DNA and You

Steven Pinker of the PGP in the NY Times Magazine

Very interesting article by Steven Pinker of the Personal Genome Project in the NY Times Magazine.  Check it out here.

If You Think Wired Is a Good Place to Go for Medical Advice, Think Again...

Andrew Yates at Think Gene wrote today about the new Wired Wiki home genomics how-to guide, "Check Yourself for Genomic Abnormalities."  Check out Andrew's post for a great discussion of the maturity, or, rather, the lack thereof, of the personal genomics market.

Something caught my eye though as I read through "Check Yourself for Genomic Abnormalities" at the Wired Wiki site.  The wiki post describes several options for "checking yourself for genomic abnormalities": 1) Visit a Genetic Counselor; 2) Scan Your Whole Genome; and 3) Perform Lab Tests at Home. 

Interestingly, the author(s), who otherwise did an ok job of briefly explaining what genetic counselors do, utilized consideration of a diagnosis of celiac sprue as an example of a situation in which someone would want to see a genetic counselor rather than "scanning their whole genome" or "performing lab tests at home."

I think the world of Wired, but in case it is not clear to the early adopters out there...

Wired is probably not where you want to get your medical advice.

Celiac disease (aka gluten-sensitive enteropathy or non-tropical sprue), the condition mentioned in the hypothetical scenario, is diagnosed via a blood antibody test and small intestinal biopsies.  Thus, rather than seeing your local genetic counselor if you think you might have CD, you would do well to discuss it with your primary care doctor and a gastroenterologist. 

The wiki writer's confusion likely stems from the fact that genetic factors do play a role in risk for Celiac disease; however, the genetics are complex, and the genes involved are not deterministic.  For example, risk of Celiac disease is higher if you have certain forms ("alleles") of HLA genes.  About 30% of the population has one of the Celiac disease-associated HLA alleles; however, only 3% of individuals with the Celiac disease-associated allele develop CD.

High Throughput Sequencing, Moore's Law, The Next Generation, and Storage Options

It will be interesting to see if DNA sequencing technology continues to follow a Moore's law-like trajectory over the coming decades.  Clearly, next generation technologies are going to have a massive impact both in the research setting and on medical resequencing. 

Alexis Madrigal at Wired Science wrote a nice piece on the technological advances leading to the current generation of high-throughput sequencers and also the next generation: Pacific Biosciences and Helicos.

Also notable is a post from the always excellent Daniel MacArthur at Genetic Future on options for storage of personal genome sequences.

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!

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?