SAN FRANCISCO (GenomeWeb) – One year after the Garvan Institute of Medical Research in Australia launched startup Genome.One to provide sequencing-based diagnostics for rare disease, the firm has said it will now offer whole-genome sequencing to any curious individual wishing to know his or her genetic risk for a suite of diseases.
The startup, which is wholly owned by the Garvan Institue, is one of just a handful of firms to offer whole-genome sequencing and disease risk assessments to otherwise healthy individuals. For instance, in the US, the HudsonAlpha Institute for Biotechnology and Veritas Genetics, both offer such services.
Marcel Dinger, CEO of Genome.One, said that the firm decided to offer the service as a step toward answering the question of whether one day everyone will have their genomes sequenced. "That predicates that we sequence people before they get disease," he said. "And this is a step in that direction, looking at how we start building the capability, know-how, and putting the infrastructure in place to make the switch from diagnostics to early detection and, ultimately, prevention by being aware of predisposition."
Initially, although the company will perform whole-genome sequencing, it will only analyze and return disease risk and pharmacogenomics-related results for just over 230 genes. Those genes impact 49 conditions: 31 cancer-related conditions and 13 heart conditions, where knowing a person's genetic predisposition can point to monitoring and intervention actions. They also include pharmacogenomically relevant genes related to more than 220 medications.
Genome.One is offering the service, called GoNavigate, in partnership with Life First, a health maintenance service with facilities at St. Vincent's Clinic. Life First will conduct a comprehensive medical assessment of individuals, including a physical exam, resting and stress ECG, a physiology review, and blood tests.
"By bringing these together, we can leverage evidence from the individual's physical health assessment and their genetics to get a more complete picture," Dinger said. For instance, "if a physician finds that an individual has high cholesterol, but is then able to put that in the context of also having a mutation in the hypercholesterolemia gene, that gives a stronger narrative," he said, and could help increase urgency in bringing down the patient's cholesterol.
Although any interested individual can receive the test, it will be done under the supervision of a clinician at Life First. Genome.One will perform the sequencing on the Illumina HiSeq X Ten in its laboratory, which is accredited for diagnostic whole-genome sequencing, and will also conduct the analysis and provide pre- and post-test genetic counseling.
The service will cost AUD 6,400 ($4833) and consumers will pay out of pocket. Genome.One plans to donate 5 percent of revenues from GoNavigate to support Australian families looking for a diagnosis for a rare genetic disorder through the iHope Network.
Dinger said the team spent a lot of time determining which genes and conditions to analyze. They used the American College of Medical Genetics and Genomics' list of actionable genes as a jumping-off point, expanded on that, and added PGx genes, he said.
"It's a very different interpretation for healthy individuals than what you do to try to identify the cause of a disease," he said.
Although the company will only analyze and report pathogenic variants from the 200-odd genes, Dinger said the firm wanted to use a whole-genome sequencing approach for a variety of reasons. For one, Dinger believes that ultimately, the field is moving toward whole-genome sequencing. In addition, he said, sequencing the whole genome from the outset would make it easier to later include additional genes when there was evidence of actionability. Individuals who use the service will also have the option of making their data available for research purposes, and having whole-genome data would facilitate that as well.
Genome.One is still working out a number of details, including data storage. Dinger said that the raw data would be stored for at least three years and the clinical report indefinitely. In addition, he said, the firm plans to revisit the data as new evidence becomes available, and over the next year, will build the infrastructure needed to re-contact patients if there are new findings. "It's something we're exploring in order to keep that continuous engagement with consumers and their health," he said. He anticipates that the firm would consider adding new genes on an annual basis.
Currently, Dinger said, the clinical report that is delivered to the patient does not automatically go into the patient's medical record, although Genome.One is exploring whether and how to give customers that option. "That's where the utility of the information gets realized," he said. However, he also acknowledged that there is a general concern around privacy and who has access to personal health data. "We want to keep the consumer empowered."
Dinger added that Genome.One anticipates eventually delivering the full raw dataset back to the customer. "Unleashing the whole data onto someone is complicated," he acknowledged. "We want to make sure we do that responsibly, but we recognize that people may want their data." Consumers could then take that dataset elsewhere for interpretation on genes that Genome.One does not analyze. "We're working out how we counsel and inform individuals appropriately around what they might find if they do that," Dinger said.
Because Genome.One's lab is already accredited by Australia's National Association of Testing Authorities and meets ISO 15189 requirements, Dinger said that it did not need to go through any additional regulatory clearances to offer the GoNavigate service.
Aside from this new GoNavigate service to search for disease predisposition variants, Dinger said that Genome.One is continuing to build on its diagnostic services.
Currently, it offers diagnostic whole-genome sequencing for both pediatric and adult patients with rare diseases and in the future, it is considering developing a somatic cancer test, although Dinger could not say when that would happen. For somatic cancer testing, the firm would likely use a targeted panel. "In somatic cancer, sequencing depth is so important because of heterogeneity, and so, whole-genome sequencing becomes prohibitively expensive," Dinger said.
Genome.One's diagnostic whole-genome sequencing test has an average diagnostic rate of 58 percent over a broad spectrum of diseases. That rate varies depending on the disorder, with the highest yields seen in patients with polycystic kidney disorders — around 86 percent of those patients receive a molecular diagnosis, Dinger said. He added that the company tends to evaluate hard-to-diagnosis patients. Those for whom the doctor suspects a disorder are typically evaluated by single-gene or panel sequencing.
When genetic testing companies and academic medical centers first began offering clinical exome and whole-genome sequencing, diagnostic rates hovered in the 25 percent to 30 percent range, but those patients had usually undergone a battery of other diagnostic tests.
Dinger attributed Genome.One's significantly higher rate to a combination of factors, including improvements in the sequencing technology and coverage of relevant genes, the quality of variant databases and algorithms, and increased knowledge around molecular causes of genetic disease. "It's amazing how fast this is improving," he said.