More efficient method to sequence the human genome

Researchers at Baylor College of Medicine have been tabbed to find a more efficient method to sequence the human genome.

The National Human Genome Research Institute, part of the National Institutes of Health, has awarded $37 million in grants to develop innovative technologies that significantly reduce the cost of DNA sequencing.

Among the 11 groups funded in NIH’s near-term goal to sequence a mammalian-size genome for about $100,000 – roughly 100 times less than what is possible today – is a BCM research team led by principal investigator Dr. Michael Metzker, assistant professor of molecular and human genetics at Baylor’s Human Genome Sequencing Center. Seven other groups have been designated to find ways to sequence the human genome for $1,000 or less.

Metzker’s team, which received a three-year, $2 million grant, will focus on sequencing-by-synthesis by creating reversible terminating nucleotides. The study also involves enhancing enzymes called DNA polymerase to incorporate the nucleotides efficiently into strands of DNA. The combination of modified nucleotides and mutant DNA polymerases would be used in this approach to sequence as many as 500,000 reactions simultaneously on a single chip – about one-sixth of the entire human genome.

“We are simplifying the process of whole genome sequencing by hopefully using a single chip with a single device and one researcher,” Metzker said.

Some of the technologies funded by the grant may lead to the public availability of genome sequencing within the next five years, and researchers would also be able to sequence the genomes of hundreds or even thousands of people to identify pathogenic genes. Finding an affordable way to sequence a person’s genome would lead to individualized genetic profiles and personalized medicine. That means the diagnosis and treatment of disorders like cancer, diabetes and heart disease could be tailored to the patient.

“It is a way of making medicine safer and providing the appropriate therapy for individuals,” Metzker said. “Physicians would be able to better prescribe what medicine is going to be best for a particular patient.”

In the long term, Metzker foresees a Phase II of his research, which would involve developing a chip to make it possible to sequence an entire genome at the same time using a highly sensitive fluorescent imager, also under development by Metzker and his colleagues. The BCM team is also collaborating with Texas A&M and Penn State Universities as well as LaserGen, Inc.

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