Variations in Chromosome Structure and Number

Figure 4
Cri-du-chat syndrome, the result of the deletion of part of one of the copies of human
chromosome 5.

a) Karyotype (G banding) b) Individual with Cri-du-chat syndrome

Duplication Duplications have played an important role in the evo-

A duplication is a chromosomal mutation that results in lution of multiple genes with related functions (a
the doubling of a segment of a chromosome. The size of multigene family). For example, hemoglobin molecules
the duplicated segment varies widely, and duplicated seg- contain two copies each of two different subunits: the
ments may occur at different locations in the genome or a-globin polypeptide and the b -globin polypeptide. At dif-
adjacent to each other. Consider a normal chromosome, ferent developmental stages, from the embryo to the adult,
as shown in Figure 5a. When the mutation generates a human individual has different hemoglobin molecules
duplicated segments that are adjacent to each other with assembled from different types of a-globin and b -globin
the order of the genes in both segments the same as the polypeptides. The genes for each of the a-globin type of
order of the original, the mutation is a tandem duplication polypeptides are clustered together on one chromosome,
(Figure 5b, left). When the order of genes in the duplicat- while the genes for each of the b -globin type of poly-
ed segment is the opposite of the order of the original, the peptides are clustered together on another chromosome.
mutation is a reverse tandem duplication (Figure 5b, cen-
ter); when the duplicated segments are arranged in tan- Figure 5
dem at the end of a chromosome, the mutation is a Forms of chromosome duplications. (a) Normal chromosome.
terminal tandem duplication (Figure 5b, right). (b) Duplications.
Heterozygous duplications result in unpaired loops simi-
a) Normal chromosome b) Duplications
lar to those described for chromosome deletions and
therefore may be detected cytologically.
Duplications of particular genetic regions can have A A A A
unique phenotypic effects, as in the Bar mutant on the X B B B B
chromosome of Drosophila melanogaster, first studied by
Alfred Sturtevant and Thomas H. Morgan in the 1920s. In C C C A
strains homozygous for the Bar mutation (not to be con- D
C
B B
fused with the Barr body), the number of facets of the B
compound eye is less than that of the normal eye (shown E C C
in Figure 6a), giving the eye a bar-shaped (slitlike), rather F D D D
than an oval, appearance (shown in Figure 6b). Bar G
resembles an incompletely dominant mutation, because E E E
H
females heterozygous for Bar have more facets, and hence
F F F
a somewhat larger bar-shaped eye, than do females
G G G
homozygous for Bar. Males hemizygous for Bar have very
small eyes like those of homozygous Bar females. The Bar H H H
trait is the result of a duplication of a small segment Tandem Reverse Terminal
(16A) of the X chromosome (Figure 6b). tandem tandem

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 Variations in Chromosome Structure and Number
Figure 6
Chromosome constitutions of Drosophila strains, showing the relationship between
duplications of region 16A of the X chromosome and the production of reduced-eye-size
phenotypes.

Genotype Polytene bands Phenotype

E
F
a) Wild type 15
16
16A
A
16A B

X chromosomes

b) Homozygous Bar mutant

16
16A 16A A
16
16A 16A A

The sequences of the a-globin genes are all similar, as are Typically, genetic material is not lost when an inver-
the sequences of the b -globin genes. It is thought that each sion takes place, although there can be phenotypic con-
assembly of genes evolved from a different ancestral gene sequences when the breakpoints (inversion ends) occur
by duplication and subsequent divergence in the within genes or within regions that control gene expres-
sequences of the duplicated genes. This chapter’s Focus on sion. Homozygous inversions can be identified through
Genomics box describes the duplications of the genes in the non-wild-type linkage relationships that result
the androgen-binding protein family that have occurred between the genes within the inverted segment and the
during evolution of some mammalian lineages. genes that flank the inverted segment. For example, if the
order of genes on the normal chromosome is ABCDEFGH
and the BCD segment is inverted (shown next in bold),
Inversion the gene order will be ADCBEFGH, with D now more
An inversion is a chromosomal mutation that results closely linked to A than to E and B now more closely
when a segment of a chromosome is excised and then linked to E than to A (see Figure 7a).
reintegrated at an orientation 180 degrees from the origi- The meiotic consequences of a chromosome inver-
nal orientation (Figure 7). There are two types of inver- sion depend on whether the inversion occurs in a
sions: A paracentric inversion does not include the cen- homozygote or a heterozygote. If the inversion is
tromere (Figure 7a), and a pericentric inversion homozygous, then meiosis is normal and there are no
includes the centromere (Figure 7b). problems related to gene duplications or deletions. For an
inversion heterozygote, there are no meiotic problems if
crossing-over is absent in the inversion, but serious
genetic consequences ensue if crossing-over occurs in
Figure 7 the inversion, as we will now see.
Inversions. Let us consider a paracentric inversion heterozygote,
genotype 䡩ABCDEFGH/䡩ADCBEFGH, with the cen-
a) Paracentric inversion b) Pericentric inversion tromere (䡩) to the left of gene A. In meiosis, the homolo-
(does not include centromere) (includes centromere)
gous chromosomes attempt to pair such that the best pos-
A
sible base pairing occurs. Because of the inverted segment
A A A
D
on one homolog, pairing of homologous chromosomes
D
B B B requires the formation of loops containing the inverted
C
C C segments, called inversion loops. Inversion heterozygotes,
C C
B B F F then, may be identified by looking for those loops. If no
D D crossovers occur in the inversion loop of a paracentric
E E E E E inversion heterozygote, then all resulting gametes receive a
D D
complete set of genes (two gametes with a normal gene
F F F order, 䡩ABCDEFGH, and two gametes with the inverted
G G G G segment, 䡩ADCBEFGH), and they are all viable. Figure 8
H H H H
shows the effects of a single crossover in the inversion loop,
here between genes B and C. During the first meiotic

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