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ARDEA

Stars with stripes: zebrafish are the focus of a genome sequencing initiative in Britain.

The UK Wellcome Trust is set to fund an effort, costing £5 million (US$7 million) in the first year, to sequence the genome of the zebrafish (Danio rerio) at the Sanger Centre near Cambridge. All the data will be made freely available in the public domain.

The zebrafish is a model organism for the study of vertebrate development. The fish also has transparent embryos, allowing developmental abnormalities to be spotted by eye. The female lays 200–300 eggs each week — enough for the identification of candidate genes and positional cloning, and the embryos mature within a couple of months. Millions of fish can also be bred in a small space.

The project emerged from discussions last year between John Sulston, then director of the Sanger Centre, and Christiane Nüsslein-Volhard, of the Max Planck Institute for Developmental Biology. Nüsslein-Volhard recently launched a complementary, $10 million project called the Tübingen 2000 Screen, which should allow point mutagenesis of the entire zebrafish genome to yield embryos with developmental abnormalities. The US National Institutes of Health may spend US$5 million on a similar screening project.

Fish genomes have long regions of 'synteny', where the order of the genes is similar to that found in humans, says Leonard Zon, a zebrafish researcher at the Children's Hospital of Boston. "This will allow genome 'ping-ponging'," he says. "If a zebrafish mutant falls in a region of synteny, the [corresponding] local region of the human genome can be searched."

The zebrafish genome has about 1.7 billion base-pairs. The full sequence and the massive mutant screen should allow every developmental gene to be isolated, from which the mutated genes can then be cloned. Many of the genes isolated will be relevant to human systems, so that research on zebrafish mutants will assist the annotation of the human genome.