Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance

• DOI: 10.1101/gr.123430.111
• Publication Date: 2011-10-29T02:10:56Z
• Authors: Tim Downing; Hideo Imamura; Saskia Decuypere; Taane G. Clark; Graham H. Coombs; James A. Cotton; James D. Hilley; Simonne de Doncker; Ilse Maes; Jeremy C. Mottram; Mike A. Quail; Suman Rijal; Mandy Sanders; Gabriele Schönian; Olivia Stark; Shyam Sundar; Manu Vanaerschot; Christiane Hertz-...; Jean-Claude Dujardin; Matthew Berriman
• Keywords: Population Structure

Visceral leishmaniasis is a potentially fatal disease endemic to large parts of Asia and Africa, primarily caused by the protozoan parasite Leishmania donovani . Here, we report high-quality reference genome sequence for strain L. from Nepal, use this study variation in set 16 related clinical lines, isolated visceral patients same region, which also differ their response vitro drug susceptibility. We show that whole-genome data reveals genetic structure within these lines not shown multilocus typing, suggests resistance has emerged multiple times closely lines. Sequence comparisons with other species analysis single-nucleotide diversity our sample showed evidence selection acting range surface- transport-related genes, including genes associated resistance. Against background relative homogeneity, found extensive chromosome copy number between Other forms structural were significantly resistance, notably gene dosage an experimentally verified circular episome present all described here first time. This provides basis more powerful molecular profiling leishmaniasis, providing additional power track epidemiology important human pathogen.