An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
Key Concepts
Organisms with multiple chromosome sets (polyploids) are generally larger than diploid
organisms, but meiotic pairing anomalies make some polyploid organisms sterile.
An even number of polyploid sets is generally more likely to result in fertility. Then the
single-locus segregation ratios are different from those of diploids.
Crosses between two different species followed by the doubling of the chromosome number in
the hybrid produces a special kind of fertile interspecific polyploid.
Variants in which a single chromosome has been gained or lost generally arise by
nondisjunction (abnormal chromosome segregation at meiosis or mitosis).
Such variants tend to be sterile and show the abnormalities attributable to gene imbalance.
When fertile, such variants show abnormal gene segregation ratios for the misrepresented
chromosome only.
Introduction
The second major type of chromosome mutation is change in chromosome number. Few
aspects of genetics impinge on human affairs quite so directly as this one. Chromosome
numbers change spontaneously as accidents within cells, and this process has been going on
for as long as life has existed on the planet. In fact, changes in chromosome number have been
instrumental in molding genomes during evolution. For examples of such changes, we have to
look no farther than the food on our dining tables because many of the plants (and some of the
animals) that we eat arose through spontaneous changes in chromosome number in the course
of the evolution of those species. Today, breeders emulate this process by manipulating
chromosome number to improve productivity or some other useful feature of the organism.
But perhaps the main relevance of chromosome numbers is for members of our own species in
that a large proportion of genetically determined ill health in humans is caused by abnormal
chromosome numbers.
In this chapter, we shall investigate the processes that produce new chromosome numbers, the
diagnostic tests for detecting such changes, and the properties of cells and individual
organisms carrying the different kinds of variant chromosomal complements. As with any area
of cytogenetics, the techniques are a combination of genetics and microscopy. Changes in
chromosome number are usually classified into two types—changes in whole chromosome
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
sets and changes in parts of chromosome sets—and these two types are dealt with in the next
two sections.
Aberrant euploidy
The number of chromosomes in a basic set is called the monoploid number (x). Organisms
with multiples of the monoploid number of chromosomes are called euploid. We learned in
earlier chapters that eukaryotes normally carry either one chromosome set (haploids) or two
sets (diploids). Haploids and diploids, then, are both cases of normal euploidy. Euploid types
that have more than two sets of chromosomes are called polyploid. The polyploid types are
named triploid (3x), tetraploid (4x), pentaploid (5x), hexaploid (6x), and so forth. Polyploids
arise naturally as spontaneous chromosomal mutations and, as such, they must be considered
aberrations because they differ from the previous norm. However, many species of plants and
animals have clearly arisen through polyploidy, so evidently evolution can take advantage of
polyploidy when it arises. It is worth noting that organisms with one chromosome set
sometimes arise as variants of diploids; such variants are called monoploid (1x). In some
species, monoploid stages are part of the regular life cycle, but other monoploids are
spontaneous aberrations.
The haploid number (n), which we have already used extensively, refers strictly to the number
of chromosomes in gametes. In most animals and many plants with which we are familiar, the
haploid number and monoploid number are the same. Hence, n or x (or 2n or 2x) can be used
interchangeably. However, in certain plants, such as modern wheat, n and x are different.
Wheat has 42 chromosomes, but careful study reveals that it is hexaploid, with six rather
similar but not identical sets of seven chromosomes. Hence, 6x = 42 and x = 7.
However, the gametes of wheat contain 21 chromosomes, so n = 21 and 2n = 42.
Monoploids
Male bees, wasps, and ants are monoploid. In the normal life cycles of these insects, males
develop parthenogenetically—that is, they develop from unfertilized eggs. However, in most
species, monoploid individuals are abnormal, arising in natural populations as rare aberrations.
The germ cells of a monoploid cannot proceed through meiosis normally, because the
chromosomes have no pairing partners. Thus, monoploids are characteristically sterile. (Male
bees, wasps, and ants bypass meiosis in forming gametes; here, mitosis produces the gametes.)
If a monoploid cell does undergo meiosis, the single chromosomes segregate randomly, and
the probability of all chromosomes going to one pole is (1/2)x−1 where x is the number of
chromosomes. This formula estimates the frequency of viable (whole-set) gametes, which is a
small number if x is large.
Monoploids play an important role in modern approaches to plant breeding. Diploidy is an
inherent nuisance when breeders want to induce and select new gene mutations that are
favorable and to find new combinations of favorable alleles at different loci. New recessive
mutations must be made homozygous before they can be expressed, and favorable allelic
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
combinations in heterozygotes are broken up by meiosis. Monoploids provide a way around
some of these problems. In some plant species, monoploids can be artificially derived from the
products of meiosis in a plant's anthers. A cell destined to become a pollen grain can instead
be induced by cold treatment to grow into an embryoid, a small dividing mass of cells. The
embryoid can be grown on agar to form a monoploid plantlet, which can then be potted in soil
and allowed to mature (Figure 18-1).
Plant monoploids can be exploited in several ways. In one, they are first examined for
favorable traits or allelic combinations, which may arise from heterozygosity already present
in the parent or induced in the parent by mutagens. The monoploid can then be subjected to
chromosome doubling to achieve a completely homozygous diploid with a normal meiosis,
capable of providing seed. How is this achieved? Quite simply, by the application of a
compound called colchicine to meristematic tissue. Colchicine—an alkaloid drug extracted
from the autumn crocus—inhibits the formation of the mitotic spindle, so cells with two
chromosome sets are produced (Figure 18-2). These cells may proliferate to form a sector of
diploid tissue that can be identified cytologically.
Another way in which the monoploid may be used is to treat its cells basically like a
population of haploid organisms in a mutagenesis-and-selection procedure. A population of
cells is isolated, their walls are removed by enzymatic treatment, and they are treated with
mutagen. They are then plated on a medium that selects for some desirable phenotype. This
approach has been used to select for resistance to toxic compounds produced by one of the
plant's parasites and to select for resistance to herbicides being used by farmers to kill weeds.
Resistant plantlets eventually grow into haploid plants, which can then be doubled (with the
use of colchicine) into a pure-breeding, diploid, resistant type (Figure 18-3).
These powerful techniques can circumvent the normally slow process of meiosis-based plant
breeding. The techniques have been successfully applied to several important crop plants, such
as soybeans and tobacco.
The anther technique for producing monoploids does not work in all organisms or in all
genotypes of an organism. Another useful technique has been developed in barley, an
important crop plant. Diploid barley, Hordeum vulgare, can be fertilized by pollen from a
diploid wild relative called Hordeum bulbosum. This fertilization results in zygotes with one
chromosome set from each parental species. In the ensuing somatic cell divisions, however,
the chromosomes of H. bulbosum are eliminated from the zygote, whereas all the
chromosomes of H. vulgare are retained, resulting in a haploid embryo. (The haploidization
appears to be caused by a genetic incompatibility between the chromosomes of the different
species.) The chromosomes of the resulting haploids can be doubled with colchicine. This
approach has led to the rapid production and widespread planting of several new barley
varieties, and it is being used successfully in other species too.
MESSAGE
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
To create new plant lines, geneticists produce monoploids with favorable genotypes
and then double the chromosomes to form fertile, homozygous diploids.
Polyploids
In the realm of polyploids, we must distinguish between autopolyploids, which are composed
of multiple sets from within one species, and allopolyploids, which are composed of sets from
different species. Allopolyploids form only between closely related species; however, the
different chromosome sets are homeologous (only partly homologous)—not fully homologous,
as they are in autopolyploids.
Triploids
Triploids are usually autopolyploids. They arise spontaneously in nature or are constructed by
geneticists from the cross of a 4x (tetraploid) and a 2x (diploid). The 2x and the x gametes
unite to form a 3x triploid.
Triploids are characteristically sterile. The problem, like that of monoploids, lies in pairing at
meiosis. Synapsis, or true pairing, can take place only between two chromosomes, but one
chromosome can pair with one partner along part of its length and with another along the
remainder, which gives rise to an association of three chromosomes. Paired chromosomes of
the type found in diploids are called bivalents. Associations of three chromosomes are called
trivalents, and unpaired chromosomes are called univalents. Hence in triploids there are two
pairing possibilities, resulting either in a trivalent or in a bivalent plus a univalent. Paired
centromeres segregate to opposite poles, but unpaired centromeres pass to either pole
randomly. We see in Figure 18-4 that the net result of both the pairing possibilities is an
uneven segregation, with two chromosomes going in one direction and one in the other. This
happens for every chromosome threesome.
If all the single chromosomes pass to the same pole and simultaneously the other two
chromosomes pass to the opposite pole, then the gametes formed will be haploid and diploid.
The probability of this type of meiosis will be (1/2)x−1, and this proportion is likely to be low.
All other possibilities will give gametes with chromosome numbers intermediate between the
haploid and diploid number; such genomes are aneuploid—“not euploid.” It is likely that
these aneuploid gametes will not lead to viable progeny; in fact, this category is responsible
for the almost complete lack of fertility of triploids. The problem is one of genome imbalance,
a phenomenon that we shall encounter repeatedly in this chapter. For most organisms, the
euploid chromosome set is a finely tuned set of genes in relative proportions that seem to be
functionally significant. Multiples of this set are tolerated because there is no change in the
relative proportions of genes. However, the addition of one or more extra chromosomes is
nearly always deleterious because the proportions of genes in those extra chromosomes are
altered. Although the action of some genes can be regulated to compensate for extra gene
“dosage,” the overall effect of the extra genetic material seems too great to be overcome by
gene regulation. The deleterious effect can be expressed at the level of gametes, making them
nonfunctional, or at the level of the zygote, resulting in lethality, sterility, or lowered fitness.
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
In triploids, it is possible that some haploid or diploid gametes will form, and some may unite
to form a euploid zygote, but the likelihood of this possibility is inherently low. Consider
bananas. The bananas that are widely available commercially are triploids with 11
chromosomes in each set (3x = 33). The probability of a meiosis in which all univalents
pass to the same pole is (1/2)x−1, or (1/2)10 = 1/1024, so bananas are effectively sterile. The
most obvious expression of the sterility of bananas is that there are no seeds in the fruit that we
eat. Another example of the commercial exploitation of triploidy in plants is the production of
triploid watermelons. For the same reasons that bananas are seedless, triploid watermelons are
seedless, a phenotype favored by some for its convenience.
MESSAGE
Some types of chromosome mutations are themselves aneuploid; other types produce
aneuploid gametes or zygotes. Aneuploidy is nearly always deleterious because of
genetic imbalance—the ratio of genes is different from that in euploids and interferes
with the normal operation of the genome.
Autotetraploids
Autotetraploids arise naturally by the spontaneous accidental doubling of a 2x genome to a 4x
genome, and autotetraploidy can be induced artificially through the use of colchicine.
Autotetraploid plants are advantageous as commercial crops because, in plants, the larger
number of chromosome sets often leads to increased size. Cell size, fruit size, flower size,
stomata size, and so forth, can be larger in the polyploid (Figure 18-5). Here we see another
effect that must be explained by gene numbers. Presumably the amount of gene product
(protein or RNA) is proportional to the number of genes in the cell, and this number is higher
in the cells of polyploids compared with diploids.
MESSAGE
Polyploid plants are often larger and have larger organs than their diploid relatives.
Because 4 is an even number, autotetraploids can have a regular meiosis, although this is by
no means always the case. The crucial factor is how the four homologous chromosomes, one
from each of the four sets, pair and segregate. There are several possibilities, as shown in
Figure 18-6. Pairings between four chromosomes are called quadrivalents. In tetraploids, the
two-bivalent and the quadrivalent pairing modes tend to be most regular in segregation, but
even here there is no guarantee of a 2:2 segregation. If all chromosome sets segregate 2:2 as
they do in some species, then the gametes will be functional and a formal genetic analysis can
be developed for such autotetraploids.
Let's consider the genetics of a fertile tetraploid. We can consider an experiment in which
colchicine is used to double the chromosomes of an A/a plant to form an A/A/a/a
auto-tetraploid, which we will assume shows 2:2 segregation. We now have a further concern
because polyploids such as tetraploids give different phenotypic ratios in their progeny,
depending on whether the locus in question is tightly linked to the centromere. First, we
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
consider a centromere-linked gene. The three possible pairing and segregation patterns are
presented in Figure 18-7; these patterns occur by chance and with equal frequency. As Figure
18-7 shows, the 2x gametes produced are A/a, A/A, or a/a, in a ratio of 8:2:2, or 4:1:1. If such a
plant is selfed, the probability of an a/a/a/a phenotype in the offspring is 1/6 × 1/6 =1/36.
In other words, a 35:1 phenotypic ratio of A/–/–/–:a/a/a/a will be observed if A is fully
dominant over three a alleles.
If, in the same kind of plant, a genetic locus having the alleles B and b is very far removed
from the centromere, crossing-over must be considered. This example forces us to think in
terms of chromatids instead of chromosomes; there are four B chromatids and four b
chromatids (Figure 18-8). Because the number of crossovers in such a long region will be
large, the genes will become effectively unlinked from their original centromeres. The
packaging of genes two at a time into gametes is very much like grabbing two balls at random
from a bag of eight balls: four of one kind and four of another. The probability of picking two
b genes is then
So, in a selfing, the probability of a b/b/b/b phenotype is 2/4 × 3/14 = 9/196, which is
approximately 1/22. Hence, there will be a 21:1 phenotypic ratio of B/–/–/–:b/b/b/b. For
genetic loci of intermediate position, intermediate ratios will result.
Allopolyploids
The “classic” allopolyploid was synthesized by G. Karpechenko in 1928. He wanted to make a
fertile hybrid that would have the leaves of the cabbage (Brassica) and the roots of the radish
(Raphanus). Each of these species has 18 chromosomes, and they are related closely enough to
allow intercrossing. A viable hybrid progeny individual was produced from seed. However,
this hybrid was functionally sterile because the nine chromosomes from the cabbage parent
were different enough from the radish chromosomes that pairs did not synapse and disjoin
normally:
However, one day a few seeds were in fact produced by this (almost) sterile hybrid. On
planting, these seeds produced fertile individuals with 36 chromosomes. All these individuals
were allopolyploids. They had apparently been derived from spontaneous, accidental
chromosome doubling to 2n1 + 2n2 in the sterile hybrid, presumably in tissue that
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An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
eventually became germinal and underwent meiosis. Thus, in 2n1 + 2n2 tissue, there is a
pairing partner for each chromosome and balanced gametes of the type n1 + n2 are
produced. These gametes fuse to give 2n1 + 2n2 allopolyploid progeny, which also are
fertile. This kind of allopolyploid is sometimes called an amphidiploid, which means “doubled
diploid” (Figure 18-9). (Unfortunately for Karpechenko, his amphidiploid had the roots of a
cabbage and the leaves of a radish.)
When the allopolyploid was crossed with either parental species, sterile offspring resulted. The
offspring of the cross with radish were 2n1 + n2 constituted from an n1 + n2 gamete from
the allopolyploid and an n1 gamete from the radish. The n2 chromosomes had no pairing
partners, so sterility resulted. Consequently, Karpechenko had effectively created a new
species, with no possibility of gene exchange with its parents. He called his new species
Raphanobrassica.
Today, allopolyploids are routinely synthesized in plant breeding. Instead of waiting for
spontaneous doubling to occur in the sterile hybrid, the plant breeder adds colchicine to induce
doubling. The goal of the breeder is to combine some of the useful features of both parental
species into one type. This kind of endeavor is very unpredictable, as Karpechenko learned. In
fact, only one synthetic amphidiploid has ever been widely used. This amphidiploid is
Triticale, an amphidiploid between wheat (Triticum, 2n = 6x = 42 and rye (Secale,
2n = 2x = 14 Triticale combines the high yields of wheat with the ruggedness of rye.
Figure 18-10 shows the procedure for synthesizing Triticale.
In nature, allopolyploidy seems to have been a major force in speciation of plants. There are
many different examples. One particularly satisfying one is shown by the genus Brassica, as
illustrated in Figure 18-11. Here three different parent species have hybridized in all possible
pair combinations to form new amphidiploid species.
A particularly interesting natural allopolyploid is bread wheat, Triticum aestivum(2n =
6x = 42). By studying various wild relatives, geneticists have reconstructed a probable
evolutionary history of bread wheat (Figure 18-12). In a bread wheat meiosis, there are always
21 pairs of chromosomes. Furthermore, it has been possible to establish that any given
chromosome has only one specific pairing partner (homologous pairing)—not five other
potential partners (homeologous pairing). The suppression of such homeologous pairing
(which would make the species more unstable) is maintained by an allele, Ph, on the long arm
of chromosome 5 of the B set. Thus, Ph ensures a diploidlike meiotic behavior for this
hexaploid species. Without Ph, bread wheat could probably never have arisen. It is interesting
to speculate about whether Western civilization could have begun or progressed without this
species—in other words, without the Ph mutation.
Somatic allopolyploids from cell hybridization
Another innovative approach to plant breeding is to try to make allopolyploid-like hybrids by
fusing asexual cells. Theoretically, such a technique would allow us to combine widely
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
differing parental species. The technique does indeed work, but the only allopolyploids that
have been produced so far can also be made by the sexual methods that we have considered
already. In the cell-fusion procedure, cell suspensions of the two parental species are prepared
and stripped of their cell walls by special enzyme treatments. The stripped cells are called
protoplasts. The two protoplast suspensions are then combined with polyethylene glycol,
which enhances protoplast fusion. The parental cells and the fused cells proliferate on an agar
medium to form colonies (in much the same way as microbes). If these colonies, or calluses as
they are called, are examined, a fair percentage of them are found to be allopolyploid-like
hybrids with chromosome numbers equal to the sum of the parental numbers. Thus, not only
do the protoplast cell membranes fuse to form a kind of heterokaryon, but the nuclei fuse, too,
to give rise to a 2n1 + 2n2 amphidiploid.
Another good example of an allopolyploid-like hybrid is commercial tobacco, Nicotiana
tabacum, which has 48 chromosomes. This species of tobacco was originally found in nature
as a spontaneous amphidiploid. The two probable parents are N. sylvestris and N.
tomentosiformis, each of which has 24 chromosomes. A sexual cross between N. tabacum and
either of these two probable parents give a 36-chromosome hybrid containing 12 chromosome
pairs plus 12 unpaired chromosomes. A cross between N. sylvestris and N. tomentosiformis
yields a 24-chromosome hybrid in which there is no pairing at all. Hence, it appears that part
of the N. tabacum genome is from N. sylvestris and part is from N. tomentosiformis. This
amphidiploid can be recreated either sexually, by using colchicine as described previously, or
somatically by cell fusion. When cells of the prospective parental species are fused, a
48-chromosome hybrid cell line is produced, from which plants identical in behavior to N.
tabacum may be grown. (Note that, in the latter method, colchicine is not required, because the
fusion product is already amphidiploid.)
The recovery of somatic hybrids may be enhanced if a selective system is available. In one
example in N. tabacum, two monoploid lines were fused to form a diploid hybrid culture by
using complementation as the selection system. The first line had whitish, light-sensitive
leaves due to a recessive mutation w. The other had yellowish, light-sensitive leaves due to a
mutation y at a separate locus. When the cells were combined in a petri dish, the diploid
w+/w · y+/y calluses could be selected by their resistance to light and their normal green color.
The calluses can be grown into plantlets, which then are either grafted onto a mature plant to
develop or potted themselves. The protocol for this experiment is illustrated in Figure 18-13.
Two allotetraploids of Petunia, one produced by sexual hybridization and the other by somatic
hybridization, are compared in Figure 18-14. Note that the two are identical in appearance and
produce the same range of progeny types.
MESSAGE
Allopolyploids can be synthesized either by crossing related species and doubling the
chromosomes of the hybrid or by asexually fusing the cells of different species.
Polyploidy in animals
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
You may have noticed that most of the discussion of polyploidy so far has concerned plants.
Indeed, polyploidy is more common in plants than in animals; nevertheless there are many
cases of polyploid animals. Examples are found in flatworms, leeches, and brine shrimp. In
these cases, reproduction is by parthenogenesis, the development of a special type of
unfertilized egg into an embryo, without the need for fertilization. However, examples are not
confined to these so-called lower forms. Polyploid amphibians and reptiles are surprisingly
common. They show several modes of reproduction. The males and females of polyploid frogs
and toads participate in their sexual cycles, whereas polyploid salamanders and lizards are
parthenogenetic.
Some fish also are polyploid; in two cases, it appears that a single polyploid event gave rise to
an entire taxonomic family in evolution. This situation contrasts with that of amphibians and
reptiles because in those cases the polyploids all have closely related diploid species, and,
hence, the polyploid events do not seem to have been important in the evolution of the group
as a whole. The Salmonidae family of fishes (containing salmon and trout) is a familiar
example of a group that appears to have originated through polyploidy. Salmonids have twice
as much DNA as have related fish. Different salmonid species have different chromosome
numbers, but the group has an almost invariant number of chromosome arms (some fused in
some species) that is twice the number of arms in related groups. Hence, the evidence points to
the salmonids' having evolved from a single event that gave rise to a tetraploid.
You might also be interested to know that the sterility of triploids has been commercially
exploited in animals as well as plants. Triploid oysters have been developed, and they have a
commercial advantage over their diploid relatives. The diploids go through a spawning season,
during which they are unpalatable. Triploids, however, because of their sterility, do not spawn
and are palatable the whole year round.
Human polyploid zygotes do arise through various kinds of mistakes in cell division. Most die
in utero. Occasionally, triploid babies are born, but none survive.
Aneuploidy
Aneuploidy is the second major category of chromosome mutations in which chromosome
number is abnormal. An aneuploid is an individual organism whose chromosome number
differs from the wild type by part of a chromosome set. Generally, the aneuploid chromosome
set differs from wild type by only one or a small number of chromosomes. Aneuploids can
have a chromosome number either greater or smaller than that of the wild type. Aneuploid
nomenclature is based on the number of copies of the specific chromosome in the aneuploid
state. For example, the aneuploid condition 2n − 1 is called monosomic (meaning “one
chromosome”) because only one copy of some specific chromosome is present instead of the
usual two found in its diploid progenitor. The aneuploid 2n + 1 is called trisomic,2n − 2
is nullisomic, and n + 1 is disomic.
Nullisomics (2n − 2)
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
Although nullisomy is a lethal condition in diploids, an organism such as bread wheat, which
behaves meiotically like a diploid although it is a hexaploid, can tolerate nullisomy. The four
homoeologous chromosomes apparently compensate for a missing pair of homologs. In fact,
all the possible 21 bread wheat nullisomics have been produced; they are illustrated in Figure
18-15. Their appearances differ from the normal hexaploids; furthermore, most of the
nullisomics grow less vigorously.
Monosomics (2n − 1)
Monosomic chromosome complements are generally deleterious for two main reasons. First,
the missing chromosome perturbs the overall gene balance in the chromosome set. (We
encountered this effect earlier). Second, having a chromosome missing allows any deleterious
recessive allele on the single chromosome to be hemizygous and thus to be directly expressed
phenotypically. Notice that these are the same effects produced by deletions.
Nondisjunction in mitosis or meiosis is the cause of most aneuploids. Disjunction is the
normal separation of homologous chromosomes or chromatids to opposite poles at nuclear
division. Nondisjunction is a failure of this disjoining process, and two chromosomes (or
chromatids) go to one pole and none to the other. Nondisjunction occurs spontaneously; it is
another example of a chance failure of a basic cellular process.
In meiotic nondisjunction, the chromosomes may fail to disjoin at either the first or second
division (Figure 18-16). Either way, n + 1 and n − 1 gametes are produced. If an n −
1 gamete is fertilized by an n gamete, a monosomic(2 n − 1) zygote is produced. The
fusion of an n + 1 and an n gamete yields a trisomic 2n + 1
The precise molecular processes that fail in nondisjunction are not known, but, in experimental
systems, the frequency of nondisjunction can be increased by interference with microtubule
action. It appears that disjunction is more likely to go awry in meiosis I. This likelihood may
not be surprising, because normal anaphase I disjunction requires that proper homologous
associations be maintained during prophase I and metaphase I. In contrast, proper disjunction
at anaphase II or at mitosis requires that the centromere splits properly but does not require
nearly as elaborate a process during prophase and metaphase.
Meiosis I nondisjunction can be viewed as the failure to form or maintain a tetrad (a group of
four chromatids) until anaphase I. Crossovers are implicit in this process normally. In most
organisms, the amount of crossing-over is sufficient to ensure that all tetrads will have at least
one exchange per meiosis. In Drosophila, many of the nondisjunctional chromosomes in
newly arising disomic gametes are nonrecombinant, with one nondisjunctional homolog
carrying the markers of one input chromosome and the other homolog carry- ing the markers
of the other chromosome. Similar observations have been made in human trisomies. In
addition, in several different experimental organisms, mutations that interfere with
recombination have the effect of massively increasing the frequency of meiosis I
nondisjunction. This effect points to an important role of crossing-over in maintaining
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
chromosomal associations in the tetrad; in the absence of these associations, chromosomes are
vulnerable to anaphase I nondisjunction.
In humans, a sex-chromosome monosomic complement of 44 autosomes + 1 X produces a
phenotype known as Turner syndrome. Affected people have a characteristic, easily
recognizable phenotype: they are sterile females, are short in stature, and often have a web of
skin extending between the neck and shoulders (Figure 18-17). Although their intelligence is
near normal, some of their specific cognitive functions are defective. About 1 in 5000 female
births have this monosomic chromosomal complement. Monosomics for all human autosomes
die in utero.
Geneticists have used viable plant nullisomics and monosomics to identify the chromosomes
that carry the loci of newly found recessive mutant alleles. For example, a geneticist may
obtain different monosomic lines, each of which lacks a different chromosome. Homozygotes
for the new mutant allele are crossed with each monosomic line, and the progeny of each cross
are inspected for expression of the recessive phenotype. The phenotype appears in some of the
progeny of the parent that is monosomic for the locus-bearing chromosome and thus identifies
it. Figure 18-18 shows that this test works because meiosis in the monosomic parent produces
some gametes that lack the chromosome bearing the locus. When one of these gametes forms
a zygote, the single chromosome contributed by the other homozygous recessive parent
determines the phenotype.
Genetic analysis of humans occasionally reveals a similar unmasking of a recessive phenotype
by an n − 1gamete. For example, two people whose vision is normal may produce a
daughter who has Turner syndrome and who is also red-green colorblind. This coincidence is
interpreted as follows. First, because the father is not colorblind, the mother must be
heterozygous for the recessive allele and must have passed this allele on to the Turner
daughter. Nondisjunction must have occurred in the father, resulting in an n − 1 sperm,
which combined with an egg bearing the colorblind allele from the mother.
MESSAGE
Monosomics show the deleterious effects of genome inbalance, as well as unexpected
expression of recessive alleles carried on the monosomic chromosome.
Trisomics (2n + 1)
The trisomic condition also is one of chromosomal imbalance and can result in abnormality or
death. However, there are many examples of viable trisomics. You might remember that we
studied the trisomics of the Jimson weed Datura stramonium in Chapter 3 (see Figure 3-7).
Furthermore, trisomics can be fertile. When cells from some trisomic organisms are observed
under the microscope at the time of meiotic chromosome pairing, the trisomic chromosomes
are seen to form a trivalent, an associated group of three, whereas the other chromosomes form
regular bivalents. What genetic ratios might we expect for genes on the trisomic chromosome?
Let us consider a gene, A, that is close to the centromere on that chromosome, and let us
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assume that the genotype is A/a/a. Furthermore, if we postulate that two of the centromeres
disjoin to opposite poles as in a normal bivalent and that the other chromosome passes
randomly to either pole, then we can predict the three equally frequent segregations shown in
Figure 18-19. These segregations result in an overall gametic ratio of 1A:2A/a:2a:1a/a. This
ratio and the one corresponding to a trisomic of genotype A/A/a are observed in practice. If a
trisomic tester set is available (much like the nullisomic tester set described earlier), then a
new mutation can be located to a chromosome by determining which of the testers gives the
special ratio.
There are several examples of viable trisomics in humans. The combination XXY (1 in 1000
male births) results in Klinefelter syndrome, males with lanky builds who are mentally
retarded and sterile (Figure 18-20). Another combination, XYY, also occurs in about 1 in 1000
male births. Attempts have been made to link the XYY condition with a predisposition toward
violence. This linkage is still hotly debated, although it is now clear that an XYY condition in
no way guarantees such behavior. Nevertheless, several enterprising lawyers have attempted to
use the XYY genotype as grounds for acquittal or compassion in crimes of violence. The XYY
males are usually fertile. Their meioses are of the XY type; the extra Y is not transmitted, and
their gametes contain either X or Y, never YY or XY.
The most common type of viable human aneuploid is Down syndrome (Figure 18-21),
occurring at a frequency of about 0.15 percent of all live births. We have already encountered
the translocation form of Down syndrome in Chapter 17. However, by far the most common
type of Down syndrome is trisomy 21, caused by nondisjunction of chromosome 21 in a
parent who is chromosomally normal. Like any mechanism, chromosome disjunction is error
prone and sometimes produces aneuploid gametes. In this type of Down syndrome, there is no
family history of aneuploidy, unlike the translocation type described earlier.
Down syndrome is related to maternal age; older mothers run a greatly elevated risk of having
Down-syndrome children (Figure 18-22). For this reason, fetal chromosome analysis (by
amniocentesis or by chorionic villus sampling) is now recommended for older mothers. A less
pronounced paternal-age effect also has been demonstrated.
Even though the maternal-age effect has been known for many years, its cause is still not
known. Nonetheless, there are some interesting biological correlations. It is possible that one
aspect of the strong maternal-age effect on nondisjunction is an age-dependent decrease in the
probability of keeping the chromosomal tetrad together during prophase I of meiosis. Meiotic
arrest of oocytes (female meiocytes) in late prophase I is a common phenomenon in many
animals. In female humans, all oocytes are arrested at diplotene before birth. Meiosis
continues only at menstruation, which means that proper chromosome associations in the
tetrad must be maintained for decades. If we speculate that, by accident through time, these
associations have an increasing probability of breaking down, we can envision a mechanism
contributing to increased maternal nondisjunction with age. Consistent with this speculation,
most nondisjunction related to the maternal-age effect is due to nondisjunction at anaphase I,
not anaphase II.
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The multiple phenotypes that make up Down syndrome include mental retardation, with an IQ
in the 20 to 50 range; broad, flat face; eyes with an epicanthic fold; short stature; short hands
with a crease across the middle; and a large, wrinkled tongue. Females may be fertile and may
produce normal or trisomic progeny, but males have never reproduced. Mean life expectancy
is about 17 years, and only 8 percent survive past age 40.
The only other human autosomal trisomics to survive to birth are afflicted with either trisomy
13 (Patau syndrome) or trisomy 18 (Edwards syndrome). Both show severe physical and
mental abnormalities. The generalized phenotype of trisomy 13 includes a harelip; a small,
malformed head; “rockerbottom” feet; and a mean life expectancy of 130 days. That of
trisomy 18 includes “faunlike” ears, a small jaw, a narrow pelvis, and rockerbottom feet;
almost all babies with trisomy 18 die within the first few weeks after birth.
Chromosome mutation in general plays a prominent role in determining genetic ill health in
humans. Figure 18-23 summarizes the surprisingly high levels of various chromosome
abnormalities at different human developmental stages. In fact, the incidence of chromosome
mutations ranks close to that of gene mutations in human live births (Table 18-1). This fact is
particularly surprising when we realize that virtually all the chromosome mutations listed in
Table 18-1 arise anew with each generation. In contrast, gene mutations (as we shall see in
Chapter 24) owe their level of incidence to a complex interplay of mutation rates and
environmental selection that spans many human generations.
When the frequencies of various chromosome mutations in live births are compared with the
corresponding frequencies found in spontaneous abortions (Table 18-2), it becomes clear that
the chromosome mutations that we know about as clinical abnormalities are just the tip of an
iceberg of chromosome mutations. First, we see that many more types of abnormalities are
produced than survive to birth; for example, trisomies of chromosome 2, 16, and 22 are
relatively common in abortuses but never survive to birth. Second, the specific aberrations that
survive are part of a much larger number that do not survive; for example, Down syndrome
(trisomy 21) is produced at almost 20 times the frequency in live births. The comparison is
even more striking for Turner syndrome (XO). An estimated minimum of 10 percent of
conceptions have a major chromosome abnormality; our reproductive success depends on the
natural weeding-out process that eliminates most of these abnormalities before birth.
Incidentally, no evidence suggests that these aberrations are produced by environmental insult
to our reproductive systems or that the frequency of the aberrations is increasing.
MESSAGE
Trisomics show the deleterious effects of genome inbalance and produce
chromosome-specific modified phenotypic ratios.
Disomics (n + 1)
A disomic is an aberration of a haploid organism. In fungi, they can result from meiotic
nondisjunction. In the fungus Neurospora (a haploid), an n − 1 meiotic product aborts and
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does not darken like a normal ascospore; so we may detect MI and MII nondisjunctions by
observing asci with 4:4 and 6:2 ratios of normal to aborted spores, respectively, as shown here.
These diagrams correspond exactly to the outcomes of the chromosomal events shown in
Figure 18-16. In these organisms, the disomic (n + 1) meiotic product becomes a disomic
strain directly. The abortion patterns themselves are diagnostic for the presence of disomics in
the asci. Another way of detecting disomics in fungi is to cross two strains with homologous
chromosomes bearing multiple auxotrophic mutations; for example:
From such a cross, large populations of ascospores are plated onto minimal medium. Only
ascospores of genotype ++++++ can grow and form colonies. Most of these colonies are
found to be disomics and not multiple crossover types.
MESSAGE
Disomics in fungi can be selected from asci showing special spore abortion patterns
or as meiotic progeny that must contain homologous chromosomes from both parents.
Somatic aneuploids
Aneuploid cells can arise spontaneously in somatic tissue or in cell culture. In such cases, the
initial result is a genetic mosaic of cell types.
Human sexual mosaics—individuals whose bodies are a mixture of male and female
tissue—are good examples. One type of sexual mosaic, (XO)(XYY), can be explained by
postulating an XY zygote in which the Y chromatids fail to disjoin at an early mitotic division,
so both go to one pole:
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The phenotypic sex of such individuals depends on where the male and female sectors end up
in the body. In the type of nondisjunction being considered, nondisjunction at a later mitotic
division would produce a three-way mosaic (XY)(XO)(XYY), which contains a clone of
normal male cells. Other sexual mosaics have different explanations; as examples, XO/XY is
probably due to early X-chromosome loss in a male zygote (Figure 18-24), and (XX)(XY) is
probably the result of a double fertilization (fused twins). In general, sexual mosaics are called
gynandromorphs.
Geneticists working with many species of experimental animals occasionally find
gynandromorphs among their stocks. A classic example is the Drosophila gynandromorph
shown in Figure 18-25. In this case, the zygote started out as a female heterozygous for two
X-linked genes, white eye and miniature wing (w+m+/w m). Loss of the wild-type
allele–bearing X chromosome at the first mitotic division resulted in the two cell lines and
ultimately in a fly differing from one side to the other in sex, eye color, and size of wing. A
similar gynandromorph in the Io moth is shown in Figure 18-26.
MESSAGE
Mitotic nondisjunction and other types of aberrant mitotic chromosome behavior can
give rise to mosaics consisting of two or more chromosomally distinct cell types,
including aneuploids.
Somatic aneuploidy and its resulting mosaics are often observed in association with cancer.
People suffering from chronic myeloid leukemia (CML), a cancer of the white blood cells,
frequently harbor cells containing the so-called Philadelphia chromosome. This chromosome
was once thought to represent an aneuploid condition, but it is now known to be a
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translocation product in which part of the long arm of chromosome 22 attaches to the long arm
of chromosome 9. However, CML patients often show aneuploidy in addition to the
Philadelphia chromosome. In one study of 67 people with CML, 33 proved to have an extra
Philadelphia chromosome and the remainder had various aneuploidies; the most common
aneuploidy was trisomy for the long arm of chromosome 17, which was detected in 28 people.
Of 58 people with acute myeloid leukemia, 21 were shown to have aneuploidy for
chromosome 8; 16 for chromosome 9; and 10 for chromosome 21. In another study of 15
patients with intestinal tumors, 12 had cells with abnormal chromosomes, at least some with
trisomy for chromosome 8, 13, 15, 17, or 21. Such studies merely established correlations, and
it is not clear whether the abnormalities are best thought of as a cause or as an effect of cancer.
MESSAGE
Aneuploids are produced by nondisjunction or some other type of chromosome
misdivision at either meiosis or mitosis.
Mechanisms of gene imbalance
In considering aberrant euploidy, we noted that an increase in the number of full chromosome
sets correlates with increased organism size but that the general shape and proportions of the
organism remain very much the same. In contrast, autosomal aneuploidy typically alters the
shape and proportions in characteristic ways. Plants tend to be somewhat more tolerant of
aneuploidy than are animals. Studies of the jimsonweed, Datura, provide a classic example of
the effects of aneuploidy and polyploidy. In the jimsonweed, the haploid chromosome number
is 12. As is expected, the polyploid jimsonweed is proportioned like the normal diploids, only
larger. In contrast, each of the 12 possible trisomics is disproportionate, but in ways different
from one another, as exemplified by changes in the shape of the seed capsule (see Figure 3-7).
The 12 different trisomies lead to 12 different and characteristic shape changes in the capsule.
Indeed, these and other characteristics of the individual trisomies are so reliable that the
phenotypic syndrome can be used to identify plants carrying a particular trisomy. Similarly,
the 12 monosomies are themselves different from one another and from each of the trisomies.
In general, a monosomic for a particular chromosome is more severely abnormal than is the
corresponding trisomic.
We see similar trends in aneuploids of animals as well. In the fruit fly, Drosophila, the only
autosomal aneuploids that survive to adulthood are trisomics and monosomics for
chromosome 4, which is the smallest Drosophila chromosome, representing from only about 1
to 2 percent of the genome. Trisomics for chromosome 4 are only very mildly affected and are
much less severely abnormal than are monosomic-4 flys. In humans, no autosomal monosomic
survives to birth, whereas three autosomal trisomies survive, as mentioned earlier. As is true
with aneuploid jimsonweed, the three surviving trisomies produce unique phenotypic
syndromes, owing to the special effects of altered dosages of each of these chromosomes.
Why are aneuploids so much more abnormal than polyploids? Why do aneuploids for different
chromosomes each have their own characteristic phenotypic effects? And why are
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monosomics typically more severely affected than the corresponding trisomics? The answers
seem certain to be a matter of gene balance. In a euploid, the ratio of genes on any one
chromosome to genes on other chromosomes is 1:1 (that is, 100 percent), regardless of
whether we are considering a monoploid, diploid, triploid, or tetraploid. In contrast, in an
aneuploid, the ratio of genes on the aneuploid chromosome to genes on the other
chromosomes differs from wild type by 50 percent (50 percent for monosomics; 150 percent
for trisomics). Thus, we can see that the aneuploid genes are out of balance. How does this
help us to answer the questions raised?
A key fact is that, in general, the amount of transcript produced by a gene is directly
proportional to the number of copies of that gene in a cell. That is, for a given gene, the rate of
transcription is directly related to the number of DNA templates. Thus, the more copies of that
gene, the more transcripts are produced. Because of this gene-dosage relation, segmental
aneuploids, in which pieces of individual chromosomes are trisomic or monosomic
(effectively, duplications and deletions), have proved to be very useful in locating the
positions of genes encoding various cellular enzymes. The approach is to look for segments of
the genome that change the amount of an enzyme proportionally to the dosage of that genomic
segment. This approach has been exploited extensively in Drosophila, where there has been
about a 90 percent success rate in identifying enzymecoding gene loci by this method.
We can infer that normal physiology in a cell depends on the proper ratio of gene products in
the euploid cell. This ratio is the normal gene balance. If the relative dosage of certain genes
changes—for example, owing to the removal of one of the two copies of a chromosome or a
segment thereof—physiological imbalances in cellular pathways can arise.
In some cases, the imbalances of aneuploidy are due to a few “major” genes. Such genes can
be viewed as haplo-abnormal or triploabnormal or both and contribute significantly to the
aneuploid phenotypic syndrome. For example, the study of persons trisomic for only part of
human chromosome 21 has made it possible to localize determinants specific to Down
syndrome to various regions of chromosome 21, hinting that some aspects of the phenotype
might be due to trisomy for single major genes in these chromosomal regions. In addition to
these major-gene effects, other aspects of aneuploid syndromes are likely to be due to
cumulative effects of aneuploidy for numerous genes whose products are all out of balance.
Undoubtedly, the entire aneuploid phenotype is a synthesis of the imbalance effects of a few
major genes, together with a cumulative imbalance of many minor genes.
However, the gene-balance idea does not tell us why having too few gene products
(monosomy) is much worse for an organism than having too many gene products (trisomy).
Along the same lines, in well-studied organisms, there are many more haploabnormal genes
than triploabnormal ones. An important factor in explaining the abnormality of monosomics is
that any deleterious recessives present on the autosome will be automatically expressed. This
same effect is relevant to deletion mutations.
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How do we apply the idea of gene balance to cases of sex-chromosome aneuploidy? Gene
balance holds for sex chromosomes as well, but we also have to take into account the special
properties of the sex chromosomes. In organisms with X-Y sex determination, the Y
chromosome seems to be a degenerate X chromosome in which there are very few functional
genes other than some involved in sex determination itself or in sperm production or both. On
the other hand, the X chromosome contains many genes involved in basic cellular processes
(“housekeeping genes”) that just happen to reside on the chromosome that eventually evolved
into the X chromosome. X-Y sex-determination mechanisms have probably evolved
independently from 10 to 20 times in different taxonomic groups. Thus, there appears to be
one sex-determination mechanism for all mammals, but it is completely different from the
mechanism governing X-Y sex determination in fruit flies.
In a sense, X chromosomes are naturally aneuploid. Females have two of them, whereas males
have only one. Nonetheless, it has been found that the X chromosome's housekeeping genes
are expressed to equal extents per cell in both females and males. How is this accomplished?
The answer depends on the organism. In fruit flies, the male's X chromosome appears to be
hyperactivated, allowing it to be transcribed at twice the rate of either X chromosome in the
female. In mammals, in contrast, the rule is that no matter how many X chromosomes are
present, there is only one transcriptionally active X chromosome in each somatic cell. This
dosage compensation is achieved by random Xchromosome inactivation. (A person with two
or more X chromosomes is a mosaic of two cell types in which one or the other X is active.)
Thus, XY and XX mammals produce the same amount of X-chromosome housekeeping gene
products. X-chromosome inactivation also explains why triplo-X humans are phenotypically
normal, inasmuch as only one of the three X chromosomes is transcriptionally active in a
given cell. Similarly, an XXY male is only moderately affected because only one of his two X
chromosomes is active in each cell.
Why are XXY persons abnormal at all, given that triplo-X persons are phenotypically normal?
It turns out that a small part of the X chromosome near one telomere—the pseudoautosomal
region—is not inactivated by the mechanism of dosage compensation. In XXY males, this
region is active at twice the level of the pseudoautosomal region in XY males. This level
appears to have the consequence of slightly feminizing the phenotype of XXY males, although
exactly which pseudoautosomal genes contribute to this effect is currently unknown. In XXX
females, on the other hand, the pseudoautosomal region is active at only 1.5 times the level
that it is in XX females. This lower level of functional aneuploidy in XXX than that in XXY
plus the fact that the pseudoautosomal genes appear to lead to feminization may explain the
feminized phenotype of XXY males. The severity of XO, Turner syndrome, can be interpreted
as being due to the considerable deleterious effects of monosomy for the pseudoautosomal
region of the X. As is usually observed for aneuploids, monosomy for this segment of the X
chromosome produces a more abnormal phenotype than does having an extra copy of the same
region (triplo-X females or XXY males).
As noted earlier, occasionally human polyploids are born, but none survive. This fact seems to
violate the principle discussed earlier in this section—namely, that polyploids are more normal
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than aneuploids. The explanation for this violation seems to lie with X-chromosome dosage
compensation. Part of the rule for the single active X seems to be that there is one active X for
every two copies of the autosomal chromosome complement. Thus, some cells in triploid
mammals are found to have one active X, whereas others have two. Neither situation is in
balance with autosomal genes. Presumably this functional underactivation of housekeeping
genes (in 3n cells with one active X) or functional overactivation (in 3n cells with two active
X's) leads to substantial functional aneuploidy and the inviability of triploid humans.
Chromosome mechanics in plant breeding
What we know about chromosome mutation can be used in the type of genetic engineering
that produces and maintains new crop types in our hungry world. The classic example,
performed by E. R. Sears in the 1950s, concerns the transfer of a gene for leaf-rust resistance
from a wild grass, Aegilops umbellulata, to bread wheat, which is highly susceptible to this
disease, to offset a major problem in the wheat industry (Figure 18-27).
The first problem that Sears encountered was that these two species (Figure 18-28) are not
interfertile, so the feat of gene transfer seemed impossible. Sears sidestepped this problem
with a bridging cross, in which he crossed A. umbellulata to a wild relative of bread wheat
called emmer, Triticum dicoccoides. (Follow the process in Figure 18-29.) A. umbellulata is a
diploid, 2n = 2x = 14. We will call its chromosome sets CC. T. dicoccoides is a
tetraploid, 2n = 4x = 28, with sets AA BB. From this cross, the resulting sterile hybrid
A B C was doubled into a fertile amphidiploid AA BB CC with 42 chromosomes. This
amphidiploid was fertile in crosses with bread wheat (T. aestivum), which is represented as
2n = 6x = 42, AA BB DD. The offspring, AA BB CD, were almost completely sterile
owing to pairing irregularities between the C and D sets. However, backcrosses to wheat did
produce a few rare seeds, some of which grew into plants that were resistant to leaf rust, like
the wild parent in the first cross. Some of these plants were almost the desired type, having 43
chromosomes (42 of which were wheat, plus one Aegilops chromosome bearing the resistance
gene). Thus, in the AA BB CD hybrid, some aberrant form of chromosome assortment had
produced a gamete with 22 chromosomes: A B D plus one from the C group.
Unfortunately, the extra chromosome carried just too many undesirable Aegilops genes along
with the good one, and the plants were weedy and low producers. So the Aegilops gene
linkage had to be broken. Sears did so by using irradiated pollen from these plants to pollinate
wheat. He was looking for translocations of part of the Aegilops chromosome tacked onto the
wheat chromosomes. These translocations were quite common, but only one turned out to be
ideal—a very small, insertional, unidirectional translocation (Figure 18-30). When bred to
homozygosity, the resistant plants were indistinguishable from wheat.
The study of chromosome mutation is of great importance—not only in pure biology, where
there are ramifications in many areas (especially in evolution), but also in applied biology. The
application of such studies is especially important in agriculture and medicine. Rather
curiously, very little is known about the mechanisms of chromosome mutation, especially at
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the molecular level. More details are needed about the normal chemical architecture of
chromosomes.
Summary
When chromosome mutation changes the number of whole chromosome sets present, aberrant
euploids result; when chromosome mutation changes parts of sets, aneuploids result.
Polyploids such as triploids (3x) and tetraploids (4x) are common in the plant kingdom and are
even represented in the animal kingdom. An odd number of chromosome sets makes an
organism sterile because there is not a partner for each chromosome at meiosis, whereas even
numbers of sets can produce standard segregation ratios. Allopolyploids (polyploids formed
by combining sets from different species) can be made by crossing two related species and
then doubling the progeny chromosomes through the use of colchicine; they can also be made
through somatic cell fusion. These techniques have important applications in crop breeding,
because allopolyploids combine features of both parental species. Polyploidy can result in an
organism of larger dimensions; this discovery has permitted important advances to be made in
horticulture and in crop breeding.
Aneuploids have also been important in the engineering of specific crop genotypes, although
aneuploidy itself usually results in an unbalanced genome with an abnormal phenotype.
Examples of aneuploids include monosomics (2n − 1), trisomics (2n + 1), and disomics
n + 1).Aneuploid conditions are well studied in humans. Down syndrome (trisomy 21),
Klinefelter syndrome (XXY), and Turner syndrome (XO) are well-documented examples. The
spontaneous level of aneuploidy in humans is quite high and produces a major percentage of
genetically based ill health in human populations. Most instances of aneuploidy result from
chromosome nondisjunction at meiosis or chromatid nondisjunction at mitosis. Mitotic
nondisjunction can lead to somatic mosaics.
Solved Problems
1. There is a controversy about the type of chromosome pairing seen in autotetraploids formed
between two geographical races of a certain plant. It is known that chromosomes associate
by pairs, but three hypotheses are put forward concerning how pairs form:
a. Pair formation is random.
b. Pairs form only between chromosomes of the same race.
c. Pairs form only between chromosomes of different races. Consider a locus, A, that is
closely linked to the centromere. The following cross is made:
The autotetraploid is then selfed. What ratio of phenotypes can be expected under each
hypothesis of chromosome pairing? Explain your answer.
See answer
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Solution
a. Under random pairing, all possible pairing combinations are equally likely. If we label the
four homologous chromosomes 1, 2, 3, and 4, then the equally probable combinations are
1-2/3-4, 1-3/2-4, and 1-4/2-3. This kind of situation in an A/A/a/a tetraploid was examined in
the chapter (see page 560). We saw that a/a gametes are produced at a frequency of 1/6 and
that the frequency of a/a/a/a progeny from selfing must therefore be 1/36 All other progeny
types contain at least one A allele. Hence, the expected ratio is 35 A/–/–/–:1 a/a/a/a.
b. In this alternative, the chromosome pairs look like this:
because both the chromosomes carrying A come from race 1 and both the chromosomes
carrying a come from race 2. This diagram shows how being methodical can help in problem
solving, because it makes it very clear that the only possible segregation is that of one A and a
to each pole. Hence, all gametes are A/a and, on self-fertilization, all genotypes would be
A/A/a/a; only the A phenotype would be seen.
c. Here the pairing looks like this:
Because segregation of the pairs is independent, the gametic population can be represented as
follows:
Self-fertilization would produce a/a/a/a progeny at a frequency of 1/4 × 1/4 = 1/16.
Therefore, 15/16 of the progeny are A/–/–/– and a 15:1 phenotypic ratio is predicted. In
conclusion, the ratio of phenotype A to phenotype a in each case is a. 35:1 b. 1:0 c. 15:1
2. Owing to the small size of the Drosophila chromosome 4, monosomics and trisomics for
this chromosome are viable, but tetrasomics and nullisomics are not. A fly that is trisomic
for chromosome 4 and carries the recessive gene for bent bristles (b) on all copies of
chromosome 4 is crossed to a phenotypically normal fly that is monosomic for chromosome
4.
a. What genotypes and phenotypes can be expected in the progeny and in what proportions?
b. If trisomics from these progeny are interbred, what phenotypic ratio can be expected in
the next generation? Assume that only one copy of b+ is needed to produce normal
(nonbent) bristles, that unpaired chromosomes pass to either pole at random, and that
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aneuploid gametes of any kind survive. See answer
Solution
a. The cross is
From the bent-bristled parent, the gametes will be 1/2b/b and 1/2b From the monosomic
parent, the gametes will be 1/2b+ and 1/20 (the latter contain no chromosome 4). Hence, the
progeny will be 1/4b+/b/b, 1/4b/b, 1/4b+/b, and 1/4b, which provides a phenotypic ratio of 1:1.
b. The trisomics referred to are of genotype b+/b/b. If we label these chromosomes 1, 2, and 3,
then
and segregation produces
Fertilization can be represented as follows:
The ×'s represent tetrasomics, which, we are told, are not viable. Of the remaining 27/36,
8/36, are of b phenotype; therefore, a ratio of 19:8 is predicted.
Problems
1. Distinguish between Klinefelter, Down, and Turner syndromes in humans.
See answer
2. List two ways in which you could make an allotetraploid between two related diploid plant
species 2n = 28.
3. a. Suppose that nondisjunction of Neurospora chromosome 3 occurs at the second division
of meiosis. Show the content of each of the eight resultant ascospores with regard to
chromosome 3.
b. Neurospora normally has seven chromosomes. How many chromosomes are present in
each of the ascospores in part a?
See answer
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
4. a. How would you synthesize a pentaploid (5x)?
b. How would you synthesize a triploid (3x) of genotype A/a/a?
c. You have just obtained a rare recessive mutation a* in a diploid plant, which Mendelian
analysis tells you is A/a*. From this plant, how would you synthesize a tetraploid (4x) of
genotype A/A/a*/a*?
d. How would you synthesize a tetraploid of genotype A/a/a/a?
e. How would you synthesize a plant that is resistant to a chemical herbicide? (Assume that
mutation to this trait is very infrequent, and you are lucky to get one mutant.)
5. Which of the following phrases correctly completes the sentence? Allopolyploids are (a) not
fertile at all; (b) fertile only among themselves; (c) fertile with one parent only; (d) fertile
with both parents only; (e) fertile with both parents and themselves.
See answer
6. Tetraploid yeast can be created by fusing two diploid cells. These tetraploids undergo
meiosis like any other tetraploid and produce four diploid products of meiosis. Assume that
homologous chromosomes synapse randomly in pairs and that there is no crossing-over in
the region between the B locus and the centromere. What nonlinear tetrads are produced by
a tetraploid of genotype B/B/b/b? What are the frequencies of the ascus types? (Note: This
question requires tetrad analysis of tetraploid cells instead of the usual diploid cells.)
7. Consider a tetraploid of genotype A/A/a/a in which there is no pairing between
chromosomes from the same parent. In another tetraploid of genotype B/B/b/b, pairs form
only between chromosomes from the same parent. What phenotypic ratios result from
selfing in each of these cases? (Assume that one parent carries the dominant allele and that
the other carries the recessive allele in each case.)
See answer
8. In the plant genus Triticum, there are many different polyploid species, as well as diploid
species. Crosses were made between some different species, and hybrids were obtained. The
meiotic pairing was observed in each hybrid and is recorded in the following table. (A
bivalent is two homologous chromosomes paired at meiosis, and a univalent is an unpaired
chromosome at meiosis.)
Explain these results and, in doing so,
a. deduce the somatic chromosome number of each species used.
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An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
b. state which species are polyploid, and whether they are auto- or allopolyploids.
c. account for the chromosome pairing pattern in the three hybrids.
9. The New World cotton species Gossypium hirsutum has a 2n chromosome number of 52.
The Old World species G. thurberi and G. herbaceum each have a 2n number of 26.
Hybrids between these species show the following chromosome pairing arrangements at
meiosis:
Draw diagrams to interpret these observations phylogenetically, clearly indicating the
relations between the species. How would you go about proving that your interpretation is
correct? (Problem 9 after A. M. Srb, R. D. Owen, and R. S. Edgar, General Genetics, 2d ed.
W. H. Freeman and Company, 1965.)
10. The genotype of an autotetraploid that is heterozygous at two loci is F/F/f/f ; G/G/g/g.
Each locus affects a different character, and the two loci are located very close to the
centromere on different (nonhomologous) chromosomes.
a. What gametic genotypes are produced by this individual and in what proportions?
b. If the individual is self-fertilized, what proportion of the progeny will have the genotype
F/F/F/f ; G/G/g/g? the genotype f/f/f/f ; g/g/g/g?
11. Which of the following abnormalities are not caused by meiotic nondisjunction? (a) Turner
syndrome; (b) cri du chat syndrome; (c) Down syndrome; (d) Klinefelter syndrome; (e)
XYY syndrome; (f) achondroplastic dwarfism; (g) Edwards syndrome; (h) Marfan
syndrome.
See answer
12. A woman with Turner syndrome is found to be colorblind. Both her mother and father
have normal vision. How can her colorblindness be explained? Does this outcome tell us
whether nondisjunction occurred in the father or in the mother? If the colorblindness gene
were close to the centromere (it is not, in fact), would the available facts tell us whether the
nondisjunction occurred at the first or at the second meiotic division? Repeat the question
for a colorblind man with Klinefelter syndrome.
See answer
13. Individuals have been found who are colorblind in one eye but not in the other. What
would this finding suggest if these individuals were (a) only or mostly females? (b) only or
mostly males? (Assume that this trait is X-linked recessive.)
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
14. When geneticists treat human sperm with quinacrine dihydrochloride, about half the sperm
show a fluorescent spot thought to be the Y chromosome. About 1.2 percent of normal
human sperm show two fluorescent spots. Geneticists examined the sperm of some
industrial workmen who were exposed for about 1 year to the chemical
dibromochloropropane. They found the frequency of sperm with two spots to be on
average 3.8 percent. Propose an explanation for this result, and explain how you would test
your explanation.
15. A person with Turner syndrome is also found to have the phenotype nystagmus (an eye
disorder).
a. What event or events can explain the coincidence of the two hereditary conditions?
b. In which parent and at which stage did the event or events occur?
16. In British Columbia, the mean age of women giving birth to Down syndrome babies fell
from 34 years to 28 years between 1952 and 1972. What are two possible causes of this
population trend, and how could the two hypotheses be tested?
17. Several kinds of sexual mosaicism are well documented in humans. Suggest how each of
the following examples may have arisen:
a. (XX)(XO) (that is, there are two cell types in the body, (XX and XO)
b. (XX)(XXYY) c. (XO)(XXX)
d. (XX)(XY) e. (XO)(XX)(XXX)
See answer
18. The discovery of chromosome banding in eukaryotes has greatly improved the ability to
distinguish various cytogenetic events. Particularly useful are banding polymorphisms,
because the “morphs” can be used as chromosome markers. These morphs make
chromosomes cytologically distinguishable by virtue of minor variation in band size,
position, and so forth. Consider chromosome 21 in humans. Assume that one set of parents
is 21a21b ♀ × 21c21d ♂, where a, b, c, and d represent morphs of a polymorphism for this
chromosome. Also assume that fetuses of the following types are produced (where 42A
stands for the rest of the autosomes):
1. 42A + 21b21b21c + XY
2. 42A + 21a21b21d + XX
3. 42A + 21b21d + XY
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
4. 42A + 21a21c21c + XX
5. 42A + 21a21b + XY
6. 42A + 21a21c + XYY
7. (42A + 21a + XY)(42A + 21a21c21c + XY) (mosaic)
8. (42A + 21a21c + XY)(42A + 21b21d + XX) (mosaic)
In each case:
a. State the genetic term for the condition.
b. Diagram the events that give rise to the condition.
c. State the individual in which the events took place.
19. Suppose that you have a line of mice that has cytologically distinct forms of chromosome
4. The tip of the chromosome can have a knob (called 4K), or a satellite (4S), or neither (4).
Here are sketches of the three types:
You cross a 4K 4S female with a 4 4 male and find that most of the progeny are 4K 4 or 4S
4, as expected. However, you occasionally find some rare types as follows (all other
chromosomes are normal):
a. 4K 4K 4 b. 4K 4S 4 c. 4K
d. 4/4K 4K 4 mosaic e. 4K 4/4S 4 mosaic
Explain the rare types that you have found. Give as precisely as possible the stages at
which they originate, and state if they are present in the male parent, the female parent, or
the zygote. (Give reasons briefly.)
See answer
20. In Drosophila, a cross (cross 1) is made between two mutant flies, one homozygous for the
recessive mutation bent wing (b) and the other homozygous for the recessive mutation
eyeless (e). The mutations e and b are alleles of two different genes that are known to be
very closely linked on the tiny autosomal chromosome 4. All the progeny were wild-type
phenotype. One of the female progeny was crossed to a male of genotype b e/b e; call this
cross 2. The progeny of cross 2 were mostly of the expected types, but there was also one
rare female of wild-type phenotype.
a. Explain what the common progeny are expected to be from cross 2.
b. Could the rare wild-type female have arisen by
(1) crossing-over?
(2) nondisjunction?
Explain.
c. The rare wild-type female was testcrossed to a male of genotype b e/b e (cross 3). The
progeny were
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
Which of the explanations in part b are compatible with this result? Explain the genotypes
and phenotypes of progeny of cross 3 and their proportions.
Unpacking the Problem
1. Define homozygous, mutation, allele, closely linked, recessive, wild type, crossing-over,
nondisjunction, testcross, phenotype, and genotype.
2. Does this problem concern sex linkage? Explain.
3. How many chromosomes does Drosophila have?
4. Draw a clear pedigree summarizing the results of crosses 1, 2, and 3.
5. Draw the gametes produced by both parents in cross 1.
6. Draw the chromosome 4 constitution of the progeny of cross 1.
7. Is it surprising that the progeny of cross 1 are wild-type phenotype? What does this
outcome tell you?
8. Draw the chromosome 4 constitution of the male tester used in cross 2, and the gametes
that he can produce.
9. With respect to chromosome 4, what gametes can the female parent in cross 2 produce
in the absence of nondisjunction? Which would be common and which rare?
10. Draw first- and second-division meiotic nondisjunction in the female parent of cross 2,
as well as the resulting gametes.
11. Are any of the gametes from part 10 aneuploid?
12. Would you expect the aneuploid gametes to give rise to viable progeny? Would these
progeny be nullisomic, monosomic, disomic, or trisomic?
13. What progeny phenotypes would be produced by the various gametes considered in
parts 9 and 10?
14. Consider the phenotypic ratio in the progeny of cross 3. Many genetic ratios are based
on halves and quarters, but this ratio is based on thirds and sixths. What might this point
to?
15. Could there be any significance to the fact that the crosses concern genes on a very
small chromosome? When is chromosome size relevant in genetics?
16. Draw the progeny expected from cross 3 under the two hypotheses, and give some idea
of relative proportions.
See answer
21. A cross is made in tomatoes between a female plant that is trisomic for chromosome 6 and
a normal diploid male plant that is homozygous for the recessive allele for potato leaf
(p/p).
a. A trisomic F1 plant is backcrossed to the potato-leaved male. What is the ratio of
normal-leaved plants to potato-leaved plants when you assume that p is on chromosome 6?
b. What is the ratio of normal- to potato-leaved plants when you assume that p is not
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
located on chromosome 6?
22. A tomato geneticist attempts to assign five recessive genes to specific chromosomes using
trisomics. She crosses each homozygous mutant (2n) to each of three
trisomics—chromosomes 1, 7, and 10. From these crosses, the geneticist selects trisomic
progeny (which are less vigorous) and backcrosses them to the appropriate homozygous
recessive. The diploid progeny from these crosses are examined. Her results follow, in
which the ratios are wild type:mutant.
Which of the genes can the geneticist assign to which chromosomes? (Explain your answer
fully.)
23. Petunia plants have four loci, A, B, C, and D, that are known to be very closely linked. A
plant of genotype a B c D/A b C d is irradiated with γ rays and then crossed to an a b c d/a
b c d plant. In the progeny, plants of phenotype A B C D are occasionally found. What are
two possible modes of origin, and which is the more likely?
See answer
24. A cross in Neurospora between strains carrying the multiply marked chromosomes a b+c
d+e and a+b c+d e+ produces one product of meiosis that grows on minimal medium.
(Assume that a, b, c, d, and e determine nutritional requirements.) When the rare colony
grows up, some asexual spores are a b+c d+e in genotype, some are a+b c+d e+, and the
remainder grow on minimal medium. Explain the origin of the rare product of meiosis and
the origin of the three types of asexual spores.
25. Two Neurospora auxotrophs are crossed: pan1 × leu2. These loci are linked on the same
chromosome arm, with leu2 between the centromere and pan1. Most octads from this cross
were of the type expected, but the following unexpected types also were obtained:
a. fully prototrophic
fully prototrophic
fully prototrophic
fully prototrophict
abort
abort
abort
abort
b. pan-requiring
pan-requiring
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
abort
abort
Leu-requiring
Leu-requiring
Leu-requiring
Leu-requiring
c. fully prototrophic
fully prototrophic
abort
abort
Leu-requiring
Leu-requiring
pan-requiring
pan-requiring
Give explanations for these three types.
*26. The ascomycete Sordaria brevicollis has two closely linked complementing markers, b1
and b2, that result in buff-colored (light-brown) ascospores. In the cross b1 × b2, if one or
both centromeres divide and separate precociously at the first division of meiosis, what
patterns of spore colors are produced in those asci? How can these asci be distinguished
from normal asci and from asci in which nondisjunction has occurred? (Note: Ascospores
in this fungus are normally black, and nullisomic ascospores are white; assume that there
is no crossing-over between b1 and b2.)
27. Design a test system for detecting agents in the human environment that are potentially
capable of causing aneuploidy in eukaryotes.
See answer
28. Two alleles determine flower color in the plant Datura: P determines purple; and p, white.
The P locus is on the smallest chromosome, number 3. In plants trisomic for this
chromosome, n + 1 pollen is never functional, and only half the n + 1 eggs are
functional. Assume that P is always completely dominant to any number of p's, and that
the locus is close to the centromere. What is the expected ratio of purple:white in the
progeny of the following crosses?
a. P/P/p ♀ × P/P/p ♂
b. P/p/p ♀ × P/p/p ♂
c. P/p/p ♀ × p/p ♂
29. There are six main species in the Brassica genus: B. carinata, B. campestris, B. nigra, B.
oleracea, B. juncea, and B. napus. You can deduce the interrelationships between these six
species from the following table:
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
a. Deduce the chromosome number of B. campestris, B. nigra, and B. oleracea.
b. Show clearly any evolutionary relationships between the six species that you can deduce
at the chromosomal level.
30. In the fungus Ascobolus (similar to Neurospora), ascospores are normally black. The
mutation f, producing fawn ascospores, is in a gene just to the right of the centromere on
chromosome 6, whereas mutation b, producing beige ascospores, is in a gene just to the
left of the same centromere. In a cross of fawn with beige parents (1f × b 1) most octads
show four fawn and four beige ascospores, but three rare exceptional octads were found as
shown here. In the sketch, black represents the wild-type phenotype, a vertical line
represents fawn, a horizontal line represents beige, and an empty circle represents an
aborted (dead) ascospore.
a. Provide reasonable explanations for these three exceptional octads.
b. Diagram the meiosis that gave rise to octad 2.
31. The life cycle of the haploid fungus Ascobolus is similar to that of Neurospora. A
mutational treatment produced two mutant strains, 1 and 2, both of which when crossed to
wild type gave unordered tetrads all of the following type (fawn is a light-brown color;
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
normally, crosses produce all black ascospores):
a. What does this result show? Explain.
The two mutant strains were crossed. Most of the unordered tetrads were of the following
type:
b. What does this result suggest? Explain.
When large numbers of unordered tetrads were screened under the microscope, some rare
ones that contained black spores were found. Four cases are shown here:
(Note: Ascospores with extra genetic material survive, but those with less than a haploid
genome abort.)
c. Propose reasonable genetic explanations for each of these four rare cases.
d. Do you think the mutations in the two original mutant strains were in one single gene?
Explain.
32. In a certain tropical plant there are two genes, each of which produces color pigment. The
R (red color;>r) and B (blue color; > b loci are centromere linked and on separate
chromosomes. Tetraploid plants are made in which the chromosomes pair in twos at
meiosis. The following cross is made:
and an F1 is obtained and then selfed to give an F2. If only one dominant allele is required
to give the dominant phenotype at each locus, what phenotypes are expected in the F2 and
in what proportions?
33. A tomato geneticist working on Fr, a dominant mutant allele that causes rapid fruit
ripening, decides to find out which chromosome contains this gene by using a set of lines,
each of which is trisomic for one chromosome. To do so, she crosses a homozygous
diploid mutant to each of the wild-type trisomic lines.
a. A trisomic F1 plant is crossed to a diploid wild-type plant. What is the ratio of fast- to
slow-ripening plants in the diploid progeny of this second cross if Fr is on the trisomic
chromosome? Use diagrams to explain.
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勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
b. What is the ratio of fast- to slow-ripening plants in the diploid progeny of this second
cross if Fr is not located on the trisomic chromosome? Use diagrams to explain.
c. Here are the results of the crosses. On which chromosome is Fr and why?
(Problem 33 from Tamara Western.)
Chapter 18*
1. Klinefelter syndrome XXY male
Down syndrome trisomy 21
Turner syndrome XO female
3. a. 3, 3, 3, 3, 3/3, 3/3, 0, 0
b. 7, 7, 7, 7, 8, 8, 6, 6
5. b
7. If there is no pairing between chromosomes from the same parent, then all pairs are A/a.
The gametes are 1 A/A : 2 A/a : 1 a/a. With selfing, the progeny are 1/16 A/A/A/A, 4/16
A/A/A/a, 6/16 A/A/a/a, 4/16 A/a/a/a, 1/16 a/a/a/a. If there is no pairing between
chromosomes from different parents, then all pairs are B/B and b/b and all gametes are B/b.
Thus 100% of the progeny are B/B/b/b.
11. b, f, and h, and sometimes c
12. Colorblindness appears to be an X-linked recessive disorder. That means that the woman
with Turner syndrome had to have obtained her sole X from her mother. She did not obtain
a sex chromosome from her father, which indicates that nondisjunction occurred in him.
The nondisjunction could have occurred at either MI or MII.
If the colorblind patient had Klinefelter syndrome (XXY), then both X's must carry the
allele for colorblindness. Therefore, nondisjunction had to occur in the mother. Remember
that during meiosis I, given no crossover between the gene and the centromere, allelic
32
勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.
An Introduction to Genetic Analysis
Chapter 18
Chromosome Mutation II: Changes in Chromosome Number
alternatives separate from each other. During meiosis II, identical alleles on sister
chromatids separate. Therefore, the nondisjunctive event had to occur during meiosis II
because both alleles are identical.
17. a. Loss of one X in the developing fetus after the two-celled stage.
b. Nondisjunction leading to Klinefelter syndrome (XXY) followed by a nondisjunctive
event in one cell for the Y chromosome after the two-celled stage, leading to XX and
XXYY.
c. Nondisjunction for X at the one-celled stage.
d. Either fused XX and XY zygotes or fertilization of an egg and polar body by one sperm
bearing an X and another bearing a Y, followed by fusion.
e. Nondisjunction of X at the two-celled stage or later.
19. a. The extra chromosome must be from the mother. Because the chromosomes are
identical, nondisjunction had to have occurred at MII.
b. The extra chromosome must be from the mother. Because the chromosomes are not
identical, nondisjunction had to have occurred at MI.
c. The mother correctly contributed one chromosome, but the father did not contribute any
chromosome 4. Therefore, nondisjunction occurred in the male at either meiotic division.
d. One cell line lacks a maternal contribution, whereas the other has a double maternal
contribution. Because the two lines are complementary, the best explanation is that
nondisjunction occurred in the developing embryo in mitosis.
e. Each cell line is normal, indicating that nondisjunction did not occur. The best
explanation is that the second polar body was fertilized and was subsequently fused with
the developing embryo.
20. a. The common progeny are b e+/b e and b+e/b e.
b. The rare female could have come from crossing-over, which would have resulted in a
gamete that was b+e+. The rare female also could have come from nondisjunction that
resulted in a gamete that was b e+/b+e. Such a gamete might give rise to viable progeny.
c. The female was a product of nondisjunction.
23. Radiation could have caused point mutations or induced recombination, but nondisjunction
is a more likely explanation.
27. Aneuploidy is the result of nondisjunction. Therefore, any system that will detect
nondisjunction will work. One of the easiest follows. Cross white-eyed females with
red-eyed males and look for the reverse of X linkage in the progeny. Compare populations
unexposed to any environmental pollutants with those exposed to different suspect agents.
33
勇者并非无所畏惧,而是能判断出有比恐惧更重要的东西.