PUBLICATION
Zebrafish as a genomics model for human neurological and polygenic disorders
- Authors
- Becker, T.S., and Rinkwitz, S.
- ID
- ZDB-PUB-110511-3
- Date
- 2012
- Source
- Developmental Neurobiology 72(3): 415-428 (Review)
- Registered Authors
- Becker, Thomas S., Rinkwitz, Silke
- Keywords
- transgenes, cis-regulation, human enhancers, GWAS, regulatory mutations
- MeSH Terms
-
- Animals
- Disease Models, Animal*
- Genome-Wide Association Study/methods
- Genomics/methods*
- Humans
- Multifactorial Inheritance/genetics*
- Nervous System Diseases/genetics*
- Nervous System Diseases/physiopathology
- Zebrafish/genetics*
- PubMed
- 21465670 Full text @ Dev. Neurobiol.
Citation
Becker, T.S., and Rinkwitz, S. (2012) Zebrafish as a genomics model for human neurological and polygenic disorders. Developmental Neurobiology. 72(3):415-428.
Abstract
Whole exome sequencing and, to a lesser extent, genome-wide association studies, have provided unprecedented advances in identifying genes and candidate genomic regions involved in the development of human disease. Further progress will come from sequencing the entire genome of multiple patients and normal controls to evaluate overall mutational burden and disease risk. A major challenge will be the interpretation of the resulting data and distinguishing true pathogenic mutations from rare benign variants. While in model organisms such as the zebrafish, mutants are sought that disrupt the function of individual genes, human mutations that cause, or are associated with, the development of disease, are often not acting in a Mendelian fashion, are frequently of small effect size, are late onset, and may reside in non-coding parts of the genome. The zebrafish model is uniquely poised for understanding human coding- and non-coding variants because of its sequenced genome, a large body of knowledge on gene expression and –function, rapid generation time and easy access to embryos. A critical advantage is the ease of zebrafish transgenesis, both for the testing of human regulatory DNA driving expression of fluorescent reporter proteins, and the expression of mutated disease-associated human proteins in specific neurons to rapidly model aspects of neurological disorders. The zebrafish affords progress both through its model genome and its rapidly developing transparent model vertebrate embryo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping