This Article Free Full Text Free Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boorman, G. A. Articles by Portier, C. J. Search for Related Content PubMed PubMed Citation Articles by Boorman, G. A. Articles by Portier, C. J. Social Bookmarking                   What's this?

Variation in the Hepatic Gene Expression in Individual Male Fischer Rats

¹ Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
² Battelle Science and Technology International, Columbus, Ohio 43201, USA
³ Paradigm Genetics Inc., Research Triangle Park, North Carolina 27709, USA
⁴ Constella Group, Inc., Research Triangle Park, North Carolina 27709, USA

Correspondence: Address correspondence to: Dr. Gary. A Boorman, ETP, NIEHS, P.O. Box 12233, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA; e-mail:boorman{at}niehs.nih.gov

A new tool beginning to have wider application in toxicology studies is transcript profiling using microarrays. Microarrays provide an opportunity to directly compare transcript populations in the tissues of chemical-exposed and unexposed animals. While several studies have addressed variation between microarray platforms and between different laboratories, much less effort has been directed toward individual animal differences especially among control animals where RNA samples are usually pooled. Estimation of the variation in gene expression in tissues from untreated animals is essential for the recognition and interpretation of subtle changes associated with chemical exposure. In this study hepatic gene expression as well as standard toxicological parameters were evaluated in 24 rats receiving vehicle only in 2 independent experiments. Unsupervised clustering demonstrated some individual variation but supervised clustering suggested that differentially expressed genes were generally random. The level of hepatic gene expression under carefully controlled study conditions is less than 1.5-fold for most genes. The impact of individual animal variability on microarray data can be minimized through experimental design.

Key Words: Liver • rat • mRNA • differential gene expression • microarray • variation • transcriptome • controls

Abbreviations: F344, Fischer 344/N • DGE, Differential Gene Expression • NTP, National Toxicology Program • PCA, Principal Components Analysis • SAM, Significance Analysis of Microarrays • QA, Pathology Quality Assurance

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Mori, P. E. Blackshear, E. K. Lobenhofer, J. S. Parker, D. P. Orzech, J. H. Roycroft, K. L. Walker, K. A. Johnson, T. A. Marsh, R. D. Irwin, et al. Hepatic Transcript Levels for Genes Coding for Enzymes Associated with Xenobiotic Metabolism are Altered with Age Toxicol Pathol, February 1, 2007; 35(2): 242 - 251. [Abstract] [Full Text] [PDF]

				H. Wang, R. A. Ach, and B. Curry Direct and sensitive miRNA profiling from low-input total RNA RNA, January 1, 2007; 13(1): 151 - 159. [Abstract] [Full Text] [PDF]

				J. Fostel, D. Choi, C. Zwickl, N. Morrison, A. Rashid, A. Hasan, W. Bao, A. Richard, W. Tong, P. R. Bushel, et al. Chemical Effects in Biological Systems--Data Dictionary (CEBS-DD): A Compendium of Terms for the Capture and Integration of Biological Study Design Description, Conventional Phenotypes, and 'Omics Data Toxicol. Sci., December 1, 2005; 88(2): 585 - 601. [Abstract] [Full Text] [PDF]

				G. A. Boorman, P. E. Blackshear, J. S. Parker, E. K. Lobenhofer, D. E. Malarkey, M. K. Vallant, D. K. Gerken, and R. D. Irwin Hepatic Gene Expression Changes throughout the Day in the Fischer Rat: Implications for Toxicogenomic Experiments Toxicol. Sci., July 1, 2005; 86(1): 185 - 193. [Abstract] [Full Text] [PDF]