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Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches^,, and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes^,, this number falls considerably short of the more than 22,000 mouse protein-coding genes. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning, insertional mutagenesis^,,, antisense morpholino oligonucleotides, targeted re-sequencing^,,, and zinc finger and TAL endonucleases^,,, have made substantial contributions to our understanding of …