PUBLICATION
Examining craniofacial variation among crispant and mutant zebrafish models of human skeletal diseases
- Authors
- Diamond, K.M., Burtner, A.E., Siddiqui, D., Alvarado, K., Leake, S., Rolfe, S., Zhang, C., Kwon, R.Y., Maga, A.M.
- ID
- ZDB-PUB-230302-40
- Date
- 2023
- Source
- Journal of anatomy 243(1): 66-77 (Journal)
- Registered Authors
- Kwon, Ronald
- Keywords
- computational anatomy, cranial morphology, geometric morphometrics, klippel-feil syndrome, osteogenesis imperfecta, osteoporosis, sclerosteosis
- MeSH Terms
-
- Animals
- Bone and Bones
- Genome-Wide Association Study*
- Humans
- Phenotype
- Wnt Proteins/genetics
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- PubMed
- 36858797 Full text @ J. Anat.
Citation
Diamond, K.M., Burtner, A.E., Siddiqui, D., Alvarado, K., Leake, S., Rolfe, S., Zhang, C., Kwon, R.Y., Maga, A.M. (2023) Examining craniofacial variation among crispant and mutant zebrafish models of human skeletal diseases. Journal of anatomy. 243(1):66-77.
Abstract
Genetic diseases affecting the skeletal system present with a wide range of symptoms that make diagnosis and treatment difficult. Genome-wide association and sequencing studies have identified genes linked to human skeletal diseases. Gene editing of zebrafish models allows researchers to further examine the link between genotype and phenotype, with the long-term goal of improving diagnosis and treatment. While current automated tools enable rapid and in-depth phenotyping of the axial skeleton, characterizing the effects of mutations on the craniofacial skeleton has been more challenging. The objective of this study was to evaluate a semi-automated screening tool can be used to quantify craniofacial variations in zebrafish models using four genes that have been associated with human skeletal diseases (meox1, plod2, sost, and wnt16) as test cases. We used traditional landmarks to ground truth our dataset and pseudolandmarks to quantify variation across the 3D cranial skeleton between the groups (somatic crispant, germline mutant, and control fish). The proposed pipeline identified variation between the crispant or mutant fish and control fish for four genes. Variation in phenotypes parallel human craniofacial symptoms for two of the four genes tested. This study demonstrates the potential as well as the limitations of our pipeline as a screening tool to examine multi-dimensional phenotypes associated with the zebrafish craniofacial skeleton.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping