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

基本信息

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
项目类别：
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&apos 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

项目摘要

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

抽象的个体的基因组变异可能是遗传的（即通过种系传播）或由合子后细胞中的诱变产生，这导致任何个体中没有两个细胞具有相同的基因组克隆造血是与年龄相关的血液中体细胞克隆的生长现象。生长与全因死亡率、血癌和心血管疾病风险增加有关在拟议的项目中，我们将发现并分析体细胞。使用 All of Us 队列中的全基因组测序 (WGS) 数据的 CNV 我们将把 CNVpytor 应用于所有 All of Us 队列。使用 WGS 数据发现体细胞 CNV，并将发现的 CNV 作为资源提供给所有领域的研究人员该资源将包括 CNV、已处理文件和小文件的分层列表。用于即时手动检查 CNV，以及文档和视频教程以及如何访问的示例，检查、分析和可视化 IGV 中发现的 CNV 此外，我们还将包括 CNV 的分层。按年龄分类类型（即缺失、重复、LOH），定义其可能发生的年龄，确定其精确的断点，并分析断点处的序列以揭示其可能的起源。该项目将对“我们所有人”队列中个体血液中的体细胞 CNV 进行大规模评估并将为此类体细胞 CNV 的病因学提供新的见解。应用于未来生成的数据，因为我们所有人都扩大了样本收集。 1