IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12824.html
   My bibliography  Save this article

Loss of RNA expression and allele-specific expression associated with congenital heart disease

Author

Listed:
  • David M. McKean

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard University)

  • Jason Homsy

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard University
    Cardiovascular Research Center, Massachusetts General Hospital)

  • Hiroko Wakimoto

    (Harvard Medical School)

  • Neil Patel

    (The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai)

  • Joshua Gorham

    (Harvard Medical School)

  • Steven R. DePalma

    (Harvard Medical School
    Howard Hughes Medical Institute, Harvard University)

  • James S. Ware

    (Harvard Medical School
    National Institute for Health Research Cardiovascular Biomedical Research Unit at Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London
    National Heart and Lung Institute, Imperial College London)

  • Samir Zaidi

    (Yale University School of Medicine)

  • Wenji Ma

    (Columbia University Medical Center)

  • Nihir Patel

    (The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai)

  • Richard P. Lifton

    (Yale University School of Medicine
    Howard Hughes Medical Institute, Yale University)

  • Wendy K. Chung

    (Columbia University Medical Center)

  • Richard Kim

    (Section of Cardiothoracic Surgery, University of Southern California Keck School of Medicine)

  • Yufeng Shen

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Martina Brueckner

    (Yale University School of Medicine)

  • Elizabeth Goldmuntz

    (The Perelman School of Medicine, University of Pennsylvania)

  • Andrew J. Sharp

    (The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Christine E. Seidman

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard University
    Howard Hughes Medical Institute, Harvard University)

  • Bruce D. Gelb

    (The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • J. G. Seidman

    (Harvard Medical School)

Abstract

Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression.

Suggested Citation

  • David M. McKean & Jason Homsy & Hiroko Wakimoto & Neil Patel & Joshua Gorham & Steven R. DePalma & James S. Ware & Samir Zaidi & Wenji Ma & Nihir Patel & Richard P. Lifton & Wendy K. Chung & Richard K, 2016. "Loss of RNA expression and allele-specific expression associated with congenital heart disease," Nature Communications, Nature, vol. 7(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12824
    DOI: 10.1038/ncomms12824
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12824
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12824?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12824. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.