Children marveling at mutants of Medaka and Zebrafish

Zebrafish provide valuable insights into human development and disease, and a new study promises to make this research still more effective. An international team of researchers, writing in the journal Nature, has shown exactly how our genes line up with those of this amazing fish.

At first glance, zebrafish may not seem very similar to people. However, we both have spinal columns and in fact share a common ancestor (but this was long ago, in our floppier days). Zebrafish have been widely used to understand how genes affect our health and development, and are recognised as a key model organism. Zebrafish research has already led to biological advances in cancer and heart disease research, and is advancing our understanding of muscle and organ development. This latest study shows that the greater part of disease-associated genes in humans have counterparts in the zebrafish.

“To realize the benefits the zebrafish can make to human health, we need to understand the genome in its entirety – both the similarities to the human genome and the differences,” says Professor Christiane Nüsslein-Volhard, author and Nobel laureate from the Max Planck Institute for Developmental Biology. “Armed with the zebrafish genome, we can now better understand how changes to our genomes result in disease."

The team compared a very high-quality zebrafish genome sequence with the human reference genome. This was painstaking work because the zebrafish has duplicated its genome since we parted ways 400 million years ago. To make matters more complicated, many of the fish’s duplicated genes have ‘dropped out’ over the course of evolution, so the copies are not exactly the same. Until now, this has made the process of making a one-to-one comparison between zebrafish and human genes very frustrating. The new study provides an essential resource that can be used to streamline future studies.

“Because zebrafish are used to study human disease, it’s important that we know exactly how its genes correspond to our own,” explains Javier Herrero, co-author from EMBL-EBI. “Our role in this study was to disentangle all of this information using the data available in the Ensembl genome browser, and to figure out precisely how the genomes line up to one another. We could see that the zebrafish genome has kept a duplicate for a quarter of the genes that it shares with humans – that has been a real impediment in research. The reference we’ve provided will help these studies go a lot more smoothly."

“Our aim with this project, like with all biomedical research, is to improve human health,” says Dr Derek Stemple, senior author from the Wellcome Trust Sanger Institute. “This genome will allow researchers to understand how our genes work and how genetic variants can cause disease in ways that cannot be easily studied in humans or other organisms.” 

Source article

Howe, K., et al. (2013) The zebrafish reference genome sequence and its relationship to the human genomeNature (in press); published online 17 April. DOI: 10.1038/nature12111

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"Family ties: relationship between human and zebrafish genomes" - press release on the Wellcome Trust Sanger Institute's website