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3: Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes

3: Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes

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Chromosome Variation

(a) Nondisjunction in meiosis I

(c) Nondisjunction in mitosis
Gametes

MEIOSIS I

179

Zygotes

MITOSIS

MEIOSIS II
Fertilization

Nondisjunction

Trisomic
(2n + 1)

Nondisjunction

Monosomic
(2n – 1)

Cell
proliferation

Normal
gamete

(b) Nondisjunction in meiosis II
Gametes
MEIOSIS I

Zygotes

MEIOSIS II
Fertilization

Trisomic
(2n + 1)

Nondisjunction

Monosomic
(2n – 1)

Normal
gamete

Somatic clone
of monosomic
cells (2n – 1)

Somatic clone
of trisomic
cells (2n + 1)

Normal diploid
(2n)

7.17 Aneuploids can be produced through nondisjunction in meiosis I, meiosis II, and mitosis. The gametes
that result from meioses with nondisjunction combine with a gamete (with blue chromosome) that results from normal
meiosis to produce the zygotes. (a) Nondisjunction in meiosis I. (b) Nondisjunction in meiosis II. (c) Nondisjunction in mitosis.
concentrations of gene products and often interfering with
normal development.
A major exception to the relation between gene number
and protein dosage pertains to genes on the mammalian X
chromosome. In mammals, X-chromosome inactivation
ensures that males (who have a single X chromosome) and
females (who have two X chromosomes) receive the same
functional dosage for X-linked genes (see pp. 80–81 in
Chapter 4 for further discussion of X-chromosome inactivation). Extra X chromosomes in mammals are inactivated; so
we might expect that aneuploidy of the sex chromosomes
would be less detrimental in these animals. Indeed, it is the
case for mice and humans, for whom aneuploids of the sex
chromosomes are the most common form of aneuploidy
seen in living organisms. Y-chromosome aneuploids are
probably common because there is so little information on
the Y chromosome.

Concepts
Aneuploidy, the loss or gain of one or more individual chromosomes, may arise from the loss of a chromosome subsequent to
translocation or from nondisjunction in meiosis or mitosis. It disrupts gene dosage and often has severe phenotypic effects.

✔ Concept Check 5
A diploid organism has 2n = 36 chromosomes. How many chromosomes will be found in a trisomic member of this species?

Aneuploidy in Humans
For unknown reasons, an incredibly high percentage of all
human embryos that are conceived possess chromosome
abnormalities. Findings from studies of women who are
attempting pregnancy suggest that more than 30% of all

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Chapter 7

conceptions spontaneously abort (miscarry), usually so early
in development that the mother is not even aware of her
pregnancy. Chromosome defects are present in at least 50%
of spontaneously aborted human fetuses, with aneuploidy
accounting for most of them. This rate of chromosome
abnormality in humans is higher than in other organisms
that have been studied; in mice, for example, aneuploidy is
found in no more than 2% of fertilized eggs. Aneuploidy in
humans usually produces such serious developmental problems that spontaneous abortion results. Only about 2% of all
fetuses with a chromosome defect survive to birth.

Sex-chromosome aneuploids The most common aneuploidy seen in living humans has to do with the sex chromosomes. As is true of all mammals, aneuploidy of the human
sex chromosomes is better tolerated than aneuploidy of
autosomal chromosomes. Both Turner syndrome and Klinefelter syndrome (see Chapter 4) result from aneuploidy of
the sex chromosomes.
Autosomal aneuploids Autosomal aneuploids resulting
in live births are less common than sex-chromosome aneuploids in humans, probably because there is no mechanism
of dosage compensation for autosomal chromosomes. Most
autosomal aneuploids are spontaneously aborted, with the
exception of aneuploids of some of the small autosomes such
as chromosome 21. Because these chromosomes are small
and carry fewer genes, the presence of extra copies is less
detrimental than it is for larger chromosomes. For example,
the most common autosomal aneuploidy in humans is trisomy 21, also called Down syndrome (discussed in the
introduction to the chapter). The number of genes on different human chromosomes is not precisely known at the present time, but DNA sequence data indicate that chromosome
21 has fewer genes than any other autosome, with only about
230 genes of a total of 20,000 to 25,000 for the entire
genome.
The incidence of Down syndrome in the United States
is similar to that of the world, about 1 in 700 human births,
although the incidence increases among children born to
older mothers. Approximately 92% of those who have Down
syndrome have three full copies of chromosome 21 (and
therefore a total of 47 chromosomes), a condition termed
primary Down syndrome (Figure 7.18). Primary Down
syndrome usually arises from spontaneous nondisjunction
in egg formation: about 75% of the nondisjunction events
that cause Down syndrome are maternal in origin, most arising in meiosis I. Most children with Down syndrome are
born to normal parents, and the failure of the chromosomes
to divide has little hereditary tendency. A couple who has
conceived one child with primary Down syndrome has only
a slightly higher risk of conceiving a second child with Down
syndrome (compared with other couples of similar age who
have not had any Down-syndrome children). Similarly, the

7.18 Primary Down syndrome is caused by the presence of
three copies of chromosome 21. Karyotype of a person who has
primary Down syndrome. [L. Willatt, East Anglian Regional Genetics
Service/Science Photo Library/Photo Researchers.]

couple’s relatives are not more likely to have a child with primary Down syndrome.
About 4% of people with Down syndrome have 46
chromosomes, but an extra copy of part of chromosome 21
is attached to another chromosome through a translocation
(Figure 7.19). This condition is termed familial Down syn-

7.19 The translocation of chromosome 21 onto another
chromosome results in familial Down syndrome. Here, the
long arm of chromosome 21 is attached to chromosome 15. This
karyotype is from a translocation carrier, who is phenotypically normal
but is at increased risk for producing children with Down syndrome.
[Dr. Dorothy Warburton, HICCC, Columbia University.]

181

Chromosome Variation

drome because it has a tendency to run in families. The phenotypic characteristics of familial Down syndrome are the
same as those for primary Down syndrome.
Familial Down syndrome arises in offspring whose parents are carriers of chromosomes that have undergone a
Robertsonian translocation, most commonly between chromosome 21 and chromosome 14: the long arm of 21 and the
short arm of 14 exchange places. This exchange produces a
chromosome that includes the long arms of chromosomes
14 and 21, and a very small chromosome that consists of the
short arms of chromosomes 21 and 14. The small chromosome is generally lost after several cell divisions. Although
exchange between chromosomes 21 and 14 is the most-common cause of familial Down syndrome, the condition can
also be caused by translocations between 21 and other chromosomes such as 15 (illustrated in Figure 7.19).
Persons with the translocation, called translocation
carriers, do not have Down syndrome. Although they possess only 45 chromosomes, their phenotypes are normal
because they have two copies of the long arms of chromosomes 14 and 21, and apparently the short arms of these
chromosomes (which are lost) carry no essential genetic
information. Although translocation carriers are completely
healthy, they have an increased chance of producing children
with Down syndrome (Figure 7.20).

P generation

Normal
parent

21 14

Few autosomal aneuploids besides trisomy 21 result in
human live births. Trisomy 18, also known as Edward syndrome, arises with a frequency of approximately 1 in 8000
live births. Babies with Edward syndrome are severely
retarded and have low-set ears, a short neck, deformed feet,
clenched fingers, heart problems, and other disabilities. Few
live for more than a year after birth. Trisomy 13 has a
frequency of about 1 in 15,000 live births and produces features that are collectively known as Patau syndrome.
Characteristics of this condition include severe mental retardation, a small head, sloping forehead, small eyes, cleft lip
and palate, extra fingers and toes, and numerous other problems. About half of children with trisomy 13 die within the
first month of life, and 95% die by the age of 3. Rarer still is
trisomy 8, which arises with a frequency ranging from about
1 in 25,000 to 1 in 50,000 live births. This aneuploid is characterized by mental retardation, contracted fingers and toes,
low-set malformed ears, and a prominent forehead. Many
who have this condition have normal life expectancy.

Aneuploidy and maternal age Most cases of Down syndrome and other types of aneuploidy in humans arise from
maternal nondisjunction, and the frequency of aneuploidy
correlates with maternal age (Figure 7.21). Why maternal age
is associated with nondisjunction is not known for certain, but

1 A parent who is a carrier for a
14–21 translocation is normal.

Parent who is a
translocation carrier

2 Gametogenesis produces
gametes in these possible
chromosome combinations.

21

Gametogenesis

14–21
14
translocation

Gametogenesis
(a)

(b)

(c)

Gametes
14–21

21 14

Translocation
carrier

Normal

14–21 21

14

14–21

14

21

F1 generation
Gametes

Zygotes

2/3 of

3 If a normal person mates
with a translocation carrier,…

live births

Down
syndrome
1/3 of

4 …two-thirds of their offspring will be healthy and
normal—even the translocation carriers—…

Monosomy
21 (aborted)

Trisomy
14 (aborted)

Monosomy
14 (aborted)

live births
5 …but one-third will
have Down syndrome.

7.20 Translocation carriers are at increased risk for producing children with Down syndrome.

6 Other chromosomal combinations
result in aborted embryos.

Chapter 7

90
80
Number of children afflicted with
Down syndrome per thousand births

182

Older mothers are more
likely to give birth to a
child with Down syndrome…

One in
12

70

Concepts

60

In humans, sex-chromosome aneuploids are more common than
are autosomal aneuploids. X-chromosome inactivation prevents
problems of gene dosage for X-linked genes. Down syndrome
results from three functional copies of chromosome 21, either
through trisomy (primary Down syndrome) or a Robertsonian
translocation (familial Down syndrome).

50
40
30

…than are
younger mothers.

✔ Concept Check 6

20
10

Aneuploidy and cancer Many tumor cells have extra or
missing chromosomes or both; some types of tumors are
consistently associated with specific chromosome mutations, including aneuploidy and chromosome rearrangements. The role of chromosome mutations in cancer will be
explored in Chapter 15.

One in
2000

20

One in
900

Briefly explain why, in humans and mammals, sex-chromosome
aneuploids are more common than autosomal aneuploids?

One in
100

30
40
Maternal age

50

7.21 The incidence of primary Down syndrome and other
aneuploids increases with maternal age.
the results of recent studies indicate a strong correlation
between nondisjunction and aberrant meiotic recombination.
Most chromosomes that failed to separate in meiosis I do not
show any evidence of having recombined with one another.
Conversely, chromosomes that failed to separate in meiosis II
often show evidence of recombination in regions that do not
normally recombine, most notably near the centromere.
Although aberrant recombination appears to play a role
in nondisjunction, the maternal-age effect is more complex.
Female mammals are born with primary oocytes suspended
in the diplotene substage of prophase I of meiosis. Just before
ovulation, meiosis resumes and the first division is completed, producing a secondary oocyte. At this point, meiosis
is suspended again and remains so until the secondary
oocyte is penetrated by a sperm. The second meiotic division
takes place immediately before the nuclei of egg and sperm
unite to form a zygote.
Primary oocytes may remain suspended in diplotene for
many years before ovulation takes place and meiosis recommences. Components of the spindle and other structures
required for chromosome segregation may break down in
the long arrest of meiosis, leading to more aneuploidy in
children born to older mothers. According to this theory, no
age effect is seen in males, because sperm are produced continuously after puberty with no long suspension of the meiotic divisions.

7.4 Polyploidy Is the Presence
of More Than Two Sets
of Chromosomes
Most eukaryotic organisms are diploid (2n) for most of their
life cycles, possessing two sets of chromosomes.
Occasionally, whole sets of chromosomes fail to separate in
meiosis or mitosis, leading to polyploidy, the presence of
more than two genomic sets of chromosomes. Polyploids
include triploids (3n), tetraploids (4n), pentaploids (5n), and
even higher numbers of chromosome sets.
Polyploidy is common in plants and is a major mechanism by which new plant species have evolved.
Approximately 40% of all flowering-plant species and from
70% to 80% of grasses are polyploids. They include a number of agriculturally important plants, such as wheat, oats,
cotton, potatoes, and sugar cane. Polyploidy is less common
in animals but is found in some invertebrates, fishes, salamanders, frogs, and lizards. No naturally occurring, viable
polyploids are known in birds, but at least one polyploid
mammal—a rat in Argentina—has been reported.
We will consider two major types of polyploidy:
autopolyploidy, in which all chromosome sets are from a
single species; and allopolyploidy, in which chromosome
sets are from two or more species.

Autopolyploidy
Autopolyploidy occurs when accidents of meiosis or mitosis
produce extra sets of chromosomes, all derived from a single
species. Nondisjunction of all chromosomes in mitosis in an
early 2n embryo, for example, doubles the chromosome

Chromosome Variation

(a) Autopolyploidy through mitosis
MITOSIS

Replication

Separation of
chromatids

Nondisjunction
(no cell division)

Autotetraploid
(4n) cell

Diploid (2n) early
embryonic cell
(b) Autopolyploidy through meiosis

Zygotes

Gametes

MEIOSIS I

MEIOSIS II

Replication

Nondisjunction

2n
1n

Diploid (2n)

Fertilization
Fertilization
2n

7.22 Autopolyploidy can arise through nondisjunction
in mitosis or meiosis.

number and produces an autotetraploid (4n) (Figure 7.22a).
An autotriploid (3n) may arise when nondisjunction in
meiosis produces a diploid gamete that then fuses with a
normal haploid gamete to produce a triploid zygote (Figure
7.22b). Alternatively, triploids may arise from a cross
between an autotetraploid that produces 2n gametes and a
diploid that produces 1n gametes.
Because all the chromosome sets in autopolyploids are
from the same species, they are homologous and attempt to
align in prophase I of meiosis, which usually results in sterility. Consider meiosis in an autotriploid (Figure 7.23). In
meiosis in a diploid cell, two chromosome homologs pair
and align, but, in autotriploids, three homologs are present.
One of the three homologs may fail to align with the other
two, and this unaligned chromosome will segregate randomly (see Figure 7.23a). Which gamete gets the extra chromosome will be determined by chance and will differ for
each homologous group of chromosomes. The resulting
gametes will have two copies of some chromosomes and one
copy of others. Even if all three chromosomes do align, two
chromosomes must segregate to one gamete and one chromosome to the other (see Figure 7.23b). Occasionally, the
presence of a third chromosome interferes with normal
alignment, and all three chromosomes segregate to the same
gamete (see Figure 7.23c).

Nondisjunction in meiosis I
produces a 2n gamete…

Triploid (3n)
…that then fuses with a
1n gamete to produce
an autotriploid.

No matter how the three homologous chromosomes
align, their random segregation will create unbalanced
gametes, with various numbers of chromosomes. A
gamete produced by meiosis in such an autotriploid might
receive, say, two copies of chromosome 1, one copy of
chromosome 2, three copies of chromosome 3, and no
copies of chromosome 4. When the unbalanced gamete
fuses with a normal gamete (or with another unbalanced
gamete), the resulting zygote has different numbers of the
four types of chromosomes. This difference in number
creates unbalanced gene dosage in the zygote, which is
often lethal. For this reason, triploids do not usually produce viable offspring.
In even-numbered autopolyploids, such as autotetraploids, the homologous chromosomes can theoretically
form pairs and divide equally. However, this event rarely
happens; so these types of autotetraploids also produce
unbalanced gametes.
The sterility that usually accompanies autopolyploidy
has been exploited in agriculture. Wild diploid bananas
(2n ϭ 22), for example, produce seeds that are hard and
inedible, but triploid bananas (3n ϭ 33) are sterile, and produce no seeds—they are the bananas sold commercially.
Similarly, seedless triploid watermelons have been created
and are now widely sold.

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