title: Imprinted expression of UBE3A in non-neuronal cells from a Prader-Willi syndrome patient with an atypical deletion.
abstract: 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.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Martins-Taylor
authors.forename: Jack S
authors.initials: JS
authors.lastname: Hsiao
authors.forename: Pin-Fang
authors.initials: PF
authors.lastname: Chen
authors.forename: Heather
authors.initials: H
authors.lastname: Glatt-Deeley
authors.forename: Adam J
authors.initials: AJ
authors.lastname: De Smith
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Marc
authors.initials: M
authors.lastname: Lalande
authors.forename: Stormy J
authors.initials: SJ
authors.lastname: Chamberlain
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases