Estimating the effect of SNP genotype on quantitative traits from pooled DNA samples.docVIP

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Estimating the effect of SNP genotype on quantitative traits from pooled DNA samples.doc

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Estimating the effect of SNP genotype on quantitative traits from pooled DNA samples

Henshalletal.GeneticsSelectionEvolution2012,44:12 /content/44/1/12 G enetics Selection Evolution RESEARCH OpenAccess EstimatingtheeffectofSNPgenotypeon quantitativetraitsfrompooledDNAsamples JohnMHenshall1*,RachelJHawken2,3,4,SonjaDominik1andWilliamBarendse2,3 Abstract Background:StudiestodetectassociationsbetweenDNAmarkersandtraitsofinterestinhumansandlivestock benefitfromincreasingthenumberofindividualsgenotyped.PerformingassociationstudiesonpooledDNA samplescanprovidegreaterpowerforagivencost.Forquantitativetraits,theeffectofanSNPismeasuredinthe unitsofthetraitandhereweproposeanddemonstrateamethodtoestimateSNPeffectsonquantitativetraits frompooledDNAdata. Methods:ToobtainestimatesofSNPeffectsfrompooledDNAsamples,weusedlogisticregressionofestimated allelefrequenciesinpoolsonphenotype.Themethodwastestedonasimulateddataset,andabeefcattledataset usingamodelthatincludedprincipalcomponentsfromagenomiccorrelationmatrixderivedfromtheallele frequenciesestimatedfromthepooledsamples.Theperformanceoftheobtainedestimateswasevaluatedby comparisonwithestimatesobtainedusingregressionofphenotypeongenotypefromindividualsamplesofDNA. Results:Forthesimulateddata,theestimatesofSNPeffectsfrompooledDNAaresimilarbutasymptotically differenttothosefromindividualDNAdata.Errorinestimatingallelefrequencieshadalargeeffectonthe accuracyofestimatedSNPeffects.Forthebeefcattledataset,theprincipalcomponentsofthegenomiccorrelation matrixfrompooledDNAwereconsistentwithknownbreedgroups,andcouldbeusedtoaccountforpopulation stratification.Correctlymodelingthecontemporarygroupstructurewasessentialtoachieveestimatessimilarto thosefromindividualDNAdata,andpoolingDNAfromindividualswithingroupswassuperiortopoolingDNA acrossgroups.Forafixednumberofassays,pooledDNAsamplesproducedresultsthatweremorecorrelatedwith resultsfromindividualgenotypingdatathanwereresultsfromonerandomindividualassayedfromeachpool. Conclusions:UseoflogisticregressionofallelefrequencyonphenotypemakesitpossibletoestimateSNPeffects onqua