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Genome sequencing of Leishmania donovani clinical lines reveals dynamic phylogenetic variation

Downing, T (Wellcome Trust Sanger Institute)
Wednesday 22 June 2011, 10:00-10:20

Seminar Room 1, Newton Institute


Leishmaniases are a range of debilitating neglected parasitic illnesses that have several forms: cutaneous, mucocutaneous and most potently, the visceral, which has a global incidence of approximately half a million cases per year. Consequently, a range of early-detection and treatment programs are implemented to limit the spread of the disease, but these are forced to combat the emergence of drug resistance in patients. The causative agent of visceral leishmanisis, the species of the Leishmania donovani complex, is found most frequently in equatorial regions and has a range from southern Europe to Africa to southern Asia. This presentation focuses on distinct regions of India and Nepal where the pathogen displays extensive variation in its response to the drugs most commonly used in treatment. Despite a low level of genetic diversity, clinical samples of these parasites manifest pronounced differences in phenotype. We sequenced, assembled and annotated the genome sequence fo r L. donovani, and used this as a basis for exploring variation in 17 samples cloned from patients with varying treatment outcomes. Many layers of diversity between these genome-sequenced strains were evident at the level of single DNA nucleotides, repetitive gene copies, whole chromosome duplications and extra-chromosomal fragments. By combining this population-level picture with the other sequenced Leishmania species genomes, candidate variants relevant to drug resistance were identified. This study provides evidence of the power and scope of genome-level surveillance of emergent drug resistance in pathogens.


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