Mouse Models of Neurological Disease

神经疾病小鼠模型

• 批准号: 8320232
• 负责人: LEAH RAE B DONAHUE
• 金额: $ 21.08万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320232
• 关键词: Alleles; Animals; Area; Biocompatible Materials; Bypass; Clinical; Clinical Sciences; Collection; DNA Sequence Rearrangement; Data; Development; Disease; Disease model; Dysmorphology; Elements; Funding; Future; Genes; Genome; Goals; Hearing; Homologous Gene; Human; Human Genetics; Human Genome; Inbred Strain; Institutes; Maps; Modeling; Mus; Mutant Strains Mice; Mutation; Mutation Detection; National Center for Research Resources; Neurologic; Phenotype; Pilot Projects; Population; Population Analysis; Process; Resources; Sequence Analysis; Technology; Testing; The Jackson Laboratory; Time; Translational Research; Universities; Variant; Vision; Washington; base; clinical phenotype; cost; craniofacial; exome; gene discovery; high throughput analysis; human disease; mouse genome; mouse model; mutant; nervous system disorder; next generation; patient oriented; positional cloning; programs; tool

DESCRIPTION (provided by applicant): This request seeks to extend a collaborative effort between The Jackson Laboratory (JAX) and the Washington University (Wash U) Institute for Clinical and Translational Sciences (ICTS) to establish an integrated, reciprocal pipeline between mouse and human genetics related to neurological disease. Toward this end, we propose to bring together the NCRR funded Animal and Biological Materials Resource (ABMR) at The Jackson Laboratory (P40 RR001183, Mouse Mutant Resource) and Wash U ICTS in a combined effort to use high throughput sequencing to identify the causative mutations in up to 40 mutants with clinical manifestations of neurological disease. This pilot project is a proof of principle that high throughput sequencing can provide a path by which mutant alleles can be defined at an unprecedented rate by obviating the positional cloning process. We propose to establish a high-throughput sequencing pipeline for spontaneous mutation identification, and critically, we propose to develop the sequence analysis tools needed to apply this pipeline, not only to models of neurological disease, but also to other disease areas that are appropriately modeled by spontaneous mouse mutants (i.e. vision, hearing, vestibular function, craniofacial dysmorphology, etc).

描述（由申请人提供）：此请求旨在扩大杰克逊实验室 (JAX) 和华盛顿大学 (Wash U) 临床和转化科学研究所 (ICTS) 之间的合作，以在与神经系统疾病相关的小鼠和人类遗传学之间建立一个集成的、互惠的管道。为此，我们建议将 NCRR 资助的 Jackson 实验室动物和生物材料资源 (ABMR)（P40 RR001183，小鼠突变体资源）和 Wash U ICTS 联合起来，利用高通量测序来识别多达 40 个具有神经系统疾病临床表现的突变体的致病突变。该试点项目证明了高通量测序可以提供一条途径，通过避免定位克隆过程，可以以前所未有的速度定义突变等位基因。我们建议建立一个用于自发突变识别的高通量测序流程，更重要的是，我们建议开发应用该流程所需的序列分析工具，不仅适用于神经系统疾病模型，而且适用于由自发小鼠突变体适当建模的其他疾病领域（即视觉、听力、前庭功能、颅面畸形等）。