孟德尔定律课件

1、第二章 孟德尔定律Chapter 2 Mendels LawsThis is a review chapter that you need to review on your own.第1页，共61页。1-1 Law of SegregationGregor J. Mendel 1822-1884第2页，共61页。Why was Mendel successful?选材（Chose a good genetic organism）: short life cycle(生活周期短); large progeny(大量的后代); Several variable characters with t

2、wo discrete traits(许多稳定的、易于区分的性状）, easy to score (yellow or green) Self fertilize(自花受粉), can produce pure lines(纯系) can cross fertilize(杂交) 量化结果（Quantified results）.第3页，共61页。Peas(Pisum sativum L.) can self fertilize.胚珠柱头花粉囊子房龙骨瓣第4页，共61页。Peas(Pisum sativum L.) can cross fertilize.第5页，共61页。孟德尔实验及其分析 孟

3、德尔实验及其分离定律的归纳孟德尔分析的关键性名词概念第6页，共61页。Mendel chose seven traits to study.Trait on the left is dominant（显性）. Trait on the right is recessive（隐性）.第7页，共61页。The first experiment: monohybrid crossPure breeding round Pure breeding wrinkled Hybrids all round(round is dominant;wrinkled is recessive)Round peas

4、wrinkled peas5,474 1,850 Parental Generation (P)First Filial Generation (F1)Second Filial Generation (F2)Wrinkled reappears in F2, unchanged in phenotype and breeding behavior.Ratio of round:wrinkled 3:1.All wrinkledwrinkled round(3:1)第8页，共61页。5,474 round peasGrow 565 into plantsallow to self fertil

5、ize（自交）193 plants produced 372 plants produced only round peas round and wrinkled peasRatio of F2 plants producing (only round) : (round and wrinkled F3 progeny) is 1:2.Therefore 3:1 phenotypic ratio is 1:2:1 ratio based on breeding behavior (pure breeding round:hybrids:pure breeding wrinkled.Third

6、Filial Generation (F3)第9页，共61页。豌豆的性状：种子：圆粒或皱缩种子颜色：黄色或绿色成熟豆夹的形态：饱满或压缩未成熟豆夹的颜色：绿色或黄色 花的颜色：紫花或白花花着生的位置：枝腋生或枝顶生茎的长度：高茎(9-18英吋) 或矮茎(6-7英呎)第10页，共61页。孟德尔推断(Mendels Inferences)中的三原则1. 单位性状原则：一个遗传因子（hereditary factor）决定一个性状。2. 显隐性原则：决定相对性状的遗传因子在一起的时候，有显性和隐性的区别。3. 分离原则：遗传因子在体细胞里成双存在，形成配子时成对遗传因子分离，因此遗传因子在生殖细胞里

7、成单存在，受精以后又恢复到成双状态。由于分离和显隐性的关系，在豌豆杂交的子一代中得到3:1的比例。第11页，共61页。How did Mendel explain the 3:1and 1:2:1 ratios?第12页，共61页。How to test his inferences?测交Test Cross:Breeding a homozygous recessive with a dominant phenotype (unknown genotype) can determine an unknown allele.第13页，共61页。Mendels First Conclusion:

8、分离定律（Law of Segregation） All allele pairs randomly segregate during gamete formation（配子形成过程中等位基因随机分离） Paired condition restored with fusion (fertilization)（成对基因在受精后得到恢复）Aaa1:1A第14页，共61页。实现孟德尔分离比的条件：1. F1代个体形成的配子数目相等，生活力相同；2. 配子结合的机会是相等的；3. 到观察时，F2代 3 种基因型个体的存活率相等；4. 显性是完全的；5. F2应有足够的个体。第15页，共61页。孟德尔

9、规律走在了时代的前面孟德尔时代的生物学水平对受精现象没有肯定下来，细胞的减数分裂还没有发现，还不知道什么东西在体细胞里成双存在，在性细胞里成单存在，孟德尔走在了其时代的前面。孟德尔曾把他的论文送给当时欧洲有名望的植物学家，但他们不置可否。第16页，共61页。Basic Terminology性状(Character): is a feature that is heritable.生物表现出来的形态特征和生理生化特征.基因(gene): a part of a chromosome which determines a certain trait.基因座(locus): Location on

10、 a chromosome of gene表示在给定的一条染色体上的一个基因的位置。等位基因(allele): An alternative form of a gene表示在一个给定基因座内一个基因的替代形式(一个或多个形式)。显性基因(dominant gene): a gene allele which is always expressed when it is present, regardless of whether it is homozygous or heterozygous.隐性基因(recessive gene): a gene allele which is not

11、expressed if it is in the heterozygous state.第17页，共61页。基因型(genotype): the genetic makeup of an organism 一个生物体的全部基因组成，可以指一个基因座，也可以指限制性的若干基因座.表现型(phenotype): 指一个生物体能够被观察到的总体特征，是基因型和环境因素相互作用下的可见结果。纯合体(homozygous): a pair of alleles which are identical某个体在一个给定的基因座上具有两个相同的等位基因杂合体(heterozygous): a single

12、pair of alleles which are unlike each other某个体在其一个给定的基因座上具有两个不同的等位基因杂交（hybrid）: offspring resulting from crossbreeding two true breeding lines.测交（testcross): Breeding a homozygous recessive with a dominant phenotype (unknown genotype).P True breeding parent generation;F1 First “filial” generation;F2

13、 Second “filial” generation.第18页，共61页。1-2 Law of Independent Assortment一、孟德尔的双因子杂交试验二、自由组合定律的归纳及其扩展三、孟德尔学说的核心四、人类简单孟德尔遗传五、豌豆皱缩性状的分子机制第19页，共61页。Dihybrid crossesR/R; Y/Y(round, yellow)r/r; y/y(wrinkled, green)R; Yr; yParental combinationRecombination第20页，共61页。Two hypotheses: dependent or independent a

14、ssortment（自由分离）9:3:3:1 RATIO第21页，共61页。We can use a Punnett Square to show that a self cross of dihybrids producing gametes in a 1:1:1:1 will generate a 9:3:3:1 phenotypic ratio.RR YYround, yellowRR yYround, yellowrR YYround, yellowrR yYround, yellowRR Yyround, yellowRR yyround, greenrR Yyround, yell

15、owrR yyround, greenRr YYround, yellowRr yYround, yellowrr YYwrinkled, yellowrr yYwrinkled, yellowRr Yyround, yellowRr yyround, greenrr Yywrinkled, yellowrr yywrinkled, greenfemale gameteRY Ry rY ryRYRyrYrymalegamete第22页，共61页。Mendels Second Conclusion:自由组合定律（Law of Independent Assortment） 形成配子时，同一对等位

16、基因发生分离，不同对的基因自由组合。AaBbABAbaBab1:11:1:第23页，共61页。parentsRrYyrryygametesRY, Ry, rY, ryryprogenyRrYyRryyrrYyrryy RY yellow, round Ry green, round rY yellow, wrinkled ry green, wrinkled测交验证（Dihybrid Test Cross）Test Cross with multiple traits: Same as with one trait!the test cross is RrYy rryy第24页，共61页。二、

17、自由组合定律的归纳及其扩展一般情况下：F1 配子分离比为1:1:1:1F 2表型分离比为（3:1）2 ，即（3/41/4）2二项式展开的各项系数第25页，共61页。表2-4 杂交所包括的基因对数及基因型和表型杂交中包括的基因对数显性完全时F2的表型数F1杂种形成的配子数F1配子的可能组合数 F2的基因型数分离比1234248162481641664256392781(3/4+1/4)1(3/4+1/4)2(3/4+1/4)3(3/4+1/4)4n2n 2n 4n3n(3/4+1/4)n第26页，共61页。三、孟德尔学说的核心颗粒遗传（particulate inheritance)每一个遗传因

18、子是一个相对独立的功能单位；因子的纯洁性；因子的等位性。 -孟德尔遗传的精髓第27页，共61页。1902年，英国Garrod医生认为黑尿酸症是常染色体隐性遗传病；1903年，人类家族性A1型短指（趾）症是常染色体显性遗传病；1908年发现ABO血型是常染色体单基因遗传性状；至1991年，发现的人类单基因遗传性状达4325个。四、人类简单孟德尔遗传第28页，共61页。雀斑第29页，共61页。第30页，共61页。徐道觉最先报道了折叠舌性状抗日战争胜利后，浙江大学由贵州迁回杭州。在一次遗传学课上，徐道觉介绍卷舌性状，一位钱姓女生举手发言，告诉大家她的舌头不仅会卷，还会向上折叠，并做了表演。徐道觉以此

19、为线索进行了调查研究，发表了两篇论文报道了这个性状。Hsu T. C. Tongue upfolding: A newly reported heritable character in man. Journal of heredity, 1948, 39: 186188.Liu T. T., Hsu T. C. Tongue-folding and tongue-rolling in a sample of the Chinese population. Journal of heredity, 1949, 40: 1920.第31页，共61页。第32页，共61页。人类常染色体遗传病常染色体

20、单基因显性遗传病 人类家族性A1型短指（趾）症、软骨发育不全、高胆固醇血症、神经纤维瘤、视网膜母细胞瘤、Huntington舞蹈病等常染色体单基因隐性遗传病 黑尿酸症、白化病、苯丙酮尿症、半乳糖血症、镰刀形细胞贫血症等第33页，共61页。人类家族性A1型短指（趾）症第34页，共61页。A1型短指（趾）症：1903年，哈佛大学医学院博士毕业生法拉比（Farabee）首次在其毕业论文中报道，即世界上第一例孟德尔常染色体显性遗传病，以后作为遗传学的经典例子被全世界的生物学和遗传学教材广泛引用。上海交大贺林实验室利用布依族、苗族和汉族的三个A1型短指（趾）症大家系，对该病的致病基因进行了定位（定位于2

21、q35-36区）、克隆，首次发现人IHH基因和该基因上的三个突变位点是导致A1型短指（趾）症的直接原因。人类家族性A1型短指（趾）症第35页，共61页。第36页，共61页。上海交大贺林克隆了人类家族性A1型短指（趾）症基因Xinping Yang, Chaowen She, Jingzhi Guo, et al. A Locus for Brachydactyly Type A-1 Maps to Chromosome 2q35-q36. The American Journal of Human Genetics, 66(3): 892-903 (March 2000)Bo Gao, Jin

22、gzhi Guo, Chaowen She, et al. Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1. Nature Genetics 28, 386-388 (16 July 2001)Bo Gao, Jianxin Hu, Sigmar Stricker, et al. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature 458, ( 2009

23、) 高波和胡建新等. IHH基因点突变通过改变IHH蛋白信号能力和信号距离导致指(趾)畸形 nature ，2009年3月揭示了A-1型短指（趾）症致病机理. 第37页，共61页。五、豌豆皱缩性状的分子机制Bhattacharyya, M.K., Smith, A.M., Noel Ellis, T.H., Hedley, C. and Martin, C. The wrinkled-seed character of pea described by Mendel is caused by a transposon-like insertion in a gene encoding star

24、ch-branching enzyme. Cell, 1990, 6: 115-122.Lester, D.R., Ross, J. J., Davies, P. J. and Reid, J. B. Mendels stem length (Le) encodes a gibberellin(赤霉素) 3 beta-hydroxylase. Plant Cell, 1997, 9: 1435-1443.第38页，共61页。豌豆圆粒(RR)和皱粒(rr)在淀粉含量和性质上存在差异。1903年，R. P. Gregory发现，RR豌豆种子淀粉粒数目多、大且单一；而rr种子淀粉粒数目少、小且多角。

25、RR种子淀粉的含量比rr的高，并且支链淀粉与直链淀粉的比例也要高(greenwood &Thomson, 1962).rr种子可溶性蔗糖的含量高于RR种子。以上证据表明，rr种子的淀粉合成受到了阻碍(Smith, 1988)。rr种子淀粉合成量减少，且直链淀粉转变成支链淀粉的过程受阻，细胞中游离的葡萄糖和蔗糖含量升高，渗透压增高，细胞吸收的水分多，因而在种子发育早期，种子吸水膨胀；干燥时，种子收缩，于是产生皱缩的表型。1988年，英国John Innes研究所的Smith等发现淀粉分支酶(SBE1, isoform 1 of starch-branching enzyme)的活性在确定rr种子

26、淀粉含量方面起重要作用，淀粉分支酶是催化直链淀粉转变为支链淀粉的一种酶。第39页，共61页。1989年，巴塔卡雅(M. K. Bhattacharyya)和Smith等克隆了编码淀粉分支酶 (SBE1)的DNA片段，并确证它位于r位点。RRmRNASBE1蛋白DNA 5 3 SBE1基因3.3KbrrDNA 5 3 SBE1基因4.1KbmRNASBE1蛋白(缺失了最后61个氨基酸)0.8Kbr基因是在R基因靠近3端插入了一个0.8kb的类转座子(transposon-like)Ips-r，Ips-r的两个末端为12bp的倒转重复序列：TAGGGGTGGCAA ATCCCCACCGTT。在类转

27、座子的两个侧翼为8bp的正向重复序列：AGTAGAAT TCATCTTA第40页，共61页。Efficient form of Starch Branching Enzyme in Early DevelopmentInefficient form of Starch Branching Enzyme in Early developmentEnzyme + substrateEnzyme + substrateHighStarch Output (more amylopectin than amylose)LowStarch Output (more amylose than amylope

28、ctin)RRrrLowSucrose ContentHighSucrose ContentGranules large and kidney bean shapedGranules small and fissured (sand dollar-like)High Osmotic PotentialNormalOsmotic PotentialNormal Water ContentWater AccumulatesAltered Metabolism Late in Seed DevelopmentOther Starch Producing Enzymes StimulatedSeed

29、Remains Plump During DehydrationSeed Shrivels Easily during DehydrationRound PhenotypeWrinkled PhenotypeFigure 1. The influence of R and r alleles on phenotype. AKA Why do Mendels Peas Wrinkle?Read Bhattacharyya et. al., 1990.有效的淀粉分支酶同工酶无效的淀粉分支酶同工酶支链淀粉直链淀粉高糖-高渗透压-水分降低第41页，共61页。在玉米、大麦等其它植物中也发现了皱缩表型，其

30、皱缩性状的产生机理与豌豆类似。r座位上SBE1的克隆有助于理解显性和隐性的实质：显性基因和隐性基因是类似的DNA片段；显性基因一般形成有功能的酶，当它发生突变，例如其中插入另一段DNA，那么它就不能正常行使功能而成为隐性基因；隐性基因形成的酶可能是异常的，或者根本不能形成有功能的蛋白质。第42页，共61页。豌豆皱皮基因的克隆是正向遗传学的典范经典的正向遗传学是通过杂交等手段研究品种表型的变化、并推测遗传基因的组成和传递规律，其认知路线是由表及里。反向遗传学是在已知基因序列的基础上，利用现代生物理论与技术，通过核苷酸序列的突变、插入等手段创造突变体并研究其表型效应，分析鉴定基因的功能。反向遗传学

31、的认知路线是由里及表，即直接从生物的遗传物质入手来研究基因的生物学功能。第43页，共61页。1-3 遗传学数据的统计学处理一、两个重要的概率法则二、分支法计算遗传比率三、适合度测验第44页，共61页。 乘法法则 The Product rule (the AND rule): The probability of two independent outcomes occurring simultaneously is the product of their individual probabilities. 加法法则 The Sum rule (the OR rule): The proba

32、bility of two mutually exclusive outcomes occurring is the sum of their individual probabilities.Two important probability rules第45页，共61页。But we can use the product rule（乘法法则）The probability of getting round, yellow peas is the probability of getting round peas AND the probability of getting yellow

33、peas.(3/4)(3/4) = 9/16The probability of getting round, green peas is the probability of getting round peas AND the probability of getting green peas.(3/4)(1/4) = 3/16The probability of getting wrinkled, yellow peas is the probability of getting wrinkled peas AND the probability of getting yellow pe

34、as.(1/4)(3/4) = 3/16The probability of getting wrinkled, green peas is the probability of getting wrinkled peas AND the probability of getting green peas.(1/4)(1/4) = 1/16第46页，共61页。二、分支法(Branching Pathway)计算遗传比率:F1 genotypeRrYyF1 phenotypeAll yellow, roundF2 generation:F2 phenotypic ratiofor Rr Rr3/

35、4 R_1/4 rrF2 phenotypic ratiofor Yy Yy1/4 yy3/4 Y_Combined F2 ratios3/16 rrY_ yellow, wrinkled3/16 R_yy green, round9/16 R_Y_yellow, round1/16 rryy green, wrinkled 1/4 yy3/4 Y_第47页，共61页。F2 generation:F2 genotypic ratiofor Rr Rr1/4 RR1/4 rrF2 genotypic ratiofor Yy YyCombined F2 ratios2/4 Rr1/4 YY2/4 Yy1/4 yy1/4 YY2/4 Yy1/4 yy1/16 RRYY1/4 YY2/4