MICROARRAY EXPRESSION PROFILING OF RODENT MODELS OF HUMA

HUMA 啮齿动物模型的微阵列表达谱分析

• 批准号: 6391256
• 负责人: HARALAMBOS GAVRAS GAVRAS
• 金额: $ 7.28万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391256
• 关键词: blood; complementary DNA; cooperative study; disease /disorder model; gene environment interaction; gene expression; genotype; heart; laboratory mouse; laboratory rat; lung; microarray technology; phenotype

PROPOSED PROGRAM (Adapted from the Applicant's Abstract) The theme of this application is examining gene/environment interactions in rodent models of human disease using cDNA microarrays to link phenotype to genotype. Disease phenotypes arise from complex interactions of organisms with their environments. While the investigators have a long history of associating genes and gene defects with a large array of disease phenotypes, a growing body of data suggests that many disease phenotypes arise from the interactions of genes with their environments, including the genetic background in which the genes are expressed. The goal is to begin an exploration of these interactions using rodent models of human disease and cDNA microarray assays to elucidate patterns of gene expression. This PGA brings together biologists, statisticians, computer scientists, engineers, and physicists who are will lend their expertise to the achievement of the common goals. The proposal builds on existing expertise at TIGR in the analysis of gene expression using cDNA microarrays, the mouse mutagenesis and phenotyping programs that have been developed by The Jackson Laboratories and their collaborators at Penn, Duke, and Boston Universities, and the efforts in rat genomics underway at the Medical College of Wisconsin, including the generation of phenotypically characterized consomic and congenic rat strains. Linking these programs are coordinated efforts in informatics that will both facilitate data exchange between consortium members and will make that data easily accessible to the wider research community. Underlying this is a commitment to continuing to develop and improve the reagents and assays to provide a firm statistical basis for any inferences that the assays provide. Finally, the investigators maintain a commitment to community service and will provide reagents, software, and data generated as part of this PGA to the wider research community. The investigators will develop high-density mouse and rat cDNA microarrays and use these to characterize gene expression in mouse and rat models of heart, lung, and blood diseases as well as sleep disorders. The rodent models to be surveyed will be ascertained by measuring phenotypic response of congenic, consomic, and mutagenized animals to environmental challenges known to elicit responses relevant to these diseases. Gene expression data will be integrated with genotype and phenotype data and analyzed to begin to develop a more complete understanding of the mechanistic basis for these diseases as well as the modifying and mitigating factors contributed by the environment.

拟议的计划（根据申请人的摘要进行改编） 该应用程序的主题是检查基因/环境相互作用 使用cDNA微阵列将表型联系起来的人类疾病的啮齿动物模型 基因型。 疾病表型来自生物体的复杂相互作用 环境。 虽然调查人员有悠久的历史 具有大量疾病表型的基因和基因缺陷，增长 数据主体表明，许多疾病表型来自相互作用 具有环境的基因，包括遗传背景 表达基因。 目标是开始探索这些 使用人类疾病和cDNA微阵列分析的啮齿动物模型的相互作用 阐明基因表达的模式。 该PGA汇集了生物学家，统计学家，计算机科学家， 工程师和物理学家将为成就提供专业知识 共同目标。 该提案建立在TIGR现有专业知识的基础上 使用cDNA微阵列，小鼠诱变和 杰克逊实验室开发的表型程序和 他们在宾夕法尼亚州，杜克大学和波士顿大学的合作者，以及 威斯康星州医学院正在进行的大鼠基因组学，包括 具有表型特征的综合和先天大鼠菌株的产生。 将这些程序链接到信息学方面是协调的努力 促进财团会员之间的数据交换，并将提供该数据 更广泛的研究社区很容易获得。 基础是 致力于继续开发和改善试剂和测定的承诺 为分析提供的任何推论提供牢固的统计基础。 最后，调查人员保持对社区服务的承诺，并将 提供作为此PGA的一部分生成的试剂，软件和数据 更广泛的研究社区。 研究人员将开发高密度小鼠和大鼠cDNA微阵列，以及 使用这些来表征小鼠和心脏大鼠模型中的基因表达， 肺，血液疾病以及睡眠障碍。 啮齿动物模型是 测量的调查将通过测量Encenic的表型反应来确定 综合动物和诱变的动物应对引起的环境挑战 与这些疾病有关的反应。 基因表达数据将集成 有了基因型和表型数据，并进行了分析以开始开发更多 完全了解这些疾病的机理基础 环境贡献的修改和缓解因素。