Variation in chromosome structure and number chapter 8

1. PowerPoint Presentation Materials
to accompany
Genetics: Analysis and Principles
Robert J. Brooker
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CHAPTER 8
VARIATION IN
CHROMOSOME STRUCTURE
AND NUMBER

2. 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
8-2
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3. 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
8-3
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8.1 Variation in Chromosome
Structure

4. 8-4
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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
Cytogenetics

5. 8-5
Figure 8.1
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Short arm;
For the French, petite
Long arm

6. 8-6
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Since different chromosomes can be the same size
and have the same centromere 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
Cytogenetics

7. 8-7
Figure 8.1
Banding
pattern
during
metaphase
Banding
pattern
during
prophase

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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
Cytogenetics
8-8

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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
8-9
Mutations Can Alter
Chromosome Structure

10. 8-10
Deficiency (or 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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11. Figure 8.2
8-11
Human
chromosome 1
Human
chromosome 21

12. 8-12
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A chromosomal deficiency occurs when a
chromosome breaks and a fragment is lost
Deficiencies
Figure 8.3

13. 8-13
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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
Deficiencies

14. 8-17
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A chromosomal duplication is usually caused by
abnormal events during recombination
Duplications
Figure 8.5

15. 8-15
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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
Duplications

16. 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
8-16
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Duplications can provide additional
genes, forming gene families

17. 8-28
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Figure 8.6
Genes derived
from a single
ancestral gene

18. 8-18
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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

19. 8-30
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Figure 8.7
Duplication
Better at binding
and storing
oxygen in muscle
cells
Better at binding
and transporting
oxygen via red
blood cells
Expressed very early
in embryonic life
Expressed maximally during the
second and third trimesters
Expressed after birth

20. 8-27
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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
Duplications and Gene
Families

21. 8-21
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Chromosomal deletions and duplications have
been associated with human cancers
May be difficult to detect with karyotype analysis
Comparative genomic hybridization can be used
Developed by Anne Kallioniemi and Daniel Pinkel in 1992
Largely used to detect changes in cancer cell chromosomes
Experiment : Comparative
Genomic Hybridization to
detect deletions and
duplications

22. 8-21
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23. 8-22
A chromosomal inversion is a segment that has
been flipped to the opposite orientation
Inversions
Figure 8.9
Centromere lies
within inverted
region
Centromere lies
outside inverted
region

24. 8-23
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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

25. 8-24
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Individuals with one copy of a normal chromosome and one
copy of an inverted chromosome
Inversion Heterozygotes
Such individuals may be phenotypically normal
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 meiosis I, homologous chromosomes synapse with
each other
For the normal and inversion chromosome to synapse properly, an
inversion loop must form
If a cross-over occurs within the inversion loop, highly abnormal
chromosomes are produced
Refer to figure 8.10

26. Figure 8.10
8-25

27. 8-26
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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
Translocations

28. 8-27
Figure 8.11
Telomeres prevent
chromosomal DNA from
sticking to each other

29. 8-28
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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
Translocations

30. 8-29
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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
Example: Familial Down Syndrome
In this condition, the majority of chromosome 21 is
attached to chromosome 14
The individual would have three copies of genes found
on a large segment of chromosome 21
Therefore, they exhibit the characteristics of Down syndrome

31. 8-30
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Familial Down Syndrome is an example of
Robertsonian translocation
This translocation occurs as such
Breaks occur at the extreme ends of the short arms of
two non-homologous acrocentric chromosomes
The small acentric fragments are lost
The larger fragments fuse at their centromeric regions to
form a single chromosome which is metacentric or
submetacentric
This type of translocation is the most common type
of chromosomal rearrangement in humans
Approximately one in 900 births

32. 8-31
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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, slide 8-33
Balanced Translocations and
Gamete Production

33. 8-41
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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

34. Figure 8.13
8-33

35. 8-34
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Alternate and adjacent-1 segregations are the likely
outcomes when an individual carries a reciprocal
translocation
Indeed, these occur at about the same frequency
Moreover, adjacent-2 segregation is very rare
Therefore, an individual with a reciprocal
translocation usually produces four types of
gametes
Two of which are viable and two, nonviable
This condition is termed semisterility

36. 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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8.2 VARIATION IN
CHROMOSOME NUMBER
8-35

37. Figure 8.14
8-36
Polyploid organisms
have three or more
sets of chromosomes
Individual is said
to be trisomic
Individual is said
to be monosomic

38. 8-37
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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
Aneuploidy

39. 8-38
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Figure 8.15
In most cases, these
effects are detrimental
They produce
individuals that are
less likely to survive
than a euploid
individual

40. 8-39
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The harmful effects of aneuploidy were first
discovered in the 1920s by Albert Blakeslee and his
colleagues
They studied the Jimson weed (Datura stramonium)
All of its 12 possible trisomies produce capsules (dried
fruit) that are phenotypically different
In addition, the aneuploid plants have other
morphologically distinguishable traits
Including some detrimental ones
Refer to Figure 8.16
Aneuploidy

41. 8-49
Figure 8.16
Blakeslee noted that
this plants is “weak
and lopping with the
leaves narrow and
twisted.”

42. 8-41
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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
Refer to Table 8.1
Aneuploidy

43. 8-42

44. 8-43
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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

45. 8-44
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

46. 8-45
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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

47. 8-46
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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
A few examples of vertebrate polyploid animals have
been discovered
Euploidy

48. 8-47
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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
Euploidy

49. 8-51
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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
Euploidy

50. 8-52
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
Figure 8.21
Each cell receives
one copy of some
chromosomes
and two copies of
other chromosomes

51. 8-53
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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
Developed by Burpee (Seed producers)
Keep blooming since the don’t form desired end product
(competitors can’t sell seeds grown from their plants)

52. 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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8.3 NATURAL AND EXPERIMENTAL
WAYS TO PRODUCE VARIATIONS
IN CHROMOSOME NUMBER
8-54

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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
8-55

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8-56
Figure 8.22
All four gametes are abnormal
During
fertilization,
these gametes
produce an
individual that
is trisomic
for the
missing
chromosome
During
fertilization,
these gametes
produce an
individual that
is monosomic
for the
missing
chromosome

55. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
8-57
Figure 8.22
50 % Abnormal
gametes
50 % Normal
gametes

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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
8-58

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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
8-59

58. 8-60
Figure 8.23
This cell will be
monosomic
This cell will be
trisomic
Will be degraded if
left outside of the
nucleus when nuclear
envelope reforms
This cell will be
monosomic
This cell will be
normal

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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
8-61

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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
8-62
The XX cell is the
precursor for this side of
the fly, which developed
as a female
The X0 cell is the
precursor for this side of
the fly, which developed
as a male
This peculiar and rare individual is termed a bilateral
gynandromorph
Figure 8.24