title: Transcriptional changes in trichothiodystrophy cells.
abstract: Mutations in three of the genes encoding the XPB, XPD and TTDA components of transcription factor TFIIH can result in the clinical phenotype of trichothiodystrophy (TTD). Different mutations in XPB and XPD can instead cause xeroderma pigmentosum (XP). The completely different features of these disorders have been attributed to TTD being a transcription syndrome. In order to detect transcriptional differences between TTD and XP cells from the XP-D complementation group, we have compared gene expression profiles in cultured fibroblasts from normal, XP and TTD donors. Although we detected transcriptional differences between individual cell strains, using an algorithm of moderate stringency, we did not identify any genes whose expression was reproducibly different in proliferating fibroblasts from each type of donor. Following UV-irradiation, many genes were up- and down-regulated in all three cell types. The microarray analysis indicated some apparent differences between the different donor types, but on more detailed inspection, these turned out to be false positives. We conclude that there are minimal differences in gene expression in proliferating fibroblasts from TTD, XP-D and normal donors.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Offman
authors.forename: Nipurna
authors.initials: N
authors.lastname: Jina
authors.forename: Therina
authors.initials: T
authors.lastname: Theron
authors.forename: Jacky
authors.initials: J
authors.lastname: Pallas
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.forename: Alan
authors.initials: A
authors.lastname: Lehmann
mesh_terms: D002478:Cells, Cultured; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D054463:Trichothiodystrophy Syndromes / Q000235:genetics* / Q000473:pathology; D014466:Ultraviolet Rays