Whole Genome Sequencing Testing Is Available At The New York Genome Center
By Dava Stewart
January 20, 2017 | The New York Genome Center (NYGC) has received conditional approval from the New York State Department of Health to offer whole genome sequencing (WGS) testing. The test, which is done using the Illumina HiSeq X Ten, is particularly valuable for patients with undiagnosed conditions who have undergone all other available tests. However, there is good reason to believe that WGS testing could soon become a first line approach in precision medicine.
Conditional approval was granted in the summer of 2016, and the Center expects full approval will be granted soon. The state Department of Health receives a large volume of applications, and it is thanks to a history of providing good service and following regulations the NYGC was approved to conduct WGS testing while their assay validation is being formally reviewed by the Department of Health.
The NYGC is certified through New York’s Clinical Laboratory Evaluation Program (CLEP), which conducts on-site inspections and evaluations. The goal of the program is to protect the public safety of the residents. The program has been acknowledged as excellent by the Centers for Medicare and Medicaid (CMS).
Technological Advances Are Coming Fast
WGS at the NYGC is performed using the Illumina HiSeq X Ten system, about which Vaidehi Jobanputra, the director of molecular diagnostics at NYGC, says, “The chemistry for the X Ten is much better than [previous generations of sequencing systems] and allows much faster and cheaper sequencing.”
Ilumina introduced the HiSeq X Ten in January 2014. The system, which consists of 10 machines, is designed for labs that need the capability to conduct high throughput sequencing. In 2015, Illumina introduced the HiSeq X Five, which is a five-machine system. Just last week at the J.P. Morgan Healthcare Conference, Illumina announced their most recent innovation, the NovaSeq series. Currently the NYGC is the only facility with approval from the state department of health in New York to perform WGS testing with the HiSeq X Ten.
Who Gets WGS Testing?
Jobanputra says that currently there are two main groups of patients seeking WGS testing; the majority are those who have been unable to get a diagnosis through other means. “Most of the time it is being used for undiagnosed disease, in cases where people have run out of other options,” she says, but adds that more physicians are recognizing that WGS is better than sequential single gene or panel testing and are referring their patients sooner.
The second group are people without symptoms, who appear healthy and are seeking predispositional testing. As genetic testing becomes more common, people are learning the importance of genetic predisposition to diseases, even relatively common conditions such as cardiovascular disease, which Jobanputra describes as “complex”.
The American College of Medical Genetics and Genomics (ACMG) issued guidelines in 2013 advising that the possibility of incidental findings, unrelated to the indication leading to the recommendation to be tested, should be discussed with patients before they undergo genetic testing. It is those incidental findings that could cause a healthy person to seek pre-dispositional genetic testing. A likely scenario would be that a patient with an undiagnosed condition undergoes genetic testing, and there is an incidental finding of a risk unrelated to the condition that originally prompted the testing. In this case, the patient’s family may be at risk, and benefit from WGS.
A More Complete Picture
WGS provides a more complete picture of the genes than single gene or even whole exome sequencing (WES), Jobanputra explains. “[Whole exome sequencing] may be uneven or heterogeneous, so it’s biased a little bit, but with whole genome sequencing there is no capture, you’re just sequencing the genome,” she says.
However, the volume of information generated through WGS is a bit of a double edged sword. Nelly Jouayed Oundjian, a clinical geneticist in New York, says that in most cases, WES is sufficient to meet the needs of her patients, noting that about 80% of the mutations and variations which lead to a diagnosis are detectable through WES. She says, “We do not understand yet the functions of approximately 14,000 genes and their role in causing disease.”
Oundjian does acknowledge the value of WGS testing, though. “Geneticists work in gray areas,” she says. “Sometimes the genetic testing detects in the gene variation of unknown clinical significance and the outcome is not clear. We have to work through that or the field is not going to go forward.”
There is a gap between available technology and practical applications, but the technological breakthroughs are allowing progress that would have been unimaginable just a few years ago. Jobanputra says researchers are working to match genetic variations to clinical phenotypes in order to identify possible treatments across a number of specialties.
More Tests, More Knowledge
At the end of 2016, the NYGC had sequenced more than 20,000 genomes, which is one of the largest volumes of research-related whole genome sequences in the United States. As tests are conducted, more uses for the results are revealed. Researchers who are working to pinpoint treatments for specific diseases, physicians who are working to provide the best care for individual patients, and even patients themselves are finding unexpected ways to test that results are relevant.
Patients, clearly, have a different perspective compared to researchers and geneticists when it comes to genetic testing. Amanda Warren lives in South Carolina and underwent predispositional testing at the suggestion of her primary care provider. She said that although she was already aware of several things the results revealed, there were also some surprises. For example, Warren learned that she has a sensitivity to blood thinners that she didn’t know about and which could be important “down the line somewhere.”
Jobanputra says that some physicians are already beginning to use WGS as a first step because “the phenotypes and the symptoms are so heterogeneous. It’s easier to do one test to obtain much more comprehensive results than the available individual tests, such as sequencing panels, exomes, and chromosomal microarrays.” Results such as Warren’s—where a sensitivity to a particular drug was revealed—offers a way to provide individualized care. With knowledge that a particular patient has a genetic predisposition to addiction or to cardiovascular disease, physicians would have more information guiding treatment decisions or in advising patients.