors that modify disease risk or phenotype. To enable genetic studies of FTLD the Genetics Core, as an integral part of this Program Project Grant, will collect and bank DNA from Clinical Core B subjects with FTLD and autopsy brains characterized in the Neuropathology Core as well as control samples. For participating individuals, a study coordinator trained as a certified genetic counselor will provide genetic education to foster a better understanding of the research and to obtain informed consent. Banked DNA will be used for genetic analysis by the Core itself, as well as by Project 1, and other collaborators within and outside of UPenn. Genetic analysis of FTLD associated genes will be performed by the Core and in collaboration with Project 1. Genotype data will enable clinical, pathologic and genetic correlations with data from Projects 1 and 3 and the Clinical and Neuropathology Cores with statistical analysis by the Biostatistics and Data Management Core. Projects 2 and 4 will use genotype data for case selection for analysis. Finally, the Genetics Core will coordinate with the Hosp. of the Univ. of Penn Molecular Pathology Lab to make CLIA-certified genetic testing available. To this end, the Core will identify new genetic tests which are ready for translation into clinical tests and assist with validation by providing primer sequences, protocols, and samples

项目概要：额颞叶变性（FTLD）在临床上表现为进行性行为和/或语言缺陷。 FTLD 的亚型根据细胞包涵体的蛋白质组成在神经病理学上进行分类。 FTLD 最常见的神经病理学相关因素是 TAR DNA 结合蛋白 (TDP-43) 内含物 (FTLD-TDP) 或 tau 内含物 (FTLD-tau)。 FTLD 通常具有家族性，并且可以作为常染色体显性遗传性疾病发生。引起 FTLD 的突变基因包括 /W/APT（编码 tau）和 GRN（编码颗粒体蛋白前体）等，其中每一个都与特定的 FTLD 病理亚型相关：GRN 突变伴有 FTLD-TDP，MAPT 突变伴有 FTLD-tau。研究 FTLD 的遗传学有助于阐明其病因和病理生理学，提供治疗目标，并确定改变疾病风险或表型的危险因素。为了实现 FTLD 的遗传学研究，遗传学核心作为该计划项目拨款的一个组成部分，将从具有 FTLD 的临床核心 B 受试者和神经病理学核心中表征的尸检大脑以及对照样本中收集和储存 DNA。对于参与个人，经过认证遗传咨询师培训的研究协调员将提供遗传教育，以促进对研究的更好理解并获得知情同意。储存的 DNA 将用于核心本身、项目 1 以及宾夕法尼亚大学内外的其他合作者进行遗传分析。 FTLD 相关基因的遗传分析将由核心与项目 1 合作进行。基因型数据将实现与项目 1 和 3 以及临床和神经病理学核心的数据的临床、病理和遗传相关性，以及生物统计和数据的统计分析管理核心。项目2和4将使用基因型数据进行病例选择进行分析。最后，遗传学核心将与医院协调。大学的。宾夕法尼亚大学分子病理学实验室提供 CLIA 认证的基因检测。为此，核心将确定新的基因测试，这些测试已准备好转化为临床测试，并通过提供引物序列、方案和样本来协助验证