醫(yī)學(xué)遺傳學(xué) 10人類染色體畸變課件

10人類染色體畸變

chromosomeaberration

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Anytypeofchangeinthechromosomestructureornumber(deficiencies,duplications,translocations,inversions,etc.).醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Althoughitcanbeamechanismforenhancinggeneticdiversity,suchalterationsareusuallyfatalorill-adaptive,especiallyinanimals.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變1.factorsinducingchromosomeaberration

A.Ionizingradiation

Ionizingradiationproducesrearrangementsofthegenome.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變WhenirradiationoccursduringtheG0/G1phaseofthecellcycle,large-scalerearrangementsappearasexchange-typechromosomeaberrationsatthenextmitosis.Suchaberrationscanaltercellularphenotypes,andareimportantinvariousareasofbiology:醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Medicalandpublic-healthapplicationsincludeperinataldiagnosticscharacterizationofspecificcancertypes,carcinogenesisriskestimation,radiationbiodosimetryandradiotherapeutictreatmentplanning.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Analyzingchromosomeaberrationshelpscharacterizerepair/misrepairpathwaysinvolvedintheprocessingofDNAdamage.Ionizingradiationhassomeuniquefeaturesasaprobeofsuchpathways.Comparedtoothergenotoxicagents,itproducescopiousquantitiesofDNAdoublestrandbreaks(DSBs),anditstimingcanbecontrolledmoreaccurately.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Moreover,initialradiationdamagehasadiscrete,stochasticcharacterthatcanbemodulatedbyusingdifferentkindsofradiation(e.g.a-particlesversusx-rays)havingdifferentionizationdensities.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Thespectrumofdifferentradiation-inducedchromosomeaberrationsisinformativeaboutthegeometryofchromosomesduringinterphase,andviceversa.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Chromosomalinstability,inwhichnewaberrations(thoughoftennotofthetypecharacteristicofG0/G1damage)continuetoarisemanygenerationsafterirradiation,representsaformofgenomicinstability,andgenomicinstabilityisprominentduringneoplasticprogression.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變B.chemicalmutagen

Akindofsubstances,suchasdrugsortoxins,thatcauseschromosomalaberrationsoflivingorganisms,orincreasetherateofmutation.

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變2.chromosomalaberrationsA.

chromosomenumericalaberrationNumericalaberrationisachangeinthenumberofchromosomesfromthenormalnumbercharacteristicofthehumanbeings.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(1)Euploidyistheconditionofhavinganormalnumberofstructurallynormalchromosomes.

Euploidhumanfemaleshave46chromosomes(44autosomesandtwoXchromosomes).醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Polyploidyisamultipleofthehaploidchromosomenumber(n)otherthanthediploidnumber(i.e.,3n,4nandsoon).醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(2)

Aneuploidyistheconditionofhavinglessthanormorethanthenormaldiploidnumberofchromosomes,andisthemostfrequentlyobservedtypeofcytogeneticabnormality.

Inotherwords,itisanydeviationfromeuploidy,althoughmanyauthorsrestrictuseofthistermtoconditionsinwhichonlyasmallnumberofchromosomesaremissingoradded.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Generally,aneuploidyisrecognizedasasmalldeviationfromeuploidyforthesimplereasonthatmajordeviationsarerarelycompatiblewithsurvival,andsuchindividualsusuallydieprenatally.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Thetwomostcommonlyobservedformsofaneuploidyaremonosomyandtrisomy.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Monosomyislackofoneofapairofchromosomes.Anindividualhavingonlyonechromosome6issaidtohavemonosomy6.AcommonmonosomyseeninmanyspeciesisXchromosomemonosomy,alsoknownasTurner'ssyndrome.Monosomyismostcommonlylethalduringprenataldevelopment.

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Trisomyishavingthreechromosomesofaparticulartype.Acommonautosomaltrisomyinhumansin

Downsyndrome,ortrisomy21,inwhichapersonhasthreeinsteadofthenormaltwochromosome21s.Trisomyisaspecificinstanceofpolysomy,amoregeneraltermthatindicateshavingmorethantwoofanygivenchromosome.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Anothertypeofaneuploidyistriploidy.Atriploidindividualhasthreeofeverychromosome,thatis,threehaploidsetsofchromosomes.Atriploidhumanwouldhave69chromosomes(3haploidsetsof23).醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Productionoftriploidsseemstoberelativelycommonandcanoccurby,forexample,fertilizationbytwosperm.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變However,birthofalivetriploidisextraordinarilyrareandsuchindividualsarequiteabnormal.Theraretriploidthatsurvivesformorethanafewhoursafterbirthisalmostcertainlyamosaic,havingalargeproportionofdiploidcells.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(3)Chromosomenon-disjunction

Thefailureofapairofhomologouschromosomestoseparateproperlyduringmeiosis.Thefailureofhomologues(atmeiosis)orsisterchromatids(atmitosis)toseparateproperlytooppositepoles,thatistwochromosomesorchromatidsgotoonepoleandnonetotheother.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Non-disjunctioncanoccurduringmeiosisIormeiosisII.

AnerrorinthepropersegregationofthechromosomesduringbothmeiosisIandIIarepicturedbelow.

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變InmeiosisI,theerroroccurswhenthehomologouspairsbothtravelintothesamedaughtercell.

Theresultistwodaughtercellsthathavetwocopiesofthechromosome(calleddisomiccells)andtwocellsthataremissingthatchromosome(callednullisomiccells).

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Non-disjunctioninMeiosisI:

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變InmeiosisII,theerroroccurswhenthesisterchromatidswillnotseparateandthustravelintothesamedaughtercell.

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Non-disjunctioninMeiosisII:醫(yī)學(xué)遺傳學(xué)10人類染色體畸變FertilizationfollowingMeiosisIerror:

醫(yī)學(xué)遺傳學(xué)10人類染色體畸變FertilizationfollowingMeiosisIIerror:醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變B.ChromosomeStructuralAberration

Structuralaberrationisachangeinchromosomestructuredetectablebymicroscopicexaminationofthemetaphasestageofcelldivision,observedasdeletionsandfragments,intrachangesorinterchanges.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(1)

Achromosomedeletionoccurswhenthechromosomebreaksandapieceislost.Thisofcourseinvolveslossofgeneticinformationandresultsinwhatcouldbeconsidered"partialmonosomy"forthatchromosome.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(2)Arelatedabnormalityisachromosomeinversion.

Inthiscase,abreakorbreaksoccurandthatfragmentofchromosomeisinvertedandrejoinedratherthanbeinglost.Inversionsarethusrearrangementsthatdonotinvolvelossofgeneticmaterialand,unlessthebreakpointsdisruptanimportantgene,individualscarryinginversionshaveanormalphenotype.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(3)ChromosomeDuplicationisjustthat,aduplicationofasectionofachromosome.

Aduplicationissometimesreferredtoasa'partialtrisomy'.Trisomyreferstothree.Thereforeifaduplicationexists,thatindividualhasthreecopiesofthatareainsteadoftwo.Thismeansthereareextrainstructions(genes)presentthatcancauseanincreasedriskforbirthdefectsordevelopmentalproblems.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(4)Aringchromosomecanhappenintwoways.Oneisdemonstratedinthepicture;theendofthepandqarmbreaksoffandthensticktoeachother.Thebluepartsofeacharelostthusresultinginlossofinformation.Second,theendsofthepandqarmsticktogether(fusion),usuallywithoutlossofmaterial.Howevertheringcancauseproblemswhenthecelldividesandcancauseproblemsfortheindividual.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變(5)

Translocationsarechromosomalabnormalitieswhichoccurwhenchromosomesbreakandthefragmentsrejointootherchromosomes.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Therearemanystructurallydifferenttypesoftranslocations.Aswithinversions,thereisnolossofgeneticmaterial,althoughthebreakpointcancausedisruptionofacriticalgeneorjuxtaposepiecesoftwogenestocreateafusiongenethatinducescancer.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Ingeneralhowever,theproblemwithtranslocationsoccursduringmeiosisandismanifestasreductionsinfertility.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變Reciprocaltranslocations

Inareciprocaltranslocation,twonon-homologouschromosomesbreakandexchangefragments.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Individualscarryingsuchabnormalitiesstillhaveabalancedcomplementofchromosomesandgenerallyhaveanormalphenotype,butwithvaryingdegreesofsubnormalfertility.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變醫(yī)學(xué)遺傳學(xué)10人類染色體畸變

Translocationsarethusheritableandcanbeperpetuatedinpopulations.醫(yī)學(xué)遺傳學(xué)10人類染色體畸變CentricFusions

Acentricfusionisatranslocationinwhichthecentromeresoftwoacrocentricchromosomesfusetogenerateonelargemetacentricchromosome.