rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Analysis of Genomic Imprinting of UBE3A in Neurons
  name:
    name part: Hillman, Paul Randolph
    role:
      role term: creator
    role:
      role term: author.
  name:
    name part: Dindot, Scott
    role:
      role term: thesis advisor.
  name:
    name part: Leibowitz, Julian
    role:
      role term: thesis advisor.
  name:
    name part: Texas A & M University
    role:
      role term: degree granting institution.
  type of resource: text
  genre: bibliography
  origin info:
    place:
      place term: txu
    date issued: 2015
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: remote
    extent: 1 online resource.
  abstract: Angelman syndrome (AS), chromosome 15q11-q13 duplication syndrome (Dup15q), and Prader-Willi syndrome (PWS) are neurodevelopmental disorders associated with dysregulated expression of imprinted genes located within the human 15q11-13 imprinted region. Angelman syndrome is caused by loss-of-function or loss-of-expression of the maternally inherited UBE3A allele; Dup15q syndrome is attributed to maternally inherited copy number gains of UBE3A; and, paternally inherited deletions of the SNORD116 cluster cause PWS. The UBE3A gene is imprinted in the brain with maternal-specific expression and biallelically expressed in all other cell types. The imprint is regulated by expression of the UBE3A antisense transcript (UBE3A-AS), which is expressed only in neurons and imprinted with paternal-specific expression. The UBE3A-AS represents the 3` end of a long polycistronic transcript that includes the SNORD116 and SNORD115 gene clusters. Thus, the genes causing AS, Dup15q, and PWS are transcriptionally linked; however, the functional significance of the neuron specific imprint is largely unknown. In this dissertation, it was hypothesized that imprinting of UBE3A evolved as a mechanism to negatively regulate UBE3A protein levels in neurons. This hypothesis was tested by examining allelic expression patterns and associated protein levels of the mouse 7c imprinted region, the orthologous region of human 15q11-q13. Analyses revealed that imprinted expression of Ube3a in the brain resulted in elevated RNA and protein levels compared to tissues where Ube3a was biallelically expressed. Likewise, Snord116, Snord115, and Ube3a-AS transcripts were highly expressed in the brain. The elevated Ube3a protein levels in the brain were due to increased maternal-allelic expression during neurogenesis concurrent with paternal-allelic suppression. Analysis of UBE3A expression in the opossum, a metatherian mammal lacking an orthologous imprinted region, showed that the UBE3A imprint did not evolve t…
  note: by Paul Hillman.
  note: "Major Subject: Medical Sciences"
  note: Includes vita.
  note: Doctor of Philosophy Texas A & M University 2015 http://hdl.handle.net/1969.1/155041
  note: Includes bibliographical references.
  note: Text (Dissertation)
  subject:
    topic: Major Medical Sciences
  subject:
    topic: Angelman syndrome
  subject:
    topic: Imprinting
  subject:
    topic: Genomics
  subject:
    topic: Next generation sequencing
  subject:
    topic: RNA-seq
  subject:
    topic: Neuordevelopment
  identifier: http://hdl.handle.net/1969.1/155041
  record info:
    record content source: TXA
    record creation date: 160307
    record change date: 20170928112113.0
    record identifier: in00003615638
    language of cataloging:
      language term: eng