This article has been updated to correct that since May, Counsyl no longer offers its carrier screening test without a doctor's order and to include additional comments from a Counsyl official.
By Julia Karow
Ambry Genetics over the next four to six weeks plans to start offering a commercial genetic carrier-screening test that uses targeted sequencing to screen for known variants involved in more than 90 severe or common genetic diseases with onset in childhood.
The test, called AmbryScreen, is in its final validation phase and is expected to cost $450. At present, it runs on the Illumina Genome Analyzer, although the company is considering alternative sequencing platforms.
Ambry's test must be ordered through a physician. According to Anja Kammesheidt, Ambry's chief scientific officer, the CAP-accredited and CLIA-certified clinical laboratory has been developing the test internally since last fall, drawing on the expertise of its nine in-house genetic counselors.
The test covers several hundred well-understood disease-causing mutations linked to more than 90 genetic diseases that were chosen because they are severe or common and start in childhood.
"We think we have an extensive screening test, but will always address new information to integrate in the future if warranted," Kammesheidt said.
Even though it is a genotyping test that looks for known mutations only, it runs on a sequencing platform, currently the Illumina Genome Analyzer, which Ambry has had in house since 2007. According to Kammesheidt, sequencing allows the firm to cover variants that are "trickier" to assess with other genotyping platforms, and is easier to scale.
The test uses traditional multiplexed PCR to generate amplicons for sequencing and pools several bar-coded samples per flow cell lane. It does not sequence entire genes but only those sections containing the variants of interest.
The company, based in Aliso Viejo, Calif., has been validating the test internally on an undisclosed number of previously tested DNA samples with known mutations. It expects validation to be completed in four to six weeks, after which it plans to start marketing the test to obstetricians and gynecologists.
The test is expected to cost $450 and have a yet undisclosed turnaround time. The company anticipates that it will be covered by health insurance plans.
According to Ardy Arianpour, Ambry's vice president of business development, the firm will initially dedicate two Illumina GA platforms to run the test but is currently validating new sequencing technologies from undisclosed vendors to achieve "faster turnaround times and cheaper tests."
Ambry, no newcomer to the genetic-testing market, will lean on its existing customer base to market the new test. According to Arianpour, Ambry has provided genetic tests for the last 10 years and is particularly well-known for its cystic fibrosis genetic testing.
Ambry is quick to point out that it does not offer its test directly to consumers, but it will likely compete with Counsyl's genetic carrier test, which has been on the market since 2009 and until recently, was available directly to consumers.
Balaji Srinivasan, Counsyl's chief technology officer, told In Sequence that the company phased out direct to consumer testing earlier this month in favor of an online booking system that lets consumers make their own test appointment at a clinic and provide their own billing information.
The test now requires a doctor's order, and results go directly to the physician for interpretation. Counsyl's Universal Genetic Test, offered at $349, uses a microarray platform to cover variants involved in more than 100 life-threatening genetic diseases.
Both tests cover known disease variants only, which some experts say is not enough because they do not include rare variants that have not been previously described.
"If the Ambry test is confined to (a subset of) the established mutations, such as the Counsyl test, it can only rule out a fraction of the risk for recessive disorders," said Hilger Ropers, department head of human molecular genetics at the Max Planck Institute for Molecular Genetics in Berlin.
He and his colleagues at the National Center for Genome Resources in Santa Fe, NM, are working on a more comprehensive genetic carrier screening test that is expected to cover 414 genes linked to 422 recessive catastrophic childhood diseases, and 100 genes involved in several X-linked mental retardation (IS 3/30/2010).
That test, which will undergo validation later this year, will sequence entire genes, including exons and certain non-exonic regions, and look for both known mutations and variants of unknown significance.
"[We] see significant benefit from establishing a database of Variants of Unknown Significance," said NCGR President Stephen Kingsmore.
However, Ambry argues that excluding these variants makes it easier to interpret the test results.
"Our focus has been on the relevant variants that have been described for a lot of the diseases many times," Kammesheidt said. "Therefore, we don't have a problem with this whole question of unknown variants."