Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans
- Huriya Beyan1,
- Thomas Down2,
- Sreeram Ramagopalan3,
- Kristina Uvebrant4,
- Anita Nilsson4,
- Michelle Holland1,
- Carolina Gemma1,
- Gavin Giovannoni1,
- Bernhard Boehm5,
- George Ebers3,
- Ake Lernmark4,
- Corrado Cillio4,
- David Leslie1 and
- Vardhman Rakyan1,6
- 1 Barts and The London School of Medicine and Dentistry,;
- 2 Cambridge University;
- 3 Oxford University;
- 4 Lund University;
- 5 Ulm University
- ↵* Corresponding author; email: v.rakyan{at}qmul.ac.uk
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, though prospective birth-cohort studies are expensive and time-consuming. Here we propose 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 inter-individual DNA methylation variation that is present both at birth and three years 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 inter-individual epigenomic variation in a range of common human diseases.
- Received November 14, 2011.
- Accepted June 8, 2012.
- © 2012, Published by Cold Spring Harbor Laboratory Press
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