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US company claims to have 90%of human genome on its database

BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7229.206 (Published 22 January 2000) Cite this as: BMJ 2000;320:206
  1. Deborah Josefson
  1. San Francisco

    The US biotechnology company Celera Genomics has announced that it has the DNA sequence of 90%of the human genome in its databases, far outpacing both its own schedule and that of the publicly funded human genome project, which was established in 1990.

    Celera, founded in May 1998 by Craig Venter, claims to have sequenced 81%of the genome on its own. It has inferred an additional 9%from the publicly available data published by the National Institutes of Health in Maryland and by the Sanger Centre in Cambridge, England.

    The company estimates that 97%of all human genes are already represented in its database, given a genome size of about 80000 genes.

    Celera, which began its sequencing project on 8 September 1999, expects to complete the entire sequence by June 2000. The achievement, which ushers in the era of pharmacogenomics, is remarkable for its rapid pace and has widespread medical, ethical, and financial implications, especially since Celera is a private commercial enterprise.

    Celera's success in outpacing the competition can be explained somewhat by the fact that it is a single company rather than a group of academic and national research centres, thus eliminating irrelevant bureaucracy.

    The human genome project is being conducted by eight university centres funded by the National Institutes of Health, and by the US Department of Energy and the Sanger Centre in Cambridge, England.

    Moreover, Celera takes a different sequencing approach from that of the public consortium. Celera uses a “shotgun” technique, whereby the DNA of a single anonymous male is sheared into many small and large fragments, which are then reassembled in a manner akin to putting together a large jigsaw puzzle. This is accomplished by inserting the fragments into a plasmid vector and propagating them in Escherichia coli to produce millions of copies of each fragment.

    Linking DNA sequences of known length are added to fill in the gaps, and when these missing pieces are found, the linkers can be deleted. The millions of DNA base pairs are then reassembled with the help of a supercomputer. Celera's computer is believed to be the second most powerful in the world and is active 24 hours a day, 7 days a week. Two billion base pairs are sequenced by the Celera computer each month.

    In contrast, the human genome project is sequencing the DNA of multiple anonymous donors and mapping the genes to a precise location in a more painstaking manner. Their protocol entails inserting the genes into bacterial artificial chromosomes, mapping their positions on these chromosomes, and then sequencing them.

    The Celera approach skips the mapping and the use of bacterial artificial chromosomes, which can hold on average only 150000 DNA bases each.

    Furthermore, Celera benefits from the publication by the human genome project of all newly sequenced DNA fragments on its website. Under the Bermuda Agreement, the public consortium is obliged to publish newly sequenced genes onto a publicly accessible website within 24 hours. Celera is not bound by such constraints, but takes advantage of them.

    As Celera is a commercial enterprise and is patenting many of the genes that it is discovering, interesting medical and ethical questions arise. Many fear that the success of Celera in trouncing its competition will lead to decreased federal funding for the public initiative.

    The consortium's project is important as the data are free and available to everyone, while Celera may choose to withhold some information, particularly those related to geneticpolymorphisms.


    Embedded Image

    Craig Venter, who founded Celera in 1998, appears on the company's website at www.celera.com/home.asp

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