q115/random_k2/random_1.md

Course  Name: Human Cytogenetics

Paper code: MZO(508)

Unit 5: Mutation and Repair of DNA

Dr. Mukta Joshi

Department of Zoology
Uttarakhand Open University

Haldwani

Mutation

Introduction:

 Sudden change in genetic material or character of an organism

is known as mutation.

 Individuals showing these changes are known as mutants.
 A mutation occurs when a DNA gene is changed  or damaged
in such a way as to alter the genetic message carried by that
gene.

 An individual showing an altered phenotype due to mutation

are known as variant.

 Factor or agents causing mutation are known as mutagens.

 A mutagen is an agent of substance that can bring about a

permanent alteration to the physical composition of a DNA
gene such that the genetic message is changed.

 Mutation which causes change in base sequence of a gene are

known as gene mutation or point mutation

 Gene mutations have the exclusive effect of adding to the

number of alleles available at a locus, and so increasing the
number of alleles available at a locus, and so increasing the
gene pool.

 The gene mutations are the only source of new genetic

variability, and without them evolution could not progress for
a long time.

 Mutant gene do not become expressed immediately because

most of them are recessive.

History

 Seth Wright recorded case of mutation first time in 1791 in

male lamb with unusual short legs.

 1901- Hugo deVries first used the term mutation to describe
the sudden heritable phenotypic change  in evening primrose
Oenothera  lamarckiana.
Oenothera  lamarckiana.

 Systematic study of mutation was started in 1910 when

Morgan genetically analyzed white eye mutant of Drosophila.
 H . J. Muller induced mutation in Drosophila by using X-rays

in 1927; he was awarded with  Nobel prize in 1946.

Spontaneous Mutation

• Spontaneous mutation occur frequently in nature without any

cause.

• During the study heredity since1900, Spontaneous mutation

have been recognized in a large number of organisms.
• Various species of Drosophila have contributed the greatest
number of gene mutations. Hundreds of normal genes and
number of gene mutations. Hundreds of normal genes and
their mutant alleles are known in these flies.

• The known gene mutations in Drosophila are those causing

white eyes, pink eyes, black body colour, yellow body colour
and vestigial  wings.

• Similarly in man, many characters as hair colour, eyes colour,
skin pigmentation and several body deformities are due to
mutant gene.

Induced Mutations

•

•

•
•

Induced mutations are alterations in the gene after it has come
in contact with mutagens and environmental causes.
Induced mutations artificially through the use of radiations,
chemicals and other agent.
It has been shown that the mutation rate can be raised well
It has been shown that the mutation rate can be raised well
above the spontaneous’ rate by various experimental
above the spontaneous’ rate by various experimental
procedures.

• Temperature shocks were one of the first methods used to raise

•

the mutation rate.
In Drosophila, short exposures to both low and high
temperature extremes outside the normal range result in higher
rate of mutation.

• X-rays and other ionizing radiations (alpha, beta and gamma
rays) induce mutations and cause chromosomal breakage. At
present, X-rays are considered to be the most effective
physical mutagens.

• Several chemicals are also strongly mutagenic. The chemicals
like formaldehyde and urethane when mixed with food on
which  Drosophila larvae grow cause mutations.
which  Drosophila larvae grow cause mutations.

• Triazine diepoxide, caffeine, phenol and several cancer

producing compounds cause mutations.

• Mutations are also produced by the analogues of DNA bases
e.g., 5-Bromouracil, 5 Chlorouracil, which are incorporated
into newly formed DNA strands.

Types  of Mutation

• Chromosomal Mutation
i) Deletion
ii) Duplication
Inversion
iii)
iv) Translocation
v) Nondisjunction
•
•
Gene Mutation
Gene Mutation
i) Point Mutation

Silent
Missense
Nonsense

ii) Frameshift  Mutation

Insertion
Deletion

Chromosome Mutation

• A  chromosome mutation  is missing extra or

irregular portion of a chromosomal DNA. It can be
from an atypical number of chromosomes or a
from an atypical number of chromosomes or a
structural abnormality in one or more chromosomes.

Types of Chromosome Mutation

Deletion:
• Deletion occurs when nucleotides are left out of a gene.
• They also usually cause a shift in reading frame that will

ultimately truncate the protein.

• Deletions can be caused by errors in chromosomal crossover

during meiosis, which causes several serious

Duplication:
Duplication:
• A portion of the chromosome is duplicated, resulting in extra

genetic material

• Duplications arise from an event termed unequal crossing-over
that occurs during meiosis between misaligned homologous

Inversion:
• A portion of the chromosome has broken off, turned upside
down, and reattached, therefore, the genetic material is
inverted.

Translocation :

• Chromosome translocation is caused by rearrangement of

parts between non homologous chromosome.

Nondisjunction:
Nondisjunction:
• Failure of chromosome to separate during meiosis
• Causes gamete to have too many or too few chromosomes
• Disorder:
- Down syndrome
- Turner syndrome
- Klinefelter’s  syndrome

Gene Mutation

• A gene mutation is a permanent alteration in the DNA

sequence that makes up a gene, such that the
sequence differ from what is found in most people.

• Mutation range in size; they can affect anywhere
• Mutation range in size; they can affect anywhere
from a single DNA building block (base pair) to a
large segment of a chromosome that include multiple
genes.

Types of Gene Mutation

Point mutation:
• Point mutation are the most common type of gene mutation.
Also called a base-pair substitution,  this type of mutation
changes a single nucleotide base pair. Point mutation can be
categorized into three types:

i)   Missense Mutation:

Change in nucleotide sequence brings different types of
Change in nucleotide sequence brings different types of
protein.

ii)   Silent Mutation:

Change in nucleotide sequence brings no change in protein
type. It is due to degeneracy of genetic.

iii)   Non- Sense Mutation:

Change in nucleotide sequence brings non-sense codon
(UAA, UAG, UGA) at a new position in the mRNA as a
result, protein synthesis adversely stops.

Frameshift  Mutation:
• Mutation caused by the addition or deletion of a base
pair or base pairs in the DNA of a gene resulting in
the translation of the genetic code in an unnatural
the translation of the genetic code in an unnatural
reading frame from the position of the mutation to the
end of the gene

Causes of mutation

• Acquired mutations occur at sometime during a person’s life
and are present only in certain cells, not in every cell in the
body. These changes can be caused by environmental factors
such as ultraviolet radiation from the sun, or can occur if an
error is made as DNA copies itself during cell division.
error is made as DNA copies itself during cell division.

• Mutations can also be caused by exposure to specific

chemicals or radiation. These agents cause the DNA to break
down. So the cell would end up with DNA slightly different
than the original DNA and hence, a mutation.

The cause of mutations

Repair of DNA

•

In order to repair damage to one of the two paired molecules
of DNA, there exist a number of excision repair mechanisms
that remove the damaged nucleotide and replace it with an
undamaged nucleotide complementary to that found in the
undamaged DNA
undamaged DNA
strand.

• The different types of DNA repair include direct repair, base
excision repair, nucleotide excision repair (NER), double-
strand break repair (including homologous recombination and
non-homologous end joining), and crosslink repair (Sancar et
al., 2004).

• DNA repair is a collection of processes by which a cell identifies

•

and corrects damage to the DNA molecules that encode its genome.
In human cells, both normal metabolic activities and environmental
factors such as radiation can cause DNA damage, resulting in as
many as 1 million individual molecular lesions per cell per day.
• Many of these lesions cause structural damage to the DNA molecule
and can alter or eliminate the cell's ability to transcribe the gene that
the affected DNA encodes. Other lesions induce potentially
harmful mutations in the cell's genome, which affect the survival of
its daughter cells after it undergoes mitosis.
its daughter cells after it undergoes mitosis.

• As a consequence, the DNA repair process is constantly active as it
responds to damage in the DNA structure. When normal repair
processes fail, and when cellular apoptosis does not occur,
irreparable DNA damage may occur, including double-strand breaks
and DNA cross linkages (interstrand cross links or ICLs).This can
eventually lead to malignant tumors, or cancer as per the two hit
hypothesis.

• The rate of DNA repair is dependent on many factors,

including the cell type, the age of the cell, and the extracellular
environment.

• A cell that has accumulated a large amount of DNA damage,

or one that no longer effectively repairs damage incurred to its
DNA, can enter one of three possible states:

1. an irreversible state of dormancy, known as senescence
2. cell suicide, also known as apoptosis or programmed cell
2. cell suicide, also known as apoptosis or programmed cell

death
death

3. unregulated cell division, which can lead to the formation of

a tumor that is cancerous

• The DNA repair ability of a cell is vital to the integrity of its

genome and thus to the normal functionality of that organism.
Many genes that were initially shown to influence life span
have turned out to be involved in DNA damage repair and
protection.

Thank  you
Thank  you