The chromosome 15 imprinting centre (IC) region has undergone multiple duplication events and contains an upstream exon of SNRPN that is deleted in all Angelman syndrome patients with an IC microdeletion

Imprinting of the Prader-Willi/Angelman syndrome region on human chromosome 15 is regulated by an imprinting centre (IC), which spans 5' exons of the gene encoding the small nuclear ribonucleoprotein N (SNRPN), The IC/SNRPN t ranscripts are initiated at two alternative start sites, which share a high degree of sequence similarity with each other and with two newly identifie d sites 63 and > 700 kb further upstream. Three of these sites are hypermet hylated on the maternal chromosome, whereas one displays an opposite methyl ation pattern. We have also identified novel splice variants of the IC/SNRP N transcripts and hitherto undetected exons, One of these exons, which we d esignate u5, is deleted in all Angelman syndrome patients with a microdelet ion of the IC, We conclude that elements of the IC region have undergone mu ltiple duplication events and that u5 or a sequence close by may play a rol e in maternal imprinting.