MICROARRAY EXPRESSION PROFILING OF RODENT MODELS OF HUMA

建议课程(改编自申请者摘要) 这个应用程序的主题是研究基因和环境之间的相互作用 利用基因芯片将表型与人类疾病相关联的啮齿动物模型 基因分型。 疾病表型产生于生物体与其自身的复杂相互作用 环境。虽然调查人员有很长一段时间 基因和基因缺陷伴随着大量的疾病表型，越来越多 大量数据表明，许多疾病表型是由这种相互作用产生的 基因与其环境的关系，包括基因背景 这些基因得到了表达。我们的目标是开始探索这些 利用人类疾病啮齿动物模型与基因芯片分析的相互作用 以阐明基因表达的模式。 本届PGA汇聚了生物学家、统计学家、计算机科学家、 工程师和物理学家将为这一成就贡献他们的专业知识 共同的目标。该提案建立在TIGR现有的专业知识基础上 用基因芯片分析基因表达，小鼠的诱变和 由杰克逊实验室开发的表型程序和 他们在宾夕法尼亚大学、杜克大学和波士顿大学的合作者，以及在 威斯康星医学院正在进行老鼠基因组学研究，包括 产生具有表型特征的共生和同源大鼠品系。 将这些项目联系在一起的是信息学方面的协调努力，它将既 促进联盟成员之间的数据交换，并将这些数据 更广泛的研究社区可以轻松访问。这背后是一个 致力于继续开发和改进试剂和分析方法，以 为化验提供的任何推论提供坚实的统计基础。 最后，调查人员保持对社区服务的承诺，并将 将作为本PGA一部分生成的试剂、软件和数据提供给 更广泛的研究社区。 研究人员将开发高密度的小鼠和大鼠基因芯片，并 用这些来表征小鼠和大鼠心脏模型中的基因表达， 肺部疾病、血液疾病以及睡眠障碍。未来的啮齿动物模型 调查将通过测量同源基因的表型反应来确定， 共生和诱变动物对环境的挑战已知会引发 与这些疾病相关的反应。基因表达数据将被整合 随着基因型和表型数据的分析，开始发展出更多 对这些疾病的机制基础以及 环境对环境的改造和缓解因素。

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.