microCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system

  1. Matthew Hur
  2. Charlotte A Gistelinck
  3. Philippe Huber
  4. Jane Lee
  5. Marjorie H Thompson
  6. Adrian T Monstad-Rios
  7. Claire J Watson
  8. Sarah K McMenamin
  9. Andy Willaert
  10. David M Parichy
  11. Paul Coucke
  12. Ronald Y Kwon  Is a corresponding author
  1. University of Washington, United States
  2. Ghent University, Belgium
  3. Boston College, United States
  4. University of Virginia, United States

Abstract

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

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The following data sets were generated

Article and author information

Author details

  1. Matthew Hur

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Charlotte A Gistelinck

    Center for Medical Genetics, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Philippe Huber

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jane Lee

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Marjorie H Thompson

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Adrian T Monstad-Rios

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Claire J Watson

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Sarah K McMenamin

    Department of Biology, Boston College, Chestnut Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Andy Willaert

    Center for Medical Genetics, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  10. David M Parichy

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Paul Coucke

    Center for Medical Genetics, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  12. Ronald Y Kwon

    Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, United States
    For correspondence
    ronkwon@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9760-3761

Funding

University of Washington (A88052)

  • Ronald Y Kwon

National Institutes of Health (AR066061)

  • Ronald Y Kwon

Belgian Science Policy Office Interuniversity Attraction Poles Program (IAP P7/43-BeMGI)

  • Paul Coucke

National Institutes of Health (GM105874)

  • Sarah K McMenamin

National Institutes of Health (HD091634)

  • Sarah K McMenamin

National Institutes of Health (GM11233)

  • David M Parichy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All studies were performed on an approved protocol (#4306-01) in accordance with the University of Washington Institutional Animal Care and Use Committee (IACUC).

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: February 15, 2017
  2. Accepted: August 21, 2017
  3. Accepted Manuscript published: September 8, 2017 (version 1)
  4. Version of Record published: September 20, 2017 (version 2)

Copyright

© 2017, Hur et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Matthew Hur
  2. Charlotte A Gistelinck
  3. Philippe Huber
  4. Jane Lee
  5. Marjorie H Thompson
  6. Adrian T Monstad-Rios
  7. Claire J Watson
  8. Sarah K McMenamin
  9. Andy Willaert
  10. David M Parichy
  11. Paul Coucke
  12. Ronald Y Kwon
(2017)
microCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system
eLife 6:e26014.
https://doi.org/10.7554/eLife.26014

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