VARIATION IN

CHROMOSOME STRUCTURE
AND NUMBER
INTRODUCTION
 Genetic variation refers to differences
between members of the same species or
those of different species
 Allelic variations are due to mutations in
particular genes
 Chromosomal aberrations are substantial
changes in chromosome structure or number
 These typically affect more than one gene
 They are quite common, which is surprising

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8.1 Variation in Chromosome
Structure
 Cytogenetics -The field of genetics that involves
the microscopic examination of chromosomes
 A cytogeneticist typically examines the
chromosomal composition of a particular cell or
organism
 This allows the detection of individuals with abnormal
chromosome number or structure
 This also provides a way to distinguish between
species
 Refer to Figure 8.1a

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Cytogenetics
 Cytogeneticists use three main features to identify
and classify chromosomes
 1. Location of the centromere
 2. Size
 3. Banding patterns

 These features are all seen in a Karyotype

 Figure 8.1c

 The procedure for making a karyotype was discussed

in Chapter 3 (See Figure 3.2)

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Short arm;
For the French, petite

Long arm

Figure 8.1

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Cytogenetics
 Since different chromosomes can be the same size
and have the same cetromere position,
chromosomes are treated with stains to produce
characteristic banding patterns
 Example: G-banding
 Chromosomes are exposed to the dye Giemsa
 Some regions bind the dye heavily
 Dark bands
 Some regions do not bind the stain well
 Light bands

 In humans
 300 G bands are seen in metaphase
 2,000 G bands in prophase
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 Banding Banding
pattern pattern
during during
metaphase prophase

Figure 8.1
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Cytogenetics

 The banding pattern is useful in several

ways:

 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

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Mutations Can Alter
Chromosome Structure
 There are two primary ways in which the structure
of chromosomes can be altered
 1. The total amount of genetic information in the
chromosome can change
 Deficiencies/Deletions
 Duplications

 2. The genetic material remains the same, but is

rearranged
 Inversions
 Translocations

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 Deletion
 The loss of a chromosomal segment
 Duplication
 The repetition of a chromosomal segment compared to
the normal parent chromosome
 Inversion
 A change in the direction of part of the genetic material
along a single chromosome
 Translocation
 A segment of one chromosome becomes attached to a
different chromosome
 Simple translocations
 One way transfer
 Reciprocal translocations
 Two way transfer

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Human
chromosome 1

Human
chromosome 21

Figure 8.2
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Deletions
 A chromosomal deficiency occurs when a
chromosome breaks and a fragment is lost

Figure 8.3
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Deletions
 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 syndrome in humans
 Caused by a deletion in the short arm of chromosome 5

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Duplications
 A chromosomal duplication is usually caused by
abnormal events during recombination

Figure 8.5
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Duplications
 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

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Duplications can provide additional
genes, forming gene families
 The genes in a duplicated region may accumulate
mutations which alter their function
 After many generations, they may have similar but
distinct functions
 They are now members of a gene family
 Two or more genes derived from a common ancestor are
homologous
 Homologous genes within a single species are paralogs

 Refer to figure 8.6

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Genes derived
from a single
ancestral gene

Figure 8.6
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 The globin genes all encode subunits of proteins
that bind oxygen
 Over 500-600 million years, the ancestral globin gene
has been duplicated and altered so there are now 14
paralogs in this gene family on three different
chromosomes

 Different paralogs carry out similar but distinct functions

 All bind oxygen
 myoglobin stores oxygen in muscle cells
 different globins are in the red blood cells at different
developmental stages
 provide different characteristics corresponding to the oxygen
needs of the embryo, fetus and adult

 Refer to figure 8.7

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Expressed very early Expressed maximally during the Expressed after birth
in embryonic life second and third trimesters

Duplication
Better at binding Better at binding
and storing and transporting
oxygen in muscle oxygen via red
cells blood cells

Figure 8.7
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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

 This can ultimately lead to the formation of gene

families
 A gene family consists of two or more genes that are
similar to each other

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Inversions
 A chromosomal inversion is a segment that has
been flipped to the opposite orientation

Centromere lies Centromere lies

within inverted outside inverted
region region

Figure 8.9
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 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
 Break point effect
 The breaks leading to the inversion occur in a vital gene
 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
 Most of these individuals are phenotypically normal
 However, a few an produce offspring with genetic abnormalities

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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
 Refer to Figure 8.11

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Telomeres prevent
chromosomal DNA from
sticking to each other

Figure 8.11
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Translocations
 Reciprocal translocations lead to a rearrangement
of the genetic material, not a change in the total
amount
 Thus, they are also called balanced translocations

 Reciprocal translocations, like inversions, are

usually without phenotypic consequences
 In a few cases, they can result in position effect

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 In simple translocations the transfer of genetic
material occurs in only one direction
 These are also called unbalanced translocations

 Unbalanced translocations are associated with

phenotypic abnormalities or even lethality

 This type of translocation is the most common type

of chromosomal rearrangement in humans
 Approximately one in 900 births

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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
 Refer to Figure 8.13

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 Meiotic segregation can occur in one of three ways
 1. Alternate segregation
 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
 2. Adjacent-1 segregation
 Adjacent non-homologous chromosomes segregate into the
same cell
 Leads to unbalanced gametes
 Both have duplications and deletions and are thus inviable
 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

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Figure 8.13

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8.2 VARIATION IN
CHROMOSOME NUMBER
 Chromosome numbers can vary in two main ways
 Euploidy
 Variation in the number of complete sets of chromosome
 Aneuploidy
 Variation in the number of particular chromosomes within a set

 Euploid variations occur occasionally in animals and

frequently in plants
 Aneuploid variations, on the other hand, are regarded
as abnormal conditions

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Polyploid organisms
have three or more
sets of chromosomes
Individual is said
to be trisomic

Individual is said
to be monosomic
Figure 8.14
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Aneuploidy
 The phenotype of every eukaryotic species is
influenced by thousands of different genes
 The expression of these genes has to be intricately
coordinated to produce a phenotypically normal individual
 Aneuploidy commonly causes an abnormal
phenotype
 It leads to an imbalance in the amount of gene products
 Three copies will lead to 150% production
 A single chromosome can have hundreds or even
thousands of genes
 Refer to Figure 8.15
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 In most cases, these
effects are detrimental
They produce
individuals that are
less likely to survive
than a euploid
individual

Figure 8.15
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Aneuploidy
 Alterations in chromosome number occur frequently
during gamete formation
 About 5-10% of embryos have an abnormal chromosome
number
 Indeed, ~ 50% of spontaneous abortions are due to such
abnormalities

 In some cases, an abnormality in chromosome

number produces an offspring that can survive
 Refer to Table 8.1

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8-35
 The autosomal aneuploidies compatible with survival
are trisomies 13, 18 and 21
 These involve chromosomes that are relatively small

 Aneuploidies involving sex chromosomes generally

have less severe effects than those of autosomes
 This is explained by X inactivation
 All additional X chromosomes are converted into Barr bodies

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 Some human aneuploidies are influenced by the age
of the parents
 Older parents more likely to produce abnormal offspring
 Example: Down syndrome (Trisomy 21)
 Incidence rises with the age of either parent, especially mothers

Figure 8.17
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 Down syndrome is caused by the failure of
chromosome 21 to segregate properly
 This nondisjunction most commonly occurs during
meiosis I in the oocyte

 The correlation between maternal age and Down

symdrome could be due to the age of oocytes
 Human primary oocytes are produced in the ovary of the
female fetus prior to birth
 They are however arrested in prophase I until the time of ovulation
 As a woman ages, her primary oocytes have been arrested
in prophase I for a progressively longer period of time
 This added length of time may contribute to an increased frequency
of nondisjunction

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Euploidy
 Most species of animals are diploid
 In many cases, changes in euploidy are not tolerated
 Polyploidy in animals is generally a lethal condition
 Some euploidy variations are naturally occurring
 Female bees are diploid
 Male bees (drones) are monoploid
 Contain a single set of chromosomes

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Euploidy
 In many animals, certain body tissues display normal
variations in the number of sets of chromosomes

 Diploid animals sometimes produce tissues that are

polyploid
 This phenomenon is termed endopolyploidy
 Liver cells, for example, can be triploid, tetraploid or even
octaploid (8n)

 Polytene chromosomes of insects provide an

unusual example of natural variation in ploidy

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Polytene Chromosomes
 Occur mainly in the salivary glands of Drosophila
and a few other insects

 Chromosomes undergo repeated rounds of

chromosome replication without cellular division
 In Drosophila, pairs of chromosomes double approximately
nine times (29 = 512)
 These doublings produce a bundle of chromosomes
that lie together in a parallel fashion
 This bundle is termed a polytene chromosome

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 Each chromosome attaches to the
chromocenter near its centromere

Central point where

chromosomes aggregate
Figure 8.19
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Euploidy
 In contrast to animals, plants commonly exhibit
polyploidy
 30-35% of ferns and flowering plants are polyploid
 Many of the fruits and grain we eat come from polyploid
plants

 In many instances, polyploid strains of plants display

outstanding agricultural characteristics
 They are often larger in size and more robust

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 Polyploids having an odd number of chromosome
sets are usually sterile
 These plants produce highly aneuploid gametes
 Example: In a triploid organism there is an unequal separation of
homologous chromosomes (three each) during anaphase I

Each cell receives

one copy of some
chromosomes
and two copies of
other chromosomes

Figure 8.21
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 Sterility is generally a detrimental trait
 However, it can be agriculturally desirable because it
may result in
 1. Seedless fruit

 Seedless watermelons and bananas

 Triploid varieties
 Asexually propagated by human via cuttings
 2. Seedless flowers
 Marigold flowering plants
 Triploid varieties

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8.3 NATURAL AND EXPERIMENTAL
WAYS TO PRODUCE VARIATIONS
IN CHROMOSOME NUMBER
 There are three natural mechanisms by
which the chromosome number of a
species can vary
 1. Meiotic nondisjunction
 2. Mitotic abnormalities
 3. Interspecies crosses

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Meiotic Nondisjunction
 Nondisjunction refers to the failure of chromosomes
to segregate properly during anaphase

 Meiotic nondisjunction can produce haploid cells

that have too many or too few chromosomes
 If such a gamete participates in fertilization
 The resulting individual will have an abnormal

chromosomal composition in all of its cells

 Refer to Figure 8.22

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 During During
fertilization, fertilization,
these gametes these gametes
produce an produce an
individual that individual that
is trisomic is monosomic
for the for the
missing missing
chromosome chromosome

All four gametes are abnormal

Figure 8.22
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50 % Abnormal 50 % Normal
gametes gametes

Figure 8.22
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Meiotic Nondisjunction
 In rare cases, all the chromosomes can undergo
nondisjunction and migrate to one daughter cell

 This is termed complete nondisjunction

 It results in a diploid cell and one without chromosomes

 The chromosome-less cell is nonviable

 The diploid cell can participate in fertilization with a
normal gamete
 This yields a triploid individual

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Mitotic Abnormalities
 Abnormalities in chromosome number often occur
after fertilization
 In this case, the abnormality occurs in mitosis not meiosis

 1. Mitotic disjunction (Figure 8.23a)

 Sister chromatids separate improperly
 This leads to trisomic and monosomic daughter cells

 2. Chromosome loss (Figure 8.23b)

 One of the sister chromatids does not migrate to a pole
 This leads to normal and monosomic daughter cells

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This cell will be This cell will be
trisomic monosomic

This cell will be

monosomic
This cell will be
normal
Will be degraded if
left outside of the
nucleus when nuclear
envelope reforms

Figure 8.23
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Mitotic Abnormalities
 Genetic abnormalities that occur after fertilization
lead to mosaicism
 Part of the organism contains cells that are genetically
different from other parts

 The size and location of the mosaic region depends

on the timing and location of the original abnormality
 In the most extreme case, an abnormality could take place
during the first mitotic division
 Refer to Figure 8.24 for a bizarre example

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 Consider a fertilized Drosophila egg that is XX
 One of the X’s is lost during the first mitotic division
 This produces an XX cell and an X0 cell

The XX cell is the The X0 cell is the

precursor for this side precursor for this side
of the fly, which of the fly, which
developed as a female developed as a male

Figure 8.24

 This peculiar and rare individual is termed a bilateral

gynandromorph

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Interspecies Crosses
 Complete nondisjunction can produce an individual
with one or more sets of chromosomes
 This condition is termed autopolyploidy

Figure 8.25
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Interspecies Crosses
 A much more common mechanism for changes in
the number of sets of chromosomes is alloploidy
 It is the result of interspecies crosses
 Most likely occurs between closely related species

Figure 8.25
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Experimental Treatments Can
Promote Polyploidy
 Polyploid and allopolyploid plants often exhibit
desirable traits
 Thus, the development of polyploids is of considerable
interest among plant breeders
 Can be induced by abrupt temperature changes and drugs
 The drug colchicine is commonly used to promote
polyploidy
 It binds to tubulin (a protein found in the spindle apparatus)
 Thus, it promotes nondisjunction

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 Caused by
complete
nondisjunction

Figure 8.28
8-58
Cell Fusion Techniques Can Be
Used to Make Hybrid Plants
 Researchers have recently developed techniques to
produce hybrids with altered chromosome
composition
 In cell fusion, individual cells are mixed together and
made to fuse
 It can create new strains of plants
 It allows the crossing of two species that cannot interbreed
naturally
 Refer to Figure 8.29

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 Festuca Lolium
arundinacea multiflorum

Cells without
cell walls

Cells with two

separate nuclei
Phenotypic
characteristics are
intermediate between
the “parents”

Figure 8.29
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Experimental Production of
Monoploids
 The production of monoploids can be used to
develop homozygous diploid strains of plants

 In 1964, Sipra Guha and Satish Maheswari

developed a method to produce monoploid plants
from pollen grains
 This experimental technique is called anther culture
 It is described in Figure 8.30

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Parental plant is
diploid but not Induces pollen grains
homozygous for to begin development
all its genes

Is homozygous
for all its genes

Figure 8.30
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