Identification, conservation, and expression of tiered pharmacogenes in zebrafish

The number of adverse drug events in the United States is critically high, with annual rates exceeding 1 million cases over the last nine years. One cause of adverse drug events is the underlying genetic variation that can alter drug responses. Pharmacogenomics is a growing field that seeks to bette...

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Bibliographic Details
Published in:PloS one 2022-08, Vol.17 (8), p.e0273582-e0273582
Main Authors: Demery-Poulos, Catherine, Chambers, Joseph M
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Animal models
Biology and Life Sciences
Clinical trials
Conservation
Danio rerio
Drug efficacy
Engineering and Technology
Gene expression
Gene sequencing
Genes
Genetic aspects
Genetic diversity
Genetic engineering
Genetics
Genomes
Genomics
Identification and classification
Medicine and Health Sciences
Modelling
Ontology
Pharmacogenetics
Pharmacogenomics
Pharmacology
Precision medicine
Research and Analysis Methods
Zebra fish
Zebrafish
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Summary:The number of adverse drug events in the United States is critically high, with annual rates exceeding 1 million cases over the last nine years. One cause of adverse drug events is the underlying genetic variation that can alter drug responses. Pharmacogenomics is a growing field that seeks to better understand the relationship between a patient's genetics and drug efficacy. Currently, pharmacogenomics relies largely on human trials, as there is not a well-developed animal model for studying preventative measures and alternative treatments. Here, we analyzed pharmacogene expression at two developmental time points in zebrafish to demonstrate the potential of using this model organism for high-throughput pharmacogenomics research. We found that 76% of tiered human pharmacogenes have a zebrafish ortholog, and of these, many have highly conserved amino acid sequences. Additional gene ontology analysis was used to classify pharmacogenes and identify candidate pathways for future modeling in zebrafish. As precision medicine burgeons, adopting a high-throughput in vivo model such as the zebrafish could greatly increase our understanding of the molecular pathology underlying adverse drug events.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0273582