Structure and function of the human chromosome 15 imprinting center

Abstract

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.