Zebrafish Core

斑马鱼核心

基本信息

批准号：
10201759
负责人：
Monte Westerfield
金额：
$ 25.42万
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/10201759
关键词：
Adult Affect Alleles Anatomy Animal Model Antisense Oligonucleotides Bioinformatics Biology Budgets CRISPR/Cas technology Candidate Disease Gene Categories Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Collection Communities Complex Data Development Diagnosis Diagnostic Disease Documentation Drosophila genus Effectiveness Family Fishes Funding Future Gene Expression Profile Gene Proteins Generations Genes Genetic Genome Goals Heritability Human Human Development Human Genetics Human Pathology Informatics Information Networks International Knockout Mice Leadership Medical Genetics Medicine Methods Missense Mutation Modeling Mus Mutation Ontology Oregon Organ Orthologous Gene Pathologic Patients Pattern Phase Phenotype Process Proteins RNA Interference Rare Diseases Reagent Research Resources Role Services Site Synteny System Techniques Testing Universities Validation Variant Zebrafish base body system candidate validation clinical research site cohort college cost effective design experience experimental study fly gain of function gain of function mutation gene function genetic resource genetic variant genome editing high throughput analysis human disease human genomics human model in vivo innovation innovative technologies knock-down loss of function loss of function mutation mutant new technology novel strategies phenotypic data screening symposium therapy development tool zebrafish genome

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.

项目概要拟议的针对未确诊患者的模式生物筛查中心（MOSC）的第二阶段延续疾病网络 (UDN) 建立在我们在第一阶段建立的广泛工具、试剂和管道的基础上。领导团队代表果蝇、斑马鱼和人类医学遗传学领域的国际专业知识。在第一阶段，MOSC 在 UDN 网关中开发了一个接口，支持提交病例、基因、以及临床中心为模式生物研究提出的变体。 MOSC 还开发了 MARRVEL (www.MARRVEL.org)，一种在线工具，集成人类和模型生物体数据并帮助确定优先级变种。 MOSC 进一步与独立资助的罕见疾病收藏建立合作我们使用贝勒医学院 (BCM) 的队列来识别 UDN 表型和遗传的匹配变种。 MOSC 定期与临床中心举行电话会议，并提供工具帮助他们选择变体。 MOSC 将继续与这些站点通话，审查信息分析，然后分配变体（估计每年 45 个），用于对变体和基因进行深入的模式生物研究。在 BCM 的果蝇核心每年利用创新技术研究约 30 个基因和变异在苍蝇中。对于影响脊椎动物特定基因或生物学的 15 个额外基因/变体，斑马鱼核心位于俄勒冈大学将利用 CRISPR/Cas9 在斑马鱼中诱导新突变，然后实现高通量表型分析。 MOSC 还将开发用于果蝇未来变异研究的工具和试剂斑马鱼每年额外增加 100 个基因。我们将与更广泛的人分享这些额外资源研究界通过创新的 ModelMatcher 服务，还将优先考虑基因的生成与敲除小鼠表型项目 (KOMP) 合作进行小鼠敲除。因此，拟议的中心将提供信息学选择、人类遗传学专业知识、广泛的多功能模型生物资源以及对 UDN 病例的深入研究以帮助诊断。 MOSC 采用了最具创新性的人类基因组学以及果蝇和斑马鱼遗传学技术，基于广泛的先前研究模拟人类疾病的经验。