Grant to develop high speed DNA sequence reader

Nov 1 2004

Sequencing of the human genome is one of the major scientific advances of our time. But with 3 billion base pairs, initial sequencing of the human genome took 11 years and cost $1 billion to complete in 2002. Today, it costs up to $50 million to sequence 3 billion base pairs.

That may soon change as the National Human Genome Research Institute of the National Institutes of Health, awarded a $1.7 million grant to a team of researchers led by Peter Williams, professor of chemistry and biochemistry at Arizona State University.

The grant, one of two awarded to ASU in this program, is part of a round of NIH funding totaling $38 million going to several research teams to spur the development of innovative techniques to dramatically reduce the cost of DNA sequencing, a move aimed at broadening the application of genome information in medical research and health care.

Goal of the three-year ASU grant is to develop a system that can read DNA sequence up to one thousand times faster and costing only a hundredth as much as current methods. If successful, Williams said the project could lead to relatively cheap machines that can read the genome for use in research, and it could possibly bring the technology to the brink of clinical use.

Williams will be working with Sergei Aksyonov, Ian Gould and Mark Hayes of ASU; Mike Bittner of Translational Genomics Research Institute, Phoenix; Linda Reha-Krantz of the University of Alberta, Edmonton, Canada; and Linda Bloom of the University of Florida, Gainesville.

NHGRI’s near term goal (of which Williams grant is part) is to lower the cost of sequencing a mammalian sized genome (human, chimpanzee, cow or dog, for example) to $100,000. It would enable researchers to compare different species with humans and sequence the complete genomes of hundreds or thousands of people as part of studies to identify genes that contribute to cancer, diabetes and other common diseases.

The ASU team is utilizing part of the machinery of a human cell, which can read out the entire genome and make an exact complimentary copy of human DNA in about 24 hours. The team plans to use the DNA polymerase enzyme, which Williams calls, “a magic little molecule” that reads DNA sequence quickly and accurately, making an exact copy of the DNA sequence as it reads.

“We have a way to look over the enzyme’s shoulder as it does its job,” Williams said. “We are going to use this little biomechanical marvel to report back on sequences.”

The technique’s high speed and low cost come from the idea of multiplexing, reading tens of thousands of DNA base pairs simultaneously.

When completed, Williams group plans to capture up to 20,000 human genes on a glass slide and to read out all of their sequences simultaneously, greatly speeding up the process and dramatically lowering the costs. A single slide could provide sequence data about 10 times more rapidly than today’s large sequencing centers for about a hundredth of the cost.

NHGRI’s long-term goal is to cut the cost of whole genome sequencing to $1,000 or less, which would enable the sequencing of individual genomes as part of medical care. The ASU researchers said that by focusing on the relatively tiny fraction of human DNA that comprises the individual genes, a single sequencing slide could read out all of the information for genes now known to play a role in hereditary human diseases and diseases such as cancer that arise from damage to genetic material, also for about $1,000.

The ability to sequence each person’s genome could give rise to more individualized strategies for diagnosing, treating and preventing disease. Such information would enable doctors to tailor therapies to each person’s genetic profile.

“It would usher in the era of molecular medicine,” Williams said.