Epigenetics and imprinted genes: insights from the imprinted Gnas locus.

The hallmarks of epigenetics--the memory of defining earlier developmental events and the distinction of active and inactive genes--are exemplified by imprinted genes. In this article, I shall consider the imprinted Gnas locus in some detail. Gnas encodes the stimulatory G-protein subunit, Gsalpha, an essential intermediate between receptor coupling and cyclic adenosine monophosphate generation. It provides an excellent illustration of the pleiotropic effects of imprinted genes, particularly on skeletal growth and metabolism, and is a powerful example of the conflicting effects of imprinted genes with opposing patterns of imprinting. I shall describe the effects of Gsalpha deficiency in humans and the knowledge gained from genetic manipulation in the mouse. Finally, given the pervasive effects of imprinted genes, I shall discuss the likelihood that epigenetic deregulation, for example of imprinted genes, could contribute to the developmental programming of chronic adult diseases.