《醫(yī)學(xué)遺傳學(xué)》第四章 人類染色體與染色體病課件

第四章人類染色體和染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病PainterTS.Studiesinmammalianspermatogenesis.II.Thespermatogenesisofman.JExpZool.1923;37:291-336DarkAges《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病HsuTC.Mammalianchromosomesinvitro.I.Thekaryotypeofman.JHered.1952;43:167-172TjioJH,LevanA.Thechromosomenumberofman.AmJObstetGynecol.1956;130:723-724HypotonicPeriodDarkAges《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病TrisomyPeriodLejeuneJ,etal.Etudedeschromosomessomatiquesdeneufenfantsmongoliens.G.R.Acad.Sciences.1959;248:1721-1722FordCE,etal.Asexchromosomalanomalyinacaseofgonadaldysgenesis(Turner'ssyndrome).Lancet.1959;1:711-713JacobPA,etal.AcaseofhumanintersexualityhavingapossibleXXYsexdeterminingmechanism.Nature.1959;183:302-303.HypotonicPeriodDarkAges《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病BandingEraCasperssonT,etal.Differentialbandingofalkylatingfluorochromesinhumanchromosomes.ExpCellRes.1970;60:315-319HypotonicPeriodDarkAgesTrisomyPeriod《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病MolecularEraPardueML,etal.MolecularhybridizationofradioactiveDNAtotheDNAofcytologicalpreparations.Proc.Natl.Acad.Sci.USA.1969;64:600-604PinkelD,etal.Cytogeneticanalysisusingquantitative,high-sensitivity,fluorescencehybridization.Proc.Natl.Acad.Sci.USA.1986;83:2934-2938.HypotonicPeriodDarkAgesBandingEraTrisomyPeriod《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DenverSystemThekaryotypeisaphotographofallofthechromosomesofanindividualcell;thetermcoversthenumber,relativesizesandstructureofthechromosomes.核型：一個體細(xì)胞中的全部染色體，按其大小、形態(tài)特征順序排列所構(gòu)成的圖像。《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Chromosomecanbedistinguishedbythe

relativesizesand

thepositionofthecentromere.Metacentric(1,3,16,19,20)Submetacentric(2,4-12,17,18,X)Acrocentric(13,14,15,21,22,Y)DenverSystem《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Karyotypeanalysis:

arrangingthechromosomesofacellintoakaryotype,thenanalysisandcomparewith

Denversystem.DenverSystemThekaryotypeisaphotographofallofthechromosomesofanindividualcell;thetermcoversthenumber,relativesizesandstructureofthechromosomes.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DenverSystem《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病BandingPatternBand（帶）:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.Bandingpattern（帶型）：treatedwithchemicaldyes,24typesofchromosomesappearitsuniquestriationsindividually.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Q-banding：QMBandingPatternBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Q-banding：QMG-banding：pancreatin＋GiemsaBandingPatternBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病R-banding：treatedspecimen＋GiemsaorAcridineOrangeBandingPatternQ-banding：QMG-banding：pancreatin＋GiemsaBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病C-banding：Ychromosome,centromere,secondaryconstrictionBandingPatternR-banding：treatedspecimen＋GiemsaorAcridineOrangeQ-banding：QMG-banding：pancreatin＋GiemsaBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病T-banding：endingofchromosomeBandingPatternC-banding：Ychromosome,centromere,secondaryconstrictionR-banding：treatedspecimen＋GiemsaorAcridineOrangeQ-banding：QMG-banding：pancreatin＋GiemsaBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病N-banding：AgNO3＋Giemsa,NORT-banding：endingofchromosomeBandingPatternC-banding：Ychromosome,centromere,secondaryconstrictionR-banding：treatedspecimen＋GiemsaorAcridineOrange

Q-banding：QMG-banding：pancreatin＋GiemsaBand:

treatedwithchemicaldyes,thechromosomewillappearasaseriesofalternatedarkandlightstriations.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病LandmarkXpXqRegionBand112212345678Xq28BandingPattern《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Development1.Highresolutionbandingchromosome(HRBC)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH(fluorescenceinsituhybridization)3.MolecularcytogeneticsDevelopment2.Microcytogenetics1.Highresolutionbandingchromosome(HRBC)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病X染色體Y染色體13號染色體18號染色體21號染色體FISH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病

FISH(fluorescenceinsituhybridization)

DNAfiber-FISH3.MolecularcytogeneticsDevelopment2.Microcytogenetics1.Highresolutionbandingchromosome(HRBC)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DNAfiber-FISH3cosmidfromMHClocus35～40Kb/cosmid《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH(fluorescenceinsituhybridization)DNAfiber-FISH

ChromosomePainting3.MolecularcytogeneticsDevelopment2.Microcytogenetics1.Highresolutionbandingchromosome(HRBC)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomePainting《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomePainting《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomePainting《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病FISH(fluorescenceinsituhybridization)DNAfiber-FISH

ChromosomePainting

CGH(comparativegenomichybridization)3.MolecularcytogeneticsDevelopment2.Microcytogenetics1.Highresolutionbandingchromosome(HRBC)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病CGH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病CGH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病CGH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病AdvantagesWholegenomein1experimentNoneedtoculturetumorcellsSensitivedetectionofgeneamplificationDisadvantagesLimitedresolution(~10Mbdel/dup)LaboriousOnlygainsandlosses/nobalancedrearrangementsNoinformationonthenatureoftheaberrationsRetrospectiveanalysisCGH《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病HeteromorphismBandingpatternpolymorphismChromosomeheteromorphismsarenormalvariationsintheappearanceofchromosomes.BeinheritedinaMendelianfashionConstitutiveheterochromatinNotchromosomalabnormalityinclinical《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病HeteromorphismBandingpatternpolymorphismChromosomallengthSatelliteSecondaryconstrictionPolymorphismofQ,G,Cbanding《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomalAberrationNumericalAbnormalityStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病NumericalAbnormality單倍體:22+X,22+Y二倍體:44+XX,44+XY《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病NumericalAbnormalityVariationinchromosomenumbercantake2forms:整倍體:

thatwhichinvolveswholesets(genomes)ofchromosomes非整倍體:

thechromosomenumberisnotanexactmultipleofthehaploid（單倍體）number《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病整倍體三倍體:thecellwhichhas3sets(genomes)ofchromosomes——3n＝69NumericalAbnormality《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病NumericalAbnormality整倍體三倍體:thecellwhichhas3sets(genomes)ofchromosomes——3n＝69Tripolarspindle《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病

雙雄受精:

fertilizationof1oocyteby2spermatozoa

雙雌受精:

non-expulsionofthe2ndpolarbodyNumericalAbnormality整倍體三倍體:thecellwhichhas3sets(genomes)ofchromosomes——3n＝69《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病整倍體——多倍體四倍體:thecellwhichhas4sets(genomes)ofchromosomes——4n＝92核內(nèi)復(fù)制NumericalAbnormality《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病核內(nèi)復(fù)制雙分染色體《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病

Diplochromosome整倍體——多倍體四倍體:thecellwhichhas4sets(genomes)ofchromosomes——4n＝92核內(nèi)復(fù)制NumericalAbnormality核內(nèi)有絲分裂《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病BefoundmorecommonlythanEuploid(整倍體)亞二倍體:lessthanthenormal2nnumberofchromosomesNumericalAbnormality非整倍體超二倍體:morethanthenormal2nnumberofchromosomes《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病單體型:isthepresenceofonlyonecopyofanychromosomeLossofautosomesisnottoleratedTurnersyndrome:45,XNumericalAbnormality非整倍體亞二倍體《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病BefoundmorecommonlythanMonosomyTrisomy

ofsexchromosomeismorecommonlyNumericalAbnormality非整倍體超二倍體三體型:isthepresenceofonlythreecopyofanychromosome《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Meiotic(減數(shù)分裂)non-disjunctionMitotic(有絲分裂)non-disjunctionChromosomenon-disjunctionNumericalAbnormalityMechanismofAneuploid(非整倍體)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Meiosisinanimals.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病MeioticNon-DisjunctionMeioticnon-disjunctionarisesfromfailureofpairedhomologouschromosomesorsisterchromatidtodisjoinatmeioticanaphase.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病MeioticNon-Disjunction2NNN＋1N－12N＋12N＋12N－12N－1N＋1N＋1N－1N－12N2N2N＋12N－12NNNNNN－1N＋1《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Primarynon-disjunctionPrimarynon-disjunction

isthefailureofchromosomesor

sisterchromatid

toseparateinmeiosis.Thegametethushastwocopiesofachromosome.Fertilizationaddsanothercopytogiveatotalof3copies.Secondarynon-disjunctionTrisomyoffspringarisefromsegregationatmeiosisofanalready-trisomyparent.MeioticNon-Disjunction《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病MeioticNon-Disjunction2N+1N2N2N2N＋12N＋1NN＋1NNN＋1N＋1《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Meioticnon-disjunctionMitoticnon-disjunctionChromosomenon-disjunctionNumericalAbnormalityMechanismofAneuploid《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Mitosisinanimalcells.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病MitoticNon-DisjunctionMitoticnon-disjunctionarisesfromfailureofsisterchromatidstodisjoinatmitoticanaphase.2N2N2N2N2N2N－12N＋12N2N－12N＋147/45Mosaic46/47/45Mosaic《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Meioticnon-disjunctionMitoticnon-disjunctionChromosomenon-disjunctionChromosomelossNumericalAbnormalityMechanismofAneuploid《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Thecausalitywhereachromosomeismissingfromthenewcellcreatedviacelldivision.Anaphaselag(染色體分裂后期延滯)

maybeduetodelayedmovementofachromosomeatanaphase.ChromosomeLoss《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病TheBreakage

andthe

Rejoin

afterbreakagearethebasisofchromosomalstructuralaberration.ChromosomalrearrangementRearrangementchromosomeStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病TerminalDeletionStructuralAberration4q27《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病InterstitialDeletionStructuralAberration4q134q25《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ParacentricInversionStructuralAberration4q134q24《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病PericentricInversionStructuralAberration4p144q21《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationPericentricInversion《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationPericentricInversion《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病InversionloopStructuralAberrationPericentricInversion《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationPericentricInversion《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病InversionloopStructuralAberrationPericentricInversion《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病RingChromosomeStructuralAberration2q312p21《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病RingChromosomeStructuralAberration2q312p21p21q31《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病RingChromosomeStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病RingChromosomeStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ReciprocalTranslocationStructuralAberration4q2520q12《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationReciprocalTranslocation《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationReciprocalTranslocation《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ABCDFour-wayjunctionStructuralAberrationReciprocalTranslocation《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病RobertsonianTranslocationStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病StructuralAberrationRobertsonianTranslocation《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病WholeArmTranslocationStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ComplexTranslocationStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病IsochromosomeStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病IsochromosomeStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DicentricChromosomeStructuralAberration6q2211p15《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DirectInsertionStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病InverseInsertionStructuralAberration《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomeDiseaseinClinicalClinicalfeatureThegeneralfeaturesinautosomeabnormalitiesareatriadof

growthretardation,mentalretardation,and

specificsomaticabnormalities.Changeof

sexchromosome

alsohavetheabnormalitiesandmalformationsofinternalorexternalgenitalorgans.《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病DownSyndrome(trisomy21syndrome)ChromosomeDiseaseinClinical《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病CharacteristicsGrowthretardationVaryingdegreesofmentalretardationFlattenedfaceUpwardslantingoftheeyeswithepicanthalfolds(內(nèi)眥贅皮)1in600~800newbornsChromosomeDiseaseinClinicalDownSyndrome(trisomy21syndrome)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病1.

Trisomy

——

95%,47,XX(XY),＋21Causedbynon-disjunctionofchromosome21,correlatedwithageofmother.ChromosomeDiseaseinClinicalDownSyndrome(trisomy21syndrome)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病Karyotypeofaffected：46,XX(XY),－14,＋t(14q21q)2.

Mosaic

——

2%~4%,46/473.

UnbalancetranslocationKaryotypeofbalancecarrier：45,XX(XY),－14,－21,＋t(14q21q)ChromosomeDiseaseinClinical1.

Trisomy

——

92.5%,47,XX(XY),＋21DownSyndrome(trisomy21syndrome)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病1in3500~8000newbornsEdwardsSyndrome(trisomy18syndrome)CharacteristicsGrowthretardationMentalretardationCongenitalheartdiseaseRocker-bottomfeetfixedflexiondeformityofthefingersChromosomeDiseaseinClinical《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病ChromosomeDiseaseinClinical1in3500~8000newbornsEdwardsSyndrome(trisomy18syndrome)《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病1in25000newbornsPatauSyndrome(trisomy13syndrome)CharacteristicsVaryingdegreesofmentalretardationCleftlip&CleftpalatePolydactyly(postaxial)EquinovarusChromosomeDiseaseinClinical《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體與染色體病1in50000newborns5p-

Syndrome(CatCrysyndrome)CharacteristicsRound,moon-shapedface“Cryofthecat”VaryingdegreesofmentalretardationLowsetearsChromosomeDiseaseinClinical《醫(yī)學(xué)遺傳學(xué)》第四章人類染色體