The zebrafish reference genome sequence and its relationship to the human genome
Kerstin Howe, Matthew D. Clark, Carlos F. Torroja, James Torrance, Camille Berthelot, Matthieu Muffato, John E. Collins, Sean Humphray, Karen McLaren, Lucy Matthews, Stuart McLaren, Ian Sealy, Mario Caccamo, Carol Churcher, Carol Scott, Jeffrey C. Barrett, Romke Koch, Gerd-Jörg Rauch, Simon White, William Chow, Britt Kilian, Leonor T. Quintais, José A. Guerra-Assunção, Yi Zhou, Yong Gu et al.
Affiliations Contributions Corresponding author
Nature (2013) doi:10.1038/nature12111
Received 23 August 2012 Accepted 21 March 2013 Published online 17 April 2013
Zebrafish have become a popular organism for the study of vertebrate gene function1, 2. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease3, 4, 5. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes6, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.