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题目:: Transcription profiling of rat liver display strain-specific, hereditary and AHR-Dependent Components
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状态:: 发布时间Nov. 28, 2009 , 更新时间 May 2, 2014 , 提交时间 Feb. 8, 2008,
物种:: Rattus norvegicus
摘要:: Background; The rat is a major model organism in toxicogenomics and pharmacogenomics, and the use of steady-state hepatic mRNA levels to predict and understand drug toxicity and mechanism is well-established. Surprisingly, the inter- and intra-strain variability of rat mRNA expression has not been evaluated, nor has the extent of its hereditability been established. We address these issues by studying three rat strains (Long-Evans, Hans/Wistar, and Sprague-Dawley) and two F2 lines derived from Long-Evans x Hans/Wistar crosses. Results; Using three independent techniques – variance analysis, linear modelling, and unsupervised pattern recognition – we characterize large amounts of both intra- and inter-strain variability in mRNA levels. Importantly, both sources of variability are highly non-random, and are enriched for specific functional groups. Specific transcription-factor binding-sites are enriched in their promoter regions, and these genes occur in “islands” throughout the rat genome. Using the two F2 crosses we study the hereditability of hepatic mRNA levels and show that the majority of rat genes appear to exhibit directional genetics, with only a small fraction having evidence for interacting loci. Finally, a comparison of inter-strain heterogeneity between mouse and rat orthologs shows more heterogeneity in rats than mice, and find that rat and mouse heterogeneity are uncorrelated. Conclusions; Our results establish that hepatic mRNA levels are relatively homogeneous within rat strains, but highly variable between them. This variability may be related to increased activity specific transcription-factors, and has clear functional consequences. Future toxicogenomic and pharmacogenomic studies may take advantage of this phenomenon by surveying panels of rat strains. Experiment Overall Design: We profiled the basal mRNA levels in three strains and two lines of rat, each using four biological replicates.
实验种类:: transcription profiling by array
样本量:: 20
实验设计:
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数据号:: E-GEOD-10448, GSE10448
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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