Multiple var2csa-Type PfEMP1 Genes Located at Different Chromosomal Loci Occur in Many Plasmodium falciparum Isolates 英文参考文献.docVIP

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Multiple var2csa-Type PfEMP1 Genes Located at Different Chromosomal Loci Occur in Many Plasmodium falciparum Isolates 英文参考文献.doc

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Multiple var2csa-Type PfEMP1 Genes Located at Different Chromosomal Loci Occur in Many Plasmodium falciparum Isolates 英文参考文献

Multiplevar2csa-TypePfEMP1GenesLocatedat DifferentChromosomalLociOccurinManyPlasmodium falciparumIsolates AdamF.Sander1,AliSalanti1,ThomasLavstsen1,MortenA.Nielsen1,PamelaMagistrado1,2 ,John Lusingu2,NicaiseTuikueNdam3,DavidE.Arnot1,4* 1CentreforMedicalParasitology,DepartmentofInternationalHealth,ImmunologyMicrobiology,FacultyofHealthSciences,UniversityofCopenhagenDepartment ofInfectiousDiseases,CopenhagenUniversityHospital(Rigshospitalet),Copenhagen,Denmark,2JMP-ENRICAProject,NationalInstituteforMedicalResearch,Korogwe Laboratory, Tanga, Tanzania, 3Institut de Recherche pour le Developpment, UR010, Universite Paris Descartes, Paris, France, 4Institute of Immunology Infection Research,SchoolofBiology,UniversityofEdinburgh,Edinburgh,Scotland,UnitedKingdom Abstract Background: The var2csa gene encodes a Plasmodium falciparum adhesion receptor which binds chondroitin sulfate A (CSA).ThisvargeneismoreconservedthanotherPfEMP1/vargenesandisfoundinallP.falciparumisolates.Inisolates3D7, FCR3/It4 and HB3, var2csa is transcribed from a sub-telomeric position on the left arm of chromosome 12, but it is not knownifthislocationisconservedinallparasites.Genomesequencingindicatesthatthevar2csageneisduplicatedinHB3, butwhetherthisistrueinnaturalpopulationsisuncertain. Methodology/PrincipalFindings:ToassessglobalvariationintheVAR2CSAprotein,sequencevariationintheDBL2Xregion of var2csa genes in 54 P.falciparum samples was analyzed. Chromosome mapping of var2csa loci was carried out and a quantitativePCRassaywasdevelopedtoestimatethenumberofvar2csagenesinP.falciparumisolatesfromtheplacentaof pregnantwomenandfromtheperipheralcirculationofothermalariapatients.Sequenceanalysis,genemappingandcopy numberquantitationinP.falciparumisolatesindicatethatthereareatleasttwolociandthatbothvar2csa-likegenescanbe transcribed.AllVAR2CSADBL2Xdomainsfallintooneoftwodistinctphylogeneticgroupspossessingoneortheothervariant ofalarge(,26aminoacid)dimorphicmotif,butwhethereithermotifvariantislinkedtoaspe