PUBLICATION

Computational anatomy and geometric shape analysis enables analysis of complex craniofacial phenotypes in zebrafish

Authors
Diamond, K.M., Rolfe, S.M., Kwon, R.Y., Maga, A.M.
ID
ZDB-PUB-220126-38
Date
2022
Source
Biology Open   11(2): (Journal)
Registered Authors
Kwon, Ronald
Keywords
Computational anatomy, Cranial morphology, Geometric morphometrics, Osteogenesis imperfecta
MeSH Terms
  • Animals
  • Humans
  • Phenotype
  • Skull*/anatomy & histology
  • X-Ray Microtomography
  • Zebrafish*/genetics
PubMed
35072203 Full text @ Biol. Open
Abstract
Due to the complexity of fish skulls, previous attempts to classify craniofacial phenotypes have relied on qualitative features or sparce 2D landmarks. In this work we aim to identify previously unknown 3D craniofacial phenotypes with a semiautomated pipeline in adult zebrafish mutants. We first estimate a synthetic 'normative' zebrafish template using microCT scans from a sample pool of wildtype animals using the Advanced Normalization Tools (ANTs). We apply a computational anatomy (CA) approach to quantify the phenotype of zebrafish with disruptions in bmp1a, a gene implicated in later skeletal development and whose human ortholog when disrupted is associated with Osteogenesis Imperfecta. Compared to controls, the bmp1a fish have larger otoliths, larger normalized centroid sizes, and exhibit shape differences concentrated around the operculum, anterior frontal, and posterior parietal bones. Moreover, bmp1a fish differ in the degree of asymmetry. Our CA approach offers a potential pipeline for high-throughput screening of complex fish craniofacial shape to discover novel phenotypes for which traditional landmarks are too sparce to detect. The current pipeline successfully identifies areas of variation in zebrafish mutants, which are an important model system for testing genome to phenome relationships in the study of development, evolution, and human diseases.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping