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Rewriting Life

Genomes for the Masses

The proliferation and plummeting cost of DNA sequencing heralds the year of the personal genome.

This year may be remembered as the year of the personal genome. Last month, two companies announced plans to decode the genomes of individual human beings. A company in Branford, CT, 454 Life Sciences, is sequencing the genome of James Watson, the codiscoverer of the structure of DNA and an eminent figure in the genomics field (see “Sequencing in a Flash”). And Illumina, a DNA analysis company headquartered in San Diego, CA, is sequencing the genome of one of the Yoruba people participating in the international HapMap project, the first effort to probe the structure of diversity in the human genome on a large scale (see “Genes, Medicine, and the New Race Debate,” June 2003).

Whereas the DNA sequence produced by the Human Genome Project in 2003 was a mosaic drawn from a number of different human genomes, the efforts by 454 Life Sciences and Illumina, which could be completed in the next few months, will be the first sequences of individual genomes. As such, they herald the era of “personalized genomics.” An individual genome sequence shows the particular combination of genetic variants in an individual’s DNA, allowing scientists to explore the relationship between a person’s genotype and his or her biological traits. This has been done at the level of single genes for decades, but never before on the genome-wide scale.

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What has brought genetics to this point is the rapid development of new sequencing technologies over the last few years. Both Illumina and 454 are marketing DNA-sequencing instruments that depart in their chemistries and methods of detection from the traditional “Sanger sequencing” technology, which has dominated the field for the last 30 years. Following close behind Illumina and 454 are several other companies that expect to have new sequencing instruments on the market this year.

Much of this activity is driven by an $83 million investment by the NIH’s National Human Genome Research Institute, which sponsors development of sequencing technologies to produce a $100,000 genome and eventually a $1,000 genome. These new technologies should deliver a human draft genome–meaning a sequence with gaps and some errors–for $100,000 by next year. Will this drop to $1,000 by 2013? I would not bet against it, given the progress since a few years ago, when the cost of a draft sequence was 150 times what it is now.

Some technical challenges still lie ahead. A draft sequence is assembled from millions of random, short component sequences; the longer the components, the easier the whole genome is to assemble, with fewer gaps in the finished product. In Sanger sequencing, the fragments are 800 bases long; with 454’s technique, they are about 250 bases; and with Illumina’s, they are 30 bases. This year we will begin to learn the utility of draft DNA sequences produced by the new technologies.

By the way, a $1,000 human sequence would mean that a bacterial sequence would cost around $1. The human body has more than 10 times as many bacterial cells colonizing it (the human microbiome) as human cells. And unlike the human cells, which are all pretty much the same, bacterial cells represent tens of thousands of species. So it is not surprising that NIH and other agencies worldwide are beginning to mobilize for a Human Microbiome Project. But that’s a story for another time.

George M. Weinstock is codirector of the Human Genome Sequencing Center at Baylor College of Medicine in Houston, TX.

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