医学遗传学英文版教学课件：Chromosome Disorders

ChapterFive

ChromosomeDisorders通知医学遗传学周测：时间：10月18早上8点至19日24点内容：“geneticsinmedicineandgenestructure”、“monogenicdisorders”和“chromosomaldisorders”。每单元约20题，90分钟答题时间。以后每周日0点至24点开放周测。网址：/Portal/index.html请用IE游览器上网，用户名和初始密码均为学号。如有问题邮件咨询助教：lricy1991@1.ChromatinandchromosomeEuchromatin:Slightlyandevenlystained,non-orlow-repetitiveDNAregionsHeterochromatin:Darklyandunevenlystained,highlyrepetitiveDNAregionsChromatininnucleusChromatincompositionDoublehelixNucleosomefiberSolenoidInterphasenucleusChromatinisthebasiccomponentsinthecellnucleusComposedofDNA,histonesandnon-histoneproteinsFromChromatintoChromosome

DifferentmodeofchromatininmetaphaseResultedfromhighlycompactionofchromatin:CellCycle

ChromosomePreparation

Cellculture:Peripheralblood:PHAstimulatingFibroblastfromvarouscellsBonemarrowforleukemiaAmnioticfluidcellforfetaldiagnosisColchicinearrestingmetaphase–

Harvestagreatnumberofmetaphases

HypotonictreatmentChromosomespreadpreparation

IdentifyeachchromosomescaffoldTelomereLongArmShortArmChromatid

Chromatids,twoafterS-phaseCentromereLongarmandshortarmTelomere2.Chromosomeidentification1.MorphologyofchromosomeLength

RL:Relativelength,ChL/totalLofahaploidsetPositionofcentromereAI:Armindex,LongarmL(q)/ShortarmL(p)CI:Centromereindex,q/ChLMetacentricCh.CI:1/2～5/8

SubmetacentricCh.CI:5/8～7/8AcrocentricCh.CI:>7/8

SatelliteCentromereMetacentricChSubmetacentricChAcrocentricChShortArmLongArmSatellitearmInternationalSystemforHumanCytogeneticNomenclature

ISCN,Denver1.Rl:fromlargetosmallChromosomelength:fromlongtoshort2.CI:fromsmalltolargeCentromereposition:fromlowtohigh3.Variableheterochromaticregion:1qh,9qh,16qh,YqSatelliteandsatellitearmofacrocentricchromosomesSexCh.46,XYKaryotyping,7GroupsAB

groupC

groupDE

groupFGMMSubmMSubmSubmacrocacrocM2.BandingofchromosomeQbands:Caspersson(1970)QuinacrinemustardFluorescencemicroscopyBrightanddimbands

Giemsabands:TrypsindigestionGiemsastainingPermanentDarkandlightbandsGBandsReversedbands:Heated,KOHGiemsastainingPermanentDarkandlightbandsreversedtoGbandsRBanding

Heated,KOHGiemsastainingHeterochromatininthecentromeres,longarmoftheYand1qh,9qhand16qhCBands

Nomenclatureofhumanchromosome

SisterchromatidsShortArm,pLongArm,qTelomereZoneBandCentromereheterochromatinZonesandbandsofthechromosmebandzonearmChChromosomesindifferentstagesofphasesofcellcycleMoredetailedanalysisHigh-resolutionbandsFluorescenceInSituHybridization

（FISH）UsingDNAprobelabeledwithacertainmarkerHybridizingwithDNAinchromosomesandnucleionslidesProbeshybridizedwiththefragmentinchromosomearedetectedbysignalsfromthelabeledmarkersCh.+ProbeCo-(denature)(anneal)RapidmappingofgenesandsequencesinchromosomeDetectingsmallfragmentininterphase.Detectingcrypticrearrangementsorsmalldeletions–

Bandingcouldnotbedetected<4MbFragileSites46,Y,fra(X)(q27-28)Non-staininggapsthatoccasionallyobserveratcharcteristicsitesonseveralchromosomesDependongrowthconditionsHeritablevariantsLabletestDNA

withgreenHybrizedontomalechromosomalpreparation1：1mixedLablenormalDNAwithredComparativeGenomicHybridization(CGH)CGHComparetheintensityoftwofluorochromesalongthechromosomeset.Detectionofduplicationordeletionofchromosomalsegment.ArrayCGH，aCGHEuploid46,XX46,XYarr(12)(pter-qter)×1,-12arr(9)(q12-qter)×3,(15)(q12-qter)×1,dert(12q;15q)3.Chromosomeabnormalities

(1).Numericalchromosomalabnormalities

Heteroploidy:Achromosomecomplementwithchromosomenumberotherthan46Euploidy:AchromosomecomplementwithanexactmultipleofthehaploidchromosomenumberAneuploidy:

Achromosomecomplementwithchro-mosomenumberotherthananmultipleofthehaploidchromosomenumberA.Euploidy:

Monoploidy

andPolyploidy1N:Monoploidy23Xor23Y:inparthenogenesis3N:Triploidy69,XXXor69,XXYinpartialmole,abortedfetusandlivebornwhodoesnotsurvivelong4N:Tetraploid92,XXXXor92,XXYYinabortedfetusTriploidy13-green,21-redTriploidyPat.diploidyover-growthoftrophoblastCompletemoleMat.diploidyover-growthofinnermasscellTeratomasTriploidyTwospermfertilizedwithanormaloocytePartialmoleparthenogenesisImprinting:Theexpressionofthephenotypedependsonwhetherthegeneorgenomeinheritedfromthefatherormother.

Lossorgainofchromosomes(notmultipleofahaploidy)Monosomy2n-1:oneinsteadofapairofhomologouschromosomesTrisomy2n+1:threeinsteadofapairofhomologouschromosomes(2).AneuploidyMonosomyResultedfromnondisjunctionofthehomologouschromosomes(meiosisI)orsisterchromatids(mitosisormeiosisII).Trisomya.MonosomyAlmostallmonosomyforanentirechromosomeislethalTurner’