Genetic Diversity and Strain Sub-structuring Among Zebrafish

Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of zebrafish CNVs, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly-used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising of 6,080 CNV elements (CNVE) and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of CNVEs exhibited strain-specificity with the highest number of total and strain-specific CNVEs observed for Tubingen. This variation likely arose, in part, from Tubingen’s large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and sub-structure of the other commonly-used laboratory strains. This extensive variation among and within zebrafish strains undoubtedly has unpredictable functional effects with the potential to confound analyses. If not properly addressed, such extensive levels of germ-line variation and population sub-structure in this commonly-used model organism can potentially confound studies intended for translation to human diseases.