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Leishmania Case

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Researchers at the University of Glasgow have uncovered new information towards understanding the parasite which causes leishmaniasis. Leishmania is a flesh eating disesase carried through the bite of female sand flies which affects the white blood cells and is usually treated with chemotherapy. The project was led by researchers at The Wellcome Trust Centre for Molecular Parasitology at the University of Glagsow and was aimed at further understanding what the World Health Organization is calling a neglected tropical disease which currently affects 12 million people worldwide.

The researchers analyzed the genomes of the parasite to find a surprising level of variation. First, they took a sample of L. donovani from an infected patient in Nepal and used it to generate a genome. 16 other patients with Leishmania, displaying different responses to anitbiotics, were also examined using the first sample as a reference. In the second study, the team produced a reference genome for L. mexicana from a sample taken in Guatemala and comparing it with existing reference genomes for various Leishmania species on the spectrum of cutaneous to visceral disease.

The results of these two experiments have led to a much deeper knowledge of Leishmania: its genome structure and drug resistance. The DNA sequence of individual strains of each species populations is almost completely identical. This most likely means that only a small number of genes causes symptoms of the infection. Also, the parasite's evolutionary development and success may be driven by a genetic abnormality leading to multiple copies of chromosomes known as copy number variation. One example is chromosome 31, which is present in almost all Leishmania genomes in more than the standard two copies. This occurrence would be fatal to most organisms but appears to be beneficial to Leishmania, allowing it to cause disease and resist antibiotics. After studying 4 different isolates of the parasite, the research team discovered that each of the Leishmania species that have been fully sequenced has roughly 8,000 genes, yet L. mexicana has only two genes that are unique to it. "This variation in the copy numbers of chromosomes and genes provides a new dimension to monitoring the evolution of drug resistance in these parasites," says Tim Downing from Sanger Institute.

The investigation of Leishmania at University of Glagsow has been a big step towards treating the disease. It has greatly enhanced the genomic understanding of the species and provided clues to explaining its drug resistance. "This basic biological difference in the way that drug resistance emerges in Leishmania is essential for tracking strains and resistance. We can't simply look for the single-letter changes, but must include structural changes. We have to search differently, more smartly," says Jean-Claude Dujardin, senior author from the Institute of Tropical Medicine in Antwerp. There



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