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Biomedicine

New Test Screens Prospective Parents for 100-Plus Diseases

Startup aims for routine preconception genetic testing.

Counsyl, a Stanford startup based in Redwood City, CA, has developed a genetic test for prospective parents that determines their risk for passing more than 100 different genetic diseases on to their child. The test, which costs $349 and is already covered by some major insurers, could rapidly expand preconception screening for rare inherited conditions. For most people, screening recommendations are currently limited to the chronic lung disease cystic fibrosis, with broader testing offered to some ethnic groups.

Prepregnancy screening: To determine the risk of passing rare inherited diseases to their offspring, prospective parents spit in a tube (shown here) and then send the sample to Counsyl, a California-based startup. The company screens the sample for genetic mutations linked to more than 100 diseases.

While the genetic culprits for more than 1,000 rare inherited diseases have been identified, screening for them has been limited, largely due to cost. The comprehensive nature of Counsyl’s test and its reasonable price tag reflect rapid advancements in screening technologies. “When cystic fibrosis testing first started in the early ’90s, it cost on the order of $350,” says Philip Reilly, a clinical geneticist, now with Third Rock Ventures, a Boston-based investment firm. “Now [Counsyl] is offering to test for 100 disorders for the same price, and it will fall lower.” In the late 1990s, Reilly, who is not involved with Counsyl, launched a similar company, which he says failed partly because testing was still too expensive.

Counsyl’s test detects genetic variants linked to rare inherited conditions such as cystic fibrosis, Tay-Sachs disease, and Pompe disease, a metabolic disorder featured in the new film Extraordinary Measures. (Counsyl, which until recently was operating in stealth mode, appears to have pegged its public debut to the film’s release.) While individuals carrying a single copy of the mutation for such diseases are typically healthy, those who inherit two copies, one from each parent, are guaranteed to develop it. Many of these diseases are incurable and have devastating consequences, including early death.

The rate of single-gene disorders in the United States is estimated at about 0.3 to 0.5 percent of live births. According to Counsyl, about 35 to 40 percent of people who have taken its test are carriers for at least one disease in the test. Both prospective parents carry the mutation about 0.6 to 0.8 percent of the time. Those couples would have a 25 percent chance of having a child with the disease, thanks to a 50 percent chance of inheriting the disease variant from each parent.

The genetic variants screened in Counsyl’s test themselves aren’t new–all can be tested for individually or as part of other screens. (Ashkenazi Jews, for example, often undergo screening for a handful of inherited disorders that occur more frequently in that group.) The novelty in Counsyl’s test comes in grouping together such a large number of conditions–the company’s founders say it can detect several hundred variants responsible for more than 100 different genetic diseases.

If parents discover that they both carry risk variants for the same disease, they can choose to undergo in vitro fertilization and have embryos screened for the disease prior to being implanted in the womb. Or the woman can choose to get pregnant the normal way and then they can have the fetus screened during pregnancy.

Testing is likely to lead to an increase in techniques such as in vitro fertilization and preimplantation genetic diagnosis, which together cost about $12,000 to $17,000. But that figure is still drastically lower than the hundreds of thousands to millions of dollars it can cost to take care of a child with a severe genetic disorder. “That’s why we got insurance coverage so rapidly, which is extremely unusual for a new diagnostic test,” says Balaji S. Srinivasan, chief technology officer at Counsyl.

In addition to getting the test through fertility clinics, consumers can order it directly through the Internet, similar to services provided by startups 23andMe, Navigenics, and DecodeMe. While these companies have largely pioneered the concept of direct-to-consumer genetic testing–and garnered extensive media attention doing so–their goal is much different than Counsyl’s. Their screens are designed to detect common genetic variants that have a fairly minor impact on an individual’s risk for a number of common diseases, while Counsyl’s test detects rare genetic variants linked to serious diseases in people carrying two copies of it.

Reilly predicts other companies will soon follow suit. “I think there will be lots of other groups offering similar tests in the future,” he says. “There’s no reason why 23andme couldn’t do this, or Navigenics or Baylor or the Mayo clinic.”

Counsyl uses a technology called a molecular inversion probe array, which can capture small, select pieces of DNA and allow them to be analyzed with high accuracy. Srinivasan says the company will publish details of the method as well as its accuracy in a peer-reviewed journal this week. He says the company also plans to change its screening methods in the near future, using gene sequencing technology, which determines every letter of the selected genes.

The test is not foolproof. It doesn’t detect a number of genetic and environmental factors that can affect a healthy pregnancy. In addition, many of the mutations underlying the conditions encompassed by the test have not yet been discovered, meaning someone may still be a carrier.

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