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CIDR to Offer Whole-Genome Genotyping Services On Illumina Platform as Microsatellite Usage Wanes

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The US Center for Inherited Disease Research said last week that it will now offer genome-wide association services on the Illumina HumanHap300 BeadChip platform, an expansion from the SNP linkage and custom genotyping services it has offered for several years.

CIDR's announcement comes one month after Montreal-based Genizon Biosciences said it will also employ Illumina's HumanHap300 chips in its genome-wide association studies, and according to a variety of sources, the decisions likely foreshadow a mass migration of genotyping services from older technologies, like microsatellite analysis, to microarrays (see BAN 1/17/06).

"I think it's been driven by the science," Jerry Roberts, the executive director of CIDR's board of governors, said of CIDR's decision to offer association services on the Illumina platform.

"The whole idea of the HapMap Project was to get a number of tag SNPs so that one could query populations with roughly 300,000 to 500,000 SNPs to try to correlate the SNP with disease and see if you can hone in on the actual variant that might be contributing to the disease," Roberts told BioArray News last week.

"To do this in most of the populations you need about 500,000 SNPs and it turned out that Affymetrix has such a platform and now Illumina has this platform," he said. "We have done some pilot studies with the Illumina system and have gotten very good data from it."


"I know the technology will be surpassed. Whether it's by Illumina or someone else, I don't know."

For CIDR, genome-wide association studies using arrays are a new thing. The first application deadline for investigators funded by the National Institutes of Health is March 1, although Roberts said that CIDR's services are "open to anyone if they want to use [them], but they will have to pay a higher rate."

But Roberts added that the service will be cheaper when it's done with arrays. A SNP linkage scan using Illumina's platform costs an NIH-funded researcher $138, while a similar scan using microsatellite genotyping on Applied Biosystems' 3730 system costs $192 per scan, Roberts explained.

John Hooper, CEO of Genizon Biosciences, told BioArray News this week that his company made the jump to Illumina's arrays for similar reasons.

In particular, Hooper said that high-density SNP chips, like Illumina's, are well suited for Genizon's association studies of the Quebecois founder population. He said Genizon uses 8 Illumina BeadLabs to perform 65 million genotypes per day.

"We are applying this chip…to conduct whole-genome association studies on eight to 10 common diseases this year. Typically, each disease involves over half a billion genotypes," Hooper explained. He added that Genizon does not currently offer genome-wide association services for other researchers, but that it could, with Illumina's approval.

A third Illumina user that will most likely follow CIDR and Genizon's path is Genome Quebec. According to Daniel Tessier, senior vice president for operations and business development, Genome Quebec is "envisioning offering [genome-wide association analysis] as a service to all Genome Canada-funded projects."

Genome Quebec has offered the Illumina technology for custom genotyping and linkage analysis since last year, but this is its first foray into whole-genome genotyping using an array platform. It has offered microsatellite genotyping for linkage studies since it was founded five years ago.

The Demise of Microsatellite Genotyping?

The decision by organizations like CIDR, Genizon, and Genome Quebec to discard older technology in favor of high-density SNP chips is certainly welcomed by microarray vendors.

"This is very significant for our business, since [we estimate] the genotyping market will experience the fastest growth of any microarray segment over the next two to four years," Illumina spokesman Bill Craumer told BioArray News in an e-mail last week.

Craumer said that Illumina plans to supplement the HumanHap300 chip it rolled out in January with a 230K chip to tide researchers over until its HumanHap500 chip ships in June. Illumina's CEO Jay Flatley announced the new product launches during a conference call discussing the company's fourth-quarter results earlier this month (see BAN 2/7/2006).

Illumina's most direct rival in the whole-genome genotyping market is Affymetrix, which offers its Mapping Array 500K Set for genotyping applications, but both companies present stiff competition for vendors in the microsatellite genotyping market.

Roberts said that CIDR has recently decided to discontinue mouse microsatellite genotyping services because it's "cheaper and faster to do SNP genotyping than to do the microsatellite genotyping."

Roberts said that CIDR will still offer human microsatellite genotyping, but mostly to finish large projects that were started on that platform before the new Illumina and Affy chips hit the market.

Microsatellite genotyping is "no longer cost-effective," said Genizon's Hooper. It also "does not have the resolution that can be achieved with SNPs" and suffers from having "too few microsatellites validated for a whole-genome association study, and inaccuracy in assessing genotype calls."

Those sentiments are not limited to Illumina users. Xiangdong Liu, the scientific director of Toronto's University Health Network Analytical Genetics Center, which offers SNP genotyping on the Affymetrix and Sequenom platforms, said he's not surprised that customers are making the switch.

"Of course, people are using less and less microsatellite genotyping and switching to the newer technology," he said.

Genome Quebec's Tessier said that his center hasn't had one microsatellite customer in the past 12 months. "There are fewer clients than there were before for microsatellite genotyping," Tessier said. "We do have the instruments, know-how, and capacity if people want to go back to using that technology, but we haven't had a [microsatellite] client for about a year," he said.

Roberts said that CIDR has been using Applied Biosystems 3730 systems, and other centers across the country also appear to be using ABI's 3730 system for microsatellite genotyping.

ABI did not return phone calls or e-mails by press time to discuss current demand for its 3730 system for genotyping applications. Still, Tessier said that just because the new high-density SNP chips are in fashion doesn't mean they will continue to dominate.

"I'll bet you that in 18 months something new is going to be around," Tessier said. And although Genome Quebec is a beta-testing site for Illumina technology, Tessier said that his organization will go with the best technology, regardless of the manufacturer.

"I know the technology will be surpassed," Tessier said. "Whether it's by Illumina or someone else, I don't know, but [whatever it is] we will be the first resource to offer it here in Canada and to larger strategic initiatives around the world."

Kim Doheny, the director of CIDR's Genotyping Laboratory, said that the SNP arrays "probably will be replaced with [next-generation] sequencing eventually," but that there is debate on how soon that will be a reality.

"I'm sure it will change again," Doheny said.

— Justin Petrone ([email protected])

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