Kettleborough, R.N.W. et al. Nature 496, 494–497 (2013).
Howe, K. et al. Nature 496, 498–503 (2013).
Although cataloging all genes in model organisms is no longer a bottleneck, assigning function to genes still is. Despite the availability of several good gene-targeting tools, a large number of the 22,000 genes in mouse and of the 26,000 in zebrafish remain uncharacterized. Replacing the current gene-by-gene approach with an effort to phenotype disruptive mutations exome wide, Kettleborough et al. combined chemical mutagenesis with high-throughput sequencing. Aided by the latest well-annotated zebrafish genome (from the work of Howe et al.), the researchers designed exome-wide baits and used them to enrich exomes of the F1 generation of a chemically mutagenized parent for sequencing. From 808 sequenced exomes, they found mutations in 75% of protein-coding genes. For rapid phenotypic analysis of the mutant alleles, the researchers examined the frequency of homozygous mutations in F3 embryos of incrossed F2 individuals.
About this article
Cite this article
Finding function. Nat Methods 10, 464 (2013). https://doi.org/10.1038/nmeth.2499