Mouse Models of Neurological Disease

描述（由申请方提供）：本申请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，以在小鼠和人类神经系统疾病相关遗传学之间建立一个集成的互惠管道。为此，我们建议将杰克逊实验室（P40 RR001183，小鼠突变体资源）的NCRR资助的动物和生物材料资源（ABMR）与华盛顿大学ICTS结合起来，共同努力使用高通量测序来鉴定多达40种具有神经系统疾病临床表现的突变体中的致病突变。该试验项目证明了高通量测序可以提供一种途径，通过该途径，可以通过避免定位克隆过程以前所未有的速度定义突变等位基因。我们建议建立一个高通量的测序管道自发突变识别，关键是，我们建议开发应用这个管道所需的序列分析工具，不仅神经系统疾病的模型，而且其他疾病领域，适当地模仿自发小鼠突变（即视觉，听力，前庭功能，颅面畸形等）。

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).