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Microarray Industry Appears Ready To Race to SNP High-Density Finish Line

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“To perform good [disease] association studies, you need about 200,000 to 500,000 SNPs,” Susan Eddins, Illumina’s global marketing manager told BioArray News.

Illumina last week didn’t hit that metric with the introduction of a new product, but it will have a single chip that will contain probes and an assay for 100,000 SNPs — the SNP genotyping BeadChip. The chip will be available for beta-testing by year-end, the company said.

Packing SNP probes en masse on a single microarray seems to be shaping up to be next the technical challenge to overcome, the next milestone along the way for this maturing industry, which last year raced to manufacture and sell the whole human genome arrayed on one chip.

Just a little over a year ago, the final sequence of the human genome was released, and the microarray manufacturing companies raced each other to spot its transcripts on single-chip products.

Scientists went from having no single-chip choices to today having at least a half dozen different providers of these products in volume. But, along the way, scientists began asking for more return on their investments in gene-expression profiling platforms and other biochips (see BAN 3/10/2004).

Faster than you can say “seeking alternate revenue streams,” the microarray industry has donned running shoes to sprint to this goal. Affymetrix in early April announced the early-access availability of the GeneChip Mapping 100K Array Set, a two-chip product the company said would be commercially available “in the summer.”

Illumina, a relative newcomer to the gene-expression analysis microarray market (See BAN 1/21/2004, but not the genotyping arena, reached back to its core competency for the new product offering.

Eddins, appointed head of worldwide marketing at the company 18 months ago from her post as director of genomic assays at Applied Biosystems, told BioArray News that getting 500,000 SNPs on a single chip is a holy-grail type of goal. For the moment, the company is ready to launch the initial product from an R&D project that was first conceptualized in 2001 and went into development at the end of 2003.

The product, however, hinges on having a good field from which to select 100,000 SNPs to array.

The International HapMap collaboration of scientists in Japan, the UK, Canada, China, Nigeria, and the US, which started at about the same time that Eddins went to work for Illumina, is expected to approach somewhat of a critical mass of data somewhere near the end of 2005 (see Pharmacogenomics Reporter 2/12/2004).

At some point along the way, the HapMap research should sniff out certain SNP sets associated with disease. Illumina is looking to complement that data with density. Illumina said it would create SNP products for analyzing haplotype tag SNPs once the International HapMap Project, for which Illumina is both a contributor and technology supplier, defines them.

“Our initial thrust is to get out a chip with as many SNPs as possible packed onto it,” said Eddins.

The SNP product is built on the Sentrix BeadChip platform, which is the company’s 1 by 3-inch oligonucleotide-bead technology microarray format.

The SNP genotyping BeadChip will contain over 200,000 sequence-specific bead types (each locus requires two allele-specific probe sequences), with greater than 30 times average redundancy of each bead, or feature.

The chip will have 12 stripes containing a total of 10 million features. Each of the stripes contain thousands of wells, with each holding a 3-micron bead coated with DNA probes 25 base pairs long. The wells are situated six microns (center to center) from their neighbors.

The company manufactures microarrays by flooding chips with beads that self-assemble into the microwells etched into an array substrate. A subsequent electronic decoding process identifies which bead type occupies each microwell, creating a digital map that is used in downstream analysis and operates as a quality-control metric for each bead in each array. If a bead doesn’t exhibit sufficient intensity, it is excluded from the map, according to the company.

The beta-testing process usually lasts for three months to six months, depending on how testing progresses, said Eddins. “A 100,000 SNPs is a fairly complex thing. We want to analyze the data to make sure what you got out is valid and useful,” she said.

Along with the SNPs, the company is offering a new GoldenGate assay.

“With the HapMap content coming along, there has to be a way to offer that to people in an economic way,” said Eddins.

Illumina’s new GoldenGate assay protocol used for this application features single-tube sample preparation and does not require PCR or ligation steps as the assay begins with genomic data, rather than amplified pieces.

The company declined to provide details of its new assay, saying it has a commitment to provide information on the new assay at “The Biology of the Genomes,” conference May 12-16 at Cold Spring Harbor Laboratory in New York. Kevin Gunderson of Illumina will make the presentation..

—MOK

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