Genetic Control of Variegated KIR Gene Expression Polymorphisms of the Bi-Directional KIR3DL1 Promoter Are Associated with Distinct Frequencies of Gene Expression 英文参考文献.docVIP

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Genetic Control of Variegated KIR Gene Expression Polymorphisms of the Bi-Directional KIR3DL1 Promoter Are Associated with Distinct Frequencies of Gene Expression 英文参考文献.doc

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Genetic Control of Variegated KIR Gene Expression Polymorphisms of the Bi-Directional KIR3DL1 Promoter Are Associated with Distinct Frequencies of Gene Expression 英文参考文献

GeneticControlofVariegatedKIRGeneExpression: PolymorphismsoftheBi-DirectionalKIR3DL1Promoter AreAssociatedwithDistinctFrequenciesofGene Expression HongchuanLi1,2,Ve′roniquePascal2,MaureenP.Martin1,2,MaryCarrington1,2,StephenK.Anderson1,2 * 1Basic ResearchProgram,SAIC-Frederick Inc., NationalCancerInstitute-Frederick,Frederick,Maryland,United States ofAmerica, 2CancerandInflammation Program, LaboratoryofExperimentalImmunology,CenterforCancerResearch,NationalCancerInstitute-Frederick,Frederick,Maryland,UnitedStatesofAmerica Abstract Naturalkiller (NK)cellsplay animportantrole inthedetectionandeliminationof tumorsandvirus-infected cells bythe innate immune system. HumanNK cells usecell surface receptors (KIR) for class IMHC tosense alterations of class Ion potentialtargetcells.IndividualNKcellsonlyexpressasubsetoftheavailableKIRgenes,generatingspecializedNKcellsthat canspecificallydetectalterationofaparticularclassImoleculeorgroupofmolecules.Theprobabilisticbehaviorofhuman KIR bi-directional promoters is proposed to control the frequency of expression of these variegated genes. Analysis of a panelofdonorshasrevealedthepresenceofseveralfunctionallyrelevantpromoterpolymorphismsclusteredmainlyinthe inhibitory KIR family members, especially the KIR3DL1 alleles. We demonstrate for the first time that promoter polymorphisms affecting the strength of competing sense and antisense promoters largely explain the differential frequencyofexpressionofKIR3DL1allotypesonNKcells.KIR3DL1/S1subtypeshavedistinctbiologicalactivityandcoding regionvariantsoftheKIR3DL1/S1genestronglyinfluencepathogenesisofHIV/AIDSandotherhumandiseases.Wepropose that the polymorphisms shown in this study to regulate the frequency of KIR3DL1/S1 subtype expression on NK cells contributesubstantiallytothephenotypicvariationacrossallotypeswithrespecttodiseaseresistance. Citation:LiH,PascalV,MartinMP,CarringtonM,AndersonSK(2008)GeneticControlofVariegatedKIRGeneExpression:PolymorphismsoftheBi-Directiona