复杂性状遗传课件

1、2022/7/27Inheritance of Complex Traits1Chapter 10Inheritance of Complex Traits2022/7/27Inheritance of Complex Traits2Chapter OutlineComplex Patterns of InheritanceStatistics of Quantitative GeneticsAnalysis of Quantitative traitsQuantitative Genetics of Human Behavioral Traits2022/7/27Inheritance of

2、 Complex Traits3航空报国英模：罗阳2012年11月24日舰载机成功起降“辽宁”号2012年11月25日总指挥罗阳因心肌梗死逝世原因何在？2022/7/27Inheritance of Complex Traits4Cardiovascular Disease: A Combination of Genetic and Environmental Factors2022/7/27Inheritance of Complex Traits5Section 1Complex Patterns of InheritanceBreeding experiments and compari

3、sons between relatives reveal that complex phenotypes may be influenced by a combination of genetic and environmental factors.2022/7/27Inheritance of Complex Traits61. Quantitative TraitsNature is full of examples of traits that vary continuouslybody size, height, weight, the activity of a particula

4、r enzyme, reproductive ability, and general vigor and fitness, to name just a few.These are among the most interesting traits in biology, especially from an evolutionary standpoint.2022/7/27Inheritance of Complex Traits7One phenotype seems to blend imperceptibly into the next; however, if we examine

5、 many individuals in a population, we usually find significant differences among them.Often this type of variation can be quantified by measuring the trait in a sample of individuals from the population.2022/7/27Inheritance of Complex Traits8We might, for example, capture mice in a barn and weight t

6、hem or collect corncobs from a field and count the number of kernels on each.With such a quantitative approach, the phenotype of every individual in the sample is reduced to a number.These numbers can be analyzed with a variety of statistical techniques, enabling us to study the trait and , in parti

7、cular to investigate its genetic basis.2022/7/27Inheritance of Complex Traits9Traits that are amenable to this kind of treatment are called quantitative traits (数量性状).Their essential characteristic is that they can be measured.2022/7/27Inheritance of Complex Traits10If can we link the evolution with

8、 genetics? 2022/7/27Inheritance of Complex Traits11A growing body of evidence suggested that the complex inheritance of quantitative traits could be explained by Mendelian theory.Two insights made this possible:Quantitative traits are influenced by many genes.Quantitative traits are influenced by ma

9、ny factors in environment.It is the combination of genetic and environmental influences that makes quantitative traits difficult to study.These traits depend on a complex mix of factors; that is, they are multifactoral.2022/7/27Inheritance of Complex Traits12Wilhelm Johannsen1857-1921One of the firs

10、t people to show that variation in a quantitative trait is due to genetic and environment factors.He studied the weight of seeds from the broad bean, Phaseolus vulgaris (蚕豆).Among the plants available to him, seed weight varied from 150 mg to 900 mg.He established lines from individual seeds across

11、this range and maintained each line by self-fertilization for several generation.丹麦生物学家基因概念的提出者2022/7/27Inheritance of Complex Traits13Johannsen observed that seed weight also varied within each of the pure lines.This residual variation in this trait is due to genetic differences because each line h

12、ad been systematically inbred to make it homozygous for its genes.Rather, it must have been due to variation in uncontrolled factors in the environment.His work led to the realization that phenotypic variation in a quantitative trait has two componentsone genetic, the other environmental.2022/7/27In

13、heritance of Complex Traits14H. Nilsson-Ehle He provided evidence that the genetic component of this variation could involve the contributions of several different genes.Nilsson-Ehle studied color variation in wheat grains.When he crossed a white-grained variety with a dark red-grained variety, he o

14、btained an F1 with an intermediate red phenotype.Self-fertilization of the F1 produced an F2 with seven distinct classes, ranging from white to dark red.2022/7/27Inheritance of Complex Traits15Inheritance of grain color in wheat.Three independently assorting genes (A, B, and C) are assumed to contro

15、l grain color.Each gene has two alleles.The alleles for pigmentation (upper case letter) are semidominant over the alleles for lack of pigmentation (lower case letters).这就能用多基因的分离和组合来解释2022/7/27Inheritance of Complex Traits16The American geneticist East extended Nilsson-Ehles studies to a trait that

16、 did not show simple Mendelian ratios in the F2.East studied the lengthen of the corolla in tobacco flowers.In one pure line, the corolla length averaged 41mm; in another, it averaged 93 mm.2022/7/27Inheritance of Complex Traits172022/7/27Inheritance of Complex Traits18Within each pure line, East ob

17、served some phenotypic variationpreassembly the result of environmental influences.By crossing the two lines, East obtained an F1 that had intermediate corolla length and approximately the same amount of variation that had seen within each of the parental strains.When East intercrossed the F1 plants

18、, he obtained an F2 with about same corolla length, on average, that he saw in the F1; however, the F2 plants were much more variable than the F1.2022/7/27Inheritance of Complex Traits19The variability was due to two sources:the segregation and independent assortment of different pairs of alleles co

19、ntrolling corolla length, andenvironmental factors.Each inbred some of the F2 plants to produce an F3 and observed less variation within the different F3 lines than in the F2.The reduced amount of variation within the F2 lines was presumably due to the segregation of fewer allelic differences.2022/7

20、/27Inheritance of Complex Traits20Thus, the complex inheritance pattern that East observed with corolla length could be explained by a combination of genetic segregation and environmental influences.2022/7/27Inheritance of Complex Traits21How many genes were involved in determining corolla length in

21、 Easts strains of tobacco?We can make a crude guess by comparing the F2 plants with each of the inbred parental strains.Lets suppose that the strain with the shorter corollas was homozygous for one set of alleles and that the strain with the longer corollas was homozygous for another set of alleles.

22、2022/7/27Inheritance of Complex Traits22Furthermore, lets suppose that the long-corolla alleles are semidominant, that all length-controlling genes assort independently, and that each gene makes an equal contribution to the phenotype.If corolla length were determined by one gene, with alleles a (for

23、 short corolla) and A (for long corolla), we would expect of F2 to have short corollas (like the short parental strain) and to have long corollas (like long parental strain). 2022/7/27Inheritance of Complex Traits23If two genes determined corolla length, we would expect 1/16 to resemble the long-cor

24、olla parent.If three genes were involved, the frequency of each parental type in F2 would be 1/64, and if four genes were involved, it would be 1/256.With five genes, the parental frequencies in the F2 would each be 1/1024.2022/7/27Inheritance of Complex Traits24East studied 444 F2 plants and failed

25、 to find even one with either of the parental phenotypes.This failure would seem to rule out the hypothesis of four or fewer genes controlling corolla length.Thus, we can conclude that at least five genes are responsible for the difference in corolla length between Easts two inbred strains.至少有5个基因参与

26、了花冠长度的调控！2022/7/27Inheritance of Complex Traits252. Threshold Traits (阈性状) Continuously varying traits such as corolla length, grain color, and bean size are controlled by multiple factors, both genetic and environmental.Geneticists have found that some discontinuous traits also appear to be multifa

27、ctorial.For example, some humans are born with cleft lip, a condition due to an error in embryological development.2022/7/27Inheritance of Complex Traits26Although family studies have suggested that cleft lip is caused by genetic and environmental factors, it is not a quantitative trait in the usual

28、 sense; individuals either express it or they do not.Nonetheless, the genetic and environmental factors that predispose an individual to show it appear to vary quantitatively.Thus, although cleft lip is manifested discontinuously, its underlying variation seems to be continuous.2022/7/27Inheritance

29、of Complex Traits27Geneticists theorize that when the underlying variable exceeds a certain level, the trait appears.This type of trait is therefore called a threshold trait.当潜在的变量超出一定水平的时候，性状就会表现出来，这就是阈性状A model for expression of a threshold trait.When the underlying variable, the “liability(易患性),”

30、 reaches a threshold value, the trait is expressed. This variable is assumed to be continuously distributed in the population.2022/7/27Inheritance of Complex Traits28There is, in effect, a genetic “liability” to develop the condition.However, only those individuals whose liability crosses the thresh

31、old are actually at risk.The underlying variable is a function of factors in the genotype as well as factors in the environment.Some individuals carry alleles that predispose them to develop cleft lip.2022/7/27Inheritance of Complex Traits29In humans, the evidence that traits such as cleft lip are i

32、nfluenced by genetic factors comes from comparisons between relatives, especially twins.Occasionally a fertilized human egg splits and forms two genetically identical zygotes.The individuals who develop from these zygotes are referred to as one-egg, or monozygotic (MZ), twins; they share 100% of the

33、ir genes.2022/7/27Inheritance of Complex Traits30单羊膜腔2022/7/27Inheritance of Complex Traits31More frequently, two independently fertilized eggs develop at the same time in the mother wombs.These two-egg, or dizygotic (DZ), twins are closely related as ordinary siblings; thus, they share 50% of their

34、 genes.Because of their genetic identity, we would expect MZ twins to be phenotypically similar than DZ twins.2022/7/27Inheritance of Complex Traits32Similarity with respect to a trait like cleft lip is assessed by determining the concordance rate (一致率)the fraction of twin pairs in which both twins

35、show the trait among pairs in which at least one of them does.For cleft lip, the concordance rate has been estimated to be about 40% for MZ twins and about 4% for DZ twins.The much greater concordance rate for MZ twins strongly suggests that genetic factors influence an individuals likelihood of bei

36、ng born with cleft lip. 2022/7/27Inheritance of Complex Traits33Mental illnesses such as schizophrenia and manic-depressive disorder can also be regarded as threshold traits.For schizophrenia, the concordance rate ranges from 30 to 60% for MZ twins and from 6 to 18% for DZ twins; for manic-depressiv

37、e disorder, the concordance rate is 70-80% for MZ twins and about 20% for DZ twins.Thus, twin studies suggest that both of these mental illness are influenced by genetic factors.2022/7/27Inheritance of Complex Traits34Key PointsResemblances between relatives and responses to selective breeding indic

38、ate that complex traits have a genetic basis.Some complex traits can be quantified to permit genetic analysis based on Mendelian principles.Many genetic and environmental factors influence the variation observed in quantitative traits.2022/7/27Inheritance of Complex Traits35Key PointsPhenotypic segr

39、egations may provide a way to estimate the number of genes that influence a quantitative trait.Traits that are manifested when an underlying continuous variable (the liability) reaches a threshold value may be influenced by genetic factors.In humans, evidence that a threshold trait has a genetic bas

40、is comes from studies with twins.The concordance rate is the fraction of twin pairs in which both twins show a trait among pairs in which at least one of them does.2022/7/27Inheritance of Complex Traits36Section 2Statistics of Quantitative GeneticsThe frequency distributions of quantitative traits c

41、an be characterized by summary statistics.2022/7/27Inheritance of Complex Traits37The hallmark of quantitative traits is that they vary continuously in a population of individuals.This type of variation poses a formidable problem for the geneticist.Segregation ratios are difficult, if not impossible

42、, to discern because the number of phenotypes is large and one phenotype blends imperceptibly into the next.2022/7/27Inheritance of Complex Traits38For quantitatively varying traits, routine genetic analyses of the sort that we have done with seed color in peas and with human disorders such as albin

43、ism are out of the question.For these types of traits we must resort to a different kind of analysis, one that is based on statistical descriptions of phenotype in a population.2022/7/27Inheritance of Complex Traits391. Frequency DistributionThe first step in the study of any quantitative trait is t

44、o collect measurements of the trait from individuals in a population.Usually, only a small fraction of all the individuals in the population can be measured.We call this group the sample (样本).The data from the sample can be presented graphically as a frequency distribution (频数分布).2022/7/27Inheritanc

45、e of Complex Traits40Frequency distributions and descriptive statistics of time to maturity in four populations of wheat.A and B are inbred strains that were crossed to produce F1 hybrids.The F1 plants were intercrossed to produce an F2.Seed from all four populations was planted in the same season t

46、o determine the time to maturity.In each case, data were obtained from 40 plants.2022/7/27Inheritance of Complex Traits412. The Mean and the Modal ClassThe essential characteristics of a frequency distribution can be summarized by simple statistics calculated from the data.One of these summary stati

47、stics is called the mean or average =(Xk)/n2022/7/27Inheritance of Complex Traits42The modal class (众数组) in a sample that contains the most observations.In each of the distributions the mean is within or very close to the model class. Like the mean, it also captures the “center” of the distribution.

48、This coincidence reflects the symmetry of the distributions; in each case, roughly equal numbers are above and below the mean and the modal class.Not all distributions have this feature.2022/7/27Inheritance of Complex Traits43Some are skewed(偏离的), with most of the observations clustered at one end a

49、nd only a few at the other end forming a long tail.Statisticians have developed an extensive theory about a particular type of symmetrical distribution called a normal distribution (正态分布).In this bell-shaped distribution, the mean and the modal class are located exactly in the center.2022/7/27Inheri

50、tance of Complex Traits443. The variance and the Standard DeviationThe data in a frequency distribution could be dispersed, or they could be clustered.To measure the spread of data in a frequency distribution, we use a statistic called variance (方差).Data that are widely dispersed produce a large val

51、ue for the variance, whereas data that are tightly clustered produce a small value.s2 = (X -)2/(n-1)s2 = (X - 2022/7/27Inheritance of Complex Traits45We should note two features of the variance.Firstly, it measures the dispersion of the data around the mean.When we calculate the variance, we take th

52、e mean to be central value of the distributions in the sample.Second, the variance is always positive.When we calculate the variance, we square the difference between each observation and the mean, and then sum the squared differences. 2022/7/27Inheritance of Complex Traits46Although the variance ha

53、s desirable mathematical properties, it is difficult to interpret because the units of measurement are squared.Consequently, another statistic, called the standard deviation, is often used to be describe the variability of a sample.The standard deviation (s) is the square root of the sample variance

54、.S=2022/7/27Inheritance of Complex Traits47Key PointsThe mean ( = (X )/n) and modal class point to be center of a frequency distribution.The variance (s2=(X - )2/(n-1) and standard deviation s= are statistics that indicate the extent to which data are scattered around the mean in a frequency distrib

55、ution.2022/7/27Inheritance of Complex Traits48Section 3Analysis of Quantitative traitsQuantitative geneticists focus their analyses on phenotypic variability as measured by the variance.2022/7/27Inheritance of Complex Traits49The key idea in quantitative genetics is that traits are controlled by man

56、y different factors in the environment and in the genotype.Fisher hypothesized that a particular value of a quantitative trait, T, is the result of the combined influence of genetic and environmental factors.1 The Multiple Factor Hypothesis2022/7/27Inheritance of Complex Traits50He represented the e

57、ffects of these factors as deviations from the over all population mean:T=+g+eIn this equation, the represents the population mean, g represents the deviation from the genetic factors, and e represents the deviation from the mean that is due to environmental factors.2022/7/27Inheritance of Complex T

58、raits51Quantitative phenotypes and the deviations of individual measurements from the population mean.2022/7/27Inheritance of Complex Traits52Some factors produce large values of T, and some produce small value of T.For each individual, these factors are different.Furthermore, Fisher emphasized that

59、 a multitude of factors are involved.He hypothesized that many genes contribute to a quantitative trait, and he assumed that many genes contribute to a quantitative trait, and he assumed that many aspect of the environment also make contributions.A trait that is controlled by many genes is polygenic

60、 (多基因的).2022/7/27Inheritance of Complex Traits532 Partitioning the Phenotypic Variance (表型方差的分割)VT= Vg + VeVe=(VA+ VB + VC)/3=(1.92 days2 + 2.05 days2 + 2.88 days2)/3=2.28 days2Vg= VT Ve=14.26 days2 2.28 days2=11.98 days22022/7/27Inheritance of Complex Traits54VT= VG + Ve14.26 days2 = 11.98 days2 +