African American Sarcoidosis Genetics Resource

非洲裔美国人结节病遗传学资源

• 批准号: 7854835
• 负责人: Courtney Montgomery
• 金额: $ 170万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854835
• 关键词: Admixture; Affect; African; African American; American; Bioinformatics; Candidate Disease Gene; Clinical; Collection; Computing Methodologies; Conserved Sequence; DNA Sequence; Data; Databases; Disease; Environmental Exposure; Family; Family member; Follow-Up Studies; Foundations; Funding; Genes; Genetic; Genetic Databases; Genetic Research; Genome; Genomics; Genotype; German population; Goals; Granulomatous; Gray unit of radiation dose; Individual; Inflammatory; Internet; Investigation; Joints; Knowledge; Linkage Disequilibrium; Location; Maps; Measures; Methods; Multiple Birth Offspring; Nucleic Acid Regulatory Sequences; Occupations; Pathway interactions; Patients; Phenotype; Population; Predisposition; Recording of previous events; Research; Research Infrastructure; Resources; Sampling; Sarcoidosis; Scanning; Services; Single Nucleotide Polymorphism; Sum; Susceptibility Gene; Variant; base; case control; cohort; experience; genetic resource; genetic variant; genome wide association study; genome-wide linkage; insertion/deletion mutation; interest; novel; public health relevance; repository; research study; response; sample collection; tool; tool development; web based interface

DESCRIPTION (provided by applicant): Sarcoidosis is a multiorgan granulomatus inflammatory disorder likely resulting from an exaggerated T-dell response in genetically susceptible individuals. African-Americans are more frequently and severely affected by Sarcoidosis yet few collections of African American patients exist. We however, have amassed a large, well phenotyped cohort of close to 3,000 Sarcoidosis patients, family members and controls on which to perform an extensive search of the genome to identify potential susceptibility loci. Specifically, this "Grand Opportunity" proposal will, using a unique and easily-accessible cohort, perform the first, and much needed, genome-wide association (GWA) scan in African Americans using the first and only commercially available genotyping product that results in adequate coverage (>85%) of the African genome. Because of the size of our cohort, we are poised to replicate our findings in an independent sample and therefore propose candidate genes and regions for further characterization. We can further characterize the population origin of these effects based on ancestry data already obtained. Finally, we will develop a bioinformatics tool for the repository and investigation of genetic data (e.g. single nucleotide polymorphisms, copy number variants, etc), genomic data (e.g. physical location, genic location, function, degree of conservation, etc), and statistical data from prior linkage, admixture and candidate gene association studies as well as this and other GWA studies. This project aligns with the goals of the GO mechanism in that we can begin immediately upon funding, the discoveries made herein will birth multiple follow-up studies, the database resource will allow our field to take the next step beyond association into pathway-based and bioinformatics-driven analyses and finally, we will stimulate the American research enterprise via the purchase of over $2M in domestically produced goods and services and the creation and retention of several biotech and administrative jobs. In sum, our extensive African American cohort and our genotyping, analysis and bioinformatics resources as well as the extensive experience of our team of experts in AA Sarcoidosis genetics make an experiment of this magnitude and scope very unlikely to be completed by any other group. PUBLIC HEALTH RELEVANCE: This project will fast-forward Sarcoidosis, and likely other granulomatus or inflammatory disorders, genetics research by 1) identifying and replicating association to genetic variants throughout the genome and 2) facilitating characterization of these effects using related statistical, genetics and genomics data. In addition, this project will generate extensive revenue for American biotech products and jobs.

描述（由申请人提供）： 结节病是一种多器官肉芽肿炎症性疾病，可能是由遗传易感个体过度的 T-dell 反应引起的。非裔美国人更频繁、更严重地受到结节病的影响，但非洲裔美国患者的收集很少。然而，我们已经积累了一个由近 3,000 名结节病患者、家庭成员和对照组成的大型、表型良好的队列，对它们进行广泛的基因组搜索，以确定潜在的易感位点。具体来说，这一“大机遇”提案将利用独特且易于访问的队列，使用第一个也是唯一一个商业化的基因分型产品对非裔美国人进行首次且急需的全基因组关联（GWA）扫描，从而产生非洲基因组的足够覆盖率（>85%）。由于我们队列的规模，我们准备在独立样本中复制我们的发现，因此提出候选基因和区域以进行进一步表征。我们可以根据已经获得的祖先数据进一步描述这些影响的人口起源。最后，我们将开发一个生物信息学工具，用于存储和研究遗传数据（例如单核苷酸多态性、拷贝数变异等）、基因组数据（例如物理位置、基因位置、功能、保守程度等）和统计数据来自先前连锁、混合和候选基因关联研究以及本研究和其他 GWA 研究的数据。该项目与 GO 机制的目标一致，因为我们可以在获得资助后立即开始，本文中的发现将催生多项后续研究，数据库资源将使我们的领域能够迈出下一步，超越关联，进入基于路径的和最后，我们将通过购买超过 200 万美元的国产商品和服务以及创造和保留一些生物技术和行政工作岗位来刺激美国研究企业的发展。总之，我们广泛的非裔美国人队列和我们的基因分型、分析和生物信息学资源，以及我们的 AA 结节病遗传学专家团队的丰富经验，使得这种规模和范围的实验不太可能由任何其他小组完成。 公共卫生相关性： 该项目将通过以下方式快速推进结节病以及可能的其他肉芽肿或炎症性疾病的遗传学研究：1）在整个基因组中识别和复制与遗传变异的关联；2）利用相关的统计、遗传学和基因组学数据促进对这些效应的表征。此外，该项目将为美国生物技术产品和就业机会带来大量收入。