New DNA sequencing methods put to work

By Nicole Davis, Communications, February 8th, 2008
  • Image by Bang Wong, Broad Institute

While the economy may (or may not) be in a nosedive, the methods available to decode DNA are, without a doubt, in the midst of a major growth spurt. It is arguably one of the most significant metamorphoses to occur in the 20-year history of modern genetic technology.

The frenzy originates from new technologies that read — or “sequence” — DNA faster, better and cheaper than the once predominant technique, the Sanger method. That tried and true way of reading genes reached its heyday with the sequencing of the human genome and that of many other organisms, large and small.

But despite those awesome achievements, some important biological questions have been difficult to approach. These include very complex — and very expensive — questions, such as what are all of the genetic misspellings that appear in different types of human tumors? With the advent of new DNA sequencing methods, answers to questions like these may now be tantalizingly within reach.

One of the latest advancements to appear on the sequencing scene was described by Broad Institute researcher Carsten Russ at the annual Advances in Genome Biology and Technology conference in Marco Island, Florida. Russ presented the work of Andreas Gnirke, Alex Melnikov, and several other colleagues in the Broad Institute’s Genome Sequencing and Analysis Program to apply technology developed by Agilent Technologies to reduce the cost of implementing new DNA sequencing methods in the laboratory.

Indeed, with new techniques for sequencing, it is now cheaper to decode entire genomes. But that cost could be lowered even further if it were possible to sequence only the most relevant parts. For example, a cancer researcher may only be interested in the small cohort of genes that can fuel tumor growth. That cohort amounts to about 10% of all human genes, which themselves comprise just 2% of the genome.

The new Agilent technology enabled Broad researchers to devise an inexpensive, efficient and scalable method to isolate and sequence just the 20,000 or so human genes — or any subset thereof that may be of interest. And in a first head-to-head comparison with the traditional Sanger method, the team was able to correctly identify more genetic misspellings in a sample of tumors, including both known and novel misspellings, at a fraction of the cost.

On the growth chart of DNA sequencing, the work represents a significant milestone — probably just one of many yet to come.