Zebrafish Core

项目总结 拟议为未确诊患者继续建立模式生物筛选中心(MOSC)的第二阶段 疾病网络(UDN)建立在我们在第一阶段建立的广泛的工具、试剂和管道之上。 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……里面 第一阶段，MOSC在UDN网关中开发了一个接口，支持提交病例、基因、 以及临床站点为模型生物体研究提出的变种。MOSC还开发了MARRVEL (www.MARRVEL.org)，这是一个集成了人类和模型生物体数据的在线工具，有助于确定优先顺序 变种。MOSC进一步与独立资助的罕见疾病集合建立了合作关系 贝勒医学院(BCM)的队列，我们用来识别与UDN表型和基因匹配的 变种。MOSC定期与临床站点举行电话会议，并提供工具帮助他们 选择变体。MOSC将继续与站点通话，以审查信息分析，然后分配 变种(估计每年45个)，用于对变种和基因进行深入的模式生物研究。在 果蝇核心在BCM，每年大约有30个基因和变种被创新技术研究 在苍蝇中。有关影响脊椎动物特有基因或生物学的另外15个基因/变体，斑马鱼核心网站 俄勒冈大学将通过CRISPR/Cas9诱导斑马鱼新的突变，随后将高通量 表型分析。MOSC还将为未来对果蝇的变异研究开发工具和试剂 斑马鱼和斑马鱼每年额外增加100个基因。我们将与更广泛的 通过创新的ModelMatcher服务建立研究社区，并将为下一代确定基因的优先顺序 与Knokout Mouse表型项目(KOMP)合作，对鼠标基因敲除进行了研究。因此， 拟建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，以及对UDN病例的深入研究，以帮助诊断。MOSC雇佣了最具创新精神的 人类基因组学、果蝇和斑马鱼遗传学技术 体验对人类疾病的建模。

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.