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All about Craig: the first 'full' genome sequence

Revealing that the genetic pioneer has wet earwax, and more...

Controversial genomics pioneer Craig Venter has sequenced his own genome. In a preliminary analysis published this week (S. Levy et al. PLoS Biol. 5, e254; 2007), Venter's team has picked apart the sequences belonging to both chromosomes in each of the 23 chromosome pairs found in his cells, providing the first glimpse of the variation found within a single genome.

The paper also highlights some features of Venter's genome. The sequence of his ABCC11 gene, for example, indicates that Venter is likely to have wet earwax, as opposed to dry. In a finding likely to disappoint some critics of the maverick scientist, Venter has four repeat sequences located just before his MAOA gene. Having only three of the repeats is associated with an increased risk of antisocial behaviour. On a more sobering note, Venter's APOE sequence is associated with a higher risk of Alzheimer's and cardiovascular diseases, and his SORL1 gene also contains several variants that are associated with Alzheimer's disease.

For more about his personal genomic and family history, Venter aficionados can refer to his upcoming book, A Life Decoded. Venter has placed references to how his genome sequence may have affected his life throughout the book, says Jan Witkowski, executive director of the Banbury Center at Cold Spring Harbor Laboratory in New York, who is reviewing the book for the 4 October issue of Nature.

Venter's sequence also provides important new information about the human genome. Previous sequencing efforts have not distinguished between the two copies of each chromosome, or even between DNA from different donors. “What we were doing was mixing up alleles,” says Samuel Levy — who led the study at the J. Craig Venter Institute in Rockville, Maryland — referring to DNA sequences from specific spots on the chromosome. “We were creating Frankenstein versions of chromosomes.”

This time, armed with an additional 13 million sequences — added to the 19 million generated from Venter's own DNA during the first genome project — and fresh algorithms designed to pick apart sequences from different versions of the same chromosomes, Levy and his team could look at the variation within the genome. They found more than 4 million variations between the two sequences, including single nucleotide differences, sequence insertions and deletions, and differences in the number of copies of a given gene. Some 44% of Venter's genes contained a genetic difference between copies found on each chromosome. Venter's two sets of chromosomes differed by 0.5%, suggesting that there may be seven times more DNA variation than previously expected, says Levy.

The man within: enthusiasts will be able to examine the genetic make-up of Craig Venter. Credit: M. NAGLE/GETTY

This approach provides a clearer picture of the human genome, says Edward Rubin, director of the Joint Genome Institute in Walnut Creek, California. Before, the sequence gave a “statistical view” of the genome, Rubin says. “And in fact the genome is not statistical, it's really a linear array of bases.”

Venter notes that single genetic changes are unlikely to seal his fate. “I take it very seriously,” he says. “But most diseases are going to be some huge compilation of human factors and environmental factors.” Witkowski agrees, but says that reading about someone's genome can strike an emotional chord. “Somehow there's a sense that when you tell people that sequence, you're telling them in a very deep way about yourself,” he says. “It's like looking at their medical records.”


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Related external links

J. Craig Venter Institute

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Ledford, H. All about Craig: the first 'full' genome sequence. Nature 449, 6–7 (2007).

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