chapter 08 *lecture outline copyright © the mcgraw-hill companies, inc. permission required for...
TRANSCRIPT
Chapter 08
*Lecture Outline
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*See separate FlexArt PowerPoint slides for all figures and tables pre-inserted into PowerPoint
without notes.
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 or number• These typically affect more than one gene• They are quite common, which is surprising
8-2Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
8.1 Variation in Chromosome Structure
• Cytogenetics -The field of genetics that involves the microscopic examination of chromosomes
• A cytogeneticist typically examines the chromosomal composition of a particular cell or organism– This allows the detection of individuals with abnormal
chromosome number or structure– This also provides a way to distinguish between
species• Refer to Figure 8.1a
8-3Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
© Scott Camazine /Photo Researchers
Human Fruit fly Corn
© Michael Abbey/Photo Researchers© Carlos R Carvalho/Universidade
Federal de Viçosa.
Figure 8.1
8-4Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
(a) Micrographs of metaphase chromosomes
8-5Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Cytogeneticists use three main features to identify and classify chromosomes 1. Location of the centromere 2. Size 3. Banding patterns
These features are all seen in a Karyotype A micrograph in which all of the chromosomes within
a single cell are arranged in a standard fashion The procedure for making a karyotype was discussed
in Chapter 3 (See Figure 3.2)
Cytogenetics
A karyotype of a diploid human cell
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-6Figure 3.2
(c) For a diploid human cell, two complete sets of chromosomes from a single cell constitute a karyotype of that cell.
11 m
© Leonard Lessin/Peter Arnold
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22
XY
Metacentric Submetacentric Acrocentric Telocentric
P
q
P
q
P
q
P
q
(b) A comparison of centromeric locations
8-7
Figure 8.1
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Short arm; For the French, petite
Long arm
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
8-8Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Since different chromosomes can be the same size and have the same centromere position, 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 dye well
Light bands
In humans 300 G bands are seen in metaphase 800 G bands in prometaphase
Cytogenetics
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-9Figure 8.1
Banding pattern during metaphase
Banding pattern during prometaphase
P
q
P
q
(d) Conventional numbering system of G bands in human chromosomes
XY22212019181716151413
1
12
3
3
2
1
1
2
34
121110987654321
654321
2132112
121234
12345
543216543211234
1234567
1234
76543214321123123456789
654321
12345678
123
12345
54
3211234512312345
54321
1234561234567
21
21543211
12123456
32121123
1
234
4321321123121234
543211
123456
54321123412345
32
1123451234
3211234
1234
12
21
12312345678
1321123
12
1234
3211231234
3211212345
321123
321123
321123
1
2
13211
12
12
21
123
32112345123456
1
1
23
1
1
2
1
1
2
1
1
2
1
1
2
1
1
1
1
112
1
1
1
12
11
2
2
1
1
2
3
2
1
1
2
1
1
2
3
1
1
2
3
2
1
1
2
2
1
12
3
2
1
1
2
2
1123
1
1
2
1
1
2
1
1
2
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The banding pattern is useful in several ways:
1. It distinguishes Individual chromosomes from each other
2. It detects changes in chromosome structure 3. It reveals evolutionary relationships among
the chromosomes of closely related species
Cytogenetics
8-10
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
There are two primary ways in which the structure of chromosomes can be altered 1. The total amount of genetic material in the
chromosome can change Deficiencies/Deletions Duplications
2. The total amount of genetic material remains the same, but is rearranged
Inversions Translocations
8-11
Mutations Can Alter Chromosome Structure
8-12
• 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 part 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• A piece of a chromosome is attached to another chromosome
– Reciprocal translocations• Two way transfer• Two different types of chromosomes exchange pieces, producing
two abnormal chromosomes with translocations
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
(a)
(b)
(c)
(d)
(e)
q p
Deletion
Duplication
Inversion
Simple
Reciprocal
4 3 2 1 1 2 3 4 3 1 1 2 3
4 3 2 1 1 2 3 4 3 2 3 2 1 1 2 3
4 3 2 1 1 2 3 4 32 1 1 2 3
1 1 2 3
11 1 2 32
4 3 2 1 1 2 3
4 3 2 2 1112 1
1 1
4 3 2 1
4 3 2 11
1 2 3
translocation
translocation
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
2
Figure 8.28-13
Human chromosome 1
Human chromosome 21
(a) Terminal deletion (b) Interstitial deletion
Single breakTwo breaks andreattachmentof outer pieces
(Lost and degraded)
+
(Lost and degraded)
+
4 3 2 1 1 2 3
4 3
4 3
2 1 1 2 3
2
3 2
1 1 2 3
4 1 1 2 3
8-14Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
A chromosomal deficiency occurs when a chromosome breaks and a fragment is lost
Deficiencies
Figure 8.3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
8-15Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 in the short arm of chromosome 5 Refer to Figure 8.4
Deficiencies
(a) Chromosome 5 (b) A child with cri-du-chat syndrome
Deletedregion
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© Biophoto Assocates/Science Source/Photo Researchers © Jeff Noneley
8-16
Figure 8.4
8-17Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
A chromosomal duplication is usually caused by abnormal events during recombination
Repetitive sequences can cause misalignment between homologous chromosomes.
If a crossover occurs, nonallelic homologous recombination results
Duplications
Figure 8.5
Repetitive sequences
Misalignedcrossover
A
A
B
B
C
C
D
D
A
A
B
B
C
C
D
D
Duplication
Deletion
A B C D
A B C D
A B C C
A B D
D
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
8-18Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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
8-19Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The majority of small chromosomal duplications have no phenotypic effect
However, they are vital because they provide the raw material for the addition of genes to a species
This can ultimately lead to the formation of gene families A gene family consists of two or more genes that are
derived from the same ancestral gene
Duplications and Gene Families
Duplications can provide additional genes, forming gene families
• Over time, duplicated genes may accumulate mutations which alter their function– As a result, they may 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
– Refer to figure 8.6
8-20Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Abnormal genetic event thatcauses a gene duplication
Gene
Over the course of many generations,the 2 genes may differ due to thegradual accumulation of DNAmutations.
Paralogs (homologous genes)
GeneGene
Mutation
Gene Gene
8-21Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Figure 8.6
Genes derived from a single ancestral gene
8-22Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The globin genes all encode subunits of proteins that bind oxygen Over 500 million years, the ancestral globin gene has
been duplicated and altered so there are now 14 paralogs in this gene family on three different chromosomes
Different paralogs carry out similar but distinct functions All bind oxygen Myoglobin stores oxygen in muscle cells Hemoglobins bind and transport oxygen via red blood cells Different globins are expressed in the red blood cells during
different developmental stages provide different characteristics corresponding to the oxygen
needs of the embryo, fetus and adult
Refer to figure 8.7
Myoglobins
chains chains
Hemoglobins
Mill
ions
of y
ears
ago
1,000
800
600
400
200
0
Mb
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
ζ ψζ ψα2ψα1 α2 α1
ε G A ψβ δ β
Ancestral globin
8-23Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Figure 8.7
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
8-24Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Copy Number Variation (CNV) A segment of DNA that varies in copy number among
members of same species May be missing a particular gene May be a duplication
Surprisingly common in animals and plants 1-10% of a genome may show CNV Associated with some human diseases
schizophrenia autism susceptibility to infectious disease cancer
Copy Number Variation is Relatively Common
8-25Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Chromosomal deletions and duplications have been associated with human cancers May be difficult to detect with karyotype analysis Comparative genomic hybridization can be used
Developed by Anne Kallioniemi and Daniel Pinkel in 1992 Largely used to detect changes in cancer cell chromosomes
Experiment 8A-Comparitive Genomic Hybridization to detect
deletions and duplications
8-26Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Experimental level Conceptual level
Isolate DNA from human breast cancercells and normal cells. This involvedbreaking open the cells and isolating theDNA by chromatography. (SeeAppendix for description ofchromatography.)
1.
Label the breast cancer DNA with agreen fluorescent molecule and thenormal DNA with a red fluorescentmolecule. This was done by using theDNA from step 1 as a template, andincorporating fluorescently labelednucleotides into newly made DNAstrands.
2.
The DNA strands were then denatured by heat treatment. Mix together equalamounts of fluorescently labeled DNAand add it to a preparation of metaphasechromosomes from white blood cells.The procedure for preparing metaphasechromosomes is described in Figure 3.2.The metaphase chromosomes were alsodenatured.
3.
Allow the fluorescently labeled DNA tohybridize to the metaphasechromosomes.
4.
Visualize the chromosomes with afluorescence microscope. Analyze theamount of green and red fluorescencealong each chromosome with acomputer.
5.
DNA
From breastcancer cells
From normalcells
Metaphasechromosomes
Slide
Metaphasechromosome
Deletions in the chromosomes of cancer cells show a green to redratio of less than 1, whereaschromosome duplications showa ratio greater than 1.
Rat
io o
f g
reen
an
d r
ed f
luo
resc
ence
inte
nsi
ties
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
2.0
2.5
Deletion
DeletionDeletion
Deletion
DuplicationChr. 1 – 20 Mb
Chr. 9
Chr. 11 Chr. 17
Chr. 16
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
THE DATA
8-27Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Interpreting the Data
The data shows the ratio of green fluorescence (cancer DNA) to red (normal DNA). Chromosome 1 shows a Duplication (ratio of 2) Chromosome 9, 11, 16, 17 show Deletions (ratio of 0.5)
Allows the detection of large chromosomal changes
Newer techniques use microarrays (see Chapter 20)
8-28
A chromosomal with an inversion has a segment that has been flipped to the opposite orientation
Inversions
Figure 8.10
Inverted region Inverted region
A
(a) Normal chromosome
B C D E FG H I
A
(b) Pericentric inversion
B C GF E D H I A
(c) Paracentric inversion
E D C B FG H I
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Centromere lies within inverted
region
Centromere lies outside inverted
region
8-29Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 An inversion break point occurs 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, some individuals with inversions may produce offspring
with phenotypic abnormalities
8-30Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 total genetic content The abnormality is due to crossing over within the inverted segment
During meiosis I, pairs of homologous sister chromatids 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
Refer to figure 8.11
Replicated chromosomes
A B C D E F G H I
A
A
B
B
C
C
D
D
E
E
A
B
C D
E
F
F
G
G
H
H
I
A B C D E F G H I
F e d h iGHI
A B C D E f g c b a
I F G H I
a b c g f e d h i
a
a
b
b
c
c
g
g g
f
ff
e
ee
d
dd
h
h
i
a b c g f e d h i
ia
bc
gf
ed
h i
Replicated chromosomes
Withinversion:
Homologous pairingduring prophase
Crossover site
Products after crossing over
Normal:
Withinversion:
Acentricfragment
Duplicated/deleted
Dicentricchromosome
Dicentric bridge
Normal:
(a) Pericentric inversion (b) Paracentric inversion
Crossover site
A B C D E F G H I
A B C D E F
A B C d e a
G H I
I H G F E D c b f g h i
a de c b f g h i
A B C D E F G H I
a e d c b f g h i
a e d c b f g h i
Homologous pairingduring prophase
Products after crossing over
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 8.118-31
No centromere, chromosome is
lost
Chromosome will break if
centromeres move to opposite
poles
8-32Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 Refer to Figure 8.12
Translocations
8-33Figure 8.12
22
Environmentalagent causes 2chromosomesto break.
Reactive ends
Nonhomologouschromosomes
Reciprocaltranslocation
1 1 7 7
22
2 2
DNA repairenzymes recognizebroken ends andincorrectly connectthem.
(a) Chromosomal breakage and DNA repair
(b) Nonhomologous crossover
71
Reciprocaltranslocation
Crossoverbetweennonhomologouschromosomes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Telomeres prevent chromosomal DNA from sticking to each other
8-34Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 effects
Translocations
8-35Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 8.13a) 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 8.13b
Person with a normal phenotype whocarries a translocated chromosome
Translocated chromosomecontaining long arms ofchromosome 14 and 21
Fertilizationwith a normalgamete
Gamete formation
14 1421
21
Possible gametes:
Possible offspring:
Normal Balancedcarrier
Familial Downsyndrome(unbalanced) Unbalanced, lethal
(a) Possible transmission patterns
(b) Karyotype of a male with familial Down syndrome
(c) Child with Down syndrome
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© Will Hart/PhotoEdit
© Paul Benke/University of Miami School of Medicine
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
46, XY,214,1t(14q21q)
Figure 8.13
8-36
8-37Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Familial Down Syndrome is an example of Robertsonian translocation
This translocation occurs as such Breaks occur near the centromeres of two non-
homologous acrocentric chromosomes The small acentric fragments are lost The larger fragments fuse at their centromeric regions to
form a single chromosome which is metacentric or submetacentric
This type of translocation is the most common chromosomal rearrangement in humans
Approximately one in 900 births
8-38Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Individuals carrying balanced translocations have a greater risk of producing gametes with unbalanced combinations of chromosomes This 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 Refer to Figure 8.14
Balanced Translocations and Gamete Production
Figure 8.14
8-39
Translocation cross
Two normal haploid cells+ 2 cells withbalanced translocations
Possible segregation during anaphase of meiosis I
Normalchromosome 1
Chromosome 1plus a piece ofchromosome 2
Normalchromosome 2
Chromosome 2plus a piece ofchromosome 1
All 4 haploid cellsunbalanced
All 4 haploid cellsunbalanced
1
1
1
12
2
2
1
1
2
2
1
1
2
2
1
1
2
2
1
2
1
1 1
2
2 2
21 1
21 1
2 22
2
2
1
1
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(a) Alternate segregation (c) Adjacent-2 segregation (very rare)(b) Adjacent-1 segregation
8-40Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Meiotic segregation can occur in one of three ways 1. Alternate segregation
Chromosomes diagonal to each other within the translocation cross segregate into the same cell following meiosis I
One cell receives 2 normal chromosomes and the other receives 2 translocated chromosomes
Leads to viable gametes 2. Adjacent-1 segregation
Adjacent non-homologous chromosomes segregate into the same cell after meiosis I
Both cells have one normal and one translocated chromosome Leads to 4 genetically unbalanced gametes
3. Adjacent-2 segregation Centromeres do not segregate properly during meiosis I One cell receives both copies of the centromere on chromosome
1 and the other both copies of the centromere on chromosome 2 Leads to 4 genetically unbalanced gametes
8-41 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Alternate and adjacent-1 segregations are the likely outcomes when an individual carries a reciprocal translocation Indeed, these occur at about the same frequency
Moreover, adjacent-2 segregation is very rare
Therefore, an individual with a reciprocal translocation usually produces four types of gametes Two of which are viable and the other two, nonviable This condition is termed semisterility
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
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-42
1(X)
Normalfemalefruit fly:
(a)Diploid; 2n (2 sets)
Triploid; 3n (3 sets)
Tetraploid; 4n (4 sets)
Chromosome composition
Polyploidfruit flies:
(b) Variations in euploidy
Trisomy 2 (2n + 1)
Monosomy 1 (2n – 1)
Aneuploidfruit flies:
(c) Variations in aneuploidy
2 3 4
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 8.158-43
Polyploid organisms have three or more sets of chromosomes
Individual is said to be trisomic
Individual is said to be monosomic
8-44Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 Three copies of a gene will lead to 150% production A single chromosome can have hundreds or even
thousands of genes Refer to Figure 8.16
Aneuploidy
100%
1
Normal individual
Trisomy 2 individual
Monosomy 2 individual
2 3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
100% 100%
100% 150% 100%
100%
50% 100%
8-45Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.16
In most cases, these effects are
detrimentalThey produce
individuals that are less likely to survive
than a euploid individual
8-46Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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
8-47
8-48Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The autosomal aneuploidies compatible with survival are trisomies 13, 18 and 21 These involve chromosomes that are relatively small Carrie fewer genes than larger chromosomes
Aneuploidies involving sex chromosomes generally have less severe effects than those of autosomes This is explained by X inactivation
In an individual with more than one X chromosome, 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
8-49
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 8.17
Infa
nts
wit
h D
ow
n s
yn
dro
me
(pe
r 1
00
0 b
irth
s)
Age of mother
80
50
100
20 25 5045403530
6070
90
203040
1/1925
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1/1205 1/8851/365
1/110
1/32
1/12
8-50Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 syndrome 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 arrested in prophase of meiosis 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
Paternal non-disjunction causes Down syndrome 5% of the time
8-51Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 Refer to Figure 8.18
Euploidy
(b) Hyla versicolor(a) Hyla chrysoscelis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© A.B. Sheldon © A.B. Sheldon
8-52Figure 8.18
Diploid Tetraploid
8-53Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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)
May enhance ability of cell to produce specific gene products
Polytene chromosomes of insects provide an unusual example of natural variation in ploidy
Euploidy
8-54Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Occur 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
8-55Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Figure 8.19
(a) Repeated chromosome replication producespolytene chromosome.
(c) Relationship between a polytene chromosome and regular Drosophila chromosomes
L
R
Chromocenter
Each polytene armis composed ofhundreds ofchromosomesaligned side by side.
432
x
L
R
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Each chromosome attaches to the chromocenter near its centromere
Central point where chromosomes aggregate
8-56Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Because of their size, polytene chromosomes lend themselves to an easy microscopic examination They are so large, they can even be seen in interphase
Polytene chromosomes exhibit a characteristic banding pattern (Figure 8.19b) 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
(b) A polytene chromosome
Figure 8.198-57
8-58Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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 8.20a
In many instances, polyploid strains of plants display outstanding agricultural characteristics They are often larger in size and more robust
Euploidy
(a) Cultivated wheat, a hexaploid species
Figure 8.20 8-59Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
8-60
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 8.21
Each cell receives one copy of some
chromosomes
and two copies of other chromosomes
8-61Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
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) Energy goes into flower production instead of making seeds (competitors can’t sell seeds grown from their plants)
8.3 NATURAL AND EXPERIMENTAL WAYS TO PRODUCE VARIATIONS
IN CHROMOSOME NUMBER
• There are three natural mechanisms by which the chromosome number of a species can vary– 1. Meiotic nondisjunction– 2. Mitotic abnormalities– 3. Interspecies crosses
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-62
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Meiotic Nondisjunction
Nondisjunction refers to the failure of chromosomes to segregate properly during anaphase
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
Refer to Figure 8.22
8-56
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-64
Figure 8.22
All four gametes are abnormal
During fertilization,
these gametes produce an
individual that is trisomic
During fertilization,
these gametes produce an
individual that is monosomic
for the missing
chromosomen + 1
(a) Nondisjunction in meiosis I
Nondisjunctionin meiosis I
Normal meiosis II
n – 1n + 1 n – 1
Nondisjunction in Meiosis I
Nondisjunctionin meiosis II
Normalmeiosis I
(b) Nondisjunction in meiosis II
n nn + 1 n – 1
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-65Figure 8.22
50% Abnormal gametes
50% Normal gametes
Nondisjunction in Meiosis II
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Meiotic 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 This yields a triploid individual
8-66
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Mitotic Abnormalities Abnormalities in chromosome number often occur
after fertilization In this case, the abnormality occurs during mitosis not
meiosis
1. Mitotic disjunction (Figure 8.23a) Sister chromatids separate improperly
This leads to trisomic and monosomic daughter cells
2. Chromosome loss (Figure 8.23b) One of the sister chromatids does not migrate to a pole
This leads to normal and monosomic daughter cells
8-67
8-68Figure 8.23
This cell will be monosomic
This cell will be trisomic
Will be degraded if left outside of the
nucleus when nuclear envelope reforms
This cell will be monosomic
This cell will be normal
(a) Mitotic nondisjunction
(b) Chromosome loss
Not attachedto spindle
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Mitotic Abnormalities
Genetic abnormalities that occur after fertilization lead to mosaicism The organism contains a subset of cells that are
genetically different from the rest f the organism
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 Refer to Figure 8.24 for a bizarre example
8-69
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Consider a fertilized Drosophila egg that is XX One of the X’s is lost during the first mitotic division
This produces an XX cell and an X0 cell
8-70
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
Figure 8.24
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Complete nondisjunction can produce an individual with one or more sets of chromosomes This condition is termed autopolyploidy
8-71
Figure 8.25
Diploid species
(a) Autopolyploidy (tetraploid)
Polyploid species (tetraploid)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Interspecies Crosses A much more common mechanism for changes in
the number of sets of chromosomes is alloploidy It is the result of interspecies crosses Most likely occurs between closely related species
8-72
Figure 8.25
Species 1 Species 2
(b) Alloploidy (allodiploid)Alloploid
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(c) Allopolyploidy (allotetraploid)
Allopolyploid
Species 1 Species 2
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
An allodiploid has one set of chromosomes from two different species
An allopolyploid contains a combination of both autopolyploidy and alloploidy
8-73
Figure 8.25
An allotetraploid: Contains two
complete sets of chromosomes
from two different species
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
In two very closely related species, the number and types of chromosomes might be very similar
8-74
Figure 8.26 shows the karyotype of an interspecies hybrid between the roan antelope (Hippotragus equinus) and the sable antelope (Hippotragus niger)
These two closely related species have the same number of chromosomes that are
similar in size have similar banding patterns
Evolutionary related chromosomes from two diferrent species are termed homeologous chromosomes
The allodiploid is fertile because the homeologous chromosomes can properly synapse during meiosis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Robinson, T.J. & Harley, E.H. "Absence of geographic chromosomal variation in the roan and sable antelope and the cytogenetics of a naturally occurring hybrid." Cytogenet Cell Genet. 1995; 71(4): 363-9. Permission granted by S. Karger AG, Basel. Reprinted with permission.
1 2 3 4 5 6
7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 23 24
25 26 27 28 29
XX
8-75Figure 8.26
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
In 1928, the Russian cytogeneticist G. Karpechenko conducted an interspecies cross between raddish (Raphanus) and cabbage (Brassica) Both are diploid and contain 18 chromosomes
Therefore the interspecies hybrid contains 18 chromosomes too However, the radish and cabbage are not closely related
species Their chromosomes are distinctly different from one another and
cannot synapse Thus, the radish/cabbage hybrid is sterile
However, an allotetraploid would be fertile It contains 36 chromosomes which undergo proper synapsis
Refer to Figure 8.27
8-76
(b) Allotetraploid with a diploid set from each species
Metaphase I
(a) Allodiploid with a monoploid set from each species
Metaphase I
Radishchromosome
Cabbagechromosome
8-77Figure 8.27
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
No synapsis between the 9 radish and 9
cabbage chromosomes
Proper synapsis between the 18
radish chromosomes
and the 18 cabbage
chromosomes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Experimental Treatments Can Promote Polyploidy
Polyploid and allopolyploid plants often exhibit desirable traits Thus, the development of polyploids is of considerable
interest among plant breeders Can be induced by abrupt temperature changes and drugs
The drug colchicine is commonly used to promote polyploidy It binds to tubulin (a protein found in the spindle apparatus)
Thus, it promotes nondisjunction
8-78
Diploid plant
A tetraploid plant
Treat with colchicine.
Allow to grow.
Take a cutting ofthe tetraploidportion.
Root the cuttingin soil.
Tetraploid portionof plant (note thelarger leaves)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
8-79Figure 8.28
Caused by complete
nondisjunction
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Cell Fusion Techniques Can Be Used to Make Hybrid Plants
Researchers have recently developed techniques to produce hybrids with altered chromosome composition
In cell fusion, individual cells are mixed together and made to fuse It can create new strains of plants It allows the crossing of two species that cannot interbreed
naturally Refer to Figure 8.29
8-80
8-81
Festuca arundinacea
Lolium multiflorum
Cells without cell walls
Cells with two separate nuclei
Figure 8.29
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Tall fescuegrass
Italian ryegrass
Protoplasts
Cell wall
Heterokaryon
Hybrid cell
Allotetraploid
Add agent that digests cell walls.
Treat protoplasts with agents to promotecellular fusion.
Grow on laboratory media to generate ahybrid plant.
Spontaneous nuclear fusion produces hybridcell with single nucleus.Phenotypic
characteristics are intermediate between
the “parents”
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Experimental Production of Monoploids
The production of monoploids can be used to develop homozygous diploid strains of plants
In 1964, Sipra Guha-Mukherjee and Satish Maheswari developed a method to produce monoploid plants from pollen grains This experimental technique is called anther culture It is described in Figure 8.30
8-82
Treat section with colchicine.
Colchicine treated
Diploid plant
Propagate treated section.
Anthers
Plantlets
Transplant and grow.
Grow several weeks.
Cold shock
8-83Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Parental plant is diploid but not
homozygous for all its genes
Figure 8.30
Is homozygous for all its genes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Induces pollen grains to begin development
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Experimental Production of Monoploids
In certain animal species, monoploids can be produced by treatments that induce the eggs to develop without sperm fertilization This is know as parthenogenesis In many cases, the haploid zygote is short-lived
Example: Zebrafish (Danio rerio) Haploid egg is induced to begin development by exposure
to UV-irradiated (inactivated) sperm
8-84