The effect of paternal haploinsufficiency for Dnmt3L

There is increasing evidence that epigenetic information can be inherited across generations in mammals, despite extensive reprogramming both in the gametes and the early developing embryo. One corollary to this is that disruption of the establishment of epigenetic state in the gametes of a parent, as a result of heterozygosity for mutations in genes involved in reprogramming, could affect the phenotype of offspring that do not inherit the mutant allele. Here we show that such effects do occur following paternal inheritance in the mouse. We detect changes to transcription and chromosome ploidy in adult animals. Paternal effects of this type have not been reported previously in mammals and suggest that the untransmitted genotype of male parents can influence the phenotype of their offspring. Keywords: Offspring of Dnmt3L+/- sires compared to offspring of Dnmt3L+/+ sires Offspring of Dnmt3L+/- sires compared to offspring of Dnmt3L+/+ sires