Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene
Nature GeneticsPublished 1 October 1996
Bärbel Dittrich, Karin Buiting, Bernd Korn, Sarah Rickard, Jessica L. Buxton, Shinji Saitoh
Citations257
SJR quartileQ1
SJR score16.59
SNIP6.64
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Novel transcripts are identified which represent alternative transcripts of the SNRPN gene that are expressed from the paternal chromosome only and intragenic deletions and a point mutation in patients who have Angelman or Prader–Willi syndrome due to a parental imprint switch failure are identified.
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.
Keywords
Biochemistry, Genetics and Molecular Biology
CellThe product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus
1,031 Citations1992Neil Brockdorff, Alan Ashworth +6 more
Analysis of the entire mouse Xist gene supports a role for Xist in X inactivation, possibly as a functional RNA or as a chromatin organizer region.
NatureGenetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome
887 Citations1989Robert D. Nicholls, Joan H.M. Knoll +3 more
It is concluded that a gene or genes in region 15q11q13 must be inherited from each parent for normal human development.
New England Journal of MedicineDeletions of Chromosome 15 as a Cause of the Prader–Willi Syndrome
622 Citations1981David H. Ledbetter, Vincent M. Riccardi +4 more
The Prader–Willi syndrome consists of muscular hypotonia, obesity, short stature, small hands and feet, hypogonadism, and mental retardation.
Nature GeneticsInherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15
598 Citations1995Karin Buiting, Shinji Saitoh +5 more
A subset of patients with Angelman and Prader–Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DMA methylation at several loci within chromosome 15q11–13, and probably have a defect in imprinting.
American Journal of Medical GeneticsAngelman and Prader‐Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion
583 Citations1989Joan H.M. Knoll, Robert D. Nicholls +6 more
Maternal inheritance of the deleted chromosome 15 was demonstrated in the AS patients by restriction fragment length polymorphisms (RFLPs) and the molecular deletions between AS and those previously reported for PWS did not appear to differ.
Nature GeneticsDeletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region
422 Citations1994James S. Sutcliffe, Mitsuyoshi Nakao +5 more
The authors' data imply the presence of a paternal imprinting control region near exon α of SNRPN, which would imply the molecular basis of Prader-Willi syndrome and Angelman syndrome.
The LancetUniparental paternal disomy in Angelman's syndrome
328 Citations1991S Malcolm, Jill Clayton‐Smith +6 more
In 2 patients with Angelman's syndrome the authors found evidence of uniparental paternal disomy, strong evidence in man for genomic imprinting, in which the same gene has different effects dependent upon its parental origin.
Nature GeneticsSmall nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader–Willi syndrome critical region
296 Citations1992Tayfun Özçelık, Stuart E. Leff +6 more
The gene encoding the small nuclear RNA associated polypeptide SmN (SNRPN) to human chromosome 15q12 and a processed pseudogene SNRPNP1 to chromosome region 6pter–p21 was mapped to the minimal deletion interval that is critical for PWS.
Human Molecular GeneticsIdentification of a novel paternally expressed gene in the Prader - Willi syndrome region
244 Citations1994Rachel Wevrick, Julie A. Kerns +1 more
A novel gene from the Prader-Willi syndrome (PWS) smallest region of deletion overlap in proximal human chromosome 15q was isolated using the direct selection method and yeast artificial chromosomes localized to the deletion region, suggesting that it functions as an RNA, similar to H19 and XIST.
American Journal of Medical GeneticsIs angelman syndrome an alternate result of del(15)(qllql3)?
241 Citations1987R. Ellen Magenis, Michael G. Brown +6 more
The findings of ataxic-like movements, frequent, unprovoked and prolonged bouts of laughter and facial appearance are more compatible with the diagnosis of Angelman syndrome.
PubMedGene structure, DNA methylation, and imprinted expression of the human SNRPN gene.
236 Citations1996Christopher C. Glenn, Shinji Saitoh +5 more
Two previously unidentified 5' exons of the SNRPN gene are characterized and it is demonstrated that exons -1 and 0 are included in the full-length transcript and these findings are consistent with a key role for DNA methylation in the imprinted inheritance and subsequent gene expression of the human SNRpn gene.
PubMedImprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes.
224 Citations1994André Reis, Bärbel Dittrich +6 more
A model in which a cis-acting mutation prevents the resetting of the imprinting signal in the germ line and thus disturbs the expression of imprinted genes in this region of Prader-Willi/Angelman syndrome is proposed.
Human Molecular GeneticsImprinting mutations in the Beckwith—Wiedemann syndrome suggested by an altered imprinting pattern in the <i>IGF2–H19</i> domain
215 Citations1995Wolf Reik, Keith Brown +4 more
It is suggested that the altered pattern of allelic methylation and expression arises in the germline or in the early embryo from defects in resetting or setting of imprinting in maternal germline.
GenomicsA DNA methylation imprint, determined by the sex of the parent, distinguishes the angelman and Prader-Willi syndromes
211 Citations1992Daniel J. Driscoll, Michael F. Waters +5 more
It is proposed that expression of the gene detected by DN34 is regulated by genomic imprinting and, therefore, that it is a candidate gene for PWS and/or AS, and DNA methylation may be used as a reliable, postnatal diagnostic tool in these syndromes.
Human GeneticsMolecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13
203 Citations1992B�rbel Dittrich, WendyP. Robinson +5 more
A rapid diagnostic test is devised for patients suspected of having PWS and AS that finds that an MspI/HpaII restriction site at the D15S63 locus in 15q11-13 is methylated on the maternally derived chromosome, but unmethylation on the paternallyderived chromosome.
Proceedings of the National Academy of SciencesMinimal definition of the imprinting center and fixation of chromosome 15q11-q13 epigenotype by imprinting mutations.
175 Citations1996Shinji Saitoh, Karin Buiting +8 more
Four new microdeletions of the imprinting center (IC) are described, the smallest of which currently defines the minimal region sufficient to confer an AS imprinting mutation, and these data strongly support a model in which the paternal chromosome of these PWS patients carries an ancestral maternal epigenotype, and the maternal chromosomes of these AS patients carry an ancestral paternal epigenotype.
American Journal of Medical GeneticsClinical heterogeneity associated with deletions in the long arm of chromosome 15: Report of 3 new cases and their possible genetic significance
171 Citations1987Lawrence C. Kaplan, Robert H. Wharton +6 more
It is proposed that different molecular abnormalities involving specific points or segments along the long arm of chromosome 15 might account for the clinical diversity seen among these and other patients.
Nature GeneticsMaternal imprinting of human SNRPN, a gene deleted in Prader–Willi syndrome
162 Citations1994Martha L. Reed, Stuart E. Leff
Maternal imprinting ofSNRPN supports the hypothesis that paternal absence of SNRPN is responsible for the PWS phenotype and characterized a sequence polymorphism within expressed portions of human SNRpn and show that human SN RPN is monoallelically expressed in fetal brain and heart and in adult brain.
Human Molecular GeneticsFunctional imprinting and epigenetic modification of the human <i>SNRPN</i> gene
156 Citations1993Christopher C. Glenn, Kathleen A. Porter +3 more
The findings indicate that SNRPN is expressed only from the paternally derived chromosome 15 in humans and therefore may fulfill one major criterion for being involved in the pathogenesis of the Prader-Willi syndrome.
Current Opinion in Genetics & DevelopmentChromatin multiprotein complexes involved in the maintenance of transcription patterns
151 Citations1995Valerio Orlando
Molecular analysis of the components, apparently acting in large multiprotein complexes, has allowed a substantial advancement in understanding of the role of chromatin higher order structures in gene regulation and nuclear organization in Drosophila.
Journal of Medical GeneticsMolecular mechanisms in Angelman syndrome: a survey of 93 patients.
145 Citations1993Christopher T. Chan, Jill Clayton‐Smith +5 more
Two cases were observed with a de novo deletion starting close to the locus D15S11 (IR4-2R), providing evidence for the development of classical AS with smaller deletions, while cytogenetic analysis proved limited in its ability to detect deletions.
Human Molecular GeneticsModification of 15q11 — q13 DNA methylation imprints in unique Angelman and Prader — Willi patients
140 Citations1993Christopher C. Glenn, Robert D. Nicholls +6 more
An AS sibship and three PWS patients in which chromosome 15 rearrangements alter the methylation state at ZNF127, even though this locus is not directly involved in the rearrangement.
Human Molecular GeneticsImprinting analysis of three genes in the Prader — Willi/Angelman region: SNRPN, E6-associated protein, and PAR-2 (D15S225E)
123 Citations1994Mltsuyoshl Nakao, James S. Sutcliffe +4 more
The ability to analyze for imprinting and expression of SNRPN and other genes in this region in cultured human cells will be a valuable tool for analyzing the molecular basis of the Prader-Willi and Angelman syndromes, although imprinting may differ between cultured cells and tissues.
Journal of Medical GeneticsThe association of Angelman's syndrome with deletions within 15q11-13.
123 Citations1989Marcus Pembrey, Sarah Fennell +8 more
Data map the Angelman locus to 15q11-13 and suggest that de novo visible deletions (associated with a low recurrence risk) and autosomal recessively inherited cases combine to give an overall sib recurrencerisk of less than 25%.
Human Molecular GeneticsA strategy for the selection of transcribed sequences in the Xq28 region
120 Citations1992Bernhard Korn, Zdeněk Sedláček +5 more
A protocol allowing the rapid isolation of transcripts defined by overlapping clone libraries, based on the hybridisation of cDNA inserts, resulted in the identification of 81 cDNA clones, of which 54 clones were mapped back to the cosmid contigs.
Nature GeneticsMaternal but not paternal transmission of 15q11–13–linked nondeletion Angelman syndrome leads to phenotypic expression
98 Citations1992John Wagstaff, Joan H.M. Knoll +4 more
It is shown that AS in this family is caused by a mutation in 15q11–13 that results in AS when transmitted from mother to child, but no phenotype when transmitted paternally, suggesting that the loci responsible for AS and PWS, although closely linked, are distinct.
GenomicsA complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11–q13) and refined localization of the SNRPN gene
93 Citations1993Apiwat Mutirangura, Arumugam Jayakumar +8 more
This YAC contig will be a useful resource for more detailed physical mapping of the region, for generation of new DNA markers, and for mapping or cloning candidate genes for the Prader-Willi and Angelman syndromes.
Human Molecular GeneticsCharacterization of a methylation imprint in the Prader — Willi syndrome chromosome region
85 Citations1993Bärbel Dittrich, Karin Buiting +2 more
The findings suggest that the PW71 methylation imprint is established in the germline and that extraembryonic tissues and tumors are hypomethylated.
Proceedings of the National Academy of SciencesEvaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse.
79 Citations1993Robert D. Nicholls, William P. Gottlieb +4 more
Four evolutionarily conserved sequences from human 15q11-q13, including two cDNAs from fetal brain, a microdissected clone, and the gene for the beta 3 subunit of the gamma-aminobutyric acid type A receptor were mapped in mouse chromosome 7 by analysis of deletions at the pink-eyed dilution (p) locus.
Human Molecular GeneticsDetection of aberrant DNA methylation in unique Prader — Willi syndrome patients and its diagnostic implications
48 Citations1994Karin Buiting, Bärbel Dittrich +5 more
The results suggest that a DNA sequence close to SNRPN determines the methylation status of D15S63 and that themethylation test does not only detect the common deletions and uniparental disomy, but other rare lesions as well.
Human GeneticsDetection of submicroscopic deletions and a DNA polymorphism at the retinoblastoma locus
45 Citations1987Bernhard Horsthemke, Valerie Greger +3 more
The H3-8 probe detects a restriction fragment length polymorphism that is a useful genetic marker in some families and provides a basis for DNA diagnosis in nearly 20% of patients with bilateral and multifocal unilateral retinoblastoma.
PubMedLinkage analysis in familial Angelman syndrome.
42 Citations1993John Wagstaff, Yin Yao Shugart +1 more
Analysis of two sibling pairs with AS and a larger family with four AS offspring of three sisters with several recently described microsatellite polymorphisms in the AS region provides the first clear demonstration of a new mutation in nondeletion AS.
GenomicsThe syntenic relationship between the critical deletion region for the Prader-Willi/Angelman syndromes and proximal mouse chromosome 7
34 Citations1991J. Richard Chaillet, Joan H.M. Knoll +2 more
Because the Prader-Willi and Angelman syndromes are postulated to result from genomic imprinting within the common deletion, probes found within and flanking this deletional region may define a genomically imprinted region on mouse chromosome 7.
American Journal of Medical GeneticsFurther evidence for dominant inheritance at the chromosome 15q11‐13 locus in familial angelman syndrome
30 Citations1992Jill Clayton‐Smith, T. Webb +7 more
Analysis of 6 polymorphic DNA markers supported the conclusion that AS sibs inherit the same maternal 15, but often different paternal 15s, and support the hypothesis that familial AS is due to maternal transmission of a mutation within 15q11-13.