title: Whole genome sequencing of field isolates provides robust characterization of genetic diversity in Plasmodium vivax.
abstract: BACKGROUND
  An estimated 2.85 billion people live at risk of Plasmodium vivax transmission. In endemic countries vivax malaria causes significant morbidity and its mortality is becoming more widely appreciated, drug-resistant strains are increasing in prevalence, and an increasing number of reports indicate that P. vivax is capable of breaking through the Duffy-negative barrier long considered to confer resistance to blood stage infection. Absence of robust in vitro propagation limits our understanding of fundamental aspects of the parasite's biology, including the determinants of its dormant hypnozoite phase, its virulence and drug susceptibility, and the molecular mechanisms underlying red blood cell invasion.
  
  
  RESULTS
  Here, we report results from whole genome sequencing of five P. vivax isolates obtained from Malagasy and Cambodian patients, and of the monkey-adapted Belem strain. We obtained an average 70-400 X coverage of each genome, resulting in more than 93% of the Sal I reference sequence covered by 20 reads or more. Our study identifies more than 80,000 SNPs distributed throughout the genome which will allow designing association studies and population surveys. Analysis of the genome-wide genetic diversity in P. vivax also reveals considerable allele sharing among isolates from different continents. This observation could be consistent with a high level of gene flow among parasite strains distributed throughout the world.
  
  
  CONCLUSIONS
  Our study shows that it is feasible to perform whole genome sequencing of P. vivax field isolates and rigorously characterize the genetic diversity of this parasite. The catalogue of polymorphisms generated here will enable large-scale genotyping studies and contribute to a better understanding of P. vivax traits such as drug resistance or erythrocyte invasion, partially circumventing the lack of laboratory culture that has hampered vivax research for years.
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
authors.forename: Ernest R
authors.initials: ER
authors.lastname: Chan
authors.forename: Didier
authors.initials: D
authors.lastname: Menard
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
authors.forename: Arsène
authors.initials: A
authors.lastname: Ratsimbasoa
authors.forename: Saorin
authors.initials: S
authors.lastname: Kim
authors.forename: Pheaktra
authors.initials: P
authors.lastname: Chim
authors.forename: Catherine
authors.initials: C
authors.lastname: Do
authors.forename: Benoit
authors.initials: B
authors.lastname: Witkowski
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: David
authors.initials: D
authors.lastname: Serre
mesh_terms: D000293:Adolescent; D002160:Cambodia; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018503:Genome, Protozoan; D006801:Humans; D008270:Madagascar; D016780:Malaria, Vivax / Q000469:parasitology; D008297:Male; D010966:Plasmodium vivax / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D016054:DNA, Protozoan