DNA and You

Genetics Takes Over The New England Journal of Medicine

One only has to briefly scan the table of contents of tomorrow's issue (Jan. 10) of The New England Journal of Medicine to figure out that 2008 is going to be a big year at the crux of genetics and medicine!  The issue includes the following (note that only a subset of the following full articles are available without subscription):

• A perspective by Drs. David Hunter, Muin Khoury, and Jeffrey Drazen on the medical implications - or lack thereof - of personalized genotyping services (i.e., 23andMe, Navigenics, and deCodeMe).  More on this in a follow-up post later this evening.  However, I can tell you that these three are not fans of personalized genotyping companies.  There is also an audio interview with Dr. Khoury available here.
• Dr. John Bissler and colleagues from Cincinnati Children's Hospital Medical Center present the results of a study of sirolimus treatment of angiomyolipomas in tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis.  TSC is a Mendelian genetic disease in which the genetic defects lead to constitutive activation of the "mammalian target of rapamycin" (mTOR, a key cellular signaling pathway intermediate).  As sirolimus suppresses signaling through mTOR, this study represents a rational use of sirolimus to treat angiomyolipomas in TSC.  More on this soon at my other blog, Cancer and Your Genes.
• Dr. Antonio Pelliccia and colleagues present the results of a study looking at implications of EKG abnormalities referred to as "repolarization abnormalities."  They show that out of 81 athletes with a particular type of EKG abnormality (see free full text here for details), 5 (6%) ultimately developed cardiomyopathies (including one individual who died from arrhythmogenic right ventricular cardiomyopathy - which has a genetic basis). 
• Dr. Melanie Percy and colleagues demonstrate that an oxygen sensing gene called HIF2A is mutated in a family with Familial Erythrocytosis (i.e., a heritable condition in which affected individuals have too many red blood cells).
• There is also a review of the book, "Reprogenetics: Law, Policy, and Ethical Issues," edited by Lori P. Knowles and Gregory E. Kaebnick.
• As if all that were not enough, an article in the NEJM "Clinical Problem" series focuses on the approach to Long QT syndrome, an inherited, genetically heterogeneous condition that predisposes individuals to life-threatening arrhthymias (abnormal heart rhythms). 
• Last, but certainly not least, in an online article published today, Mark Daly and colleagues report the identification of a small, sub-microscopic region of chromosome 16 that when deleted or duplicated leads to autism susceptibility!  Although this is probably only responsible for about 1% or so of cases, this is a huge accomplishment.

In looking at just this single issue of NEJM, I think it is safe to say that we have a very interesting year ahead of us.  Stay tuned to DNA and You for more detailed posts on the above!

What a week...

What a wild couple of days...

First, deCODE Genetics unstealths its deCODEme foray into the personalized genomics market.

Then, just when you think they've been completely beaten to the punch, 23andMe throws a counterpunch.

I'd been wondering for a while what deCODE was up to in this arena, as they clearly have the infrastructure and the track record to make a serious play in personalized genomics.

Interestingly, even though many would argue that the Navigenics approach is the most responsible one, getting results on 20 or so SNPs is looking so "last week" right now. 

Just in case you've been in a sound-proof bubble the last few days, here are some links to a few articles and posts about the events of the last few days:

• NY Times article about deCODEme launch
• CNN Money on deCODEme launch
• NY Times article about 23andMe launch
• Wired article mostly focusing on 23andMe
• Garett Rogers post

While much has been said about the product launches, I find it interesting that there has been relatively little talk about something that is being left out of the products offered to the public (at least at the moment as far as I can tell).  Specifically, that something is copy number variation. 

For those not familiar with the concept, in addition to variation at single DNA base pairs, it is also crystal clear that individuals differ enormously from each other in terms of the presence or absence or elevated copy number of entire large "chunks" of DNA.  These studies, pioneered by Evan Eichler and others, have shown that our genomes are more dynamic than was previously recognized.  Thus, when copy number variation involves important genes or other important stretches of DNA not in genes, it can have an important impact on disease susceptibility.  For example, copy number for a stretch of DNA containing the CCL3L1 gene has been beautifully shown to very significantly influence HIV/AIDS susceptibility.  Likewise, low copy number of a gene called FCGR3B is associated with the development of the kidney disease, glomerulonephritis, in individuals with systemic lupus erythematosus.

Although first generation SNP genotyping approaches didn't always do so well with detecting copy number variation, more recent iterations have the ability to detect copy number variation (although a different technique called array comparative genomic hybridization is more commonly utilized to detect this clinically).  For example, Affymetrix states on their website that their 500K arrays provide copy number variation information (Navigenics is partnering with Affymetrix for genotyping).  Likewise, Illumina (23andMe's genotyping partner) points out that their product can also identify copy number variants.

Although the launch of genotyping services by 23andMe and deCODE Genetics appears likely to provide dramatically more information to the consumer than the small number of SNP results that will be reported by Navigenics, it would appear that both 23andMe and deCODE may have access to information related to copy number variation that can have important implications with respect to disease risk and which may not be reported back to the consumer.  It will be interesting to see how this is dealt with in the future.