biotech

The new Genome Biology has a perspective piece by Jacob Tennessen and colleagues, titled "The promise and limitations of population exomics for human evolution studies" [1]. Exomics is the study of the coding part of the genome, which is only 30 megabases as opposed to the 3 gigabases of a whole genome. Today it is possible to apply methods that sequence only the protein-coding parts of the genome, by combining methods that capture such regions with next-generation sequencing. The result is vastly cheaper than a whole genome, and some of this cost savings can be applied to increase the coverage, which increases the sequence accuracy.

Tossing away 99% of the genome is not an ideal sampling strategy for many purposes. However, when it comes to phenotype prediction, we can make some predictions about how changes in amino acid sequences will affect protein function. Many important phenotypic changes are caused by non-coding variations in gene regulation, but genetics has not yet reached a state of knowledge where these can be readily predicted. So, if we're sequencing people's genomes for the purposes of finding disease or phenotype variants, exome sequences give much of the information that we can presently evaluate.

James Hadfield noted the spree of exome sequencing publications at his blog, Core Genomics ("Exome capture comparison publication splurge"). He tags the rationale for

A lot of people I have talked to are now looking at screening pipelines which use Exome-Seq ahead of WGS to reduce the number of whole Human genomes to be sequenced. The idea being that the exome run will find mutations that can be followed up in many cases and only those with no hits can be selected for WGS.

I have heard a number of geneticists looking at exome sequencing as an intermediate step in population genetics, a way to increase the size of samples more affordably than whole genome sequencing makes possible at present. I don't think this will last long, as whole genomes offer much more for population genetic analysis and are rapidly dropping in price, but that depends on how technology develops. If we are consistently in the situation where researchers can multiplex 50 exomes at high coverage for the same price as one whole genome, it may make sense to use that strategy for a long time.

23andMe is starting an exome sequencing project. Daniel MacArthur's comments on G+ and the subsequent reader comments are interesting.

References

The Wall Street Journal has an op-ed by Matt Ridley, on the topic of possible regulation of consumer genetic testing. He writes that after years of relative non-interest in such tests, he ordered his own because of the likelihood that the FDA will limit their ability in the near future.

The champions of regulation respond that some firms in the direct-to-consumer genetic-testing industry are sometimes much exaggerating the health benefits of genotyping. As I said above, most results are anodyne and close to useless in terms of telling you how to live your life, but that is not how it sounds on the websites. However, this is not an argument for FDA medical-device regulation or requiring doctors' prescriptions before testing. It is an argument for plain, old-fashioned truth-in-advertising regulation of the kind effected by the Federal Trade Commission.

The AMA always seems to think it's fighting Doc Brinkley. Personally, I'd say the supplement industry is a far greater threat to the public health than DTC genetic testing, and is surely a better use of the FDA's time.

UPDATE (2011-04-24): More on Gene Expression. Much tweeting of the final line of the op-ed, as well:

Genetic knowledge, whether the high priests like it or not, is going to be a crowd-sourced phenomenon.

Dan MacArthur reads the American Medical Association's letter to the FDA about direct-to-consumer genetics testing, and doesn't like what he sees ("American Medical Association: You Can’t Look At Your Genome Without Our Supervision").

In other words, the AMA is seeking to maintain its members’ traditional monopoly over the interpretation of genetic information – and they expect regulators to act as their enforcers, beating down the upstart DTC genomics companies who have wandered onto their sacred turf.

This is, of course, an absurd, desperate demand. If doctors think that people should consult them about their genomes, they shouldn’t run crying to the regulators to provide the necessary force; instead, they need to convince the public that a medical consultation adds genuine value to their genomic information. Unfortunately for the AMA, right now it’s far from clear that this is true: in many cases, DTC genomics customers are far better equipped to interpret their results than their doctors are.

Seems to me they're taking more or less the same approach with direct-to-consumer genomics as they did with Doc Brinkley's goat gland operations. (Just to be clear, not a good reaction.)

Razib takes the point and concludes that Brinkley's Mexican radio model -- that is, offshore sequencing and genotyping -- will probably win the day. Still, maybe it's time for a data rush before somebody pulls the regulatory plug ("Run as fast as you can"):

But here’s the important point, I’ve got the markers on several computers and in Gmail. Once the information is out, it’s out. There’s no way that the government can put the genie back in the bottle for those of us who have raced ahead of feared regulation. So run, just in case. Once you cross the threshold they can’t drag you back, no matter how powerful their lobbyists and marketers are.

I'm thinking it would be notably helpful if we came up with a more useful application of nuclear SNP data to genealogy. Hard to regulate away genealogy research. But lots of challenges interpreting SNP data in genealogical terms.

Now, if I can just find a way to embed advertisements in SNP data. Ooooh! Better yet, June Carter.