DNA and You

KNOME, George Church, and Personalized Whole Genome Sequencing

I just received the following (copied and pasted) information in an email from Knome:

Human Whole-genome sequencing hits commercial market

20 individuals to be among first in history to be fully sequenced

CAMBRIDGE , Massachusetts —  Nov. 29, 2007  ­­­ — Knome, a personal genomics company, today announced the launch of the first commercial whole-genome sequencing and analysis service for individuals.

"In 2003, the Human Genome Project completed a 12-year effort to sequence the first human genome at a cost of $3 billion. Only very recently have costs come down to a level where it is now feasible for private individuals to be sequenced and analyzed. We expect this evolution to quickly usher in a new era in personalized medicine," said Dr. George Church, PhD, a co-founder of the firm and Professor of Genetics at Harvard Medical School.

First to know, first to benefit

Knome today opens enrollment for its first sequencing flight. Because the sequencing and analysis process is both labor and computationally intensive, initial capacity is expected to be limited to approximately 20 clients.

"To date, Craig Venter and James Watson are the only named individuals to have their genome sequenced. Our first 20 clients will have a historic opportunity to help pioneer the emerging field of personal genomics. They will be among the first to know and the first to benefit from the latest advances in our rapidly developing understanding of the human genome," said Jorge Conde, the firm's CEO.

Building the gold standard

Whole-genome sequencing decodes the 6 billion bits of information that make up an individual's genome. Unlike existing genome scanning or "SNP chip" technologies that provide useful but limited information on approximately 20 conditions, whole-genome sequencing allows for the analysis of up to 2,000 common and rare conditions, and over 20,000 genes – numbers that are rapidly growing.   

"Whole-genome sequencing is the endgame," according to Mr. Conde. "It will enable us to look at nearly 100% of your genetic code compared to the less than 0.02% currently available on SNP chips.  This is the approach that most fully reveals what our genomes can tell us about ourselves."

Pricing for Knome's service will start at $350,000, including whole-genome sequencing and a comprehensive analysis from a team of leading geneticists, clinicians and bioinformaticians. This team will also provide continued support and counseling. 

"Knome's goal is to establish the gold standard in personal genomic services for individuals. We are bringing our clients the latest sequencing technology, Knome's proprietary analytic engine and security solutions, and access to top genomic scientists and medical professionals," said Conde. "Analytics, privacy and on-going client service are as important to us as the actual sequencing."

Core to the fundamental principles of the company, clients will retain full ownership of their personal genome and have the ability to anonymously share all or portions of their genome with researchers and other medical professionals.

About Knome

Based in Cambridge, Massachusetts, Knome has the distinction of being the first personal genomics company to commercially offer whole-genome sequencing and analysis services for individuals. Working alongside leading geneticists, clinicians and bioinformaticians from Harvard and MIT, Knome enables its clients to obtain, understand, and share their genomic information in a manner that is both anonymous and secure. Knome is a privately funded company. Please visit www.knome.com for more information.

Knome is a trademark of Knome, Inc. All other company and product names may be trademarks of the respective companies with which they are associated.

For more information CONTACT

info@knome.com

Clearly, it will be interesting to see how this plays out.  I would be particularly interested to know what the specific plans are for the implied analysis and counseling from clinicians and other team members.

Anybody got a spare $350K they would like to part with?

NY Times Personalized Genomics Feedback

For those who haven't seen it yet, a series of letters responding to the NY Times coverage of 23andMe, Navigenics, and deCODE Genetics are available here.

Interestingly, the author of the last letter in the NY Times series, Dr. Hugh Rienhoff, has made some news himself of late. 

Who's your daddy?

Once a year, I teach a case-based discussion section in the medical genetics course for the 2nd year med students at the University of Washington.  Each year, there is an anomalous result in one of the cases that has several potential explanations.  We encourage the students to think through the possible explanations...and one of them is non-paternity.  That case sticks out in my mind, because one year, a student suggested that I was being sexist by suggesting that non-paternity was a possibility (i.e., if I bring up non-paternity...I must propose non-maternity as an option as well).  The class laughed and another student pointed out that generally maternity is a little more difficult to fake than paternity.  Now I look back on this with some amusement. 

Over the past decade, (non)paternity has really been in the public eye - via Jerry Springer and other daytime TV, via court room drama, and via the increasing availability of cheap paternity testing.  In my clinical genetics training, an oft quoted number was that ~5% of individuals in a clinic were not fathered by the person who is ostensibly their father.  I've never been able to track down the primary reference for this; however, estimates in the literature range from a minimum of ~1% to ~20%.  Regardless of the specific number, it is a substantial fraction of people.  The beginning of an era of personalized direct-to-consumer genomics that may be utilized by a substantial fraction of the population may transform the way we think about this issue.  At the very least, if companies like 23andMe and deCODE Genetics are successful in getting large numbers of families to utilize their genotyping services, there will be more...umm...transparency brought to this issue. 

I'm confident that these companies have spent a lot of time thinking about this issue, and I'm not suggesting that it is a reason to regulate or ban the personalized genomic testing by any means.  Nevertheless, inadvertent demonstration of nonpaternity is another way in which the personalized genomics revolution will affect the social fabric of our world.

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.