A paper describing the use of whole-genome deep sequencing to pinpoint mutations in the worm C. elegans is published online in Nature Methods. The approach is not limited to C. elegans - it should, in principle, be applicable to any model organism whose genome has been sequenced.
A standard approach to study the function of genes in model organisms is to perform genetic screens. In a traditional genetic screen, scientists induce mutations in the organism's genome with a chemical and the animals are then monitored for the altered phenotype of interest. However, the next step - the actual identification of the gene that is lesioned in mutant individuals - is often very laborious and time-consuming.
Oliver Hobert, Itsik Pe'er and colleagues show, in a proof-of-principle study in the popular genetic model organism Caenorhabditis elegans, that it is possible to pinpoint the single-nucleotide change responsible for an altered phenotype by simply sequencing the genome of mutant animals. They first identified the approximate region of the genome in which the change was located, then sequenced this region using Illumina technology and compared the sequence to that of the reference worm genome. They thus revealed the identity of a previously unknown mutant gene.
The implications of the time savings with this approach are many. Not only will it substantially save on personnel labour, but the fact that mutant alleles can be more rapidly identified will mean that larger genetic screens can be carried out and that genes involved in subtle phenotypes can be more easily identified.
Oliver Hobert (Columbia University, New York, NY, USA)
Itsik Pe'er (Columbia University, New York, NY, USA)
Abstract available online.
(C) Nature Methods press release.
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