Molecular Genetics Support to Identify Gene/Environment Interactions in Disease

分子遗传学支持识别疾病中的基因/环境相互作用

• 批准号: 8554151
• 负责人: Richard Paules
• 金额: $ 204.29万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8554151
• 关键词: Accounting; Age; Automation; Back; Bioinformatics; Blood; Code; Complex; Consult; Core Facility; DNA; DNA Resequencing; Data Analyses; Databases; Development; Disease; Environmental Health; Epidemiologic Studies; Ethnic Origin; Gel; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Goals; Health; Individual; Internet; Link; Manuals; Methods; Molecular Genetics; Mus; National Institute of Environmental Health Sciences; Nucleic Acids; Other Genetics; Predisposition; Prevention therapy; Productivity; Race; Reaction; Recruitment Activity; Registries; Reporting; Research; Research Infrastructure; Research Personnel; Research Support; Resources; Robotics; Role; Sampling; Scientist; Services; Tail; Technology; Time; Toxic effect; Translational Research; Work; clinical phenotype; cost; design; follow-up; gene environment interaction; genetic technology; human disease; improved; interest; method development; sex; tool

Dissecting complex disease has become more feasible due to the availability of large-scale DNA resources and advances in high-throughput genomic technology. While these tools help scientists identify potential susceptibility loci, subjects with very specific relevant genotypes are needed for clinical phenotyping and toxicity studies. For this reason, NIEHS has developed the Environmental Polymorphism Registry (EPR); a resource of subjects and their DNAs to use for translational research of environmental diseases. Over 11,000 individuals of diverse sex, age, race and ethnicity have been recruited by the EPR. DNA was isolated from their bloods and coded with personal identification numbers (PINs) linked back to their identities. This linked resource of subjects and their DNAs allow scientists to screen for individuals with genotypes of interest and invite them to participate in follow-up studies. The EPR further aims to characterize health effects of polymorphisms, and to conduct epidemiologic studies of gene-environment interactions. The Molecular Genetics Core Facility (MGCF) infrastructure was created to perform nucleic acid sample isolation, sample management and genetics studies to support the EPR and other genetics efforts at NIEHS, and currenty manages extraction, sample databasing and genotyping for the EPR. The MGCF has completed an Illumina genotyping study of 768 SNPs across 4000 EPR samples. During the past year, robotic automation in the MGCF was improved to further decrease the cost of genetic studies performed at NIEHS. We have continued to develop a dynamic web portal to manage the core facility, and an associated database to track both work product and cost of each study. Cost-accounting features were improved to make annual and quarterly reporting automated. We established automated gene resequencing infrastructure at 1/64 scale, which provides support from primer design through data analysis, while dramatically reducing cost per reaction. We also developed an automated gel-free mouse tail genotyping method to reduce labor and expense of this time consuming and costly aspect of maintaining mouse colonies. Both the methods automation and methods development aspects of our workgroup offer opportunities for accelerated development of new therapies for prevention of environmentally induced disease.

由于大规模DNA资源的可获得性和高通量基因组技术的进步，解剖复杂疾病变得更加可行。虽然这些工具有助于科学家识别潜在的易感基因座，但临床表型和毒性研究需要具有非常特定的相关基因型别的受试者。 为此，NIEHS开发了环境多态注册表(EPR)；这是用于环境疾病翻译研究的受试者及其DNA的资源。EPR招募了11000多名不同性别、年龄、种族和民族的人。从他们的血液中分离出DNA，并用与他们身份相关的个人识别码(PIN)进行编码。这种受试者及其DNA的关联资源使科学家能够筛选具有感兴趣的基因型别的个体，并邀请他们参与后续研究。EPR进一步旨在描述多态对健康的影响，并对基因-环境相互作用进行流行病学研究。 分子遗传学核心设施(MGCF)的创建是为了进行核酸样本分离、样本管理和遗传学研究，以支持NIEHS的EPR和其他遗传学工作，目前负责EPR的提取、样本数据库和基因分型。MGCF已经完成了对4000个EPR样本中768个SNPs的Illumina基因分型研究。 在过去的一年里，MGCF的机器人自动化得到了改进，以进一步降低NIEHS进行的基因研究的成本。我们继续开发一个动态的门户网站来管理核心设施，以及一个相关的数据库来跟踪每项研究的工作成果和费用。改进了成本核算功能，使年度和季度报告自动化。 我们建立了1/级别的自动化基因重测序基础设施，通过数据分析提供了从引物设计到数据分析的支持，同时显著降低了每次反应的成本。我们还开发了一种自动化的无凝胶小鼠尾巴基因分型方法，以减少维持小鼠群体这一耗时和昂贵方面的劳动力和费用。我们工作组的方法自动化和方法开发方面都为加速开发预防环境引起的疾病的新疗法提供了机会。