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Mouse Genetics

小鼠遗传学

基本信息

批准号：
10219085
负责人：
Fernando Pardo-Manuel de Villena
金额：
$ 34.29万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-05 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219085
关键词：
Affect Alleles Animals Archives Automobile Driving Biological Models Breeding CRISPR/Cas technology Candidate Disease Gene Communities Complex Core Facility Data Data Set Databases Detection Disease Disease Outcome Elements Epigenetic Process Exhibits Experimental Designs Gene Expression Gene Expression Profiling Generations Genes Genetic Genetic Epistasis Genetic Polymorphism Genetic Transcription Genetic Variation Genetic study Genome Genotype Goals Human Human Genetics Immune Response Genes Inbred Strains Mice Infection Knock-out Link Maps Mouse Strains Mus Mutant Strains Mice Mycobacterium tuberculosis North Carolina Nucleic Acid Regulatory Sequences Online Systems Outcome Pathogenesis Pathology Pathway interactions Phenotype Population Heterogeneity Predisposition Protein Isoforms Quantitative Trait Loci Resources Role Scheme System Technology Testing Tuberculosis Universities Variant Visualization base clinically relevant cohort congenic data dissemination design experience experimental analysis flexibility gene function gene interaction genetic analysis genetic association genetic resource genetic variant in vivo interest molecular phenotype mouse genetics phenotypic data programs public repository response trait variant detection whole genome

项目摘要

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.

核心A：小鼠遗传学。抽象的：了解宿主遗传变异影响结核分枝杆菌的机制（结核分枝杆菌）易感性和疾病病理学需要优化且灵活的模型系统，通过该系统影响 Mtb 的基因变异可以在一系列基因中被识别、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发生的遗传多态性驱动结核分枝杆菌疾病结果的变化，然后调查这些变异在一系列遗传背景下的机制。我们将通过分析来协助项目遗传关联研究，以确定导致小鼠品系之间差异的遗传变异，从而创建小鼠杂交以评估基因转录变异如何影响下游结核分枝杆菌疾病结果，并且还产生突变小鼠品系，从而在之间交换推定的遗传变异小鼠系来评估其疾病影响。我们将为人类遗传学核心提供基因组含有影响小鼠结核分枝杆菌疾病的变异体，用于在人类队列中进行测试。这提供了直接联系实验数据与临床相关性。最后我们将负责策展、归档和传播将整个计划生成的数据存储到公开可用的存储库中。