PUBLICATION
Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases
- Authors
- Machado, R.G., Eames, B.F.
- ID
- ZDB-PUB-170803-4
- Date
- 2017
- Source
- Journal of dental research 96(11): 1192-1199 (Review)
- Registered Authors
- Eames, Brian F., Machado, Rafaela Grecco
- Keywords
- CRISPR, GWA, adult phenotype, noncoding mutations, transgenesis, zebrafish genetics
- MeSH Terms
-
- Alleles
- Animals
- Clustered Regularly Interspaced Short Palindromic Repeats/genetics
- Craniofacial Abnormalities/embryology
- Craniofacial Abnormalities/genetics*
- Disease Models, Animal
- Gene Expression Regulation, Developmental*/genetics
- Genetic Association Studies
- Genetic Therapy
- Genome-Wide Association Study*
- Humans
- Maxillofacial Development/genetics*
- Mutation
- Zebrafish/genetics*
- PubMed
- 28767277 Full text @ J. Dent. Res.
Citation
Machado, R.G., Eames, B.F. (2017) Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases. Journal of dental research. 96(11):1192-1199.
Abstract
Genome-wide association studies (GWASs) opened an innovative and productive avenue to investigate the molecular basis of human craniofacial disease. However, GWASs identify candidate genes only; they do not prove that any particular one is the functional villain underlying disease or just an unlucky genomic bystander. Genetic manipulation of animal models is the best approach to reveal which genetic loci identified from human GWASs are functionally related to specific diseases. The purpose of this review is to discuss the potential of zebrafish to resolve which candidate genetic loci are mechanistic drivers of craniofacial diseases. Many anatomic, embryonic, and genetic features of craniofacial development are conserved among zebrafish and mammals, making zebrafish a good model of craniofacial diseases. Also, the ability to manipulate gene function in zebrafish was greatly expanded over the past 20 y, enabling systems such as Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles identified from human GWASs in coding and noncoding regions of DNA. With the optimization of genetic editing methods, large numbers of candidate genes can be efficiently interrogated. Finding the functional villains that underlie diseases will permit new treatments and prevention strategies and will increase understanding of how gene pathways operate during normal development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping