Mouse Genetics

小鼠遗传学

基本信息

批准号：
9359031
负责人：
Fernando Pardo-Manuel de Villena
金额：
$ 30.32万
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：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9359031
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 Imagery 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 base clinically relevant cohort congenic design experience experimental analysis flexibility gene function gene interaction genetic analysis genetic association genetic resource genetic variant in vivo interest molecular phenotype phenotypic data programs repository response trait 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（MTB）敏感性和疾病病理需要优化，灵活的模型系统可以在一系列遗传中识别，表征和操纵影响MTB的遗传变异背景。我们建议使用高度多样化的协作跨鼠标面板以自然识别发生遗传多态性导致MTB疾病结果的变化，然后研究这些变体在一系列遗传背景之间的机制。我们将通过分析来协助项目遗传关联研究以鉴定遗传变异驱动小鼠线之间的差异，创造小鼠交叉评估基因转录的变异如何影响下游MTB疾病结果，还产生突变的小鼠线，从而将假定的遗传变异交换在小鼠线以评估其疾病的影响。我们将为人类遗传学核心提供一组基因包含影响小鼠MTB疾病进行人类研究的变体。这提供了直接的领带实验数据与临床相关性。最后，我们将负责策划，归档和传播在整个程序中生成的数据，用于公开可用的存储库。