FUNCTIONAL IMPRINTING AND EPIGENETIC MODIFICATION OF THE HUMAN SNRPN GENE

The SNRPN gene encodes a small nuclear ribonucleoprotein subunit, SmN, thought to be involved in splicing of pre-mRNA. A closely related pro tein, SmB/B', is constitutively expressed in all tissues except the br ain, where SmN is predominantly expressed. The mouse homolog of the SN RPN gene has been shown to be functionally imprinted in mouse brain, b eing expressed only from the paternally derived chromosome. SNRPN has been mapped to human chromosome 15q11-q13 within the shortest region o f deletion overlap for the Prader-Willi syndrome. We have now demonstr ated functional imprinting of the human SNRPN gene using reverse trans cription followed by the polymerase chain reaction (RT-PCR). No expres sion was observed in cultured skin fibroblasts of Prader-Willi patient s, but was found in all Angelman patients and normal controls examined . We have also demonstrated a parent-specific DNA methylation imprint within intron 5 of the SNRPN gene, which suggests an epigenetic mechan ism by which parent-specific expression of this gene might be inherite d. Our findings indicate that SNRPN is expressed only from the paterna lly derived chromosome 15 in humans and therefore may fullfill one maj or criterion for being involved in the pathogenesis of the Prader-Will i syndrome.