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Emory to Convert Dx Gene Panels from SOLiD to Ion Torrent; Plans to Launch Clinical Exome on HiSeq


By Monica Heger

This story was originally published March 16.

Emory Genetics Laboratory
is in the midst of converting its targeted-sequencing based diagnostic panels from Life Technologies' SOLiD to the Ion Torrent PGM and plans to launch a clinical exome sequencing test this summer on the Illumina HiSeq.

Additionally, the laboratory plans to begin offering a targeted sequencing-based test for autism this month and, by August, additional tests for Noonan syndrome, short stature, cardiomyopathy, epilepsy, and ciliopathies. It is also validating Ion's AmpliSeq Cancer panel.

The CLIA- and CAP-certified laboratory has been offering sequencing-based tests for X-linked intellectual disability, congenital muscular dystrophy, and congenital disorders of glycosylation on the SOLiD since 2010 (IS 5/25/2010).

Madhuri Hegde, scientific director of the lab, told Clinical Sequencing News that the lab recently purchased three PGMs and is converting its existing tests to that platform because it is more robust than the SOLiD, has a quicker turnaround time, and is more cost-effective.

In conjunction with Life Technologies' researchers, the Emory team has re-run all of its samples for its X-linked intellectual disability panel, comparing results from the PGM to the SOLiD, and found that the PGM accurately identifies all the mutations. The researchers plan to publish a paper on the comparison soon.

Hegde said that the data quality for the PGM has "improved with time," and that the platform offers advantages in terms of speed and cost compared to the SOLiD. "It allows us to do the same number of samples in under a week that would take about two to three weeks on the SOLiD." Its size and cost offer additional advantages, particularly for a clinical laboratory, she said.

Once the validation on the PGM is complete, Hegde said that the SOLiD will be phased out.

This month, the lab will also launch an autism test that includes a 62-gene panel plus a chip to measure known deletions and duplications that are causative of autism.

This summer, the lab will begin offering a clinical exome sequencing service on the HiSeq. While there is no HiSeq in the Emory Genetics Laboratory, Emory's core facility has one and is also CLIA-certified, so the sequencing for the exome service will be done there, said Hegde.

Hegde said that the lab will offer three levels of exome sequencing. The most comprehensive version will include sequencing, Sanger confirmation, and interpretation. The lab will also offer just Sanger confirmation and interpretation for patients who already have sequencing data, and interpretation alone for those who have validated sequence results.

Hegde said the interpretation services are based on an in-house library of all known disease-associated genes and an internal annotated database of disease variants.

The lab has also developed specialized protocols for Sanger sequencing. "People go back and forth on whether to do Sanger sequencing" for confirmation from next-gen sequencing done in a CLIA setting, Hegde said. But, she noted, there's "still a high false-positive rate for exome and whole-genome sequencing," which makes the confirmation necessary even when done in a CLIA lab.

Hegde added that in her experience offering clinical next-gen sequencing panels, there is typically a significant amount of follow-up testing needed for the patients' family members. Parents, siblings, and even grandparents are frequently tested for the mutations, she said.

This additional testing prompted her lab to develop automated protocols for primer design for Sanger sequencing. "It's important to have that PCR fragment in which the mutation is in ready to go," she said.

Over the last two years, Emory has also been developing its own internal database of variants, which she said will be especially important when interpreting whole-exome sequencing data because variants are often incorrectly reported in public databases. "People that run clinical labs can tell you how much curation we do on a daily basis," she said.

She said she is still figuring out the exact protocol for offering the clinical exome test, but said that like other academic groups offering clinical exomes, orders will first be reviewed internally to make sure that exome sequencing is the best option. Additionally, there will be a team of geneticists, genetic counselors, physicians, and specialists in the specific phenotype area of the patient that will discuss the sequencing results and create the report that will be returned to the patient's physician. Families will also have options for receiving results of incidental findings.

Emory joins a number of other academic groups and companies that now offer clinical exome sequencing, including the University of California, Los Angeles; Washington University's School of Medicine; and Ambry Genetics (CSN 3/7/2012). In addition, researchers at the Radboud University Nijmegen Medical Center in the Netherlands are offering clinical exome sequencing for specific diseases in a pilot project to demonstrate the cost-effectiveness of reimbursement (CSN 10/19/2012).

The Medical College of Wisconsin and the Children's Hospital of Wisconsin have already gone one step further and are offering clinical whole-genome sequencing for patients with undiagnosed diseases. Illumina also offers clinical whole-genome sequencing through its CLIA laboratory.

Have topics you'd like to see covered by Clinical Sequencing News? Contact the editor at mheger [at] genomeweb [.] com.