医学遗传学绪论.ppt
Medical Genetics医学遗传学绪论 Still waters run deep.流静水深流静水深,人静心深人静心深 Where there is life,there is hope。有生命必有希望。有生命必有希望Medical GeneticsArrangementIntroductionMedicalGeneticsGeneticdiseaseMedical GeneticsArrangementTeacher:LiuWenPhDassociateprof()LiuXiaoyuPhDassistantProf()AlexanderEndlerPhDMedical Genetics1.5creditsLecture:2classes/week(9weeks)Lab:4classes/week(4weeks)Medical GeneticsWeek Date Day Course Content Teacher1011.11Thu3-4MedicalGenetics&GeneticdiseaseLiuWen1111.18Thu3-4SingleGeneDisorderAlexanderEndler1211.25Thu3-4PolygeneDisorderLiuWen1312.2Thu3-4ChromosomalDiseaseAlexanderEndler1412.9Thu3-4MitochondrialDiseaseLiuWen1512.16Thu3-4GeneticsandCancerLiuWen1612.23Thu3-4BirthdefectLiuWen1712.30Thu3-4StudentspresentationLiuWen181.7Thu3-4ExamLiuWenClassroom：14021402LecturesMedical GeneticsWeekDateDayCourseContentTeacher111111.1911.19FriFri5-8Preparation of chromosome samplesPreparation of chromosome samplesLiu XiaoyuLiu Xiaoyu121211.2611.26FriFri5-8Gbanding&samplesofchromosomediseasesLiu XiaoyuLiu Xiaoyu141412.1012.10FriFri5-8ExtractionofGenomicDNALiu XiaoyuLiu Xiaoyu151512.1712.17FriFri5-8DetectionofgenemutationbyPCRLiu XiaoyuLiu XiaoyuLabLab：13-214 13-214 LabtrainingMedical GeneticsTextbookReferenceThompson&ThompsonGeneticsinMedicine,7thPrinciplesofMedicalGenetics(Williams&Wikins)Medical GeneticsExam:Exam40%Presentation30%Labreport20%Homework10Medical GeneticsIntroduction46,XYkaryotypeMedical GeneticsAndrogeninsensitivitysyndrome,AISAndrogeninsensitivitysyndrome,AISMechanismCausedbymutationsofthegeneencodingtheandrogenreceptor.symptomsApersonwithcompleteandrogeninsensitivitysyndrome(CAIS)hasafemaleexternalappearance,andsuppressedmenstruation.Medical Geneticsandrogeninsensitivitysyndrome，AIS（雄激素不敏感综合征雄激素不敏感综合征）XR46,XYkaryotyperetainedtestisMedical GeneticsIntroduction47,XXY(extrachromosome)Klinefeltersydromemania?MechanismMedical GeneticsIntroduction-DiseaseandGeneticsA.Diseasecausedby(orrelatedto)environmentalstress.Bird FluSARS H1N1 FluMedical GeneticsIntroduction-DiseaseandGeneticsB.Diseasecausedby(orrelatedto)geneticfactors.ManyofthecommonphysicalfeaturesLowIQDownsyndromeMedical GeneticsMedical GeneticsIntroduction-DiseaseandGeneticsDuchennemusculardystrophycausedbyagenemutationMedical GeneticsMedical GeneticsIntroduction-DiseaseandGeneticsC.diseasescausedbythecombinedactionofgeneandenvironment.ConjoinedTwinsconnaterachitisMedical GeneticsGenetic Disorders Genetic Disorders:disorderscausedwhollyorpartlybygeneticfactors.Medical GeneticsWhatisMedicalGenetics?human geneticshuman geneticsMedical GeneticsWhatisMedicalGenetics?human genetics:human genetics:Thescienceofvariationandheredityinhumanbeings.Medical GeneticsTonguerollingTonguerollingFree/attachedearlobeFree/attachedearlobeHairlineoftheforeheadHairlineoftheforeheadwidowpeakwidowpeakEvaginablethumbdominatedominatedominatedominaterecessiverecessiveMedical GeneticsHomework Pedigree：Nov25thMedical GeneticsSymbolsMedical GeneticsWhatisMedicalGenetics?Medical GeneticsMedical Genetics:Medical geneticsMedical geneticsdealswithhumangeneticvariationofmedicalsignificance.Majorrecognizedareasofspecializationarethestudyofchromosomes,andthestructureandfunctionofindividualgenes.Medical GeneticsWhatisMedicalGenetics?Medical GeneticsMedical Genetics Wilsons diseaseWilsons diseaseMechanismofGeneticDiseaseMedical GeneticsWhatisMedicalGenetics?Clinical GeneticsClinical GeneticstheapplicationtodiagnosisandpatientcareMedical GeneticsWhat is Medical Genetics?diagnosisSicklecellanemiaalbinismMedical GeneticsWhatisMedicalGenetics?Imagining DiagnosisMedical GeneticsharelipMedical GeneticsWhatisMedicalGenetics?MolecularDiagnosisincisionenzymeGel electrophoresisMedical GeneticsWhatisMedicalGenetics?PreventionPKU/PAH(Phenylalaninehydroxylase)phenylphruvicacidprenataldiagnosisMedical GeneticsWhatisMedicalGenetics?TherapyConsultMedical GeneticsGeneticdiseaseA.Whatisgeneticdisorder?AgeneticdisorderisadiseasethatiscausedbyanabnormalityinanindividualsDNA.Abnormalitiescanrangefromasmallmutationinasinglegenetotheadditionorsubtractionofanentirechromosomeorsetofchromosomes.Medical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical GeneticsalbinismDownsyndromeMedical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical Genetics3PedigreeofGeneticDiseaseMedical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical Geneticsxhemophiliahemophilia（Bloodclotting，tobleed）Medical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical GeneticsFamilynumberofDMDMedical GeneticsGeneticdiseaseB.Characteristicsofgeneticdisorders1.congenital2.modeofinheritance 3.populationdistribution4.familial5.infectiousMedical GeneticsGeneticdiseasehuman prion diseaseshuman prion diseasesgeneticandinfectiousNeuron：VacuolardegenerationMedical GeneticsCreutzfeldtJakobdiseasetribeMedical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsGeneticdiseaseSingle-genedisordersresultwhenamutationcausestheproteinproductofasinglegenetobealteredormissing.Medical Genetics表表 一些常染色体显性遗传病举例一些常染色体显性遗传病举例疾病中文名称疾病英文名称 OMIM染色体定位家族性高胆固醇血症familial hypercholesterolemia14389019p13.2遗传性出血性毛细血管扩张hemorrhagic telangiectasia1873009q34.1遗传性球形红细胞症elliptocytosis1305001p36.2-p34急性间歇性卟淋症porphyria,acute intermittent17600011q23.3迟发性成骨发育不全症osteogenesis imperfecta,type I16620017q21.31-q22成年多囊肾病polycystic kidney disease,adult17390016p13.3-p13.12-珠蛋白生成障碍性贫血alpha-thalassemias14180016pter-p13.3短指（趾）症A1型brachydactyly,type A11125002q35-q36特发性肥大性主动脉瓣下狭窄supravalvular aortic stenosis1855007q11.2遗传性巨血小板病，肾炎和耳聋Fechtner syndrome15364022q11.2Noonan综合征Noonan syndrome 116395012q24.1神经纤维瘤neurofibromatosis,type I16220017q11.2结节性脑硬化tuberous sclerosis19110016p13.3，9q34多发性家族性结肠息肉症adenomatous polyposis of the colon1751005q21-q22Peutz-Jeghers综合征Peutz-Jeghers syndrome17520019p13.3Von Willebrand病Von Willebrand disease19340012p13.3肌强直性营养不良dystrophia myotonica 116090019q13.2-q13.3Medical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsInchromosomedisorders,entirechromosomes,orlargesegmentsofthem,aremissing,duplicated,orotherwisealtered.Medical GeneticsMedical GeneticsPatau syndromePatau syndromeTrisomy13-thepresenceofanextra(third)chromosome13inallofthecells.Medical GeneticsSymptomsPhysicalcharacteristicsOrgandefectsMentalretardationMedical Geneticsphysicalcharacteristicscleft lip,cleft palatesmall eyeslow-set earsMedical Geneticsphysicalcharacteristicsphysicalcharacteristicsrocker footMedical GeneticsheartdefectsspinaldefectsOrgandefectsOrgandefectsMedical GeneticsabnormalgenitaliagastrointestinalherniaspolycystickidneydiseaseMedical GeneticsmentalretardationIncompletebraindevelopmentLowIQMedical Genetics99donotsurvivegestationandarespontaneouslyaborted82-85%donotsurvivepast1monthofage,85%donotsurvivepast1yearofageMedical GeneticsDiagnosis&TreatmentDiagnosis:chromosomeanalysisNOTREATMENTMedical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsMultiplegenesaremissingasaresultofthisdeletion,andeachmaycontributetothesymptomsofthedisorder.OneofthedeletedgenesknowntobeinvolvedisTERT(telomerasereversetranscriptase).Thisgeneisimportantduringcelldivisionbecauseithelpstokeepthetipsofchromosomes(telomeres)intact.Medical GeneticsGeneticdiseaseMultifactorial disordersresultfrommutationsinmultiplegenes,oftencoupledwithenvironmentalcauses.Medical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsGeneticdisease Somatic cell genetic diseases:resultfromthealteredgeneticmaterialsinsomaticcells.Medical GeneticsMedical GeneticsGeneticdiseaseC.ClassificationofGeneticDisorders1.single-genedisorders2.chromosomedisorders3.multifactorialdisorders4.somaticcellgeneticdisorders5.mitochondrialdisordersMedical GeneticsGeneticdiseaseMitochondrial genetic diseases:DuetothemutationofmitochondrialDNA.Medical Genetics一些一些mtDNA突变相关的疾病突变相关的疾病突变相关基因表型mt-3243tRNALeu(UUR)MELAS、PEO、NIDDM/耳聋mt-3256tRNALeu(UUR)PEOmt-3271tRNALeu(UUR)MELASmt-3303tRNALeu(UUR)心肌病mt-3260tRNALeu(UUR)心肌病/肌病mt-4269tRNAIle心肌病mt-5730tRNAAsn肌病(PEO)mt-8344tRNALysMERRFmt-8356tRNALysMERRF/MELASmt-15990tRNAPro肌病mt-8993A6NARP/LEIGHmt-11778ND4LHONmt-4160ND1LHONmt-3460ND1LHONmt-7444COX1LHONmt-14484ND6LHONmt-15257Cyt6LHONMedical GeneticsThe End
