| Summary: | <p>Abstract</p> <p>Background</p> <p>We have previously shown that deviations from the average transcription profile of a group of functionally related genes are not only heritable, but also demonstrate specific patterns associated with age, gender and differentiation, thereby implicating genome-wide nuclear programming as the cause. To determine whether these results could be reproduced, a different micro-array database (obtained from two types of muscle tissue, derived from 81 human donors aged between 16 to 89 years) was studied.</p> <p>Results</p> <p>This new database also revealed the existence of age, gender and tissue-specific features in a small group of functionally related genes. In order to further analyze this phenomenon, a method was developed for quantifying the contribution of different factors to the variability in gene expression, and for generating a database limited to residual values reflecting constitutional differences between individuals. These constitutional differences, presumably epigenetic in origin, contribute to about 50% of the observed residual variance which is connected with a network of interrelated changes in gene expression with some genes displaying a decrease or increase in residual variation with age.</p> <p>Conclusion</p> <p>Epigenetic variation in gene expression without a clear concomitant relation to gene function appears to be a widespread phenomenon. This variation is connected with interactions between genes, is gender and tissue specific and is related to cellular aging.</p> <p>This finding, together with the method developed for analysis, might contribute to the elucidation of the role of nuclear programming in differentiation, aging and carcinogenesis</p> <p>Reviewers</p> <p>This article was reviewed by Thiago M. Venancio (nominated by Aravind Iyer), Hua Li (nominated by Arcady Mushegian) and Arcady Mushegian and J.P.de Magelhaes (nominated by G. Church).</p>
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