Racial and Ethnic Diversity in Human Extracellular RNA

描述(由申请人提供)： 项目摘要：RNA可能是细胞外RNA(ExRNA)，这种多样化的exRNA群体包括microRNAs、小核仁RNAs、piRNA、非编码RNAs和环境来源的RNAs。在人类体内，exRNAs存在于各种体液中，包括血浆和尿液。特定的exRNAs调节对正常内稳态和疾病发病机制至关重要的关键过程。尽管越来越多的报告表明，选定的exRNAs可能反映或调节疾病，但尚未产生一个标准的exRNAs参照组。在这项建议中，我们假设，在健康成年人中，循环中的血浆和尿液中exRNAs的水平；i)与性别、种族和民族有关；ii)与细胞基因表达有关；iii) 可能随年龄而变化；以及；iv)与基因组变异性有关。这种RFA的主要目标是在健康个体中产生exRNA图谱。这些概况将定义人口，并用作促进疾病诊断和发现的参考。为了实现这一目标，有几个标准是至关重要的，具体地说，样本必须：(I)来自能够准确确定没有疾病的全面特征的队列，(Ii)在种族和民族上与美国人口有关，以及(Iii)有基因组和表型数据可用。因此，我们将利用两项具有美国人群代表性的社区队列研究，即弗雷明翰心脏研究(FHS)和动脉粥样硬化多种族研究(MESA)。将使用一种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外源RNA，以提取高产量的血浆RNA。我们将对所有1600个样本进行高通量测序，以确定已知和尚未发现的循环exRNA。将有一个正式的绩效、沟通和数据共享计划，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、新技术和定义明确、全面表征的观察队列来识别血浆和尿液中的exRNA，并确定其在健康成年人中的表达模式。

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.