Results of a recent study published in the New England Journal of Medicine may lead to greater adoption of genetic tests like array comparative genomic hybridization, researchers and vendors say.
The paper, “Association between Microdeletion and Microduplication at 16p11.2 and Autism,” appeared online Jan. 9 and describes how three separate microarray platforms were used to identify a chromosomal deletion believed to be a high-risk contributor to around 1 percent of all cases of pediatric autism.
Working with the Autism Genetic Resource Exchange, a collaborative gene bank for autism research, teams of scientists at Children’s Hospital Boston, Massachusetts General Hospital, and DeCode Genetics used microarray platforms from Agilent, Affymetrix, and Illumina respectively, to locate the de novo deletion of nearly 600 kilo bases on chromosome 16.
“I can tell you that this study was intended more for the autism community” than the array community, paper co-author Bai-Lin Wu, director of the Genetics Diagnostic Lab at Children’s Hospital Boston, told BioArray News this week. “This [deletion] is recurrent and is found in 1 percent of cases, making it by far the largest deletion associated with the disease.”
Beyond the scientific discovery, though, Wu said the findings could also add legitimacy to using microarrays in clinical diagnostic applications. “We have proved that [the technology] can be used as a diagnostic,” he said. “Smaller labs don’t have the resources for validation, but larger labs are able to confirm” deletions like the one discussed in the NEJM paper.
Additionally, Wu said that the fact that three different platforms produced the same finding at different sites was also encouraging. “MGH used Affy, DeCode used Illumina, Children’s used Agilent,” he said. “All three used different platforms and produced the same results. So that’s a good thing; every platform was equivalent.”
According to Wu, Children’s Hospital Boston has been using custom Agilent CGH arrays for over a year to identify genetic imbalances in children suspected of having autism spectrum disorder.
Agilent’s catalog chips are manufactured for research use only, but an increasing number of the array vendor’s clients are asking the company to design custom chips to use as laboratory-developed tests in line with the US Clinical Laboratory Improvement Acts’ standards.
Yvonne Linney, Agilent’s general manager of genomics, told BioArray News this week in an e-mail that as more clinically relevant discoveries are made using its chips, it is likely that the firm will see a rise in demand in diagnostic custom projects.
“The ability for labs to offer testing services based on genetic information is becoming increasingly important as more discoveries are made and as the genetic foundations of specific diseases or disorders become better understood,” Linney said.
She added that Agilent’s CGH arrays in particular may see an increased presence in diagnostic labs due to this phenomenon. “CGH allows the researcher to perform a high resolution look into the chromosome and identify much more information than the previously used karyotype,” Linney said. “In conjunction with a confirmatory [fluorescent in situ hybridization] assay, this is proving to be very attractive to the laboratories Agilent serves.”
In a separate study in the January issue of The American Journal of Human Genetics, a team of researchers from the Hospital for Sick Children in Toronto also reported that a deletion on chromosome 16 could be responsible for 1 percent of all autism cases.
“It adds to the credibility of the test, and by publishing it allows the test to become better known to a larger audience.”
Steve Scherer, a senior scientist at the Hospital for Sick Children and an author on the AJHG paper, has also recently collaborated with CombiMatrix Molecular Diagnostics to develop a specific array-based test for autism (see BAN 1/2/2008).
Scherer told BioArray News this week that his lab plans in coming months to add CGH-based testing for the deletion on chromosome 16, and that he expects that the NEJM and AJHG findings will encourage more clinicians to seek array-based tests for their patients.
“There has been a ton of interest in the test in Canada because of the media coverage, so as the word gets out there will be a lot of interest,” Scherer said. “As is always the case, if the families want testing they will eventually figure out how to get it done. In Canada most of the [testing] will be in hospital-based labs, most of which will be setting it up this year.”
Lisa Shaffer, CEO of Spokane, Wash.-based Signature Genomic Laboratories, also expects to see an increase in testing as a result of the recent papers. “It adds to the credibility of the test, and by publishing it allows the test to become better known to a larger audience,” she told BioArray News last week. “There may be neurologists out there that see patients with autism that weren’t aware of array CGH.”
Signature, which offers CGH-based testing for genetic abnormalities, has also been watching the region on chromosome 16 and has linked the deletion to developmental delay in general, according to Shaffer.
"We need to be cautious about associating DNA copy number alterations with a specific diagnosis, such as autism," she said. "It may be that these alterations have broader clinical consequences and we need careful clinical correlations in these cases."
Agilent’s Linney also stressed that the NEJM findings need to be further researched even as they are integrated into existing genetic tests. “Autism is a very complex disorder and it is very early days to be developing diagnostics tests to identify the disorder either prenatally or in young children,” she said.
“Having said that, with the increase in the number of genetic studies on autism and the number of important research findings now being reported, it is clear that better diagnostic tools will be available in the foreseeable future,” said Linney.
“My hope would be to see more solid therapeutic associations and prognoses which is what every parent is looking for as they explore various therapeutic and psycho-social interventions blindly at this stage,” she added.