New sequencing technologies speed up large sequencing projects—for scientists prepared for a flood of data.

Gail Mandel, an HHMI investigator at the Oregon Health & Science University (OHSU), wanted to understand the role of a particular protein in nerve cell function. She wanted to prove that it was a master regulator for neuronal genes. Using techniques she developed with colleagues at Brookhaven National Laboratory and OHSU, her lab prepared to sequence all the genes in the mouse genome that bound this protein. Before they could determine the extensive sequence of the thousands of DNA nucleotides, they had to prepare numerous pools of DNA, each representing a particular section of the region to be sequenced. The entire process took more than a year.

Meanwhile, another group of researchers at Caltech studying the same protein came up with virtually the same result. “Our data were very similar. But it took them much less time to get more sequence information,” says Mandel.

While her lab's approach relied on traditional sequencing methods that yield a maximum of 96 short stretches of DNA sequence at a time, the other group used the “next-generation” Solexa sequencing platform from Illumina, Inc., which produces tens of millions of DNA sequences in a single run.

Welcome to the new world of warp-speed DNA sequencing.

Researchers agree that Solexa and two competing systems (the Roche (454) GS FLX sequencer and the SOLiD sequencer from Applied Biosystems) represent a breakthrough in sequencing that is speeding the pace of discovery, making it feasible for researchers to conduct experiments once considered too expensive or simply impossible.

In 1975, biochemist Frederick Sanger developed one of the first manual sequencing systems that enabled scientists to determine the order of the nucleotides—known by the letters A, T, C, and G—that make up DNA. The process became automated in the 1980s. In today's version of Sanger sequencing, each type of nucleotide is labeled with a different colored fluorescent tag. DNA fragments differing by only a single nucleotide are separated on the basis of size. Special optics detect the fluorescent nucleotides, creating images that can be “read” as a DNA sequence.

Illustration: Greg Hannon

	PAGE 1 2 3	Continue