DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome

Ollikainen, Miina, Smith, Katherine R, Joo, Eric Ji-Hoon, Ng, Hong Kiat, Andronikos, Roberta, Novakovic, Boris, Abdul Aziz, Nur Khairunnisa, Carlin, John B, Morley, Ruth, Saffery, Richard and Craig, Jeffrey M 2010, DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome, Human molecular genetics, vol. 19, no. 21, pp. 4176-4188, doi: 10.1093/hmg/ddq336.

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Title DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome
Author(s) Ollikainen, Miina
Smith, Katherine R
Joo, Eric Ji-Hoon
Ng, Hong Kiat
Andronikos, Roberta
Novakovic, Boris
Abdul Aziz, Nur Khairunnisa
Carlin, John B
Morley, Ruth
Saffery, Richard
Craig, Jeffrey MORCID iD for Craig, Jeffrey M orcid.org/0000-0003-3979-7849
Journal name Human molecular genetics
Volume number 19
Issue number 21
Start page 4176
End page 4188
Total pages 13
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2010-11-01
ISSN 0964-6906
1460-2083
Keyword(s) CpG Islands
DNA Methylation
Female
Genetic Variation
Genome, Human
Humans
Infant, Newborn
Insulin-Like Growth Factor II
RNA, Long Noncoding
RNA, Untranslated
Uterus
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
Summary Mounting evidence from both animal and human studies suggests that the epigenome is in constant drift over the life course in response to stochastic and environmental factors. In humans, this has been highlighted by a small number of studies that have demonstrated discordant DNA methylation patterns in adolescent or adult monozygotic (MZ) twin pairs. However, to date, it remains unclear when such differences emerge, and how prevalent they are across different tissues. To address this, we examined the methylation of four differentially methylated regions associated with the IGF2/H19 locus in multiple birth tissues derived from 91 twin pairs: 56 MZ and 35 dizygotic (DZ). Tissues included cord blood-derived mononuclear cells and granulocytes, human umbilical vein endothelial cells, buccal epithelial cells and placental tissue. Considerable variation in DNA methylation was observed between tissues and between unrelated individuals. Most interestingly, methylation discordance was also present within twin pairs, with DZ pairs showing greater discordance than MZ pairs. These data highlight the variable contribution of both intrauterine environmental exposures and underlying genetic factors to the establishment of the neonatal epigenome of different tissues and confirm the intrauterine period as a sensitive time for the establishment of epigenetic variability in humans. This has implications for the effects of maternal environment on the development of the newborn epigenome and supports an epigenetic mechanism for the previously described phenomenon of 'fetal programming' of disease risk.
Language eng
DOI 10.1093/hmg/ddq336
Field of Research 06 Biological Sciences
11 Medical And Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2010, The Author
Persistent URL http://hdl.handle.net/10536/DRO/DU:30119162

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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