When bioinformaticians Joel Dudley and Konrad Karczewski set out to write a new text on genomics, they took the task personally. Their book, Exploring Personal Genomics, is an introduction to the rapidly developing field of personal genomics.
But instead of approaching the topic with endless equations and abstract examples, Dudley, director of biomedical informatics at Mount Sinai School of Medicine, and Karczewski, a doctoral student in biomedical informatics at Stanford University, lent their own genomic data to create a practical primer for DNA hobbyists and medical professionals alike. Each had his whole genome sequenced by Illumina at a cost of $5,000 per genome as part of the inaugural Understand Your Genome Symposium, which they attended in San Diego. The New York Genome Center recently spoke with the authors about the impact their book might have on this fast-moving field.
NYGC: How do you think this book might hasten the use of personal genomics in the doctor’s office and elsewhere?
Joel Dudley: I hope one of the things it does is demystify personal genomics so that, instead of doctors and patients just saying, “This is confusing,” they’ll think, “I can get a handle on this.” We talk about what we can do now, and what we can’t do yet, where the data exist, and where opportunities for development are. We hope people take up arms, take up their compilers and their text editors, start writing software systems or start building other materials that address these needs.
Konrad Karczewski: A big part will be correcting misconceptions — ideas like, “if you have a particular gene variant, you’re going to die of this disease.” The best way to get beyond that misconception is simply to have your genome sequenced, and learn what your data actually mean. Then it becomes way less scary.
NYGC: What are some ways to train doctors and other medical professionals about personal genome data?
Dudley: Doctors don’t have a lot of spare time, so one of the traditional mechanisms that they’ll use to come up to speed on the latest, greatest stuff is continuing medical education courses. We’re definitely interested in, and already starting to talk with people about, starting CME courses on personal genomics. Also, Mount Sinai offers the first graduate and medical student course in the country where students work with their own full genome data. That’s something we’d like to explore expanding, too.
NYGC: What new medical professions might emerge around personal genomics?
Dudley: I can definitely see an industry of non-medical health advice popping up. That’s not necessarily a bad thing. I think there’s going to be a whole slew of legitimate services for tying real-time monitoring of behaviors to genomic information and overall health.
Karczewski: There are already companies forming around the space of getting patient samples, running the genome sequence and interpreting genomic data—sort of professional genome interpreters. But in terms of medical professions, I think it could very well become its own subspecialty: Like a radiologist reads scans, a genomic doctor (I don’t know what to call them yet) will read genome sequences and interpret genomic data. It’s not the same as reading a lipid panel. There is a lot of information there, and it is often more subtle.
NYGC: How did you make a book about this cutting-edge field accessible to college students and lay people, as well as MDs?
Dudley: We tried to limit the amount of jargon, equations, and computational lingo, and we focused on showing people what information is out there already. We even hope that college-level computer science students may be motivated to say, “Oh, I can solve this lack of a good database problem. Let me try to build this tool.”
Karczewski: We put a lot of work into illustrating what kind of information can you get. There’s about one figure per page. We ran our own genomes through a lot of these analyses, and we’re showing our own data wherever possible.
NYGC: What are some important concepts for a person to understand when he or she hands over personal genome data to a doctor?
Dudley: There’s huge potential for pharmacogenomics discussions. I have Crohn’s disease, and I have a rare variant of the gene that metabolizes thiopurinol drugs like 6MP, a drug that’s often prescribed for patients with Crohn’s disease. That gene affects the dose of 6MP I should take so I don’t get dangerous effects like bone marrow toxicity.
There’s huge potential for pharmacogenomics discussions.
Karczewski: It’s important to understand the basic concept of disease risk. When a patient hears, “Scientists discovered the gene for X disease,” then the logical conclusion would be, if you have this variant gene, you will develop this disease. That is definitely not true for the overwhelming majority of cases. Maybe the general population has a five percent risk, whereas you have a seven percent risk. It’s a fairly large relative increase, but it’s still a low risk in general.
NYGC: Are you happy you had your own genomes sequenced?
Dudley: Yes, I’m quite happy to have had my genome sequenced. I’ve been diagnosed with Crohn’s disease and Tourette’s/OCD/ADHD so I was hoping my genome could shed light on a possible genetic basis for either. And of course genome variation isn’t all about disease. It’s fun to find rare variants that might explain personal traits. For example, I have excellent night vision. One of the most severe variants in my genome is the gene involved in re-energizing the visual signaling transduction cascade. I’m also happy to have done it because, well, how lame would it be to write a book on personal genomics and not have your own genome sequenced? In a way I’m lucky my genome is so broken so I have all these great personal anecdotes to share.
Karczewski: Absolutely. I would not take that back in any way, shape, or form. I’m of the opinion that the more I know, the better off I am. If you don’t know what your risk factors are, how do you know what to look out for? It’s a very good start to making healthy lifestyle changes. We’re getting to the point that I really don’t understand why you wouldn’t want to know these things.