SARS genome sequenced by researchers

While most of the world works to contain the spread of the virus that causes severe acute respiratory syndrome (SARS), the Genome Sequencing Center (GSC) in the School of Medicine has become part of the international effort to understand the microbe.

Elaine Mardis

Researchers at the GSC were called upon to sequence the new virus and poorly understood human pathogen. They completed the task in what is possibly record time — less than a week.

“As genome sequencing goes, that’s very, very fast,” said GSC co-director Elaine Mardis, Ph.D., assistant professor of genetics and of molecular microbiology.

Mardis, who led the effort, used a new technique she and her colleagues developed that speeds the sequencing process.

“The method enables us to quickly identify the genetic makeup of an unknown virus, and that helps determine what can be done to diagnose and prevent the infection,” she said. “The process works whether the virus is a product of bioterrorism or of Mother Nature.”

SARS was identified as a disease in late February. (For a description of SARS and the University’s response to it, see story, Page 6.)

Richard Wilson
Richard Wilson

Researchers quickly suspected that a new human virus was responsible for the disease. When they observed the virus under an electron microscope, it appeared to be a coronavirus, a group of microbes most famous for causing colds. No coronaviruses were then known to cause a serious human disease like SARS.

To help confirm the virus’s identity, the Centers for Disease Control and Prevention sent samples of the microbe to a number of laboratories, including that of Joseph DeRisi, Ph.D., assistant professor of biochemistry and biophysics, at the University of California, San Francisco. DeRisi isolated the genome of the virus and compared it to the genomes of other viruses known to cause human disease using a “virochip” microarray he developed for identifying unknown viruses.

Microarrays enable scientists to compare an experimental genetic sample with thousands of known gene samples simultaneously. DeRisi’s microarray contained genomes from the best-known disease-causing viruses.

DeRisi’s virochip quickly identified the virus as a coronavirus, but one with closer ties to animal coronaviruses than to known human ones.

To learn what made the new virus unique, the genome needed to be sequenced. For this, DeRisi called on Mardis and GSC Director Richard K. Wilson, Ph.D., professor of genetics and associate professor of molecular microbiology.

The new rapid sequencing method Mardis and her GSC colleagues had developed allowed the isolation and sequencing of DNA, which are normally two separate steps in the sequencing process, to occur almost simultaneously.

“We received samples on Friday, we completed the sequencing by Monday, and we sent out the sequence data the following Friday,” Wilson said. “That rate of completion is unheard of.”

Mardis added that “using the viral chip and the new sequencing method together can give us a lot of information about a new virus in less than a week’s time. That’s a very powerful method, compared to commonly used clinical tests.”