The advantages and disadvantages of using zebrafish for validation of GWAS loci from DILI studies
Advantages
Disadvantages
Ease of application of drugs dissolved in the embryonic media in embryos and early larvae
Ease of liver imaging in intact organism
Differences in the liver architecture between zebrafish and humans may alter pathogenesis of DILI species-specifically
Ability to screen a high number of biological replicates using a wide range of doses
Most GWAS loci are non-coding and may not be well conserved between species
Availability of various mutant strains of GWAS loci as ready-to-use models
Speedy generation of knockout and transgenic strains
Difficulty in functional assessment of knock-out and knock-in strains because of the presence of paralogous copies of genes in zebrafish (one-to-many genes)
Presence of many GWAS human loci with orthologs in the zebrafish genome
Not all human GWAS loci have orthologs in zebrafish
Observed similarity between humans and zebrafish in their pathogenic response to drugs
Varying levels of sequence similarity between protein coding genes of zebrafish and humans
Potential for generating specialized zebrafish cohorts for eQTL studies
Requirement of a large collection of strains/individuals for idiosyncratic DILI studies in zebrafish