医学遗传学-10人类染色体畸变-课件

10人类染色体畸变

chromosomeaberration

10人类染色体畸变

chromosomeaber1Anytypeofchangeinthechromosomestructureornumber(deficiencies,duplications,translocations,inversions,etc.).Anytypeofchangein2Althoughitcanbeamechanismforenhancinggeneticdiversity,suchalterationsareusuallyfatalorill-adaptive,especiallyinanimals.Althoughitcanbea31.factorsinducingchromosomeaberration

A.Ionizingradiation

Ionizingradiationproducesrearrangementsofthegenome.1.factorsinducingchromosome4医学遗传学-10人类染色体畸变-课件5WhenirradiationoccursduringtheG0/G1phaseofthecellcycle,large-scalerearrangementsappearasexchange-typechromosomeaberrationsatthenextmitosis.Suchaberrationscanaltercellularphenotypes,andareimportantinvariousareasofbiology:Whenirradiationoccurs6Medicalandpublic-healthapplicationsincludeperinataldiagnosticscharacterizationofspecificcancertypes,carcinogenesisriskestimation,radiationbiodosimetryandradiotherapeutictreatmentplanning.Medicalandpublic-hea7Analyzingchromosomeaberrationshelpscharacterizerepair/misrepairpathwaysinvolvedintheprocessingofDNAdamage.Ionizingradiationhassomeuniquefeaturesasaprobeofsuchpathways.Comparedtoothergenotoxicagents,itproducescopiousquantitiesofDNAdoublestrandbreaks(DSBs),anditstimingcanbecontrolledmoreaccurately.Analyzingchromosomeab8Moreover,initialradiationdamagehasadiscrete,stochasticcharacterthatcanbemodulatedbyusingdifferentkindsofradiation(e.g.a-particlesversusx-rays)havingdifferentionizationdensities.Moreover,initialradi9Thespectrumofdifferentradiation-inducedchromosomeaberrationsisinformativeaboutthegeometryofchromosomesduringinterphase,andviceversa.Thespectrumofdiffe10Chromosomalinstability,inwhichnewaberrations(thoughoftennotofthetypecharacteristicofG0/G1damage)continuetoarisemanygenerationsafterirradiation,representsaformofgenomicinstability,andgenomicinstabilityisprominentduringneoplasticprogression.Chromosomalinstability11B.chemicalmutagen

Akindofsubstances,suchasdrugsortoxins,thatcauseschromosomalaberrationsoflivingorganisms,orincreasetherateofmutation.

B.chemicalmutagen122.chromosomalaberrationsA.

chromosomenumericalaberrationNumericalaberrationisachangeinthenumberofchromosomesfromthenormalnumbercharacteristicofthehumanbeings.2.chromosomalaberrationsA.13(1)Euploidyistheconditionofhavinganormalnumberofstructurallynormalchromosomes.

Euploidhumanfemaleshave46chromosomes(44autosomesandtwoXchromosomes).(1)Euploidyisthecondition14

Polyploidyisamultipleofthehaploidchromosomenumber(n)otherthanthediploidnumber(i.e.,3n,4nandsoon).Polyploidyisamultip15(2)

Aneuploidyistheconditionofhavinglessthanormorethanthenormaldiploidnumberofchromosomes,andisthemostfrequentlyobservedtypeofcytogeneticabnormality.

Inotherwords,itisanydeviationfromeuploidy,althoughmanyauthorsrestrictuseofthistermtoconditionsinwhichonlyasmallnumberofchromosomesaremissingoradded.(2)Aneuploidyistheconditio16Generally,aneuploidyisrecognizedasasmalldeviationfromeuploidyforthesimplereasonthatmajordeviationsarerarelycompatiblewithsurvival,andsuchindividualsusuallydieprenatally.医学遗传学-10人类染色体畸变-课件17Thetwomostcommonlyobservedformsofaneuploidyaremonosomyandtrisomy.Thetwomostcommonl18

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

Monosomyislackofon19

Trisomyishavingthreechromosomesofaparticulartype.Acommonautosomaltrisomyinhumansin

Downsyndrome,ortrisomy21,inwhichapersonhasthreeinsteadofthenormaltwochromosome21s.Trisomyisaspecificinstanceofpolysomy,amoregeneraltermthatindicateshavingmorethantwoofanygivenchromosome.Trisomyishavingthr20Anothertypeofaneuploidyistriploidy.Atriploidindividualhasthreeofeverychromosome,thatis,threehaploidsetsofchromosomes.Atriploidhumanwouldhave69chromosomes(3haploidsetsof23).Anothertypeofaneup21Productionoftriploidsseemstoberelativelycommonandcanoccurby,forexample,fertilizationbytwosperm.Productionoftriplo22However,birthofalivetriploidisextraordinarilyrareandsuchindividualsarequiteabnormal.Theraretriploidthatsurvivesformorethanafewhoursafterbirthisalmostcertainlyamosaic,havingalargeproportionofdiploidcells.However,birthofali23(3)Chromosomenon-disjunction

Thefailureofapairofhomologouschromosomestoseparateproperlyduringmeiosis.Thefailureofhomologues(atmeiosis)orsisterchromatids(atmitosis)toseparateproperlytooppositepoles,thatistwochromosomesorchromatidsgotoonepoleandnonetotheother.(3)Chromosomenon-disjunction24Non-disjunctioncanoccurduringmeiosisIormeiosisII.

AnerrorinthepropersegregationofthechromosomesduringbothmeiosisIandIIarepicturedbelow.

Non-disjunctioncanoc25InmeiosisI,theerroroccurswhenthehomologouspairsbothtravelintothesamedaughtercell.

Theresultistwodaughtercellsthathavetwocopiesofthechromosome(calleddisomiccells)andtwocellsthataremissingthatchromosome(callednullisomiccells).

InmeiosisI,theerro26Non-disjunctioninMeiosisI:

Non-disjunctioninMeiosisI:

27InmeiosisII,theerroroccurswhenthesisterchromatidswillnotseparateandthustravelintothesamedaughtercell.

InmeiosisII,theerro28Non-disjunctioninMeiosisII:Non-disjunctioninMeiosisII:29FertilizationfollowingMeiosisIerror:

FertilizationfollowingMeiosi30FertilizationfollowingMeiosisIIerror:FertilizationfollowingMeiosi31医学遗传学-10人类染色体畸变-课件32B.ChromosomeStructuralAberration

Structuralaberrationisachangeinchromosomestructuredetectablebymicroscopicexaminationofthemetaphasestageofcelldivision,observedasdeletionsandfragments,intrachangesorinterchanges.B.ChromosomeStructuralAberr33(1)

Achromosomedeletionoccurswhenthechromosomebreaksandapieceislost.Thisofcourseinvolveslossofgeneticinformationandresultsinwhatcouldbeconsidered"partialmonosomy"forthatchromosome.(1)Achromosomedeletionoccu34医学遗传学-10人类染色体畸变-课件35医学遗传学-10人类染色体畸变-课件36医学遗传学-10人类染色体畸变-课件37(2)Arelatedabnormalityisachromosomeinversion.

Inthiscase,abreakorbreaksoccurandthatfragmentofchromosomeisinvertedandrejoinedratherthanbeinglost.Inversionsarethusrearrangementsthatdonotinvolvelossofgeneticmaterialand,unlessthebreakpointsdisruptanimportantgene,individualscarryinginversionshaveanormalphenotype.(2)Arelatedabnormalityisa38医学遗传学-10人类染色体畸变-课件39医学遗传学-10人类染色体畸变-课件40医学遗传学-10人类染色体畸变-课件41医学遗传学-10人类染色体畸变-课件42(3)ChromosomeDuplicationisjustthat,aduplicationofasectionofachromosome.

Aduplicationissometimesreferredtoasa'partialtrisomy'.Trisomyreferstothree.Thereforeifaduplicationexists,thatindividualhasthreecopiesofthatareainsteadoftwo.Thismeansthereareextrainstructions(genes)presentthatcancauseanincreasedriskforbirthdefectsordevelopmentalproblems.(3)ChromosomeDuplicationis43医学遗传学-10人类染色体畸变-课件44医学遗传学-10人类染色体畸变-课件45(4)Aringchromosomecanhappenintwoways.Oneisdemonstratedinthepicture;theendofthepandqarmbreaksoffandthensticktoeachother.Thebluepartsofeacharelostthusresultinginlossofinformation.Second,theendsofthepandqarmsticktogether(fusion),usuallywithoutlossofmaterial.Howevertheringcancauseproblemswhenthecelldividesandcancauseproblemsfortheindividual.(4)Aringchromosomecanhapp46医学遗传学-10人类染色体畸变-课件47医学遗传学-10人类染色体畸变-课件48(5)

Translocationsarechromosomalabnormalitieswhichoccurwhenchromosomesbreakandthefragmentsrejointootherchromosomes.(5)Translocationsarechromos49Therearemanystructurallydifferenttypesoftranslocations.Aswithinversions,thereisnolossofgeneticmaterial,althoughthebreakpointcancausedisruptionofacriticalgeneorjuxtaposepiecesoftwogenestocreateafusiongenethatinducescancer.Therearemanystructu50

Ingeneralhowever,theproblemwithtranslocationsoccursduringmeiosisandismanifestasreductionsinfertility.Ingeneralhowever,th51Reciprocaltranslocations

Inareciprocaltranslocation,twonon-homologouschromosomesbreakandexchangefragments.Reciprocaltranslocations52医学遗传学-10人类染色体畸变-课件53医学遗传学-10人类染色体畸变-课件54

Individualscarryingsuchabnormalitiesstillhaveabalancedcomplementofchromosomesandgenerallyhaveanormalphenotype,butwithvaryingdegreesofsubnormalfertility.Individualscarrying55医学遗传学-10人类染色体畸变-课件56

Translocationsarethusheritableandcanbeperpetuatedinpopulations.Translocationsaret57CentricFusions

Acentricfusionisatranslocationinwhichthecentromeresoftwoacrocentricchromosomesfusetogenerateonelargemetacentricchr