A Platform for Large-Scale Discovery in Common Disease

 描述（由申请人提供）：一个大规模发现常见疾病的平台：项目摘要对遗传性人类疾病表型和保护性等位基因的基因组结构变异的全面了解将有助于改善诊断，预后，疾病管理和开发新的治疗方法，为全球数亿人。为了支持这一目标，我们建议应用我们已建立的最先进的DNA测序和分析平台，全面识别影响常见复杂疾病易感性的罕见变异，这些变异对应于三种疾病主题：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，和3）发育和退行性疾病，包括唇腭裂，特发性脊柱侧凸和黄斑变性。在可能的情况下，我们将利用新兴的方法和技术来推进该领域的发展，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，以全面询问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发了这些研究，他们的持续参与和疾病特异性专业知识对于成功至关重要。最终，我们提出的项目的多样性-在疾病表型，样本祖先和研究设计方面-将更好地了解常见疾病的遗传结构及其在世界人口中的共享程度。

 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.