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TR: What’s the most exciting finding so far?

CV: For me, the most exciting finding is that human-to-human variation is substantially higher than was anticipated from versions of the human genome done in 2001. If fact, it might be as much as tenfold higher: rather than being 99.9 percent identical, it’s more like 99 percent identical. It’s comforting to know we are not near-identical clones, as many people thought seven years ago.

TR: How will scientists use your genome sequence?

CV: It will serve as a reference genome. This is probably the first and last time anyone will spend the time, money, and energy to sequence a diploid genome using highly accurate Sanger sequencing. Future genomes, like those from 454 or George Church’s Personal Genome Project, will be layered onto [existing] data, adding to the completeness of this genome. (See “The Personal Genome Project.”) [The traditional Sanger sequencing method, used for the Human Genome Project and to generate Venter’s sequence, generates longer pieces of DNA than do newer methods, such as that used by 454, making it easier to assemble the overlapping pieces.]

TR: James Watson released a version of his own genome earlier this summer. How is yours different?

CV: There has been nothing published yet on his genome, so we have no idea. But as I understand it, in contrast to really assembling a genome, they sequenced short fragments that are layered onto the sequence assembled at the NIH. So there are a lot of technical differences, but until it’s published, we won’t really know.

TR: You’ve had sections of your genome in the public domain for several years now. Any second thoughts about putting the entire high-quality sequence out there?

CV: No. And I applaud Watson for doing this as well. A key part of the message here is that people should not be afraid of their genetic codes or afraid to have other people see them. That’s in contrast to the notion that this is dangerous information that should be kept under lock and key. We’re not just our genetic code. There is very little from the code that will be 100 percent interpretable or applied.

TR: Have you searched your genome for disease-related mutations?

CV: Yes. I have a book coming out in October called A Life Decoded where I look at many variants and try to put them in context of my life. For example, I have a high statistical probability of having blue eyes, but you can’t be 100 percent sure from my genome that I have them. The message is that everything in our genomes will be a statistical uncertainty. We’re really just in the first stages of learning that.

Previous published genomes don’t represent anyone, so we can’t interpret human biology based on these. But now we can start to make human-genome inferences. We’ll need tens of thousands to millions of genomes to put together a database that would allow interpretation of multiple rare variants and what they mean. That will take decades.

TR: How much did the project cost?

CV: The goal was not to see how cheaply we could sequence a genome; it was to see how accurately we could do it. It was clearly a multimillion-dollar project over the years.

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Credit: J. Craig Venter Institute

Tagged: Biomedicine, DNA, genome, genomics, copy number variation

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