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Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo

Derakhshan, Maria; Kessler, Noah J; Ishida, Miho; Demetriou, Charalambos; Brucato, Nicolas; Moore, Gudrun E; Fall, Caroline HD; ... Silver, Matt J; + view all (2022) Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo. Nucleic Acids Research , Article gkac503. 10.1093/nar/gkac503. (In press). Green open access

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Abstract

We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs (‘hvCpGs’) with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

Type: Article
Title: Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/nar/gkac503
Publisher version: https://doi.org/10.1093/nar/gkac503
Language: English
Additional information: © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/)
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10150967
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