Counting the cost of genome projects

December 27, 1999

What price knowledge? In the opinion of scientists, at least, the expense of sequencing genomes will be more than offset by the medical and scientific gains to follow. Taxpayers, however, surely hope the cost of these gains remains reasonable. Now, in this month's issue of Genome Research, a team led by Eric Lander of the Whitehead Institute for Biomedical Research analyzes the efficiency of current sequencing approaches and proposes a strategy to slash the price tag on genome projects.

Deciphering the typical mammalian genome requires scientists to break up its millions of DNA base pairs into manageable fragments, sequence the pieces, and (the tricky part) somehow assemble them back together. In an approach called "walking," researchers reassemble the genome by first sequencing a random selection of the genome fragments. They then search for fragments that partially overlap with these finished pieces, sequence the new fragments, and so on. The scientists can thus sequence sizeable segments of the genome in orderly procession, finishing when all the segments meet.

Where does excess cost arise? Making the segments meet involves sequencing some parts of the genome twice, a necessary evil that balloons the final tab. By constructing a mathematical model of the walking process, Lander and colleagues determine several methods to reduce this obligatory "redundant sequencing." The strategies they propose may substantially decrease the cost of sequencing enterprises, including the billion-dollar Human Genome Project.
Contact (author):

Eric Lander
Whitehead institute for Biomedical Research
Nine Cambridge Center
Cambridge, MA 02142
Fax: 617-252-1902

Cold Spring Harbor Laboratory

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