New Genetic Analyzer Enhances Research Capabilities
Wake Forest School of Medicine recently acquired one of the most advanced DNA sequencing machines. It promises to .
"We had been outsourcing some of our sequencing, but it was time to buy our own machine," explained Gregory A. Hawkins, PhD, associate professor of Genomics and Personalized Medicine. "It was taking a long time to get the analyses returned to us because of backlogs. The demand for these next-generation machines is incredible."
Up to 50 investigators will benefit from the machine over the coming year, Hawkins estimated. It will aid ongoing studies into how genes influence diabetes, cancer and asthma and can compare the genomes of family members to see how they pass on disease-causing mutations. It can search for rare variants, mutations that may exist in only one person. Hawkins said researchers on the Physics faculty at the Reynolda campus also want to use the sequencer for a study.
"These days, to win National Institutes of Health research funding, it helps to be able to show that you have this technology on-site," Hawkins noted. "It helps them know that you understand the technology and also that you have the capacity to generate data in a timely fashion."
A look inside
The Applied Biosystems 5500xl Genetic Analyzer, about 4-feet wide with two glass doors across the front, looks a bit like a commercial oven. Inside, the resemblance ends. On the right, there is a flat-panel monitor and keyboard to operate the machine. Under the monitor, a platform holds two glass plates, each about the size of an index card, for DNA samples. Each plate has six stripes, or "lanes," allowing the machine to process multiple samples simultaneously. On the left side, a lattice of small reservoirs, like a painter's pallet, hold chemical solutions called reagents that are used in the DNA sequencing reaction. A syringe-tipped robotic arm dips into the wells, ingesting reagents and dispensing them precisely onto the glass plates holding the DNA samples. The process repeats many times.
"Some of the runs can last eight to 12 days," Hawkins said. "Most of that time the DNA sequencing reactions are occurring."
How it works
Sequencing DNA is the process of identifying pairs of nitrogen-based molecules that make up genes. Four types of molecules, labeled C, G, A and T, form these "base pairs," which can be visualized as the rungs of a ladder that has been twisted like a spiral staircase-the familiar DNA double helix. Reagents split the rungs in two and cause reactions that identify each molecule by glowing in one of four colors. An extremely powerful optical lens and digital camera record these fluorescent bursts of color, and a graphical processing computer maps each reaction to establish the sequence of molecules that make each person's genetic code unique.
Hawkins, who joined the faculty in 2000, began sequencing DNA in 1984. He has seen the technology advance from the days of "brute force," with each step done by hand, to high-tech, automated instruments that analyze billions of reactions at once-making it possible to sequence a person's entire genome, which contains about 3.2 billion base pairs.
"Basically, what was done in 10 to 15 years, we now can do in a week," he noted.