High Throughput Linkage Mapping in C. elegans... tool for forward geneticists?

Hi all,

Full disclosure: I represent a company which has developed a quick, high throughput assay for SNP-based linkage mapping of chemically induced mutations. While the overarching aim of our technique isn’t anything novel, we have ported the process to the new high-throughput sequencing machines which reduces the cost of genotyping. To date we have successfully applied our technology to map several mutations in zebrafish, stickleback, neurospora and other selected model organisms.

This is where the worm community can assist us. We are trying to assess the market and general interest for said mapping application in forward genetic screens within C. elegans. It has been my observation that worm labs have been moving away from traditional forward genetics and into reverse strategies such as RNAi screens because of the throughput and relative ease of screening. While there are some downsides with RNAi or insertional mutagenesis, on the whole these techniques seem to be vastly favored over chemical mutagenesis followed by screening.

Do you feel that a rapid and cheap mapping tool would change this meta-trend in the worm community? To provide a case study on what this technology could do, based on recombination frequency of C. elegans and polymorphism rates between N2 and CB4856, using our technique, we project mapping an recessive, non-lethal mutation to within a 150-200 kilobase region using a standard mapcross, F1 incross and three subsequent backcrosses. Time elapsed including crosses, sequencing and data analysis would take a total of about two and half to three months. Does this seem exciting or particularly useful to you as a member of the worm community?

Opinions, thoughts and criticism would be appreciated.

Hi -

this tool would definitely be of high interest if it would enable labs to subcontract mapping at reasonable cost and high reliability. Obviously, if you could get the mapping down to a single gene or smaller interval, that would be better. Based on the reported density of polymorphisms between N2 Briston and the Hawaiian strain CB4856, shouldn’t you be able to get higher mapping precision?

I’d be interested in talking to you further about this since we’re embarking on a bunch of mapping in the near future.


I would also be interested in learning more about what you are proposing. We do a lot of RNAi screening, but also would like to perform mutagenesis screens. The main reason we haven’t is becasue of the time involved in mapping.

Thanks, Keith