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Ch7. Chromosome Mutation Variation in Number and Arrangement. Although most members of diploid species normally contain precisely two haploid chromosome sets, many known cases vary from this pattern.

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ch7 chromosome mutation variation in number and arrangement

Ch7. Chromosome MutationVariation in Number and Arrangement

Although most members of diploid species normally contain precisely two haploid chromosome sets, many known cases vary from this pattern.

Modifications include a change in the total number of chromosomes, and changes of chromosomal structures, the deletion or duplication of genes or segments of a chromosome, and rearrangements of the genetic material either within or among chromosomes.

Taken together, such changes are called chromosome mutations or chromosome aberrations, to distinguish them from gene mutations.
  • Because, according to Mendelian laws, the chromosome is the unit of genetic transmission, chromosome aberrations are passed on to offspring in a predictable manner, resulting in many unique genetic outcomes.
7.1 Variation in Chromosome Number :An Overview
  • 7.2 Nondisjunction :The origin of Aneupoidy
  • 7.3 Monosomy
  • 7.4 Trisomy
  • 7.5 Polypoidy and its Origin
  • 7.6 Variation in Chromosome Structure and Arrangement: An Overview
  • 7.7 Deletion
  • 7.8 Duplication
  • 7.9 Inversion
  • 7.10 Translocation
  • 7.11 Fragile Sites In Humans

A change in Genetic material---mutation

  • Numbers of chromosomes

Euploidy(整倍体): monoploidy and polyploidy

polyploidy :Autopolyploidy(同源) Allopolyploids(异源)

Aneuploidy(非整倍体): loss 2n- 1 or more and add 2n+1 or more of the whole set of chromosomes

  • Rearrangement (Structural alterations) of chromosomes





1 variation in chromosome number overview
1.Variation in Chromosome Number:Overview
  • Changes in chromosome number can occur by the addition of or the loss of all or part of an entire set of chromosomes
  • Aneuploidy: the loss or the gain of one or more of normal set chromosomes. Each of these conditions is a variation on the normal diploid number of chromosomes.
  • EuploidyChanges by an entire set of chromosomes ,Euploidy - an entire set of chromosomes is duplicated once or several times

Species A


Species B


Species C
























In addition to these conditions, more than one pair of homologous chromosomes may be involved. For example,
  • a double monosomic is missing one chromosome from each of two pair of homologous chromosome (designated 2N-1-1),
  • a double tetrasomic contains an extra pair of two pairs of homologous chromosomes (2N+2+2).
telocentrics which are chromosomes that have a terminal centromere. These structures represent chromosomes that are missing the genetic material beyond that centromere. (Stocks containing these types of chromosomes are called
  • monotelosomics or monotelos (单端体)for short.
  • isochromosome which is a chromosome that contains the same genetic material on both arms.
2 nondisjunction the origin of aneuploidy
2.Nondisjunction(不分离) :The origin of Aneuploidy
  • The development of aneuploids is not well understood, but they may have arisen by a process called nondisjunction. Nondisjunction occurs when paired chromosomes do not separate either during meiosis I or meiosis II. The direct result of this event is that gametes develop that have too few or too many chromosomes. If this occurs during meiosis I normal gametes are not developed, and if it occurs during meiosis II half of the gametes will be normal and the other half will be abnormal.
Non-disjunction can also occur during mitosis and the result is an individual that expresses chromosomal mosaicism(嵌合体).
  • If this occurs during the early stages of cell divisions different portions of the body which descended from the different altered cells will beformed.
  • (See figure 19.20.) Many sex chromosome mosaics have been detected for example X/XX, X/XY, XX/XY and XXX/XXXXY. Mild to severe phenotypic symptoms have been associated with these mosaics
7 3 monosomy
7.3 Monosomy
  • We turn now to a consideration of variations in the number of autosomes and the genetic consequence of such changes. The most common examples of aneuploidy where an organism has a chromosome number other than an exact multiple of the haploid set, are cases in which a single chromosome is either added to, or lost from, a normal diploid set. The loss of one chromosome produces a 2n - 1 complement and is called monosomy.
  • Although monosomy for the X chromosome occurs in humans, as we have seen in 45,X Turner syndrome, monosomy for any of the autosomes is not usually tolerated in human or other animals.
  • 大多数单体动植物不能存活。象玉米、番茄等植物,尽管单倍体能存活,但单体却不能成活,说明遗传物质的平衡很重要。
  • 多倍体植物中单体容易得到,并能存活。例如异源六倍体小麦2n=42,理论上可以得到21种单体,并且事实上也确实如此
  • 单体自交可得缺体(2n-II)。小麦利用21种单体,获得了21种缺体 。
  • 利用单体和缺体可以把基因定位在某个染色体上
  • 理论上,单体2n-I减数分裂时,可形成n和n-1两种配子。自交产生二倍体、单体、缺体三种类型。。
  • 单体丢失

(2)n-1 与n配子参与受精的能力

(3)2n-II 和2n-1的胚胎发育

The failure of monosomic individuals to survive in many animal species is at first quite puzzling, since at least a single copy of every gene is present in the remaining homolog.
  • However, if just one of those genes is represented by a lethal allele, the unpaired chromosome condition leads to the death of the organism.
  • This occurs because monosomy unmasks recessive lethals that are tolerated in heterozygotes carrying the corresponding wild-type alleles.
Aneuploidy is better tolerated in the plant kingdom.
  • Monosomy for autosomal chromosomes has been observed in maize, tobacco, the evening primrose Oenoihera, and the Jimson weed Datura, among other plants.
  • Nevertheless, such monosomic plants are usually less viable than their diploid derivatives.
  • Haploid pollen grains, which undergo extensive development before participating in fertilization, are particularly sensitive to the lack of one chromosome and are seldom viable.

Cri-du-Chat Syndrome

In humans, autosomal monosomy has not been reported beyond birth. There are, however, examples of survivors where only part of one chromosome is lost. These cases are sometimes referred to as segmental deletions.

One such case was first reported by Jerome LeJeune in 1963 when he described the clinical symptoms of the cri-du-chat (cry of the cat) syndrome. This syndrome is associated with the loss of part of the short arm of chromosome 5 (Figure 7-2). of

Thus, the genetic constitution may be designated as 46,5p-, meaning that such an individual has all 46 chromosomes but that some


7.4 Trisomy

  • 三倍体自交或与二倍体杂交,由于三倍体可产生n+1或n两种配子,两种配子结合则可产生三体。另外自然条件下染色体分裂异常也可以产生三体。
  • 三体减数分裂理论上可产生n+1或n两种配子。由于多一条染色体的配子在减数分裂后期I常有落后的现象,n+1配子通常少于50%,而且n+1雄性配子成活率低,很少与雌配子结合。n+1 配子通常由卵细胞传递。
  • 三体若为二显性,与正常二倍体隐性测交比例为5:1,而非1:1。
genetics of aneuploids in fruit fly
Genetics of Aneuploids in fruit fly
  • Monosomics and trisomics are usually inviable in Drosophila. The exception are those aneuploids involving chromosome IV. Therefore the effects of aneuploidy on inheritance has been investigated using stocks with altered chromosome IV.
  • haplo-IV (monosomic for chromosome IV; 2n-1);
  • diplo-IV (normal; 2n) and
  • triplo- IV (trisomic for chromosome IV; 2n+1). Located on chromosome IV is the gene for eyeless (ey) that is recessive to normal eye. The following crosses illustrate several genetic principles of aneuploids. The first is a cross between a diplo-IV eyeless female (ey ey) and a haplo-IV normal eye male (ey+).

例如: P a/a x +/+/+

F1 a/+/+ 与 a/a测交

配子 2/6 a/+ 2/6 + 1/6 +/+ 1/6 a

5: 1


PATAU syndrome = trisomy 13

- facial defects, polydactyly, heart defects, die within a few months of birth

EDWARDS syndrome = trisomy 18

- small + muliple defects, usually die in first year of life

DOWN syndrome = trisomy 21



The karyotype and phenotypic depiction of an infantwith Patau syndrome, where three members of the D-group chromosome 13 are present, creating the 47,13+ condition.

7 5 polyploidy and its origins euploidy
7.5 Polyploidy and Its OriginsEuploidy:
  • 早在19世纪末,狄.弗里斯在月见草(Oenothera lamarckiana)中发现一种比普通月见草的组织器官大得多的变异型,并在1901年把他定为巨型月见草(O,新种)
  • 当时弗里斯在以为巨月件草是普通月见草通过基因突变而产生的。后来(1907,1909)细胞学的研究得知,月见草的核染色体数是28个(2n=28),正好比普通的月见草 的染色体数(2n=14)多一倍。
  • 这就启发人们开始认识染色体数目的变异可以导致遗传性状的变异,特点是按一个基本的染色体数目(基数)成倍的增加或减少。此后,细胞学的研究发现当初按形态分类所划定的不同属或不同种,有许多是和染色体数目的变异联系着的。

The term polyploidy describes instances in which more than two multiples of the haploid chromosome set are found. The naming of polyploids is based on the number of sets of chromosomes found:

  • A triploid has 3n chromosomes;
  • a tetraploid has 4n;
  • a pentaploid, 5n; and so forth.
  • Several general statements can be made about polyploidy. This condition is relatively infrequent in many animal species, but is well known in lizards, amphibians, and fish.
It is much more common in plant species.
  • Odd numbers of chromosome sets are not usually maintained reliably from generation to generation, because a polyploid organism with an uneven number of homologs often does not produce genetically balanced gametes.
  • For this reason, triploids, pentaploids, and so on, are not usually found in plant species that depend solely on sexual reproduction for propagation.
Polyploidy originates in two ways:
  • (1) The addition of one or more extra sets of chromosomes, identical to the normal haploid complement of the same species, resulting in autopolyploidy; and
  • (2) the combination of chromosome sets from different species occurring as a consequence of hybridization, resulting in allopolyploidy (from the Greek word allo, meaning other or different). The distinction between auto- and allopolyploidy is based on the genetic origin of the extra chromosome sets, as shown in Figure 7-6.
Euploidy in Animals
  • A genome that contains three or more full copies of the haploid chromosome number are polyploid. As a general rule polyploids can be tolerated in plants, but are rarely found in animals. One reason is that the sex balance is important in animals and variation from the diploid number results in sterility.
  • Those few animals, such as brine shrimp, that avoid the hazards of polyploidy, utilize parthenogenesis, the development of the an individual from an egg without fertilization, to initiate embryo development.
Euploidy in plants
  • Before we discuss polyploidy in plants in detail, first a distinction must be made between the two major classes of polyploids, autopolyploids and allopolyploids.
  • The following definitions will rely on these chromosomal descriptions. Two species will be considered, A and B. The chromosomal compositions of one species is: A = a1 + a2 + a3 . . . an
  • where a1, a2, etc. represent individual chromosomes and n is the haploid chromosome number.
The chromosomal composition of the second species will be:
  • B = b1 + b2 + b3 . . . bn
  • Autopolyploid - an individual that has an additional set of chromosomes that are identical to parental species;
  • an autotriploid would have the chromosomal composition of AAA and an autotetraploid would be AAAA; both of these are in comparison to the diploid with the chromosomal composition of AA

An autotriploid could occur if a normal gamete (n) unites with a gamete that has not undergone a reduction and is thus 2n. The zygote would be 3n.

  • Triploids could also be produced by mating a diploid (gametes = n) with a tetraploid (gametes = 2n) to produce an individual that is 3n. The difficulty arises when autotriploids try to mate because unbalanced gametes are produced because of pairing problems with the additional chromosome set. Thus, these are invariably sterile.
Allopolyploid - an individual that has an additional set of chromosomes derived from another species; these typically occur after chromosomal doubling and their chromosomal composition would be AABB; if both species have the same number of chromosomes then the derived species would be an allotetraploid
Autotetraploids occur from a doubling of the chromosomal composition. This can occur naturally by doubling sometime during the life cycle or artificially through the application of heat, cold or the chemical colchicine秋水仙素. Because an additional set of chromosomes exists, autotetraploids can undergo normal meiosis.

FIGURE 7-6 Contrasting chromosome origins of an autopolyploid versus an allopolyploid karyotype.


FIGURE 7-7 The potential involvement of colchicine(秋水仙素) in doubling the chromosome number, as occurs during the production of an autotetraploid. Two pairs of homologous chromosomes are followed. While each chromosome has replicated its DNA earlier during interphase, the chromosomes do not appear as double structures until late prophase. When anaphase fails to occur normally, the chromosome number doubles if the cell reenters interphase.


FIGURE 7-9 The origin and propagation of an amphidiploid(双二倍体).

Species I contains genome A consisting of three distinct chromosomes, a,, a2, and a3.

Species 2 contains genome 6 consisting of two distinct chromosomes, b1 and b2.

Following fertilization between members of the two species and chromosome doubling, a fertile amphidiploid containing two complete diploid genomes (AABB) is formed.

  • An individual that contains one half the normal number of chromosomes is a monoploid and exhibits monoploidy. Monoploids are very rare in nature because recessive lethal mutations become unmasked, and thus they die before they are detected. These alleles normally are not a problem in diploids because their effects are masked by dominant alleles in the genome. Some species such as bees, ants and male bees are normally monoploid because they develop from unfertilized eggs.
  • A stage in the life cycle of some fungal species can also be monoploid.
  • Consequently, these individuals will be sterile.
  • 正常的单倍体生物:低等生物的配子体,一些昆虫的雄体(蜜蜂等膜翅目),都是正常的的单倍体;有些动植物中也得到过单倍体,形成的配子也是单倍体。
  • 异常的单倍体生物:二倍体生物成为单倍体后,情况则不同,通常形成的配子高度不育。因此单倍体通常是不育的,也就很难留下后代,得以保存。
  • 其原因是形成正常具有完整的一套染色体组的配子的几率很低,取决于染色体数目,几率为(1/2)n
Monoploidy has been applied in plant biotechnology to rapidly develop plants from anthers that have a fixed genotype. F1 plants derived from a cross of two parents are grown and anther tissue is used to regenerate new plants using tissue culture techniques.

The plants that are derived from this tissue will be monoploid, and the genetics of these individuals can be studied or they can be treated with a chemical to double the chromosome number.

What are the advantages of this technique? Theoretically, different recombination products can be fixed much faster than with conventional plant breeding techniques. Plant breeders make crosses and begin selecting in the F2 generation for individuals that show desirable traits. But these selections are then tested in subsequent generations because the lines are not genetically homogeneous or homozygous. Several more generations of testing are normally required before the desired trait is fixed in a line.
Using anther culture, though, these recombinants in the F1 gametes are fixed immediately after the chromosomes are doubled (with a drug such as colchicine). They are fixed because after doubling the individual will be homozygous for every gene in the genome. Thus, selection for lines with desirable traits can be accelerated significantly. To date, the limiting factor has been the development of anther culture techniques for different crops. Wheat has been the best success story to date with this technique.
One generalization that has been made is that autopolyploids are larger than their diploid counterpart.
  • For example, their flowers and fruits are larger in size which appears to be the result of larger cell size than cell number. This increased size does offer some commercial advantages.
  • 具有3个以上相同染色体组的细胞或生物称为同源多倍体(autopolyploid) ,是由同种生物的染色体加倍形成的






Genotype Gamete Ratio Phenotypes

三显性 AAAa 1AA:1Aa all A

二显性 AAaa 1AA:4Aa:1aa 35A:1a

单显性 Aaaa 1Aa:1aa 3A:1a










  • a1 + a2 a2 + a3 a1 + a3
  • a3 a1 a2
  • 这么个分离方式,结果得到平衡配子(2n或n)的机会很少,(1/2)n-1。绝大多数配子的染色体数目介于2n——n之间,而且能形成平衡配子的机会则更低。所以同源三倍体是高度不育的,只能靠营养体繁殖。
The analysis of plant genomes has provided insight into how these evolutionary events occurred and the rate at which evolution can take place. The three plants genera that will be discussed are Brassica, wheat and Spartina.
Important triploid plants include, some potatoes, bananas, watermelons and Winesap apples. All of these crops must be propagated asexually.
  • Examples of tetraploids are alfalfa, coffee, peanuts and McIntosh apples. These also are larger and grow more vigorously.
The chromosomal composition of allopolyploids is derived from two different species.
  • The classic experiment that initiated research in allopolyploids was performed by G. Karpechenko in 1928.
  • He knew that cabbage and radish both had a diploid number of 18 chromosomes, and he surmised that if he crossed these two species he should be able to derive offspring with 18 chromosomes.
  • His applied goal was to develop a new plant that contained radish roots and cabbage heads.
  • To his disappointment all of the progeny from the cross appeared to be sterile.
  • It is suggested ,incorrect pairing or no synapsis

Surprisingly, though, one day he noticed that some seeds did appear.

  • These were grown, and chromosomal analysis revealed that their diploid number was 36.
  • Apparently, chromosomal doubling had occurred. Therefore balanced gametes were generated because each chromosome had a partner with which to pair.
  • 根——甘蓝
  • 叶——萝卜
  • 检查染色体得只2n=36
  • 萝卜染色体记作R9
  • 甘蓝染色体记作B9
This type of situation where a polyploid is formed from the union of complete sets of chromosomes from two species and their subsequent doubling is called amphidiplpoidy and the species is called an amphidiploid.
  • As a side note, Karpechenko's experiment produced plants with cabbage roots and radish tops.
Euploidy and Plant Speciation
  • One goal of plant breeding has been to develop allopolyploids that have new traits that are not seen in other species. The one beneficial allopolyploid developed to date is Triticale.
  • This amphidiploid was developed from the pollination of wheat (Triticum, 2n=42) with rye (Secale, 2n=14). The goal of this experiment was to combine the rugged phenotype of rye with the high yielding characteristics of wheat.
  • The final chromosomal composition was 2n=56 chromosomes. Allopolyploidy has now been demonstrated to have been a major genetic event during plant speciation.
Wheat Speciation
  • Wheat has played a major role in the development of the world civilization. The domestication of wheat was a major event in world civilization because it allowed humans to change from nomadic hunter gathers to permanent residents of specific locations. The following is the current suggested development of modern bread wheat.
  • Triticum urartu (AA) X Aegilops speltoides (BB) >>Triticum turgidum (AABB) X Triticum tauschii (DD) >> Triticum aestivum (AABBDD)


  • 最典型的例子,是小麦属。
  • 小麦属包括许多的种,按小穗粒数:一粒、二粒、普通小麦
  • 按染色体数目:14、28、42
  • 有有稃的、有裸粒的、有野生的、有栽培的种,总之多种多样。
  • 如何划分小麦属的种,一直是一个有争议的问题。其原因是,同一类内有的杂交可育,有的高度不育,不同类型间的杂交有的又是可育的。


  • 例如小麦属:

种 学名 亚种 染色体数

二倍体小麦 滔氏麦草 T tauschii 14

斯氏麦草 T searsii 14

一粒小麦 T monocum 野生种 14

栽培种 14

四倍体小麦 二粒小麦 T dicocum 28

提莫非维 T timopheari 28

茹科夫斯基 T zhukovskyi 42

普通小麦 T aestivum 许多种 42


Archaeological evidence has shown that Triticum turgidum (AABB) was being grown in both Mesopatamia (Tigris and Euphrates River Valley) and in the Nile River Valley 10,000 years ago.
  • Because wild T. tauschii is found only in the mountain region of southern Russia, western Iran and northern Iraq 。
  • it is thought that the hybridization that produced T. aestivum occurred in these region.
It has been suggested that this occurred as recently as 8,000 years ago which coincides with the development of collective settlements by man.
  • The wheats that were developed by the above hybridization scheme are each cultivated today. Cultivated T. turgidum is called durum wheat. North Dakota is essentially the only state in the US that grows durum wheat. This wheat is processed and used for pasta.

To describe these species it is necessary to introduce the final symbol X.

  • X is the base number of chromosomes for a specific series of species. For wheat 2n=14 and the base number of chromosomes (X) is 7. So for diploid wheat 2n=2X=14. For the series though, the tetraploid species are 2n=4X=28 chromosomes, the pentaploid are 2n=5X=35 chromosomes and the hexaploid is 2n=6X=42 chromosomes.
Brassica Speciation
  • Three Brassica species form a triad from which three other species in the same genera were derived.
  • B. oleracea (broccoli and cauliflower) has a haploid chromosome number of n=9 and
  • the haploid number for B. campesteris (turnip) is n=10.
  • Another Brassica species, B. napus has a haploid number of n=19. This species appears have to been derived by the hybridization of B. oleracea with B. campesteris followed by a doubling of the chromosomes to produce the new species.
Spartinia Speciation
  • The last allopolyploid example is the recent development of a new saltmarsh grass species. In the early nineteenth century seed of American saltmarsh grass (Spartinia alterniflora) was accidentally transported to the southern coast of England and the northern coast of France. The grass began growing in the same location that European saltmarsh grass (S. maritima) was grown. Soon a new species of saltmarsh grass appeared called Townsend's grass (S. townsendii).
The growth pattern of this species was more vigorous and soon it had crowded out the other two native species.
  • These characteristics were recognized and soon it was introduced into Holland to stabilize the dikes and subsequently into other locations for the same reason.
Chromosomal analysis suggested that Townsend's grass was an amphidiploid because its chromosomal number, 2n=122, could be derived from the American (2n=62) and European (2n=60) chromosome numbers. Apparently a hybridization occurred on the beaches followed by a chromosomal doubling to produce the current species. An important point to consider is how quickly speciation can occur from allopolyploid.
Clearly, the Townsend's grass species appeared and became established within 100 years because of its vigorous growth.
  • It has been estimated that about 50% of all angiosperm (flowering plants) are polyploid. The following are some examples of common cultivated plants that are autopolyploids.
  • Wild Species and Cultivated Species

Wild potato (2n=24)Cultivated Potato (2n=48)

Wild Cotton (2n=26)Cultivated Cotton (2n=52)

Dahlia (2n=32)Garden Dahlia (2n=64)

Wild Tobacco (2n=24)Cultivated Tobacco (2n=48)

For some plant species a series of successive ploidy levels are seen.



The New World cotton species Gossypium hirsutum has a 2n chromosome number of 52. The Old World species G. thurberiand G. herbaceum each have a 2n number of 26. Hybrids between these species show the following chromosome pairing arrangements at meiosis:

Fern species exhibit some of the largest chromosome numbers and these are a result of polyploidy. Adder's tongue fern (Ophiglossum) has a base number of 120 chromosomes. The diploid species is 2n=2X=240 chromosomes.
  • One related species has 2n=10X=1200 chromosomes. This demonstrates the high end of the number of chromosomes that are found in eukaryotic species.

7.6 Variation in Chromosome Structure and Arrangement: An Overview

The second general class of chromosome aberrations includes structural changes that delete, add, or rearrange substantial portions of one or more chromosomes

  • origin of changes in chromosome structure
  • deletions
  • duplications
  • inversions
  • translocations
  • practice questions

chromosomal mutations

    • structure
    • number (ploidy)...
  • chromosome structure mutations  phenotypes...
    • abnormal gene # or position
    • break points  disrupt gene function

chromosome properties

    • pairing affinity during meiotic prophase
      • abnormal patterns in rearrangement
    • chromosome breakage
      • changes structure
      • ends highly reactive (normal telomeres not)
    • loss or gain of chromosome pieces
      • genetic imbalance
      • segmental aneuploidy

rearrangements can be

    • spontaneous
    • induced
  • maintained & studied in rearrangement heterozygotes... mainly

types of changes

  • 2 general processes
    • break / rejoining
      • spontaneous
      • radiation
  • 断裂后染色体可能有三种途径发展下去:




  • 三种途径除(1)之外,都可带来染色体结构的变化, 归纳有四种类型


  • 2.重复
  • 3.易位
  • 4.倒位


    • terminal  1 chromosome break
    • interstitial  2 chromosome breaks

7.7 Deletions


Vitality by DELETIONS

  • size
    • intragenic  within 1 gene
      • do not revert ( point mutations)
      • can be viable if gene not vital
    • multigenic  > 1 gene
      • do not revert
      • usually homozygous lethal
      • sometimes heterozygous lethal

Cell or chromosome behavior DELETIONS

  • appearance in polytene chromosomes
    • deletion loop

Genetic effect by DELETIONS

  • genetic properties
    • homozygous lethal (~ size, genes)
    • do not revert
    • recombination not possible in deleted segment
    • uncovers recessive alleles on homologue
      • pseudodominance
      • deletion mapping...





DELETION mapping

  • deletion mapping ~ corresponds with linkage maps
  • 用唾腺染色体进行研究的,结果见图15—9。图中红色区域代表X染色体的258一11、258—14等13个不同缺失类型的缺失区,带有这13个缺失类型的个体分别与白眼一缺刻翅的突变型进行杂交。缺失类型N—8及缺失类型246—38、264—36.264—30、264—31、264—32都使基因fa(facet),小眼面不齐)表现假显性效应,表明这6个缺失类型都丢失了fa+基因(fa的显性等位基因),它们都包括了睡腺染色体的3C7。而缺失类型264-33、264-37、264-39、264-2和264-19,只丢失了3C7中的一条带纹,也使大显示假显性效应。于是可以将fa基因准确定位在3C7带纹处。

DELETIONS deletions & human disease

  • 如猫叫综合症(cridu-chat syndrome)即第5染色体短臂缺失(5P-),是最常见的缺失综合征。由于患儿喉部发育不良,哭声似猫叫而得名。患者身体与智能发育不全,小头畸型,满月形脸,眼距宽,低耳位,通常在婴儿期和幼儿期夭折。研究其染色体核型,发现第5号染色体短臂缺失(5p15.2直至短臂末端),故又称5p-综合征。
慢性骨髓性白血病(chronic myelocvtic leukemia,CML)的特异性标记染色体是 Ph染色体。用荧光显带法检查这类病人的染色体发现,约有90%的患者骨髓细胞的第22号染色体长臂缺失了一大段,缺失染色体的 DNA含量大约相当于正常 22号染色体的 61%(即约丢失了 40 %)。
  • Ph1(费城一号)染色体是慢性粒细胞性白血病的标记染色体,是1960年Nowell和Hungerford首先在美国费城(PhiladelPhia)发现,因而命名为Ph1、Ph染色体是由于22号染色体长臂缺失(22q-)一段的结果、以后应用显带技术证明,Ph不是单纯的缺失,其断裂片段通常易位到9号染色体长臂的末端t(9;22)(q34;q11)。





  • deletions & human disease
    • cancer



FIGURE 7-11 The origin of duplicated and deficient regions of chromosomes as a result of unequal crossing over. The tetrad on the left is mispaired during synapsis. A single crossover between chromatids 2 and 3 results in deficient and duplicated chromosomal regions (see chromosomes 2 and 3, respectively, on the right).The two chromosomes uninvolved in the crossover event remain normal in their gene sequence and content


types of changes

  • 2 general processes
    • break / rejoining
      • spontaneous
      • radiation
    • crossing over
      • illegitimate


  • types (2 chromosome breaks)
    • tandem  adjacent, same order
    • reverse  adjacent, reverse order


  • size... similar to deletions
    • intragenic  within 1 gene
      • do not revert ( point mutations,)
      • can be viable if genetic balance not critical
    • multigenic  > 1 gene
      • do not revert (see below)
      • homozygous lethal if genetic balance critical
      • can be heterozygous lethal if balance critical


  • genetic properties
    • homozygous lethal (~ size, genes)
    • do not revert (see below)
    • illegitimate recombination possible
    • can rescue phenotypes associated with deleted

segments on homologue

    • explanation for evolution of gene families


  • tandem duplications & gene evolution
    • human hemoglobin genes


  • tandem duplications & gene evolution
    • human hemoglobin genes

Gene Redundancy and Amplification—Ribosomal RNA Genes

Although many gene products are not needed in every cell of an organism, other gene products are known to be essential components of all cells. For example, ribosomal RNA mustbe present in abundance in order to support protein synthesis. The more metabolically active a cell is, the higher is the demand for this molecule. We might hypothesize that a single copy of the gene encoding rRNA is inadequate in many cells. Studies using the technique of molecular hybridization, which allows the determination of the percentage of the genome coding for specific RNA sequences, show that our hypothesis is correct! Indeed, multiple copies of genes code for rRNA. Such DNA is called rDNA, and the general phenomenon is called gene redundancy.

For example, in the common intestinal bacterium Escherichia coli , about 0.4 percent of the haploid genome consists of rDNA. equivalent to 5-10 copies of the gene.
  • In Drosophila melanogaster, 0.3 percent of the haploid genome, 130 copies rDNA.
  • Although the presence of multiple copies of the same gene is not restricted to those coding for rRNA, we focus on them in this section.
  • In some cells, particularly oocytes, even the normal redundancy of rDNA is insufficient to provide adequate amounts of rRNA and ribosomes. Oocytes store abundant nutrients in the ooplasm for use by the embryo during early development. In addition, more ribosomes are included in the oocytes than in any other cell type.
By considering how the amphibian Xenopus laevis acquires this abundance of ribosomes, we shall see a second way in which the amount of rRNA is increased. This phenomenon is called gene amplification.
  • The genes that code for rRNA are located in an area of the chromosome known as the nucleolar organizer region (NOR). The NOR is intimately associated with the nucleolus, which is a processing center for ribosome production. Molecular hybridization analysis has shown that each NOR in the frog Xenopus contains the equivalent of 400 redundant gene copies coding for rRNA. Even this number of genes is apparently inadequate to synthesize the vast amount of ribosomes that must accumulate in the amphibian oocyte to support development following fertilization.

The Role of Gene Duplication in Evolution

  • During the study of evolution, it is intriguing to speculate on the possible mechanisms of genetic variation. The origin of unique gene products present in more recently evolved organisms but absent in ancestral forms is a topic of particular interest. In other words, how do "new" genes arise?In 1970, Susumo Ohno published a provocative monograph, Evolution by Gene Duplication, in which he suggested that gene duplication is essential to the origin of new genes during evolution. Ohno's thesis is based on the supposition that the gene products of unique genes, present as only a single copy in the genome, are indispensable to the survival of members of any species during evolution. Therefore, unique genes are not free to accumulate mutations sufficient to alter their primary function and give rise to new genes.

7.9 Inversions

  • types (2 chromosome breaks)
    • paracentric  does not include centromere
    • pericentric  does include centromere


  • types (2 chromosome breaks)
    • pericentric  does include centromere



倒位纯合体(inversion homozygote)

倒位杂合体(inversion heterozygote)

臂内倒位(paracentric inversion)

臂间倒位(pericentric inversion)



  • genetic properties
    • no change in total genetic material
    • breakpoints can (but not always) disrupt genes
      • no disruption  viable homozygotes
      • disruption  heterozygotes only (majority)
    • do not revert
    • recombination in inversion  segm. aneuploidy
      • recombinant gametes lethal  fertility 
      • “recombination suppression”


  • inversion loops


  • crossing over in a pericentric inversion
    • 1 normal  viable
    • 1 inversion  viable
    • 1 duplication  lethal
    • 1 deletion  lethal
  • (1)概念:染色体片段倒转180度,基因的排列顺序颠倒。
  • 一个染色体上同时出现两处断裂,中间的片段倒转180。重新连接起来随之使这一片段上的基因排列的顺序颠倒。倒位是自然界常见的一种染色体结构变异,它不改变染色体上基因的数量,只造成基因的重排。它有许多特殊的细胞遗传行为,可用于遗传设计和植物育种。倒位也是某些动、植物种属问遗传差异的基础,是推动物种形成和分化的因素之一
  • (2)类型
  • 倒位纯合体(inversion homozygote)
  • 倒位杂合体(inversion heterozygote)
  • 臂内倒位(paracentric inversion)
  • 臂间倒位(pericentric inversion)




B、杂合倒位 两个相关的染色体不能一直线方式配对,通常形成一个环结构,以便使同源部分配对——形成所谓的倒位环

②. 倒位杂合体形成桥和断片


③. 倒位杂合体不形成桥和断片



  • 前面细胞学行为② 和③中我们知道:无论着丝点在倒位环外还是内,只要发生交换形成不是重复或缺失的染色体,染色体不平衡,进入配子,配子不能发育而死亡。因此形成的有活力的配子几乎都是没有交换发生染色单体的。


  • 可以抑制或降低倒位环内基因的重组。过去在果蝇当中发现一些性状间有时没有重组,认为有一个交换抑制因子存在。后来研究清楚,实际就是倒位杂合体,倒位环内单交换的产物不能形成有活力的配子,好象是交换被抑制了。
6 balanced lethal system
(6) 平衡致死系(balanced lethal system)
  • 平衡致死系(balanced lethal system):利用倒位杂和体的交换抑制效应,保存隐性致死基因。
  • 一般品系都是以纯合系保存的,它可真实遗传。但是带有隐性致死基因的品系则不行,纯合致死无法保存。因此就得以杂合状态保存。
  • 例如:果蝇No.3号染色体上的展翅D,对正常翅显性,同时也是隐性致死基因。
  • D/+ ♀ x D/+♂
  • 2/3D/+ : 1/3 +/+ :(1/4DD个体致死)
  • 留种
  • 但问题是:
D/+ ♀ x D/+♂组合交配,每个世代所产的子代数只为+ / + ♀ x + / +♂所产子代数的75%
  • 后代群体中如果不进行淘汰+/+ 个体,多代繁殖后, D/+ 个体数必然大量减少,甚至消失。
  • 如果人工观察淘汰,费时费力。
  • 为了解决这些问题,Muller想出了一种利用平衡致死品系的方法:即两个基因彼此紧密连锁(无交换发生),纯合时又都是致死的,只有杂合体得以生存。
  • 如:粘胶眼Gl,也是No.3染色体的显性基因,纯合致死。那么

D / +

+ /Gl


永久杂种(permanent hybrid)。


展翅 粘胶眼

D+/++ × +Gl/++

++/++ D+/++ D+/+G l ++/+Gl

D+/D+ D+/+Gl +Gl/+Gl

致死 致死

  • 那么利用倒位的抑制交换则可解决这个问题。





Cy + Cy +

+ A + A

Cy + Cy + + A

Cy + + A + A

致死 致死

  • (1)一对同源染色体的两个成员各带有一个座位不同的隐性致死基因。
  • (2)两个非等位基因都是纯合致死的,并始终处于个别的同源染色体上,也就是说,要有包含两个基因在内的倒位。

7.10 Translocations

  • reciprocal translocations
    • nonreciprocal translocation
    • Robertsonian translocation 着丝粒融合(centric fusion)和着丝粒裂解( centric fission):
    • can restructure genomes


  • genetic properties
    • no change in total genetic material
    • do not revert
    • meiosis  segmental aneuploidy
      • lethality
      • semi-sterility
    • rearrangement of linkage groups
3 translocation
3. 易位(translocation)
  • (1)概念:染色体片段转移到非同源染色体上去。
  • (2)易位类型
  • 相互易位(reciprocal translocation):非同源染色体相互交换染色体片段
  • 非相互易位(nonreciprocal translocation):单向易位或转座(transposition)
  • 整臂易位(whole-arm translocation)
  • 罗伯逊式易位(Robertsonian translocation):


  • 易位 细胞学行为比较复杂。常见的是相互易位,纯合易位可正常配对,染色体正常传递,没有明显的细胞学特征
  • 杂合易位体,由于涉及到2对同源染色体,粗线期同源配对时,可行成明显的十字架;在向两极移动过程中又可形成O或8字形结构。花粉母细胞中各占50%,表明4条染色体向两极移动是随机的。



(alternate segregation)


(adjacent segregation)




  • 例如:雄果蝇2和3号染色体分别带有bw(褐眼)和e(黑檀体)基因。
  • 雄果蝇2和3染色体易位杂合体,当该杂合体与纯合隐性雌蝇回交时,仅产生野生型(bw/+ e/+)和双突变型(bw/bw e/e)



bw+/bw、e/e )不存在。

  • 在肿瘤的分子生物学研究中,近年来突出的进展之一是发现染色体畸变与致癌基因的表达有关。Burkitt淋巴瘤是一种发生在B细胞中的恶性肿瘤。在这种癌细胞中存在一种特征性的异常染色体那第8号染色体长臂末端(8q24—ter)和第14号染色体长臂末端(lq32—ter)之间的相互易位所产生的两类异常的染色体——14q+ 和8q-染色体。其核型记为t(8;14)(q24;q32)(图15一22)。
Burkitt淋巴瘤存在 3种类型的染色体易位,其中以 t(8;14)发生频率最高(80%~90%)。另外2种易位染色体分别为t(8;22)(q24 ;q11)、t(2;8)(p11;q24)发生频率分别为15%和5%
  • 基因定位研究证明,8q24存在癌基因c-myc,而14q32有IgH基因(免疫球蛋白重链基因)。
  • t(8:14)的Burkitt淋巴瘤细胞中,是由于染色体 8一端的片段断裂后易位到染色体 14q的末端;反向转移是把染色体14q的末端一小片段移至染色体8,这样的相互易位把来自染色体8的一个致癌基因c-myc从正常位置插入通常编码抗体分子一个部分产物的染色体14上的IgH基因内部,激活了癌基因,使c-myc基因大量表达
易位造成花斑型位置效应(variegated type of position effect)
  • 一个基因的表型表达受它所在基因组中的位置的影响。例如倒位和易位,可以使基因的位置发生改变,同时也改变了基因的原有邻近关系,位置的改变引起个体表型改变的遗传效应通称为位置效应(position effect)。花斑型位置效应是其中的一种类型。
  • 原来处于常染色质区的基因,经过易位而移到染色体的异染色质区或其附近,引起这一基因的异染色质化,使它的作用受到抑制。
  • 例如果蝇X染色体的染色体上的白眼基因,当它处于杂合状态时w+/w应表现为红眼。但是,如果在某些细胞中处在常染色质区的w+(红眼基因座)的一段染色体易位到第4染色体的异染色质区,而第4染色体的一段异染色质易位到X染色体的常染色质区。该杂合体的复眼表现为红。
  • 花斑型位置效应与另一种位置效应——稳定型位置效应相比是不稳定的。最先在玉米中发



(Activator-Dis sociation system)




  • in heterozygotes
    • adjacent-1 

2 lethal

    • adjacent-2 


2 lethal

    • alternate 

1 normal

1 carrier



  • in heterozygotes
    • consider





  • rearrangement of linkage groups
    • T heterozygote a/; a+b+/b x tester a/a; b/b

Translocations in Humans:Familial Down Syndrome

  • Research conducted since 1959 has revealed numerous translocations in members of the human population.
  • One common type of translocation involves breaks at the extreme ends of the short arms of two nonhomologous acrocentric chromosomes.
  • These small segments are lost, and the larger segments fuse at their centromeric region. This type of translocation produces a new, large submetacentric or metacentric chromosome, often called a Robertsonian translocation.
One such translocation accounts for cases in which Down syndrome is inherited or familial. Earlier in this chapter we pointed out that most instances of Down syndrome are due to trisomy 21.
  • This chromosome composition results from nondisjunction during meiosis in one parent. Trisomy accounts for over 95 percent of all cases of Down syndrome. In such instances, the chance of the same parents producinga second afflicted child is extremely low.
  • However, in the remaining families with a Down child, the syndrome occurs in a much higher frequency over several generations.

Cytogenetic studies of the parents and their offspring from these unusual cases explain the cause of familial Down syndrome.

  • Analysis reveals that one of the parents contains a 14/21 D/G translocation (Figure 7-16). That is, one parent has the majority of the G-group chromosome 21 translocated to one end of the D-group chromosome 14. This individual is phenotypically normal even though he or she has only 45 chromosomes.

During meiosis, one-fourth of the individual's gametes have two copies of chromosome 21: a normal chromosome and a second copy translocated to chromosome 14. When such a gamete is fertilized by a standard haploid gamete, the resulting zygote has 46 chromosomes but three copies of chromosome 21. These individuals exhibit Down syndrome. Other potential surviving offspring contain either the standard diploid genome (without a translocation) or the balanced translocation like the parent. Both cases result in normal individuals. Knowledge of translocations has allowed geneticists to resolve the seeming paradox of an inherited trisomic phenotype in an individual with an apparent diploid number of chromosomes.


7.11 Fragile脆性 Sites in Humans

  • Ending this chapter with a brief discussion of the results of an intriguing discovery made around 1970 during observations of metaphase chromosomes prepared following human cell culture.
  • In certain individuals, a specific area along one of the chromosomes failed to stain, giving the appearance of a gap. In other individuals whose chromosomes displayed such morphology, the gaps appeared at other positions within the set of chromosomes.
  • Such areas eventually became known as fragile sites, since they appeared to be susceptible to chromosome breakage when cultured in the absence of certain chemicals such as folic acid叶酸, 维生素B, which is normally present in the culture medium.
Fragile sites were at first considered curiosities, until a strong association was subsequently shown to exist between one of the sites and a form of mental retardation.The cause of the fragility at these sites is unknown. Because they represent points susceptible to breakage, these sites may indicate regions where the chromatin is not tightly coiled.
  • Note that even though almost all studies of fragile sites have been carried out in vitro using mitotically dividing cells, clear associations have been established between several of these sites and the corresponding altered phenotype, including mental retardation and cancer

Fragile X Syndrome (Martin-Bell Syndrome

  • Most fragile sites do not appear to be associated with any clinical syndrome. However, individuals bearing a fragile-sensitive site on the X chromosome (Figure 7-17) exhibit the fragile X syndrome (or Martin-Bell syndrome), the most common form of inherited mental retardation.

This syndrome affects about 1 in 1250 males and 1 in 2500 females. Because it is a dominant trait, females carrying only one fragile X chromosome can be mentally retarded. Fortunately, the trait is not fully expressed, as only about 30 percent of fragile X females are retarded, whereas about 80 percent of fragile X males are mentally retarded.

In addition to mental retardation, affected males have characteristic long, narrow faces with protruding chins, enlarged ears, and increased testicular size. A gene that spans the fragile site may be responsible for this syndrome.
  • This gene, known as FMR-1, is one of a growing number of genes that have been discovered in which a sequence of three nucleotides is repeated many times, expanding the size of the gene. This phenomenon, called trinucleotide repeats, is also recognized in other human disorders, including Huntington disease.
  • In FMR-1, the trinucleotide sequence CGG is repeated in an untranslated area adjacent to the coding sequence of the gene (called the "upstream" region). The number of repeats varies immensely within the human population, and a high number correlates directly with expression of fragile X syndrome.
Normal 6 and 54 repeats,
  • Those with 55-200 repeats are considered "carriers" of the disorder. Above 200 repeats leads to expression of the syndrome.It is thought that when the number of repeats reaches this level, the CGG regions of the gene become chemically modified so that the bases within and around the repeat are methylated, causing inactivation of the gene. The normal product of the gene is an RNA-binding protein known to be expressed in the brain. However, the relationship between the absence of this protein and fragile X syndrome is not yet clear..
From a genetic standpoint, perhaps the most interesting aspect of fragile X syndrome is the instability of the CGG repeats. An individual with 6-54 repeats transmits a gene containing the same number to his or her offspring. However, those with 55-200 repeats, while not at risk to develop the syndrome, may transmit to their offspring a gene with an increased number of repeats. The number of repeats continues to increase in future generations, demonstrating the phenomenon known as genetic anticipation, first introduced in Chapter 4. Once the threshold of 200 is exceeded, expression of the malady becomes more severe in each successive generation as the number of trinucleotide repeats increases.
While the mechanism that leads to the trinucleotide expansion has not yet been established, several factors are known that influence the instability. Most significant is the observation that expansion from the carrier status (55-200 repeats) to the syndrome status (over 200 repeats) occurs during the transmission of the gene by the maternal parent, but not by the paternal parent. Furthermore, several reports suggest that male offspring are more likely to receive the increased repeat size leading to the syndrome than are female offspring. Obviously, we have much to learn about the genetic basis of instability and expansion of DNA sequences

Fragile Sites and Cancer

  • A second link between a fragile site and a human disorder was reported in 1996 by Carlo Croce, Kay Huebner, and their colleagues, who demonstrated an association between an autosomal fragile site and cancer.
  • They showed that the gene FHIT (standing for fragile histidine triad), located within a well-defined fragile site on chromosome 3, is often altered in cells taken from tumors of individuals with lung cancer.
  • A variety of mutations were found in cells derived from the tumors where the DNA had apparently been broken and incorrectly refused, resulting in deletions within the gene. In most cases, these mutations caused the FHIT gene to become inactivated.
This gene is part of the fragile region of the autosome designated FRA3B, which has been linked to other cancers, including the esophagus, colon, and stomach. The nature of the genetic alterations found in cancer cells suggests that the FHIT gene, because it is within a fragile region, may be highly susceptible to induced breaks in DNA.
  • If these breaks areincorrectly repaired, cancer-specific chromosome alterations may occur. Thus, this region of the chromosome appears to be particularly sensitive to carcinogen-induced damage, creating a susceptibility to cancer.
  • It will be important to determine experimentally whether molecular polymorphism exists at this and other fragile sites within the human population, causing some individuals to be more susceptible to the effects of carcinogens than others.