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Tip
Sheet: Medical Science & Health Tip sheets highlight timely news and events at Washington University in St. Louis. For more information on any of the stories below or for assistance in arranging interviews, please see the contact information listed with each story. For comments on the Medical Science & Health news tips service, please contact the editor, Jim Dryden at (314) 286-0110 or drydenj@msnotes.wustl.edu. Only a few genes determine parasite's ability to cause disease Media assistance: Jim Dryden - (314) 286-0110 Source: L. David Sibley's Web page Related: Outlook Magazine article: The New Microbiology Related: Full article: Identification of quantitative trait loci controlling acute virulence in Toxoplasma gondii
The study suggests that the ability of the pathogen to cause disease -- its virulence -- i s controlled mainly by one or a few genes, rather than by hundreds or thousands of genes, which many researchers suspected would be the case. "It was really good news to learn that one gene is largely responsible," says lead investigator L. David Sibley, associate professor of molecular microbiology. "Having only one or a few genes involved in virulence may make it less complicated to develop new drugs to control this infection." Sibley and a team of researchers led primarily by postdoctoral fellow Chunlei Su, found that a short region on chromosome 7 is responsible for about 50 percent of the organism's virulence, and a small region of chromosome 4 is responsible for about 10 percent of virulence. Identifying the remaining 40 percent will require further research. People may become infected with T. gondii by ingesting contaminated food or water or accidentally inhaling or ingesting soil, for example during gardening. More commonly, infections are acquired by contact with cat feces or eating raw or undercooked meat, especially pork, lamb or venison. Toxoplasmosis causes flu-like symptoms, but severe disease can damage the eye and brain. Infants infected by their mother before birth can be born with mental and physical problems.
"Infection by just one organism from the so-called virulent strain kills a mouse in ten days," says Sibley. "We wanted to know what made those strains different." The investigators used an approach known as linkage analysis, a long-favored technique for studying animal and plant genetics but rarely applied to parasites. "It's a conventional tool that we applied in an unconventional way," says Sibley. Linkage analysis couples a physical trait of an organism to an area on one of the organism's chromosomes. The trait in this case was the parasite's ability to cause illness or death in mice. To help them link the trait to the chromosomes, the researchers used 75 known DNA markers scattered across the parasite's 11 chromosomes. DNA markers are physical landmarks in an organism's genome that are identified in the course of genetic research on the organism. By crossing a highly virulent strain of T. gondii with a less virulent strain, the researchers developed parasites showing a range of virulence. Some caused only very mild illness in mice, and some were deadly. With the help of powerful statistical methods, the investigators analyzed the various strains and carefully matched which DNA markers were consistently present in the most virulent strains. This first showed that chromosomes 7 and 4 carried the virulence genes, and then enabled them to pin-point the region on each chromosome where the genes are located. The researchers now are working to identify the genes themselves by studying the uncompleted map of the T. gondii genome and by sequencing the DNA in the still-unmapped areas of the region. Mapping of the parasite's entire genome is in-progress, and the work of Sibley and his colleagues will add to the effort by determining which regions of the genome are important for virulence. The findings are published in the Aug. 6 issue of the Proceedings of the National Academy of Sciences. |
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