Forward genetic screens have elucidated molecular pathways required for innumerable aspects of life, however identifying the causal mutations from such screens has long been the bottleneck in the process, particularly in vertebrates. Now, researchers at Fred Hutchinson Cancer Research Center have developed an RNA-seq based approach that identifies both the region of the genome linked to a mutation and candidate lesions that may be causal for the phenotype of interest. They show that their method successfully identifies zebrafish mutations that cause nonsense or missense changes to codons, alter transcript splicing, or alter gene expression levels. Furthermore, they have developed an online accessible or downloadable bioinformatics pipeline allowing for easy implementation of all steps of the method. Overall, they show that RNA-seq is a fast, reliable, and cost effective method to map and identify mutations that will greatly facilitate the power of forward genetics in vertebrate models.
Availability – RNAmapper is online accessible or downloadable at: http://www.rnamapper.org/
- Miller AC, Obholzer ND, Shah AN, Megason SG, Moens CB. (2013) RNA-seq based mapping and candidate identification of mutations from forward genetic screens. Genome Res [Epub ahead of print]. [abstract]