Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map 英文参考文献.docVIP

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Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map 英文参考文献.doc

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Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map 英文参考文献

GeneticCrossoversArePredictedAccuratelybythe ComputedHumanRecombinationMap PavelP.Khil,R.DanielCamerini-Otero* GeneticsandBiochemistryBranch,TheNationalInstituteofDiabetesandDigestiveandKidneyDiseases,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStates ofAmerica Abstract Hotspotsofmeioticrecombinationcanchangerapidlyovertime.Thisinstabilityandthereportedhighlevelofinter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summationofpastgeneticcrossovers.Toestimatetheaccuracyofthecomputedrecombinationratemap,wehavemapped geneticcrossoverstoamedianresolutionof70Kbin10CEPHpedigrees.Wethencomparedthepositionsofcrossoverswith the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributionsofcrossoverswiththedistributionsexpectedfromthecalculatedrecombinationratemaps.Hereweshowthata population-averagedhotspotmapcomputedfromlinkagedisequilibriumdatapredictswellpresent-daygeneticcrossovers. Wefindthatcomputedhotspotmapsaccuratelyestimateboththestrengthandthepositionofmeiotichotspots.Anin-depth examinationofnot-predictedcrossoversshowsthattheyarepreferentiallylocatedinregionswherehotspotsarefoundin otherpopulations.Insummary,wefindthatbycombiningseveralcomputedpopulation-specificmapswecancapturethe variationinindividualhotspotstogenerateahotspotmapthatcanpredictalmostallpresent-daygeneticcrossovers. Citation: Khil PP, Camerini-Otero RD (2010) Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map. PLoS Genet 6(1): e1000831.doi:10.1371/journal.pgen.1000831 Editor:GilMcVean,UniversityofOxford,UnitedKingdom ReceivedJuly21,2009;AcceptedDecember28,2009;PublishedJanuary29,2010 Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsPublicDomaindeclarationwhichstipulatesthat,onceplacedinthepublic domain,thisworkmaybefreelyreproduced,distributed,transmitted,modified,builtupon,orotherwiseusedbyanyonefo