Direct Determination of Mouse Genome-Wide, Allele-specific DNA Methylation from Nanopore Long-Read Sequencing

Asymmetric expression patterns between the two parental alleles are critical for development of the mammalian embryo. This process known as imprinting involves differential DNA methylation of the parental genomes. We sequence mouse embryonic placenta tissue on the Oxford Nanopore MinION and exploit the long reads to determine, using novel methods, both haplotype and CpG methylation levels. Comparison with matched Reduced-Representation Bisulfite Sequencing data confirms the accuracy of the methylation calls, and highlights the improvement in haplotyping conferred by the longer reads. We successfully identify known imprinting control regions, as well as novel differentially methylated regions. Based on their proximity to hitherto unknown monoallelically expressed genes, we propose that some of these regions could constitute new imprinting control regions.