Mammalian zygotes receive functionally distinct haploid genomes from each parent. Parent-of-origin differential allelic methylation dictates parentally biased expression in the offspring, a phenomenon known as genomic imprinting. This ensures a fine dosage of the gene expression levels that is crucial for development.
Identifying the regions subject to genomic imprinting is challenging with short read sequencing or Sanger bisulfite. We demonstrate the utility and efficiency of long-read nanopore sequencing in detecting allele-specific methylation in reciprocal crosses in mice. We derive phased whole genome methylomes that we combine with deep transcriptome sequencing, improving the resolution of imprinting control regions and identifying novel secondary DMRs. In addition to its usefulness in refining our knowledge of genomic imprinting in mammals, we envisage our method to be widely applicable to the phasing of genetic variants and methylation in more complex genetic set ups, including non-model species and cancer.