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. 2015 Mar;25(3):338–352. doi: 10.1101/gr.180273.114

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© 2015 Spiers et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0.

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Figure 1. — DNA methylation changes during human brain development are widespread across the genome. (A) Overview of the 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 DPC profiled in this study. (B) Manhattan plot showing the widespread distribution of Bonferroni-significant fetal brain dDMPs (P-value corresponds to association with age). (C) The four top-ranked dDMPs showing increased DNA methylation with fetal age (hypermethylated dDMPs). DNA methylation (%) is plotted against DPC. Females are shown in pink, males in blue. (D) The four top-ranked dDMPs showing decreased DNA methylation with fetal age (hypomethylated dDMPs). DNA methylation (%) is plotted against DPC. Females are shown in pink, males in blue. (E) Many loci are characterized by regions of extended differential DNA methylation associated with fetal brain development. Shown is the TTYH3 gene that contains three discrete differentially methylated regions (DMRs), which become hypomethylated during fetal brain development. The top panel depicts the association statistic for individual probes, with color corresponding to significance. The bottom panel depicts the regression coefficient between DNA methylation and brain development for individual probes, with a line of best-fit highlighting three domains characterized by hypomethylation across brain development.