National Epidemiologic Survey on Alcohol and Related Conditions: DNA Repository

描述(由申请人提供)：全国酒精及相关疾病流行病学调查(NESARC I和II)是关于美国平民非住院人群中酒精中毒及相关疾病的最大规模和最雄心勃勃的流行病学调查。NESARC-III甚至更加雄心勃勃，它的目标是从多达46,500名受试者那里收集唾液样本，并从每个受试者中提取DNA，努力通过大规模的DNA重新测序来识别酒精使用障碍(AUD)和共病疾病的遗传风险因素，并检查基因与环境的相互作用。我们建议为NIAAA NESARC-III研究建立唾液DNA储存库。我们的目标是：1.从人类唾液样本中提取基因组DNA：我们将使用最先进的自动化和基于珠粒的化学方法来丰富相对没有污染、没有RNA和不受欢迎的DNA物种(即细菌DNA污染)的高分子量人类基因组DNA。2.全面的核酸质量控制：我们设计并验证了一种新颖的、全面的分析和功能质量控制(QC)计划，以确保最高质量的DNA及其在未来测序分析中的实用性。分析质量控制包括吸光度和基于染料的浓度和纯度测量，精确的非接触体积测量，以及对每个样本中人类基因组DNA数量的特定量化。功能质控采用高通量、分子遗传指纹SNP分析(RUID)。我们还将使用几个不同的下一代测序平台来演示这种唾液DNA在未来测序中的效用。3.综合核酸存储和分配：所有NESARC-III样本将存储在-80摄氏度的专用冰柜中，并在一个安全的设施中进行全天候监控，该设施包含最先进的冗余电力和暖通空调系统。所有样品提取、质量控制、储存、生物材料请求和分配工作流程都由RUCDR STARLIMS记录和管理，这是一个企业级实验室信息管理系统。 与公共健康相关：酒精使用障碍(AUD)给我们国家造成了数十亿美元的损失，原因是生产力下降、医疗保健提供、事故、暴力和社会秩序的瓦解。此外，它们对人类的许多苦难和苦难负有责任。如果我们要制定更好的治疗和预防策略，我们必须通过流行病学和遗传学研究了解AUDS的病因、发病和终生进展。

DESCRIPTION (provided by applicant): The National Epidemiological Surveys on Alcohol and Related Conditions (NESARC I and II) are the largest and most ambitious epidemiological surveys on alcoholism and related disorders in the civilian, non-institutionalized US population. NESARC-III is even more ambitious as it aims to collect saliva samples from as many as 46,500 subjects and extract DNA from each in an effort to identify genetic risk factors for alcohol use disorders (AUDs) and co-morbid disorders through large-scale DNA re-sequencing and to examine gene-environment interactions. We propose to establish the Saliva DNA Repository for the NIAAA NESARC-III study. Our Aims are: 1. Genomic DNA Extraction from Human Saliva Samples: We will employ state-of-the-art automation and bead-based chemistry to enrich for high molecular weight human genomic DNA relatively free of contaminants and of RNA and undesirable DNA species (i.e., bacterial DNA contamination). 2. Comprehensive Nucleic Acid Quality Control: We have engineered and validated a novel, comprehensive analytical and functional quality control (QC) program that ensures the highest quality of DNA and its utility for future sequencing analyses. Analytical QC consists of absorbance and dye-based concentration and purity measurements, precision non-contact volume measurements, and specific quantification of the amount of human genomic DNA in each sample. Functional QC employs a high-throughput, molecular genetic fingerprinting SNP assay (the RUID). We will also use several different Next Generation sequencing platforms to demonstrate the utility of this saliva DNA for future sequencing. 3. Integrated Nucleic Acid Storage and Distribution: All NESARC-III samples will be stored at -80 degrees C in dedicated freezers that are monitored 24/7/365 in a secure facility that contains state-of-the-art redundant power and HVAC systems. All sample extraction, QC, storage, biomaterial requests and distribution workflows are documented and managed by the RUCDR STARLIMS, an enterprise-level laboratory information management system. PUBLIC HEALTH RELEVANCE: Alcohol use disorders (AUDs) cost our nation billions of dollars due to lost productivity, provision of medical care, accidents, violence and the breakup of social order. In addition, they are responsible for much human misery and suffering. We must understand the causes, onset and lifetime progression of AUDs through epidemiology and genetics studies if we are to develop better treatment and prevention strategies.