CHAPTER 8 part 2
VARIATION IN CHROMOSOME STRUCTURE AND NUMBER
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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
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
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Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila
Figure 8.6
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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Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila
The Hypothesis Information concerning the nature of the bar and
ultra-bar phenotypes may be revealed by a cytological examination of polytene chromosomes
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Testing the Hypothesis
Refer to Figure 8.7
8-22Figure 8.7
The Data
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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
Interpreting the Data
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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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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
Interpreting the Data
Figure 8.8
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The bar and ultra-bar alleles are also associated with the phenomenon of position effect
Interpreting the Data
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
The positioning of three copies next to each other on the X chromosome increases the severity of the defect
Figure 8.6
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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
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Figure 8.9
Genes derived from a single ancestral gene
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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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Figure 8.10
DuplicationBetter 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
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A chromosomal inversion is a segment that has been flipped to the opposite orientation
Inversions
Figure 8.11
Centromere lies within inverted
region
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
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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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
Figure 8.128-34
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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
Translocations
8-36Figure 8.13
Telomeres prevent chromosomal DNA from sticking to each other
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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
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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 (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 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
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
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.16
Polyploid organisms have three or more sets of chromosomes
Individual is said to be trisomic
Individual is said to be monosomic
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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
Refer to Figure 8.17
Aneuploidy
8-47Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.17
In most cases, these effects are
detrimentalThey produce
individuals that are less likely to survive
than a euploid individual
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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
8-51
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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 X-
inactivation 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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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 Rat - Argentinean
Euploidy
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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
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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
Polytene Chromosomes
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Figure 8.21
Each chromosome attaches to the chromoventer near its centromere
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
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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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 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
Euploidy
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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
Figure 8.23
Each cell receives one copy of some
chromosomes
and two copies of other chromosomes
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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)
UGA UAG UAA