Random Shotgun Fire
This extract was created in the absence of an abstract.
Craig Venter’s and Perkin-Elmer’s May 9th announcement of a new joint venture to complete the sequence of the human genome in just 3 years set off a furor among the scientific community. The uproar, however, was unsurprising given that the earliest newspaper articles presented the plan as if it were afait accompli and accused the publicly funded Human Genome Project of being a “waste” of money. The announcement, made just prior to the Genome Mapping, Sequencing, and Biology Meeting, held May 13–17 at Cold Spring Harbor Laboratory, was discussed, at least briefly, at the sequencing center director’s meeting that preceded the CSHL meeting, in a very well-attended session during the CSHL meeting, and in numerous speculative debates over meals and beers among attending scientists.
The Facts
The publicly funded projects are generally sequencing the human genome by a strategy that might be called map and then shotgun. Physical maps of human chromosomes are constructed, typically first with YACs (yeast artificial chromosomes) and then with BACs (bacterial) or PACs (P1). A “minimal tiling path” of BACs/PACs that overlaps by the least amount is then selected and sequenced by a shotgun approach. All sequence data, both unfinished assembled sequence and completely finished clones, are released daily as agreed upon at the international sequence strategy meeting, held each of the last 3 years in Bermuda. The complete human sequence is anticipated in 2005, ending a 15-year project, with the last sequencing phase costing roughly $1 billion.
The basic plan of the Venter/Perkin-Elmer venture for sequencing the human genome is to use a whole-genome shotgun sequencing approach. This means sequencing random inserts from completely unmapped clones from libraries containing fragmented DNA from the whole human genome. The new company will perform at least 108 sequence reads (a 10-fold redundancy—or what some might call a …
