Figure 5

Identification of hypomethylation at the GNAS locus in MLMD samples. Upper panel: Genomic location from the UCSC genome browser, illustrating the GNAS locus and three regions of high CpG density harbouring differentially methylated regions. Lower panel: graphical presentation of 450 k DNA methylation data across the GNAS locus TND-MLMD 2 (red) and BWS-MLMD 4 (blue). The x-axis corresponds to the genomic location as illustrated in the upper panel. The primary y-axis (left) represents the CH P value (solid lines); the secondary y-axis (right) represents the difference in M values between cases and controls (dashed lines). Note the hypomethylation clearly visible at three locations in TND-MLMD 2, coinciding with the more subtle hypomethylation detectable in BWS-MLMD 4 primarily through significance of P value. BWS-MLMD, Beckwith-Wiedemann syndrome-multi-locus methylation disorders; TND-MLMD, transient neonatal diabetes-multi-locus methylation disorders.