Chromosomal Aberration

Chromosomal aberrations are abnormalities in the structure or number

of chromosomes and are often responsible for genetic disorders.

Chromosomal abnormalities occur

• when there is a defect in a chromosome, or in the arrangement of the
genetic material on the chromosome.
• Very often, chromosome abnormalities give rise to specific physical
symptoms, however, the severity of these can vary from individual to
individual.
Types of chromosomal aberration

Chromosomal aberrations are of two types

(i) Structural changes of chromosome
(ii) Numerical changes of chromosome

(i) Structural changes of chromosome

Chromosomes are the vehicle of hereditary material or genes. Any alteration,
addition or deletion of chromosomal part leads to position or sequence of genes in
the chromosome.
When the chromosome's structure is altered, this can take
several forms
• Deletion or Deficiency: It is due to loss of a part of a
chromosome so chromosome becomes shorter.
Known disorders in humans include Wolf-Hirschhorn
syndrome, which is caused by partial deletion of the short arm
of chromosome 4; and Jacobsen syndrome, because
this deletion occurs at the end (terminus) of the long (q) arm
of chromosome 11.
Deletions start with chromosomal breaks induced by:
• Heat or radiation (especially ionizing)
• Viruses Fig. A deletion of a
chromosome segment
• Chemicals
• Transposable elements
• Errors in recombination.
•Duplications: Duplication of
chromosome may take place due to
attachment of some deleted part of
another chromosome with it. This brings
addition of some new genes not
belonging to it.

Known human disorders include

Charcot-Marie-Tooth disease type 1A,
which may be caused by duplication of
the gene encoding peripheral myelin
protein 22 (PMP22) on chromosome 17. Fig. Duplication, with a chromosome
segment repeated
 Inversions: An inversion is
produced when there are two breaks
in a chromosome and the intercalary
segment reunites in reverse order
i.e., the segment rotate by 180°.
•Translocations: Translocation involves
transfer of a segment of a chromosome to a
different part of the same chromosome or to a
different chromosome. Translocation are of
two types
i. Reciprocal translocation: two non-
homologous chromosomes exchange genetic
material
Reciprocal translocations arise from two
different mechanisms
1. Chromosomal breakage and DNA repair
2. Abnormal crossovers
ii. Robertsonian translocation:
An entire chromosome has
attached to another at the
centromere - in humans these
only occur with chromosomes
13, 14, 15, 21, and 22.
•Rings: A portion of a chromosome has broken off and formed a circle or ring. This can
happen with or without loss of genetic material.

•Isochromosome: Formed by the mirror image copy of a chromosome segment

including the centromere.
(ii) Numerical Changes in chromosome:
The organisms are usually diploid (2n), i.e., they possess two sets of chromosomes.
Variation in the normal diploid chromosome number is termed ploidy. Numerical
change in chromosome or variations in chromosome number (heteroploidy), can be
mainly of two types, namely
(a)aneuploidy and
(b)euploidy.

(a) Aneuploidy:
It involves addition or deletion of one or few chromosomes to the usual diploid set of
chromosomes. The aneuploids arise due to failure of the separation of homologous
chromosomes of particular pair during meiosis. It is known as non-disjunction. As a
result two types of gametes are produced; one type contain more chromosomes than
the normal number and the other type of gamete contain less chromosomes.
Aneuploids are of following types:
(i) Monosomies:
They arise by the loss of one chromosome from the diploid set i.e., 2n-l. They can
form two types of gametes, (n) and (n-1).
(ii) Nullisomics:
These arise by the loss of a particular pair of chromosomes i.e., 2n-2. They arise by
the fusion of two (n-1) type of gametes.
(iii) Trisomies:
These arise by addition of an extra chromosome to the normal diploid set with the
genetic formula, 2n + 1. Such individuals are formed by the union of a (n + 1) gamete
with a normal gamete (n).
(iv) Tetrasomics:
These arise by the addition of an extra pair of chromosome to the diploid set with a
chromosomal formula 2n + 2. By this a particular chromosome is represented in four
doses instead of normal two.
(b)Euploidy: Normally organism possesses two sets of chromosomes i.e., they are
diploid (2n). At times there is addition or loss of complete one set (n) or more than
one set of chromosomes is observed. It is called as euploidy.

Euploidy is of following types:

(i) Haploidy or Monoploidy:

Out of two sets of chromosomes of a normal organism when one set is lost, the
resulting offspring’s have just one set of chromosomes (n).

(ii) Polyploidy:
Organisms having more than two normal sets of chromosomes (2n) are called
polyploids. Organisms with three sets of chromosomes (2n + n) = 3n are triploids;
those with four sets of chromosomes (2n + 2n) = 4n are tetraploids and those with five
sets (2n + 3n) = 5n and six sets (2n + 4n) = 6n are known as pentaploid and
hexaploidy, respectively.
Importance of chromosome Aberration
1. Role in Evolution: In some cases, even if the genes are identical they may be
ordered in a different way, owing to alterations of the chromosomal segments. These
changes have an important bearing on the evolution of species.
Observation of chromosomal organization and of the different karyotypes in the
individual, the species, genera, and the major systematic groups indicates that
chromosomal aberration is involved in the process of evolution. One of the most
frequent causes of evolution is a change in the order of genes as a result of
chromosomal aberrations. Thus, chromosomal aberrations play a vital role in evolution
as they generate variation in a natural population.
2. Role in Genetic Analysis: Chromosomal aberrations have been very helpful in
genetic analysis. Trans-located strains of maize were used to demonstrate that a
cytological exchange of chromosome parts results into genetic recombination. In
different crop species, translocations, duplications and deficiencies have been used in
mapping of gene locus.
3.Role in Plant Breeding: Aberrations result in altered linkage relationships and this
has been exploited for breeding experiments.
Definition of Gene Mutation

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene,
such that the sequence differs from what is found in most people. Mutations range in
size; they can affect anywhere from a single DNA building block (base pair) to a large
segment of a chromosome that includes multiple genes.
Tautomeric shift:
Watson and Crick pointed out that the
structures of the bases in DNA are not
static. Hydrogen atoms can move from
one position in a purine or pyrimidine to
another position, for example from an
amino group to ring nitrogen. Such
chemical fluctuations are called
tautomeric shifts.
Types of mutation via tautomeric shift A
1. Transition mutation
2. Transversion mutation
T C
3. Frame shift mutation

1. Transition mutation: When a purine in one strand G

of DNA with the another purine and the replacement Transition mutation
of a pyrimidine in the complementary strand with the
other pyrimidine. Such base-pair substitutions are
called transition mutation. Therefore, transitions are
of four types. A
2. Transversion mutation: Base pair substitutions
involving the substitution of a purine for a pyrimidine
or a pyrimidine for a purine are called transition T C

mutation. Therefore, transversions are of eight types.

G

Transversion mutation
Frame shift mutation:
The addition or deletion of one or few base-pairs collectively referred to as frame shift
mutation. Because they alter the reading frame of all base pairs in the gene distal to the
mutation; that is specifying codons in the mRNA and amino acids in the poly nucleotide
gene product.
A T G A A A G G G C C C T T T etc. A T G A A A C G G G C C C T T T etc.
T A C T T T C C C G G G A A A etc. T A C T T T G C C C G G G A A A etc.

Transcribed strand Transcribed strand

A U G A A A G G G C C C U U U etc. A U G A A A C G G G C C C U U U etc.

Codon Codon Codon Codon Codon Codon Codon Codon Codon Etc.
Codon
1 2 3 4 5 1 3 4
2 5
Polypeptide Met Lys Gly Pro Phe Met Lys Arg Ala Leu

Diagram of frameshift mutation that results from the addition of a single base-pair. The mutant is
produced by the insertion of a CG base-pair between the sixth and seventh base-pairs of a wild type gene.
This alters the reading frame of that portion of the gene distal. As a result, all the codons of the mRNA
and all the amino acids of the polypeptide that correspond to base-pair triplets distal to the mutation are
altered.
What is Mutagen?

A mutagen is a physical or chemical agent that changes the genetic material,

usually DNA, of an organism and thus increases the frequency of mutations above
the natural background level.
Different Types of Mutagen
Physical mutagens
• Ionizing radiations such as X-rays, gamma rays and alpha particles cause DNA
breakage and other damages. The most common laboratory sources
include cobalt-60 and cesium-137.

• Ultraviolet radiations with wavelength above 260 nm are absorbed strongly by

bases, producing pyrimidine dimers, and cytosine hydrate which can cause
error in replication if left uncorrected.

• Radioactive decay, such as 14C in DNA which decays into nitrogen.

DNA reactive chemicals
A large number of chemicals may interact directly with DNA. However, many such as
PAHs, aromatic amines, benzene are not necessarily mutagenic by themselves, but
through metabolic processes in cells they produce mutagenic compounds.
• Reactive oxygen species (ROS): Examples, 15-hydroperoxyicosatetraenocic,
lipoxygenases etc.
• Deaminating agents: Example, nitrous acid
• Polycyclic aromatic hydrocarbon (PAH):
• Alkylating agents: Example, ethylnitrosourea, nitrosamines etc
• Aromatic amines and amides: Examples, 2-Acetylaminofluorene
• Alkaloid from plants: Examples, Vinca species
• Bromine and some compounds
• Sodium azide,
• Psoralen
• Benzene
The causes of gene mutations
Mutations happen for several reasons.
DNA fails to copy accurately
Most of the mutations olution are "naturally-occurring." For example, when a cell
divides, it makes a copy of its DNA — and sometimes the copy is not quite perfect.
That small difference from the original DNA sequence is a mutation.

External influence can cause mutation

Mutations can also be caused by exposure to specific chemicals or radiation. These
agents cause the DNA to break down. This is not necessarily unnatural (induced)
even in the most isolated and pristine environments, DNA breaks down.
Nevertheless, when the cell repairs the DNA, it might not do a perfect job of the
repair. So the cell would end up with DNA slightly different than the original DNA
and hence, a mutation.
Effect of Mutation

Beneficial Mutations
• Some mutations have a positive effect on the organism in which they occur. They
are called beneficial mutations. They lead to new versions of proteins that help
organisms adapt to changes in their environment. Beneficial mutations are essential
for evolution to occur.
• Mutations in many bacteria that allow them to survive in the presence of antibiotic
drugs. The mutations lead to antibiotic-resistant strains of bacteria.
• New genotype can be obtained.
• Recombination is possible through gene mutation

Harmful Mutations
Mutation cause random change in a gene's DNA is likely to result in a protein that
does not function normally or may not function at all. Such mutations are likely to be
harmful. Harmful mutations may cause genetic disorders or cancer.
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