Fig. 5: Validation of a novel cell-type-specific parental-ASM region in the CHD7 gene.
From: Atlas of imprinted and allele-specific DNA methylation in the human body
A Fragment-level analysis of a novel parent-of-origin cell-type-specific ASM region we identified (chr8:61627212-61627412, hg19) shows biallelic methylation (red) in endothelial cells, neurons, fibroblasts, and blood cells, but bimodal methylation patterns in hepatocytes and epithelial cells (1:1 ratio of fully methylated and fully unmethylated sequenced fragments of ≥3 CpGs). B–F Genetic/epigenetic analysis of parental allele-specific methylation in tongue-epithelial cells, validated across 15 families (a total of 33 children and their parents, Data S7). For each trio, we used targeted-PCR next-generation sequencing (after bisulfite conversion) to measure the genotype (rs7826035, C/T, chr8:61627312 hg19) and the methylation status of six CpG sites (chr8:61627190-61627349 hg19, measured on the bottom strand). B A trio (family ID IMP017) showing homozygous C/C for the mother, with C/T heterozygosity for the father. The child T allele is therefore of paternal origin. Blue bars correspond to relative allelic read count. Unmethylated DNA fragments (green bars) are limited to the parental T allele, suggesting maternal-specific methylation. C same as (B) for a family with three heterozygous children (family ID IMP012). D A family where the T allele of heterozygous child 1 is maternal, whereas unmethylated fragments (green) are all from the paternal C allele. Two additional siblings are C/C homozygous and not shown (family ID IMP005). E–F Examples of a C/C homozygous family and a C/T heterozygous family, where the parent-of-origin of unmethylated fragments cannot be associated with a parent-of-origin (family IDs IMP014, IMP011). All remaining families were homozygous (C/C, not shown). G Bimodal tissue count track (orange) and -log10 of Fisher’s method for combining Fisher’s exact p values for allele-specific methylation at individual samples (blue track), along with a gene annotation track showing the region surrounding the identified DMR.
