Medical Genetics04 基因突变的分子细胞生物学效应 cellular effects of gene mutationMedical Genetics1.GenescanbemutatedinmanywaysThemostcommongenechangeinvolvesasinglebasemismatch-amisspelling-placingthewrongbaseintheDNA.Atothertimes,asinglebasemaybedroppedoradded.AndsometimeslargepiecesofDNAaremistakenlyrepeatedordeleted.Medical GeneticsMedical GeneticsWhenagenecontainsamutation,theproteinencodedbythatgeneislikelytobeabnormal.Medical GeneticsMedical GeneticsMedical Genetics2.SomaticversusgermlinemutationsGenemutationscanbeeitherinheritedfromaparentoracquired.Medical GeneticsMedical GeneticsHereditarymutationsarecarriedintheDNAofthereproductivecells.Whenreproductivecellscontainingmutationscombinetoproduceoffspring,themutationwillbeinalloftheoffspringsbodycells.Medical GeneticsThefactthateverycellcontainsthegenechangemakesitpossibletousecheekcellsorabloodsampleforgenetesting.Medical GeneticsMedical GeneticsAcquiredmutationsarechangesinDNAthatdevelopthroughoutapersonslifetime.Medical GeneticsAlthoughmistakesoccurinDNAallthetime,especiallyduringcelldivision,acellhastheremarkableabilitytofixthem.ButifDNArepairmechanismsfail,mutationscanbepassedalongtofuturecopiesofthealteredcell.Medical GeneticsMedical Genetics3.Typesofmutationeffects(1)Morphologicalmutationsgiverisetoalteredforms.Medical GeneticsMedical GeneticsMedical Genetics(2)Lethalmutationsresultinnonviableorganisms.Medical Genetics(3)Conditionalmutationsgivesamutantphenotypeunderrestrictiveconditions(environmental)andcausesawildtypephenotypeunderpermissiveconditions.Medical Genetics(4)Biochemicalmutationsresultintheinabilitytocarryoutaspecificbiochemicalpathway(inbornerrorsofmetabolism).Medical Genetics(5)Loss-of-function(null)mutations(lof)resultinnogenefunctionareusuallyrecessivealthoughsomehaploinsufficientdominantlofmutationsexist.Medical GeneticsMedical GeneticsAcommonlofmutationisthepartialloss-of-functionorleakymutation.Medical GeneticsMedical Genetics(6)Gain-of-functionmutation(gof)resultinalteredgenefunctionthatactasadominantalleleandproducesanovelphenotype.Medical Genetics