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 Skeletal Phenomics in Zebrafish Reveals Virtues of Deep Phenotyping at the Whole-Organism Scale
AID  - 10.1101/105569
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 105569
4099  - http://biorxiv.org/content/early/2017/03/02/105569.short
4100  - http://biorxiv.org/content/early/2017/03/02/105569.full
AB  - Phenomics–in-depth phenotyping at the whole-organism scale-holds promise to significantly enhance our functional understanding of genes and genomic variation, yet methods in vertebrates are limited. Here, we demonstrate rapid whole-body profiling of hundreds of traits 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, even when the latter is performed at higher resolution. 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 discriminate mutant phenotypes masked by growth alterations in growth. Our studies demonstrate virtues of deep phenotyping in a single organ system. Phenomic pattern analysis may increase productivity in genetic screens, and facilitate the study genetic variants of smaller effect size, such as those that underlie complex diseases.