Mouse Genetics

核心A：小鼠遗传学。 摘要： 了解宿主基因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，通过这些系统 影响结核分枝杆菌的遗传变异可以在一系列基因上被识别、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来自然识别 正在发生的基因多态导致结核分枝杆菌疾病预后的变化，然后调查 这些变异的机制跨越了一系列的遗传背景。我们将通过分析来协助这些项目 遗传关联研究，以确定驱动小鼠品系之间差异的遗传变异，创造 评估基因转录变异如何影响下游结核分枝杆菌病的小鼠杂交 结果，并产生突变的小鼠品系，由此推测的遗传变异在 以评估它们对疾病的影响。我们将为人类遗传学核心提供一组基因 含有影响小鼠结核分枝杆菌病的变种，用于在人类队列中进行测试。这提供了与 实验数据与临床相关。最后，我们将负责管理、存档和传播 将在整个计划中生成的数据存储到公共可用的存储库。

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.