多基因病的分子遺傳學

PolygenicDisordersPolygenicDisorders:由兩對以上等位基因和環(huán)境因素共同作用所致的疾病，稱為多基因病。PolygenicDisorders

arethosewhichresultfromaninteractionbetweenmultiplegenesandmultipleenvironmentalfactors.

Section1PolygenicInheritance一、Definition1.Geneticbasis:multiplegenes3.Minorgene，Additiveeffect2.Codominance4.multipleenvironmentalfactors

一些遺傳性狀或遺傳病受兩對或更多對等位基因控制，每對基因彼此間沒有顯性與隱性的關系，而是共顯性。每對等位基因對表型的效應都很小，但是各對基因的作用有累加效應，此外，這些遺傳性狀或遺傳病也受環(huán)境因素的作用，這種遺傳方式稱為多基因遺傳（poly-genicinheritance）。二、Characteristics

QualitativeTraitandQuantitativeTraitQualitativeTraitMonogenictraitPituitarydwarfismQualitativeTraitMonogenictrait120cm165cm

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AAORAaHeightofpituitarydwarfism&normal0~5%45~50%100%aaAaAAPAHactivityofPKU,carrier&normalQualitativetrait:genetictraitswhicharepresentorabsent.Onehasthetraitornot.單基因遺傳的性狀在群體中，往往可以分出具有和不具有該性狀的2~3個小群體，這一性狀的變異在一個群體中的分布是不連續(xù)的，稱為質量性狀。QuantitativeTraitQuantitativetrait:genetictraitswhicharemeasurablecharacteristics.多基因遺傳的性狀在一個群體中的變異分布是連續(xù)的，只有一個峰，稱為數(shù)量性狀。130140150160170180190200Height(cm)8070605040302010VariabilityGaussiandistributionPthetallesttheshortest

AABBA’A’B’B’F1themedian

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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.在多基因遺傳病中，由遺傳基礎決定一個個體患病的風險稱為易感性。Liability:

beameasureofallofthefactorsthataffecttheprobabilityofmultifactorialdisorder,bothgenetic(innate)andenvironmental.

在多基因遺傳病中，由遺傳因素和環(huán)境因素共同作用并決定一個個體是否易患某種遺傳病的可能性則稱為易患性。605040302010LowHighLiabilityVariabilityThresholdAffected由易患性決定的多基因病的發(fā)病限度稱為閾值。二、HeritabilityHeritability(H,h2)Measure(%)oftheproportionofthetotalphenotypicvariancethatisduetothegeneticbasis.在多基因遺傳病中，易患性的高低受遺傳因素和環(huán)境因素的雙重影響。其中遺傳因素在決定該疾病中所起的作用的大小，稱之為遺傳率。IfHishigh——phenotypicvariationislargelygeneticIfHislow——phenotypicvariationislargelyenvironmental常見多基因遺傳病和先天性畸形的患病率和遺傳率

疾病與畸形群體患病率（%）患者一級親屬患病率遺傳率哮喘4.02080精神分裂癥1.01080原發(fā)性高血壓4~820~3062消化性潰瘍4.0837強直性脊椎炎0.2男性先證者770女性先證者2早發(fā)性糖尿病0.22~575遲發(fā)性糖尿病2~335冠狀動脈硬化性心臟病2.5735先天性幽門狹窄0.3男性先證者275女性先證者10常見多基因遺傳病和先天性畸形的患病率和遺傳率疾病與畸形群體患病率（%）患者一級親屬患病率遺傳率先天性髖關節(jié)脫位0.07470先天性畸形足0.1368先天性巨結腸0.02男性先證者280女性先證者8無腦畸形0.2260脊柱裂0.3460唇裂+腭裂0.17476腭裂0.04276

三、CharacteristicsofPolygenicDisordersMostofcommondiseasesandcommoncongenitalmalformation,incidence＞1/1000.2.Tendtoaggregateinfamilies.Recurrencerate≈1%～10%3.Ethnicdifference病名發(fā)病率日本美國

脊柱裂0.0030.002無腦兒0.0060.005唇裂±腭裂0.00170.001先天性畸形足0.0140.055先天性髖關節(jié)脫位0.010.007Mostofcommondiseasesandcommoncongenitalmalformation,incidence＞1/1000.2.Tendtoaggregateinfamilies.Recurrencerate≈1%～10%3.Ethnicdifference4.Consanguinityalsoincreasestheprobabilityofanaffectedchildforamultifactorialtrait.

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