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Korean CDC and Macrogen Partner with Roche NimbleGen for CNV-Association Study

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By Justin Petrone

The Korean Centers for Disease Control and Prevention and Macrogen, a Seoul-based genomic tool and service provider, will use Roche NimbleGen arrays in a forthcoming copy number variation-association study, Roche said last week.

Led by researchers at KCDC's Centers for Genome Sciences, the eight-month, two-phase study aims to characterize CNVs in Korean populations and analyze common CNVs for complex disease including diabetes. It is an expansion of the Korean Association Resource project that has used the Affymetrix platform to identify SNPs associated with complex diseases (see BAN 6/12/2007).

According to officials from both Macrogen and Roche, the study is an example of what they see as a growing desire from customers involved in SNP association studies to also look at CNVs across the same populations.

The interest in so-called CNV-association studies has prompted all major array vendors to produce high-density chips with CNV content. Agilent Technologies, for example, has launched two arrays so far this year with a third planned to address the potentially lucrative CNV-association market (see BAN 4/7/2009).

Roche NimbleGen spokesperson Kary Staples told BioArray News this week that the Madison, Wis.-based company "absolutely plans on being an integral part of future large CNV-association studies" like the Korean study.

To that end, NimbleGen plans to launch two catalog CNV-focused arrays this fall, Staples said. The company will offer users the ability to run one sample on a 2.1-million-feature array synthesized on one slide, or three samples on three, 720,000-feature arrays synthesized on one slide. Staples said the formats "will provide the most comprehensive and up-to-date coverage of common and rare CNVs."

Additionally, Staples said the "extremely exciting and fast-paced" CNV-association studies market has been "fueled by high-resolution microarray technologies that have revealed the extent of structural variation in the human genome.

"As more and more CNV data are collected from studies such as the KCDC study … the impact of CNVs on human disease within specific populations and sub-populations will be explored," Staples said. "This market has seen a clear shift away from solely SNP-based research to incorporate the role of CNVs in common complex disease."

Kap-Seok Yang, Macrogen's chief technology officer, told BioArray News that the company anticipates running more CNV studies on the NimbleGen platform after the current project concludes next year.

"Throughout this study we expect to discover a lot of Korean or Asian common CNVs, which will definitely help researchers to interrogate more defined CNVs in their large CNV association studies," he said.

Researchers at the Korean CDC did not return an e-mail seeking comment in time for this article.

Study Design

The first phase of the Korean CNV study will analyze 50 apparently healthy individuals with a set of custom 2.1-million-feature NimbleGen comparative genomic hybridization arrays. The set consists of 42 million probes distributed across the human genome and will enable researchers to detect CNVs down to 500 base-pair resolution, creating a high-resolution map of CNVs in Korean populations, Roche said.

Staples noted that Roche NimbleGen has provided "similar high-resolution designs for other CNV discovery projects," such as one recently completed by the Genome Structural Variation Consortium, which includes researchers from the Wellcome Trust Sanger Institute in Hinxton, UK; Brigham and Women's Hospital in Boston; and the Hospital for Sick Children in Toronto. He added that the custom set used in the Korean study could inform the creation of future catalog arrays for the detection of genome-wide CNVs.

In the second phase of the Korean CDC study, the researchers will focus on the relationship between CNVs and type 2 diabetes mellitus. Samples from 6,000 individuals from Anseong and Ansan, two Korean cities south of Seoul, will be analyzed using the NimbleGen 3x720K CNV version 1.0 Array. This array is one of the two NimbleGen plans to launch in the fall, Staples said.

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Macrogen will perform all sample and data processing using NimbleGen's CGH workflow, which includes sample and array processing kits, software, a hybridization system, microarray dryer, and the NimbleGen MS 200 Microarray Scanner with 2-micron scanning resolution.

In the past, NimbleGen had primarily served its customers via its services arm. The company launched the scanner last month as part of an effort to build out its consumables business. Roche has local and regional sales and technical support specialists who will directly support this project, backed by its R&D group in Madison, Staples said.

Macrogen is not an official NimbleGen distributor or service provider, but has offered NimbleGen arrays as part of its service in the past. Founded in 1997, the company has expanded from offering transgenic mice to offering its own bacterial artificial chromosome-based research chip, the MacArray.

Since then, the company has also debuted MacArray Karyo, which is used by Korean clinicians for identifying chromosomal abnormalities. In 2005, Macrogen opened an American service lab in Rockville, Md. A Japanese subsidiary was established in 2007, and a European office in the Netherlands opened last year.

In addition to its own platform, Macrogen offers SNP-genotyping services on the Illumina platform. It also offers custom arrays on the CombiMatrix system. Recently, Macrogen began offering second-generation sequencing services on the Applied Biosystems SOLiD sequencer, the Illumina Genome Analyzer II, and Roche 454 Life Sciences' GS-FLX Titanium.

Yang said that Macrogen has used NimbleGen arrays in various projects "for a few years but very occasionally" as NimbleGen's offering was "limited mostly for service in their own service labs rather than the delivery of chips and reagents to customers."

Prior to signing on for the Korean CDC project, the company had "most instrumentation needed" for use with its BAC CGH platform service, Yang said. Macrogen's main investments for the new project were the scanner and array dryer, "which are important to achieve high-throughput data processing demanded by this study," he said.

Though this is Macrogen's first CNV association study, Yang said the firm is prepared for such a large project. "We have been doing large-scale studies in the sequencing and SNP genotyping fields" and are "also are performing a lot of CNV chip experiments in the course of our extensive R&D endeavors," he said.

Yang added that Roche NimbleGen and Macrogen will collaborate on data analysis. "Copy number variation is quite a new field [and] the analysis is still very challenging," he said. "We are prepared for the analysis of the high-throughput study through our extensive R&D experience and we are working very closely with many collaborators worldwide," he said. He did not elaborate.

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