Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles

• DOI: 10.1371/journal.pgen.1001252
• Publication Date: 2010-12-23T21:36:20Z
• 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
• Keywords: Epigenome; Epigenomics; Epigenesis; Genomic Imprinting; Reprogramming

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 early embryo then maintained lineages, resulting dramatic systemic interindividual variation regulation. In mouse, maternal nutrition affects this process, with permanent phenotypic consequences for offspring. MEs have not previously been identified humans. Here, using an innovative 2-tissue parallel epigenomic screen, we putative human genome. autopsy samples, showed that DNA methylation at these loci highly correlated tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance loci, suggesting their state stochastically. We tested persistent effects periconceptional rural Gambians, who experience seasonal fluctuations nutritional status. was elevated individuals conceived during nutritionally challenged rainy season, providing first evidence a permanent, effect environment on epigenotype. MEs, regulation internal organs varies among can be deduced from peripheral blood DNA. should therefore facilitate improved understanding role disease.