Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene

Abstract

Imprinting on human chromosome 15 is regulated by an imprinting centre, which has been mapped to a 100-kb region including exon 1 of SNRPN. From this region we have identified novel transcripts, which represent alternative transcripts of the SNRPN gene. The novel exons lack protein coding potential and are expressed from the paternal chromosome only. We have also identified intragenic deletions and a point mutation in patients who have Angelman or Prader-Willi syndrome due to a parental imprint switch failure. This suggests that imprint switching on human chromosome 15 may involve alternative SNRPN transcripts.

Genomic imprinting and its relevance to genetic diseases

“…On the other hand, 7 AS patients with an imprinting mutation had either a minute deletion or a base substitution at a region more proximal to SNRPN-exon 1. Novel alternative transcripts of S N R P N were identified from this region (Dittrich et al, 1996). Imprinting mutations do not disturb the whole imprinting phenomenon but may specifically involve only the P W S / A S region.…”

“…The abnormality in these patients is referred to as an imprinting mutation. Detailed study demonstrated that three such PWS patients with imprinting mutations actually had a minute deletion involving exon 1 of S N R P N (Buiting et aL, 1994;Sutcliffe et al, 1994;Dittrich et al, 1996). On the other hand, 7 AS patients with an imprinting mutation had either a minute deletion or a base substitution at a region more proximal to SNRPN-exon 1.…”

“…From these findings, a hypothesis was proposed: at this 5' region of SNRPN, there must be an imprinting center (IC) or imprintor which controls in a cis-acting manner a putative imprinting switch initiation site (SIS) located at exon 1 (Fig. 3) (Dittrich et aL, 1996). Normally, in the female germline, the paternally-derived IC suppresses the SIS function, and therefore the paternal imprint would switch to that for the maternal chromosome by a trans-acting factor in the germ cell.…”

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

“…69,70 The SNRPN gene has a number of alternative transcripts, and AS-imprinting center overlaps with exons of such transcripts. 71,72 Therefore, one possible explanation for some cases would be that the deletions affect oocyte-specific alternative transcripts traversing the SNRPN ICR, and this results in a failure in imprint establishment. Prader-Willi syndrome (PWS) is another neurogenetic disorder that results from the abnormalities of the same imprinted cluster as AS.…”

Quantitative and Qualitative Analyses of the SNRPN Gene Using Real-Time PCR with Melting Curve Analysis

“…6 -8 Nearly all the cytosine phosphodiester guanine dinucleotides around the promoter region of the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene are methylated on the maternal chromosome and completely devoid of methylation on the paternal chromosome. 9 The promoter methylation status of SNRPN is recognized as a valid diagnostic characteristic. 10 SNRPN, therefore, is a candidate gene for PWS and AS.…”