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Chapter 08
Lecture Outline
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1
•  Genetic variation refers to differences in alleles and
chromosomes, either between members of the same
species or between different species
8.1 Microscopic Examination
of Eukaryotic Chromosomes
–  Allelic variations are variations in specific genes
•  Typically single or a few nucleotide changes
•  The characteristics that are used to classify and identify
chromosomes
–  Variations in chromosome structure and number
•  Typically affect more than one gene
•  Important in evolution
•  Can cause disease
•  Important for new strains of crops
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Variations in Chromosomes Can be Seen
by Light Microscopy
•  Different chromosomes of the same species can be also
distinguished from each other
•  Structure and number of chromosomes typically studied by
light microscopy
–  Cytogeneticist – Scientist who studies chromosomes
under the microscope
•  Different species can be distinguished from each other
based on the number and size of chromosomes
•  Chromosomes can be classified by
–  Size
–  Position of centromere
–  Banding pattern
•  Staining reveals bands
•  Example: Giemsa stain – G bands
© Scott Camazine /Photo Researchers
© Michael Abbey/Photo Researchers
Human
© Carlos R Carvalho/Universidade Federal de Viçosa.
Fruit fly
Corn
5
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Banding
pattern
during
metaphase
Centromere position
•  Metacentric – centromere near the middle
•  Submetacentric – slightly off center
p
3
2
1
1
•  Acrocentric – more off center
q
•  Telocentric – centromere at the end
2
3
4
6
5
4
3
2
1
2
2
1
3
2
1
1
2
1
2
3
4
5
1
2
1
2
3
4
1
Short arm;
For the French, petite
q
p
q
Metacentric
3
2
1
1
2
7
6
5
4
3
2
1
4
3
2
1
1
2
3
1
2
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1
1
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2
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2
1
1
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1
2
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1
2
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4
5
4
1
1
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5
4
3
2
1
2
1
1
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1
2
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7
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1
1
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2
1
5
4
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1
1
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1
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2
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5
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2
1
2
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1
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1
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4
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2
1
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8
1
1
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5
4
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9
2
5
4
3
2
1
1
2
3
4
1
2
3
4
5
p
p
q
Submetacentric
q
1
2
3
3
2
1
1
2
3
4
1
2
1
2
3
4
1
1
2
3
13
1
3
2
1
1
2
3
1
2
3
4
1
2
1
2
14
3
2
1
1
2
3
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5
1
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3
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6
10
1
1
2
15
3
2
1
1
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1
2
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4
1
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2
3
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1
1
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1
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4
5
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1
1
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1
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2
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1
21
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2
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1
2
11
12
1
1
3
2
1
1
2
3
3
2
1
2
1
p
2
1
p
Long arm
1
5
4
3
2
1
6
5
4
3
2
1
1
2
3
4
1
2
3
4
1
2
3
4
5
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Banding
pattern during
prometaphase
1
1
1
2
1
2
22
2
1
1
1
2
3
1
2
3
4
5
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7
8
Y
X
q
Acrocentric
7
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•  A karyotype is a micrograph of metaphase
chromosomes from a cell arranged in standard fashion
8.2 Changes in Chromosome Structure:
An Overview
•  Karyotypes can be used to
–  Detect abnormal chromosome number or structure,
but not small changes of a few to a few thousand
nucleotides
q 
The four types of changes in chromosome structure
9
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Mutations Can Alter Chromosome Structure
Mutations Can Alter Chromosome Structure
•  Primary ways chromosome structure can be altered:
–  Deletion (also called Deficiency)
•  Simple translocations
–  One way transfer
•  Portion of the chromosome is missing
–  Duplication
4 3
2
•  A change in the direction of part of the genetic material
along a single chromosome
1
3
1 2
3
Simple
21 1
•  Reciprocal translocations
–  Two way transfer
4 3 2
•  Portion of the chromosome is repeated
–  Inversion
1 1 2
translocation
1 1
2
4 3
2
4 3
2
21 1
21 1
3
1
2
3
Reciprocal
2 1 1
translocation
1 1
–  Translocation
•  Segment of one chromosome becomes attached to a nonhomologous chromosome
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q
4 3
p
2
1 1 2
3
4 3 1
1 2
3
Deletion
8.3 Deletions and Duplications
(a)
4 3
2
1 1 2
3
4 3
2
3
2
1 1 2
4
3
1 1 2
3
1
3
3
Duplication
(b)
4 3
2
1 1 2
3
2
q 
How deletions and duplications occur
Inversion
(c)
q 
4 3
2
1 1 2
3
1 2
How deletions and duplications may affect the phenotype
of an organism.
Simple
21 1
4 3
translocation
2
21 1
q 
(d)
4 3
2
1 1
2
21 1
3
1
2
Definition of copy number variation
3
Reciprocal
2 1 1
4 3
translocation
2
1 1
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(e)
Deletions
•  When deletions have a phenotypic effect, they are usually
detrimental
–  Example: cri-du-chat syndrome in humans
•  Caused by a deletion in the short arm of chromosome
•  The phenotypic consequences of deletions depends on
–  Size of the deletion
–  Chromosomal material deleted
•  Are the lost genes vital to the organism?
4 3
2
1
1
2
3
4 3
2
1
1
2
3
Deleted
region
Two breaks and
reattachment
of outer pieces
Single break
3
4 3
2
(Lost and degraded)
(Lost and degraded)
+
2
1
+
1
2
4
3
1
1
2
3
© Jeff Noneley
(a) Terminal deletion
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(b) Interstitial deletion
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Duplications
•  Like deletions, the phenotypic consequences of duplications
tend to be correlated with size
–  Duplications are more likely to have phenotypic effects if
they involve a large piece of the chromosome
•  A chromosomal duplication is usually caused by abnormal
events during recombination
•  Called nonallelic homologous recombination
•  Repetitive sequences can cause this
Repetitive sequences
B C
D
A
A
B
A
A
C
B
B
D
C
C
D
Misaligned
crossover
A
B
C
A
B
A
B
A
B C
C
•  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
•  Example: Charcot-Marie-Tooth disease
D
C
D
Duplication
D
D
Deletion
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D
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•  Duplications can provide additional genes, forming
gene families - two or more genes that are similar to each
other
•  Duplicated genes accumulate mutations which alter their
function
– 
– 
– 
– 
After many generations, they 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
Gene
•  Example: The globin genes
–  Ancestral globin gene has been duplicated and altered
•  14 paralogs on three different chromosomes
–  Different paralogs carry out similar but distinct functions
•  All bind oxygen
•  Myoglobin stores oxygen in muscle cells
•  Different globins in the red blood cells at different
developmental stages
– Characteristics correspond to the oxygen needs
of the embryo, fetus and adult
Abnormal genetic event that
causes a gene duplication
Gene
Paralogs (homologous genes)
Gene
Over the course of many generations, the 2 genes
may differ due to the gradual accumulation of DNA
mutations.
Mutation
19
Gene
Gene
Better at binding
and storing
oxygen in muscle
cells
Better at binding
and transporting
oxygen via red
blood cells
20
Copy Number Variation
•  Copy number variation – a type
of structural variation in which a
DNA segment 1000bp or larger
has copy number differences in
members of the same species
•  A gene normally in two copies in
a diploid cell may be found in
one, three, or even more copies
•  Some chromosomes are
missing the gene
•  Some chromosomes have
extra copies
•  These carry a segmental
duplication
8.4 Inversions and Translocations
q 
A
A
A
A
A
(a) Some members
of a species
Segmental
duplication
(b) Other members of
the same species
q 
q 
q 
Definition of pericentric and paracentric inversions
How inversion heterozygotes produce abnormal
chromosomes due to crossing over
Two mechanisms that result in reciprocal translocations
How reciprocal translocations align during meiosis and
how they segregate.
21
22
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Inversions
•  A chromosomal inversion is a segment that has been flipped
to the opposite orientation
–  Total amount of genetic information stays the same
•  Therefore, the great majority of inversions have no
phenotypic consequences
•  Pericentric inversion – the centromere is within the inverted
region
•  Paracentric inversion – the centromere is outside the inverted
region
Centromere lies
within inverted region
A B C
D E
FG H I
Centromere
lies outside
inverted region
(a) Normal chromosome
A B C
GF
E DH I
Inverted region
(b) Pericentric inversion
A E D
C B
FG H I
Inverted region
•  In rare cases, inversions can alter the phenotype of an
individual
–  Breakpoints
•  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 carry inversions that
are detectable with a light microscope
–  Most of these individuals are phenotypically normal
–  However, a few can produce offspring with genetic
abnormalities
24
(c) Paracentric inversion
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•  During meiosis I, homologous chromosomes synapse
with each other
–  For the normal and inversion chromosome to synapse
properly, an inversion loop must form
–  If a crossover occurs within the inversion loop, highly
abnormal chromosomes are produced
Inversion Heterozygotes
•  Individuals with one copy of a normal chromosome and one
copy of an inverted chromosome
Replicated chromosomes
A B C
D E
F G H I
A B C
Normal:
•  Such individuals may be phenotypically normal
–  But they have a high probability of producing abnormal
gametes
•  Due to crossing-over in the inverted segment
Replicated chromosomes
D E
F G H I
Normal:
A B C
D E
F G H I
e d
a b
With
inversion:
c
g f
a b
c
g f
e d h i
Homologous pairing
during prophase
With
inversion:
D E
a e
d
c
b
a e
d
c
b
Crossover site
F
E
D
A BC
h i
A B C
e
f
d ef g
d g
C
B
G H I
a b c
h
A
b
c
a
i
D E
A B C
D E
I
H G F
A B C
F G H I
f g
c
b a
e d h i
Duplicated/
deleted
25
a b
c
g f
e d
h i
Acentric
fragment
f g
D
d
e
Crossover site
E
I
FGH
D E
F G H I
A B C
d e
a
I
G
F
E D c b
d
c
Dicentric
chromosome
a
H
e
h i
f g h i
Homologous pairing
during prophase
f g
h i
Products after crossing over
Products after crossing over
A B C
F G H I
f g h i
Dicentric bridge
b
f g h i
26
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(a) Pericentric inversion
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
Nonhomologous
chromosomes
•  A chromosomal translocation
occurs when a segment of one
chromosome becomes attached
to another
22
22
2
2
Environmental
agent causes 2
chromosomes
to break.
•  In reciprocal translocations two
non-homologous chromosomes
exchange genetic material
–  Reciprocal translocations arise
from two different mechanisms
1. Chromosomal breakage
and DNA repair
2. Non-homologous
crossovers
(b) Paracentric inversion
1
1
7
7
Crossover
between
nonhomologous
chromosomes
Reactive ends
1
DNA repair
enzymes recognize
broken ends and
incorrectly connect
them.
7
Reciprocal
translocation
•  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
(b) Nonhomologous crossover
•  Unbalanced translocations are associated with phenotypic
abnormalities or even lethality
Reciprocal
translocation
27
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(a) Chromosomal breakage and DNA repair
•  Example: the Robertsonian translocation
–  Most common type of chromosomal rearrangement in humans
•  Approximately one in 900 births
–  The majority of chromosome 21 is attached to chromosome 14
8.5 Changes in Chromosome Number:
An Overview
•  This translocation occurs such that
–  Breaks occur at the extreme ends of two non-homologous
chromosomes
–  The small acentric fragments are lost
–  Larger fragments fuse at centromeric regions to form a single
chromosome
21
Robertsonian
translocation
q 
Definition of euploid and aneuploid
q 
Polyploidy and aneuploidy
21
+
14
21
14
14
Crossover
Translocated chromosome
containing long arms of
chromosome 14 and 21
Translocated chromosome
containing short arms of
chromosome 14 and 21
(usually lost)
30
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Chromosome composition
Normal
female
fruit fly:
Variation in Chromosome Number
Polyploid organisms
have three or more
(a)
sets of chromosomes
•  Chromosome numbers can vary in two main ways
–  Aneuploidy
•  Variation in the number of particular chromosomes within a set
•  Regarded as abnormal
•  Examples: trisomy (2n+1), monosomy (2n-1)
Polyploid
fruit flies:
1(X)
2
3
Individual is
said to be
trisomic
4
Diploid; 2n (2 sets)
Aneuploid
fruit flies:
Triploid; 3n (3 sets)
Trisomy 2 (2n + 1)
–  Euploidy
•  Variation in the number of complete sets of chromosomes
•  Occur occasionally in animals and frequently in plants
•  Examples: triploid (3n), tetraploid (4n)
Tetraploid; 4n (4 sets)
(b) Variations in euploidy
Monosomy 1 (2n – 1)
(c) Variations in aneuploidy
Individual is said to
be monosomic 32
31
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8.6 Variation in the Number of
Chromosomes Within a Set: Aneuploidy
Aneuploidy
•  Aneuploidy – Variation in the number
of particular chromosomes within a set
1
100%
2
100%
3
100%
Normal individual
•  Aneuploidy commonly causes an
abnormal phenotype
–  It leads to an imbalance in the
amount of gene products
–  Three copies can lead to 150%
production of the hundreds or even
thousands of gene products from a
particular chromosome
Why aneuploidy usually has a detrimental effect on
phenotype
q 
Examples of aneuploidy in humans
q 
100%
100%
33
150%
100%
Trisomy 2 individual
50%
Monosomy 2 individual
100%
34
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•  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
• 
But this is relatively rare
•  Autosomal aneuploidies that are most compatible with
survival are trisomies 13, 18 and 21
•  Sex chromosome aneuploidies generally have less severe
effects
–  Explained by X inactivation
•  All but one X chromosome transcriptionally suppressed
•  Phenotypes of X chromosome aneuploidies may be due to
–  Expression of X-linked genes prior to X-inactivation
–  Imbalance in the expression of pseudoautosomal genes
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•  Some human aneuploidies are influenced by parental age
–  Older parents more likely to produce abnormal offspring
–  Example: Down syndrome (Trisomy 21)
•  Incidence rises with the age of either parent,
especially mothers
•  Age of oocytes may play a role
–  Primary oocytes are produced in the ovary of fetus prior
to birth
•  Oocytes arrested in prophase I until the time of
ovulation
•  Length of time that oocytes are arrested in prophase I
may contribute to an increased frequency of
nondisjunction
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Infants with Down syndrome
(per 1000 births)
90
1/12
80
70
60
50
40
1/32
30
20
10
1/1925
1/1205
1/885
25
30
1/365
1/110
0
20
35
40
45
•  Down syndrome
–  Failure of chromosome 21 to segregate properly due to
chromosomal nondisjunction, usually in meiosis I in
the oocyte
50
Age of mother
37
38
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8.7 Variation in the Number of
Sets of Chromosomes
Euploidy
•  Euploidy – Variation in the number of complete sets of
chromosomes
q 
Examples in animals that involve variation in euploidy
q 
Definition of endopolyploidy
q 
The process of polytene chromosome formation
•  Most species of animals are diploid
q 
•  In many cases, changes in euploidy are not tolerated
–  Polyploidy in animals is generally a lethal condition
The effects of polyploidy among plant species and its
impact in agriculture
39
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40
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Polyploidy
•  Some euploidy variations are naturally occurring
–  Example: Bees are haplodiploid
•  Common in plants
–  30-35% of ferns and flowering plants are polyploid
–  Many fruits and grains are polyploids
•  Female bees are diploid
•  Male bees (drones) are monoploid
–  Contain a single set of chromosomes
•  A few examples of vertebrate polyploid animals have been
discovered
–  Example: The frog Hyla
•  In many instances, polyploid strains of plants display
outstanding agricultural characteristics
–  They are often larger in size and more robust
Tetraploid
41
© James Steinberg/Photo Researchers
(a) Cultivated wheat, a hexaploid species
Diploid
(b) A comparison of
diploid and tetraploid
petunias
42
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•  Polyploids having an odd number of chromosome sets
are usually sterile
–  These plants produce highly aneuploid gametes
•  Although sterility is generally a detrimental trait it can be
agriculturally desirable
•  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
–  Seedless fruit
•  Watermelons and bananas
– Triploid varieties
– Propagated by cuttings
–  Seedless flowers
•  Marigold flowering plants
– Triploid varieties
– Keep blooming
– Need to buy seeds
43
8.8 Mechanisms That Produce Variation
in Chromosome Number
44
Chromosome Number Variation
•  There are three natural mechanisms by which the
chromosome number of a species can vary
How meiotic and mitotic nondisjunction occur and their
possible phenotypic consequences
1.  Meiotic nondisjunction
q 
Autopolyploidy, alloploidy, and allopolyploidy
2.  Mitotic nondisjunction
q 
How colchicine is used to produce polyploid species
3.  Alloploidy (interspecies crosses)
q 
45
46
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Meiotic Nondisjunction
•  Nondisjunction – Failure of chromosomes to segregate
properly during anaphase
•  Meiotic nondisjunction can produce cells that have too many
or too few chromosomes
–  If such a gamete participates in fertilization, the zygote
will have an abnormal number of chromosomes
–  Nondisjunction can occur in meiosis I
–  Nonduisjunction can occur in meiosis II
47
These
gametes
can
produce a
trisomic
zygoyte
These
gametes
can
produce a
monosmic
zygote
All four gametes are abnormal
48
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•  In rare cases, all the chromosomes can undergo nondisjunction
and migrate to one daughter cell
•  This is termed complete nondisjunction
–  It results in one diploid cell and one without chromosomes
•  The chromosome-less cell is nonviable
•  The diploid cell can participate in fertilization with a
normal gamete, yielding a triploid individual
50 %
Abnormal
gametes
50 %
Normal
gametes
49
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Mitotic Nondisjunction
•  Occurs after fertilization
•  Usually only a subset of cells
affected - mosaicism
This cell will be monosomic
•  The size and location of the mosaic region depends on the
timing and location of the original abnormality
This cell will be
trisomic
–  Most severe example is when abnormality occurs during
the first mitotic division after fertilization
–  Mitotic nondisjunction
–  Sister chromatids separate improperly
–  Leads to trisomic and monosomic
daughter cells
–  Chromosome loss
50
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This cell will be
monosomic
This cell will be
normal
–  One of the sister chromatids does not
migrate to a pole and is degraded if not
included in reformed nucleus
–  Leads to normal and monosomic
daughter cells
Will be degraded if
left outside of the
nucleus when
nuclear envelope
reforms
52
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Alloploidy
Autopolyploidy
•  Complete nondisjunction can produce an individual with one
or more extra sets of chromosomes
•  Much more common mechanism for changes in the number of
sets of chromosomes
–  Result of interspecies crosses
–  Most likely occurs between closely related species
Diploid species
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Species 1
Species 2
Polyploid species (tetraploid)
Alloploid
(a) Autopolyploidy (tetraploid)
(b) Alloploidy (allodiploid)
53
54
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Experimental Treatments Can Promote Polyploidy
Allopolyploidy
•  Polyploid and allopolyploid
plants often exhibit desirable
traits
•  An allopolyploid contains a combination of both
autopolyploidy and alloploidy
Species 1
Caused by
complete
nondisjunction
•  Can be induced by abrupt
temperature changes or drugs
–  The drug colchicine is
commonly used to promote
polyploidy
•  Binds to tubulin (a protein
found in the spindle
apparatus), promoting
nondisjunction
Species 2
An allotetraploid:
Two complete
sets of
chromosomes
from two different
species
Allopolyploid
(c) Allopolyploidy (allotetraploid)
55
56
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