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PMID: 8571960 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene.

American journal of human genetics ·Vol. 58 ·No. 2 ·1996-02-00 ·Pages 335-46

Glenn CC, Saitoh S, Jong MT, Filbrandt MM, Surti U, Driscoll DJ, Nicholls RD

Abstract

The human SNRPN (small nuclear ribonucleoprotein polypeptide N) gene is one of a gene family that encode proteins involved in pre-mRNA splicing and maps to the smallest deletion region involved in the Prader-Willi syndrome (PWS) within chromosome 15q11-q13. Paternal only expression of SNRPN has previously been demonstrated by use of cell lines from PWS patients (maternal allele only) and Angelman syndrome (AS) patients (paternal allele only). We have characterized two previously unidentified 5' exons of the SNRPN gene and demonstrate that exons -1 and 0 are included in the full-length transcript. This gene is expressed in a wide range of somatic tissues and at high, approximately equal levels in all regions of the brain. Both the first exon of SNRPN (exon -1) and the putative transcription start site are embedded within a CpG island. This CpG island is extensively methylated on the repressed maternal allele and is unmethylated on the expressed paternal allele, in a wide range of fetal and adult somatic cells. This provides a quick and highly reliable diagnostic assay for PWS and AS, which is based on DNA-methylation analysis that has been tested on > 100 patients in a variety of tissues. Conversely, several CpG sites approximately 22 kb downstream of the transcription start site in intron 5 are preferentially methylated on the expressed paternal allele in somatic tissues and male germ cells, whereas these same sites are unmethylated in fetal oocytes. These findings are consistent with a key role for DNA methylation in the imprinted inheritance and subsequent gene expression of the human SNRPN gene.

MeSH Terms
Adolescent Adult Amino Acid Sequence Angelman Syndrome/genetics,metabolism Autoantigens/chemistry,genetics Base Sequence Child Child, Preschool Chromosome Mapping Cloning, Molecular Codon, Initiator/genetics CpG Islands DNA/genetics,metabolism Exons/genetics Female Genomic Imprinting/genetics Humans Infant Male Methylation Molecular Sequence Data Polymerase Chain Reaction Prader-Willi Syndrome/genetics,metabolism RNA Splicing Ribonucleoproteins, Small Nuclear/chemistry,genetics snRNP Core Proteins
Chemicals
Autoantigens Codon, Initiator Ribonucleoproteins, Small Nuclear SNRPN protein, human snRNP Core Proteins DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Glenn C C
R. C. Philips Research and Education Unit, Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610, USA.
Saitoh S
Jong M T
Filbrandt M M
Surti U
Driscoll D J
Nicholls R D
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1996-02-00
Pages
335-46
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1914536
Subset
IM
Grants
NICHD NIH HHS · HD31491 · United States
Databases
GENBANK
U41303
External Links
PubMed source PMC Full Text View journal details
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