National Epidemiologic Survey on Alcohol and Related Conditions: DNA Repository

酒精和相关疾病的全国流行病学调查（NESARC I和II）是美国平民非制度化人群中最大和最雄心勃勃的酒精中毒和相关疾病流行病学调查。NESARC-III更雄心勃勃，因为它的目标是从多达46，500名受试者中收集唾液样本，并从每个人中提取DNA，以通过大规模DNA重新测序来确定酒精使用障碍（AUD）和共病疾病的遗传风险因素，并检查基因-环境相互作用。 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。从人类唾液样品中提取基因组DNA：我们将采用最先进的自动化和基于珠粒的化学方法来富集相对不含污染物和RNA以及不期望的DNA种类（即，细菌DNA污染）。 2.全面的核酸质量控制：我们设计并验证了一种新型的、全面的分析和功能质量控制（QC）程序，可确保DNA的最高质量及其在未来测序分析中的实用性。分析QC包括吸光度和基于染料的浓度和纯度测量、精密度非接触体积测量以及每个样品中人类基因组DNA量的特定定量。功能性QC采用高通量分子遗传指纹SNP分析（RUID）。我们还将使用几种不同的下一代测序平台来证明这种唾液DNA在未来测序中的实用性。 3.集成的核酸储存和分配：所有NESAR-III样本将在-80 ℃下储存在专用冰柜中，该冰柜在安全设施中进行24/7/365监控，该设施包含最先进的冗余电源和HVAC系统。所有样品提取、QC、储存、生物材料请求和分配工作流程均由RUCDR STARLIMS（企业级实验室信息管理系统）记录和管理。 公共卫生相关性：酒精使用障碍（AUD）使我们的国家损失了数十亿美元，原因是生产力损失、医疗保健提供、事故、暴力和社会秩序的崩溃。此外，它们还造成许多人类苦难和痛苦。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.