Fig. 2

Genome-wide methylation analysis of tissue heterogeneity within the human placenta. a–c Four samples were taken from the maternal to the fetal side of a single full-term human placenta. The term placenta was not from the MARBLES study and had no known pathologies. Average methylation was calculated in non-overlapping 20 kb windows tiled across the autosomes. CpG islands were not removed. For comparison, the 24 MARBLES typical placental samples are shown in gray. a Methylation across the p arm of chromosome 1 and b the q arm of chromosome 21 as examples. Curves were smoothed with a first order local polynomial. c Distribution of average window methylation across all autosomes with kernel density smoothing. d Average methylation of CpG sites in PMDs/HMDs on each individual autosome. PMD/HMD boundaries were determined as in Fig. 1e. e Blinded methylation pyrosequencing of two PMDs and HMDs from 24 placental samples. Samples were randomly selected from six placental regions in ten non-MARBLES placentas with no known pathologies. Data were jittered along the y axis for visibility. Data from Schroeder et al. (2013). f Effect of maternal blood contamination on PMD methylation in male placentas. To epigenetically quantify maternal blood contamination levels, DNA methylation was assessed in the CpG island promoters of genes in chrX HMDs. These regions normally have low methylation in males but higher methylation in females due to X chromosome inactivation