Fig. 4.
Extension of the WGBS data to a comprehensive set of newborns and nonagenarians and the observed overlap in premature aging disorders. (A) The curves of the distance correlation between the methylation status of the neighboring CpG sites of newborns (blue line) and nonagenarians (red line) samples determined by the 450 K microarray. A more pronounced declining curve indicates lower correlation in terms of the methylation status of nearby CpGs. (B) Unsupervised hierarchical clustering of the 283,579 CpGs present in the 450 K methylation array (after exclusion of SNP-associated and X and Y chromosome CpG sites) in the newborn and nonagenarian groups. (C) Schematic overview of the assessment of differentially methylated CpG sites between the initial newborn and 103-y-old sample and the cohort of 19 newborns and 19 nonagenarians. (D) Hierarchical clustering approach using the 1,149 WGBS-derived dmCpGs in the newborn and nonagenarian groups. (E) Supervised clustering analysis with the 165 DMRs (214 dmCpG dinucleotides) that distinguished the two groups. (F) Hierarchical clustering approach using the additional 5,774 450K-dmCpG sites in the newborn and nonagenarian groups. (G) (Upper) The 450K-dmCpG distribution among different genomic sequences; (Lower) Distribution of the 450K-dmCpGs according to the direction of the DNA methylation change and the type of promoter (with or without a CpG island).