University of Arkansas Researcher Part of National Initiative to Reduce Cost of Mapping Human Genome

FAYETTEVILLE, Ark. –Some researchers are calling it the largest biology project ever undertaken by scientists: mapping out the DNA sequence of the human genome. The mapping that once took years is now taking months, but the cost is astronomical — producing a high quality sequence of a mammal-sized genome can cost from $10 to $50 million dollars.

A new $20-million dollar initiative by the National Human Genome Research Institute, part of the National Institutes of Health, aims to reduce that cost to $1,000, which will one day enable sequencing to become part of routine medical care. Physicist Jiali Li has won a three-year, $830,000 grant from the Genome Research Institute to develop a nanopore-based sensing system able to better differentiate the electrical signal differences among DNA bases.

Li, an associate professor in the J. William Fulbright College of Arts and Sciences at the University of Arkansas, will work first on finding an approach that will enable her to sequence a piece of DNA about 1,000 base pairs in length. Her long-term goal is to sequence much longer and more complex DNA molecules.

Her research team includes David McNabb, associate professor of biological sciences, and graduate students Brad Leddon and Edward Graef.

“The ability to comprehensively sequence any person’s genome is the type of quantum leap needed to usher in an age of personalized medicine where health care providers can use an individual’s genetic code to prevent, diagnose and treat diseases,” said Alan Guttmacher, acting director of the National Human Genome Research Institute.

A nanopore is a small pore in an electrically insulating membrane that can be used as a molecular probe. Nanopore sequencing, introduced in the mid-1990s, requires a sensor comparable in size to the DNA molecule itself. The sensor interacts with the individual nucleotides in a DNA chain and distinguishes between them on the basis of chemical, physical or electrical properties.

McNabb will provide various DNA molecules for Li to test as she develops the system. Currently they are generating both double- and single-stranded DNA molecules and plan to begin with relatively short DNA molecules of 1,000 bases in length. They then add a biotin, or water soluble B-complex vitamin, to every base. The resulting DNA molecules are heavier as they pass through the nanopores, thus generating a larger change in the electrical current.

“This bulkiness of certain bases in the DNA should make them more distinguishable during nanopore sequencing,” said McNabb. “The major goal at this stage is to make the electrical sensing technology reliable.”

Li and her research team have built a nanopore fabrication apparatus that can make several nanometer-sized solid state nanopores. Fabricating usually takes a week. Initially they create several hundred and then refine them, a process that takes an hour for each nanopore.

At its most effective, a nanopore sensor system would be able to provide high quality sequence reads, from tens of thousands to millions of bases. The National Human Genome Research Institute anticipates that such readings may take as long as 10 years to achieve.