 Old or young, big or small, animal or human, every living creature has a genome. It's a collection of tightly packed bundles of DNA. Those bundles, called chromosomes, contain thousands of genes that carry the information needed to make and maintain all of our body's cells. Think of it as a master instruction manual. Now, at the National Institutes of Health, researchers are looking deep within this manual to unravel the mysteries of human health. They've embarked on a groundbreaking new study called ClinSeq that may very well change the future of modern medicine, and ordinary people are helping to make it happen. 52-year-old Jonathan Graham is one of the volunteers who's agreed to have his gene sequenced. He saw the project advertised in a local newspaper and decided to come in and roll up his sleeves to help. He sees it as a unique opportunity to further science and to gain some invaluable insight into his own health. Well, genetic information is always something that you don't get in a physical. You're a typical annual physical. They give you a cursory examination and let you know, yeah, you do have a heart rate. It's not too high. They may do your blood cholesterol, but this seemed like an opportunity to get a little bit more detailed information, more of a workup, something almost like an executive physical. Right now, the ClinSeq project is using genetic information to zero in on heart disease. Dr. Les Beeseker is the principal investigator for the project. Heart disease is an important medical problem, and it's a good model for starting with, although ultimately we're interested in looking at all genes and all conditions in these patients. But heart disease has many of the attributes that we're looking for, such as high heritability, plenty of medical interventions that one can implement to deal with conditions in a patient. So over the next two years, the ClinSeq research team hopes to enroll a thousand people and scan their genomes for warning signs of coronary artery disease. We can take a set of subjects, human subjects, bring them into a research facility, acquire a data set that includes every gene in their genome, and use that to ask questions that are specific and powerful as to how we can change that person's individual risk for developing a disease over time. The researchers will look specifically at genes they know are linked to heart disease, plus some they suspect might be involved. The volunteers can be healthy or have known risk factors for heart disease. It makes a lot of sense that we're doing a thousand references. Dr. Eric Green heads the high-tech sequencing lab where the work is being done. We are as much interested in looking at variants that perhaps give you a very healthy disposition as we are in looking at variants that give a not as healthy characteristic, and we're going to be studying both. Take Jonathan. He runs his own landscape design firm. He eats right, stays active and likes to think he's in pretty good shape, but he admits you never know. Heart troubles run in Jonathan's family, and he wants to find out more about his risk. He gets some information in exchange for being willing to provide genetic information, family medical background, be poked and prodded. They give you feedback on your current and possibly future conditions, which sound like a win-win. The project is open to men and women of all races and from all walks of life, but participants need to be between 45 and 65 years of age and have a primary care physician. They also should not have smoked for at least the past year. Of course, a real desire to learn about your genetic makeup will also come in handy since the study may last a decade or more. These are individuals that we plan to follow for many years, with the idea that when the technology is ready, and I think that may not be that far away, we may sequence the entire genome of all of these individuals and probably continue to bring them back to the clinical center to be able to do subsequent clinical studies of them. If you're selected for this study, here's what you can expect. First, you'll be asked to make an initial visit to the NIH Clinical Center in Bethesda, Maryland to undergo a series of simple tests and evaluations. We get a snapshot of the current state of that person's heart health, if you will, and we can use that as the starting point, but only as the starting point to begin to dissect their long-term risk of having heart disease. That snapshot will include an echocardiogram and electrocardiogram, both painless ways of peering at the inner workings of your heart. You would also have a type of x-ray called a CAT scan, taken of your coronary arteries. In most patients who have heart disease, the thickening of the arteries that is atherosclerosis is accompanied by the deposit of calcium flecks within those blood vessels, and x-rays are very good at seeing those calcium flecks. Well, not as dramatic as the scans, one key part of the process will be drawing a small amount of your blood. From those blood samples, researchers will purify DNA and send it to the NIH Intramural Sequencing Center. Sequencing is a complicated process, and the precious samples will change hands many times. Technicians like Cassandra Montemayor prepare the DNA, so researchers can get the information they're looking for out of it. The process starts here with the genomic DNA, and then we actually end up passing it to production, who then passes it to the sequencers. Initially, the team will be looking to sequence between 200 and 400 genes that may be involved in coronary artery disease. They're hunting for important variants or genomic changes that may mean someone's at increased risk. There's probably a handful of variants I could specifically look at that might give some insights about predispositions to specific diseases or some likelihood of certain kinds of disorders such as cancer. Making sense of it all is no easy task. Genetic scientists here will need to search hard to find those all-important telltale genomic changes. We're looking for our dramatic changes or severe changes in the genes and the DNA that will cause the person to have a high likelihood of developing a disease. This will be one of the first studies in which DNA sequencing results will be communicated back to individual patients, provided, of course, that the researchers have a strong measure of confidence in what the data reveals. Most genetic and genomic research, especially large-scale genetic and genomic research, isolates the patient volunteers, the subjects of the studies, from the individual outcome of the study. We want to break with that. We want the subjects involved in the study from beginning to end. So what are the benefits of being involved? There are many. You'll be tested free of charge for diabetes and high cholesterol. You'll also receive free of charge a CAT scan that could reveal signs of coronary artery disease. But above all, you may get information that is critical to your long-term health and the health of your entire family. People are generally very enthusiastic about participating in the CLIN6 study. I think that they understand that this is a very novel and cutting-edge study and they are excited to be part of a project of this nature. How'd it go this morning with your blood draw? Flavia Fosio is the genetic counselor for the CLIN6 project. It's her job to make sure participants understand what's happening. She also works with them to develop their family's health history. The family history may actually provide a context, a framework for what we find in this people's genes. So when I've revealed their family histories with them, I'm looking for patterns. I'm trying to see if there is a condition that may look like it's running in the family. Are there any drawbacks to taking part? There are only minor risks associated with undergoing these tests. Some people experience slight pain or minor bruising when they have blood drawn. There's a small amount of radiation exposure during the CAT scan and in some cases scans may produce results that are hard to interpret. But perhaps more significantly, there is also the possibility of an emotional or psychological toll depending on what the research uncovers. People vary enormously in their view of how much they want to know about their genes and in reality how much they really want to know about what that might be telling them about their future. The little yellow line is just looking at how your heart's contracting over time. For Jonathan Graham, there are no doubts. He says he's thrilled to be a volunteer because ultimately he may be able to keep himself and his children healthy. If I become identified as possessing potentially something that could be a risk factor for a future condition, they get a heads up. They get a genetic heads up saying you need to be aware of it, you need to be tested to see if you have it as well and then take the appropriate steps to head off any potential complications. And ultimately, it's not just you and your own family who may be helped. In the end, this groundbreaking study may offer new hope to millions of people at risk for heart disease and help all of us to lead longer, healthier lives. And the entire premise of personalized medicine is that we can take that information and implement strategies to reduce their individual risk over time. So we've been talking for years about how the Genome Project is going to revolutionize medicine and allow personalized health care. And what ClinSeq is about is making that a reality. If you want to find out more about the ClinSeq project or to see if you're eligible, visit our website, genome.gov slash ClinSeq.