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Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine

Thank you for submitting your questions on genomics, personalized medicine and our recent "omics" study. I hope my responses help you better understand the significance of our findings, how DNA sequencing may benefit patients and the health-care system and what challenges still need to be overcome for genetic testing to be useful in a clinical setting.

@TracySherman asks: How do you hope your study will help advance personalized medicine?

In the study, we demonstrated for the first time that sequencing the genome of a healthy person can provide valuable information that can help them improve their well being. My genome predicted a disease risk and by watching out for traits (such as high blood glucose levels) associated with that disease I caught my disease (diabetes) early.

The findings also demonstrated the power of frequent monitoring. Because I had been closely following my glucose levels and other molecules in my blood, I was able to identify the onset of diabetes very early. Our study could be a paradigm for heath care in general (i.e. genome sequencing to predict risk, coupled with close monitoring for symptoms of potential diseases) and emphasizes a shift from the way medicine is currently practiced. Today, treatments or therapies are prescribed after physical symptoms arise, which is often too late. We need to predict which diseases patients have an increased risk of developing and either prevent or diagnose them early when they are more manageable.

Lastly, I believe that "omics" profiling, in which we measure thousands of molecules at once from one person, could be a model for the future. Right now we identify diseases very poorly, typically by measuring only a few components in our blood. By following many more molecules (40,000, in my case), health-care providers could more-clearly see changes in common biological pathways. For example, this approach made it easy to see that I acquired diabetes during a viral infection. We hope that in the future we can routinely follow very a large number of molecules in a person and see how they change from healthy to altered states. Then we can more precisely see what is wrong with the person, particularly at an early stage, and use therapies that directly target the altered or disease state.

@miss_tmo asks: How can we expand access to genetic services so more people are able to benefit from personalized medicine?

Right now nearly all of this activity is in the research phase because scientists are still learning the power of genome sequencing - what can and cannot be learned from a person's genome. As more people realize benefits from genome sequencing there will be more demand for its use.

One way genetic testing is likely to unfold is in the effort to understand certain diseases. Take the example of cancer, a genetic disease in which not only can your DNA increase your risk, but genetic alterations are also accrued during cancer formation. Genome sequencing is already significantly impacting the study of cancer, as well as helping to identify effective treatments. Likewise, for patients with unsolved genetic diseases, genome sequencing can, in some cases, be useful in zeroing in on the underlying cause of the disease. In these circumstances, genome sequencing will become the standard of care for patients.

For healthy people the pace will move slowly. This is because the benefits are less obvious. In addition, some physicians and other experts are worried that genome sequencing could cause patients additional stress and anxiety or even result in false information. More research should help reveal the benefits of genome sequencing in healthy people and how to deliver this information as part of routine health care.

Anne Michelle asks: If you hadn't been studying your own genome, how long do you think it would have taken you to discover you were diabetic? How would this difference have impacted your life and health?

As a healthy person, I used to visit the doctor's office every 2-3 years. I estimate that had I not done this study, I would have learned about my high glucose approximately 18-20 months after I discovered it through self-monitoring. Had I unknowingly allowed the diabetes to progress in this manner, there easily could have been significant damage to my body. Examples include kidney failure and other organ problems.

A. Badea asks: Other than the cost of genome sequencing, what advances in research or changes to the health-care system are necessary for this practice to be useful in making medical decision in the clinical setting?

This is a very important question. There are many advances that need to occur. First, we need to get more accurate DNA sequencing. There are many parts of the genome that are important but not sequenced by current technology or have lots of errors.

Next, we need to better understand how to interpret genomes. We can see variants in a person's DNA relative to a reference genome but we often do not know what they mean. In my case, I have an alteration in my DNA that indicates I should have aplastic anemia, a disease that I presently do not have. My 84-year-old mother has the same change. Clearly this change does not always cause the disease. Likewise, people with changes at high risk for Alzheimer's or Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, do not always get the disease. We need to understand why this is, as well as the impact of many other DNA changes on a person's health. A very large database with people's DNA sequences and health information will be extremely valuable for interpreting genomes.

Additionally, we need to educate physicians as well as patients on several points: what can be learned from genome sequencing and assessments of relative risk, what information should be returned to the patients and what is the best way to return that information. The latter will almost certainly involve "genomicists" who can assist both physicians and patients. Lastly, we need to involve health insurance companies so they understand that genomic information can reduce health costs by catching disease early on and guiding physicians in providing targeted treatments.

Shana Seneka asks: What role do epigenetics play in gene testing?

Our health state is a combination of our DNA and our environment. The latter is a combination of everything we were exposed to in terms of what we eat, the microbes that infect us and even our maternal environments. Epigenetics often reflects a lot of this environmental exposure. Thus, together with genome sequencing, epigenetics information, which may be deduced from DNA methylation or gene expression profiles, will be very powerful in identifying and understanding human disease.

Heidi asks: What are your thoughts on a recent study from Johns Hopkins that found whole genome sequencing "fails to provide informative guidance to most people about their risk for most common diseases," and warned against complacency born of negative genome test results?

This study found that monozygotic (i.e. identical) twins do not die of the same disease and thus concluded that the genome cannot be used to predict disease. Although their observation is interesting, I think this is the wrong way to look at this issue. Genome sequencing cannot tell you exactly what disease you will get, but it will reveal a number of things that you are at risk for, which is a reasonably sized list. Although you cannot specifically say which of those conditions you will develop or whether it will be fatal, you will be at higher risk for getting one or more of those identified through genome sequencing.

The Hopkins study also focused on the most common diseases. Many of us are at risk of rare diseases, which can sometimes only be revealed by genome sequencing. Lastly, although not addressed by the Hopkins study, we know that genome sequencing can predict how a person might responds to certain drugs -- for example, which doses an individual should take and the possible side effects he or she might experience. Thus, we believe that genome sequencing can be potentially very beneficial for health care and medicine.

Previously: Ask Stanford Med: Genetics chair answers questions on gene sequencing and personalized medicine, How genome testing can help guide preventative medicine and 'Omics' profiling coming soon to a doctor's office near you?
Photo by Kate Whitley, Wellcome Images

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