Figure 1

Genomewide screen for human MEs. (a) DNA methylation in PBL is highly correlated across the two individuals included in the screen, C01 and C02. The density plot summarizes all 4.1 million 200 bp bins that were covered by sufficient read depth in both samples (R² = 0.926). (b) Interindividual DNA methylation residuals (C01-C02) in HF versus those in PBL; 3.9 million 200 bp bins were informative in all four samples. The hyperbola delineates regions containing potential MEs. (c) Genomewide, most bins showed no evidence of genetic discordance between the two individuals. Regions of systemic interindividual variation (SIVI ≥20), however, were enriched for interindividual genetic variation. (d) HF versus PBL interindividual residual plot for the 4,852 filtered ME bins (SIVI ≥20, no genetic variation, no segmental duplication). The SIVI algorithm effectively targeted the regions indicated in panel (b). (e) Targeted analysis of Blueprint Epigenome data (DNA methylation in monocytes of six healthy individuals); ME bins with six or more CpG sites exhibit greatest interindividual variation. (f) Interindividual discordance of DNA methylation (C02 versus C01) of the 109 ME bins containing 6 or more CpG sites. (g) Manhattan plot of SIVI for all 200 bp bins with 6 or more CpG sites. Bins with SIVI ≥20 (candidate MEs) are crowned; gene-associated bins with SIVI ≥25 are labeled.