Genomic Imprinting

Imprinting Mechanisms

One mechanism by which a given imprinted gene in an individual is differentially expressed is that one of the gene's parental alleles is silenced throughout the embryonic development of the individual by an alternation in parental DNA made during parental gametogenesis. The other parental allele is, therefore, allowed expression during embryonic development. An epigenetic mechanism by which this occurs is DNA methylation (the labeling of a –CH3 group to specific regions of DNA) at imprinting control regions (ICRs). Intracellular DNA reading mechanisms exist after fertilization to check that the correct parental allele has been allowed differential expression.

Imprinting and Fetal Development

Imprinting has been able to explain a number of predicaments of life in utero as experienced by mother, father, as well as offspring. A number of imprinted genes are related to the manner in which the developing human must extract resources from its environment. As experimental work has confirmed predictions made by Robert Trivers's theory of parental investment, unfortunately, mother and father have different interests in how resources are extracted. Fathers and mothers have asymmetrical parental investment in each given child. This arises from the fact that mothers can only have one child every nine months for approximately 20 years, whereas a father could conceivably impregnate a different woman every day from puberty until death.

Systematic knockout studies of key imprinted genes, especially as performed on mice, have provided support for the hypothesis that imprinted genes that allow expression of paternally inherited alleles tend to drive more extraction of nutrients from the mother during gestation and after birth to produce a larger child. In contrast, imprinted genes that allow expression of maternally inherited alleles will tend to drive mechanisms to prevent the disproportionate utilization of resources by the fetus. A commonly cited example of this differential resource transfer is the paternally expressed Igf2, which enhances fetal growth and placental nutrient transport capacity, and the maternally expressed Igf2 receptor, which degrades excessive Igf2.

Many of the effects of imprinted genes occur at the placenta, a crucial site for resource and nutrient transfer. For example, an overgrown placenta (hydatidiform mole) results when maternal imprints are missing. Additionally, in Silver-Russell syndrome, a maternal uniparetal disomy, one finds growth restriction. Similar effects are found in other cases of [Page 728]disordered imprinting, as in preeclampsia, which also demonstrates growth restriction in utero. These diseases can only be understood within the context of imprinting as a common mechanism of parental conflict and manipulation of the phenotypic outcome of children.

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