Imprinting and transgenerational modulation of gene expression; human growth as a model

Abstract

It is proposed that transgenerational modulation of gene expression might be possible, if the metabolic response of the parent to some physiological or social stress modified imprint setting. Transcription regulators could theoretically mediate this process. The nature of imprinted genes poised, as it were, between a transcriptionally active and silent state, makes them good candidates for incorporation into the evolution of transgenerational adaption systems where coordinated changes in gene expression over the generations is a selective advantage. The coordination of human fetal (head) growth with the existing size of the mother's pelvis is suggested as just such a circumstance. The reduced birth weight of Dutch babies where their grandmothers suffered acute starvation in mid pregnancy, supports the notion of transgenerational adaption to nutrition, as does the secular change (increase) in child growth over the last century. The recent indication that there may be functional polymorphism in the imprinting of the human IGF2 and IGF2R genes suggests these ideas could be explored using association studies at the population and individual level.