Whole-genome sequencing and variant discovery in C. elegans

Massively parallel sequencing instruments enable rapid andinexpensive DNA sequence data production. Because theseinstruments are new, their data require characterization withrespect to accuracy and utility. To address this, we sequenced aCaernohabditis elegans N2 Bristol strain isolate using the SolexaSequence Analyzer, and compared the reads to the referencegenome to characterize the data and to evaluate coverage andrepresentation. Massively parallel sequencing facilitates strain-to-reference comparison for genome-wide sequence variantdiscovery. Owing to the short-read-length sequences produced,we developed a revised approach to determine the regionsof the genome to which short reads could be uniquely mapped.We then aligned Solexa reads from C. elegans strain CB4858 tothe reference, and screened for single-nucleotide polymorphisms(SNPs) and small indels. This study demonstrates the utilityof massively parallel short read sequencing for wholegenome resequencing and for accurate discovery ofgenome-wide polymorphisms.In 1998 the decoding of the first animal genome sequence, thatof C. elegans, was published