By Monica Heger
German sequencing service provider Center for Genomics and Transcriptomics, or CeGaT, said last week that it is now offering sequencing-based diagnostic tests on Life Technologies' SOLiD machine for epilepsy and metabolic diseases, dementia, amyotrophic lateral sclerosis, Parkinson's disease, and hereditary eye diseases.
The Tübingen, Germany-based company joins a small but growing number of organizations offering diagnostic panels on next-generation sequencing platforms. For example, Ambry Genetics, Emory University, and GeneDx all offer sequencing-based diagnostic tests for a range of conditions (IS 5/25/2010). Additionally, the National Center for Genome Research and Good Start Genetics are planning to launch sequencing based pre-pregnancy tests in 2011 (IS 9/14/2010).
CeGaT currently offers 28 different panels, including one panel of 19 genes for epilepsy and ALS, one panel of 19 genes for Parkinson's, 15 panels covering 265 genes for epilepsy and metabolic disorders, and 11 panels covering 168 genes for hereditary eye diseases.
The company uses Agilent's SureSelect in-solution capture for target enrichment, and fragment sequencing on the SOLiD, obtaining at least 20-fold coverage of each base. The company then validates its findings with Sanger sequencing and performs bioinformatics analysis using the SOLiD BioScope software.
CeGaT charges a flat €3,000 for sequencing, and then an additional €100 per gene for bioinformatics analysis. Turnaround time for a test is two to three months.
Saskia Biskup, CeGaT's CEO, told In Sequence that the company looks for both known and novel mutations. It does a prediction assessment for each novel mutation, and only reports those that are found in clinically relevant genes. For novel mutations, the company also suggests the physician check for segregation within the family.
The company does not offer its tests directly to consumers, but instead is looking to partner with doctors, university clinics, and centers specializing in diseases covered by its panels. For example, CeGaT is collaborating with Germany's University of Tübingen to discover novel disease-causing genes for neurodegenerative disorders. Doctors at the university clinic, meantime, rely on the company's tests for epilepsy, ALS, and Parkinson's.
Biskup added that CeGaT has additional customers throughout the world, "from Canada to New Zealand," but declined to provide their names.
CeGaT is currently operating under Germany's genetic diagnostics law, which recommends counselling both before and after genetic testing, and it is scheduled to obtain accreditation in Germany at the beginning of next year for its sequencing-based tests. Under the current law, accreditation is not needed to offer the tests, but the law is changing next year, said Biskup.
Despite the falling cost of whole-genome sequencing, Biskup said that targeted sequencing for diagnostic purposes will still have a place. For at least the next few years, "I don't see a point where next-generation sequencers can sequence the whole genome at coverage high enough for diagnostic purposes cost-effectively," Biskup said. Whole-genome sequencing will also yield a lot of uninterpretable information, she added.
The company's tests would not compete with pre-pregnancy or prenatal tests from Ambry, Good Start, or NCGR, but would compete directly with tests being offered by Emory, which also uses the SOLiD. Currently, both Emory and CeGaT offer sequencing-based tests for X-linked mental retardation and congenital disorder of glycosylation. Ambry also has a sequencing-based test for XLMR. GeneDx, meantime, offers a sequencing-based test for several inherited cardiac disorders.
The advantage of a sequencing-based diagnostic test, said Biskup, is that it establishes a molecular basis for the disease.
"In some instances the diagnostic test leads to specific treatment. In addition, it allows [clinicians] to predict prognosis," she said. Additionally, pinpointing the mutation or mutations that led to an individual's disease subtype could "enable testing of relatives, and prenatal diagnosis becomes possible."
Biskup said the next step is to develop more diagnostic panels. The company next plans to launch a panel that covers many different subtypes of neuromuscular disorders. This test, which is slated for launch in the first quarter of 2011, will cover around 200 genes.
CeGaT is also looking to automate the sample-prep and sequencing steps to reduce turnaround time, although she did not specify by how much. However, Biskup said that the prime focus will still be quality, and the company will continue to validate the mutations with Sanger sequencing, and also perform individual bioinformatics analysis.
Additionally, the company is considering purchasing another SOLiD machine. Biskup said that CeGaT did not evaluate other platforms, but were convinced by looking at data produced by other groups that the SOLiD's sequencing by ligation method offered the highest accuracy. The company is currently equipped with one SOLiD and an ABI 96-capillary sequencer. Aside from molecular diagnostics, the company provides next-generation sequencing services, including exome, transcriptome, and microRNA sequencing.