Oxford Gene Technology last week launched its CytoSure DMD array, a four-array by 44,000-feature format chip manufactured by Agilent Technologies for detecting mutations in the dystrophin gene that are responsible for Duchenne muscular dystrophy.
As part of the rollout, UK-based OGT also introduced its new CytoSure Interpret Software, a new analysis platform that enables CytoSure users access to visualization tools, imported and external annotation information, databasing capabilities, and standardized formatting.
OGT Commercial Director James Clough told BioArray News this week that the DMD Array launch is one of several the firm plans in the coming months as arrays become the technology of choice in genetics laboratories.
Clough said that the DMD array was developed in partnership with Madhuri Hegde, a senior lab director at Emory Genetics Laboratory in Atlanta whose research interests include muscular distrophies and colorectal cancer. Clough said that Hegde's lab had been using multiplex PCR and multiplex ligation-dependent probe-amplification assays to identify mutations in the DMD gene, but decided to adopt an array platform to survey copy number variation as well.
"It's an interesting illustration of where things could be moving in the future, in that Emory has been using and [is] still sequencing for single-point mutation detection," Clough said of the discussions that led to the creation of the chip.
Clough noted that the DMD gene is very large at 2.2 megabases. "Point mutations in the gene explain some of the incidence of DMD, but the realization that copy-number variation within the gene is playing a role led to Emory's interest in use of CGH as a way of looking at DMD, and within our CytoSure range, we have a significant interest in copy number detection using array CGH," he said.
According to Clough, OGT believes there is a market for the array, partially because array CGH offers some advantages over traditional techniques that are used to identify mutations in the DMD gene, such as multiplex PCR and MLPA, because CGH can detect duplications as well as mutations in female carriers.
"The incidence of DMD is one in 3,500 in males, so it is not a rare disorder," said Clough. "What I think is also interesting is that the DMD gene is an example where the majority of mutations are deletions or duplications," Clough added. "This is a disease with significant prevalance and there's a lot of research in the field on deletions and mutations in this gene."
According to Clough, array CGH so far has been adopted by cytogeneticists who are interested in identifying the genetic causes for patients with congenital abnormalities, such as mental retardation or autism spectrum disorder. The DMD array, though, was designed for a particular genetic disease. In the future, focused arrays could be used to study other genetic diseases, Clough said.
"This is an interesting example of what has been pigeonholed as a cytogenetics technique being used as a molecular genetics technique," Clough said. "Over time, I think the border between molecular genetics and cytogenetics will blur."
Clough said that OGT plans to introduce more CytoSure arrays in coming months, but declined to discuss them.
OGT launched its first CytoSure arrays for cytogenetics research in 2007. Co-developed with researchers at the Cyprus Institute for Neurology and Genetics, the CytoSure Chromosome X Array was an exon-specific, high-density array with 44,000 features all focused on the X chromosome. OGT also launched its CytoSure Syndrome Plus Array, which covers 85 distinct genetic syndromes, at the time (see BAN 6/26/2007).
Last year, OGT upgraded the content on both arrays by introducing the Chromosome X High Density array and the second version of Syndrome Plus that contains markers for over 200 syndromes, including 410 genes associated with autism, mental retardation, and heart and eye diseases (see BAN 11/18/2008).
For its most recent CytoSure product, OGT worked "very closely" with Emory's Hegde and her team on the design format and then designed probe sets to interrogate the DMD gene. Clough said. OGT then designed multiple probes in the DMD region and tested their performance and picked the best set for use on the array.
[ pagebreak ]
Hegde told BioArray News this week that she believes there are "many labs that want to use arrays" to study DMD that "don’t have expertise to explore that option." According to Hegde, there is a "big market out there" for OGT's array.
"We have got a database of over 22 million probes, so with DMD where we have such high probe coverage, that's a semi-automatic process," Clough said of the array design. "We'll take in silico design probes and also do manual probe picking and curation. Then we have to have the arrays made and test them," he said. "The majority of effort goes into two rounds of iterations on the design."
The CytoSure DMD array is sold together with the firm's CytoSure Genomic DNA labelling kit and OGT's new CytoSure Interpret Software. The array is also compatible with SciGene workflow automation products. OGT in September became the European distributor for SciGene's instruments, such as its Little Dipper Microarray Processor, Mai Tai Hybridization System, and ArrayPrep Target Preparation System.
Clough said that the firm has benefited from the SciGene distribution pact, as it now can offer users equipment in addition to arrays, kits, and software.
"The key thing for us is that the cytogenetics community is rapidly moving to array CGH as a frontline tool," Clough said. "We have arrays, labeling kits, and software, but now in Europe we have equipment that's complementary to our high-quality products and allows the labs to run more samples at a time when they want to run more samples," he said. "Most customers prefer to deal with a small number of vendors," he added.
One central component to the new CytoSure DMD array release is the availability of OGT's CytoSure Interpret software. OGT launched CytoSure software for cytogenetics research in 2007. Clough said that CytoSure Interpret, though, is a replacement for what the firm had offered in the past.
"When we first started it was a visualization tool, but the software wasn't there to interpret the data," Clough said. According to Clough, Interpret differs in several aspects, including databasing capabilities, annotation information, and standardized workflow.
"When we started four or five years ago doing research projects in aCGH, people were saying that, at some stage, arrays might play some role in cytogenetics," Clough said of the new software. "What we see around the world is that arrays are becoming the first-choice technology and the question is, 'How do you deal with that'?" he said.
Clough said that the availability of higher-resolution arrays has enabled researchers to detect small genomic changes that, in turn, cause challenges in terms of interpretation. That was the main rationale behind making more annotation available in the new software, he said, which offers access to a combination of imported annotation and links to external databases.
"You want to find the significance of the change you found and this software is highly annotative in what region you found the change in," Clough said. "The more people look at a higher resolution in non-syndromic regions, the more changes they will find, so the question is, 'Are they pathogenic or not?’" he said. "Customers are looking for a fast way of interpreting the results."
Most companies that sell arrays for cytogenetics research have invested in data analysis to meet the needs of their customers. Affymetrix, for instance, provides its Chromosome Analysis Suite for customers who use its arrays in cytogenetics research. Illumina sells its KaryoStudio software for use with its HumanCytoSNP-12 BeadChip. Earlier this year, Cambridge, UK-based BlueGnome upgraded its BlueFuse software for cytogenetic analysis (see BAN 3/17/2009).