Mouse Genetics

核心A：小鼠遗传学。 摘要： 了解宿主遗传变异影响结核分枝杆菌的机制 (Mtb)易感性和疾病病理学需要优化和灵活的模型系统， 影响结核分枝杆菌的遗传变异可以在一系列遗传变异中鉴定、表征和操纵。 背景我们建议使用高度多样化的协作交叉鼠标面板， 发生基因多态性驱动的变异，结核病的疾病结果，然后调查 这些变异在一系列遗传背景中的机制。我们将通过分析， 遗传关联研究，以确定驱动小鼠品系之间差异的遗传变异， 小鼠杂交，以评估基因转录的变化如何影响下游Mtb疾病 结果，并产生突变小鼠品系，由此推定的遗传变异在 小鼠品系，以评估其疾病影响。我们将为人类遗传学核心提供一系列基因 其含有影响小鼠中的Mtb疾病的变体，用于在人类群组中测试。这提供了一个直接的联系， 实验数据与临床相关性。最后，我们将负责策展，存档和传播 将整个程序中生成的数据存储到可用的存储库中。

Core A: Mouse Genetics. Abstract: Understanding the mechanisms through which host genetic variation impacts Mycobacterium tuberculosis (Mtb) susceptibility and disease pathologies requires optimized and flexible model systems through which genetic variants affecting Mtb can be identified, characterized and manipulated across a range of genetic backgrounds. We propose usage of the highly diverse Collaborative Cross mouse panel to identify naturally occurring genetic polymorphisms driving variation in Mtb disease outcomes, and then investigate the mechanisms of these variants across a range of genetic backgrounds. We will assist the projects by analyzing genetic association studies to identify genetic variants driving differences between mouse lines, creating mouse crosses with which to assess how variation in gene transcription affects downstream Mtb disease outcomes, and also generate mutant mouse lines whereby putative genetic variants are swapped between mouse lines to assess their disease impact. We will provide the human genetics core with sets of genes containing variants affecting Mtb disease in mice for testing in human cohorts. This provides a direct tie from experimental data to clinical relevance. Lastly we will be responsible for curation, archiving and dissemination of the data generated throughout this program to publically available repositories.