Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epigenetics

Identical twins: epigenetics makes the difference

With their identical genetic make-up, monozygotic twins are firm favourites for sorting out genetic effects from those of the environment. But in a recent study it was the differences between identical twins that made them such fascinating research subjects: widespread epigenetic differences between twins that accumulate over the years indicate an important way that age and the environment might affect human health.

Manel Esteller and colleagues measured the total levels of two key epigenetic modifications — DNA methylation and histone acetylation — across the genomes of 40 pairs of monozygotic twins. For 65% of the pairs the twins had almost identical epigenetic profiles, but for the remaining 35% there were significant differences. Interestingly, there was a clear relationship between the age of the twins and the amount of difference between them. The amount of epigenetic difference was also correlated with spending large amounts of time apart and having different medical histories. So changes accumulated over time or influenced by environmental factors seem to have important effects on the epigenome.

To determine the biological significance of these epigenetic differences, the authors used a methylation fingerprinting technique in which distinct DNA bands correspond to individual methylated regions. Sequencing the bands that differed between identical twins revealed that although 52% of them corresponded to repetitive regions, the remainder reflected changes at predicted or known genes.

Importantly, the regions that were differentially methylated between twins also included CpG islands located in promoter regions, indicating potential effects on gene expression. This was confirmed by microarray analysis: whereas the expression profiles for pairs of 3-year-old twins were almost identical, there were large differences between the profiles of 50-year-old twins.

Alterations in gene expression that arise from global epigenetic changes over time are likely to have an important influence on susceptibility to many types of disease. The next challenge will be to work out how these changes arise: do they result from the cumulative effects of defects in epigenetic maintenance or transmission, or do environmental factors such as diet and exposure to pollutants have a role?

References

ORIGINAL RESEARCH PAPER

  1. 1

    Fraga, M. F. et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl Acad. Sci. 102, 10604–10609 (2005)

    CAS  Article  Google Scholar 

FURTHER READING

  1. 2

    Fazzari, M. J. & Greally, J. M. Epigenomics: beyond CpG islands. Nature Rev. Genet. 5, 446–455 (2004)

    CAS  Article  Google Scholar 

  2. 3

    Robertson, K. D. DNA methylation and human disease. Nature Rev. Genet. 6, 597–610 (2005)

    CAS  Article  Google Scholar 

Download references

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Flintoft, L. Identical twins: epigenetics makes the difference. Nat Rev Genet 6, 667 (2005). https://doi.org/10.1038/nrg1693

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing