November 1st, the morning after Halloween’s phantoms have shed their masks, HudsonAlpha Institute for Biotechnology in Huntsville begins its quest to unmask even more fearsome and elusive real life villains—unknown genetically-based diseases destroying the lives and health of human patients.
Headed by David Bick, MD, it will be the nation’s first clinic devoted to using whole genome sequencing to identify genetic clues that can help put a name to unknown and hard-to-diagnose diseases.
“Often patients with baffling disorders that have a genetic basis go on a painful, expensive diagnostic odyssey from doctor to doctor, trying to find someone who can tell them what is wrong and what can be done to help them,” Bick said. “When conventional labs and diagnostic technologies can’t provide enough clear answers to make a diagnosis, we may be able to solve the riddle by identifying genetic variants.”
The first step in vanquishing any monster is knowing what you are fighting, and where its vulnerabilities are. Since the HudsonAlpha Clinic for Genomic Medicine will be sequencing the whole genome, it will be looking at a broader range of genes that could influence how other genes are coding.
“The primary difference in our clinic is that we will be tightly focused on undiagnosed diseases, and we will exclusively sequence the whole genome, rather than just the exome,” Bick said. “Not so long ago, conventional wisdom was that the one percent of genes involved in coding proteins is where everything important happens. As it turns out, the other 99 percent includes genes that influence how the one percent are expressed and control RNA splicing.”
The clinic’s initial efforts will be directed primarily toward children who have undiagnosed conditions likely linked to genomic variants, and to adults who have a disorder that remains unidentified despite extensive diagnostic testing.
“Our purpose is to bring whole genomics into the practice of medicine so physicians have more effective tools to identify and understand the underlying causes of disorders,” Bick said. “In the future, our clinic and its genomic sequencing capabilities could be resources assisting in the development of pharmaceuticals and other interventions to treat those conditions.”
The clinic will be located on the campus of HudsonAlpha, the Huntsville-based research center known nationally and internationally for its work in genetics, genomics and its high-throughput sequencing capabilities.
Bick came to HudsonAlpha from the Medical College of Wisconsin, where he worked extensively in genomics research. He studied human genetics and did previous work in the field at Yale.
“Using whole genome sequencing, we’re successfully identifying approximately 25 percent of the disorders behind previously undiagnosed health problems in patients referred to us,” Bick said. “Even when we don’t find an immediate match to variants linked to specific conditions in our data base, the data is expanding so fast, with new input from around the world, that sometimes six months later when we run the genome again, the answer is there.”
If there isn’t yet an answer to what a condition is, there may be valuable answers to what it isn’t—sparing patients from the possible side effects of treatments that may be off target. As research continues, genomic sequencing offers great potential for identifying which interventions are most likely to be effective, with the least risk of side effects. Already, a patient’s unique genetic code can be helpful in predicting which blood thinners in which doses are likely to be most effective.
“We’ve been working in close collaboration with the genetics team at UAB, and eventually we would like to use telemedicine to make consultations available to patients in their doctor’s offices across the state,” Bick said. “As a physician, when I evaluate a patient, I look for external physical markers. Sometimes I can spot characteristics associated with a specific disorder. As I review symptoms and history with the physician, I ask whether the patient has been tested for that condition. It may not be something that would immediately come to mind—but if we test for it and the results are positive, we can solve the problem without having to go farther.”
Physicians can refer patients to the clinic, or patients can self-refer.
“As of now, the challenge is insurance. Some plans cover it. Some don’t. Sometimes I can write a letter explaining why genomic testing makes sense, and the insurer may decide to cover it, especially considering how expensive repeated rounds of conventional testing can be.”
Even if patients have to cover the cost themselves, getting an answer for a disorder that can be treated, or for one where early intervention can make a difference in quality of life can be well worth it.
“Over time, as more insurance companies see the value, more will be likely to cover it. The technology of genomic sequencing is evolving so rapidly, the cost of using it as part of real world medical practice is becoming more affordable.”
Key words
Genomic sequencing, HudsonAlpha Clinic for Genomic Medicine, David Bick MD, undiagnosed diseases
