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Richard Carson/Reuters
James Watson, co-discoverer of the DNA helix, received his genome data Thursday.

DNA pioneer Watson gets own genome map

The full genome of James Watson, who jointly discovered the structure of DNA in 1953, has been deciphered, marking what some scientists believe is the gateway to an impending era of personalized genomic medicine.

A copy of his genome, recorded on two DVDs, was presented to Watson on Thursday in a ceremony in Houston by Richard Gibbs, director of the Human Genome Sequencing Center at the Baylor College of Medicine, and by Jonathan Rothberg, founder of the company 454 Life Sciences.

"I am thrilled to see my genome," Watson said.

Rothberg's company makes an innovative DNA sequencing machine, the latest version of which proved capable of decoding Watson's genome in two months for less than $1 million, said Michael Egholm, vice president for research at 454. The sequence was verified and analyzed by Gibbs's center in Houston. It was Gibbs who proposed the idea of sequencing Watson's genome.

Watson has said he will make his genome available for researchers to study, with the exception of his apolipoprotein E gene, the status of which he does not wish to know because it predisposes a person toward Alzheimer's disease.

He emphasized the need for sequencing many more individual genomes to help researchers understand mental diseases like schizophrenia, which has struck a member of his own family, and urged others to let their full genomes and identity be put on record so that their physical and mental qualities could be correlated with their DNA.

"I'm afraid we'll begin to think of a lot of reasons for restricting release of genomes and guarding them as if they were nuclear weapons," he said.

Watson, a Nobel laureate, was "the right guy to do first" because of his discovery, with Francis Crick, that DNA is the basis of heredity, Rothberg said by e-mail. Watson was also the architect and first director of the U.S. government's $3 billion Human Genome Project, which completed the first human genome map in 2003.

But that genome sequence, at present the standard reference for the human genome, belonged to a composite of anonymous donors from Buffalo, New York, and cannot be matched with medical information from a single person.

The first two genome sequences belonging to individuals are now being made available to researchers within a few days of each other. One is Watson's, and the other belongs to J. Craig Venter, who as president of the company Celera started a human genome project in competition with the government's.

Venter left Celera after producing only a draft version of a genome, his own, in 2001, which the company did no further work on. He has now brought his genome to completion at his own institute in Rockville, Maryland, and deposited it last week in GenBank, a public DNA database, he said.

Watson and Venter are both taking a considerable personal risk in making their genomes publicly available. As is probably true for everyone, their genomes are likely to contain mutations that could lead to disease, revealing possibly unfavorable information about themselves and their relatives. Even though the interpretation of the human genome sequence has only just begun, they are, in principle, exposing all their imperfections to public view for the sake of advancing research.

Neither Venter nor 454 Life Sciences would discuss in detail the new individual genome sequences for fear of sanctions from the journals considering publications about them. But both genomes seem to be better in many ways than the current reference standard.

Both are diploid genomes, meaning that they include the DNA sequence in the chromosomes inherited from both parents, whereas the reference genome completed by the Human Genome Project did not capture these differences.

About 3.5 percent of Watson's genome could not be matched to the reference genome. One reason may be that the project scientists had to amplify human DNA by growing it in bacteria and may have lost many regions of human DNA that are toxic to bacteria, said Egholm, the 454 vice president for research. The 454 sequencer skips the bacteria stage entirely and is free of this source of bias.

Venter said that 454 would have assembled Watson's genome by comparing short lengths of analyzed DNA with the reference sequence, so the company might not have detected any structural errors present in the reference assembly.

Venter said his new genome had been assembled from scratch. There were many more differences than he had expected, including in single units of DNA that were extra or absent. "It's clear we have grossly underestimated the extent of human variation," he said.

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