Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes
Open accessAbstract
Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are neurodevelopmental disorders of genomic imprinting. AS results from loss of function of the ubiquitin protein ligase E3A ( UBE3A ) gene, whereas the genetic defect in PWS is unknown. Although induced pluripotent stem cells (iPSCs) provide invaluable models of human disease, nuclear reprogramming could limit the usefulness of iPSCs from patients who have AS and PWS should the genomic imprint marks be disturbed by the epigenetic reprogramming process. Our iPSCs derived from patients with AS and PWS show no evidence of DNA methylation imprint erasure at the cis -acting PSW imprinting center. Importantly, we find that, as in normal brain, imprinting of UBE3A is established during neuronal differentiation of AS iPSCs, with the paternal UBE3A allele repressed concomitant with up-regulation of the UBE3A antisense transcript. These iPSC models of genomic imprinting disorders will facilitate investigation of the AS and PWS disease processes and allow study of the developmental timing and mechanism of UBE3A repression in human neurons.
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Paternal-specific deletion of multiple imprinted, paternally expressed genes on the 15q11-q13 region results in Prader-Willi syndrome.
“Similarly, paternal-specific deletion of multiple imprinted, paternally expressed genes on the 15q11–q13 region results in Prader–Willi syndrome, whereas maternal deletion of a single, imprinted, maternally expressed gene encoding a ubiquitin-protein ligase (UBE3A) on this same region gives rise to the Angelman syndrome phenotype.”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [118]
Maternal deletion of a single imprinted, maternally expressed gene encoding UBE3A on 15q11-q13 gives rise to the Angelman syndrome phenotype.
“Similarly, paternal-specific deletion of multiple imprinted, paternally expressed genes on the 15q11–q13 region results in Prader–Willi syndrome, whereas maternal deletion of a single, imprinted, maternally expressed gene encoding a ubiquitin-protein ligase (UBE3A) on this same region gives rise to the Angelman syndrome phenotype.”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [118]
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- Authors
- Chamberlain, S. J., Chen, P.-F., Ng, K. Y., Bourgois-Rocha, F., Lemtiri-Chlieh, F., Levine, E. S., & Lalande, M.
- Affiliations
- University of Connecticut (US)
- Génétique et biologie du développement (FR)
- Neuroscience, University of Connecticut Health Center, Farmington, CT 06030
- UConn Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-09-27
- Volume
- 107
- Issue
- 41
- Pages
- 17668-17673
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2955112
- OpenAlex
- W2162904965
- Cited by
- 312
- References
- 34
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 13 · 2023: 10 · 2022: 10 · 2021: 17 · 2020: 23 · 2019: 15 · 2018: 21 · 2017: 18 · 2016: 25 · 2015: 28 · 2014: 29 · 2013: 27 · 2012: 32
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for Prader-Willi Research
- University of Connecticut
- Raymond and Beverly Sackler Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- Angelman syndrome, Prader-Willi syndrome, genomic imprinting, induced pluripotent stem cells, UBE3A, neuronal differentiation, epigenetic reprogramming, neurodevelopmental disorders
- MeSH terms
- Cell Differentiation, Electrophysiology, Humans, Immunohistochemistry, Models, Biological, Neurons, Prader-Willi Syndrome, Polymerase Chain Reaction, Angelman Syndrome, DNA Primers, Genomic Imprinting, Pluripotent Stem Cells, Ubiquitin-Protein Ligases
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