A Sequence-Based Variation Map of Zebrafish

Abstract

Zebrafish (Danio rerio) is a popular vertebrate model organism largely deployed using outbred laboratory animals. The nonisogenic nature of the zebrafish as a model system offers the opportunity to understand natural variations and their effect in modulating phenotype. In an effort to better characterize the range of natural variation in this model system and to complement the zebrafish reference genome project, the whole genome sequence of a wild zebrafish at 39-fold genome coverage was determined. Comparative analysis with the zebrafish reference genome revealed approximately 5.2 million single nucleotide variations and over 1.6 million insertion-deletion variations. This dataset thus represents a new catalog of genetic variations in the zebrafish genome. Further analysis revealed selective enrichment for variations in genes involved in immune function and response to the environment, suggesting genome-level adaptations to environmental niches. We also show that human disease gene orthologs in the sequenced wild zebrafish genome show a lower ratio of nonsynonymous to synonymous single nucleotide variations.

The MHC class I genes of zebrafish

“…Because of these advantages, zebrafish are routinely employed for studies of in vivo immune function (van der Vaart et al 2012), host-pathogen interactions (Kanther and Rawls 2010;Tobin et al 2012), and cell migration (Ignatius and Langenau 2011;Renaud et al 2011), as well as transplantation assays, particularly for the study of hematopoietic stem cells (de Jong et al 2011;Li et al 2011;Taylor and Zon 2009). However their use in this type of assay highlights a current limitation: attempts at generating inbred zebrafish lines met with only limited success (Shinya and Sakai 2011), resulting in standard laboratory “lines” of zebrafish harboring a multitude of polymorphisms as well as haplotypic variation especially at immune loci (Howe et al 2013;Patowary et al 2013). As immunologically compatible zebrafish donors and recipients are not readily available, genotyping strategies have been and are being developed for identifying MHC-matched zebrafish.…”

Short Stories on Zebrafish Long Noncoding RNAs

“…61 The availability of the reference genome of zebrafish along with sequences of wild-type strains has enabled a much required template and impetus for annotation of transcriptome at a genome scale. [62][63][64][65] The corpus of annotated lncRNAs in zebrafish has been majorly derived from three recent publications, with each characterizing a distinct subset of the lncRNome. [28][29][30] While Pauli et al characterized the lncRNome of eight developmental time points, 29 Ulitsky et al annotated the lncRNome from three developmental time points of zebrafish.…”

“…A number of reports in recent years have utilized the power of next-generation sequencing toward understanding the landscape of zebrafish transcriptome. [28][29][30]64,75,76 The recent discovery of a large number of ncRNAs in zebrafish, including small ncRNAs and lncRNAs, has opened up a completely new repertoire of biological regulation, which is yet to be comprehensively understood. The discovery of lncRNAs in zebrafish is suggested to impact the understanding of zebrafish biology in a variety of ways.…”

“…Recent initiatives toward assembly of the genomic variations, epigenome, and transcriptomes in line with the human ENCODE project would definitely add to the understanding of zebrafish transcriptome and its regulatory correlates. 64,65,85 Thus, understanding zebrafish lncRNome would open up new possibilities toward understanding its effects in modulating the developmental processes and homeostasis.…”

The CRISPR System—Keeping Zebrafish Gene Targeting Fresh

“…There is a high level of diversity between laboratory strains and wild-type zebrafish compared to other vertebrate model organisms. 1 With the rapid emergence of genome editing tools and improvements in their targeting efficiencies within zebrafish, scientists are uniquely positioned to study how natural and engineered genetic heterogeneity impacts a range of phenotypes. In addition, novel uses of these tools will enable many engineering applications, including large deletions and complex rearrangements, targeted sequence insertions by exploiting homology directed repair (HDR) or homologous recombination (HR), as well as multiplex applications for concurrent modifications at multiple loci.…”