性别决定和伴性遗传(英文版)

sexdeterminationfemale: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)SOX9havetherulebothonSkeletalDevelopmentandsexdeterminationSOX9Initiallyexpressedinbothmaleandfemalegenitalridge,whensryexpressed,itwillexpressinthemalegenitalridge,andthenCausepodocytedevelopmentSox9havethesamefunctionofSRY,andifSrygenedeletion,SOX9willInducemaledifferentiationtoensurenormaldevelopmentofmaleSOX3(Sry-typeHMGbox3)SOX3istheonlygenewhichlieinXchromosome.ThisgeneassociatedwiththeSrygene,SOX3andSrygenesmaybeallele.itcanencodeSry-bindingproteininmalesexembryos,andplaytheruleinembryoniccentralnervoussystemdevelopmentandundifferentiatedgonad,Wt1（Wilmstumorsuppressorgene1）,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,sexlinkedinheritance:Ageneticpatternwhichinthegeneticprocess,sometraitoftheoffspringsarecontrolledbythegeneofsexchromosomes.,Theseparationofdisease,XlinkeddominantinheritablediseaseXlinkedrecessiveinheritablediseaseYlinkedinheritabledisease,Xlinkeddominantinheritabledisease,characteristic:paroxysmwillhappeniftherehavetheDisease-causinggene,andtheparoxysmofwomenisabouttwiceasmuchasmen.ifamantobesicked,atleastoneofhisparentsalsosick(exceptgenicmutation)itcaninheritantforsuccessivegenerations,butthepatientsdaughterwhoishealthywillnotgenetictothenextgenerationmanwillgenetictohisdaughterwhilewomanwillgenetictobothherdaughterandson,andtheprobabilityisequal,somecases:,alportsyndrome（AS)vitaminD-resi-stantRicketspseudohypertrophicmusculardystrophy,CaseanalysisofXlinkeddominantinheritabledisease,alportsyndrome（AS)Hereditarynephritis(alportsyndrome,AS)isaseriousgeneticdiseasethatcanleadtoend-stagerenalfailure，Sofar,anumberofdifferentregionsandethnicgroupshavereportedtofindAS.,Geneticapproach,TheGeneticapproachofASisheterogeneous,anditisreportedthattheDisease-causinggeneisCOL4An,whichisthegeneofencodingbasementmembranecollagentypechain,theGeneticapproachandGenetargetingofAlportsyndromeseethechartoverleaf,pathogenesis,Itisnotclearofthepathogenesisofhereditarynephritis，anditpresumablybecauseofgenemutation,itresultinabnormalaboutchain,Underminetheformationoftypecollagenmolecules,thuschangingthestructureofbasementmembrane,impactingglomerularfiltrationrate,resultingindecreasedkidneyfunction.,Xlinkedrecessiveinheritabledisease,characteristic:theprobabilityformantobeaffectedistoomuchbiggerthanwomanifthewomanishealthy,herchildrenwillhealthy,butifsheissick,herfatherandhersonwillalsosick,somecases,hemophiliaachromatopsiaglucose6phosphatedehydrogenasedeficienlyectodermaldysplasiaI,CaseanalysisofXlinkedrecessiveinheritabledisease,HemophiliaHemophiliaisanXchromosomelinked,coagulationfactorVIII(FVIII)orclottingfactormeterIX(FIX)genedefectcausedseverecoagulationdisorders,Theseparationofhemophilia,1.hemophiliaA（antihemophilicglobulin,AHGorfactordeficiency）2.hemophiliaB（PTCorfactordeficiency)3.hemophiliaC（PTA）orplasmathromboplasticantecedentdeficiency,factordeficiency)4.vonWillebranddisease,TherapeuticMethod,clottingfactorreplacementtherapy(traditionalmethod)Withfreshwholeblood,plasmaorfreshfrozenplasma(FFP)replacementclottingfactor,inordertomakeupforthelackofclottingfactorThedefect:Transfusionsofreplacementofblood,plasmaorfreshfrozenplasmaarelarge.Ithavetherisktoleadtohighbloodvolumeandthetendencytoincreasedbleedinggenetherapyreferstotheexogenousnormalgeneintothetargetcellstocorrectorcompensateforgeneticdefectsandabnormalitiescausedbydisease,inordertoachievethetreatmentobjectives,genetherapy,Vectorsystem,Thechoiceoftargetcells,Thedirectionofnewtreatments,Immuneresponse,Vectorsystemwhichisneeded:,Viralvectorretrovirus,RVadenovirus,AVadeno-associatedvirus,AAVlentivirus,LVNon-viralgenetransfer,Thechoiceoftargetcells,liverSkeletalmusclecellsFibroblastsKeratinocyteBonemarrowstromalcells,Immuneresponse,Intheprocessofgenetherapycanproducealternativeforexogenousinhibitoryfactorantibody，thecombinationofInhibitoryantibodiesandclottingfactormoleculeswithaspecificregioncanchangeitsstructure,sotmakeitinactivation.Theproductionofinhibitoryantibodiesandthetypeofmutationisconcernedwiththetypeofgenicmutation,Thedirectionofnewtreatments,pre-messengerRNA,pre-mRNAbloodout