Engineering in genomics. Technical improvements in high throughput genome sequencing

High-throughput DNA sequencing of the C. elegans genome currently is ongoing at our Genome Sequencing Center (GSC) at Washington University School of Medicine in St. Louis and at the Sanger Centre in Hinxton, England. Our collaborative effort is aimed at completion of this 100 Mb genome by the end of 1998. Now just into our fifth year of sequencing, we have amassed a combined output of over 22 Mb of completed sequence. The first two years of the pilot project were spent investigating and evaluating different approaches to genome sequencing with respect to throughput, ease of associated techniques, and methods and their robustness. The resulting approach has since been used to produce almost all of the genome sequencing data for C. elegans and will, with appropriate modifications, continue to be our strategy of choice for the completion of this genome sequence and the beginning of the human genome. The basic strategy consists of three phases: a library construction phase, a production sequencing (“shotgun”) phase, and a directed “finishing” phase