Mouse Models of Neurological Disease

描述（由申请人提供）：本申请旨在扩展杰克逊实验室（JAX）和华盛顿大学（Wash U）临床与转化科学研究所（ICTS）之间的合作努力，以建立与神经疾病相关的小鼠和人类遗传学之间的综合互惠管道。为此，我们建议将NCRR资助的杰克逊实验室动物和生物材料资源（ABMR） （P40 RR001183，小鼠突变资源）和Wash U ICTS联合起来，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的致病突变。该试点项目证明了高通量测序可以提供一种途径，通过避免位置克隆过程，以前所未有的速度定义突变等位基因。我们建议建立一个用于自发突变鉴定的高通量测序管道，并且至关重要的是，我们建议开发应用该管道所需的序列分析工具，不仅用于神经疾病模型，还用于其他疾病领域，这些疾病领域适合由自发小鼠突变（即视觉，听力，前庭功能，颅面畸形等）建模。

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).