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Nature Genetics 39, 614–622 (1 May 2007) | doi:10.1038/ng2031

Modifiers of epigenetic reprogramming show paternal effects in the mouse

Suyinn Chong , Nicola Vickaryous , Alyson Ashe , Natasha Zamudio , Neil Youngson , Sarah Hemley , Tomas Stopka , Arthur Skoultchi , Jacqui Matthews , Hamish S Scott , David de Kretser , Moira O'Bryan , Marnie Blewitt & Emma Whitelaw

There is increasing evidence that epigenetic information can be inherited across generations in mammals, despite extensive reprogramming both in the gametes and in the early developing embryo. One corollary to this is that disrupting 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 detected 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.