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Updated: Aug 9, 2026

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
Hereditary profiles of disorderly transcription?
1Department of Toxicogenetics, MGC, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. j.w.i.m.simons@lumc.nl
Background:
Microscopic examination of living cells often reveals that cells from some cell strains appear to be in a permanent state of disarray without obvious reason. In all probability such a disorderly state affects cell functioning. The aim of this study was to establish whether a disorderly state could occur that adversely affects gene expression profiles and whether such a state might have biomedical consequences. To this end, the expression profiles of the 14 genes of the proteasome derived from the GEO SAGE database were utilized as a model system.
Results:
By adopting the overall expression profile as the standard for normal expression, deviation in transcription was frequently observed. Each deviating tissue exhibited its own characteristic profile of over-expressed and under-expressed genes. Moreover such a specific deviating profile appeared to be epigenetic in origin and could be stably transmitted to a clonal derivative e.g. from a precancerous normal tissue to its tumor. A significantly greater degree of deviation was observed in the expression profiles from the tumor tissues. The changes in the expression of different genes display a network of interdependencies. Therefore our hypothesis is that deviating profiles reflect disorder in the localization of genes within the nucleus. The underlying cause(s) for these disorderly states remain obscure; it could be noise and/or deterministic chaos. Presence of mutational damage does not appear to be predominantly involved.
Conclusion:
As disturbances in expression profiles frequently occur and have biomedical consequences, its determination could prove of value in several fields of biomedical research.
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