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Agilent to Debut New CGH and SNP Arrays to Support Cyto, Cancer Research


By Justin Petrone

Agilent Technologies will soon enable customers to perform SNP genotyping on its arrays in addition to comparative genomic hybridization, BioArray News has learned.

The addition of SNP probes will further enable cytogeneticists using Agilent arrays to detect constitutional abnormalities, and could make the company more competitive against firms like Affymetrix and Illumina that currently sell SNP platforms for cytogenetic research.

Until now, researchers who used Agilent's CGH arrays to detect uniparental disomy or copy-neutral loss of heterozygosity had to rely on SNP chips sold by other vendors to do so.

UPD occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. It is known to cause several genetic disorders, including Prader-Willi, Angelman, and Beckwith Wiedemann syndromes. Copy-neutral LOH is associated in some individuals with a lack of functional tumor-suppressant gene alleles.

Anniek De Witte, CGH product manager in Agilent's Life Sciences Group, told BioArray News last week that the firm's SurePrint G3 CGH microarrays will soon be extended to include a set of SNP probes on the same microarray.

The addition of the new SNP probes "allows for the detection of blocks of copy-neutral LOH or UPD down to 5 megabases without compromising the performance of the CGH probes," she said. De Witte did not provide a hard date for the new product launch, but said that they will appear "in the next couple of weeks."

According to De Witte, Agilent will launch more than one catalog SurePrint CGH+SNP array that will contain probes for approximately 60,000 SNPs. These SNPs will result in between 5 and 10 megabase resolution for LOH/UPD detection across the genome, she said. De Witte did not elaborate on how the catalog arrays will differ from each other.

In addition, Agilent will print customer-designed arrays ordered through its online eArray tool. De Witte said that Agilent will make available the 60,000-SNP probe set in addition to the 28 million CGH probes for the generation of custom SurePrint CGH+SNP arrays.

Agilent believes the availability to perform SNP genotyping to detect LOH and UPD, as well as CGH on one array will give it an advantage in the market.

"The Agilent two-color CGH microarray platform provides superior copy number change detection thanks to Agilent's high-fidelity 60-mer probes synthesized through inkjet printing technology in combination with a straightforward DNA sample processing workflow without amplification steps," De Witte said. "The ability to detect LOH/UPD was the piece that was missing. Now one microarray can detect both."

The SurePrint CGH+SNP arrays are based on Agilent's own IP, according to De Witte. She said that scientists in Agilent Laboratories developed a way to "use the restriction digestion step in the CGH protocol to genotype SNPs located at the enzymes' recognition sites."

After the labeling, hybridization, and scanning, the data are analyzed "using novel algorithms contained within Agilent Genomic Workbench software," she said.

Agilent expects that its new SurePrint G3 CGH+SNP microarrays will not just be used to study UPD related to constitutional abnormalities, but will have application in research areas like cancer. At the same time, De Witte warned that studying LOH in cancer samples will be more challenging, due to tumor heterogeneity, normal clone contamination, and the fact that many cancer samples are only available as formalin-fixed, paraffin-embedded tissue.

Over in Oxford

Agilent partner OGT has developed a proprietary methodology to combine CNV calling and SNP detection on the arrays produced for OGT by Agilent. The Oxford, UK-based company last week launched its CytoSure ISCA UPD 4 x 180K array. It enables researchers to simultaneously detect on one array DNA copy number variation on OGT's International Standard Cytogenomic Array consortium-endorsed 4 x 180K aCGH Array, along with whole-chromosome UPD using SNP probes. OGT began selling its ISCA-designed CytoSure array earlier this year (BAN 2/9/2010).

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James Clough, vice president of clinical and genomic solutions at OGT, told BioArray News this week that the firm launched the new array to meet customer demand.

"We are very much committed to the ISCA array design, which offers standardized content for the cytogenetics community," Clough said. But "when our customers said they would like UPD functionality, it made sense to integrate this into the ISCA design."

He said the company believes its chip will also save customers money. "For those customers wishing to detect both genetic aberrations and UPD, the CytoSure ISCA UPD 4 x 180K array now allows them to do so in a much more cost-effective way," Clough noted.

While manufactured by Agilent, OGT's new arrays have been designed to work with the firm's existing CytoSure CGH protocol and workflows. And although Agilent uses restriction enzymes to measure SNP genotypes on its arrays, OGT employs a different, internally developed method.

"In order to ensure our SNP content provides reliable UPD detection, we undertook multiple rounds of probe selection and validation," Clough said of OGT's approach. The CytoSure ISCA UPD protocol is therefore "virtually identical to standard CytoSure arrays, meaning that this additional UPD functionality can be rapidly and easily integrated into existing workflows."

In addition, OGT incorporated its new UPD detection functionality into its CytoSure Interpret software.

Clough added that when using OGT's new arrays, "the only difference between the standard protocol and the UPD protocol is that a longer hybridization step is required."
He noted that OGT believes the new arrays will give OGT an advantage over rival platforms that lack both SNP-genotyping and CGH capabilities.

"The CytoSure ISCA UPD array combines the acknowledged benefits of long oligo-based aCGH for detecting DNA aberrations, such as better signal-to-noise ratios, with clinically relevant SNP coverage for detecting UPD," Clough said. "This increased functionality enables identification of a broader range of genetic syndromes in a single array experiment, without any additional investment in equipment or training."