“This stuff can be life or death, and it shouldn't be taken lightly,” said Dr. Bert Vogelstein, director of Johns Hopkins Medicine's Ludwig Center for Cancer Genetics & Therapeutics and investigator for the Howard Hughes Medical Institute. “We have to come to grips with the power and challenges (of this technology), and we haven't yet because it's too new.”
Partners HealthCare is one of the first hospital systems to offer whole genome sequencing, analysis and interpretation to the public. During the next year, it expects to sequence the genomes of roughly 50 patients. It is also enrolling about 200 patients and their primary-care physicians or cardiologists in a project funded by the National Institutes of Health to study the integration of whole genome sequencing into clinical medicine. Including doctors in the project allows researchers to evaluate how physicians are using sequencing information in caring for their patients.
Partners is charging about $9,000 for an individual, including interpretation and analysis. Sequencing for a child and both parents—which is often done to better understand a child's genetic disorder—costs about $18,000.
Mary Beth Schlichte is enrolled in Partners' MedSeq project as one of 50 healthy patients undergoing predictive screening to better understand their potential health risks. Schlichte's genomic information will be included in her medical record. Other participants with cardiomyopathy are receiving sequencing to better identify and understand that disease, which is one of the most common inherited disorders.
Many clinicians predict that whole genome sequencing eventually will become the first step, rather than the last, in a diagnosis. “In not too many years, most genetic diagnosis services will be done by sequencing the genome,” said Heidi Rehm, chief laboratory director at the Partners Laboratory for Molecular Medicine. “This is clinically useful even if it's still evolving.”
As an example of that evolution in knowledge, a decade ago clinicians tested five genes for patients with suspected hypertrophic cardiomyopathy. Now the scope of testing has been expanded to look at 51 genes that may be associated with five types of cardiomyopathy.
Traditionally, clinicians order a genetic test for a suspected disease or condition. If those targeted tests do not turn up a positive result and a diagnosis is not reached, clinicians may turn to exome or genome sequencing for more information. A patient suspected of having cystic fibrosis or Fabry disease undergoes a single-gene test. In contrast, other conditions, such as cardiomyopathy, require panel testing to evaluate a dozen or more genes.
Rehm said Partners launched its clinical sequencing program to set the stage for the system to become a leader in whole genome sequencing. Starting now will provide the time “to learn how to do it well,” she said.
There are at least a few other hospital systems around the country offering whole genome sequencing to patients. Scripps Health has provided whole genome sequencing to about 30 patients with cancer and about 15 families with unidentified, serious conditions, Topol said. The Scripps program is funded by charitable grants and does not charge patients for the sequencing service.
Outside of health systems, some companies also offer whole genome sequencing to patients, though that may not include interpretation and analysis. Illumina, a San Diego-based gene-sequencing company, markets whole genome sequencing, though the service must be mediated through a physician and patients can't directly buy the service.
Meanwhile, several academic medical centers such as Baylor Scott & White Health in Texas, Emory Healthcare in Georgia and UCLA Health in California provide exome sequencing.
Last year, researchers at Geisinger Health System launched a whole genome sequencing clinical research project with 65 families who have children with undiagnosed intellectual disabilities. They are sequencing the genomes of both the children and the parents at a cost of about $5,000 to $8,000 a child, and about $18,000 per family, with the service paid for by Geisinger.