Population genetic diversity in zebrafish lines

Abstract

Toxicological and pharmacological researchers have seized upon the many benefits of zebrafish, including the short generation time, well-characterized development, and early maturation as clear embryos. A major difference from many model organisms is that standard husbandry practices in zebrafish are designed to maintain population diversity. While this diversity is attractive for translational applications in human and ecological health, it raises critical questions on how interindividual genetic variation might contribute to chemical exposure or disease susceptibility differences. Findings from pooled samples of zebrafish support this supposition of diversity yet cannot directly measure allele frequencies for reference versus alternate alleles. Using the Tanguay lab Tropical 5D zebrafish line (T5D), we performed whole genome sequencing on a large group (n = 276) of individual zebrafish embryos. Paired-end reads were collected on an Illumina 3000HT, then aligned to the most recent zebrafish reference genome (GRCz10). These data were used to compare observed population genetic variation across species (humans, mice, zebrafish), then across lines within zebrafish. We found more single nucleotide polymorphisms (SNPs) in T5D than have been reported in SNP databases for any of the WIK, TU, TL, or AB lines. We theorize that some subset of the novel SNPs may be shared with other zebrafish lines but have not been identified in other studies due to the limitations of capturing population diversity in pooled sequencing strategies. We establish T5D as a model that is representative of diversity levels within laboratory zebrafish lines and demonstrate that experimental design and analysis can exert major effects when characterizing genetic diversity in heterogeneous populations.

ahr2, But Not ahr1a or ahr1b, Is Required for Craniofacial and Fin Development and TCDD-dependent Cardiotoxicity in Zebrafish

“…The presence of background mutations in the ahr2 uab147/À line is unlikely, as heterozygotes were crossed to wild type for at least 3 generations before heterozygotes were crossed to each other to generate homozygous embryos. Third, it is possible that strain differences account for phenotypic differences between mutants, as has been suggested previously by genetic comparisons between zebrafish strains (Balik-Meisner et al, 2018). ahr2 hu3335 and ahr2 osu1 mutants were generated on the 5D wildtype strain (Garcia et al, 2018;Goodale et al, 2012), whereas ahr2 uab147 mutants were generated on the AB wild-type strain.…”

Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure

“…2015 ). The T5D zebrafish line used in our experiments presents such a genetically heterogeneous population, containing levels of interindividual diversity required for studies of differential susceptibility ( Balik-Meisner et al. 2018 ).…”

Integrating fish models in tuberculosis vaccine development

“…Compared to inbred mice strains, zebrafish are genetically heterogeneous in laboratory conditions and the ability of individuals to resist M. marinum usually varies, but this can be overcome by using adequate group sizes based on power calculations (Balik-Meisner et al, 2018). Also, this recapitulates the natural diversity in the human population (Balik-Meisner et al, 2018;Churchill et al, 2004). The studies evaluating the efficacy of BCG and novel vaccine candidates in zebrafish are summarized in the following section and in Table 3.…”