A Platform for Large-Scale Discovery in Common Disease

常见疾病大规模发现的平台

基本信息

批准号：
9205526
负责人：
SUSAN K DUTCHER
金额：
$ 1639.2万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-14 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9205526
关键词：
Age related macular degeneration Alleles Architecture Autoimmune Diseases Benchmarking Cardiovascular Diseases Communities Complex Computational Technique Computer software DNA Sequencing Facility DNA analysis DNA sequencing Data Degenerative Disorder Development Diagnosis Disease Disease Management Evaluation Faculty Family Genetic Genome Genomics Goals Haplotypes Health Human Human Genome Idiopathic scoliosis Informatics Inherited Insulin-Dependent Diabetes Mellitus Knowledge Laboratories Macular degeneration Metabolic Methods National Human Genome Research Institute Performance Phase Population Predisposition Prevention Production Research Research Design Resources Rheumatoid Arthritis Risk Sampling Stroke Technology Variant base cleft lip and palate cohort cost data integration data sharing disease phenotype experience gene discovery genome analysis genome sequencing genome-wide human disease improved innovation novel open source operation outcome forecast programs public health relevance success synergism technology development tool whole genome

项目摘要

DESCRIPTION (provided by applicant): A Platform for Large-scale Discovery in Common Disease: Project Summary A comprehensive understanding of the genome architecture variants underlying inherited human disease phenotypes and protective alleles will facilitate improved diagnosis, prognosis, disease management, and the development of new treatments for hundreds of millions of people worldwide. In support of this goal, we propose to apply our established, state-of-the-art DNA sequencing and analysis platform to comprehensively identify rare variation influencing susceptibility to common complex diseases corresponding to three disease themes: 1) cardiovascular disease and metabolic risk, 2) autoimmune disease including Type 1 diabetes and rheumatoid arthritis, and 3) developmental and degenerative diseases including cleft lip/palate, idiopathic scoliosis and macular degeneration. Where possible, we will leverage emerging methods and technology to advance the state of the field and achieve our program goals. Our approach extends the discovery power of low-cost whole genome sequencing (WGS) with innovative laboratory and computational techniques to comprehensively interrogate the full spectrum of human genome variation. We developed these studies with substantial input from expert collaborators whose continued involvement and disease-specific expertise will be critical for success. Ultimately, the diversity of our proposed projects - in ters of disease phenotypes, sample ancestries, and study designs - will provide a better understanding of the genetic architecture of common disease and the extent to which it is shared across world populations.

描述（由申请人提供）：常见疾病大规模发现平台：项目摘要对遗传性人类疾病表型和保护性等位基因背后的基因组结构变异的全面了解将有助于改善诊断、预后、疾病管理和开发为了支持这一目标，我们建议应用我们现有的最先进的 DNA 测序和分析平台来全面识别影响三种疾病对应的常见复杂疾病易感性的罕见变异。主题： 1) 心血管疾病和代谢风险，2) 自身免疫性疾病，包括 1 型糖尿病和类风湿性关节炎，以及 3) 发育性疾病和退行性疾病，包括唇/腭裂、特发性脊柱侧弯和黄斑变性。推进该领域的发展并实现我们的计划目标。我们的方法通过创新的实验室和计算技术扩展了低成本全基因组测序（WGS）的发现能力，以全面探究人类基因组变异的全谱。我们在专家合作者的大量投入下开展了这些研究，他们的持续参与和特定疾病的专业知识对于成功至关重要，最终，我们拟议项目的多样性（在疾病表型、样本谱系和研究设计方面）将提供更好的结果。了解常见疾病的遗传结构及其在世界人口中的共享程度。