Docherty, Sophia J., Davis, Oliver S. P., Haworth, Claire M. A., Plomin, Robert and Mill, Jonathan (2009) Bisulfite-based epityping on pooled genomic DNA provides an accurate estimate of average group DNA methylation. Epigenetics & Chromatin, Volume 2 . Article number 3. ISSN 1756-8935.

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Abstract

Background:
DNA methylation plays a vital role in normal cellular function, with aberrant methylation signatures being implicated in a growing number of human pathologies and complex human traits. Methods based on the modification of genomic DNA with sodium bisulfite are considered the 'gold-standard' for DNA methylation profiling on genomic DNA; however, they require relatively large amounts of DNA and may be prohibitively expensive when used on the large sample sizes necessary to detect small effects. We propose that a high-throughput DNA pooling approach will facilitate the use of emerging methylomic profiling techniques in large samples.

Results:
Compared with data generated from 89 individual samples, our analysis of 205 CpG sites spanning nine independent regions of the genome demonstrates that DNA pools can be used to provide an accurate and reliable quantitative estimate of average group DNA methylation. Comparison of data generated from the pooled DNA samples with results averaged across the individual samples comprising each pool revealed highly significant correlations for individual CpG sites across all nine regions, with an average overall correlation across all regions and pools of 0.95 (95% bootstrapped confidence intervals: 0.94 to 0.96).

Conclusion:
In this study we demonstrate the validity of using pooled DNA samples to accurately assess group DNA methylation averages. Such an approach can be readily applied to the assessment of disease phenotypes reducing the time, cost and amount of DNA starting material required for large-scale epigenetic analyses.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science, Engineering and Medicine > Science > Psychology
Library of Congress Subject Headings (LCSH):	DNA -- Methylation
Journal or Publication Title:	Epigenetics & Chromatin
Publisher:	BioMed Central Ltd.
ISSN:	1756-8935
Official Date:	10 March 2009
Dates:	Date Event 10 March 2009 Published
Volume:	Volume 2
Article Number:	Article number 3
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 July 2016
Date of first compliant Open Access:	28 July 2016
Funder:	University of London, Royal Society (Great Britain)

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