Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans
- Huriya Beyan1,6,
- Thomas A. Down2,6,
- Sreeram V. Ramagopalan1,3,6,
- Kristina Uvebrant4,
- Anita Nilsson4,
- Michelle L. Holland1,
- Carolina Gemma1,
- Gavin Giovannoni1,
- Bernhard O. Boehm5,
- George C. Ebers3,
- Åke Lernmark4,
- Corrado M. Cilio4,
- R. David Leslie1,7 and
- Vardhman K. Rakyan1,7
- 1The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom;
- 2The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, United Kingdom;
- 3Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, United Kingdom;
- 4Department of Clinical Sciences, Lund University, Skåne University Hospital SUS, 205 02 Malmö, Sweden;
- 5Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm and Center of Excellence “Metabolic Disorders” Baden-Württemberg, 89070 Ulm, Germany
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↵6 These authors contributed equally to this work.
Abstract
A major concern in common disease epigenomics is distinguishing causal from consequential epigenetic variation. One means of addressing this issue is to identify the temporal origins of epigenetic variants via longitudinal analyses. However, prospective birth-cohort studies are expensive and time consuming. Here, we report DNA methylomics of archived Guthrie cards for the retrospective longitudinal analyses of in-utero-derived DNA methylation variation. We first validate two methodologies for generating comprehensive DNA methylomes from Guthrie cards. Then, using an integrated epigenomic/genomic analysis of Guthrie cards and follow-up samplings, we identify interindividual DNA methylation variation that is present both at birth and 3 yr later. These findings suggest that disease-relevant epigenetic variation could be detected at birth, i.e., before overt clinical disease. Guthrie card methylomics offers a potentially powerful and cost-effective strategy for studying the dynamics of interindividual epigenomic variation in a range of common human diseases.
Footnotes
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↵7 Corresponding authors
E-mail v.rakyan{at}qmul.ac.uk
E-mail r.d.g.leslie{at}qmul.ac.uk
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.134304.111.
- Received November 14, 2011.
- Accepted June 8, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
