Using long-read sequencing to detect imprinted DNA methylation

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 PromethION and exploit the long reads to determine 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. Our method better defines known imprinted control regions and uncovers new regions with parent-of-origin or strain-specific methylation.