讲稿遗传学课件4modification mendelian ratios

ReviewfortheReviewforthelastTechnicalterms:phenotype,genotype,Homozygote,heterozygote,Pureline,etc.ThemonohybridTheDihybridEvaluatinggeneticdata:Evaluatinggeneticdata,Theproductrule,Thesumrule,Thebinomialexpansion,Chi-square Human1Chapter4ModificationofMendelianRatios2ChapterChapterSpecificphenotypesareoftencontrolledbyoneormoregenepairswhoseallelesexhibitmodesofexpressionotherthandominanceandrecessiveness.特定表型 Inallsuchcases,however,theMendelianprinciplesofsegregationandindependentassortmentareoperativeduringthedistributionoftheallelesintogametes.31PotentialfunctionofEachtypeofinheritancedescribedinthischapterwasinvestigatedwhenobservationsofgeneticdatadidnotconformpreciselytotheexpectedMendedianratio.4Genesoftenhavemultiplealleles（复等位 ）Genesoftenhavemultiplealleles（复等位 ）.Differentallelesarecreatedbythemutationofawild-typeallele不同等位 突变而来.Mutantallelesmaybedominant, pleydominant（不完全显性）,orco-dominant（共显性Thefunctionofmostgenesistoproduceapolypeptide（多肽）.Recessivemutationscancauseapartialorcompletelossofpolypeptideactivity.Dominantmutationscanendow（赋予）apolypeptidewithanewactivitythatmayre ceorinterfere（干扰）withtheactivityofthewild-typepolypeptide.52Symbolsoftheinitialletterofthenameofarecessivetrait---uppercaseDreferstothedominantlowercasedsymbolizerecessive6Forfruitfly:Forfruitfly:thewild-typeandmutanttraitsaresymbolizedbythesameletter,butthewild-typeisaddedwithasuperscript+Fore+/Grayhomozygotee+/Grayheterozygotee/EbonyhomozygoteEbonyn.黑檀树乌木,adj.乌木制的,黑檀 3个亲本的新类型FigdominanceshownintheflowercolorofsnapdragonAntirrhinummajusL.Scrophulariaceae44co-dominance--MNLMLMLMLNLNLNLMLXLNLLLXLL1/4LM1/2LML1/4LN9MultipleABOAB5.25.2ThebombayphenotypeThebiochemicalbasisoftheABObloodtypesystemhasnowbeencarefullyworkout.TheAandB (抗原)areactuallycarbohydrategroups（sugars）thatareboundtolipidmolecules（fattyacids）protruding(突出)fromthemembraneoftheredbloodcell.Thespecificity（特异性）oftheAandB isbasedontheterminal(终端)sugarofthecarbohydrategroup.AB抗原的特异性在于糖基的末端糖分子BoththeAandB derivedfrom( )aprecursor(先驱)moleculecalledtheHsubstance,towhichoneortwoterminalsugarsisadded.AB抗Inextremelyrareinstances,firstrecognizedinawomaninBombay,theHsubstanceis pleyformedAsaresult,itisaninadequatesubstrate(前提，底物，酶作用物fortheenzymethatnormallyaddseitherterminalsugar.ThisconditionresultsinbloodtypeOandiscalledtheBombayphenotypeHAB抗原不能形成，血型表现为OIthasbeenshowntobedueIthasbeenshowntobeduetoararerecessivemutation,h,atalocusseparatefromthatcontrollingtheAandB Thus,eventhoughanindividualmaycontaintheIAandorIBalleles,ifheorshedis thehhgenotype,neithertheAorBantigencanbeadded.Thisinformationhelpedex inwhythewomaninBombaywastypedasOeventhoughoneofherparentswastypeAB(andthussheshouldnothavebeentypeO),andwhyshewasabletodonate(赠予，给予)theIBalleletoherBombayphenotypebloodgroupFig2ApartialpedigreeofawomandisyingtheBombayphenotype.Functionally,herABObloodgroupbehavesastypeO.Genetically,sheistypeB.A抗原+少量HHHB抗原+少量H型前体未变，没有ABH抗原（孟买型Bombayphenotypehasbeenshowtobeduetoararerecessivemutationh,atalocusseparatefromthatcontrollingtheAandB.Thus,eventhoughanindividualmaycontaintheIAand/orIBalleles,ifheorshedisysthehhgenotype,neitherAorBantigencanbe 6LethalCrossesbetweenthevariouscombinationoftwoyieldedunusual agouti╳Allagoutiyellow╳2/31/3C:agouti╳1/21/2agouti深浅环纹FigureFigureInheritancepatternsinthreecrossesinvolvingthewild-typeagoutiallele(A)andthemutantyellowallele(A)inthemouse.Notethatthemutantallelebehavesdominantlytothenormalallele(A)incontrollingcoatcolor,butitalsobehavesasahomozygouslethalallele.ThegenotypeAAdoesnotsurvive.Themutationyellowallele(Ay)isdominanttothewild-typeagoutiallele(A),soheterozygousmicewillhaveyellowHowever,theyellowallelealsobehavesasahomozygousrecessivelethal.IfamousedisytheAYAY,themousewilldiebeforebirth.Inhumans,adisordercalledhuntingtonInhumans,adisordercalledhuntingtondisease(huntington’s isduetoadominantautosomal（常染色体）alleleH,wheretheonset（发作）ofthediseaseinheterozygotes(Hh)isdelayed,usuallywellintoadulthood.Affectedindividualsundergogradualnervousandmotor(肌 )degeneration( )untiltheydie.Thislethaldisorderisparticularlytragic(悲剧)becauseithassuchalateonset,typicallyataboutage40.Bythattime,theaffectedindividualmayhaveproducedafamily,i.e.theHallelehavebeentransmittingtohisorherchildrenandotheroffspring.Eachchildhasa50percentprobabilityofinheritingthelethalallele,transmittingthealleletohisorheroffspring,andeventuallydevelo disorder.TheAmericanfolksingerandcomposerWoodyGuthriediedfromthisdiseaseatage39. observed.7CombinationsoftwogeneHavingestablishedthefoundationforthemodesofinheritanceof dominance,co-dominance,multiplealleles,andlethalgenes,wecannowdealwiththesituationoftwomodesofinheritanceoccurringsimultaneously.Mendel’Mendel’sprincipleofindependentassortmentappliestothesesituations,provided假如thatthegenescontrollingeachcharacterarenotlinkedonthesameConsider,forexample,amatingthatoccursbetweentwohumanswhoarebothhetrerozygousfortheautosomalrecessivegenethatcausesalbinism(白化病,皮肤变白症)andwhoarebothofbloodtypeAB.一对夫妇都是杂合的白化病基AlbinismisinheritedinthesimplefashionMendelianratioandthebloodtypesaredeterminedbytheseriesofthreemultipleallele,IA,IBandIO(modifiedratio).白化病是 Thesolutiontothisproblemisdiagrammedinfigure4,usingtheforked-linemethod.SixphonotypeoccurinThesolutiontothisproblemisdiagrammedinfigure4,usingtheforked-linemethod.Sixphonotypeoccurina3:6:3:1:2:1ratioinsteadofa9:3:3:1ratio.ThisisjustoneofmanyvariantsofmodifiedratiospossiblewhendifferentmodesofinheritanceareFigureCalculationoftheprobabilitiesinamatinginvolvingtheABObloodtypeandalbinisminhumansusingthealbinism皮肤白 Gene Gene8.1EpistasisEpistasisoccurswhentheexpressionofonegeneorgenepairmasksormodifiestheexpressionofanothergeneorgenepair.作用中，其中一 抑制或遮盖了另一1)BombayFourphenotypesoccurina3:6:3:4ratioinsteadofa9:3:3:1ratioFigure eofamatingbetweenindividualswhoareheterozygousattwogenesdeterminingtheirABObloodtype.Finalphenotypesarecalculatedbyconsideringbothgenesseparayandthencombiningtheresultsusingtheforked-linehh掩盖了IorI2）2）MousecoatAaBbxAaBF2 A_B_A_bbaaaabphenotypeFinal3/16blackWecanenvision(想象)genein yieldingtheobserved9:3:4F2ratioasatwo-stepprocessGeneGene★TheexpressionofAgeneisonthebaseoftheexpressionofBgene.★wealsocanthusex inthatthebbgenotypemasksorsuppressestheexpressionoftheAgene,demonstratingF2F2I_YI_yiiYiiy★TheexpressionofYgeneisonthebaseoftheexpressionofthehomozygousrecessivei★wealsocanthusex inthattheI_genotypemasksorsuppressestheexpressionoftheYgene,demonstratingepitasis.4)4)SquashAaBbxAaBF2A_B_A_bbaaB_aabphenotypeFinal12/16white3/16yellow1/16green★ThedominantalleleAresultsinwhitefruitcolorregardlessofthegenotypeatthesecondlocus,B.★IntheabsenceofthedominantAallele,BBorBbresultsinyellowcolor,whitebbresultsingreencolor.★Thereforethemodifiedratioof12:3:15)5)PeaflowerAAbb(white)xaaBBAaBbxAaBbF2A_B_A_bbaaB_aabphenotypeFinal9/167/16aamaskstheexpressionofthedominantallele★Thepresenceofatleastonedominantalleleofeachoftwogenepairsisessentialforflowerstobepurple.通常叫互补作用★Allothergenotypecombinationsyieldwhiteflowersbecausethehomozygousconditionofeitherrecessiveallelemaskstheexpressionofthedominantalleleattheother南南shepherd’spurse(Capsellabursa-pastoris 荠seed 种皮 flour 面象虫,8.2OtherFigure7ThebasisofmodifieddihybridFphenotypicratios,resultingfromcrossesbetweendoublyheterozygousFAlbinoagoutisootyjet黑得发亮的Case1,2,3werediscussed99NovelphenotypeinCucurbitapepoAaBbF2 A_B_A_bbaaB_aabAaBbA_B_积加作用eFinalPhenotype9/166/161/16BothgenepairsinfluencefruitshapeBothdominantalleles(AandBarepresent,thefruitdis yaflattened.(A_B_)积加作用Thepresenceofonedominantalleleofeachoftwogenepairsensuresasphere-shapefruit(A_Intheabsenceofdominantalleles,thefruitislong(aabb)FigureFigure8Summersquashexhibitingvariousfruit-phenotypes,wheredisc(white),long(orangegooseneck),andsphere(bottomleft)areapparent.10Complementationysisysis（互补分析）seeksanswerthissimpleAretwomutationsthatyieldsimilarphenotypespresentinthesamegeneorintwodifferentgenes?Figure9Figure9 ysisofesofwinglessmutationsinDrosophila(musaandmcan).Incase1,mutationsarenotallelesofthesamegene,whileincase2,themutati4o3nsareallelesofthesamegene.Case1alloffspringdevelopnormalInterpretation:thetworecessivemutationsareinseparategenesandarenotallelesofoneanotherBecauseeachmutationisinaseparategeneandeachF1flyisheterozygousatbothloci,thenormalcopyofeachgeneareproduced.Case2Case2alloffspringfailtodevelopInterpretation:thetworecessiveaffectthesamegeneandareallelesofoneanotherBecausethetwomutationsaffectthesamegene,theF1fliesarehomozygousforthetwomutantalleles(themusaalleleandthemcanallele).Nonormalproductofthegeneis11geneontheXExample1Figure10TheFandFresultsofMorgan’sreciprocalcrossesinvolvingtheX-linkedwhitemutationinDrosophilamelanogaster.TheactualFdataareshowninparentheses.Thephotographsshowwhiteeyesandthebrick-redwild-typeeyeOneOneofthefirstcasesofX-linkageedbyThomasH.Morganaround1920duringhisstudiesofthewhitemutationintheeyesofDrosophilamelanogaster.WeusethiscasetoillustratetheX-linkage.Thenormalwild-typeredeyecolorisdominanttowhite.Unlikeeofthetypicalcross,reciprocalcrosses(互交)betweenwhite-andred-eyefliesdidnotyieldidenticalresults正反交后代表现不同.Incontrast,inallofMendel’smonohybridcrosses,F1andF2datawereverysimilarregardlessofwhichP1parentexhibitedtherecessivemutanttrait.Morgan’s ysisledtotheconclusionthatthewhitelocusispresentontheXchromosomeratherthanononeoftheautosomes(常 ).Assuch,boththegeneandthetraitaresaidtobeX-Figure11Figure11ThechromosomalexnationoftheresultsoftheX-linkedcrossesshowninFigureTheobviousdifferencesinphenotypicratiosinboththeF1andF2generationsaredependentonwhetherornottheP1white-eyedparentwasmaleorMorganMorganwasabletocorrelatetheseobservationswiththedifferencefoundinthechromosomecompositionbetweenmaleandfemaleDrosophila.HehypothesizedthattherecessivealleleforwhiteeyeisfoundontheXchromosome,butitscorrespondinglocusisabsentfromtheYFemalesthushavetwoavailablegenesites,oneoneachXchromosome,whilemaleshaveonlyoneavailablegenesiteontheirsingleSincetheYchromosomelackshomology(同源)withmostgenesontheXchromosome,whateverallelesarepresentontheXchromosomeofthemaleswillbeexpresseddirectlyintheirphenotype.BecausemalecannotbeeitherhomozygousorheterozygousforX-linkedgenesthisconditionisreferredtoasbeinghemizygous(半合子的).OneOneresultofX-linkageisthecrisscrosspatternofinheritance（交替遗传）,wherebyphenotypictraitscontrolledbyrecessiveX-linkedgenesarepassedfromhomozygousmotherstoallsons.ThispatternoccursbecausefemalesexhibitingarecessivetraitcarrythemutantalleleonbothXchromosomes.Becausemaleoffspringreceiveoneoftheirmother’stwoXchromosomesandarehemizygous(半合子的)forallelespresentonthatX,allsonswillexpressthesamerecessiveX-linkedtraitsastheirMorgan’sworkhastakenongreathistoricalBy1910,thecorrelationbetweenMendel’sworkandthebehaviorofchromosomesduringmeiosishadprovidedthebasisforthechromosometheoryofinheritance,aspostulatedbySuttonandBoveri. ExampleExampleFigure12(a)AhumanpedigreeofX-linkedcolorblindnesstrait.(b)Themostprobablegenotypesofeachindividualinthepedigree.ThephotographisofanIshiharacolorblindnesschart.Red-greencolorblindindividualsseea3ratherthanand8visualizedbythosewithnormalcolorInstillotherinstances,inheritanceisaffectedbythe ofanindividual,thoughnotnecessarilybygenesontheX 的影响.Therearenumerousexamplesindifferentorganismswherethe oftheindividual ysadeterminingroleinexpressionofcertain★insomecases,theexpressionofaphenotypesis ylimitedto ★inothers,ofaninfluencestheexressionofa eisnotlimitedto ortheThisdistinction-lnfluenced-limited家家-LimitedFigure13Henfeathering(left)andcockfeathering(right)indomesticfowl.Thefeathersinthehenareshorterandlesscurv59ed. Hen-featheredHen-Hen-featheredHen-Hen-featheredCock-Onlyinmalesdoesthehhgenotyperesultincockfeathering-InfluencedFigure14-InfluencedFigure14Patternbaldness,a -influencedautosomaltraitinhumans. NotNotNotInsuchcases,autosomalgenesareresponsibleforthecontrastingphenotypedis yedbybothmalesandfemales,buttheexpressionofthesegenesisdependentonthehormoneconstitutionoftheindividual.Thus,theheterozygousgenotypeexhibitsonephenotypeinandthecontrastingoneinthe Phenotypic PhenotypicInchapter2and3,weassumedthatthegenotypeofanorganismisalwaysdirectlyexpressedinits Wediscussedgeneexpressionasthoughthegenesoperateinaclosed,‘blackbox’systeminwhichthepresenceorabsenceoffunctionalproductsdirectlydeterminesthecollectivephenotypeofanindividual. Thesituationisactuallymuchmore★Mostgeneproductsfunctionwithintheinternalmilieu（周围，环境）ofthecell,thecell ctwithoneanotherinvarious★Furthermore,theorganismexistsunderdiverseenvironmentalinfluences.★Thus,geneexpressionandtheresultantphenotypeareoftenmodifiedthroughthe ctionbetweenanindividual’sparticulargenotypeandtheinternalandexternalanindividual’anindividual’s+Internalandmodifiedthroughthein Therefore，thephenotypicratioisnotalwaysconformtoexpectedMendedian Thedegreeofexpressionofaparticulartraitcanbestudied tativelybydeterminingthepenetranceandexpressivityofthegenotypeunderinvestigation.Thepercentageofindividualsthatshowatleastsomedegreeofexpressionofamutantdefinesthepenetranceofthe型ThephenotypicexpressionofmanymutantalleleinDrosophilacanoverlap( withwild-Type.If15%ofmutantfilesshowthewild-typeappearancethemutantgeneissaidtohaveapenetranceof85%. ExpressivityreflectstherangofexpressiononthemutantgenotypeFigure15VariablepenetranceasshownintheexpressionoftheeyelessmutationinDrosophila.Gradationsinphenotyperangefromwildtypetopartialreductiontoeyeless.TheexpressivityreflectedhererangesfromcompletelossofbotheyestocompleynormalOnsetofgeneticNotallgenetictrailsareexpressedatthesametimeduringanorganism’slifespan（生命历程）.Inmostcases,theageatwhichageneisexpressedcorrespondstothenormalsequenceofgrowthanddisease(humanTimewhentheGenetictraitsexpressionTay-sachsDuchennemusculardystrophyHuntingtonbyageofuntiltheageof3-5yearsbetweenages30andTay-sachs黑蒙 ，婴儿型黑蒙性痴呆Duchennemuscular肌营养不良症13.313.3GeneticanticipationTheheritabledisordersexhibitaprogressivelyearlierageandanincreasedseverityofthedisorderineachsuccessivegeneration连续世代的遗传疾病发生不断提早、病症ThisgeneralphenomenoniscalledgeneticExampleMyotonicdystrophy肌强直性营养失调Themostcommontypeofadultmusculardystrophy（肌肉萎缩症）,clearlyillustratesgeneticanticipation.Mildlyaffectedindividualsdevelopcataracts(白内障)asadultsbuthavelittleornomuscularweakness.Severelyaffectedonesdemonstratemoreextensivemyopathy肌病andmaybementallyretardedInitsmostextremeformthediseaseisfataljustafterbirth. genomic(parental) genomic(parental)Somephenotypicexpressionsdependstrictlyonparentaloriginofthechromosomecarryingaparticulargene,aphenomenoncalledgenomic Insomecase,certainchromosomalregionsandthegenescontainedwithinthemsomehowretainamemory,oran“imprint”oftheirparentaloriginthatinfluenceswhetherspecificgeneseitherareexpressedorremaingeneticallysilent.有时候，某些区域和其内的好像有AnexampleofimprintinginvolvestheinactivationofoneoftheXchromosomesAnexampleofimprintinginvolvestheinactivationofoneoftheXchromosomesin lianInmice,priortodevelopmentoftheembryo,imprintingoccursintissuessuchthattheXchromosomeofpaternaloriginisgeneticallyinactivatedinallcellswhilethegenesonthematernalXchromosomeremaingeneticallyactive.老鼠胚胎发育前，组织中出现 组印迹，来自父亲的X在所有细胞中都失活，而母亲的X染色体基都保持活跃状态Asembryonicdevelopmentissubsequentlyinitiated,theimprintis“released”,andrandominactivationofeitherthepaternalorthematernalXchromosomeoccurs.随着胚胎发育启动， 习机能)；印迹；烙印]--Alearningprocessoccurringearlyinthelifeofasocialanimalinwhichaspecificbehaviorpatternisestablishedthroughassociationwithaparentorotherrolemodel.社会性动物生命早期出现的认知AspecificIgf2isthegeneencodinginsulin-like(胰岛素类growthfactorIIinmouse.NextFigure16TheeffectofimprintingonthemouseIgf2gene,whichproducesdwarfmiceinthehomozygouscondition.Heterozygousoffspringthatreceivethenormalallelefromtheirfatherarenormalinsize.Heterozygotesthatreceivethenormalallelefromtheirmother,78whichhasbeenimprinted,aredwarf.ChapterTheChapterThestudyoftransmissiongeneticshasexpandedInmanycases,phenotypescanbeinfluencedbytwoormoregenes. pleteorpartialdominanceisexhibitedwhenanintermediatephenotypicexpressionofatraitoccursinanorganismthatisheterozygousfortwoalleles.Codominanceisexhibitedwhendistinctiveexpressionoftwoallelesoccursinaheterozygousorganism.Theconceptofmultipleallelismappliestopopulations,sinceadiploidorganismmayhostonlytwoallelesatanygivenlocus.Withinapopulation,however,manyalternativeallelesofthesamegenecanoccur.LethalLethalmutationsusuallyresultintheinactivationorthelackofsynthesisofgeneproductsthatareessentialduringdevelopment.Suchmutationscanberecessiveordominant.Somelethalgenes,suchastheonethatcausesHuntintondiseasearenotexpresseduntiladulthood.Mendel’sclassicF2ratioisoftenmodifiedininstanceswheregenein ctionresultsindiscontinuousvariation.PhenotypicexpressionisnotalwaysthedirectreflectionofthegenotypePenetrancemeasuresthepercentageoforganismsinagivenpopulationthatexhibitsevidenceofthecorrespondingmutantphenotype.Expressivityontheotherhand,measurestherangeofphenotypicexpressionofagivengenotype.Thetimeofonset启动ofgeneexpressioninorganismsvariesastheneedforcertaingeneproductsoccursatdifferentperiodsduringdevelopmentgrowthandaging.Geneticanticipation早现Geneticanticipation早现referstothephenomenonwheretheonsetofphenotypicexpressionoccursearlier esmoresevereineachensuing后继generation.Genomicimprintingisaprocesswherebyaregionofeitherthepaternalormaternalchromosomeismodified(markedorimprinted),therebyaffectingphenotypicexpression.Expressionthereforedependsonwhichparentcontributesamutantallele.Epistasismayoccurwhentwoormoregenesinfluenceasinglecharacteristic.Usually,theexpressionofoneofthegenesmaskstheexpressionoftheothergeneorgenes. independentlyisolatedmut