Supplementary Figure 3: P3 exhibits the same DNA hypermethylation pattern.
a, Regions with methylation gain identified in patient 1 (P1) and patient 2 (P2) fibroblasts (DNMT3AW330R/+) also gain DNA methylation in patient 3 (P3; DNMT3AD333N/+) peripheral blood leukocytes (PBLs; ‘blood samples’). Heatmaps for DMRs with methylation gain in P1 and P2 fibroblasts, and P2 and P3 PBLs, excluding DMRs absent from P3 RRBS data. C1–C4, healthy controls. b, Regions that lose DNA methylation in fibroblasts identified in P1 and P2 do not lose DNA methylation in P3 PBLs. Heatmaps for DMRs with methylation loss in P1 and P2 fibroblasts, and P2 and P3 PBLs, excluding DMRs absent from P3 RRBS data. c, Quantification of DNA methylation for DMRs depicted for P3 in a and b. Box, 25th–75th percentile; whiskers, full data range; center line, median; ∆%mCpG P3-C3, percent change of methylation in patient 3 relative to control 3. n = 282 hypo-DMRs and n = 845 hyper-DMRs. d, Representative genome browser views of hypermethylated DMRs (n = 845) demonstrating increased DNA methylation at the same developmental genes in patient P3 (compare Fig. 3f). CpGs with coverage depth of ≥5 reads in both samples are plotted. All tracks are scaled 0–100%. mCpG, DNA methylation; CGI, CpG island.
