Racial and Ethnic Diversity in Human Extracellular RNA

人类细胞外 RNA 的种族和民族多样性

• 批准号: 8775017
• 负责人: JANE E Freedman
• 金额: $ 69.99万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775017
• 关键词: Address; Adult; African American; Age; Asians; Atherosclerosis; Blood Circulation; Body Fluids; Cells; Clinical; Cohort Studies; Collaborations; Communication; Communication Programs; Communities; Complex; DNA; Data; Data Set; Databases; Deposition; Development; Disease; Epidemiology; Ethnic Origin; Framingham Heart Study; Functional RNA; Gender; Gene Expression; Generations; Genetic; Genetic Transcription; Genome; Genomics; Goals; High-Throughput Nucleotide Sequencing; High-Throughput RNA Sequencing; Hispanics; Homeostasis; Human; Individual; Laboratories; Liquid substance; Measurement; Messenger RNA; Methods; MicroRNAs; Output; Participant; Pathogenesis; Pattern; Performance; Plasma; Population; Population Heterogeneity; Process; Qualifying; RNA; RNA Sequence Analysis; Race; Reporting; Research Personnel; Resources; Sampling; Scientist; Small Nucleolar RNA; Techniques; Urine; Variant; base; cohort; data management; data sharing; disease diagnosis; experience; extracellular; human RNA sequencing; member; multidisciplinary; new technology; novel; piRNA; public health relevance; racial and ethnic; repository; sex

DESCRIPTION (provided by applicant): Project Summary: RNA may be extracellular (exRNA) and this diverse population of exRNA includes microRNAs, small nucleolar RNAs, piRNA, non-coding, and environmentally-derived RNAs. In humans, exRNAs are found in various body fluids, including plasma and urine. Specific exRNAs regulate key processes central to normal homeostasis and the pathogenesis of disease. Although a rapidly growing number of reports demonstrate that select exRNAs may reflect or regulate disease, a standard referent group of exRNAs has yet to be generated. In this proposal, we postulate that, in healthy adults, circulating plasma and urine levels of exRNAs; i) are associated with sex, race and ethnicity; ii) are associated with cellular gene expression; iii) may vary with age, and; iv) are associated with genomic variability. The primary goal of this RFA is the generation of exRNA profiles in healthy individuals. These profiles will both define populations and be used as a reference to facilitate disease diagnosis and discovery. To accomplish this goal several criteria are paramount, specifically; samples must; (i) come from a comprehensively characterized cohort that can accurately establish absence of disease, (ii) be racially and ethnically referent to the US population, and (iii) have genomic and phenotypic data available. Thus, we will utilize two community-based cohort studies representative of the U.S. population, the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). exRNA will be isolated from plasma and urine from 800 study participants using an optimized non-commercial isolation method for high-yield plasma RNA extraction. We will conduct high-throughput sequencing on all 1600 samples to identify known and as-yet undiscovered circulating exRNAs. There will be a formal performance, communication, and data sharing plan and all data will be made publically available in collaboration with the ExRNA Communication Program (ERCP) Data Management & Resource Repository (DMRR). Throughout this proposal, the studies will use state-of-the art extraction techniques, new technologies, and well-defined, comprehensively characterized observational cohorts to identify exRNA from plasma and urine and determine their patterns of expression in healthy adults.

描述（由申请人提供）： 项目摘要：RNA 可能是细胞外的 (exRNA)，这种多样化的 exRNA 群体包括 microRNA、小核仁 RNA、piRNA、非编码和环境衍生的 RNA。在人类中，exRNA 存在于多种体液中，包括血浆和尿液。特定的 exRNA 调节正常体内平衡和疾病发病机制的关键过程。尽管越来越多的报告表明特定的 exRNA 可能反映或调节疾病，但标准的 exRNA 参考组尚未产生。在这项提案中，我们假设，在健康成年人中，循环血浆和尿液中的 exRNA 水平； i) 与性别、种族和民族有关； ii) 与细胞基因表达相关；三） 可能随年龄而变化，并且； iv) 与基因组变异相关。该 RFA 的主要目标是生成健康个体的 exRNA 图谱。这些概况将定义人群并用作促进疾病诊断和发现的参考。为了实现这一目标，有几个标准至关重要，具体而言：样品必须； (i) 来自一个全面表征的队列，可以准确地确定是否存在疾病，(ii) 在种族和民族上参考美国人口，(iii) 拥有可用的基因组和表型数据。因此，我们将利用两项代表美国人口的基于社区的队列研究，即弗雷明汉心脏研究 (FHS) 和动脉粥样硬化多种族研究 (MESA)。将从 800 名研究参与者的血浆和尿液中分离出 exRNA，使用优化的非商业分离方法进行高产血浆 RNA 提取。我们将对所有 1600 个样本进行高通量测序，以识别已知和尚未发现的循环 exRNA。将有一个正式的性能、通信和数据共享计划，所有数据将与 ExRNA 通信计划 (ERCP) 数据管理和资源存储库 (DMRR) 合作公开提供。在整个提案中，研究将使用最先进的提取技术、新技术和明确、全面表征的观察队列来识别血浆和尿液中的 exRNA，并确定其在健康成人中的表达模式。