Drosophila Core

项目摘要 拟议的第二阶段继续模式生物筛选中心（MOSC）为未确诊的 疾病网络（UDN）建立在我们在第一阶段建立的广泛的工具，试剂和管道上。的 领导团队代表了果蝇、斑马鱼和人类医学遗传学方面的国际专业知识。在 第一阶段，MOSC在UDN网关中开发了一个界面，支持提交病例、基因， 以及临床研究中心建议用于模式生物研究的变体。MOSC还开发了MARRVEL （www.MARRVEL.org），这是一个在线工具，它整合了人类和模式生物的数据，并有助于确定优先顺序 变体。MOSC进一步与独立资助的罕见疾病收藏建立了合作关系。 贝勒医学院（Baylor College of Medicine）的队列，我们用它来识别与UDN表型和遗传学的匹配。 变体。MOSC定期与临床研究中心举行电话会议，并提供工具，帮助他们 选择变量。MOSC将继续致电研究中心，以审查信息分析，然后分配 变异体（估计每年45个），用于对变异体和基因进行深入的模式生物研究。在 果蝇核心研究中心每年利用创新技术研究约30个基因和变异体 苍蝇。对于影响脊椎动物特异性基因或生物学的另外15个基因/变体， 俄勒冈州大学将用CRISPR/Cas9在斑马鱼中诱导新的突变， 表型分析MOSC还将为未来的果蝇变体研究开发工具和试剂 和斑马鱼每年增加100个基因。我们将与更广泛的组织分享这些额外资源。 研究社区通过创新的ModelMatcher服务，还将优先考虑基因的产生 与敲除小鼠表型分析项目（KOMP）合作，因此 拟议的中心将提供信息学选择，人类遗传学专业知识，广泛的多功能模式生物 资源，并对UDN病例进行深入研究，以帮助诊断。MOSC采用最具创新性的 技术在人类基因组学和果蝇和斑马鱼遗传学，基于广泛的以前 模拟人类疾病

PROJECT SUMMARY The proposed Phase II continuation of the Model Organism Screening Center (MOSC) for the Undiagnosed Diseases Network (UDN) builds on extensive tools, reagents, and pipelines that we established in Phase I. The leadership team represents international expertise in Drosophila, zebrafish, and human medical genetics. In Phase I, the MOSC developed an interface in the UDN Gateway that supports submission of cases, genes, and variants that the clinical sites propose for model organism studies. The MOSC also developed MARRVEL (www.MARRVEL.org), an online tool that integrates human and model organism data and helps to prioritize variants. The MOSC further established collaborations with independently funded collections of rare disease cohorts at Baylor College of Medicine (BCM) that we use to identify matches to UDN phenotypes and genetic variants. The MOSC holds regular conference calls with clinical sites and provides tools that help them to select variants. The MOSC will continue calls with the sites to review informatic analyses and then assign variants (estimated at 45 per year) for in-depth model organism studies of variants and genes. In the Drosophila Core at BCM, approximately 30 genes and variants per year are studied with innovative technology in flies. For 15 additional genes/variants that affect vertebrate-specific genes or biology, the Zebrafish Core at the University of Oregon will induce new mutations in zebrafish with CRISPR/Cas9 followed by high throughput phenotypic analyses. The MOSC will also develop tools and reagents for future variant studies in Drosophila and zebrafish for an additional 100 genes per year. We will share these additional resources with the broader research community through an innovative ModelMatcher service and will also prioritize genes for generation of mouse knock-outs in collaboration with the Knockout Mouse Phenotyping Project (KOMP). Thus, the proposed center will provide informatics selection, human genetics expertise, broad versatile model organism resources, and in-depth studies of UDN cases to aid in diagnosis. The MOSC employs the most innovative technologies in human genomics and Drosophila and zebrafish genetics, based on extensive previous experience modeling human disease.