Gene expression profiling in Werner syndrome closely resembles that of normal aging - PubMed (original) (raw)

Comparative Study

. 2003 Oct 14;100(21):12259-64.

doi: 10.1073/pnas.2130723100. Epub 2003 Oct 3.

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Comparative Study

Gene expression profiling in Werner syndrome closely resembles that of normal aging

Kasper J Kyng et al. Proc Natl Acad Sci U S A. 2003.

Abstract

Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial to the development of the syndrome. We used cDNA microarrays to characterize the expression of 6,912 genes and ESTs across a panel of 15 primary human fibroblast cell lines derived from young donors, old donors, and WS patients. Of the analyzed genes, 6.3% displayed significant differences in expression when either WS or old donor cells were compared with young donor cells. This result demonstrates that the WS transcription defect is specific to certain genes. Transcription alterations in WS were strikingly similar to those in normal aging: 91% of annotated genes displayed similar expression changes in WS and in normal aging, 3% were unique to WS, and 6% were unique to normal aging. We propose that a defect in the transcription of the genes as identified in this study could produce many of the complex clinical features of WS. The remarkable similarity between WS and normal aging suggests that WS causes the acceleration of a normal aging mechanism. This finding supports the use of WS as an aging model and implies that the transcription alterations common to WS and normal aging represent general events in the aging process.

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Figures

Fig. 1.

Fig. 1.

(A) Replicate hybridizations. For each group of cell lines, two vials of RNA were isolated from identical cultures grown in parallel. Two independent probe preparations and hybridizations were made per pooled RNA sample, resulting in a total of four replicates. (B) Scatter plots of intra-group vs. inter-group variation. Based on three three-way comparisons, the average intra-group CV was 0.13 vs. an average inter-group CV of 0.28 based on 27 three-way comparisons. (C) Correlation between microarray data and RT-PCR. (D) Progression of gene expression analysis. Of the analyzed genes, 6.3% were differentially expressed in WS or aging. Of these, the genes with known function were categorized as being affected in WS only, aging only, or both.

Fig. 2.

Fig. 2.

Visual representation of gene expression changes associated with WS and normal aging. Shown are column charts illustrating the similar transcription profiles of old (A) and WS (B) cells when compared with young cells. Genes are plotted in the same order in A and B and are listed after expression level in old relative to young. All genes in this figure are listed in Table 6, and select examples are listed in Table 2.

Fig. 3.

Fig. 3.

Functional categories of gene expression changes associated with WS and normal aging. Percentage is given relative to all WS-old coregulated genes assigned to functional categories.

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