microCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system
- University of Washington, United States
- Ghent University, Belgium
- Boston College, United States
- 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.
Data availability
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Data from: microCT-Based Skeletal Phenomics in Zebrafish Reveals Virtues of Deep Phenotyping in a Single Organ SystemAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
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.
Reviewing Editor
- Richard M White, Memorial Sloan Kettering Cancer Center, United States
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).
Version history
- Received: February 15, 2017
- Accepted: August 21, 2017
- Accepted Manuscript published: September 8, 2017 (version 1)
- 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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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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