医学遗传学 10人类染色体畸变课件

10人类染色体畸变

chromosomeaberration

医学遗传学10人类染色体畸变Anytypeofchangeinthechromosomestructureornumber(deficiencies,duplications,translocations,inversions,etc.).医学遗传学10人类染色体畸变Althoughitcanbeamechanismforenhancinggeneticdiversity,suchalterationsareusuallyfatalorill-adaptive,especiallyinanimals.医学遗传学10人类染色体畸变1.factorsinducingchromosomeaberration

A.Ionizingradiation

Ionizingradiationproducesrearrangementsofthegenome.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变WhenirradiationoccursduringtheG0/G1phaseofthecellcycle,large-scalerearrangementsappearasexchange-typechromosomeaberrationsatthenextmitosis.Suchaberrationscanaltercellularphenotypes,andareimportantinvariousareasofbiology:医学遗传学10人类染色体畸变Medicalandpublic-healthapplicationsincludeperinataldiagnosticscharacterizationofspecificcancertypes,carcinogenesisriskestimation,radiationbiodosimetryandradiotherapeutictreatmentplanning.医学遗传学10人类染色体畸变Analyzingchromosomeaberrationshelpscharacterizerepair/misrepairpathwaysinvolvedintheprocessingofDNAdamage.Ionizingradiationhassomeuniquefeaturesasaprobeofsuchpathways.Comparedtoothergenotoxicagents,itproducescopiousquantitiesofDNAdoublestrandbreaks(DSBs),anditstimingcanbecontrolledmoreaccurately.医学遗传学10人类染色体畸变Moreover,initialradiationdamagehasadiscrete,stochasticcharacterthatcanbemodulatedbyusingdifferentkindsofradiation(e.g.a-particlesversusx-rays)havingdifferentionizationdensities.医学遗传学10人类染色体畸变Thespectrumofdifferentradiation-inducedchromosomeaberrationsisinformativeaboutthegeometryofchromosomesduringinterphase,andviceversa.医学遗传学10人类染色体畸变Chromosomalinstability,inwhichnewaberrations(thoughoftennotofthetypecharacteristicofG0/G1damage)continuetoarisemanygenerationsafterirradiation,representsaformofgenomicinstability,andgenomicinstabilityisprominentduringneoplasticprogression.医学遗传学10人类染色体畸变B.chemicalmutagen

Akindofsubstances,suchasdrugsortoxins,thatcauseschromosomalaberrationsoflivingorganisms,orincreasetherateofmutation.

医学遗传学10人类染色体畸变2.chromosomalaberrationsA.

chromosomenumericalaberrationNumericalaberrationisachangeinthenumberofchromosomesfromthenormalnumbercharacteristicofthehumanbeings.医学遗传学10人类染色体畸变(1)Euploidyistheconditionofhavinganormalnumberofstructurallynormalchromosomes.

Euploidhumanfemaleshave46chromosomes(44autosomesandtwoXchromosomes).医学遗传学10人类染色体畸变

Polyploidyisamultipleofthehaploidchromosomenumber(n)otherthanthediploidnumber(i.e.,3n,4nandsoon).医学遗传学10人类染色体畸变(2)

Aneuploidyistheconditionofhavinglessthanormorethanthenormaldiploidnumberofchromosomes,andisthemostfrequentlyobservedtypeofcytogeneticabnormality.

Inotherwords,itisanydeviationfromeuploidy,althoughmanyauthorsrestrictuseofthistermtoconditionsinwhichonlyasmallnumberofchromosomesaremissingoradded.医学遗传学10人类染色体畸变Generally,aneuploidyisrecognizedasasmalldeviationfromeuploidyforthesimplereasonthatmajordeviationsarerarelycompatiblewithsurvival,andsuchindividualsusuallydieprenatally.医学遗传学10人类染色体畸变Thetwomostcommonlyobservedformsofaneuploidyaremonosomyandtrisomy.医学遗传学10人类染色体畸变

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

医学遗传学10人类染色体畸变

Trisomyishavingthreechromosomesofaparticulartype.Acommonautosomaltrisomyinhumansin

Downsyndrome,ortrisomy21,inwhichapersonhasthreeinsteadofthenormaltwochromosome21s.Trisomyisaspecificinstanceofpolysomy,amoregeneraltermthatindicateshavingmorethantwoofanygivenchromosome.医学遗传学10人类染色体畸变Anothertypeofaneuploidyistriploidy.Atriploidindividualhasthreeofeverychromosome,thatis,threehaploidsetsofchromosomes.Atriploidhumanwouldhave69chromosomes(3haploidsetsof23).医学遗传学10人类染色体畸变Productionoftriploidsseemstoberelativelycommonandcanoccurby,forexample,fertilizationbytwosperm.医学遗传学10人类染色体畸变However,birthofalivetriploidisextraordinarilyrareandsuchindividualsarequiteabnormal.Theraretriploidthatsurvivesformorethanafewhoursafterbirthisalmostcertainlyamosaic,havingalargeproportionofdiploidcells.医学遗传学10人类染色体畸变(3)Chromosomenon-disjunction

Thefailureofapairofhomologouschromosomestoseparateproperlyduringmeiosis.Thefailureofhomologues(atmeiosis)orsisterchromatids(atmitosis)toseparateproperlytooppositepoles,thatistwochromosomesorchromatidsgotoonepoleandnonetotheother.医学遗传学10人类染色体畸变Non-disjunctioncanoccurduringmeiosisIormeiosisII.

AnerrorinthepropersegregationofthechromosomesduringbothmeiosisIandIIarepicturedbelow.

医学遗传学10人类染色体畸变InmeiosisI,theerroroccurswhenthehomologouspairsbothtravelintothesamedaughtercell.

Theresultistwodaughtercellsthathavetwocopiesofthechromosome(calleddisomiccells)andtwocellsthataremissingthatchromosome(callednullisomiccells).

医学遗传学10人类染色体畸变Non-disjunctioninMeiosisI:

医学遗传学10人类染色体畸变InmeiosisII,theerroroccurswhenthesisterchromatidswillnotseparateandthustravelintothesamedaughtercell.

医学遗传学10人类染色体畸变Non-disjunctioninMeiosisII:医学遗传学10人类染色体畸变FertilizationfollowingMeiosisIerror:

医学遗传学10人类染色体畸变FertilizationfollowingMeiosisIIerror:医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变B.ChromosomeStructuralAberration

Structuralaberrationisachangeinchromosomestructuredetectablebymicroscopicexaminationofthemetaphasestageofcelldivision,observedasdeletionsandfragments,intrachangesorinterchanges.医学遗传学10人类染色体畸变(1)

Achromosomedeletionoccurswhenthechromosomebreaksandapieceislost.Thisofcourseinvolveslossofgeneticinformationandresultsinwhatcouldbeconsidered"partialmonosomy"forthatchromosome.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变(2)Arelatedabnormalityisachromosomeinversion.

Inthiscase,abreakorbreaksoccurandthatfragmentofchromosomeisinvertedandrejoinedratherthanbeinglost.Inversionsarethusrearrangementsthatdonotinvolvelossofgeneticmaterialand,unlessthebreakpointsdisruptanimportantgene,individualscarryinginversionshaveanormalphenotype.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变(3)ChromosomeDuplicationisjustthat,aduplicationofasectionofachromosome.

Aduplicationissometimesreferredtoasa'partialtrisomy'.Trisomyreferstothree.Thereforeifaduplicationexists,thatindividualhasthreecopiesofthatareainsteadoftwo.Thismeansthereareextrainstructions(genes)presentthatcancauseanincreasedriskforbirthdefectsordevelopmentalproblems.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变(4)Aringchromosomecanhappenintwoways.Oneisdemonstratedinthepicture;theendofthepandqarmbreaksoffandthensticktoeachother.Thebluepartsofeacharelostthusresultinginlossofinformation.Second,theendsofthepandqarmsticktogether(fusion),usuallywithoutlossofmaterial.Howevertheringcancauseproblemswhenthecelldividesandcancauseproblemsfortheindividual.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变(5)

Translocationsarechromosomalabnormalitieswhichoccurwhenchromosomesbreakandthefragmentsrejointootherchromosomes.医学遗传学10人类染色体畸变Therearemanystructurallydifferenttypesoftranslocations.Aswithinversions,thereisnolossofgeneticmaterial,althoughthebreakpointcancausedisruptionofacriticalgeneorjuxtaposepiecesoftwogenestocreateafusiongenethatinducescancer.医学遗传学10人类染色体畸变

Ingeneralhowever,theproblemwithtranslocationsoccursduringmeiosisandismanifestasreductionsinfertility.医学遗传学10人类染色体畸变Reciprocaltranslocations

Inareciprocaltranslocation,twonon-homologouschromosomesbreakandexchangefragments.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变

Individualscarryingsuchabnormalitiesstillhaveabalancedcomplementofchromosomesandgenerallyhaveanormalphenotype,butwithvaryingdegreesofsubnormalfertility.医学遗传学10人类染色体畸变医学遗传学10人类染色体畸变

Translocationsarethusheritableandcanbeperpetuatedinpopulations.医学遗传学10人类染色体畸变CentricFusions

Acentricfusionisatranslocationinwhichthecentromeresoftwoacrocentricchromosomesfusetogenerateonelargemetacentricchromosome.