Transcript Brooker Chapter 8

Chromosome Aberrations
Types of Genetic variation
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Allelic variations
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mutations in particular genes (loci)
Chromosomal aberrations
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substantial changes in chromosome structure
Typically affect multiple genes (loci)
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Cytogenetics
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Microscopic examination of chromosomes
 Karyotype
Main features to identify and classify chromosomes
 1. Size
 2. Location of the centromere
 3. Banding patterns
G-Banded Metaphase Chromosomes
Figure 8.1
Categories of Chromosomal Aberrations
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Aneuploidies
 A change from euploid number
Inversions
 Pericentric – inversion about the centromere
 Paracentric – inversion not involving the
centromere
Deletions
 Loss of a region of a chromosome
Duplications
Translocations
 Exchange or joining of regions of two nonhomologous chromosomes
Variation In Chromosome Number
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Euploidy
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Normal variations of the number of complete sets
of chromosomes
Haploid, Diploid, Triploid, Tetraploid, etc…
Aneuploidy
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Variation in the number of particular
chromosomes within a set
Monosomy, trisomy, polysomy
Aneuploidies of the Sex Chromosomes
47, XXY
Klinefelter syndrome
45, X
Turner syndrome
Trisomy 13 Karyotype: 47, 13+
Karyotype of t(14;21) Familial Down Syndrome
Polyploidy v Aneuploidy
Figure 8.16
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Relationship Between Age and Aneuploidy
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Older mothers more likely to produce aneuploid
eggs
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Trisomy 21
Due to meiotic non-disjunction in during oocyte
maturation
Figure 8.19
Meiotic Nondisjunction Generates Aneuploidies
abnormal
gametes
Zygotic Ploidy
Zygotic Ploidy
Euploid Number can Naturally Vary
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Most animal species are diploid
Polyploidy in animals is generally lethal
Some naturally occurring euploidy variations
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bees - females are diploid; drones are
monoploid (ie haploid)
some amphibian & fish polyploids are known
Euploidy Variations
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Certain body tissues can display euploidy variations
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Polytene chromosomes of dipteran salivary glands
Chromosomes undergo repeated rounds of
replication
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endopolyploidy
In Drosophila, 9 rounds of replication (29 = 512)
Produces bundle of chromosome strands
Drosophila Polytene
Chromosomes
Repeated chromosome
replication produces
polytene chromosome.
L 2
R
4
3 L
R
Chromocenter
A polytene chromosome.
Each polytene
arm is composed
of hundreds of
chomosomes
aligned side
by side.
Composition of polytene
chromosome from regular
Drosophila chromosomes.
Euploidy Variations
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Plants commonly exhibit polyploidy
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30-35% of ferns and flowering plants are polyploid
Many of the fruits & grain are polyploid plants
Polyploid strains often
display desirable
agricultural
characteristics
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wheat
cotton
strawberries
bananas
large blossom flowers
Polyploidy
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Polyploids with odd #’d chromosome sets are
usually sterile
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produce mostly aneuploid gametes
rare a diploid & haploid gamete are produced
Each cell receives
one copy of some
chromosomes
and two copies of
other chromosomes
Figure 8.23
Benefit of Odd Ploidy-Induced Sterility
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Seedless fruit
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Seedless flowers
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watermelons and bananas
asexually propagated by human via cuttings
Marigold flowering plants
Prevention of cross pollination of transgenic
plants
Generation of Polyploids
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Autopolyploidy
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Complete nondisjunction of both gametes can produce an
individual with one or more sets of chromosomes
Figure 8.27
Interspecies Crosses can Generate Alloploids
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Alloploidy
Offspring generally sterile
Figure 8.27
Alloploid Antelope
Karyotype
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Hippotragus equinus x H. niger
Only slight differences between
chromosomes allow for
synapsis
Pairs of chromosomes refered
to as homeologous
Questionable if these are in fact
different species
Homologous regions of
homeologous chromosomes
called synteny
Interspecies Crosses Result in Alloploids
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Allodiploid
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one set of chromosomes from two different species
Allopolyploid
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combination of both autopolyploidy and alloploidy
An allotetraploid:
Contains two
complete sets of
chromosomes
from two different
species
Figure 8.27
Experimental Treatments Can Promote
Polyploidy
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Polyploid and allopolyploid plants often exhibit
desirable traits
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Colchicine is used to promote polyploidy
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Colchicine binds to tubulin, disrupting microtubule
formation and blocks chromosome segregation
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Variation In Chromosome Structure
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Amount of genetic information in the chromosome
can change
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Deficiencies/Deletions
Duplications
The genetic material remains the same, but is
rearranged
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Inversions
Translocations
Deficiencies (aka Deletions)
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A chromosomal deficiency occurs when a
chromosome breaks and a fragment is lost
Figure 8.3
Deficiencies
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Phenotypic consequences of deficiency depends on
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Size of the deletion
Functions of the genes deleted
Phenotypic effect of deletions usually detrimental
Cri-du-chat
Syndrome
Duplications
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A chromosomal duplication is usually caused by
abnormal events during recombination
Figure 8.5
Duplications
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Phenotypic consequences of duplications
correlated to size & genes involved
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Duplications tend to be less detrimental
Bar-Eye Phenotype in Drosophila
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Phenotype: reduced number of ommatidia
Ultra-bar (or double-bar) is a trait in which flies have even
fewer facets than the bar homozygote
Both traits are X-linked and show intermediate dominance
Bar-eye Phenotype due to Duplication
Duplications and Gene Families
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Majority of small duplications have no phenotypic
effect
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However, they provide raw material for evolutionary
change
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Lead to the formation of gene families
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A gene family consists of two or more genes that are
similar to each other
derived from a common gene ancestor
Duplications Generate Gene Families
Genes derived
from a single
ancestral gene
Figure 8.9
Gene Families
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Well-studied example is the globin gene family
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Genes encode proteins that bind oxygen
Globin gene family
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14 homologous genes derived from a single ancestral gene
Accumulation of mutations in the members of generated
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Globin genes expressed during different stages of development
Globin proteins specialized in their function
Mammalian Globin Genes
Expressed very early
in embryonic life
Expressed maximally during the
second and third trimesters
Duplication
Better at binding
and storing
oxygen in muscle
cells
Figure 8.10
Better at binding
and transporting
oxygen via red
blood cells
Expressed after birth
Inversions
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A segment of chromosome that is flipped relative to
that in the homologue
Centromere lies
within inverted
region
Figure 8.11
Centromere lies
outside inverted
region
Inversions
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No loss of genetic information
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Break point effect
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Inversion break point is within regulatory or structural portion of a
gene
Position effect
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Many inversions have no phenotypic consequences
Gene is repositioned in a way that alters its gene expression
separated from regulatory sequences, placed next to constitutive
heterochromatin
~ 2% of the human population carries karyotypically
detectable inversions
Inversion Heterozygotes
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Individuals with one copy of a normal chromosome and one
copy of an inverted chromosome
Usually phenotypically normal
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Have a high probability of producing gametes that are abnormal in
genetic content
Abnormality due to crossing-over within the inversion interval
During meiosis I, homologous chromosomes synapse with
each other
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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
Crossing Over Within Inversion Interval
Generates Unequal Sets of Chromatids
Crossing Over Within Inversion Interval
Generates Unequal Sets of Chromatids
Inversions Prevent Generation of Recombinant
Offspring Genotypes
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Only parental chromosomes (nonrecombinants) will produce normal progeny
after fertilization
Translocations
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When a segment of one chromosome becomes
attached to another
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In reciprocal translocations two non-homologous
chromosomes exchange genetic material
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Usually generate so-called balanced translocations
Usually without phenotypic consequences
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Although can result in position effect
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Nonhomologous
Fig. 8.13b(TE
Art) chromosomes
1 1
1
7 7
Crossover between
nonhomologous
chromosomes
7
Reciprocal
translocation
Nonhomologous crossover
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Fig. 8.13a(TE Art)
22
Environmental agent
2
causes 2 chromosomes
to break.
DNA repair enzymes
recognize broken ends
and connect them.
22
2
Reactive ends
Chromosomal breakage and DNA repair
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In simple translocations the transfer of genetic
material occurs in only one direction
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These are also called unbalanced translocations
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 (Figure 8.14a)
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Familial Down Syndrome is an example of
Robertsonian translocation
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This translocation occurs as such
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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 centromeic regions to
form a single chromosome
This type of translocation is the most common type
of chromosomal rearrangement in humans
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Balanced Translocations and Gamete
Production
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Individuals carrying balanced translocations have a
greater risk of producing gametes with unbalanced
combinations of chromosomes
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This depends on the segregation pattern during meiosis I
During meiosis I, homologous chromosomes
synapse with each other
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For the translocated chromosome to synapse properly, a
translocation cross must form
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Refer to Figure 8.15
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Figure 8.15
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Meiotic segregation can occur in one of three ways
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1. Alternate segregation
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Chromosomes on opposite sides of the translocation cross
segregate into the same cell
Leads to balanced gametes
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2. Adjacent-1 segregation
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Adjacent non-homologous chromosomes segregate into the
same cell
Leads to unbalanced gametes
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Both contain a complete set of genes and are thus viable
Both have duplications and deletions and are thus inviable
3. Adjacent-2 segregation
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Adjacent homologous chromosomes segregate into the same cell
Leads to unbalanced gametes
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Both have duplications and deletions and are thus inviable
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Consider a fertilized Drosophila egg that is XX
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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
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
Figure 8.26
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This peculiar and rare individual is termed a bilateral
gynandromorph
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