多基因病的分子遗传学

多基因病的分子遗传学Section1PolygenicInheritance一、Definition1、Geneticbasis:multiplegenes3、Minorgene,Additiveeffect2、Codominance4、multipleenvironmentalfactors

一些遗传性状或遗传病受两对或更多对等位基因控制,每对基因彼此间没有显性与隐性得关系,而就是共显性。每对等位基因对表型得效应都很小,但就是各对基因得作用有累加效应,此外,这些遗传性状或遗传病也受环境因素得作用,这种遗传方式称为多基因遗传(poly-genicinheritance)。二、Characteristics

QualitativeTraitandQuantitativeTraitQualitativeTraitMonogenictraitPituitarydwarfismQualitativeTraitMonogenictrait120cm165cm

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AAORAaHeightofpituitarydwarfism&normal0~5%45~50%100%aaAaAAPAHactivityofPKU,carrier&normal大家学习辛苦了，还是要坚持继续保持安静Qualitativetrait:genetictraitswhicharepresentorabsent、Onehasthetraitornot、单基因遗传得性状在群体中,往往可以分出具有与不具有该性状得2~3个小群体,这一性状得变异在一个群体中得分布就是不连续得,称为质量性状。QuantitativeTraitQuantitativetrait:genetictraitswhicharemeasurablecharacteristics、多基因遗传得性状在一个群体中得变异分布就是连续得,只有一个峰,称为数量性状。130140150160170180190200Height(cm)8070605040302010VariabilityGaussiandistributionPthetallesttheshortestAABBA’A’B’B’F1themedianAA’BB’F2ABAB’A’BA’B’ABAABBAABB’AA’BBAA’BB’AB’AABB’AAB’B’AA’BB’AA’B’B’A’BAA’BBAA’BB’A’A’BBA’A’BB’A’B’AA’BB’AA’B’B’A’A’BB’A’A’B’B’A’A’B’B’AAB’B’A’A’BBAABBA’A’BB’AABB’AA’B’B’AA’BBAA’BB’14641PAABBCCA’A’B’B’C’C’F1AA’BB’CC’Total01234561615201561F2

ABCA’BCAB’CABC’A’B’CAB’C’A’BC’A’B’C’ABCA’BCAB’CABC’A’B’CAB’C’A’BC’A’B’C’AABBCCAA’BBCCAABB’CCAABBCC’AA’BB’CCAABB’CC’AA’BBCC’AA’BB’CC’AA’BBCCA’A’BBCCAA’BB’CCAA’BBCC’A’A’BB’CCAA’BB’CC’A’A’BBCC’A’A’BB’CC’AABB’CCAA’BB’CCAAB’B’CCAABB’CC’AA’B’B’CCAAB’B’CC’AA’BB’CC’AA’B’B’CC’AA’BB’CCAA’BBCC’AABB’CC’AABBC’C’AA’BB’CC’AABB’C’C’AA’BBC’C’AA’BB’C’C’AA’BB’CCA’A’BB’CCAA’B’B’CCAA’BB’CC’A’A’B’B’CCAA’B’B’CC’A’A’BB’CC’A’A’B’B’CC’AABB’CC’AA’BB’CC’AAB’B’CC’AABB’C’C’AA’B’B’CC’AAB’B’C’C’AA’BB’C’C’AA’B’B’C’C’AA’BBCC’A’A’BBCC’AA’BB’CC’AA’BBC’C’A’A’BB’CC’AA’BB’C’C’A’A’BBC’C’A’A’BB’C’C’AA’BB’CC’A’A’BB’CC’AA’B’B’CC’AA’BB’C’C’A’A’B’B’CC’AA’B’B’C’C’A’A’BB’C’C’A’A’B’B’C’C’201515661101234562、HybridizationofF1ofintermediatetype3、Randomhybridization1、Hybridizationoftwoextremevariant(Homozygote)CharacteristicsofPolygenicInheritanceSection2PolygenicDisorders一、LiabilityandThresholdTheorySusceptibility:characterizethegeneticfactorsthataffecttheprobabilityofmultifactorialdisorder、在多基因遗传病中,由遗传基础决定一个个体患病得风险称为易感性。Liability:

beameasureofallofthefactorsthataffecttheprobabilityofmultifactorialdisorder,bothgenetic(innate)andenvironmental、

在多基因遗传病中,由遗传因素与环境因素共同作用并决定一个个体就是否易患某种遗传病得可能性则称为易患性。605040302010LowHighLiabilityVariabilityThresholdAffected由易患性决定得多基因病得发病限度称为阈值。二、HeritabilityHeritability(H,h2)Measure(%)oftheproportionofthetotalphenotypicvariancethatisduetothegeneticbasis、在多基因遗传病中,易患性得高低受遗传因素与环境因素得双重影响。其中遗传因素在决定该疾病中所起得作用得大小,称之为遗传率。IfHishigh——phenotypicvariationislargelygeneticIfHislow——phenotypicvariationislargelyenvironmental常见多基因遗传病与先天性畸形得患病率与遗传率

疾病与畸形群体患病率(%)患者一级亲属患病率遗传率哮喘4、02080精神分裂症1、01080原发性高血压4~820~3062消化性溃疡4、0837强直性脊椎炎0、2男性先证者770

女性先证者2早发性糖尿病0、22~575迟发性糖尿病2~335冠状动脉硬化性心脏病2、5735先天性幽门狭窄0、3男性先证者275

女性先证者10常见多基因遗传病与先天性畸形得患病率与遗传率疾病与畸形群体患病率(%)患者一级亲属患病率遗传率先天性髋关节脱位0、07470先天性畸形足0、1368先天性巨结肠0、02男性先证者280

女性先证者8无脑畸形0、2260脊柱裂0、3460唇裂+腭裂0、17476腭裂0、04276

三、CharacteristicsofPolygenicDisordersMostofmondiseasesandmoncongenitalmalformation,incidence＞1/1000、2、Tendtoaggregateinfamilies、Recurrencerate≈1%～10%3、Ethnicdifference病名

发病率

日本美国

脊柱裂0.0030.002

无脑儿0.0060.005唇裂±腭裂0.00170.001先天性畸形足0.0140.055先天性髋关节脱位0.010.007Mostofmondiseasesandmoncongenitalmalformation,incidence＞1/1000、2、Tendtoaggregateinfamilies、Recurrencerate≈1%～10%3、Ethnicdifference4、Consanguinityalsoincreasestheprobabilityofanaffectedchildforamultifactorialtrait、

Mostofmondiseasesandmoncongenitalmalformation,incidence＞1/1000、2、Tendtoaggregateinfamilies、Recurrencerate≈1%～10%3、Ethnicdifference4、Consanguinityalsoincreasestheprobabilityofanaffectedchildforamultifactorialtrait、

5、Firstdegreerelativeshavethesameriskofaffected、

Mostofmondiseasesandmoncongenitalmalformation,incidence＞1/1000、2、Tendtoaggregateinfamilies、Recurrencerate≈1%～10%3、Ethnicdifference4、Consanguinityalsoincreasestheprobabilityofanaffectedchildforamultifactorialtrait、

5、Firstdegreerelativeshavethesameriskofaffected、

6、Riskofaffectedrelativesfallsoffveryquicklywiththedegreeofrelationship、

亲属级别

发病风险

唇裂先天性髋关节脱位先天性幽门狭窄

一般群体0.0010.0020.005

一卵双生0.400.400.15

一级亲属0.040.050.05

二级亲属0.0070.0060.025四、EstimateofRecurrenceRiskEdwardformulaIncidence≈0、1%~1%Heritability≈70%~80%1、IncidenceandHeritability

如:CleftLip0、17%76%RR=√0、17%=4、1%Anencephalyandcleftspine0、38％60％4％2、TendtoaggregateinfamiliesRiskofaffectedrelativesfallsoffveryquicklywiththedegreeofrelationship、3、Recurrenceriskincreaseswiththenumberofaffectedinafamily、Chilopalatognathus0、17％

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