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Agilent Adds WTCCC-Designed CNV Chip to Menu to Target Association Studies


Agilent Technologies will next week introduce the second catalog array in its growing menu of copy number variation-themed chips — an effort to reach customers who are interested in surveying CNVs in genome-wide association studies, a burgeoning subset of the GWAS market that Agilent describes as a "moving target."

The new Human CNV Association 2x105K microarray is designed for studying associations between genomic CNVs and disease. It follows the company's launch last month of the 2x400K CNV array, which was designed to cover known CNV regions from the Database of Genomic Variants.

The new array is based on a design by the Wellcome Trust Case Control Consortium, which is currently conducting a study of CNVs and their relationships to a number of widespread disorders, including Crohn’s disease, tuberculosis, diabetes, and bipolar disorder.

The new chip is configured with two microarrays per slide, with each array containing 105,000 probes. The firm claims that, compared to existing arrays on the market, the design of this array will enable more calls with fewer data points because of targeted content in "high-confidence" CNV regions.

Last August, the WTCCC selected Agilent to manufacture CNV microarrays for the second phase of its study to identify genetic variants influencing disease susceptibility in a variety of rare and common diseases. Using CNV data from the WT-hosted Genome Structural Variation Consortium plus content that overlaps with the content of the Affymetrix SNP 6.0 array, the WTCCC identified a set of 11,000 disease-related loci that it used for the new Agilent arrays. To date, WTCCC has run 20,000 samples on the new arrays (see BAN 8/5/2008).

By launching this chip, Agilent is making the WTCCC design available to anybody who wants to run it. "A lot of groups are tied into what the WTCCC is doing," said Dione Bailey, Agilent’s CGH and CNV array product manager. Bailey told BioArray News last week that customers have requested access to the WTCCC array for use in similar association studies.

"It is a targeted design in that the WTCCC did upfront screening to select regions in the population that they were interested in and focused on these sets in these diseases," she said. "These are common diseases that people are looking at for SNP association studies and CNV association studies."

The Wellcome Trust’s Matthew Hurles said in a statement that the WTCCC has used the Agilent 2x105K design for "characterizing common structural variants in several different disease cohorts over the last several months," and that the group’s "preliminary estimate is that approximately 20 to 30 percent of the loci on the array are both polymorphic in our British-population study and provide sufficient data quality to assign integer copy numbers to individuals."

Hurles did not respond to an e-mail seeking comment.

'Moving Target'

Agilent debuted the first of its CNV-themed arrays together with the roll-out of its new million-feature SurePrint G3 array format last month. That first chip, called the 2x400K CNV array, was designed to cover the known CNV regions from the Database of Genomic Variants, hosted by the Center of Applied Genomics at Toronto's Hospital for Sick Children.

Agilent claims the 2x400 CNV chip provides high-density coverage of coding and non-coding regions, emphasizing known genes, promoters, miRNAs, CNVs, disease regions, pseudoautosomal and telomeric regions (see BAN 3/3/2009).

Bailey said that the 2x105K is a "more focused design that has been tested on a large number of samples," compared to the 2x400K, which the company sees as a "comprehensive design" against the content of the database. "This design focuses on common CNVs, which tend to genotype better, so you can look at data and do clustering of copy number state if you have a common CNV," Bailey said.

Part of the reason for launching multiple CNV catalog arrays is that Agilent believes it is difficult to create one product that would meet the needs of all researchers surveying copy number variation. "The CNV market is such a moving target these days that it is difficult to select a set that would be valuable for every study and every circumstance," Bailey said. "This [chip] gives you a set of CNVs that have been tested so that they are a good set to start with."

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So far, Agilent has not launched the kinds of high-density SNP genotyping arrays that are sold by rivals like Affymetrix and Illumina and which dominate GWA studies today. The launch of the new CNV catalog arrays allows Agilent to move into that market on the back of an interest in looking at CNVs as well as SNPs across a population.

According to Bailey, Agilent is watching early studies, like those performed by the WTCCC, to see how those findings impact demand for surveying CNVs in other association studies. "CNV association studies are an extension of the SNP association market," Bailey said. "Certainly, people will be doing SNP association studies. But if you expand that into CNVs, what is the additional info you learn? That is still an unknown," she said. "In the study the WTCCC just completed, they are in data crunch mode. We are interested in the outcome of that study and it will have an impact on how well this is adopted."

In the meantime, the firm is preparing to launch a third catalog CNV chip. While the 2x105K chip includes CNVs identified in previous studies, and the 2x400K is everything in the Database of Genomic Variants, the next array will be a million-feature chip that will include probes evenly tiled across the genome. "This array will give more evenly spaced, high-resolution content looking at regions not covered on these first two arrays," Bailey said. "The content is unbiased and is not selected for a specific set of CNVs or against a database," she said. The million-feature CNV chip will be launched within the next few months, she added.

It is unclear how exactly Agilent’s products will compete against arrays sold by its competitors. Most large array companies offer chips for researchers interested in looking at CNVs. One of Illumina's best selling products, for example, is its HumanCNV370-Duo DNA Analysis BeadChip. Affymetrix serves the market with its 1.8-million feature SNP 6.0 array, which contains 946,000 probes for the detection of CNVs. Roche NimbleGen sells 2.1-million probe CGH arrays, which are also available in 3 x 720K and 12 x 135K formats.

Any one of these firms could debut similar products in the coming months to compete against Agilent’s offering. Affy, for example, is preparing to launch new genotyping assays on its GeneTitan platform in the third quarter that are likely to contain new CNV content (see BAN 1/20/2009).

eArray and Bioinformatics Support

One reason that Agilent is keen on developing a market for CNV arrays is because the company’s SurePrint inkjet array fabrication capabilities allow it to quickly generate new catalog arrays, depending on demand, Bailey said.

Another facet of this capability is Agilent’s web-based eArray design tool. Bailey said that the content from Agilent’s CNV catalog chips will be uploaded to eArray so that customers can build custom designs based on the catalog formats.

Agilent is also upgrading its bioinformatics support for dealing with the arrays, specifically within its DNA Analytics software. At the same time, the company is looking to work with third parties to enable use of its chips in genome-wide association studies.

"In terms of doing real genotyping or association, it is in the pipeline and we are working on it," Bailey said. "We are also working with third-party partners," she said. "There are going to be a few options available that customers can do in the short term for analyzing these arrays."

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