Widespread non-Mendelian inheritance of DNA methylation patterns in mice

We performed long-read ONT sequencing and matched RNA sequencing on two Collaborative Cross mouse strains and their F1 crosses. Allele-specific methylation and expression analyses revealed widespread and diverse patterns of intergenerational epigenetic inheritance. Included among these are a large number of non-Mendelian inheritance patterns, many of which have not previously been observed in naturally occurring mammalian genomes. Targeted ONT sequencing of F2 crosses of the same Collaborative Cross strains enabled further characterization and validation of these epigenetic inheritance patterns, including distinguishing those patterns mediated by cis- or trans-acting regulatory factors.