醫(yī)學(xué)遺傳學(xué)緒論

醫(yī)學(xué)遺傳學(xué)緒論第1頁/共72頁ArrangementTeacher:LiuWenPhDassociateprof(liuwen@)LiuXiaoyuPhDassistantProf(liubio@163.com)

Alexander

Endler

PhD第2頁/共72頁1.5creditsLecture:2classes/week(9weeks)Lab:4classes/week(4weeks)第3頁/共72頁WeekDateDayCourseContent

Teacher1011.11Thu3-4MedicalGenetics&GeneticdiseaseLiuWen

1111.18Thu3-4SingleGeneDisorderAlexander

Endler

1211.25Thu3-4PolygeneDisorderLiuWen

1312.2Thu3-4ChromosomalDiseaseAlexander

Endler

1412.9Thu3-4MitochondrialDiseaseLiuWen

1512.16Thu3-4GeneticsandCancerLiuWen

1612.23Thu3-4BirthdefectLiuWen

1712.30Thu3-4StudentspresentationLiuWen

181.7Thu3-4Exam

LiuWen

Classroom：1402Lectures第4頁/共72頁WeekDateDayCourseContent

Teacher1111.19Fri5-8PreparationofchromosomesamplesLiuXiaoyu

1211.26Fri5-8Gbanding&samplesofchromosomediseasesLiuXiaoyu

1412.10Fri5-8ExtractionofGenomicDNALiuXiaoyu

1512.17Fri5-8DetectionofgenemutationbyPCRLiuXiaoyu

Lab：13-214Labtraining第5頁/共72頁TextbookReference

Thompson&ThompsonGeneticsinMedicine,7th

PrinciplesofMedicalGenetics(Williams&Wikins)第6頁/共72頁Exam:Exam40%Presentation30%Labreport20%Homework10％

第7頁/共72頁Introduction46,XYkaryotypeFirstStory第8頁/共72頁Androgeninsensitivitysyndrome,AISMechanismCausedbymutationsofthegeneencodingtheandrogenreceptor.symptomsApersonwithcompleteandrogeninsensitivitysyndrome(CAIS)hasafemaleexternalappearance,andsuppressedmenstruation.第9頁/共72頁androgeninsensitivitysyndrome，AIS（雄激素不敏感綜合征）XR46,XYkaryotyperetainedtestis第10頁/共72頁Introduction47,XXY(extrachromosome)Klinefeltersydromemania??MechanismSecondStory第11頁/共72頁Introduction-DiseaseandGeneticsA.Diseasecausedby(orrelatedto)environmentalstress.

BirdFluSARSH1N1Flu第12頁/共72頁Introduction-DiseaseandGenetics

B.Diseasecausedby(orrelatedto)geneticfactors.ManyofthecommonphysicalfeaturesLowIQDownsyndrome第13頁/共72頁第14頁/共72頁Introduction-DiseaseandGeneticsDuchennemusculardystrophycausedbyagenemutation第15頁/共72頁第16頁/共72頁Introduction-DiseaseandGeneticsC.diseasescausedbythecombinedactionofgeneandenvironment.ConjoinedTwinsconnaterachitis第17頁/共72頁GeneticDisorders:

disorderscausedwhollyorpartlybygeneticfactors.第18頁/共72頁WhatisMedicalGenetics?humangenetics第19頁/共72頁WhatisMedicalGenetics?humangenetics:

Thescienceofvariationandheredityinhumanbeings.第20頁/共72頁TonguerollingFree/attachedearlobeHairlineoftheforeheadwidowpeakEvaginablethumbdominatedominatedominatedominaterecessiverecessive第21頁/共72頁Homework

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Pedigree：Nov25th第22頁/共72頁Symbols第23頁/共72頁WhatisMedicalGenetics?MedicalGenetics:

Medicalgenetics

dealswithhumangeneticvariationofmedicalsignificance.Majorrecognizedareasofspecializationarethestudyofchromosomes,andthestructureandfunctionofindividualgenes.

第24頁/共72頁WhatisMedicalGenetics?MedicalGenetics

Wilson’sdiseaseMechanismofGeneticDisease第25頁/共72頁WhatisMedicalGenetics?ClinicalGenetics

theapplicationtodiagnosisandpatientcare

第26頁/共72頁WhatisMedicalGenetics?diagnosisSicklecellanemiaalbinism第27頁/共72頁WhatisMedicalGenetics?ImaginingDiagnosis第28頁/共72頁harelip第29頁/共72頁WhatisMedicalGenetics?MolecularDiagnosisincisionenzymeGelelectrophoresis

第30頁/共72頁WhatisMedicalGenetics?PreventionPKU/PAH(Phenylalaninehydroxylase)phenylphruvicacidprenataldiagnosis第31頁/共72頁WhatisMedicalGenetics?TherapyConsult第32頁/共72頁Geneticdisease

A.Whatisgeneticdisorder?Ageneticdisorderisadiseasethatiscausedbyanabnormalityinanindividual’sDNA.Abnormalitiescanrangefromasmallmutationinasinglegenetotheadditionorsubtractionofanentirechromosomeorsetofchromosomes.第33頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution4.familial5.infectious第34頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution4.familial5.infectious第35頁/共72頁albinismDownsyndrome第36頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution4.familial5.infectious第37頁/共72頁3PedigreeofGeneticDisease第38頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution4.familial5.infectious第39頁/共72頁xhemophilia（Bloodclotting，tobleed）第40頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution

4.familial5.infectious第41頁/共72頁FamilynumberofDMD第42頁/共72頁GeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance

3.populationdistribution4.familial

5.infectious第43頁/共72頁GeneticdiseasehumanpriondiseasesgeneticandinfectiousNeuron：Vacuolardegeneration第44頁/共72頁Creutzfeldt－Jakobdiseasetribe第45頁/共72頁GeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisorders第46頁/共72頁GeneticdiseaseC.ClassificationofGeneticDisorders

1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisorders第47頁/共72頁Geneticdisease

Single-genedisordersresultwhenamutationcausestheproteinproductofasinglegenetobealteredormissing.

第48頁/共72頁表一些常染色體顯性遺傳病舉例疾病中文名稱疾病英文名稱

OMIM染色體定位家族性高膽固醇血癥familialhypercholesterolemia14389019p13.2遺傳性出血性毛細(xì)血管擴(kuò)張hemorrhagictelangiectasia1873009q34.1遺傳性球形紅細(xì)胞癥elliptocytosis1305001p36.2-p34急性間歇性卟淋癥porphyria,acuteintermittent17600011q23.3遲發(fā)性成骨發(fā)育不全癥osteogenesisimperfecta,typeI16620017q21.31-q22成年多囊腎病polycystickidneydisease,adult17390016p13.3-p13.12-珠蛋白生成障礙性貧血alpha-thalassemias14180016pter-p13.3短指（趾）癥A1型brachydactyly,typeA11125002q35-q36特發(fā)性肥大性主動脈瓣下狹窄supravalvularaorticstenosis1855007q11.2遺傳性巨血小板病，腎炎和耳聾Fechtnersyndrome15364022q11.2Noonan綜合征Noonansyndrome116395012q24.1神經(jīng)纖維瘤neurofibromatosis,typeI16220017q11.2結(jié)節(jié)性腦硬化tuberoussclerosis19110016p13.3，9q34多發(fā)性家族性結(jié)腸息肉癥adenomatouspolyposisofthecolon1751005q21-q22Peutz-Jeghers綜合征Peutz-Jegherssyndrome17520019p13.3VonWillebrand病VonWillebranddisease19340012p13.3肌強(qiáng)直性營養(yǎng)不良dystrophiamyotonica116090019q13.2-q13.3第49頁/共72頁GeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders

2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisorders第50頁/共72頁

Inchromosomedisorders,entirechromosomes,orlargesegmentsofthem,aremissing,duplicated,orotherwisealtered.第51頁/共72頁第52頁/共72頁P(yáng)atausyndrome

Trisomy13--thepresenceofanextra(third)chromosome13inallofthecells.第53頁/共72頁Symptoms

PhysicalcharacteristicsOrgandefectsMentalretardation第54頁/共72頁physicalcharacteristicscleftlip,cleftpalatesmalleyeslow-setears第55頁/共72頁physicalcharacteristics

rockerfoot第56頁/共72頁

heartdefectsspinaldefectsOrgandefects第57頁/共72頁abnormalgenitaliagastrointestinalherniaspolycystickidneydisease第58頁/共72頁mentalretardation

IncompletebraindevelopmentLowIQ第59頁/共72頁

99％donotsurvivegestationandarespontaneouslyaborted82-85%donotsurvivepast1monthofage,85%donotsurvivepast1yearofage

第60頁/共72頁Diagnosis&Treatment

Diagnosis:chromosomeanalysisNOTREATMENT第61頁/共72頁GeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders

3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisorders第62頁/共72頁

Multiplegenesaremissingasaresultofthisdeletion,andeachmaycontributetothesymptomsofthedisorder.OneofthedeletedgenesknowntobeinvolvedisTERT(telomerasereversetranscriptase).Thisgeneisimportantduringcelldivisionbecauseithelpstokeepthetipsofchromosomes(telomeres)intact.第63頁/共72頁Geneticdisease

Multifactorialdisordersresultfrommutationsinmultiplegenes,oftencoupledwithenvironmentalcauses.第64頁/共72頁GeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders