Fig. 1

Genotypic differences in forward and reverse strand methylation. a (i) On reads from both strands of the wild-type C allele, the methylated C usually remains as C after bisulfite conversion, and is counted as methylated. This results in a mean difference of methylation between the strands of 0. (ii) For the allele where the methylated C is replaced by A, reads on the forward strand have the A at the CpG site and are not counted, whereas the reads on the reverse strand have the C bisulfite-converted to U and are counted as unmethylated. This results in a mixture of methylated and unmethylated reads on the reverse strand, whereas there are only methylated reads on the forward strands. b Heterozygotes that have A and C alleles (red) are compared with homozygotes that have two copies of the C allele (turquoise). We see negligible difference in methylation rate between forward and reverse strands in the 26 homozygous individuals, but an average of around 50 % more methylation on the forward versus the reverse strand in the 13 heterozygous individuals