Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles.
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 maint...
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Public Library of Science (PLoS)
2010-12-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001252&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Robert A Waterland |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-22fb21c93460465bbf41d2d3353e3175 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2010-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-22fb21c93460465bbf41d2d3353e31752025-08-20T03:19:50ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-12-01612e100125210.1371/journal.pgen.1001252Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles.Robert A WaterlandRichard KellermayerEleonora LaritskyPura Rayco-SolonR Alan HarrisMichael TravisanoWenjuan ZhangMaria S TorskayaJiexin ZhangLanlan ShenMark J ManaryAndrew M PrenticeThroughout 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001252&type=printable |
| spellingShingle | 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 Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. PLoS Genetics |
| title | Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. |
| title_full | Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. |
| title_fullStr | Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. |
| title_full_unstemmed | Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. |
| title_short | Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. |
| title_sort | season of conception in rural gambia affects dna methylation at putative human metastable epialleles |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001252&type=printable |
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