Should Healthy People Have Their Exomes Sequenced?

With its announced launch of a whole-exome sequencing service for apparently healthy individuals, Ambry Genetics is the latest company to enter this growing market. But whether these services are useful for most people remains up for debate.  

By | March 24, 2017

© BRYAN SATALINOFor people with no perceivable health issues but who are curious about some potential future ailments, there are now a handful of companies offering whole-genome or exome sequencing services to identify potential disease risks and other personal traits. The latest company to join the fray is Ambry Genetics, which plans to this year launch a whole-exome sequencing service, the firm announced at the American College of Medical Genetics and Genomics annual meeting, being held in Phoenix this week.

“Right now we are in the development stages,” said Brigette Tippin Davis, director of Emerging Genetic Medicine at the Aliso Viejo, California-based company. “The plan is that [healthy] individuals would go to their doctor and, if they are curious about their genetic risks,” she said, they can “get a comprehensive test all in one.”

Whole-genome or -exome sequencing has traditionally been reserved for patients with a symptomatic disease for which all diagnostic avenues have been exhausted, said Davis. But Ambry Genetics and other companies—including Genos, based in San Francisco, San Diego–based Human Longevity, and Veritas, of Danvers, Massachusetts—are now widening the net.

Ambry Genetics wants “to increase access to testing,” said Davis. “This is a way to bring genetic stratification and customized primary care screening to everyone before you get sick.” After all, she added, “the earlier you catch it, the better chance you have to prevent a disease from actually becoming catastrophic.”

While it is difficult to argue against the benefits of taking preventive action, the reality of exome sequencing is that “it generates so much data but so little of it can be interpreted or can be helpful,” said Yann Joly, research director at the Center of Genomics and Policy at McGill University in Montreal.

The results may even be unhelpful, Joly continued. “There can be the usual mistakes, such as false-positives or -negatives, and it can be a source of anxiety.” There can also be “errors of interpretation,” he said, adding that clinicians can have trouble understanding sequencing results.

“There is not a lot of reason to justify it at this point for healthy people,” said Joly, “[because] the medical value of doing this is low.”

Radoje Drmanac, chief scientific officer and cofounder of Complete Genomics in Mountain View, California, holds a different view. “I like that companies are offering this service,” he said. “My position is that knowing your genes is good. It’s even a right.”

While Drmanac said he believes there is a need for support and education to help consumers interpret their results (from a doctor or genetic counselor, for example), he feels the choice to purchase such screening is entirely up to the individual. “There is no reason for a physician to order it,” he said. Currently, a person wishing to purchase one of the exome sequencing services on offer is required to consult their doctor first. This appears to be a formality, however, because, if a customer’s own physician is reticent, Ambry Genetics and Genos will connect them with an independent alternative—essentially enabling a direct-to-consumer service in all but name.

Susan Wolf, a professor of law, medicine, and public policy at the University of Minnesota, told The Scientist that up-front counseling is important. A person needs to understand what they are getting into, she explained. They should be informed, for example, that the US Genetic Information Nondiscrimination Act (GINA) “only covers health insurance and some forms of employment discrimination,” she said. “It’s very rare that there is protection for disability insurance, long-term care insurance, even life insurance.” So if a person’s exome sequence reveals a high risk of, say, Alzheimer’s disease, which may require long-term care, the individual should be aware of the potential risks, she said.

Help with interpretation of the results after sequencing is also essential, Wolf added. To this end, Ambry Genetics, Genos, and Human Longevity all suggest independent genetic counselors, while Veritas provides their own.

To further assist with interpretation, Ambry Genetics plans to only provide “medically actionable” results to the customer, said Davis—such as pathogenic or likely pathogenic mutations and variants associated with drug toxicities. “We want to keep things simple for these otherwise healthy individuals, so we don’t want to confuse the matter with variants of uncertain significance, or other observations that have no known clinical impact.”

Similarly, Human Longevity and Veritas provide reports that include pathogenic mutations, disease risks, and ancestry information along with other—more obvious—traits, such as a person’s eye color, skin color, and approximate height.

Genos, on the other hand, does not give health information or recommendations, said Mark Blumling, the company’s CEO and cofounder. “It’s not interpretive and it’s not a diagnostic,” he said of his firm’s exome sequencing service. The company provides the raw data, plus “data visualization tools that allow you to explore your exome in comparison to ClinVar”—a National Institutes of Health database of clinically significant genetic variations.

The idea is to enable individuals to regularly check their sequence against the database as new variants are discovered and as health information develops, Blumling explained.

Apparently healthy folks who are curious about their DNA and have money to spend have several sequencing service options.

For $585 or $1,425, Rockville, Maryland-based Full Genomes will sequence your whole exome or genome, respectively, at a coverage depth of 30x. Currently, the company provides only ancestry information with the raw data, but “we also have a pilot health analysis that we may be able to offer soon,” said the firm’s founder and CEO, Justin Loe. For $499, Genos will sequence your whole exome at 75x coverage, providing both the raw sequence and ClinVar-compatible analysis software. For $1,400, Human Longevity will sequence your whole genome—though, for now, this service is only available to Mass Mutual life insurance customers. For $999, Veritas will sequence your whole genome at 30x coverage, plus provide health and medical recommendations and a follow-up genetic counseling session. As for Ambry Genetics’s newly announced offering, the depth of coverage and price of their soon-to-be-launched service are as yet undisclosed.

While Joly sees little medical worth in such services at this point, “if people are really curious to go through the experience, can handle the results, and are willing to pay for it, I don’t see a high level of danger,” he said.

Clarification (March 29): The ninth paragraph has been updated to make clear that, upon request, Ambry Genetics and Genos may recommend an alternative physician. The Scientist regrets any confusion.

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