1. Chapter 08 Lecture Outline
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3. 8.1 Microscopic Examination of Eukaryotic Chromosomes
The characteristics that are used to classify and identify chromosomes
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4. Allelic variations are variations in specific genes
Genetic variation refers to differences in alleles and chromosomes, either between members of the same species or between different species
Allelic variations are variations in specific genes
Typically single or a few nucleotide changes
Variations in chromosome structure and number
Typically affect more than one gene
Important in evolution
Can cause disease
Important for new strains of crops
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5. Variations in Chromosomes Can be Seen by Light Microscopy
Structure and number of chromosomes typically studied by light microscopy
Cytogeneticist – Scientist who studies chromosomes under the microscope
Different species can be distinguished from each other based on the number and size of chromosomes
Human
Fruit fly
Corn
© Carlos R Carvalho/Universidade Federal de Viçosa.
© Scott Camazine /Photo Researchers
© Michael Abbey/Photo Researchers
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6. Different chromosomes of the same species can be also distinguished from each other
Chromosomes can be classified by
Size
Position of centromere
Banding pattern
Staining reveals bands
Example: Giemsa stain – G bands

7. Centromere position Metacentric – centromere near the middle
Submetacentric – slightly off center
Acrocentric – more off center
Telocentric – centromere at the end
Metacentric
Submetacentric
Acrocentric p q
Short arm; For the French, petite
Long arm
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8. Banding pattern during metaphase Banding pattern during prometaphase6 5 5 2 4 3 p 3 4 3 2 7 2 1 6 1 6 2 5 5 4 6 5 2 2 1 4 3 2 5 4 5 1 3 1 4 1 2 4 2 1 3 3 3 1 3 2 2 2 1 4 2 2 2 1 1 1 1 1 3 1 1 1 2 2 1 1 1 1 5 2 4 2 3 4 1 1 1 2 2 2 3 5 5 3 2 3 4 1 3 2 1 1 3 1 1 2 3 1 2 1 1 4 4 2 1 1 3 1 3 1 q 1 1 1 2 2 4 2 1 2 3 2 2 1 2 2 2 3 2 2 3 5 1 3 1 1 1 1 2 1 1 1 3 4 3 1 4 1 4 4 2 5 2 1 2 5 2 1 1 1 1 1 2 5 1 3 6 6 2 1 2 1 2 1 1 2 1 3 1 2 4 7 3 8 1 3 3 3 4 3 2 1 1 4 5 2 3 3 5 1 1 2 2 1 2 1 4 6 2 2 3 2 2 1 1 2 4 3 3 1 3 2 2 4 2 1 5 7 3 3 3 3 5 4 2 2 2 4 2 3 2 3 6 8 4 4 6 5 3 3 2 3 7 5 3 5 4 4 9 5 7 6 4 4 6 5 4 1 2 3 4 5 6 7 8 9 10 11 12 2 2 1 3 3 1 1 2 1 3 1 2 1 p 1 2 1 3 1 1 1 1 2 3 2 1 1 2 1 2 2 1 1 1 3 1 2 1 2 3 1 2 1 1 2 3 3 3 4 3 4 1 1 1 1 2 1 2 1 2 3 3 1 5 2 2 1 2 1 2 1 1 1 2 q 2 1 2 2 2 1 1 2 3 2 1 1 1 1 3 1 3 3 1 1 2 1 2 1 1 1 1 2 4 2 4 2 4 2 5 3 3 3 2 2 1 3 3 1 5 2 3 4 2 3 1 3 2 6 4 2 6 4 5 3 2 7 8 13 14 15 16 17 18 19 20 21 22 Y X

9. A karyotype is a micrograph of metaphase chromosomes from a cell arranged in standard fashion
Karyotypes can be used to
Detect abnormal chromosome number or structure, but not small changes of a few to a few thousand nucleotides

10. 8.2 Changes in Chromosome Structure: An Overview
The four types of changes in chromosome structure
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11. Mutations Can Alter Chromosome Structure
Primary ways chromosome structure can be altered:
Deletion (also called Deficiency)
Portion of the chromosome is missing
Duplication
Portion of the chromosome is repeated
Inversion
A change in the direction of part of the genetic material along a single chromosome
Translocation
Segment of one chromosome becomes attached to a non-homologous chromosome
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12. Mutations Can Alter Chromosome Structure
Simple translocations
One way transfer
Reciprocal translocations
Two way transfer
Simple 1 2 3 4
translocation
Reciprocal 1 2 3 4
translocation
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13. q p 4 3 2 1 1 2 3 4 3 1 1 2 3
Deletion
(a) 4 3 2 1 1 2 3 4 3 2 3 2 1 1 2 3
Duplication
(b) 4 3 2 1 1 2 3 4 2 3 1 1 2 3
Inversion
(c)
(d)
Simple
Reciprocal 1 2 3 4
translocation
(e)

14. 8.3 Deletions and Duplications
How deletions and duplications occur
How deletions and duplications may affect the phenotype of an organism.
Definition of copy number variation
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15. Deletions The phenotypic consequences of deletions depends on
Size of the deletion
Chromosomal material deleted
Are the lost genes vital to the organism?
(a) Terminal deletion
(b) Interstitial deletion
Single break
Two breaks and
reattachment
of outer pieces
(Lost and degraded) + 4 3 2 1

16. When deletions have a phenotypic effect, they are usually detrimental
Example: cri-du-chat syndrome in humans
Caused by a deletion in the short arm of chromosome
Deleted
region
© Jeff Noneley
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17. Duplications
Like deletions, the phenotypic consequences of duplications tend to be correlated with size
Duplications are more likely to have phenotypic effects if they involve a large piece of the chromosome
A chromosomal duplication is usually caused by abnormal events during recombination
Called nonallelic homologous recombination
Repetitive sequences can cause this
Duplication
Deletion A B C D
Repetitive sequences
Misaligned
crossover

18. 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
Example: Charcot-Marie-Tooth disease

19. Duplicated genes accumulate mutations which alter their function
Duplications can provide additional genes, forming gene families - two or more genes that are similar to each other
Duplicated genes accumulate mutations which alter their function
After many generations, they 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
Gene
Abnormal genetic event that
causes a gene duplication
Gene
Gene
Over the course of many generations, the 2 genes may differ due to the gradual accumulation of DNA
mutations.
Paralogs (homologous genes)
Mutation
Gene
Gene

20. Example: The globin genes
Ancestral globin gene has been duplicated and altered
14 paralogs on three different chromosomes
Different paralogs carry out similar but distinct functions
All bind oxygen
Myoglobin stores oxygen in muscle cells
Different globins in the red blood cells at different developmental stages
Characteristics correspond to the oxygen needs of the embryo, fetus and adult
Better at binding and storing oxygen in muscle cells
Better at binding and transporting oxygen via red blood cells

21. Copy Number Variation
Copy number variation – a type of structural variation in which a DNA segment 1000bp or larger has copy number differences in members of the same species
A gene normally in two copies in a diploid cell may be found in one, three, or even more copies
Some chromosomes are missing the gene
Some chromosomes have extra copies
These carry a segmental duplication
(a) Some members
of a species
(b) Other members of
the same species A
Segmental
duplication

22. 8.4 Inversions and Translocations
Definition of pericentric and paracentric inversions
How inversion heterozygotes produce abnormal chromosomes due to crossing over
Two mechanisms that result in reciprocal translocations
How reciprocal translocations align during meiosis and how they segregate.
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23. Inversions
A chromosomal inversion is a segment that has been flipped to the opposite orientation
Total amount of genetic information stays the same
Therefore, the great majority of inversions have no phenotypic consequences
Pericentric inversion – the centromere is within the inverted region
Paracentric inversion – the centromere is outside the inverted region
Inverted region A
(a) Normal chromosome B C D E F G H I
(b) Pericentric inversion GF
(c) Paracentric inversion
Centromere lies within inverted region
Centromere lies outside inverted region

24. In rare cases, inversions can alter the phenotype of an individual
Breakpoints
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 carry inversions that are detectable with a light microscope
Most of these individuals are phenotypically normal
However, a few can produce offspring with genetic abnormalities

25. Inversion Heterozygotes
Individuals with one copy of a normal chromosome and one copy of an inverted chromosome
Such individuals may be phenotypically normal
But they have a high probability of producing abnormal gametes
Due to crossing-over in the inverted segment
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26. 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 crossover occurs within the inversion loop, highly abnormal chromosomes are produced
Replicated chromosomes A B C D E F G H I e d h i f g c b a
With
inversion:
Homologous pairing
during prophase
Crossover site
Products after crossing over
Normal:
Acentric
fragment
Duplicated/
deleted
Dicentric
chromosome
Dicentric bridge
(a) Pericentric inversion
(b) Paracentric inversion

27. Translocations 22
Environmental
agent causes 2
chromosomes
to break.
Reactive ends
Nonhomologous
Reciprocal
translocation 1 7 2
DNA repair
enzymes recognize
broken ends and
incorrectly connect
them.
(a) Chromosomal breakage and DNA repair
(b) Nonhomologous crossover
Crossover
between
nonhomologous
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. Non-homologous crossovers

28. 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
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

29. Example: the Robertsonian translocation
Most common type of chromosomal rearrangement in humans
Approximately one in 900 births
The majority of chromosome 21 is attached to chromosome 14
This translocation occurs such that
Breaks occur at the extreme ends of two non-homologous chromosomes
The small acentric fragments are lost
Larger fragments fuse at centromeric regions to form a single chromosome
Translocated chromosome
containing long arms of
chromosome 14 and 21
containing short arms of
(usually lost) 14
Crossover
Robertsonian
translocation 21 +

30. 8.5 Changes in Chromosome Number: An Overview
Definition of euploid and aneuploid
Polyploidy and aneuploidy
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31. Variation in Chromosome Number
Chromosome numbers can vary in two main ways
Aneuploidy
Variation in the number of particular chromosomes within a set
Regarded as abnormal
Examples: trisomy (2n+1), monosomy (2n-1)
Euploidy
Variation in the number of complete sets of chromosomes
Occur occasionally in animals and frequently in plants
Examples: triploid (3n), tetraploid (4n)
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32. Individual is said to be trisomic
Chromosome composition
Normal
female
fruit fly:
Individual is said to be trisomic
Polyploid organisms have three or more sets of chromosomes
1(X) 2 3 4
Diploid; 2n (2 sets)
(a)
Polyploid
fruit flies:
Aneuploid
fruit flies:
Triploid; 3n (3 sets)
Trisomy 2 (2n + 1)
Tetraploid; 4n (4 sets)
Monosomy 1 (2n – 1)
(b) Variations in euploidy
(c) Variations in aneuploidy
Individual is said to be monosomic

33. 8.6 Variation in the Number of Chromosomes Within a Set: Aneuploidy
Why aneuploidy usually has a detrimental effect on phenotype
Examples of aneuploidy in humans
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34. Aneuploidy
100% 1
Normal individual
Trisomy 2 individual
Monosomy 2 individual 2 3
150%
50%
Aneuploidy – Variation in the number of particular chromosomes within a set
Aneuploidy commonly causes an abnormal phenotype
It leads to an imbalance in the amount of gene products
Three copies can lead to 150% production of the hundreds or even thousands of gene products from a particular chromosome

35. Sex chromosome aneuploidies generally have less severe effects
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
But this is relatively rare
Autosomal aneuploidies that are most compatible with survival are trisomies 13, 18 and 21
Sex chromosome aneuploidies generally have less severe effects
Explained by X inactivation
All but one X chromosome transcriptionally suppressed
Phenotypes of X chromosome aneuploidies may be due to
Expression of X-linked genes prior to X-inactivation
Imbalance in the expression of pseudoautosomal genes

37. Infants with Down syndrome
Some human aneuploidies are influenced by parental age
Older parents more likely to produce abnormal offspring
Example: Down syndrome (Trisomy 21)
Incidence rises with the age of either parent, especially mothers
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1/12 80 70 60
Infants with Down syndrome
(per 1000 births) 50 40
1/32 30 20
1/110 10
1/1925
1/365
1/1205
1/885 20 25 30 35 40 45 50
Age of mother

38. Age of oocytes may play a role
Down syndrome
Failure of chromosome 21 to segregate properly due to chromosomal nondisjunction, usually in meiosis I in the oocyte
Age of oocytes may play a role
Primary oocytes are produced in the ovary of fetus prior to birth
Oocytes arrested in prophase I until the time of ovulation
Length of time that oocytes are arrested in prophase I may contribute to an increased frequency of nondisjunction
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39. 8.7 Variation in the Number of Sets of Chromosomes
Examples in animals that involve variation in euploidy
Definition of endopolyploidy
The process of polytene chromosome formation
The effects of polyploidy among plant species and its impact in agriculture
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40. Euploidy
Euploidy – Variation in the number of complete sets of chromosomes
Most species of animals are diploid
In many cases, changes in euploidy are not tolerated
Polyploidy in animals is generally a lethal condition
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41. Some euploidy variations are naturally occurring
Example: Bees are haplodiploid
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
Example: The frog Hyla

42. Polyploidy Common in plants
30-35% of ferns and flowering plants are polyploid
Many fruits and grains are polyploids
In many instances, polyploid strains of plants display outstanding agricultural characteristics
They are often larger in size and more robust
Diploid
(b) A comparison of diploid and tetraploid petunias
(a) Cultivated wheat, a hexaploid species
Tetraploid
© James Steinberg/Photo Researchers

43. one copy of some chromosomes and two copies of other chromosomes
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

44. Although sterility is generally a detrimental trait it can be agriculturally desirable
Seedless fruit
Watermelons and bananas
Triploid varieties
Propagated by cuttings
Seedless flowers
Marigold flowering plants
Keep blooming
Need to buy seeds

45. 8.8 Mechanisms That Produce Variation in Chromosome Number
How meiotic and mitotic nondisjunction occur and their possible phenotypic consequences
Autopolyploidy, alloploidy, and allopolyploidy
How colchicine is used to produce polyploid species
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46. Chromosome Number Variation
There are three natural mechanisms by which the chromosome number of a species can vary
Meiotic nondisjunction
Mitotic nondisjunction
Alloploidy (interspecies crosses)
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47. Meiotic Nondisjunction
Nondisjunction – Failure of chromosomes to segregate properly during anaphase
Meiotic nondisjunction can produce cells that have too many or too few chromosomes
If such a gamete participates in fertilization, the zygote will have an abnormal number of chromosomes
Nondisjunction can occur in meiosis I
Nonduisjunction can occur in meiosis II
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48. These gametes can produce a trisomic zygoyte
These gametes can produce a monosmic zygote
All four gametes are abnormal

49. 50 % Abnormal gametes 50 % Normal gametes
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50. This is termed complete nondisjunction
In rare cases, all the chromosomes can undergo nondisjunction and migrate to one daughter cell
This is termed complete nondisjunction
It results in one diploid cell and one without chromosomes
The chromosome-less cell is nonviable
The diploid cell can participate in fertilization with a normal gamete, yielding a triploid individual
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51. Mitotic Nondisjunction
This cell will be monosomic
Occurs after fertilization
Usually only a subset of cells affected - mosaicism
Mitotic nondisjunction
Sister chromatids separate improperly
Leads to trisomic and monosomic daughter cells
Chromosome loss
One of the sister chromatids does not migrate to a pole and is degraded if not included in reformed nucleus
Leads to normal and monosomic daughter cells
This cell will be trisomic
This cell will be monosomic
This cell will be normal
Will be degraded if left outside of the nucleus when nuclear envelope reforms

52. The size and location of the mosaic region depends on the timing and location of the original abnormality
Most severe example is when abnormality occurs during the first mitotic division after fertilization
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53. Autopolyploidy
Complete nondisjunction can produce an individual with one or more extra sets of chromosomes
Diploid species
Polyploid species (tetraploid)
(a) Autopolyploidy (tetraploid)

54. Alloploidy
Much more common mechanism for changes in the number of sets of chromosomes
Result of interspecies crosses
Most likely occurs between closely related species
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Species 1
Species 2
Alloploid
(b) Alloploidy (allodiploid)
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55. Allopolyploidy
An allopolyploid contains a combination of both autopolyploidy and alloploidy
Species 1
Species 2
An allotetraploid: Two complete sets of chromosomes from two different species
Allopolyploid
(c) Allopolyploidy (allotetraploid)

56. Experimental Treatments Can Promote Polyploidy
Polyploid and allopolyploid plants often exhibit desirable traits
Can be induced by abrupt temperature changes or drugs
The drug colchicine is commonly used to promote polyploidy
Binds to tubulin (a protein found in the spindle apparatus), promoting nondisjunction
Caused by complete nondisjunction