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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）临床表现为进行性行为和/或语言缺陷。FTLD的亚型在神经病理学上通过细胞包涵体的蛋白质组成来分类。FTLD最常见的神经病理学相关物具有TAR DNA结合蛋白（TDP-43）包涵体（FTLD-TDP）或tau包涵体（FTLD-tau）。FTLD通常是家族性的，可以作为常染色体显性遗传疾病发生。具有引起FTLD的突变的基因包括/W/APT（编码tau）和GRN（编码颗粒蛋白前体）等，其中每一种都与特定的FTLD病理亚型相关：GRN突变与FTLD-TDP和MAPT突变与FTLD-tau。研究FTLD的遗传学可以帮助阐明其病因学和病理生理学，并提供治疗靶点，以及确定改变疾病风险或表型的风险因素。为了进行FTLD的遗传学研究，遗传学核心作为本计划项目资助的一个组成部分，将收集并储存来自临床核心B受试者的DNA，FTLD和神经病理学核心中表征的尸检大脑以及对照样本。对于参与的个体，经过认证的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。库DNA将用于核心本身的遗传分析，以及项目1，和其他合作者内外的宾夕法尼亚大学。FTLD相关基因的遗传分析将由核心与项目1合作进行。基因型数据将使临床、病理学和遗传学与项目1和3的数据以及临床和神经病理学核心数据相关联，并通过生物统计学和数据管理核心进行统计分析。项目2和项目4将使用基因型数据进行病例选择分析。最后，遗传学核心将与宾夕法尼亚大学分子病理学实验室的医院协调，使CLIA认证的基因检测可用。为此，核心将确定新的基因检测，这些检测可以转化为临床检测，并通过提供引物序列、方案和样本来协助验证。