This system, called the “major histocompatibility complex” or MHC, is found in all mammalian immune systems. Although MHC genes are complicated, variable and difficult to read, a good “map” of the genes would help biologists understand why individuals have different responses to viruses.
Variations in the MHC genes could be key to some of medicine’s best-kept secrets: why some rare “non-progressors” do not get AIDS despite long-term infection with HIV, why some people respond poorly to vaccines, and how best to harness the immune response to defeat viruses.
Now, in a study published today (Oct. 11, 2009) in Nature Medicine, a team of researchers at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison have shown a high-speed method for analyzing the stubbornly complex MHC genes in three species of monkeys. “We have an abiding interest in the genes that are involved in immunity to pathogens,” says David O’Connor, the study's senior author and deputy director of the primate center. “People around the world, like other mammals, have encountered pathogens that have shaped the genes that control their immune systems. These genes are highly variable, and have been very difficult to study with conventional methods.”
The new study used “454 parallel sequencing,” which is typically used to create a highly detailed, “deep” genome sequence of individual organisms. The Wisconsin team tweaked this technology. Instead of attaining the greatest detail on a small number of individuals, they sacrificed a bit of accuracy to look at hundreds of samples from macaque monkeys, animals that are widely used in immunology research. They found that each monkey expresses more than two dozen MHC genes, at least four times the number in humans. The genes varied greatly, reflecting each individual’s geographic origin and the history of infection among its ancestors.
The sequencing was performed in collaboration with researchers at the University of Illinois at Urbana-Champaign, and the instrument maker, 454 Life Sciences, a division of Roche. “This study shows the tremendous potential of 454 sequencing to fundamentally change the way we study MHC genetics in human disease research,” says Michael Egholm, chief technology officer and vice president of research and development at 454 Life Sciences.
Because variations in MHC plays such a key role in immunity, the new ability to “read” the structure of MHC genes should improve the efficiency of animal research, says Roger Wiseman, a geneticist and the study’s lead author. “This will allow us to select better groups of animals for vaccine trials, perhaps allowing for fewer animals to be used in each study.”
The high-speed sequencing technology “can be used to look at any highly variable gene in large numbers of samples simultaneously,” adds O’Connor, whose laboratory has started using the technology to study immune responses and drug resistance in HIV/AIDS patients, correlating genetics with different responses to the virus. “We think this will help us understand why some people do much better than others. The global diversity of HIV and the MHC genes of infected people are complex and expensive to study.”
“This idea of looking for drug-resistant mutations has already been applied to single patients,” adds Wiseman, who is also in UW-Madison’s Department of Pathology and Laboratory Medicine. “We can now do this more economically on much larger groups of patients, which would be particularly useful in developing countries, where drug-resistance tests are seldom affordable.” The United Nations just reported that about 4 million people in the developing world are taking anti-retroviral medicines for HIV.
Another application for rapid sequencing could be to screen potential donors for bone-marrow transplants, says Wiseman. “It’s a bit down the road, but this could be used to tissue-type hundreds or thousands of individuals, maybe even an entire donor registry, in one fell swoop, and it could be faster, more thorough and less expensive than conventional techniques. This could produce better treatment outcomes by ensuring better tissue matches.”
Dave Tenenbaum | Newswise Science News
Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology
Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
18.10.2017 | Materials Sciences
18.10.2017 | Physics and Astronomy
18.10.2017 | Physics and Astronomy