遗传 three.docx

遗传 three.docx

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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，