variation in chromosome structure and number chapter 8

PowerPoint Presentation Materialsto accompany

Genetics: Analysis and PrinciplesRobert J. Brooker

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

CHAPTER 8

VARIATION IN CHROMOSOME STRUCTURE

AND NUMBER

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

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


8.1 Variation in Chromosome Structure


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 Figure 8.1c

Cytogenetics

8-5

Figure 8.1


Short arm; For the French, petite

Long arm


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 stain well

Light bands

In humans 300 G bands are seen in metaphase 2,000 G bands in prophase

Cytogenetics

8-7Figure 8.1

Banding pattern during metaphase

Banding pattern during prophase


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

8-8


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

8-9

Mutations Can Alter Chromosome Structure

8-10

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 Reciprocal translocations

Two way transfer


Figure 8.28-11

Human chromosome 1

Human chromosome 21


A chromosomal deficiency occurs when a chromosome breaks and a fragment is lost

Deficiencies

Figure 8.3


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

Deficiencies


A chromosomal duplication is usually caused by abnormal events during recombination

Duplications

Figure 8.5


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

The genes in a duplicated region may accumulate mutations which alter their function After many generations, 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


Duplications can provide additional genes, forming gene families


Figure 8.6

Genes derived from a single ancestral gene


The globin genes all encode subunits of proteins that bind oxygen Over 500-600 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 different globins are in the red blood cells at different

developmental stages provide different characteristics corresponding to the oxygen

needs of the embryo, fetus and adult

Refer to figure 8.7


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


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


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 : Comparative Genomic Hybridization to detect deletions and duplications

8-22

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

Inversions

Figure 8.9

Centromere lies within inverted

region

Centromere lies outside inverted

region


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


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

Refer to figure 8.10

Figure 8.108-25


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 8.11

Translocations

8-27Figure 8.11

Telomeres prevent chromosomal DNA from sticking to each other


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


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 The individual would have three copies of genes found

on a large segment of chromosome 21 Therefore, they exhibit the characteristics of Down syndrome


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 centromeric regions to

form a single chromosome which is metacentric or submetacentric

This type of translocation is the most common type of chromosomal rearrangement in humans

Approximately one in 900 births


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 chromosome to synapse properly, a

translocation cross must form Refer to Figure 8.13, slide 8-33

Balanced Translocations and Gamete Production


Meiotic segregation can occur in one of three ways 1. Alternate segregation

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 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 Adjacent homologous chromosomes segregate into the same

cell Leads to unbalanced gametes

Both have duplications and deletions and are thus inviable

Figure 8.13

8-33

8-34 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 two, nonviable This condition is termed semisterility

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


8.2 VARIATION IN CHROMOSOME NUMBER

8-35

Figure 8.148-36

Polyploid organisms have three or more sets of chromosomes

Individual is said to be trisomic

Individual is said to be monosomic


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 will lead to 150% production A single chromosome can have hundreds or even

thousands of genes Refer to Figure 8.15

Aneuploidy

8-38Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.15

In most cases, these effects are

detrimentalThey produce

individuals that are less likely to survive

than a euploid individual


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

Refer to Figure 8.16

Aneuploidy

8-49Figure 8.16

Blakeslee noted that this plants is “weak and lopping with the leaves narrow and

twisted.”


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


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

8-44

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


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


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

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

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


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

Euploidy

8-52

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


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) Keep blooming since the don’t form desired end product (competitors can’t sell seeds grown from their plants)

There are three natural mechanisms by which the chromosome number of a species can vary 1. Meiotic nondisjunction 2. Mitotic abnormalities 3. Interspecies crosses


8.3 NATURAL AND EXPERIMENTAL WAYS TO PRODUCE VARIATIONS IN CHROMOSOME NUMBER

8-54


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

8-55

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-56Figure 8.22

All four gametes are abnormal

During fertilization,

these gametes produce an

individual that is trisomic

for the missing

chromosome

During fertilization,

these gametes produce an

individual that is monosomic

for the missing

chromosome

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8-57Figure 8.22

50 % Abnormal gametes

50 % Normal gametes


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 a 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

8-58


Mitotic Abnormalities Abnormalities in chromosome number often occur

after fertilization In this case, the abnormality occurs in 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

8-59

8-60Figure 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


Mitotic Abnormalities Genetic abnormalities that occur 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 Refer to Figure 8.24 for a bizarre example

8-61


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

8-62

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

variation in chromosome structure and number chapter 8

Documents

mcgrawhill companies

chromosome structure

human chromosome

chromosome breaks

cytogenetics copyright

structure of chromosomes

abnormal chromosome

brooker copyright