Presented by: Euan Ashley, MD, PhD
Assistant Professor, Cardiovascular Medicine
Stanford University Medical Center
June 7, 2012
We know that genes play a crucial role in influencing how we look and act, as well as our susceptibility to disease. Now scientists are trying to use that knowledge in exciting new ways, such as preventing and treating health problems based on therapies tailored to an individual’s unique genetic makeup.
But to understand the future of genetically based personalized medicine, it’s important to understand the basics, says Euan Ashley, MD, PhD, an assistant professor of cardiovascular medicine and director of the Stanford Center for Inherited Cardiovascular Disease, who spoke at a presentation sponsored by the Stanford Health Library.
Human DNA is contained within 23 pairs of chromosomes, one half pair from each parent; genes are segments of DNA that determine specific characteristics, such as hair color or height. Some characteristics come from a single gene, while others come from gene combinations. Humans have about 20,000 genes (and so do worms), and the complete instructions they carry are called the human genome.
Genes hold the instructions for making the proteins that manage cell growth and function. When cells duplicate, this genetic information is passed along to the new cells. The genes may mutate over time, causing disease, and such variants can be passed along from parent to offspring. There are more than 3 billion units of information (letters) in the human genome.
Organizing the Information
But the human genome is not quite that straightforward. When mapping the genome, scientists found that blocks of DNA, called haplotype blocks, tend to stay together. By measuring single letter variants called SNPs in each of these blocks, they were able to look across the whole genome at once.
Using a chip to look at the genes or the cell messages that come from the genes was developed at Stanford and now is used as a tool by researchers worldwide. Over the past couple of decades, using such chips, researchers have identified more than 4,000 single genetic variants associated with disease. Most diseases, however, are caused by a multitude of variants acting together.
“Gene chips allowed researchers to look at large populations and associate a genetic variant with a disease,” said Dr. Ashley. “There was a deluge of strong associations within just a few years. Sequencing (spelling out the letters) the entire genome has come down in price dramatically: 10 years ago a human genome sequence cost about $100 million; today it runs close to $1,000, making the process accessible to most labs and hospitals, and moving toward the day when the genome is used as a routine part of medical practice.
New Clinical Tool
Another enormous step occurred when a Stanford scientist sequenced his entire genome three years ago. He had a family history of severe heart disease that was reviewed by Dr. Ashley—a genetic heart specialist—which made Dr. Ashley the first physician with access to a patient’s complete genome. He put together a team of Stanford scientists to help analyze it.
“Having the patient’s genome available allowed us to look at the possibility of disease, the clinical risk, and what drugs he would or would not respond to,” said Dr. Ashley, referring to pharmacogenetics. “Access to a person’s genome enables us to look at the genetic information in a way that makes sense for clinical medicine. We can look at a patient’s potential response to medication based on their individual genetic makeup.”
Whole-genome sequencing could identify and help prevent heart problems—and other life-threatening diseases—in patients who seem healthy but may be at risk because of an inherited predisposition, he added. Because he could review his patent’s genome, Dr. Ashley was able to make a list of drugs to avoid based on genetic variations associated with reactions with common medicines. His analysis indicated that the patient would respond well to statins.
“Personalized medicine is about individual risk for disease and targeted preventive care,” said Dr. Ashley. “We are only now taking the first steps toward integrating this information into clinical care, and we still have a lot to learn in terms of interpreting the data.”
For now, he adds, clinical applications for an individual’s complete genome have more potential in challenging cases such as rare family syndromes, and studies are underway for genetic response to stent restenosis and drug resistance.
About the Speaker
Euan Ashley, MRCP, DPhil, FACC, FAHA, is an assistant professor of cardiovascular medicine and director of the Center for Inherited Cardiovascular Disease, a multidisciplinary program that coordinates care for adults and children with genetic disorders of the heart and blood vessels. He is a member of the leadership group of the American Heart Association’s Council on Functional Genomics, deputy director of the Stanford Cardiovascular Institute, and a member of the roundtable on genomics of the Institute of Medicine. An exercise physiology graduate of the University of Glasgow, Dr. Ashley received his PhD in molecular cardiology from the University of Oxford and his MRCP in medicine from the Royal College of Physicians. He joined Stanford in 2003.
For More Information:
Dr. Ashley’s Research Laboratory