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SUMMARY:Genome sequencing of Leishmania donovani clinical lines reveals dy
 namic phylogenetic variation - Downing\, T (Wellcome Trust Sanger Institut
 e)
DTSTART:20110622T090000Z
DTEND:20110622T092000Z
UID:TALK31826@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Leishmaniases are a range of debilitating neglected parasitic 
 illnesses that have several forms: cutaneous\, mucocutaneous and most pote
 ntly\, the visceral\, which has a global incidence of approximately half a
  million cases per year. Consequently\, a range of early-detection and tre
 atment programs are implemented to limit the spread of the disease\, but t
 hese are forced to combat the emergence of drug resistance in patients. Th
 e 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 presentatio
 n focuses on distinct regions of India and Nepal where the pathogen displa
 ys 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 patient
 s with varying treatment outcomes. Many layers of diversity between these 
 genome-sequenced strains were evident at the level of single DNA nucleotid
 es\, repetitive gene copies\, whole chromosome duplications and extra-chro
 mosomal fragments. By combining this population-level picture with the oth
 er sequenced Leishmania species genomes\, candidate variants relevant to d
 rug resistance were identified. This study provides evidence of the power 
 and scope of genome-level surveillance of emergent drug resistance in path
 ogens.\n
LOCATION:Seminar Room 1\, Newton Institute
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