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Helping Patients Through Genomics

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Dongliang Ge
Title: Assistant Research Professor, Duke Institute for Genome Sciences & Policy
Education: PhD, Peking Union Medical College and Chinese Academy of Medical
Sciences, 2004
Recommended by: David Goldstein

To help patients. That's the ultimate goal of Dongliang Ge's research into genetic influences on complex human diseases. "I really want to know how to address the genetic background in each different individual to figure out why people are so different in disease susceptibility, and why people are so different in response to medication or treatment," Ge says.

Along with his postdoc mentor, David Goldstein, Ge is trying to determine what makes some hepatitis C patients respond well to standard treatment while others don't. People who respond can be cured of hepatitis C, Ge says, but the others must contend with a chronic disease. Through a genome-wide association study, Ge and Goldstein found a polymorphism associated with a two-fold change in treatment response.

Ge is also working closely with Goldstein to study why some people appear to be resistant to HIV infection. In the 1980s, before blood donors were screened for HIV, most people with hemophilia were exposed to the virus when they received blood transfusions. However, Ge says, about 20 percent of those patients "literally cannot be infected with the HIV virus." Ge and his colleagues are now applying whole genome sequencing to figure out why. They plan to sequence the genomes of 50 hemophilia individuals who appear resistant to HIV infection.

As he strikes out on his own at Duke, Ge is interested in developing software packages to detect these genetic contributions to human diseases. When looking through sequencing data, he says there are a lot of questions to answer for each SNP: does it cause a premature stop? A frame shift? Does it disrupt the normal gene function? "Now, to answer that question may not be so difficult when you look at them individually, just browsing NCBI Genome Browser or [another] genome browser, but it is if you look at millions," Ge says. He developed a package called the Sequence Variant Analyzer that allows users to annotate variations uncovered through whole genome sequencing and compare them to control genomes.

A challenge, though, in detecting those genetic contributions to complex human disease is that much of the data is walled up in different databases. "There are fantastic databases which are hosting data, but [it's] not necessarily true that these kinds of different databases are very well integrated," Ge says. That's another issue that he is addressing in his work.

Looking ahead

In the next few years, Ge hopes that the "mystery of HIV resistance" will be unraveled. "I think that will be very helpful in finally defeating HIV infection, which has been my goal for many years," he says.

Publications of note

An article in September's issue of Nature describes Ge's work on hepatitis C. In it, he and his colleague report that a polymorphism near the IL28B gene, which encodes interferon-l-3, is associated with a two-fold change in response to treatment for hepatitis C. The authors also note that this genotype is more common in people of European ancestry and could explain, at least partly, the differences in treatment response rates seen between people of African and European ancestries.

This paper, Ge says, shows that his goal of having his work directly affect patients is attainable. "The clinician is able to more confidently tell the patient whether he or she could benefit from the standard treatment by just looking at the genetic makeup of this patient and help him or her make a decision whether they should choose this kind of treatment," he says.

And the Nobel goes to...

If Ge were to fly to Stockholm, he hopes it would be for finding "a way to practically alter, modify, [or]change the human genome to fight infectious disease."

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