An Empirical Method for Establishing Positional Confidence Intervals Tailored for Composite Interval Mapping of QTL 英文参考文献.docVIP

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An Empirical Method for Establishing Positional Confidence Intervals Tailored for Composite Interval Mapping of QTL 英文参考文献.doc

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An Empirical Method for Establishing Positional Confidence Intervals Tailored for Composite Interval Mapping of QTL 英文参考文献

AnEmpiricalMethodforEstablishingPositional ConfidenceIntervalsTailoredforCompositeInterval MappingofQTL AndrewCrossett1.,NickLauter2.,TanzyM.Love1*¤ 1DepartmentofStatistics,CarnegieMellonUniversity,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2USDA-ARSCornInsectsandCropGeneticsResearchUnitand DepartmentsofPlantPathologyandAgronomy,IowaStateUniversity,Ames,Iowa,UnitedStatesofAmerica Abstract Background: Improved genetic resolution and availability of sequenced genomes have made positional cloning of moderate-effect QTL realistic in several systems, emphasizing the need for precise and accurate derivation of positional confidenceintervals(CIs)forQTL.Supportinterval(SI)methodsbasedontheshapeoftheQTLlikelihoodcurvehaveproven adequate for standard interval mapping, but have not been shown to be appropriate for use with composite interval mapping(CIM),whichisoneofthemostcommonlyusedQTLmappingmethods. Results:Basedonanon-parametricconfidenceinterval(NPCI)methoddesignedforusewiththeHaley-Knottregression methodformappingQTL,aCIM-specificmethod(CIM-NPCI)wasdevelopedtoappropriatelyaccountfortheselectionof backgroundmarkersduringanalysisofbootstrap-resampleddatasets.Coverageprobabilitiesandintervalwidthsresulting fromuseoftheNPCI,SI,andCIM-NPCImethodswerecomparedinaseriesofsimulationsanalyzedviaCIM,whereinfour geneticeffectsweresimulatedinchromosomalregionswithdistinctmarkerdensitieswhileheritabilitywasfixedat0.6fora populationof200isolines.CIM-NPCIsconsistentlycapturethesimulatedQTLacrosstheseconditionswhileslightlynarrower SIs and NPCIs fail at unacceptably high rates, especially in genomic regions where marker density is high, which is increasingly common for real studies. The effects of a known CIM bias toward locating QTL peaks at markers were also investigatedforeachmarkerdensitycase.Evaluationofsub-simulationsthatvariedaccordingtothepositionsofsimulated effectsrelativetothenearestmarkersshowedthattheCIM-NPCImethodovercomesthisbias,offeringanexplanationfor theimprovedc