Genetics. Published Articles Ahead of Print: October 28, 2008, Copyright © 2008
doi:10.1534/genetics.108.096487

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Rapid High Resolution SNP-CGH mapping in Caenorhabditis elegans

Stephane Flibotte 1, Mark Edgley 1, Jason Maydan 1, Jon Taylor 1, Rick Zapf 1, Robert Waterston 2 and Donald G. Moerman 1*

1 University of British Columbia
2 University of Washington

* To whom correspondence should be addressed. E-mail: moerman{at}zoology.ubc.ca.

Submitted on September 19, 2008
Revised on October 15, 2008
Accepted on 24 October 2008


Abstract

We have developed a significantly improved and simplified method for high-resolution mapping of phenotypic traits in Caenorhabditis elegans using a combination of Single Nucleotide Polymorphisms (SNPs) and oligo array Comparative Genome Hybridization (array CGH). We designed a custom oligonucleotide array using a subset of confirmed SNPs between the canonical wild-type Bristol strain N2 and the Hawaiian isolate CB4856, populated with densely overlapping 50mer probes corresponding to both N2 and CB4856 SNP sequences. Using this method a mutation can be mapped to a resolution of about 200 kb in a single genetic cross. Six mutations representing each of the C. elegans chromosomes were detected unambiguously and at high resolution using genomic DNA from populations derived from as few as 100 homozygous mutant segregants of mutant N2/CB4856 heterozygotes. Our method completely dispenses with the PCR, restriction digest and gel analysis of standard SNP mapping and should be easy to extend to any organism with interbreeding strains. This method will be particularly powerful when applied to difficult or hard to map low penetrance phenotypes. It should also be possible to map polygenic traits using this method.

Key Words: C. elegans, Single Nucleotide Polymorphism, comparative genome hybridization, mapping, mutant