title: Plasmodium copy number variation scan: gene copy numbers evaluation in haploid genomes.
abstract: BACKGROUND
  In eukaryotic genomes, deletion or amplification rates have been estimated to be a thousand more frequent than single nucleotide variation. In Plasmodium falciparum, relatively few transcription factors have been identified, and the regulation of transcription is seemingly largely influenced by gene amplification events. Thus copy number variation (CNV) is a major mechanism enabling parasite genomes to adapt to new environmental changes.
  
  
  METHODS
  Currently, the detection of CNVs is based on quantitative PCR (qPCR), which is significantly limited by the relatively small number of genes that can be analysed at any one time. Technological advances that facilitate whole-genome sequencing, such as next generation sequencing (NGS) enable deeper analyses of the genomic variation to be performed. Because the characteristics of Plasmodium CNVs need special consideration in algorithms and strategies for which classical CNV detection programs are not suited a dedicated algorithm to detect CNVs across the entire exome of P. falciparum was developed. This algorithm is based on a custom read depth strategy through NGS data and called PlasmoCNVScan.
  
  
  RESULTS
  The analysis of CNV identification on three genes known to have different levels of amplification and which are located either in the nuclear, apicoplast or mitochondrial genomes is presented. The results are correlated with the qPCR experiments, usually used for identification of locus specific amplification/deletion.
  
  
  CONCLUSIONS
  This tool will facilitate the study of P. falciparum genomic adaptation in response to ecological changes: drug pressure, decreased transmission, reduction of the parasite population size (transition to pre-elimination endemic area).
authors.affiliation: Institut Pasteur, Génome et Génomique des Insectes Vecteurs, Paris, France. johann.beghain@wanadoo.fr.
authors.forename: Johann
authors.initials: J
authors.lastname: Beghain
authors.affiliation: Institut Pasteur du Cambodge, Epidémiologie Moléculaire du Paludisme, Phnom Penh, Cambodia.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Langlois
authors.affiliation: Institut Pasteur, Génome et Génomique des Insectes Vecteurs, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Legrand
authors.affiliation: Institut Pasteur, Génétique Fonctionnelle des Maladies Infectieuses, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Grange
authors.affiliation: Institut Pasteur du Cambodge, Epidémiologie Moléculaire du Paludisme, Phnom Penh, Cambodia.
authors.forename: Nimol
authors.initials: N
authors.lastname: Khim
authors.affiliation: Institut Pasteur du Cambodge, Epidémiologie Moléculaire du Paludisme, Phnom Penh, Cambodia.
authors.forename: Benoit
authors.initials: B
authors.lastname: Witkowski
authors.affiliation: Institut Pasteur du Cambodge, Epidémiologie Moléculaire du Paludisme, Phnom Penh, Cambodia.
authors.forename: Valentine
authors.initials: V
authors.lastname: Duru
authors.affiliation: Institut Pasteur, Plate Forme Génomique, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institut Pasteur, Plate Forme Génomique, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.affiliation: Institut Pasteur du Cambodge, Epidémiologie Moléculaire du Paludisme, Phnom Penh, Cambodia.
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
authors.affiliation: Institut Pasteur, Génétique Fonctionnelle des Maladies Infectieuses, Paris, France.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Paul
authors.affiliation: INSERM U 1016, Institut Cochin, Université Paris Descartes Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
mesh_terms: D002160:Cambodia; D045303:Cytochromes b / Q000235:genetics; D056915:DNA Copy Number Variations; D018503:Genome, Protozoan; D023281:Genomics; D006238:Haploidy; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010961:Plasmodium / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D045303:Cytochromes b; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum
keywords: Anti-malarial drug resistance; Bioinformatics; Copy number variation; Malaria