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遗传three
遗传3
Karyotype
Thechromosomeconstitutionofanindividual.
Female:
46,XX;Male:
46,XY
Akaryotypeisdescribedby
firstlistingthenumberofchromosomesfollowedbythesexchromosomeconstitution,followedbyanyabnormalitiesinnumberormorphologyofchromosomes.
Robertsoniantranslocation
Atranslocationbetweentwoacrocentricchromosomeswithlossofsatellitematerialfromtheirshortarms.
Markerchromosome(mar)
Asmallchromosomalfragmentthespecificidentityofwhichcannotbedeterminedbyconventionalcytogenetictechniques.
ChromosomeBanding
G-banding➔mostwidelyused,trypsin+Giemsa
Q-banding➔quinacrine
R-banding➔reversetoG-banding,salinebuffer+Giemsa
C-banding➔centromeres
N-banding➔silverNORstain,NORactivity
Thedark-stainingG-bandscontainDNAthatisAT-richandarethoughttocontainfeweractivegenes.
TheDNAisinacondensedstateininterphasenucleiandisrichinLINES.
Theweaklystainingbands,orR-bands,containDNAthatisGC-richandcontainsmanytranscribedgenes.
TheDNAisinamoreextendedstateininterphasenucleiandcontainsinadditiontotranscribedgenes,increasednumbersofSINES.
Akaryotypeisdescribedbyfirstlisting
thenumberofchromosomesfollowedby
thesexchromosomeconstitution,followedby
anyabnormalitiesinnumberormorphologyofchromosomes.
Eg:
47,XY,+21➔AnXYmalewith47chromosomes,includinganextracopyofchromosome21,whichcausesDownsyndrome.
45,XY,der(14;21)(q10;q10)➔AnXYmalewith45chromosomes,inwhomonenormal14andonenormalchromosome21havebeenreplacedbyaderivativechromosomearisingfromthetranslocationofthelongarmofchromosome21tothelongarmofchromosome14.
FluorescenceInSituHybridization(FISH)
Single-strandedprobesmaybehybridizedtometaphasechromosomes(standard),butalsocanbehybridizeddirectlytoimmobilizedinterphasenucleiofnondividingcells.
Centromericprobes,telomericprobes,locus-specificprobes,andwholechromosomepaintprobes.
High-resolution“FiberFISH”.
ComparativeGenomicHybridization(CGH)--tumor
N➔thenumberofchromosomesinanormalhaploidgamete
Diploidor2N➔thenumberofchromosomesinanormalsomaticcells
Euploid➔anyexactmultipleofN
Polyploidy➔triploidy(69chromosomes)andtetraploidy(92chromosomes)
Aneuploid
Forconstitutionalchromosomedisorders,usuallyreferstoanextracopyofasinglechromosome➔trisomy(asintrisomy21Downsyndrome),ortheabsenceofasinglechromosome➔monosomy(asin45,XTurnersyndrome)
Istheresultofnondisjunction,orfailureofchromosomestoseparatenormalduringcelldivision,andcanoccurduringmeiosisormitosis.
StructuralAbnormalities
Onlyonechromosomeisinvolved
Adeletionorduplicationofaportionofthechromosome
Apericentric(involvingthecentromere)orparacentric(notinvolvingthecentromere)inversion
Formationofaringchromosomeorisochromosome
Deletion(del)Duplication(dup)Inversion(inv)Ringchromosome(r)
Isochromosome(i)Insertion(ins)Translocation(t)
ThechromosomalbasisofDownSyndrome
Trisomy21
Unbalancedtranslocation
Mosaicforatrisomy21cellline一个三体21细胞系的嵌合体
Lyonhypothesis
OneXchromosomeineachsomaticcellofthefemaleisinactivated;
Xinactivationoccursearlyinembryoniclife;
Theinactivationisrandom;
Xinactivationiscomplete;
Xinactivationispermanent.
ThechromosomalbasisofTurnerSyndrome
MonosomyX(45,X)
Structuralabnormalities
Mosaicfora45,Xcellline
clinicalconsequenceofconstitutionalchromosomalabnormalities.
1:
SpontaneousAbortions自发流产
2:
BirthDefects出生缺陷
thegeneralfeaturesareatriadofgrowthretardation,mentalretardation,andspecificsomaticabnormalities.生长迟缓、智力迟钝和特殊的躯体异常。
Autosomalchromosomedisorders(Downsyndrome,Edwardssyndrome,Patausyndrome,CriduChatsyndrome
DownSyndrome
Trisomy21
Themostcommonandbestknownofthechromosomedisordersandisthesinglemostcommongeneticcauseofmoderateintellectualdisability
Approximately1in850livebirths
Growthretardationandvaryingdegreeofmentalretardation
ClinicalFeatures
Babiesareoftenveryfloppyorhypotonic
Facialfeatures
Nasalbridge➔flat
Eyes➔upslantingpalpebralfissures,andepicanthalfolds
Ears➔smallandlow-set,acharacteristicfoldedappearance
Mouth➔open,showingaprotrudingtongue
Brachycephalywithaflatocciput
Neck➔short,withlooseskinonthenape
Hands➔shortandboard,oftenwithasingletransversepalmarcreaseandclinodactyly.
Feet➔widegapbetweenfirstandsecondtoes
IQscorerangingfrom25to75
AverageIQofyoungadultisaround40to45
40%havesignificantcongenitalheartdisease(oftenatrioventricularcanaldefects)
5%haveseriousgastrointestinalanomalies,includingduodenalstenosis
15-to20-foldincreasedriskofleukemia
PatientsdevelopAlzheimer’sdiseaseearlyinlife.
Trisomy18(Edwardssyndrome)
Smallandlow-setears,ashortsternum
Clenchedfistwithoverlappingfingers
“Rocker-bottom”feet
Trisomy13(Patausyndrome)
Cleftlipandcleftpalate
Polydactyly
CriduchatSyndrome
Approximately1in15,000livebirths.
Deletionofpartofchromosome5p.
Cryinginfantswiththisdisordersoundlikeamewingcat.
DisordersofSexChromosome
X-chromosomeinactivation➔Lyonhypothesis
Turnersyndrome
Klinefeltersyndrome
XYYsyndrome
XXXsyndrome
FragileXsyndrome
XYYSyndrome
47,XYY
Approximately1/1000males
Tendtobetallerthanaverage.
XYYmalesarenotinclinedtocommitviolentcrimes.
Increasedincidenceofminorbehavioraldisorders,suchashyperactivity,attentiondeficitdisorder,andlearningdisabilities.
XXXSyndrome
47,XXX
Approximately1/1000females
Overtphysicalabnormalitiesarerarelyseen,butthesefemalessometimeshavesterility,menstrualirregularity,ormildcognitivedisability.
Approximately90%ofcasesaretheresultofconjunctioninthemother.
FragileXSyndrome
Whenperipheralbloodlymphocyteculturesaredeprivedoffolate,orthymidinemetabolismisperturbed,apparentbreaksorgapsinchromosomes,so-calledfragilesites,canbeobserves.
Usingthesetechniques,afolate-sensitivefragilesitewasdescribeatXq27.3inmalesaffectedwithaformofX-linkedmentalretardationthatcametobeknownasthefragileXsyndrome.
thefragileXsyndromeisthemostcommoninheritedformofmentalretardationinhumans.
Facialabnormalities,includinganarrowfacewithprominentforehead,jaw,andears,macroorchidism(largetestes)in90%ofpostpubertalaffectedmales,mildconnectivetissueabnormalities,andmostimportantly,moderatetoseverementalretardation.
Locus
Aspecificpositionorlocationonachromosome.
Alleles
Alternativeformsofagene,orofaDNAsequence,atagivenlocus.
Compoundheterozygote
Anindividualwithtwodifferentmutantallelesatagivenlocus.
Doubleheterozygote
Anindividualwithonemutantalleleateachoftwodifferentloci.
Pedigree
Achartordiagramofanindividual’sancestorusedingeneticsintheanalysisofinheritanceofspecifictraits.
Theproband
Thefirstaffectedfamilymembercomingtomedicalattention.
Co-dominance
Twoallelictraitsthatarebothexpressedintheheterozygousstate.HumanABObloodgroup
Penetrance
Theproportionofobligategenecarriersforamutantallelewhoexpressthephenotype.
Expressivity
Thenatureandseverityofthephenotype.
Delayedonset
—notpresentatbirthbuthavemanifestationsonlylaterinlife.
Polycystickidneydisease
Huntingtondisease
Genomicimprinting
Thedifferentialexpressionofallelesdependingontheparentoforigin.
Eg:
染色体15q11-q13父源缺失:
Prader-WilliSyndrome(PWS)母源缺失:
angelman综合征AS
Anticipation
Anearlierageofonsetandincreasingseverityinsuccessivegenerations.eg:
Myotonicdystrophy肌强直性营养不良Themostcommonmusculardystrophyaffectingadults.Musclewasting,beginningintheface(andcausingthecharacteristicmasklikefacieswithptosisordroopingeyelids),neck,andhands,butgraduallybecominggeneralized.
Myotonia,ortheinabilityofamuscletorelaxaftercontraction.分子基础为动态突变
Carriers
Heterozygousindividualswhoareclinicallynormalbutheterozygousforthemutantallele.
Geneticheterogeneity
Differentmutationscancauseanidenticalorsimilarphenotype.
Hemizygous
X-linkedgenesarefullyexpressedinmales,whohaveonlyasingleXchromosome
Functionalcloning
Genecloningapproachmovingfromthebasicbiochemicaldefecttotheresponsiblegene.
Positionalcloning
Tolocatethegeneresponsibleforahumandiseasebasedsolelyonitsmapposition,withoutthebenefitofanyfunctionalinformation.
Holandricinheritance
ThepatternofinheritanceofgenesontheYchromosome;onlymalesareaffectedandthetraitistransmittedbyaffectedmalestotheirsonsbuttononeoftheirdaughters.
TypicalpedigreepatternforAD
1.Verticalinheritance.
2.Bothmalesandfemalesareaffectedwithequalprobability.
3.Eachaffectedindividualhasoneaffectedparent.
4.Onaverage,halfoftheoffspringofanaffectedparentbeingaffected,butnoneoftheoffspringofunaffectedparent.
TypicalpedigreepatternforAR
1.Thecharacteristicpedigreepatternishorizontal.
2.Malesandfemalesareaffectedwithequalprobability.
3.Theusualmatingisthatbetweentwocarriers,andthereisa1in4chancethateachoffspringwillaffected.
TypicalpedigreepatternforXR
1.Onlymalesareaffected.
2.Thediseaseistransmittedbyhealthyfemale(heterozygouscarriers).
3.Thediseasecanbetracedamongmalerelativesonthemother’ssideofthefamily.
CharacteristicofmtDNA(简答题)
Semi-autonomous,Geneticcodevariants,Maternalinheritance,Replicativesegregation,