September 28, 2010 | Illumina CEO Jay Flatley can have few regrets about his decision to acquire Solexa for $650 million in late 2006. The acquisition complemented Illumina’s existing platforms in genotyping and gene expression. The introduction of the HiSeq 2000 at the beginning of 2010 and its rapid uptake by BGI (137 instruments), the Broad Institute (51), and others, is further validation of the lasting power of Solexa’s sequencing technology. Flatley predicts that BGI will match the capacity of all the U.S. genome centers combined by the end of 2010. “That has very interesting implications,” he says. “We’re encouraging the U.S. centers to continue to scale up—it’s in their best interests and ours for them to keep up.”
Flatley was first in line when Illumina debuted its Individual Genome Sequencing Service (IGS), which currently costs $9,500-19,500. He told Bio•IT World he was reluctant to devote too many Illumina resources scouring his own personal genome, but two colleagues spent the better part of two months on it. “The analysis side of the human genome work is trailing significantly behind the systems technology,” he said. “We’re still very much at the infancy of trying to understand what the genome means. There is a lot of work required to ferret out what’s real and what’s not.”
Flatley says he’s generally healthy and didn’t encounter anything “revolutionary” in his genome, but the triage process left him as a confirmed carrier of variants in 11 Mendelian disease genes. “They were mostly interesting things I’d never heard of, like Hawkinsinuria and Alagille syndrome and familial cold autoinflammatory syndrome.”
Of greater concern were dozens of false positive variants that Flatley and colleagues found, particularly with regard to the Human Genome Mutation Database (HGMD) “because of what are really errors in the database,” said Flatley. All 16 of Flatley’s homozygous putative “disease-causing” mutations were discarded, as were more than 75% of the heterozygous variants. “Most of them fell out because they were very bad conditions and it was clear I would have died as an infant if I had those!” he said. Cleaning up such errors will take years, he says, “but we can’t do that obviously until we sequence lots of people. So it’s sort of a chicken-and-egg situation.”
Flatley’s personal experience convinces him there is a “dire need” to improve the state of the mutation repositories. “I think it’s a fantastic opportunity for some new start-ups to go after. There are so many dimensions to this: How do you store this information? How do you interface it with the physicians? What can the physicians see? How do you protect the consumer from the physician getting things you don’t want them to see? There’s so much infrastructure required here, not only to do the analysis but also to be able to present it and have the physician interact correctly with the consumer.”
“It’s an enormous opportunity and one that Illumina needs to help enable in order for us to continue to do more sequencing. It’s not something we feel we need to own, but we need to figure out how to enable.”
Among the first 14 genomes sequenced by the IGS were those of film actress Glenn Close, whom Flatley calls “the first woman who has had her genome done at full coverage.” Illumina also sequenced John West’s family; a couple of cancer patients; an infant that suffered from autoimmune disease, and a couple of centenarians. Since announcing a recent price drop, Flatley said there have been several clinical requests (priced at just $9,500), although Illumina does not always accede to the request, for example, if it does not judge the disease to be chronic. There hasn’t been much promotion for the IGS because of the desire to get the infrastructure running, troubleshoot the pipeline and understand potential ethical or privacy challenges. “A lot of questions did come up and we had to resolve them along the way,” he says.
Illumina provides the genotyping platform for the leading consumer genomics companies. “Our view is that people do have the right to their own genome information and we need to trust the fact that people can do responsible things with that information. In some ways, it’s analogous to the first amendment. It’s like telling people they can’t read books because they may react in some way to a particular book and they can’t have access (to it).”
But Flatley does favor greater regulation. There are three categories of markers in consumer genomics and they may end up being treated differently, he says.
While the FDA seems unconcerned by ancestry traits, on the other extreme there are markers for drug response and pharmacogenomics, which might benefit from greater analytical validation. “I think that’s appropriate and all the [consumer] companies agree with that. We’re beginning to work on ways to effect that.”
This article also appeared in the September-October 2010 issue of Bio-IT World Magazine. Subscriptions are free for qualifying individuals. Apply today.