Fig. 2
DMR detection in difficult-to-sequence regions. A Genome-wide screening of DMRs between two haplotypes using DSS in Ctr11. DMR calls that overlapped with well-characterized imprinting DMRs (iDMRs) from multiple studies and iDMRs from single studies are annotated in red and blue, respectively. The difference in methylation levels between haplotypes (X-axis) and areaStat parameter (Y-axis) from DSS is plotted. Y-axis is limited to (0,10,000) and two datapoints with high areaStat values have been removed to aid visualization. Arrow indicates H19 iDMR shown in Fig. 2B. B IGV visualization of nanopore reads for H19 iDMR in Ctr11. Haplotype-aware long-range methylation analysis revealed unmethylated CpG (blue) and methylated CpG (red) in haplotypes 1 (HP1) and 2 (HP2), respectively. The orange rectangle represents segmental duplication (Seg.Dup). C Heatmap visualization of methylation levels of two haplotypes (HP1 and HP2) at 96 well-characterized iDMRs in Ctr11. D Genome-wide screening of DMRs in a case of extreme NOTCH2NLC GGC repeat expansion (NOTCH2NLC_F3_father) and 8 healthy controls (Ctr1 to Ctr8). DMRs detected by DSS are plotted as shown in Fig. 2A. Y-axis is limited to (0,10,000) and two datapoints with high areaStat values have been removed to aid visualization. Arrow indicates aberrant DNA hypermethylation with NOTCH2NLC GGC repeat expansion. Regions with an absolute value of areaStat greater than 500 (|areaStat|> 500, blue dashed line) and an absolute value of methylation difference greater than 0.2 (|methylation difference|> 0.2, red dashed lines) are considered as significant DMRs. DMRs were annotated in the context of genome annotation by the Homer program (see methods). TSS: transcription start site, UTR: untranslated region, TTS: transcription termination site. E IGV visualization of nanopore reads of heterozygous NOTCH2NLC GGC repeat expansion with hypermethylated CpG (red), whereas non-expanded alleles are hypomethylated (blue) in a case of extreme GGC expansion of NOTCH2NLC and in Ctr. The orange rectangle represents segmental duplication (Seg.Dup). Ctr: healthy control. Sample information is listed in Supplementary Table 1