QTL Analysis in Combined Inbred Line Crosses

组合自交系杂交中的QTL分析

• 批准号: 8286865
• 负责人: Gary A Churchill
• 金额: $ 34.11万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8286865
• 关键词: Animal Model; Animals; Biochemical; Biological Models; Candidate Disease Gene; Chromosome Mapping; Complement; Complex; Computer software; Constitution; Data; Data Analyses; Development; Disease; Disease susceptibility; Experimental Designs; Gene Expression; Genes; Genetic; Genetic Polymorphism; Haplotypes; Human; Human Genetics; Inbreeding; Intervention; Language; Lesion; Maps; Meta-Analysis; Methods; Modeling; Mus; Online Systems; Outcome; Pathway interactions; Phenotype; Population; Population Heterogeneity; Process; Public Health; Quantitative Trait Loci; Randomized; Recombinant Inbred Strain; Recombinants; Research Design; Resolution; Resources; Rodent Model; Software Tools; Statistical Methods; Transcript; Variant; Work; base; computerized tools; density; design; gene discovery; genetic analysis; genome wide association study; human subject; network models; protein profiling; public health relevance; research study; response; success; tool

DESCRIPTION (provided by applicant): Forward genetics approaches using animal models are undergoing a period of change, in part in response to the changes that have occurred in human genetics in the past few years. New experimental designs, including the collaborative cross and advanced heterogeneous stock populations, have the potential to yield large populations of animals with a genetic constitution that more accurately reflects the human genetic state with regard to diversity and heterozygosity. In addition, there has been rapid development of inexpensive high- throughput phenotyping capabilities, notably with gene expression microarrays, but metabolite and protein profiling will soon cross thresholds of quality and affordability. These changes necessitate the development of new computational and statistical tools for interpreting data. Our aims are to develop statistical methods in anticipation of new experimental approaches, to develop and disseminate software and data resources, and to analyze and interpret new and historical data from forward genetics experiments in mice. Our focus will shift from the historical objectives which emphasized gene discovery to new model-based approaches that exploit high dimensional and cumulative data to model systemic responses to genetic and environmental perturbations. The timely development of statistical methods and software will be critical to the success of mouse genetics in the coming years. PUBLIC HEALTH RELEVANCE: Experimental animals provide an important complement to genetic studies in humans and are essential when experiments involve potentially harmful exposure or are impossible to carry out with human subjects. This project will develop statistical and computational tools that are needed to interpret the outcomes of these experiments including newly developed approaches which enable us to work with mouse populations that more accurately reflect the human genetic state. )

描述（由申请人提供）：使用动物模型的正向遗传学方法正在经历一段时间的变化，部分原因是对过去几年人类遗传学发生的变化的响应。新的实验设计，包括协作交叉和先进的异质种群，有可能产生大量的动物的遗传组成，更准确地反映了人类的遗传状态方面的多样性和杂合性。此外，廉价的高通量表型分析能力已经迅速发展，特别是基因表达微阵列，但代谢物和蛋白质谱分析将很快跨越质量和可负担性的阈值。这些变化需要开发新的计算和统计工具来解释数据。我们的目标是开发统计方法，预测新的实验方法，开发和传播软件和数据资源，并分析和解释来自小鼠正向遗传学实验的新数据和历史数据。我们的重点将从强调基因发现的历史目标转移到新的基于模型的方法，利用高维和累积数据来模拟遗传和环境扰动的系统反应。统计方法和软件的及时开发将是未来几年小鼠遗传学成功的关键。 公共卫生相关性：实验动物为人类遗传学研究提供了重要补充，在实验涉及潜在有害暴露或不可能对人类受试者进行实验时至关重要。该项目将开发解释这些实验结果所需的统计和计算工具，包括新开发的方法，使我们能够更准确地反映人类遗传状态的小鼠种群。)