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Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles.

Authors :
Robert A Waterland
Richard Kellermayer
Eleonora Laritsky
Pura Rayco-Solon
R Alan Harris
Michael Travisano
Wenjuan Zhang
Maria S Torskaya
Jiexin Zhang
Lanlan Shen
Mark J Manary
Andrew M Prentice
Source :
PLoS Genetics, Vol 6, Iss 12, p e1001252 (2010)
Publication Year :
2010
Publisher :
Public Library of Science (PLoS), 2010.

Abstract

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.

Subjects

Subjects :
Genetics
QH426-470

Details

Language :
English
ISSN :
15537390, 15537404, and 93460465
Volume :
6
Issue :
12
Database :
Directory of Open Access Journals
Journal :
PLoS Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.22fb21c93460465bbf41d2d3353e3175
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pgen.1001252