Genomic Imprinting and the Possible Role of Epigenetic Inheritance in Transgenerational Effects

Marcus Pembrey
Institute of Child Health; University College London

One of the big questions in imprinting is why have imprinted genes evolved and persisted in humans. None of the many theories explain all known examples of imprinting, although there is strong support for a role in the control of embryonic/fetal growth. The molecular "memory" that imprints represent is an additional mechanism for transferring information from one generation to the next. Could imprinting be involved in adaptive transgenerational effects? There are many examples of epigenetic inheritance affecting growth in experimental animals (1,2). I will explore the hypothesis that a form of transgenerational adaption has evolved in which the level of expression (or shift in the proportion of cells with monoallelic expression) of an imprinted gene in a child is influenced by environmentally-induced epigenetic events in the parent at the time of laying down the imprint (3). Human fetal growth is the model explored focusing on allelic variation at the INS VNTR which influences normal human fetal growth (4) and IGF2 expression in term placentae (5). The finding that the nature of the untransmitted paternal INS VNTR allele can alter the phenotypic effect of the transmitted allele in the offspring (6) lends support for the notion that epigenetic events in one generation can influence gene expression in the next.


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  4. Dunger et al., Nat. Genet. 19: 98-100, 1998.

  5. Paquette et al., J. Biol. Chem. 273: 14158-14164, 1998.

  6. Bennett et al., Nat. Genet. 17: 350-352, 1997.