title: Variation in the hepatic gene expression in individual male Fischer rats.
abstract: 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.
authors.affiliation: Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. boorman@niehs.nih.gov
authors.forename: Gary A
authors.initials: GA
authors.lastname: Boorman
authors.forename: Richard D
authors.initials: RD
authors.lastname: Irwin
authors.forename: Molly K
authors.initials: MK
authors.lastname: Vallant
authors.forename: Diane K
authors.initials: DK
authors.lastname: Gerken
authors.forename: Edward K
authors.initials: EK
authors.lastname: Lobenhofer
authors.forename: Milton R
authors.initials: MR
authors.lastname: Hejtmancik
authors.forename: Patrick
authors.initials: P
authors.lastname: Hurban
authors.forename: April M
authors.initials: AM
authors.lastname: Brys
authors.forename: Greg S
authors.initials: GS
authors.lastname: Travlos
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Portier
mesh_terms: D000818:Animals; D015870:Gene Expression; D020869:Gene Expression Profiling; D014644:Genetic Variation; D008099:Liver / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D012333:RNA, Messenger