基因测序，人类的福音还是奢侈品？

Genome sequencing goes clinical - April 29, 2010
Getting your entire genome sequenced – until now something reserved for a select few – is about to become open to many. Already, for $50,000, consumers can have their genomes sequenced, as did biotech CEO John West and his entire family recently (see reports in The Times, Genetic Future).

But easy access to sequencing raises a head-scratcher of a question: What’s a doctor to do if a patient walks in with a copy of her sequence and asks to be treated on its basis? An article published in the May 1 issue of The Lancet tries to answer that question, proffering the first attempt at a comprehensive clinical analysis from the full genome sequence of a relatively healthy person. (You can already get a partial genetic profile from companies such as 23andMe, but your full genome sequence will presumably contain much more information.)

That healthy person is Stanford University bioengineer Stephen Quake, also the founder of the sequencing company Helicos. Quake published his genome sequence last year. “I of course was very interested in what [the sequence] has to say about my health,” Quake says. Of particular concern was his family history of vascular disease and early sudden death.

Running the sequence through two different automated software tools and one human specialist in the genetic roots of heart disease (Euan Ashley, the study's lead author), he learned he had rare variants in three genes that were associated with serious heart disease. That led to a full-on assessment of heart function. “This is how you’d use the genome to ration healthcare,” he says – test people more frequently for conditions they are at higher risk of experiencing, and less frequently where the risk is lower. The sequence also revealed other useful information, like Quake's dosing sensitivities to specific drugs, such as the blood thinner warfarin.

There are still tons of issues with converting sequence information into clinical recommendations. Some diseases, like Alzheimer’s disease or diabetes, have so many non-genetic variables that it’s hard to know what to do with a knowledge of heightened genetic risk. Also, says Quake, “there are limits to knowledge in the literature right now – how do you deal with mistakes in the literature, and bad papers?” Another point raised by a commentary to the study published online today: if a person discovers roughly 100 important genetic risks in her sequence, who’s got the several hours needed to explain those risks to her?

A lot of these issues came up at the inaugural Genes Environments Traits (GET) conference in Cambridge, MA, earlier this week. The meeting provided one last chance to bring together most of the individuals who have had their genomes sequenced. They shared their personal experiences in dealing with both the information their sequence gave them, and the concerns such as privacy that it raised. Quake noted at the meeting, for example, that though sequencing his genome took just two weeks, clinically interpreting it took a year. Analysis, most researchers agree, is where the bottleneck is.

Participants at the meeting – both the sequenced and the sequencers (which at this point is a heavily overlapping list) – seemed convinced that such problems will be solved. Jay Flatley, CEO of Illumina, showed me a nifty iPad app the company is testing that explains risk factors in an interactive way. (Interestingly, to get your sequence done by Illumina, you need to have a prescription from a doctor.) “We’re moving towards this being a key part of healthcare,” Flatley said. But whether that vision will be realized in the 10-year time-frame he predicts remains to be seen.

Both Discover Magazine in 2006 and Time Magazine in 2010 published reports showing DNA is not man's destiny --- that the epigenome, influenced by environmental factors (temperature, radiation, food or lack of food) activate genes at the epigenomic level. Gene sequencing would detect rarer genetic disorders and would be of far less value.
---nature.com