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Whitehead Researchers Develop Method for Parallel SNP Genotyping

NEW YORK, Oct 17 – Eric Lander, director of the Whitehead Institute/MIT Center for Genome Research, has developed a method that can genotype hundreds of different SNPs simultaneously.

“Current genotyping methods are suitable for studying individual loci or at most a handful at a time,” Lander and his colleagues said in a paper published in the Oct. 24 issue of the Proceedings of the National Academy of Science , describing their new multiplexed method of SNP genotyping.

Many diseases, however, are not simply related to a single nucleotide change, but to a complex combination of polymorphisms.

And to fully exploit the public databases brimming with polymorphisms—more than 200,000 SNPs are currently in the public domain, thanks to the SNP consortium, and more than 1 million are expected within a year—requires a technology that can inexpensively genotype hundreds, or even thousands, of SNPs in parallel.

Lander’s method, called SBE-TAGS (single base extension–tag array on glass slides), uses arrays that can be made by simply placing unmodified olignucleotides on a glass slide with ordinary spotting equipment.

In the SBE-TAGS method, SNPs are identified by single base extensions. Bifunctional primers carry a unique sequence tag with a locus-specific sequence. And because each locus has a unique tag, the genotyping can be done in parallel. The resulting products are then hybridized to the reverse complements of the tags arrayed on a glass slide.

Unlike a related but pricey Affymetrix genotyping approach, the SBE-TAGS arrays cost only about $2 to produce and require no special equipment for processing.

The Whitehead researchers reported genotyping over 100 SNPs, and obtained over 5,000 genotypes, with 99 percent accuracy.

“Because of its accuracy, ease, and potential for high throughput, SBE-TAGS should facilitate genetic studies that previously required a very substantial commitment of resources,” the researchers said.