Abstract
BackgroundMethylation of DNA at CpG sites is an epigenetic modification and a potential modifier of disease risk, possibly mediating environmental effects. Currently, DNA methylation is commonly assessed using specific microarrays that sample methylation at a few % of all methylated sites.MethodsTo understand if significant information on methylation can be added by a more comprehensive analysis of methylation, we set up a quantitative method, bisulfite oligonucleotide-selective sequencing (Bs-OS-seq), and compared the data with microarray-derived methylation data. We assessed methylation at two asthma-associated genes, IL13 and ORMDL3, in blood samples collected from children with and without asthma and fractionated white blood cell types from healthy adult controls.ResultsOur results show that Bs-OS-seq can uncover vast amounts of methylation variation not detected by commonly used array methods. We found that high-density methylation information from even one gene can delineate the main white blood cell lineages.ConclusionsWe conclude that high-resolution methylation studies can yield clinically important information at selected specific loci missed by array-based methods, with potential implications for future studies of methylation-disease associations.
Highlights
DNA methylation as an epigenetic marker has gained popularity in assessing the role of potential environmental modifiers in disease pathogenesis, leading to the emergence of the concept Epigenome-Wide Association Studies (EWAS)
One sample set consisted of sorted blood cell populations (CD4 + T cells, CD8 + T-cells, CD19 + B cells, CD14 + monocytes, granulocytes, and neutrophils) and peripheral blood mononuclear cells (PBMC) from 6 healthy adult male blood donors, and one set consisted of whole blood samples from 22
When we added information on the three clinical subgroups of the school-aged children, we demonstrated that the clustering based on methylation profiling of IL13 and ORMDL3 followed the measured cellular composition in the whole blood samples (Fig. 3b)
Summary
DNA methylation as an epigenetic marker has gained popularity in assessing the role of potential environmental modifiers in disease pathogenesis, leading to the emergence of the concept Epigenome-Wide Association Studies (EWAS). The popularity of this approach has been facilitated by the ease of analyzing genome-wide. In any epigenetic methylation study there is a risk of potentially missing a large body of information, but exactly how much, is typically not assessed. Methylation of DNA at CpG sites is an epigenetic modification and a potential modifier of disease risk, possibly mediating environmental effects. DNA methylation is commonly assessed using specific microarrays that sample methylation at a few % of all methylated sites
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