Whole genome sequencing and the transformation of C. elegans forward genetics

• Whole genome sequencing (WGS) has transformed forward genetics in C. elegans.
• One-step mapping/WGS overcomes the bottleneck of high-resolution mapping.
• WGS prior to mapping can further accelerate gene discovery.
• WGS broadens the range of biological questions addressable using forward genetics.

Forward genetics has been an undeniably powerful approach in Caenorhabditiselegans and other model organisms. However, the trek from mutant isolation to identification of the causative molecular lesion can be time-consuming and fraught with obstacles. This has changed with the advent of whole genome sequencing (WGS). The widespread availability of high-throughput sequencing technology, coupled with the increasing affordability of WGS, has enabled the routine use of WGS in the analysis of forward genetic screens. The noteworthy development of one-step mapping/sequencing approaches has largely eliminated the bottleneck of conventional high-resolution mapping, greatly accelerating the journey from mutagenesis to gene discovery. By enabling the use of increasingly complex and diverse genetic backgrounds as substrates for mutagenesis, WGS is expanding the landscape of biological problems that can be interrogated using forward genetic approaches in C. elegans and other organisms.