By AMERICAN HEART ASSOCIATION NEWS
The breakthrough made headlines in 2003: Scientists had mapped the DNA sequence that makes up the genetic code of humans. Since then, scientific discoveries and transformative technologies have ushered in a genomic era that continues to peel back layers of information about traits and diseases such as heart disease and stroke.
A new scientific statement from the American Heart Association delves into a crucial component of the genome that you’ve likely never heard of — the “expressed genome.” It’s the combination of molecular-level traits that can predict health and can be altered by a person’s physical environment and lifestyle choices, such as exercise or tobacco use.
“People think of the DNA sequence as the blueprint of life. But the DNA sequence is only the starting point. When we talk about the expressed genome, particularly in the statement, you’re taking that blueprint and building off of it,” said Kiran Musunuru, M.D., Ph.D., the statement’s lead author.
Another way to understand the expressed genome is by thinking of the human genome as the alphabet. The expressed genome is how that alphabet gets arranged in words, sentences and paragraphs, said Donna Arnett, Ph.D., an epidemiology professor and dean of the University of Kentucky’s College of Public Health.
Musunuru noted “a bit of irrational exuberance” has followed the completion of the Human Genome Project, including recent buzz over DNA tests that consumers can do at home.
“Part of the intent of this statement is to offer a realistic view of how complex and lengthy the process can be of going from a discovery that you read about in the newspaper, to actually having something that can be used in patients,” said Musunuru, an associate professor of cardiovascular medicine and genetics at the University of Pennsylvania.
The statement, published Monday in Circulation: Cardiovascular Genetics, highlights two discoveries that are now commercially available and being used in clinical practice. One test uses a blood sample to locate a specific set of biomarkers, a small subset of RNA molecules that can detect coronary artery disease in people with symptoms that could indicate heart disease.
Another test allows doctors to examine heart transplant recipients after surgery for signs of organ rejection without using the traditional method of what essentially amounts to a heart biopsy. Instead, technicians can examine a specific set of RNA molecules to assess how well the patient’s body is accepting the new heart.
Musunuru stressed neither test examines genetics, but are “two examples of discoveries using the expressed genome that have culminated in commercially available tests that a physician can actually order.”
Rapidly developing technology being used to study expressed genomes could predict ailments in addition to coronary artery disease, such as stroke, heart failure and arrhythmia. Right now, doctors are limited by what they can read from traditional tests that measure blood pressure and cholesterol levels, as well as what a patient volunteers about personal habits and family history.
“But there are many people who don’t smoke or have high cholesterol or high blood pressure who develop heart disease and stroke anyway,” Arnett said. “These new technologies are going to enable us to detect those causes at a more granular level. We would be able to capture things that we could not capture before.”
Thomas J. Wang, M.D., the director of the cardiovascular medicine division at Vanderbilt Heart and Vascular Institute in Nashville, said the technology used in research is being developed at an impressive speed.
“Just like you saw with computer chips and phones, the molecular technologies that are available for characterizing these various aspects of the expressed genome are plowing ahead at a rapid pace,” said Wang, who was one of the reviewers of the AHA statement. “It’s not the same pace you might have seen 10 or 20 years ago. There’s clearly acceleration.”
He also noted that the size of studies used to test these technologies has expanded significantly.
“In the past, a study of a couple thousand people was the typical size of an epidemiologic study that might be used to determine the risk factors for disease,” he said. “Now we’re talking about studies that are in the hundreds of thousands.”
Or, in the case of a precision medicine initiative by the National Institutes of Health, 1 million volunteers are being recruited.
“These massive human studies will also allow, in combination with the technology, an accelerated pace of discovery,” Wang said.