| First Author | Bielinska B | Year | 2000 |
| Journal | Nat Genet | Volume | 25 |
| Issue | 1 | Pages | 74-8 |
| PubMed ID | 10802660 | Mgi Jnum | J:61887 |
| Mgi Id | MGI:1855736 | Doi | 10.1038/75629 |
| Citation | Bielinska B, et al. (2000) De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch [see comments]. Nat Genet 25(1):74-8 |
| abstractText | Prader-Willi syndrome (PWS) is a neurogenetic disease characterized by infantile hypotonia, gonadal hypoplasia, obsessive behaviour and neonatal feeding difficulties followed by hyperphagia, leading to profound obesity. PWS is due to a lack of paternal genetic information at 15q11-q13 (ref. 2). Five imprinted, paternally expressed genes map to the PWS region, MKRN3 (ref. 3), NDN (ref. 4), NDNL1 (ref. 5), SNRPN (refs 6-8 ) and IPW (ref. 9), as well as two poorly characterized framents designated PAR-1 and PAR-5 (ref. 10). Imprinting of this region involves a bipartite 'imprinting centre' (IC), which overlaps SNRPN (refs 10,11). Deletion of the SNRPN promoter/exon 1 region (the PWS IC element) appears to impair the establishment of the paternal imprint in the male germ line and leads to PWS. Here we report a PWS family in which the father is mosaic for an IC deletion on his paternal chromosome. The deletion chromosome has acquired a maternal methylation imprint in his somatic cells. We have made identical findings in chimaeric mice generated from two independent embryonic stem (ES) cell lines harbouring a similar deletion. Our studies demonstrate that the PWS IC element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance. |
