Microarray density continues to climb. In the past year, several companies have compressed the entire protein-coding portion of the human genome onto a single chip – that's some 30,000 to 40,000 unique gene sequences per slide. One company has reduced its arrays to the size of microtiter-plate wells, for use in high-throughput biochip analysis. And arrays to genotype 100,000 single nucleotide polymorphisms (SNPs) at once have also come to market.
"In the next few months, you're going to see more and more people doing experiments where they're interrogating the whole human genome in one experiment," predicts Gary Hardiman, director of the Biomedical Genomics Microarray Facility at the University of California, San Diego. Hardiman says human whole-genome experiments will be most useful for researchers trying to identify new biological pathways rather than for those looking in depth at smaller gene sets.
RACE TO A SINGLE CHIP
According to Mark Schena, who...
TO THE TRANSCRIPTOME
"Getting the entire genome expression assay on a single chip has been a significant advancement," says Greg Yap, senior marketing director for DNA analysis at Affymetrix. Yet he notes that many scientists don't want to limit their studies to protein-coding genes, which account for just 2% of transcription; they want to view transcription genome-wide. "Everyone has heaved a sigh of relief that the whole human-genome expression arrays were available, but those are really gene-expression arrays, and what we have to look at is genome expression, the transcriptome," says Yap. "It turns out that much more of the genome is transcribed than was originally predicted through the standard bioinformatic methods," he adds.
Affymetrix researchers are currently using a specialized GeneChip microarray to "tile" millions of DNA probes representative of the complete human genome. The company recently published data that identifies transcription factor-binding sites across human chromosomes 21 and 22.2
Advances have also been made in SNP analysis. SNPs represent the most common source of genetic variation, and the human genome is thought to contain over 10 million of them, about one every 300 bases. Working through that many markers is practically impossible without a shortcut.
In April, Affymetrix announced the early-access availability of its GeneChip Mapping 100K Array Set, a two-chip product slated for summer release. "This assay, for the first time, is enabling customers to try studies that they have always wanted to do but have never had the technologies to be able to do before," says Yap. "It was just not economical to look at hundreds of thousands of SNPs with existing technologies. Our 100K product will help get these experiments going," he adds. Illumina is also planning to release a 100,000-SNP chip for beta testing by year's end.
In putting the whole human genome onto a single chip, the microarray industry has overcome a large hurdle. But if current trends continue, chip density will increase, costs will decrease, and data analysis will grow ever more complicated (see p. 44).
Meanwhile, the technology continues to evolve. In January the European Union's Sixth Framework Programme initiated the MolTools project. A consortium of 18 academic and biotech concerns, the project aims "to develop more powerful array-based research tools to examine DNA, RNA, and proteins." MolTools will receive €9 million over three years from the European Union.
"We are seeing a maturation of the market, with various commercially available systems becoming more compatible, and the increased availability of methods that allow more standardized self-spotting," notes Brian Ayling, director and product manager of gene expression at GE Healthcare. "What you saw in the beginning was a plethora of companies wading into this very exciting market. Those who didn't cut it, made an exit, and this has made the industry stronger," he says.
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