Discovering and Analyzing Development and Age-Associated CNAs in the All of Us Cohort

发现并分析我们所有人队列中的发育和与年龄相关的 CNA

• 批准号: 10797689
• 负责人: ALEXEJ ABYZOV
• 金额: $ 16.14万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797689
• 关键词: Age; Alzheimer' s disease risk; Blood; Blood specimen; Brain; Cardiovascular Diseases; Cell division; Cells; Collection; Copy Number Polymorphism; Data; Detection; Development; Disease; Documentation; Enrollment; Etiology; Frequencies; Future; Genes; Genome; Genomics; Gilles de la Tourette syndrome; Hematopoiesis; Hematopoietic; Hematopoietic Neoplasms; Individual; Inherited; Length; Manuals; Methodology; Methods; Mosaicism; Mutagenesis; Mutation; Outcome; Phenotype; Point Mutation; Predisposition; Process; Research; Research Personnel; Resources; Risk; Role; SNP array; Schizophrenia; Signal Transduction; Somatic Cell; Somatic Mutation; Stratification; Testing; Variant; Visualization; Work; Y Chromosome; age related; autism spectrum disorder; cohort; driver mutation; genetic variant; genome sequencing; insight; mortality; neuropsychiatric disorder; sample collection; sex; tool; transmission process; whole genome

Abstract Genomic variants in an individual may be either inherited (i.e., transmitted through the germline) or generated by mutagenesis in post-zygotic cells, which results in no two cells in any individual having the same genome. Clonal hematopoiesis is the phenomenon of age-related outgrowth of somatic clones in the blood. Such an outgrowth has been associated with increased all-cause mortality, risk of blood cancer and cardiovascular diseases but reduced risks of Alzheimer’s disease. In the proposed project we will discover and analyze somatic CNVs using whole genome sequencing (WGS) data in the All of Us cohort. We will apply CNVpytor to all All of Us WGS data to discover somatic CNVs and provide discovered CNVs as a resource to researchers in the All of Us Researcher Workbench. The resource will include a tiered list of CNVs, processed and small sized files for instant manual inspection of CNVs, and documentation and video tutorial with examples how to access, inspect, analyze and visualize the discovered CNVs in IGV. Additionally, we will include stratification of CNV types (i.e., deletions, duplications, LOHs) by age, defining their likely age of occurrence, determining their precise breakpoints, and analyzing sequences at the breakpoints to reveal their likely origin. Completing the described project will result in a large-scale assessment of somatic CNVs in the blood of individuals in the All of Us cohort and will provide a new insight into the etiology of such somatic CNVs. The developed methodologies can be applied to data generated in the future, as All of Us expands the collection of samples. 1

抽象的 个体中的基因组变体可以遗传（即通过种系传输）或 由诱变产生的杂种细胞产生，这导致任何具有相同的个体中的两个细胞 基因组。克隆造血是血液中体细胞克隆与年龄有关的现象。这样的 出生与全因死亡率增加，血液癌和心血管的风险有关 疾病，但降低了阿尔茨海默氏病的风险。在拟议的项目中，我们将发现和分析躯体 使用整个基因组测序（WGS）数据中的CNV中的CNV。我们将向所有人应用cnvpytor 美国WGS数据以发现体细胞CNV并为研究人员提供发现的CNV作为资源 美国研究人员工作台。资源将包括CNV，加工和小型文件的分层列表 用于即时对CNV的手动检查，以及文档和视频教程，其中包括如何访问的示例 检查，分析和可视化IGV中发现的CNV。此外，我们将包括CNV的分层 按年龄按年龄定义了可能发生的年龄，确定其精确的类型（即删除，重复，LOHS）类型 断点，并在断点上分析序列以揭示其可能的起源。完成描述的 项目将导致对我们所有人的个体血液中的体细胞CNV进行大规模评估 并将为这种体细胞CNV的病因提供新的见解。开发的方法可以是 应用于将来生成的数据，因为我们所有人都扩展了样本的集合。 1