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Advances in microarray technology speed research

Gene expression, the study of gene activity in cells to understand the genetic causes of disease, is revolutionising drug research and aiding in the treatment of conditions such as cancer and cardiovascular disease.

To help speed such research, Agilent Technologies has announced commercialisation of its whole human genome microarray, which delivers industry-leading sensitivity, reproducibility and quality through an open platform.

Microarrays are small pieces of glass, similar to a microscope slide, with a grid of tens of thousands of microscopic spots, each with a strand of DNA that uniquely matches to a gene. Microarrays are used as a tool in gene expression to identify the activity levels of genes in diseased versus normal cells.

There have been several key barriers to human disease research. Previously, for example, the whole human genome would not fit on one microarray, which required processing at least two slides with cell samples to complete an experiment.

Researchers have access to only small, finite amounts of human cell samples, as in the case of an extracted tumour, which limits the number of experiments that can be done.

The cost of commercial microarrays required researchers to postpone experiments until funds could be raised; alternatively, they created their own ahomebrew' microarrays, which was time-consuming and did not meet increasing scientific standards.

Availability of a whole human genome microarray provides significant research benefits. Working with one microarray, rather than two, lowers experimental cost and streamlines workflow. Higher reproducibility of a single microarray reduces unnecessary variability in experimental conditions.

One microarray requires much less cell sample material to perform an experiment. In addition to the overall benefits of a whole human genome microarray, Agilent's microarrays offer:

* Higher sensitivity, allowing researchers to detect low-expressing, or rare, genes.

* Flexibility to have microarrays custom developed without significant cost.

* The company's special ink-jet printing process directly prints 1-in x 3""-in slide format microarrays, allowing researchers to use the scanners and equipment they already have in their labs rather than requiring significant start-up costs.

With increased sensitivity and lower-cost custom microarrays, Agilent believes it will helps speed drug development and disease research.

Currently worth nearly US$600m, the global market for DNA microarrays is expected to grow at about seven per cent a year until at least 2010. Agilent's competition includes companies such as Affymetrix, Amersham Biosciences, Genomic Solutions, PerkinElmer, Silicon Genetics, Spotfire, Strand Genomics and Rosetta Biosoftware.

Early technology

Affymetrix, for one, has just announced that its new GeneChip mapping 100K array set is now broadly available through an early technology access programme.

This two-microarray set can genotype over 100 000 SNPs and is the first in a family of products that will enable scientists to begin large-scale whole-genome association studies, which up to now have been unaffordable or impractical.

The 100K, which Affymetrix plans to formally launch this summer, is already being used in high-density genome scans and genome-wide association studies of the genetics of complex diseases and drug response. Twelve customers, including pharmaceutical and biotechnology companies and academic researchers, have started experiments under the initial phase of the programme, which is now expanding.

"We were amazed at how quickly we could generate highly accurate genotype calls,“ said Peter Nurnberg, head of the gene mapping centre at the Max Delbruck Centre for Molecular Medicine in Berlin. Nurnberg, who is also coordinator of the National Genotyping Platform of Germany, added: "The 100K is a significant step to allow whole genome association studies. We anticipate the 100K will have a significant impact on our research in the field of complex diseases and beyond.“

In a pharmacogenomic study funded by the US National Heart, Lung and Blood Institute, researchers at the Mayo Clinic are using the 100K to investigate the genetic basis for differential responses to antihypertensive drugs in different patients and populations. By taking a whole-genome association approach to these studies, scientists hope to identify the unknown genes influencing drug-response and to ultimately enable more effective tailoring of antihypertensive therapy in individual patients.

The 100K is the newest member of the Affymetrix DNA analysis product line, which includes comparative sequencing, custom genotyping, and whole genome SNP microarrays. It uses the same GeneChip technology that revolutionised mRNA gene expression analysis, enabling researchers to understand both the function and variation of whole genomes on a single, integrated platform.

The 100K allows researchers to genotype over 100 000 SNPs using just two reactions. Previously, genotyping 100 000 SNPs would have required 100 000 PCR reactions, a hurdle that made this kind of research impractical. Before the advent of 100K, the commercial product for genotyping the most SNPs was Affymetrix' Mapping 10K.

"The power of 100 000 SNPs in a single experiment is enabling researchers to attempt unprecedented genetic studies at a genome-wide scale,“ said Greg Yap, senior marketing director, DNA analysis. "The GeneChip Mapping 100K Set is the first in a family of products that will enable scientists to identify genes associated with disease or drug response across the whole genome instead of just studying previously known SNPs or genes, and to study complex real-world populations instead of simple ones. To do this, we are making large-scale SNP genotyping not only quick and easy, but also affordable ­ about one cent per SNP.“

Just to emphasis how keen the competition is in this sector, Amersham Biosciences ­ now part of GE Healthcare ­ has added the CodeLink human whole genome bioarray to its CodeLink range.

This is the first CodeLink bioarray to offer genome-wide expression profiling of an entire genome and is the result of significant advancements made to the CodeLink platform. This new whole genome bioarray enables researchers to significantly discover more by consolidating genome-wide expression profiling into a single chip microarray experiment and increasing the assay sensitivity.

With 54 841 gene targets, the new CodeLink human whole genome bioarray is claimed to have the highest content of any commercially available human microarray on a single chip. The majority of this content has been functionally validated to ensure each experiment generates the most biologically meaningful results.

It significantly improves productivity by consolidating genome-wide expression profiling into a single microarray experiment. The bioarray has superior sensitivity to other whole genome arrays, consistently detecting transcripts at a level of 1:900 000 (around 0.3 copies per cell). This enables researchers to detect genes expressed at very low levels.

"This new bioarray­ manufactured to established Six-Sigma standards ­ addresses researchers' need to assay whole genomes on one chip with ensured accuracy, reproducibility, and sensitivity,“ said Sam Raha, vice president of CodeLink at Amersham Biosciences.






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