December 4, 2008
Category: next-generation sequencing
David Dooling from PolITiGenomics has put together a handy little table for genomics nerds like me: statistics on the output of the various iterations of the three major competing second-generation DNA sequencing platforms (Roche's 454, Illumina's Solexa/Genome Analyzer and ABI's SOLiD).
It's probably a little inscrutable for non-genomicists, but it helps to provide some insight into the sheer scale of the DNA sequence data currently being produced by large-scale sequencing facilities. A single Illumina GA II machine, for instance, churns out on the order of 8 gigabases of sequence (that's almost three human genome equivalents) every week. Now consider that my workplace as of this week has 37 Illumina machines, all running hot pretty much 24/7 (well, most of the time), and you have some sense of the quantity of sequence currently being generated - and of the informatics infrastructure required to store, manage and process that volume of data.
Posted by Daniel MacArthur at 6:37 PM • 0 Comments
December 3, 2008
Category: genetics of normal variation
New Scientist trumpets the discovery of "the first placebo gene". The study in question is here.
I usually don't comment on this type of study, but this time the hype is just too much for me: New Scientist describes the study as "a milestone in the quest to understand" the placebo effect; an article in ScienceNow quotes a psychiatrist saying that "the findings could have major implications for research design". The article itself certainly doesn't talk down its results, with the first sentence of the discussion stating:
The present study demonstrates that the magnitude of the placebo response [...] is tied to attenuated amygdala excitability, which in turn is linked to serotonergic genetic variation.
The problem? The study examined just 25 subjects, and if there's one clear lesson from the history of candidate gene asociation studies it's that such tiny studies are essentially worthless: systematic reviews of the field (e.g. here, here and here) have consistently found that the majority of such associations are never replicated, suggesting that positive results in small studies are substantially more likely to arise through a combination of chance, error and publication bias than through a genuine causal link.
It's only relatively recently that genetic association studies have come of age, with the advent of agnostic genome-wide association studies, massive sample sizes, rigorous statistical frameworks and the use of independent replication cohorts. Unfortunately, it appears that such novelties haven't yet permeated Uppsala University's Department of Psychology - but that hasn't stopped their study from generating media attention, in publications that should really have known better.
So don't believe the hype: as a good rule of thumb, if a genetic association study contains fewer than 100 subjects, it's not a "milestone" with "major implications" - in fact, you might as well simply pretend it doesn't exist at all. (Many studies with more than 100 subjects are also crap, but at least there's a chance they're capturing a genuine causal variant.) I'm deadly serious about this. The field is so littered with the stinking carcasses of unreplicated candidate gene associations that it's a reasonable default to simply assume that any small, unreplicated study is false.
Now, if only there was a way to get the science journalists responsible to internalise that little rule of thumb...
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Posted by Daniel MacArthur at 8:45 PM • 18 Comments
Category: blog admin
Chris over at A Free Man has done a great job putting together the latest issue of genetics blog carnival Mendel's Garden - check it out.
Posted by Daniel MacArthur at 7:04 PM • 0 Comments
December 2, 2008
Category: gene patents
Reposted with a new title and minor corrections.
A sorry saga in Australian commercial genetics has apparently drawn to a close - just as another one looks set to begin.
Let's start from the beginning. Back in 2003, Australian biotech Genetic Technologies bought acquired the rights to a patent on testing of the breast cancer genes BRCA1 and BRCA2 from Myriad Genetics (see comments for details). In the face of massive public opposition to restrictions on public testing for the genes, the company announced that it wouldn't be enforcing the patent as a "gift to the people of Australia and New Zealand".
Then in July this year the company announced that it wanted its gift back: government testing laboratories around Australia received letters warning them that Genetic Technologies intended to resume enforcing its patent, and would prosecute anyone who persisted with testing beyond a November deadline.
Predictably, the move attracted a firestorm of protest, accompanied by boardroom shenanigans that warrant an article of their own. Now, with most of the board toppled from power, the company has officially announced a reversion to its previous position: the government labs can resume testing.
Breast cancer researchers, clinicians and women can all breath a sigh of relief. However, the BRCA1 and BRCA2 patents are not the only ones up Genetic Technologies' sleeve: ThinkGene points to a recent article in the Sydney Morning Herald movingly titled "Sick babies denied treatment in DNA row". The row in question is over a patent held by the company over testing of a gene involved in a severe congenital syndrome, which the company appears intent on enforcing - despite the fact that the high cost it charges for the test allegedly reduce its availability to patients and potentially delay important therapeutic intervention.
While Genetic Technologies bounces spasmodically from one PR disaster to another, the fundamental issues associated with gene patenting remain unresolved. Will government testing laboratories and researchers have to continue to rely on the unlikely generosity of biotech companies (and the pressure of public outrage) to continue their work, or will the Australian government come up with a sustainable solution? Will the government be able to tread the fine line between permitting corporate monopolies and creating an environment that stifles innovation in the biotech sector? We'll see.
Meanwhile, every time Genetic Technologies blunders into a media minefield the public perception of the field of human genetics in Australia shifts perceptibly in the same general direction as the company's stock price - an unfortunate side-effect, given the overall promise of this field for the future of personalised medicine. On the bright side, perhaps the company will implode before it manages to cause much further damage...
(Huge thanks to an anonymous reader who has kept me informed on the comings and goings of GTG.)
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Image credit: Ed.
Posted by Daniel MacArthur at 6:00 AM • 4 Comments
November 30, 2008
Category: genetics of normal variation
Disclaimer: I was one of the authors on a 2003 study reporting a link between ACTN3 and athletic performance, but I have no financial interest in ACTN3 gene testing. The opinions expressed in this post are purely my own.
An article in the NY Times yesterday describes the launch of the grandiosely named Athletic Talent Laboratory Analysis System (ATLAS). The ATLAS test looks at a common genetic variation within the ACTN3 gene, which has been associated in numerous studies with elite athlete status and with variation in muscle strength and sprint ability in the general population. The company claims that this variation "may determine the type of athlete you were born to be".
In the NY Times article ATLAS explicitly describes its target audience - the parents of young children:
Atlas executives acknowledge that their test has limitations but say that it could provide guidelines for placing youngsters in sports. The company is focused on testing children from infancy to about 8 years old because physical tests to gauge future sports performance at that age are, at best, unreliable.
Setting aside the unsettling ethical issues associated with recreational genetic testing of children, how useful will the test be to parents looking to find out whether or not their kids will be future track superstars? Here are the facts:
Read on »
Posted by Daniel MacArthur at 10:40 AM • 0 Comments
November 20, 2008
Category: disease genetics
At Gene Expression, p-ter points to two studies in this week's New England Journal of Medicine examining the predictive value of known genetic markers for type 2 diabetes.
Both studies find the additional predictive power of the genetic markers beyond traditional predictors (like age, sex, family history, body-mass index, fasting glucose levels, systolic blood pressure, high-density lipoprotein cholesterol levels, and serum triglyceride levels) to be extremely small, to the point of complete clinical insignificance. Thus while massive genome-wide association studies for T2D have been informative in terms of uncovering the molecular pathways underlying the disease, they haven't yet yielded much of value in terms of individual risk prediction.
As p-ter notes, this result is quite unsurprising given the small fraction of the overall risk variance explained by these markers, but it's still important to quantitate the extent of the disappointment...
One small ray of hope: one of the articles notes that "[t]he discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased". In other words, genetic information increases in value relative to clinical predictors when there is a long time lag between testing and disease onset - again unsurprising given that clinical variables change over time while genetic risk factors are fixed, but still important to bear in mind. This suggests that genetic information will be most valuable to clinicians for predicting the risk of adult-onset diseases in children, or predicting the risk of late-onset diseases in adults.
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Posted by Daniel MacArthur at 12:15 PM • 1 Comments
Category: personal genomics
Pharmacogenomics Reporter (subscription required) describes an intriguing twist in the ongoing struggle between the nascent personal genomics industry and regulatory bodies: apparently the FDA is exploring the possibility of collaborating with consumer genomics providers to track adverse drug reactions:
Lawrence Lesko, director of FDA's Office of Clinical Pharmacology, said the agency has already begun preliminary discussions with some undisclosed personal genomics firms "to evaluate the feasibility" of forging such alliances.
In marketing ancestry and disease-predisposition genetic testing services directly to consumers, personal genomics companies are building large electronic databases of clinical and genomic information that the FDA believes can be useful in tracking adverse drug reactions in a post-marketing setting.
The major advantage of the databases accumulated by personal genomics providers, of course, is that you can immediately look for common genetic variants associated with variation in the risk for any newly identified adverse response:
Read on »
Posted by Daniel MacArthur at 6:40 AM • 6 Comments
November 19, 2008
Category:
A
Nature News article describes the growing availability of technology that allows the screening of human embryos for hundreds of different genetic disorders prior to implantation.
The technology is based on the same type of chips used by personal genomics companies like 23andMe, but the chips used for embryo screening would initially be used to target known rare disease-causing mutations or large chromosomal abnormalities rather than performing a genome-wide scan for common variants (in the article, a screening company director describes the targeted diseases as "nasty, early-onset and ethically uncomplicated"). Such testing is generally accepted by Western society, as witnessed by the
extremely high rate of termination of trisomy 21 embryos.
However, the article also notes that there's currently nothing to stop companies from including variants on the chips that provide information about adult-onset diseases like diabetes or Alzheimers - indeed, in the UK there have already been embryos screened for breast cancer risk variants. This type of screening currently raises some serious ethical eyebrows, but perhaps not for long: the article argues that "as the technology advances, consumer demand is likely to overwhelm societal ethical qualms" - and I'd tend to agree, in general.
However, before we get too carried away by visions of a Gattaca-style future, it's worth noting a couple of serious obstacles in the path of widespread adoption of the use of this technology to screen for common disease genes.
Read on »
Posted by Daniel MacArthur at 6:49 PM • 3 Comments
November 18, 2008
Category:
A Nature News article discusses the ongoing 1000 Genomes Project, an international effort planning to sequence 1,200-1,500 human genomes. The discussion springs from project co-chair David Altshuler's update at last week's American Society of Human Genetics meeting on the progress of the project (in brief: 3.8 terabases down, 996.2 terabases to go).
The article provides a generally positive overview of the project's historical context, goals and progress. The one contrary note comes from Duke University's David Goldstein, who has previously publicly expressed skepticism regarding the value of much of the data currently emerging from genome-wide association studies looking for common variants underlying common disease risk. Goldstein is also wary about over-stating the importance of the 1000 Genomes data:
Read on »
Posted by Daniel MacArthur at 11:18 AM • 0 Comments
November 15, 2008
Category: genetic ancestry testing
Blaine Bettinger at the Genetic Genealogist has an extensive and thoughtful critique of the American Society of Human Genetics' recently released statement on genetic ancestry testing (pdf). (You can read about the Society's statement at GenomeWeb News and Science Now; 23andMe also comments from the point of view of a company engaged in ancestry testing.)
If you have comments on the issues surrounding genetic ancestry testing I'd encourage you to add them to Blaine's post.
Posted by Daniel MacArthur at 9:41 AM • 0 Comments
