Structure and function of the human chromosome 15 imprinting center

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are distinct neurogenetic disorders that are caused by a deficiency of paternal (PWS) or maternal (AS) contributions to chromosome 15. The affected genes are located in an imprinted chromosomal domain of 2 Mb, which is controlled by an imprinting center (IC). The IC has been mapped to a 100-kb region including the SNRPN gene and appears to have a bipartite structure. Mutations of the proximal part of the IC block the paternal --> maternal imprint switch during female gametogenesis, whereas mutations of the distal part of the IC block the maternal --> paternal imprint switch during male gametogenesis. Imprinting involves differential DNA methylation, which appears to be instrumental in the regulation of gene activity and can be used for diagnostic purposes. (C) 1997 Wiley-Liss, Inc.