The Sins of the Fathers and Mothers Genomic Imprinting in Mammalian Development

functions (Table 1 and http://www.mgu.har.mrc.ac.uk/ Introduction anomaly/anomaly.html). From this list two themes emerge. The genetic nonequivalence of the mammalian maternal Particularly striking is the number of imprinted genes and paternal genomes, uncovered by the elegant pronuthat act in the fetal growth pathway mediated by insulinclear transplantation studies in the 1980s (McGrath and like growth factor II (IGFII). The list includes the Igf2 Solter, 1984; Surani et al., 1984), came as quite a surprise gene itself and three genes that modulate its activity, and forced classical Mendelian genetics to undergo a the mannose-6-phosphate/IGFII receptor (Igf2r), Grb10, number of revisions. The discovery of imprinting also and H19. Targeted mutations in Igf2, Igf2r, and H19 presents us with a genetic paradox: by silencing one confirm that these genes affect the rate of fetal growth allele of an autosomal gene, mammals discard the ad(DeChiara et al., 1990; Filson et al., 1993; Lau et al., vantage of diploidy. What are parents trying to achieve 1994; Wang et al., 1994; Leighton et al., 1995a). A second with this heavy-handed way of influencing gene expresgroup of genes, including Insulin2, 57, Gnas, Rasgrf1, sion in their offspring? This article will focus on that and Mash2, are involved in regulating fetal growth and/ issue, as well as outstanding issues regarding the mechor the cell cycle. anism of imprinting. One can easily rationalize why a new genetic mecha-