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Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice

Author

Listed:
  • Axel Visel

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Walnut Creek, California 94598, USA)

  • Yiwen Zhu

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA)

  • Dalit May

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA)

  • Veena Afzal

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA)

  • Elaine Gong

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA)

  • Catia Attanasio

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA)

  • Matthew J. Blow

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Walnut Creek, California 94598, USA)

  • Jonathan C. Cohen

    (and Center for Human Nutrition, UT Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA)

  • Edward M. Rubin

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Walnut Creek, California 94598, USA)

  • Len A. Pennacchio

    (MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Walnut Creek, California 94598, USA)

Abstract

Heart disease risk identified It has been know for several years that genetic variations in a stretch of DNA on chromosome 9p21 are linked to the incidence of coronary artery disease. The nature of this link has remained unknown, not least because the 58-kilobase culprit genomic interval contains no known protein-encoding genes, and it appears unlinked to known major contributors to the disease. Now an experiment in which the corresponding stretch of DNA was deleted in mice shows that this part of the chromosome regulates cardiac expression of two genes located some 100,000 base pairs away. The genes, Cdkn2a and Cdkn2b, encode cyclin-dependent kinase inhibitors, and their down-regulation in a mouse model results in excessive aortic smooth muscle cell proliferation. This suggests that dysregulation of vascular cell proliferation underlies cardiac disease susceptibility linked to chromosome 9p21 variation.

Suggested Citation

  • Axel Visel & Yiwen Zhu & Dalit May & Veena Afzal & Elaine Gong & Catia Attanasio & Matthew J. Blow & Jonathan C. Cohen & Edward M. Rubin & Len A. Pennacchio, 2010. "Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice," Nature, Nature, vol. 464(7287), pages 409-412, March.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7287:d:10.1038_nature08801
    DOI: 10.1038/nature08801
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    Cited by:

    1. Annukka M Lahtinen & Peter A Noseworthy & Aki S Havulinna & Antti Jula & Pekka J Karhunen & Johannes Kettunen & Markus Perola & Kimmo Kontula & Christopher Newton-Cheh & Veikko Salomaa, 2012. "Common Genetic Variants Associated with Sudden Cardiac Death: The FinSCDgen Study," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-7, July.

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