Genetics

遗传学

基本信息

批准号：
10556177
负责人：
Jennifer S Yokoyama
金额：
$ 47.92万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10556177
关键词：
Alzheimer&apos s Disease Back Bioinformatics Biological Assay Biological Markers Blood Clinical DNA Data Data Analyses Dedications Dementia Development Disease Emotions Enrollment Environment Etiology Fostering Foundations Frontotemporal Dementia Functional disorder Funding Future Gene Mutation Generations Genes Genetic Genetic Counseling Genetic Risk Genetic Screening Genetic study Genomic approach Genomics Genotype Goals Heritability Image Individual Informatics Infrastructure Institution International Large-Scale Sequencing Learning Link Maps Medical Genetics Mentors Methods Mining Mutation Nature Nerve Degeneration Neurodegenerative Disorders Participant Pathogenicity Pathologic Patients Population Publications RNA Reporting Research Research Personnel Resources Risk Factors Role SNP array Sampling Stratification Subjects Selections Therapeutic Time Training Trinucleotide Repeat Expansion Work autosomal dominant mutation autosome career case-based clinical practice cohort cost data management data sharing exome sequencing gene discovery genetic approach genetic architecture genetic information genetic risk factor genetic testing genome resource genome sequencing genome-wide interdisciplinary collaboration molecular marker multidisciplinary multiple omics neurogenetics neuropathology next generation sequencing novel precision medicine programs recruit repository research study risk variant sample collection screening success tool transcriptome sequencing transcriptomics whole genome

项目摘要

PROJECT SUMMARY—Genetics Core (Core F) Mendelian mutations, common risk factors, and – more recently – rare risk-associated variants have been identified in neurodegenerative diseases. Yet, a significant proportion of the heritability for Alzheimer's disease (AD) and frontotemporal dementia (FTD) remains unexplained, suggesting that additional genetic risk factors await identification. This PPG Genetics Core has supported PPG investigators over the past ൭൫ years by ൬) collecting and storing DNA and RNA samples from the entire PPG cohort; ൭) providing genetic testing for known pathogenic causes of dementia and risk-associated variants, using both traditional and next-generation sequencing methods; ൮) contributing to the discovery of novel genes and novel risk-associated variants through data generation and case-based screening, using genetic and genomic approaches; and ൯) establishing an informatics platform to facilitate data sharing, storage, and mining, including access to dedicated computational and storage resources. In this renewal application, we propose to leverage this infrastructure and expertise to expand the portfolio of genetic and genomics assays available to the PPG. In the context of expanding roles, we propose to transition primary core activities from UCLA (Geschwind) to UCSF (Yokoyama). We will continue sample collection and banking and will expand our sequencing and genotyping efforts to include whole exome sequencing for gene screening, genome-wide SNP arrays for population mapping, fragment analysis for disease- causing trinucleotide repeat expansions, and transcriptomics in support of Project ൭: Molecular Biomarkers. Such data will be integrated with the clinical, imaging, biomarker, and neuropathological studies being conducted within the PPG to advance our understanding of the genetic architecture of neurodegenerative disease. Given the fundamental nature of genetic information in the etiology and pathophysiology of FTD, this core serves all the projects in this program and is linked to the other PPG cores.

项目摘要——遗传学核心（核心 F）孟德尔突变、常见风险因素以及最近的罕见风险相关变异已被然而，在神经退行性疾病中，阿尔茨海默氏病的遗传性占很大比例。（AD）和额颞叶痴呆（FTD）仍然无法解释，这表明额外的遗传风险因素等待鉴定。过去 ൭൫ 的 PPG 遗传学核心为 PPG 研究人员提供了支持 ൬) 收集并存储整个 PPG 队列中的 DNA 和 RNA 样本 ൭) 为已知的情况提供基因检测；使用传统和下一代技术研究痴呆症的致病原因和风险相关变异测序方法；൮) 有助于发现新的基因和新的风险相关变异使用遗传和基因组方法进行数据生成和基于病例的筛选；信息学平台促进数据共享、存储和挖掘，包括访问专用计算在此更新应用程序中，我们建议利用此基础设施和专业知识来扩大 PPG 可用的遗传和基因组学检测组合在扩大作用的背景下，我们。建议将主要核心活动从加州大学洛杉矶分校（Geschwind）转移到加州大学旧金山分校（Yokoyama）。我们将继续。样本收集和存储，并将扩大我们的测序和基因分型工作，以包括整个外显子组用于基因筛选的测序、用于群体作图的全基因组 SNP 阵列、用于疾病的片段分析引起三核苷酸重复扩增和转录组学以支持项目൭：分子生物标记。数据将与正在进行的临床、影像、生物标志物和神经病理学研究相结合 PPG 旨在增进我们对神经退行性疾病遗传结构的理解。遗传信息在 FTD 病因学和病理生理学中的基本性质，该核心服务于所有该计划中的项目并链接到其他 PPG 核心。