Figure 1

FXS-associated differentially methylated loci. (A) Modified Manhattan plot of FXS-associated methylation levels in the peripheral blood: loci are displayed with the –log10(P-value) generated by the linear mixed-effect model (y-axis). Horizontal lines reflect cutoffs for FDR <0.05 (blue line) and Bonferroni-adjusted P-value <0.05 (red line). FMR1 annotated loci are shown in red; otherwise, loci are colored black or gray on alternating chromosomes (x-axis). (B) Relative locations of FMR1 methylation. Top panel shows the methylation levels (y-axis) in FXS (orange squares) and control (blue crosses) individuals at several loci annotated in or near the FMR1 locus. Shown below are the relative CpG coverage (vertical black lines) and CpG island location (green rectangle). Bottom panel depicts a gene schematic of FMR1, indicating the relative location of the CGG repeat (expanded in FXS), the FMR1 transcription start site (TSS), and exons 1 and 2. The ideogram of the X chromosome (bottom) shows the relative location of FMR1 (red vertical bar), and the genomic position shown above is relative to HG-19 coordinates. (C and D) FMR1 promoter DNA methylation levels in peripheral blood and iPS cells. Top panel shows box and whisker plots of the methylation levels (y-axis) in FXS (orange) and control (blue) individuals at several loci annotated in the FMR1 promoter. Bottom panel is described in B.