Center for functional analysis of human UDN gene homologs in Drosophila and zebrafish

果蝇和斑马鱼人类UDN基因同源物功能分析中心

基本信息

批准号：
10201756
负责人：
HUGO J BELLEN
金额：
$ 53.52万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201756
关键词：
Affect Alleles Animal Model Bacterial Artificial Chromosomes Bioinformatics Biology CRISPR/Cas technology Cells Cellular biology Clinical Research Collaborations Collection Communities Comparative Study Complement Complementary DNA Data Databases Diagnosis Diagnostic Disease Drosophila genus Etiology Experimental Designs Fibroblasts Financial compensation Fishes Functional disorder Funding Future Generations Genes Genetic Genetic Phenomena Genomics Goals Homologous Gene Human Human Cell Line Human Genetics Informatics International Knock-in Knockout Mice Leadership Learning Medical Medical Genetics Medicine Messenger RNA Modeling Molecular Mus Mutation Oregon Organ Orthologous Gene Pathogenicity Patients Pattern Phase Phenotype Rare Diseases Reagent Research Research Infrastructure Research Personnel Resources Services Site Synteny System TNFSF5 gene Testing Tissues Transgenic Organisms Tube United States National Institutes of Health Universities Variant Zebrafish base bioinformatics pipeline bioinformatics tool body system clinical research site cohort college disease diagnosis experience experimental study fly gene conservation gene function genetic resource genetic testing genetic variant human data human disease human genomics human model human subject improved innovation innovative technologies insight interest loss of function loss of function mutation mindfulness model organisms databases mutant novel overexpression personalized approach phenotypic data programs role model screening symposium tool

项目摘要

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.

项目摘要未诊断的模型生物体筛选中心（MOSC）提出的II期延续疾病网络（UDN）以我们在第一阶段建立的广泛工具，试剂和管道为基础。领导团队代表果蝇，斑马鱼和人类医学遗传学的国际专业知识。在第一阶段，MOSC在UDN网关中开发了一个接口，该接口支持提交病例，基因，以及用于模型生物学研究的临床部位提出的变体。 MOSC还开发了摩尔维尔（www.marrvel.org），一种在线工具，可以整合人类和模型有机体数据并有助于优先级变体。 MOSC进一步建立了与独立资助的稀有疾病收集的合作我们用来识别与UDN表型和遗传的匹配的贝勒医学学院（BCM）的队列变体。 MOSC与临床站点举行常规电话会议，并提供了帮助他们的工具选择变体。 MOSC将继续与网站联系以审查信息分析，然后分配对变体和基因的深入模型生物研究的变体（估计为45个）。在 BCM的果蝇核心每年使用创新技术研究了大约30个基因和变体在苍蝇中。对于影响脊椎动物特异性基因或生物学的另外15种基因/变体，斑马鱼核俄勒冈大学将使用CRISPR/CAS9诱导斑马鱼的新突变，然后是高通量表型分析。 MOSC还将开发果蝇未来变体研究的工具和试剂斑马鱼每年再有100个基因。我们将与更广泛的资源分享这些额外的资源通过创新的ModelMatcher服务研究社区，还将优先考虑生成的基因与敲除小鼠表型项目（KOMP）合作的小鼠敲除。因此，拟议的中心将提供信息学选择，人类遗传学专业知识，广泛的多功能模型有机体资源和对UDN病例的深入研究，以帮助诊断。 MOSC采用最具创新性的人类基因组学和果蝇和斑马鱼遗传学的技术，基于广泛的先前经验建模人类疾病。