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Tissue-specific DNA methylation profiles in newborns

Emilie Herzog1, Jubby Galvez1, Anton Roks2, Lisette Stolk3, Michael Verbiest3, Paul Eilers4, Jan Cornelissen5, Eric Steegers1 and Régine Steegers-Theunissen16*

Author Affiliations

1 Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

2 Department of Internal Medicine, Section of Vascular Medicine and Pharmacology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

3 Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

4 Department of Biostatistics, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

5 Department of Haematology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

6 Department of Clinical Genetics, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands

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Clinical Epigenetics 2013, 5:8  doi:10.1186/1868-7083-5-8

Published: 31 May 2013

Abstract

Background

Epidemiological studies demonstrate that foetal growth restriction and low birth weight affect long-term health. Derangements in tissue-specific epigenetic programming of foetal and placental tissues are a suggested underlying mechanism of which DNA methylation is best understood. DNA methylation has been mostly investigated in DNA from white blood cells. To improve baseline understanding of tissue-specific DNA methylation, we examined variation in DNA methylation profiles of the imprinted foetal growth genes IGF2 and H19 in three different tissues from the same newborn obtained at the same time.

Findings

We obtained DNA from umbilical cord blood mononuclear cells (MNC; CD34+ and CD34, n = 6), foetal side of the placenta (n = 5) and umbilical cord Wharton jelly (n = 5). DNA methylation of the IGF2 differentially methylated region (DMR) and H19 DMR was measured using quantitative mass spectrometry. Analysis of variance testing showed no statistical difference between total mean methylation of CD34+ and CD34 MNC. Further comparisons were made with the pooled total MNC fraction. Mean IGF2 DMR methylation of Wharton jelly was 1.3 times higher (P = 0.001) than mean methylation of the pooled MNC. Placental mean methylation was 0.8 times lower (P <0.001) and Wharton jelly 0.9 times lower (P <0.001) than the pooled MNC of H19 DMR.

Conclusion

The total MNC fraction is a rather homogeneous cell population for methylation studies of imprinted genes in umbilical cord blood white blood cells, but may not always reflect the methylation levels of IGF2 and H19 in other organs.

Keywords:
Epigenetics; Umbilical cord blood; Wharton jelly; Placenta; IGF2/H19