IMPRINTING IN ANGELMAN AND PRADER-WILLI SYNDROMES

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by d eficiencies of gene expression from paternal or maternal chromosome 15 q11-q13, respectively. Many advances have occurred during the past yea r. The gene for necdin was mapped in the PWS candidate region and foun d to be paternally expressed in mouse and human. The bisulfite method for analysis of methylation was established for genomic sequencing and diagnostics, and the methylation of Snrpn was studied in detail in th e mouse. A region near the Snrpn promoter was shown to function as a s ilencer in Drosophila. Point mutations were found in the gene for EG-A P ubiquitin-protein ligase (UBE3A) identifying it as the AS gene, and tissue-specific imprinting (maternal expression) was shown in the huma n brain and in hippocampal neurons and Purkinje cells in the mouse.