Brooker Chapter 8

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Lecture 7 (Chapter 8)
VARIATION IN CHROMOSOME STRUCTURE AND NUMBER
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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
• These typically affect more than one gene
• They are also called chromosomal mutations

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INTRODUCTION

• A change in chromosome number is called a genome
  mutation
• It is the result of changes in the number of
• Sets of chromosomes
• OR
• Numbers of individual chromosomes in a set

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8.1 VARIATION IN CHROMOSOME STRUCTURE

• The study of chromosomal variations is important
  for three main reasons
• 1. They can have major effects on the phenotype
  of an organism
• 2. They can have major effects on the phenotype
  of the offspring of an organism
• 3. They have been an important force in the
  evolution of species

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• Cytogeneticists use three main features to
  identify and classify chromosomes
• 1. Size
• 2. Location of the centromere
• 3. Banding patterns
• These features are all seen in a karyotype

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Short arm For the French, petite
Long arm
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• For detailed identification, 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 premetaphase

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Banding pattern during metaphase
Banding pattern during premetaphase
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• The banding pattern is useful in three ways
• 1. It distinguishes Individual chromosomes from
  each other when they are similar in size and
  centromere location
• 2. It detects gross changes in chromosome
  structure
• 3. It reveals evolutionary relationships among
  the chromosomes of closely-related species

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Mutations Can Alter Chromosome Structure

• 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

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• 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 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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Human chromosome 1
Human chromosome 21
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Deficiencies

• 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 of the tip of the short arm
  of chromosome 5

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Duplications

• A chromosomal duplication is usually caused by
  abnormal events during recombination

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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
• However, large ones (e.g. whole arms of
  chromosomes) can be vaery hamrful

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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
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Inversions

• A chromosomal inversion is a segment that has
  been flipped to the opposite orientation

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

• When inversions alter the phenotype of an
  individual it usually due to
• 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, if they are heterozgous for the
  inversion (one normal copy of the chromosome, one
  inverted copy), their fertility is reduced

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Meiosis in Inversion Heterozygotes

• 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
• Therefore, the risk of producing abnormal gametes
  is directly related to the size of the inversion

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Translocations

• A chromosomal translocation occurs when a segment
  of one chromosome becomes attached to another
• In reciprocal (balanced) translocations, two
  non-homologous chromosomes exchange genetic
  material
• Often no phenotype (other than reduced fertility)
• Reciprocal translocations arise from two
  different mechanisms
• 1. Chromosomal breakage and DNA repair
• 2. Abnormal crossovers

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Meiosis in Reciprocal Translocation Heterozygotes

• Individuals carrying balanced translocations have
  a greater risk of producing gametes with
  unbalanced combinations of chromosomes
• Semi-sterility approx. 50 of gametes are
  abnormal
• Gametes viability depends on the segregation
  pattern during meiosis I
• During meiosis I, homologous chromosomes synapse
  with each other
• For the translocated chromosomes to synapse
  properly, a translocation cross must form

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• Meiotic segregation can occur in one of three
  ways
• 1. Alternate segregation (50 all viable)
• 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 (50 non are viable)
• 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 (VERY RARE)
• Adjacent homologous chromosomes segregate into
  the same cell (very rare because this is a
  non-disjunction event)
• Leads to unbalanced gametes
• Both have duplications and deletions and are thus
  inviable

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Figure 8.15
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8.2 VARIATION IN CHROMOSOME NUMBER

• 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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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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Aneuploidy

• 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

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Aneuploidy

• 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

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Blakeslee noted that this plants is weak and
lopping with the leaves narrow and twisted.
Figure 8.18
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Aneuploidy

• Alterations in chromosome number occur frequently
  during gamete formation in humans
• 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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8-51
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Down Syndrome
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Trisomy 18, Edwards Syndrome
(47, XY, 18)
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Monosomy X Turner Syndrome
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XXY Klinefelters Syndrome
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Euploidy

• 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

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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
• This phenomenon is termed endopolyploidy
• DNA replication not followed by mitosis
• Liver cells, for example, can be triploid,
  tetraploid or even octaploid (8n)

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Euploidy

• 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
  diplay outstanding agricultural characteristics
• They are often larger in size and more robust

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• Polyploids having an odd number of chromosome
  sets usually abort their embryos
• These plants produce highly aneuploid gametes
• Example In a triploid organism there is an
  unequal separation of homologous chromosomes
  (three each) during anaphase I

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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
• Small seeds are nonviable embryos
• 2. Seedless flowers
• Marigold flowering plants
• Triploid varieties
• Developed by Burpee (Seed producers)

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8.3 HOW VARIATIONS IN CHROMOSOME NUMBER ARISE

• There are three natural mechanisms by which the
  chromosome number of a species can vary
• 1. Meiotic nondisjunction
• 2. Mitotic nondisjunction
• 3. Interspecies crosses (we will not discuss
  this one)

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Meiotic Nondisjunction

• Nondisjunction refers to the failure of
  chromosomes to segregate properly during anaphase
  of either MI or MII
• 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

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After fertilization, these gametes produce an
individual that is trisomic for the missing
chromosome
After fertilization, these gametes produce an
individual that is monosomic for the missing
chromosome
All four gametes are abnormal
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50 Abnormal gametes
50 Normal gametes
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Mitotic Nondisjunction

• Genetic abnormalities that occur in the embryo
  during the rapid mitotic division 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

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• Consider a fertilized Drosophila egg that is XX
• One of the Xs 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

• This peculiar and rare individual is termed a
  bilateral gynandromorph