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Selective Survival ...
Selective Survival of Embryos Can Explain DNA Methylation Signatures of Adverse Prenatal Environments
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- Tobi, Elmar W. (author)
- Leiden University Medical Centre,Wageningen University
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- van den Heuvel, Joost (author)
- University of Newcastle upon Tyne,University of Oxford,Wageningen University
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- Zwaan, Bas J. (author)
- Wageningen University
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- Lumey, L. H. (author)
- Leiden University Medical Centre,Columbia University
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- Heijmans, Bastiaan T. (author)
- Leiden University Medical Centre
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- Uller, Tobias (author)
- Lund University,Lunds universitet,Evolutionär ekologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Evolutionary ecology,Department of Biology,Faculty of Science,University of Oxford
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 25:10, s. 4-2667
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Abstract
Subject headings
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- An adverse intrauterine environment is associated with long-term physiological changes in offspring. These are believed to be mediated by epigenomic marks, including DNA methylation (DNAm). Changes in DNAm are often interpreted as damage or plastic responses of the embryo. Here, we propose that stochastic DNAm variation, generated during remodeling of the epigenome after fertilization, contributes to DNAm signatures of prenatal adversity through differential survival of embryos. Using a mathematical model of re-methylation in the early embryo, we demonstrate that selection, but not plasticity, will generate a characteristic reduction in DNAm variance at loci that contribute to survival. Such a reduction in DNAm variance was apparent in a human cohort prenatally exposed to the Dutch famine, illustrating that it is possible to detect a signature of selection on epigenomic variation. Selection should be considered as a possible mechanism linking prenatal adversity to subsequent health and may have implications when evaluating interventions. Tobi et al. hypothesize that prenatal adversity can cause selection on epigenomic profiles in utero. Their model predicts that such selection reduces the variance in DNA methylation at genomic regions that contribute to survival, which is testable and detectable in empirical data from the Dutch famine.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Evolutionsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Evolutionary Biology (hsv//eng)
Keyword
- developmental origins
- DNA methylation
- plasticity
- selection
Publication and Content Type
- art (subject category)
- ref (subject category)
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