Nat Genet 36:1133–1137. In zebrafish, inbreeding adversely affects fecundity and survival (Mrakovcic and Haley 1979), so endeavors to create isogenic lines have not been fruitful. The T5D line is an “outbred” population of heretofore unknown genetic heterogeneity that has been used to screen thousands of chemicals for adverse biological responses (Truong et al. The adjustment of the MQ threshold from GATK’s recommendation of 40 to 35 accounted for the difference in quality score reporting between the aligner suggested by GATK (BWA) and Bowtie 2. These advantages have led to an upward trend in high-throughput zebrafish chemical screens, especially toward screens of many chemicals using large quantities of fish (Usenko et al. The VCF of 20,385,817 SNPs for T5D compared to the GRCz10 reference was used for SNP site comparisons to the NHGRI-1 line only. This was performed with the intention to more closely approximate variants that would have been called in T5D, had a pooled approach been employed instead of individual sequencing. Genetics 190:1017–1024., French JE, Gatti DM, Morgan DL et al (2015) Diversity outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. - 3). These rare variants would not be captured without a reasonably large sample of individuals. Development 142:1542–1552. When both larvae are diploid ( Fig 1A ), there are two main peaks; in addition to the G1 phase cells there is a second peak showing G2 phase cells with a 4n DNA content. Google Scholar, Ivanov DK, Escott-Price V, Ziehm M et al (2015) Longevity GWAS using the Drosophila genetic reference panel. Enter your email address to receive updates about the latest advances in genomics research. D. rerio is a common and useful scientific model organism for studies of vertebrate development and gene function. The red box contains the variant effects for the 20.1 M SNPs found in T5D. One reason for the success of zebrafish as a model organism is its amenability to genetic manipulation., Cho YS, Kim H, Kim H-M et al (2016) An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes., Oliveira R, Grisolia CK, Monteiro MS et al (2016) Multilevel assessment of ivermectin effects using different zebrafish life stages., Wilson CA, High SK, McCluskey BM et al (2014) wild sex in zebrafish: loss of the natural sex determinant in domesticated strains. All library preparation and sequencing were performed at Oregon State University’s Center for Genome Research and Biocomputing ( 1a). Google Scholar, Brown KH, Dobrinski KP, Lee AS et al (2012) Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis. PubMed  The majority of common variants in the human genome have already been discovered, but rare variants continue to be discovered via deep whole genome sequencing of cohorts of individuals from geographically/ethnically defined populations (Shen et al. After filtering, 12,179,880 SNPs remained, of which 12,009,411 were successfully mapped to the Zv9 reference genome. Finally, we explored whether the higher apparent diversity observed in our T5D line could be due to experimental design factors that tend to underestimate diversity in other published lines. 2016). 2011). Reads with a mapping quality below 20 were not included, and a minimum phred-scaled confidence threshold of 10 was required. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. And they breed very, very well., Howe K, Clark MD, Torroja CF et al (2013) The zebrafish reference genome sequence and its relationship to the human genome. There are many benefits to using zebrafish in developmental studies, including early maturation as clear embryos that are amenable to easily observable morphological endpoints, short generation time, and well-characterized development that is conserved across species during the phylotypic period (Kimmel et al. Next, 20% of each of their reads were randomly selected to create a simulated pooled sample at an average of 20× coverage. VEP (McLaren et al. All resources generated by the ZGC are publicly accessible to the biomedical research community. In order to create a RIL panel representing the genetic diversity among a more general populace of mice, the collaborative cross (CC) (Chesler et al. Individuals within one line are homogeneous, but comparisons of traits or susceptibility between lines have aided in identifying genetic associations (Cirelli et al. observable in the population, and establishing the validity of the T5D population as a heterogeneous model. Often a single fish can give you somewhere between 20 and 200 offspring in a single breeding, which is for geneticists just absolutely great. The zebrafish genome reference assembly: useful URLs. The 20.1 M SNPs equate to 13.4 SNPs per 1 kb genomic sequence. d Number of phenotype-gene associations per species (from Variants located in these non-complex regions of the genome were removed from the final T5D comparison dataset resulting in 10,301,547 SNPs and 2,375,455 indels. Thus, this model could be used for large-scale studies of chemical bioactivity that include genetic information on response mechanisms during development of exposed individuals (Baer et al. There was a region of chromosome 4 with drastically fewer variants in our study (Appendix Fig., Mackay TFC, Richards S, Stone EA et al (2012) The Drosophila melanogaster Genetic Reference Panel. We observed more intron variants in T5D, and synonymous gene transcript variant percentages fell between mouse and human (Fig. Zebrafish is a model organism widely used for the understanding of gene function, including the fundamental basis of human disease, enabled by the presence in its genome of a high number of orthologs to human genes. GRCz11 shows a significant reduction in scaffold numbers and increase in scaffold N50 whilst the overall genome size was not affected. 2007; Bai et al. We then empirically compared genomic characteristics of our zebrafish population with murine and human reference populations, as well as across other zebrafish lines. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. For these samples, 350 ng of DNA was used in the library preparation.
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