Imprinted expression of UBE3A in non-neuronal cells from a Prader–Willi syndrome patient with an atypical deletion
Open accessAbstract
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two neurodevelopmental disorders most often caused by deletions of the same region of paternally inherited and maternally inherited human chromosome 15q, respectively. AS is a single gene disorder, caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, while PWS is still considered a contiguous gene disorder. Rare individuals with PWS who carry atypical microdeletions on chromosome 15q have narrowed the critical region for this disorder to a 108 kb region that includes the SNORD116 snoRNA cluster and the Imprinted in Prader-Willi (IPW) non-coding RNA. Here we report the derivation of induced pluripotent stem cells (iPSCs) from a PWS patient with an atypical microdeletion that spans the PWS critical region. We show that these iPSCs express brain-specific portions of the transcripts driven by the PWS imprinting center, including the UBE3A antisense transcript (UBE3A-ATS). Furthermore, UBE3A expression is imprinted in most of these iPSCs. These data suggest that UBE3A imprinting in neurons only requires UBE3A-ATS expression, and no other neuron-specific factors. These data also suggest that a boundary element lying within the PWS critical region prevents UBE3A-ATS expression in non-neural tissues.
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SNORD116 is expressed exclusively from the paternally inherited allele, whereas maternally inherited alleles of UBE3A are linked to PWS.
“For example, SNORD116 is expressed exclusively from the paternally inherited allele113, whereas maternally inherited alleles of UBE3A are linked to PWS119,120.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [119]
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- Authors
- Martins-Taylor, K., Hsiao, J. S., Chen, P.-F., Glatt-Deeley, H., De Smith, A. J., Blakemore, A. I. F., Lalande, M., & Chamberlain, S. J.
- Affiliations
- UConn Health (US)
- Hammersmith Hospital (GB)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-20
- Volume
- 23
- Issue
- 9
- Pages
- 2364-2373
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3976333
- OpenAlex
- W2128696662
- Cited by
- 66
- References
- 35
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 1
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD068730)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Prader-Willi syndrome, UBE3A, genomic imprinting, induced pluripotent stem cells, imprinting center, non-neuronal cells, boundary elements
- MeSH terms
- Cell Line, Humans, Immunohistochemistry, Prader-Willi Syndrome, Angelman Syndrome, Sequence Deletion, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin-Protein Ligases, Induced Pluripotent Stem Cells
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