性别决定和伴性遗传(英文版)ppt课件

sexdetermination sex linkedinheritance JiQiuyan WangDongzhouDec 1st2010 sexdetermination sex linkedinheritance sex linkedinheritance sexdetermination sexdetermination conception mechanism conception sexdetermination Duringembryonicdevelopment aembryonicgonadwhichstillnodifferentiation todeterminetodevelopintotestesorovariesintheprocess Itistosaydioeciousbiologicalsexdeterminism anditisresultfromtheinteractionofgenetic environmentalandphysiologicalfactors Mainsexchromosomes XY ZWXO mechanism FourcelllinesinGonad germcellsteroid producingcells male leydig female theca sertolicells male sertoli female follicol relatedcells ninegenestobeconcernedwithsexdifferentiation Molecularlevel Sex determininggeneofsexchromosome Sex determiningregionofYchromosome SRYSex determiningregionofXchromosome DAX1Sex determininggeneoneuchromosome SOX SOX3 SOX9 AMH MIS WT1SF1Dmrt1Wnt4 SRY Sex determiningregionofYchromosome 1 SRYplaytheon offaction andthegeneofmanhavethefunctionoftranscription SRYcanrestrainthedevelopmentofMullerianductbydominantthesecretionofsomething italsocanproducemalestructures 2 IffemalebeshortofSRY theDSSofXchromosomewilltranscription sotopromotethedevelopmentofovary DAX1 Dosagesensitivesex reversal adrenalhypoplasiacongenital criticalregionoftheXchromosomegene1 DAX1stemfromtwogeneticlocisofXchromosomewhichnameisDSSandAHC DAX1proteinisaffectedbyretinoicacidreceptornegativeregulatoroftranscriptionfactors thereisthefunctionofovary mediated SOX Sry typeHMGbox SOX9 Sry typeHMGbox9 SOX9havetherulebothonSkeletalDevelopmentandsexdetermination SOX9Initiallyexpressedinbothmaleandfemalegenitalridge whensryexpressed itwillexpressinthemalegenitalridge andthenCausepodocytedevelopment Sox9havethesamefunctionofSRY andifSrygenedeletion SOX9willInducemaledifferentiationtoensurenormaldevelopmentofmaleSOX3 Sry typeHMGbox3 SOX3istheonlygenewhichlieinXchromosome ThisgeneassociatedwiththeSrygene SOX3andSrygenesmaybeallele itcanencodeSry bindingproteininmalesexembryos andplaytheruleinembryoniccentralnervoussystemdevelopmentandundifferentiatedgonad Wt1 Wilms tumorsuppressorgene1 Inhibitionofcelldivisionanddifferentiation andisconcernedwithmesenchymalcellsformovarian ItmaycontrolSRYatthebeginningofsexdifferentiation andactivateaseriesofgenes thenresultintheformationoftestis AMH Anti Mullerianhormone AMHisanimportantfactorinmaledifferentiation geneexpressionofAMHdegradeMullerianductinmalebody thenpreventitfromdevelopingintothefemalegenitalorgans SF1 Steroidogenicfactor1 Regulatethegeneexpressionbothingonadandadrenalgland Participateintranscriptionalregulationofmanygenesofsteroidgeneration reproduction andmalesexualdifferentiation Wnt4 Wingless relatedMMTVintegrationsite4 Potentialovariandetermininggeneofeuchromosome AtbeginningitexpressedinRenalmesenchymalandUndifferentiatedgonad ItcanInhibitemalesexualdifferentiationandsynthetichormoneandrogenbyfemalegonad Developmentalmechanismsofsexuality sex linkedinheritance 01 02 03 conception Separationofthedisease Caseanalysis conception sex linkedinheritance Ageneticpatternwhichinthegeneticprocess sometraitoftheoffspringsarecontrolledbythegeneofsexchromosomes Theseparationofdisease X linkeddominantinheritablediseaseX linkedrecessiveinheritablediseaseY linkedinheritabledisease X linkeddominantinheritabledisease characteristic paroxysmwillhappeniftherehavetheDisease causinggene andtheparoxysmofwomenisabouttwiceasmuchasmen ifamantobesicked atleastoneofhisparentsalsosick exceptgenicmutation itcaninheritantforsuccessivegenerations butthepatient sdaughterwhoishealthywillnotgenetictothenextgeneration manwillgenetictohisdaughterwhilewomanwillgenetictobothherdaughterandson andtheprobabilityisequal somecases alportsyndrome AS vitaminD resi stantRicketspseudohypertrophicmusculardystrophy CaseanalysisofX linkeddominantinheritabledisease alportsyndrome AS Hereditarynephritis alportsyndrome AS isaseriousgeneticdiseasethatcanleadtoend stagerenalfailure Sofar anumberofdifferentregionsandethnicgroupshavereportedtofindAS Geneticapproach TheGeneticapproachofASisheterogeneous anditisreportedthattheDisease causinggeneisCOL4An whichisthegeneofencodingbasementmembranecollagentype chain theGeneticapproachandGenetargetingofAlportsyndromeseethechartoverleaf pathogenesis Itisnotclearofthepathogenesisofhereditarynephritis anditpresumablybecauseofgenemutation itresultinabnormalaboutchain Underminetheformationoftype collagenmolecules thuschangingthestructureofbasementmembrane impactingglomerularfiltrationrate resultingindecreasedkidneyfunction X linkedrecessiveinheritabledisease characteristic theprobabilityformantobeaffectedistoomuchbiggerthanwomanifthewomanishealthy herchildrenwillhealthy butifsheissick herfatherandhersonwillalsosick somecases hemophiliaachromatopsiaglucose 6 phos phatedehydrogenasedeficienlyectodermaldysplasiaI CaseanalysisofX linkedrecessiveinheritabledisease HemophiliaHemophiliaisanXchromosomelinked coagulationfactorVIII FVIII orclottingfactormeterIX FIX genedefectcausedseverecoagulationdisorders Theseparationofhemophilia 1 hemophiliaA antihemophilicglobulin AHGor factordeficiency 2 hemophiliaB PTCor factordeficiency 3 hemophiliaC PTA orplasmathromboplasticantecedentdeficiency factordeficiency 4 vonWillebranddisease TherapeuticMethod clottingfactorreplacementtherapy traditionalmethod Withfreshwholeblood plasmaorfreshfrozenplasma FFP replacementclottingfactor inordertomakeupforthelackofclottingfactor Thedefect Transfusionsofreplacementofblood plasmaorfreshfrozenplasmaarelarge Ithavetherisktoleadtohighbloodvolumeandthetendencytoincreasedbleedinggenetherapy referstotheexogenousnormalgeneintothetargetcellstocorrectorcompensateforgeneticdefectsandabnormalitiescausedbydisease inordertoachievethetreatmentobjectives genetherapy Vectorsystem Thechoiceoftargetcells Thedirectionofnewtreatments Immuneresponse Vectorsystemwhichisneeded Viralvector retrovirus RV adenovirus AV adeno associatedvirus AAV lentivirus LVNon viralgenetransfer Thechoiceoftargetcells liver SkeletalmusclecellsFibroblastsKeratinocyteBonemarrowstromalcells Immuneresponse Intheprocessofgenetherapycanproducealternativeforexogenousinhibitoryfactorantibody thecombinationofInhibitoryantibodiesandclottingfactormoleculeswithaspecificregioncanchangeitsstructure sotmakeitinactivation Theproductionofinhibitoryantibodiesandthetypeofmutationisconcernedwiththetypeofgenicmutation Thedirectionofnewtreatments pre messeng