MICROARRAY EXPRESSION PROFILING OF RODENT MODELS OF HUMA

建议摘要（改编自申请人摘要） 本申请的主题是研究基因/环境相互作用， 使用cDNA微阵列将表型与人类疾病联系起来的啮齿动物模型 基因型 疾病表型是由生物体与它们的 环境. 虽然调查人员长期以来一直将 基因和基因缺陷与大量的疾病表型，一个不断增长的 大量数据表明，许多疾病表型是由这些相互作用引起的， 基因与环境的关系，包括基因背景， 基因被表达。 我们的目标是开始探索这些 使用人类疾病的啮齿动物模型和cDNA微阵列测定的相互作用 来阐明基因表达的模式 这个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把他们的专业知识用于这项成就， 的共同目标。 该提案建立在TIGR现有的专业知识基础上， 使用cDNA微阵列分析基因表达，小鼠诱变和 由杰克逊实验室开发的表型分析程序， 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 威斯康星州医学院正在进行的大鼠基因组学研究，包括 表型特征的同源和同源大鼠品系的产生。 将这些计划联系起来的是信息学方面的协调努力， 促进联合体成员之间的数据交换，并将使这些数据 更广泛的研究社区可以轻松访问。 这背后是一个 承诺继续开发和改进试剂和检测试剂， 为分析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小鼠和大鼠cDNA微阵列， 使用这些来表征小鼠和大鼠心脏模型中的基因表达， 肺部和血液疾病以及睡眠障碍。 啮齿类动物模型是 调查将通过测量同类的表型反应来确定， 致突变动物对环境挑战的耐受性 与这些疾病有关的反应。 基因表达数据将被整合 基因型和表型数据，并进行分析，以开始制定一个更 完全了解这些疾病的机制基础，以及 由环境促成的修改和缓解因素。

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.