The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles
Open accessAbstract
Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease.
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Cites
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Epigenetic differences arise during the lifetime of monozygotic twins
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Method
Cited by
Epigenetics and the environment: emerging patterns and implications
Feil, R., & Fraga, M. F. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3142 · Cited by 1,929
Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398
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Origins of lifetime health around the time of conception: causes and consequences
Fleming, T. P., Watkins, A. J., Velazquez, M. A., Mathers, J. C., Prentice, A. M., Stephenson, J., Barker, M., Saffery, R., Yajnik, C. S., Eckert, J. J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30312-x · Cited by 1,147
Self-citationFolate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role
Crider, K. S., Yang, T. P., Berry, R. J., & Bailey, L. B. (2012) · Advances in Nutrition · doi:10.3945/an.111.000992 · Cited by 1,015
Metadata
- Authors
- Waterland, R. A., Kellermayer, R., Laritsky, E., Rayco-Solon, P., Harris, R. A., Travisano, M., Zhang, W., Torskaya, M. S., Zhang, J., Shen, L., Manary, M. J., & Prentice, A. M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-23
- Volume
- 6
- Issue
- 12
- Pages
- e1001252
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2051330882
- Cited by
- 454
- References
- 49
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- gold
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- Waterland, R. A., Kellermayer, R., Laritsky, E., Rayco-Solon, P., Harris, R. A., Travisano, M., Zhang, W., Torskaya, M. S., Zhang, J., Shen, L., Manary, M. J., & Prentice, A. M. (2010). Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1001252
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