Genetics

遗传学

• 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
• 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' 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

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.

项目总结-遗传学核心（核心F） 孟德尔突变，常见的风险因素，以及-最近-罕见的风险相关变异已经被 在神经退行性疾病中发现。然而，阿尔茨海默病的遗传性中有很大一部分 (AD)额颞叶痴呆症（FTD）仍然无法解释，这表明其他遗传风险因素 等待确认身份。PPG遗传学核心在过去的2000年里一直支持PPG研究人员， 收集和储存来自整个PPG群组的DNA和RNA样品; 痴呆症的致病原因和风险相关的变异，使用传统和下一代 测序方法; 2）通过以下方法有助于发现新基因和新的风险相关变体： 利用遗传学和基因组学方法生成数据和进行基于病例的筛查;以及 信息学平台，以促进数据共享，存储和挖掘，包括访问专用计算 和存储资源。在此续订申请中，我们建议利用此基础架构和专业知识， 扩大PPG可用的遗传和基因组学检测产品组合。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（横山）。我们将继续 样本收集和银行，并将扩大我们的测序和基因分型工作，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， 导致三核苷酸重复扩增，以及支持Project E10的转录组学：分子生物标志物。等 数据将与正在进行的临床、成像、生物标志物和神经病理学研究相结合， PPG，以促进我们对神经退行性疾病的遗传结构的理解。鉴于 遗传信息在FTD病因学和病理生理学中的基本性质，这一核心服务于所有 项目在这个程序中，并链接到其他PPG核心。