Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles 英文参考文献.docVIP

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Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles 英文参考文献.doc

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Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles 英文参考文献

SeasonofConceptioninRuralGambiaAffectsDNA MethylationatPutativeHumanMetastableEpialleles RobertA.Waterland1,2*,RichardKellermayer1,EleonoraLaritsky1,PuraRayco-Solon3,R.AlanHarris2, MichaelTravisano4,WenjuanZhang1,MariaS.Torskaya1,JiexinZhang5,LanlanShen1,MarkJ.Manary1, AndrewM.Prentice3 1Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children’s Nutrition Research Center, Houston, Texas, United States of America, 2Department of MolecularandHumanGenetics,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica,3MRCInternationalNutritionGroup,LondonSchoolofHygiene and Tropical Medicine, London, United Kingdom, 4Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, Minnesota, United States of America,5DepartmentofBiostatisticsandAppliedBiomathematics,TheUniversityofTexasM.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica Abstract Throughoutmostofthemammaliangenome,geneticallyregulateddevelopmentalprogrammingestablishesdiverseyet predictableepigeneticstatesacrossdifferentiatedcellsandtissues.Atmetastableepialleles(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 permanentphenotypicconsequencesfortheoffspring.MEshavenotpreviouslybeenidentifiedinhumans.Here,usingan innovative2-tissueparallelepigenomicscreen,weidentifiedputativeMEsinthehumangenome.Inautopsysamples,we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages.MonozygotictwinpairsexhibitedsubstantialdiscordanceinDNAmethylationattheseloci,suggestingthattheir epigeneticstateisestablishedstochastically.Wethentestedforpersistentepigeneticeffectsofpericonceptionalnutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylatio