Annotation

注解

• 批准号: 8893882
• 负责人: BRUCE A BEUTLER
• 金额: $ 45.4万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893882
• 关键词: Affect; Alleles; Anatomy; Archives; Behavior; Bioinformatics; Biological Process; Cataloging; Catalogs; Categories; Charge; Communities; Data; Detection; Development; Discipline; Disease; Ethylnitrosourea; Family; Funding; Gene Expression; Gene Family; Genes; Genetic; Genome; Grant; Heart; Histocompatibility Testing; Immunity; Immunology; Individual; Induced Mutation; Inflammation; Informatics; Institution; Instruction; Journals; Laboratories; Learning; Link; Modeling; Molecular Profiling; Mus; Mutant Strains Mice; Mutation; Phenotype; Process; Proteins; Publishing; Rest; Retrieval; Science; Scientist; System; Testing; Time; Tissues; Writing; base; cell type; exome; exome sequencing; forward genetics; gene function; gene interaction; genetic variant; immune activation; interest; macrophage; member; mouse genome; mutant; mutant mouse model; positional cloning; programs; protein structure; relational database; response; reverse genetics; screening; software development; sperm cell; tool; transmission process; web site

PROJECT SUMMARY (See instructions): Core C (Annotation) will fie together all of the Cores in this U19 program, as well as Projects 1 through 3, by annotating mutations found in sequencing Gl mutant exomes and disseminating data related to phenotypic mutations. It will coordinate the activities of the U19, and also grant the scientific community ready access to germline mutant mice that are available nowhere else in the world. The central vehicle for this process will be Mutagenetix, a website developed and tested over a period of four years by the Beutler and Goodnow laboratories, and slated for further development in the context of this program. Mutagenetix catalogues both phenotypic mutations (those known to cause phenovariance in mice, because they were detected in phenotypic screening), and incidental mutations (those that may or may not cause phenotype, because they were found through whole genome or whole exome sequencing). The latter category of mutations is growing rapidly, and more than 200,000 incidental mutations will be produced in the course of the five year project we propose. Each incidental mutation will be analyzed using an automated informatic process to assess the likelihood of an effect on protein structure, and every affected gene will also be functionally annotated by knowledgeable individuals Each incidental mutation will be made available in the form of germline mutant mice, derived from sperm that have been cryopreserved and archived for quick retrieval. Guided by Project 3 and Cores B and D, the Core A (Genetics) will make mice available for advanced, hypothesis-driven phenotypic analysis of the effects of mutations induced by ENU in specific genes. Multiple alleles of a single gene may be studied, along with allelic variants of multiple genes predicted to participate in individual biological functions. The Annotation Core will therefore support two basic enterprises. Unbiased forward genetics (Projects 1 and 2) will yield data that will be disseminated via Mutagenetix. And hypothesis-driven reverse genetics (Project 3) will permit the identification of even subtle effects of mutations that would not easily be detected in forward screening. The Annotation Core may be seen as the organizational heart of the U19.

项目摘要（请参阅说明）： 核心C（注释）将通过在测序GL突变体中发现的突变并传播与表型突变相关的数据，从而结合该U19程序中的所有核心以及项目1至3。它将协调U19的活动，并授予科学界可以访问世界上其他其他地方的种系突变小鼠。该过程的中央工具将是诱变，这是一个由Beutler和Goodnow Laboratories在四年内开发和测试的网站，并计划在该计划的背景下进行进一步的开发。诱变分类均表型突变（因为在表型筛查中检测到它们是在小鼠中引起表征能力的突变）和偶然突变（可能引起或可能不会引起表型的突变，因为它们是通过整个基因组或整个外显子组测序发现的）。后一种突变类别正在迅速增长，在我们提出的五年项目过程中将产生超过200,000个偶然突变。每个偶然突变将使用自动化的信息过程进行分析，以评估对蛋白质结构的影响的可能性，并且每个受影响的基因也将在功能上通过知识渊博的个体注释 每个偶然突变将以生殖线突变小鼠的形式提供，这些突变小鼠的形式是源自冷冻保存和存档的精子，以快速检索。在项目3和核B和D的指导下，核心A（遗传学）将使小鼠可用于对特定基因中ENU诱导的突变效应的高级，假设驱动的表型分析。可以研究单个基因的多个等位基因，以及预测参与个体生物学功能的多个基因的等位基因变体。因此，注释核心将支持两个基本企业。无偏向的前向遗传学（项目1和2）将产生通过诱变将传播的数据。假设驱动的反向遗传学（项目3）将允许鉴定突变的微妙效果，而在正向筛选中不容易被检测到。注释核心可能被视为U19的组织心脏。