Racial and Ethnic Diversity in Human Extracellular RNA

描述（由申请人提供）： 项目摘要：RNA可以是细胞外的（exRNA），并且这种不同的exRNA群体包括微小RNA、小核仁RNA、皮尔纳、非编码RNA和环境来源的RNA。在人类中，exRNA存在于各种体液中，包括血浆和尿液。特异性exRNA调节对正常稳态和疾病发病机制至关重要的关键过程。尽管越来越多的报道表明选择的exRNA可以反映或调节疾病，但尚未产生标准的exRNA参考组。在这个提议中，我们假设，在健康成人中，exRNA的循环血浆和尿液水平; i）与性别、种族和民族相关; ii）与细胞基因表达相关; iii）与细胞基因表达相关。 可能随年龄而变化，和; iv）与基因组变异性相关。该RFA的主要目标是在健康个体中生成exRNA谱。这些概况将界定人口，并用作促进疾病诊断和发现的参考。为了实现这一目标，几个标准是至关重要的，具体地说;样本必须：（i）来自一个全面表征的队列，可以准确地建立没有疾病，（ii）是种族和民族的参考美国人口，（iii）有基因组和表型数据可用。因此，我们将利用两项代表美国人口的社区队列研究，即Frachial Heart研究（FHS）和多种族动脉粥样硬化研究（梅萨）。将使用用于高产量血浆RNA提取的优化的非商业分离方法从800名研究参与者的血浆和尿液中分离exRNA。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）数据管理和资源库（DMRR）合作提供。在整个提案中，这些研究将使用最先进的提取技术、新技术和定义明确、全面表征的观察队列，以鉴定血浆和尿液中的exRNA，并确定其在健康成人中的表达模式。

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.