PT  - JOURNAL ARTICLE
AU  - Matthew Hur
AU  - Charlotte A. Gistelinck
AU  - Philippe Huber
AU  - Jane Lee
AU  - Marjorie H. Thompson
AU  - Adrian T. Monstad-Rios
AU  - Claire J. Watson
AU  - Sarah K. McMenamin
AU  - Andy Willaert
AU  - David M Parichy
AU  - Paul Coucke
AU  - Ronald Y. Kwon
TI  - microCT-Based Phenomics in the Zebrafish Skeleton Reveals Virtues of Deep Phenotyping in a Distributed Organ System
AID  - 10.1101/105569
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 105569
4099  - http://biorxiv.org/content/early/2017/07/10/105569.short
4100  - http://biorxiv.org/content/early/2017/07/10/105569.full
AB  - 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 measures comprised of morphological and densitometric traits from a large number sites in 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. Analyzing phenotypic patterns may increase productivity in genetic screens, and could facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.