Identification, conservation, and expression of tiered pharmacogenes in zebrafish

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0273582

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.