医学遗传学人类染色体与染色体病PPT课件.ppt

第四章人类染色体和染色体病 1 PainterTS Studiesinmammalianspermatogenesis II Thespermatogenesisofman JExpZool 1923 37 291 336 DarkAges 2 HsuTC Mammalianchromosomesinvitro I Thekaryotypeofman JHered 1952 43 167 172TjioJH LevanA Thechromosomenumberofman AmJObstetGynecol 1956 130 723 724 HypotonicPeriod DarkAges 3 TrisomyPeriod LejeuneJ 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 HypotonicPeriod DarkAges 4 BandingEra CasperssonT etal Differentialbandingofalkylatingfluorochromesinhumanchromosomes ExpCellRes 1970 60 315 319 HypotonicPeriod DarkAges TrisomyPeriod 5 MolecularEra PardueML 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 HypotonicPeriod DarkAges BandingEra TrisomyPeriod 6 DenverSystem Thekaryotypeisaphotographofallofthechromosomesofanindividualcell thetermcoversthenumber relativesizesandstructureofthechromosomes 核型 一个体细胞中的全部染色体 按其大小 形态特征顺序排列所构成的图像 7 Chromosomecanbedistinguishedbytherelativesizesandthepositionofthecentromere Metacentric 1 3 16 19 20 Submetacentric 2 4 12 17 18 X Acrocentric 13 14 15 21 22 Y DenverSystem 8 Karyotypeanalysis arrangingthechromosomesofacellintoakaryotype thenanalysisandcomparewithDenversystem DenverSystem Thekaryotypeisaphotographofallofthechromosomesofanindividualcell thetermcoversthenumber relativesizesandstructureofthechromosomes 9 DenverSystem 10 BandingPattern Band 带 treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations Bandingpattern 带型 treatedwithchemicaldyes 24typesofchromosomesappearitsuniquestriationsindividually 11 Q banding QM BandingPattern Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 12 13 Q banding QM G banding pancreatin Giemsa BandingPattern Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 14 15 R banding treatedspecimen GiemsaorAcridineOrange BandingPattern Q banding QM G banding pancreatin Giemsa Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 16 17 18 C banding Ychromosome centromere secondaryconstriction BandingPattern R banding treatedspecimen GiemsaorAcridineOrange Q banding QM G banding pancreatin Giemsa Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 19 20 21 T banding endingofchromosome BandingPattern C banding Ychromosome centromere secondaryconstriction R banding treatedspecimen GiemsaorAcridineOrange Q banding QM G banding pancreatin Giemsa Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 22 23 N banding AgNO3 Giemsa NOR T banding endingofchromosome BandingPattern C banding Ychromosome centromere secondaryconstriction R banding treatedspecimen GiemsaorAcridineOrange Q banding QM G banding pancreatin Giemsa Band treatedwithchemicaldyes thechromosomewillappearasaseriesofalternatedarkandlightstriations 24 25 Landmark Xp Xq Region Band 1 1 2 2 12345678 Xq28 BandingPattern 26 Development 1 Highresolutionbandingchromosome HRBC 27 28 FISH fluorescenceinsituhybridization 3 Molecularcytogenetics Development 2 Microcytogenetics 1 Highresolutionbandingchromosome HRBC 29 FISH 30 FISH 31 FISH 32 FISH 33 FISH fluorescenceinsituhybridization DNAfiber FISH 3 Molecularcytogenetics Development 2 Microcytogenetics 1 Highresolutionbandingchromosome HRBC 34 DNAfiber FISH 3cosmidfromMHClocus35 40Kb cosmid 35 FISH fluorescenceinsituhybridization DNAfiber FISH ChromosomePainting 3 Molecularcytogenetics Development 2 Microcytogenetics 1 Highresolutionbandingchromosome HRBC 36 ChromosomePainting 37 ChromosomePainting 38 ChromosomePainting 39 FISH fluorescenceinsituhybridization DNAfiber FISH ChromosomePainting CGH comparativegenomichybridization 3 Molecularcytogenetics Development 2 Microcytogenetics 1 Highresolutionbandingchromosome HRBC 40 CGH 41 CGH 42 CGH 43 Advantages Wholegenomein1experiment Noneedtoculturetumorcells Sensitivedetectionofgeneamplification Disadvantages Limitedresolution 10Mbdel dup Laborious Onlygainsandlosses nobalancedrearrangements Noinformationonthenatureoftheaberrations Retrospectiveanalysis CGH 44 Heteromorphism Bandingpatternpolymorphism Chromosomeheteromorphismsarenormalvariationsintheappearanceofchromosomes BeinheritedinaMendelianfashion ConstitutiveheterochromatinNotchromosomalabnormalityinclinical 45 Heteromorphism Bandingpatternpolymorphism ChromosomallengthSatelliteSecondaryconstrictionPolymorphismofQ G Cbanding 46 ChromosomalAberration NumericalAbnormality StructuralAberration 47 NumericalAbnormality 单倍体 22 X 22 Y 二倍体 44 XX 44 XY 48 NumericalAbnormality Variationinchromosomenumbercantake2forms 整倍体 thatwhichinvolveswholesets genomes ofchromosomes 非整倍体 thechromosomenumberisnotanexactmultipleofthehaploid 单倍体 number 49 整倍体 三倍体 thecellwhichhas3sets genomes ofchromosomes 3n 69 NumericalAbnormality 50 NumericalAbnormality 整倍体 三倍体 thecellwhichhas3sets genomes ofchromosomes 3n 69 Tripolarspindle 51 双雄受精 fertilizationof1oocyteby2spermatozoa 双雌受精 non expulsionofthe2ndpolarbody NumericalAbnormality 整倍体 三倍体 thecellwhichhas3sets genomes ofchromosomes 3n 69 52 整倍体 多倍体 四倍体 thecellwhichhas4sets genomes ofchromosomes 4n 92 核内复制 NumericalAbnormality 53 核内复制 双分染色体 54 Diplochromosome 整倍体 多倍体 四倍体 thecellwhichhas4sets genomes ofchromosomes 4n 92 核内复制 NumericalAbnormality 核内有丝分裂 55 BefoundmorecommonlythanEuploid 整倍体 亚二倍体 lessthanthenormal2nnumberofchromosomes NumericalAbnormality 非整倍体 超二倍体 morethanthenormal2nnumberofchromosomes 56 单体型 isthepresenceofonlyonecopyofanychromosome Lossofautosomesisnottolerated Turnersyndrome 45 X NumericalAbnormality 非整倍体 亚二倍体 57 BefoundmorecommonlythanMonosomy Trisomyofsexchromosomeismorecommonly NumericalAbnormality 非整倍体 超二倍体 三体型 isthepresenceofonlythreecopyofanychromosome 58 Meiotic 减数分裂 non disjunction Mitotic 有丝分裂 non disjunction Chromosomenon disjunction NumericalAbnormality MechanismofAneuploid 非整倍体 59 Meiosisinanimals 60 MeioticNon Disjunction Meioticnon disjunctionarisesfromfailureofpairedhomologouschromosomesorsisterchromatidtodisjoinatmeioticanaphase 61 MeioticNon Disjunction 62 Primarynon disjunction Primarynon disjunctionisthefailureofchromosomesorsisterchromatidtoseparateinmeiosis Thegametethushastwocopiesofachromosome Fertilizationaddsanothercopytogiveatotalof3copies Secondarynon disjunction Trisomyoffspringarisefromsegregationatmeiosisofanalready trisomyparent MeioticNon Disjunction 63 MeioticNon Disjunction 64 Meioticnon disjunction Mitoticnon disjunction Chromosomenon disjunction NumericalAbnormality MechanismofAneuploid 65 Mitosisinanimalcells 66 MitoticNon Disjunction Mitoticnon disjunctionarisesfromfailureofsisterchromatidstodisjoinatmitoticanaphase 47 45Mosaic 46 47 45Mosaic 67 Meioticnon disjunction Mitoticnon disjunction Chromosomenon disjunction Chromosomeloss NumericalAbnormality MechanismofAneuploid 68 Thecausalitywhereachromosomeismissingfromthenewcellcreatedviacelldivision Anaphaselag 染色体分裂后期延滞 maybeduetodelayedmovementofachromosomeatanaphase ChromosomeLoss 69 TheBreakageandtheRejoinafterbreakagearethebasisofchromosomalstructuralaberration Chromosomalrearrangement Rearrangementchromosome StructuralAberration 70 TerminalDeletion StructuralAberration 71 InterstitialDeletion StructuralAberration 4q13 72 ParacentricInversion StructuralAberration 4q13 73 PericentricInversion StructuralAberration 4p14 74 StructuralAberration PericentricInversion 75 StructuralAberration PericentricInversion 76 Inversionloop StructuralAberration PericentricInversion 77 StructuralAberration PericentricInversion 78 Inversionloop StructuralAberration PericentricInversion 79 RingChromosome StructuralAberration 80 RingChromosome StructuralAberration 81 RingChromosome StructuralAberration 82 RingChromosome StructuralAberration 83 ReciprocalTranslocation StructuralAberration 84 StructuralAberration ReciprocalTranslocation 85 StructuralAberration ReciprocalTranslocation 86 StructuralAberration ReciprocalTranslocation 87 RobertsonianTranslocation StructuralAberration 88 StructuralAberration RobertsonianTranslocation 89 WholeArmTranslocation StructuralAberration 90 ComplexTranslocation StructuralAberration 91 Isochromosome StructuralAberration 92 Isochromosome StructuralAberration 93 DicentricChromosome StructuralAberration 94 DirectInsertion StructuralAberration 95 InverseInsertion StructuralAberration 96 ChromosomeDiseaseinClinical Clinicalfeature Thegeneralfeaturesinautosomeabnormalitiesareatriadofgrowthretardation mentalretardation andspecificsomaticabnormalities Changeofsexchromosomealsohavetheabnormalitiesandmalformationsofinternalorexternalgenitalorgans 97 DownSyndrome trisomy21syndrome ChromosomeDiseaseinClinical 98 Characteristics GrowthretardationVaryingdegreesofmentalretardationFlattenedfaceUpwardslantingoftheeyeswithepicanthalfolds 内眦赘皮 1in600 800newborns ChromosomeDiseaseinClinical DownSyndrome trisomy21syndrome 99 1 Trisomy 95 47 XX XY 21 Causedbynon disjunctionofchromosome21 correlatedwithageofmother ChromosomeDiseaseinClinical DownSyndrome trisomy21syndrome 100 101 102 Karyotypeofaffected 46 XX XY 14 t 14q21q 2 Mosaic 2 4 46 47 3 Unbalancetranslocation Karyotypeofbalancecarrier 45 XX XY 14 21 t 14q21q ChromosomeDiseaseinClinical 1 Trisomy 92 5 47 XX XY 21 DownSyndrome trisomy21syndrome 103 104 105 106 1in3500 8000newborns EdwardsSyndrome trisomy18syndrome Characteristics GrowthretardationMentalretardationCongenitalheartdiseaseRocker bottomfeetfixedflexiondeformityofthefingers ChromosomeDiseaseinClinical 107 ChromosomeDiseaseinClinical 1in3500 8000newborns EdwardsSyndrome trisomy18syndrome 108 109 1in25000newborns PatauSyndrome trisomy13syndrome Characteristics VaryingdegreesofmentalretardationCleftlip CleftpalatePolydactyly postaxial Equinovarus ChromosomeDiseaseinClinical 110 111 1in50000newborns 5p Syndrome CatCrysyndrome Characteristics Round moon shapedface Cryoft