Transcript Brooker Chapter 8

CHAPTER 8 part 2
VARIATION IN CHROMOSOME
STRUCTURE AND NUMBER
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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Bridges’ Experiment Investigating the
Bar-Eye Phenotype in Drosophila


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Bar eyes is a trait in which flies have a reduced number of
facets
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 incomplete dominance
Figure 8.6
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Bridges’ Experiment Investigating the
Bar-Eye Phenotype in Drosophila

Calvin Bridges in the 1930s investigated the
bar/ultra-bar phenomenon at the cytological level

The cells of the salivary gland of Drosophila have
gigantic chromosomes, termed polytene
chromosomes

The banding patterns on these chromosomes is easily
seen

It is thus possible to detect the duplication or deletion of single
genes
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The Hypothesis

Information concerning the nature of the bar and
ultra-bar phenotypes may be revealed by a
cytological examination of polytene chromosomes
Testing the Hypothesis

Refer to Figure 8.7
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Figure 8.7
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The Data

This is a drawing of a short segment of a polytene chromosome that
corresponds to the region of the X chromosome where the bar allele is
located. This bar allele is found within the region designated 16A
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Interpreting the Data
Bar phenotype is caused by
a duplication in region 16A
of the X chromosome
The 16A region
duplication
returned to the
wild-type banding
pattern
Ultra-bar phenotype is
caused by three copies
in the 16A region
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Interpreting the Data


The mechanism of formation of the bar allele can be
explained by a misaligned crossover
Likewise for the formation of ultra-bar and bar-revertant
alleles
Figure 8.8
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Interpreting the Data
The bar and ultra-bar alleles are also associated with the
phenomenon of position effect


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A female that is homozygous for the
bar allele has four copies of region 16A
 And 70 facets
A female that is heterozygous for the
ultra-bar and normal alleles also has
four copies of region 16A
 But only 45 facets
Figure 8.6

The positioning of three copies next to each other on the X
chromosome increases the severity of the defect
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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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Genes derived
from a single
ancestral gene
Figure 8.9
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
A well-studied example is the globin gene family

The genes encode polypeptides which function in
proteins that bind oxygen


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

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
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Expressed very early
in embryonic life
Expressed maximally during the
second and third trimesters
Expressed after birth
Duplication
Better at binding
and storing
oxygen in muscle
cells
Better at binding
and transporting
oxygen via red
blood cells
Figure 8.10
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Inversions

A chromosomal inversion is a segment that has
been flipped to the opposite orientation
Centromere lies
within inverted
region
Figure 8.11
Centromere lies
outside inverted
region
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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
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Break point effect
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Position effect
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The breaks leading to the inversion occur in a vital gene
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
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
Most of these individuals are phenotypically normal
However, a few an produce offspring with genetic abnormalities
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Inversion Heterozygotes

Individuals with one copy of a normal chromosome and one
copy of an inverted chromosome

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
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Figure 8.12
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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
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Telomeres prevent
chromosomal DNA from
sticking to each other
Figure 8.13
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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


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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 (Figure 8.14a)
The individual would have three copies of genes found
on a large segment of chromosome 21


Therefore, they exhibit the characteristics of Down syndrome
Refer to Figure 8.14b
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
Familial Down Syndrome is an example of
Robertsonian translocation

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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8.2 VARIATION IN
CHROMOSOME NUMBER

Chromosome numbers can vary in two main ways
 Euploidy


Aneuploidy
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Variation in the number of complete sets of chromosome
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 8.16
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Aneuploidy

The phenotype of every eukaryotic species is
influenced by thousands of different genes


Aneuploidy commonly causes an abnormal
phenotype


The expression of these genes has to be intricately
coordinated to produce a phenotypically normal individual
It leads to an imbalance in the amount of gene products
Refer to Figure 8.17
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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 8.17
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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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
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
The phenotypic effects listed in Table 8.1 may be due to


1. The expression of X-linked genes prior to embryonic Xinactivation
2. An imbalance in the expression of pseudoautosomal genes
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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 8.19
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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
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
Polyploidy in animals is generally a lethal condition
Some euploidy variations are naturally occurring
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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

Rat - Argentinean
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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
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This phenomenon is termed endopolyploidy
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
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
chromoventer near its centromere
Figure 8.21
Central point where
chromosomes aggregate
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
Because of their size, polytene chromosomes lend
themselves to an easy microscopic examination


They are so large, they can be even seen in interphase
Polytene chromosomes exhibit a characteristic
banding pattern (Figure 8.21b)

Each dark band is known as a chromomere
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

The DNA within the dark band is more compact than that in the
interband region
Cytogeneticists have identified about 5,000 bands
Polytene chromosomes have facilitated the study of
the organization and functioning of interphase
chromosomes
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Euploidy

In contrast to animals, plants commonly exhibit
polyploidy
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30-35% of ferns and flowering plants are polyploid
Many of the fruits and grain we eat come from polyploid
plants
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Refer to Figure 8.22a
In many instances, polyploid strains of plants display
outstanding agricultural characteristics

They are often larger in size and more robust

Refer to Figure 8.22b
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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 8.23
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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)
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UGA UAG UAA