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BIO 184
Fall 2006
LECTURE 7
Lecture 7:
Variation in Chromosome Structure and Number
Photograph of a normal human male karyotype. The autosomes are arranged in homologous pairs
from largest (1) to smallest (22). The X and Y chromosomes are often grouped together at the
end of the karyotype to make sex identification easier. Note; Molecular studies now show that
chromosome 21 is actually slightly smaller than chromosome 22. However, the numbering
system has remained unchanged. http://www.chromodisorder.org/intro.htm
Photograph of a human chromosomal abnormality. One of the homologous
pairs of chromosome 7 carries a large-scale deletion detectable by
chromosome banding (staining). The karyotype would be written
46,XY,dup(7)(q11.2q22), indicating that the duplication involves bands
11.2-22 on the long (q) arm of the chromosome.
http://www.chromodisorder.org/intro.htm
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LECTURE 7
I. MUTATIONS IN CHROMOSOME NUMBER
Normally, members of the same species have the same numbers of types of
chromosomes (with the exception of sex chromosomes in males and females if sex
is chromosomally determined). Such individuals are called euploid and have the
wild-type chromosome complement for the species.
Euploid human karyotypes are 46, XX (female) or 46 XY (male).
Chromosomal Mutations are substantial changes in chromosome structure that are
large enough to be visible by karyotyping (see lab manual) and thus typically affect
more than one gene.
If the mutation involves only one or a few chromosomes in the genome (e.g. a extra
copy of human chromosome 21), the individual carrying the mutation is said to be
aneuploid.
An example of aneuploidy is trisomy 21, in which an individual has 3, rather than 2,
copies of chromosome 21. The individual would have Down Syndrome and his/her
karyotype would be written 47,+21,XY or 47,+21,XX.
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LECTURE 7
Aneuploidy is usually caused by spindle fiber failure in meiosis I or II. Such a
failure of the separation of homologous chromosomes or sister chromatids is called
nondisjunction.
See Brooker, Fig. 8.24
If the mutation involves an entire set of chromosomes the condition is called
polyploidy (extra set or sets) or monoploidy (only one set). In humans, neither of
these conditions is viable. However, sometimes triploid babies are conceived when
two sperm enter the same egg. Such fetuses are almost always miscarried very
early in the pregnancy.
http://thefetus.net/case.php?id=597&answer=1
Only a few human triploid babies have survived to term and all have died within a
few hours of birth.
Some plants can tolerate polyploidy and, in fact, have been exploited and developed
by humans. Seedless watermelons are triploid. They cannot produce normal seeds
due to their abnormal ploidy condition and thus produce only tiny, soft seeds
(aborted watermelon fetuses). However, the plants that produce the fruit thrive
just fine in their triploid condition.
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BIO 184
Fall 2006
LECTURE 7
II. Cytogenetics
The field of genetics that involves the microscopic examination of chromosomes is
called cytogenetics. The study of chromosomal variation is important for several
reasons:
1. They can have major effects on the phenotype of an organism
2. They can have major effects on the phenotype of the offspring of an
organism
3. They have been an important force in the evolution of species
A cytogeneticist typically examines the chromosomal composition of a particular
cell or organism
o This allows the detection of individuals with abnormal chromosome
number or structure
o This also provides a way to distinguish between species
Cytogeneticists use three main features to identify and classify chromosomes
1. Size
2. Location of the centromere
3. Banding patterns
See Figure 8.1b, Brooker
For detailed identification, chromosomes are treated with stains to produce
characteristic banding patterns
o Example: G-banding
 Chromosomes are exposed to the dye Giemsa
 Some regions bind the dye heavily and produce dark bands
 Some regions do not bind the stain well and produce light bands
o In humans
 300 G bands are seen in metaphase
 2,000 G bands in prophase/prometaphase
See Figure 8.1d, Brooker
The banding pattern is useful in several ways:
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BIO 184
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LECTURE 7
1. It distinguishes individual chromosomes from each other
2. It detects changes in chromosome structure
3. It reveals evolutionary relationships among the chromosomes of
closely-related species
III. Mutations in Chromosome Structure
There are two primary ways in which the structure of single chromosomes can be
altered:
1. The total amount of genetic information in the chromosome can change
 Deletions: The loss of a chromosomal segment
 Duplications: The repetition of a chromosomal segment compared
to the normal parent chromosome
2. The genetic material remains the same, but is rearranged
 Inversions: A change in the direction of the genetic material
along a single chromosome
 Translocations
 Simple (one way transfer)
 Reciprocal (two way exchange)
See Figure 8.2, Brooker
A. DELETIONS
See Figure 8.3, Brooker
The phenotypic consequences of deficiencies depends on the
1. Size of the deletion
2. Chromosomal material deleted
 Are the lost genes vital to the organism?
When deletions have a phenotypic effect, they are usually detrimental. For
example, the disease cri-du-chat (“cry of the cat”) syndrome in humans is caused
by a deletion in the short arm of chromosome 5.
Chromosomal deletions can be detected by a variety of experimental techniques:
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LECTURE 7
1. Cytological (ie. Microscopic)
-Used to detect large deletions
2. Molecular
-Can now be used to detect sub-microscopic deletions not visible in
karyotypes
B. DUPLICATIONS
See Figure 8.5, Brooker
Like deletions, the phenotypic consequences of duplications tend to be correlated
to size
 Duplications are more likely to have phenotypic effects if they involve a
large piece of the chromosome
However, duplications tend to have less harmful effects than deletions of
comparable size
 In humans, relatively few well-defined syndromes are caused by small
chromosomal duplications
o One of these is Duplication 10q Syndrome, which duplicates a region
of the long arm of chromosome 10 from band 24 to the end of the q
arm.
 Severe mental deficiency
 High, arched eyebrows
 Flat face with high forehead
 Broad and depressed nasal bridge
 Cleft palate
 Syndactyly (second and third toes)
 Heart and renal malformations
C. DUPLICATIONS AND GENE FAMILIES
The majority of small chromosomal duplications have no phenotypic effect.
However, they are vital because they provide raw material for additional genes.
Every gene arises from another gene!
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If the time since the duplication event is short, its effect can be observed in
“gene families”
 A gene family consists of two or more genes that are similar to each other
See Figure 8.9, Brooker
A well-studied example is the globin gene family
 The genes encode polypeptides which function in hemoglobin
 The globin gene family is composed of 14 homologous genes on three
different chromosomes
 All 14 genes are derived from a single ancestral gene
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Accumulation of different mutations in the members of the gene family
created
1. Globin genes that are expressed during different stages of human
development
2. Globin proteins that are more specialized in their function
See Figure 8.10, Brooker
D. INVERSIONS
See Figure 8.11, Brooker
In an inversion, the total amount of genetic information stays the same
 Therefore, the great majority of inversions have no phenotypic consequences
In rare cases, inversions can alter the phenotype of an individual
o Break point effect
 The breaks leading to the inversion occur in a vital gene
o Position effect
 A gene is repositioned in a way that alters its gene expression
About 2% of the human population carries inversions that are detectable with a
light microscope
o Most of these individuals are phenotypically normal
o However, some can produce offspring with genetic abnormalities
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LECTURE 7
Individuals with one copy of a normal chromosome and one copy of an inverted
chromosome are called inversion heterozygotes.
 Such individuals may be phenotypically normal
o They also may have a high probability of producing gametes that are
abnormal in their genetic content
 The abnormality is due to crossing-over in the inverted segment
during prophase I of meiosis in the inversion heterozygote
 During meiosis I, homologous chromosomes synapse with each
other
o For the normal and inversion chromosome to synapse
properly, an inversion loop must form
o If a cross-over occurs within the inversion loop, highly
abnormal chromosomes are produced
See Fig. 8.12, Brooker
E. TRANSLOCATIONS
A chromosomal translocation occurs when a segment of one chromosome becomes
attached to another
In reciprocal translocations two non-homologous chromosomes exchange genetic
material. Reciprocal translocations arise from two different mechanisms:
1. Chromosomal breakage and DNA repair
2. Abnormal crossovers
See Fig. 8.13, Brooker
Reciprocal translocations lead to a rearrangement of the genetic material, not a
change in the total amount. Thus, they are also called balanced translocations.
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Reciprocal translocations, like inversions, are usually without phenotypic
consequences
In a few cases, they can result in position effect
In simple translocations the transfer of genetic material occurs in only one
direction. These are also called unbalanced translocations
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Unbalanced translocations are associated with phenotypic abnormalities or
even lethality
Example: Familial Down Syndrome
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In this condition, the majority of chromosome 21 is attached to
chromosome 14 (See Figure 8.14a and b, Brooker)
The individual would have three copies of genes found on a large
segment of chromosome 21
Therefore, they exhibit the characteristics of Down syndrome
Familial Down Syndrome is an example of Robertsonian
translocation
o Breaks occur at the extreme ends of the short arms of
two non-homologous acrocentric chromosomes
o The small acentric fragments are lost
o The larger fragments fuse at their centromeic regions to
form a single chromosome
o This type of translocation is the most common type of
chromosomal rearrangement in humans
F. BALANCED TRANSLOCATIONS AND GAMETE PRODUCTION
Individuals carrying balanced translocations have a greater risk of producing
gametes with unbalanced combinations of chromosomes
 This depends on the segregation pattern during meiosis I
During meiosis I, homologous chromosomes synapse with each other
 For the translocated chromosome to synapse properly, a translocation cross
must form
 Meiotic segregation from this cross can occur in one of three ways:
o 1. Alternate segregation
 Non-homologous chromosomes on opposite sides of the
translocation cross segregate into the same cell
 Leads to balanced gametes
 Both contain a complete set of genes and are thus viable
o 2. Adjacent-1 segregation
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Adjacent non-homologous chromosomes segregate into the
same cell
Leads to unbalanced gametes
 Both have duplications and deletions and are thus inviable
o 3. Adjacent-2 segregation
 Adjacent homologous chromosomes segregate into the same
cell
 Leads to unbalanced gametes
 Both have duplications and deletions and are thus inviable
 Is very rare because homologous chromosomes do not normally
segregate into the same cell. Such a failure is called nondisjunction (as discussed above).
See Figure 8.15, Brooker
Therefore, an individual with a reciprocal translocation usually produces four types
of gametes (2 viable ones from alternate segregation and 2 non-viable ones from
adjacent-1 segregation)
 Overall fertility is thus reduced by one-half (semi-sterility)
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