title: Structure and function correlations at the imprinted mouse Snrpn locus.
abstract: The human SNRPN gene maps within Chromosome (Chr) 15q11-q13, the region responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS). As one of several 15q11-q13 transcripts expressed from the paternal allele-only, SNRPN is a candidate gene to explain at least some of the PWS phenotype in human and in genetic mouse models. The promoter and first exon of the SNRPN gene also correspond to an imprinting center element responsible for resetting of the maternal to paternal imprints within 15q11-q13 during spermatogenesis. Through characterization of the imprinted murine Snrpn locus in mouse Chr 7C, we have found that the gene structure is very similar to the human, with ten conserved exons spanning 22 kb, the last seven of which are tightly clustered. The promoter of Snrpn is differentially methylated in ES cells and adult tissues, supporting a role for DNA methylation at this site in somatic establishment and/or maintenance of Snrpn imprinting. The first intron of the mouse and human genes contains structurally conserved G-rich clustered repeats which may play a role in establishing DNA methylation patterns associated with imprinting of this gene. On the basis of the conserved structural and imprinted features of the human SNRPN and mouse Snrpn genes, we suggest that imprinting mechanisms are conserved between human and mouse.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, Ohio 44106-4955, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Gabriel
authors.forename: T A
authors.initials: TA
authors.lastname: Gray
authors.forename: L
authors.initials: L
authors.lastname: Stubbs
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: R D
authors.initials: RD
authors.lastname: Nicholls
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics; D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D017931:DNA Primers; D018076:DNA, Complementary; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins