7.

2 Gene /Point mutation

Learning Outcome:
a)Explain gene/ point mutation
b)Classify gene mutation:
i. Base substitution
ii. Base insertion
iii. Base deletion
iv. Base inversion
c)Describe base substitution as point mutation
(eg: Sickle cell anaemia)
d)Explain frameshift mutation
e)Describe base insertion as a frameshift mutation
f) Describe base deletion as a frameshift mutation

Gene /Point Mutation

Change in the base sequence/nucleotide sequence of
genetic material/DNA/RNA at a single locus in
particular region of chromosome that represent a gene.
Arise due to spontaneous pairing errors that occur
during DNA replication.
That leads to change in amino acid sequence from the
point of mistake.
Thus changes the protein.
Also known as point mutation

Classification of gene/point mutation

1.
2.
3.
4.

Base substitution
Base inversion
Base insertion
Base deletion
Changes in
base sequence

Classification of gene/point mutation

Base substitution the replacement of one or few
nucleotide with another pair of nucleotides
Base insertion addition of 1 or a few base pairs in the
nucleotide sequences in genes
Base deletion loss of 1 or a few base pairs in
nucleotide sequences

Base inversion 2 base pairs or more are inverted in

nucleotide sequence

A
G
C
T

Normal

Base Insertion

A
G
C
G
T
T
A

T
C
G
C
A
A
T

Base
Substitution

A
G
C
G
T
A

T
C
G
C
A
T

T
A

Gene /Point
Mutation

T
C
G
A
A
T

Base Deletion

A
G
C
T
A

T
C
G
A
T

Base Inversion

A
G
T
C
T
A

T
C
A
G
A
T

Base substitution
Caused by replacement or
substitution of one or few
nucleotides on DNA sequence in a
genes.
Codon is changed and code for
different amino acid
This leads to changes in amino acid
during translation.
Changes in codon may cause:
1.Nonsense mutation
2. Missense mutation
3. Silent mutation

Base
Substitution

A
G
C
G
T
A

T
C
G
C
A
T

1. Nonsense mutation
Change an amino acid codon into a stop codon,
Nearly always leading to a non-functional protein.

2. Missense mutation
Codon still code for an amino acid but change the
indicated amino acid.
E.g.: Sickle cell anaemia

 Change 1 amino acid to another one = MISSENSE

MUTATION

Missense mutations is a mutation that results in one

wrong codon and one wrong amino acid in a polypeptide
or protein

E.g. of Base Substitution : Sickle-cell anemia

In the DNA, the mutant (sickle-cell) template strand has

an A while the wild type template has T.

The mutant mRNA has a U instead of an A in one codon.

The mutant haemoglobin has a valine (Val) instead of

glutamic acid (Glu).

Sickle-cell anemia
Example of missense mutation which happen due to
base substitution in DNA
Causing amino acid glutamic acid is replaced by valine at
a single position in the protein
Defective red blood cell
Abnormal Hb caused sickle (S) shape
Occurs more commonly in people regions where malaria
is common.
Encode by different gene
Hb-S stiff & tend to accumulate in small capillary
Hb is not efficient of transporting oxygen

Base Substitution
Change in a nucleotide pair may transform 1 codon
into another that is translated into the same amino
acid = SILENT MUTATION

e.g of Base Substitution : Sickle-cell anemia

A change in a single nucleotide from T to A in the
DNA template leads to an abnormal protein
Amino acid glutamic acid is replaced by valine at a
single position in the protein (-strand)

~ Patient suffer from anemia ~

These sickle red blood cells can
easily break or stuck in the blood
capillaries.
Sickle-cell anemia patients usually
suffer from heart problems, kidney
failure, abdominal pains, paralysis
and premature death.

ATTENTION: This analogy is just for understanding, please do not

use in the examination!!!

Base Inversion
Means more than one nucleotide/ small region of
DNA breaks and rotate 180 before rejoining the DNA

Base Insertion

Occur when one or a few bases are added to triplet

sequence in DNA
Mutation of base insertion causes frame-shift
mutation

Base Deletion

Occur when one or more nucleotides are removed

from the DNA sequence
Mutation of base deletion causes frame-shift
mutation

What is Frameshift mutation?

Involve insertion/deletion of a base pair or
more (but not in a multiple of three) into the
nucleotides sequence of DNA
Many of these deletions/insertion start in the
middle of a codon
Shifting the reading frame by one or two bases
Frameshift mutations cause the gene to be
read in the wrong three base groups (codon)

What is Frameshift mutation?

From the mutation point, It abrupts the coding
sequence of amino acid.
Changes in codons results in changes in amino
acids
Causing different polypeptide to be produced
Effect : usually harmful to human
E.g.: Major Thalasemia (mutant homozygote
alleles)

Frameshift by Base Insertion

Addition of one or a few bases to triplet sequence in
DNA
The effect is WORSE when the insertion is not in the
multiple of three
The change of all amino acid at and after the point of
mutation
Normal code: GAG-GUU-CCU-AAA-CCU
glu val pro lys pro

Insertion : GAG-GUU-CCU-GAA-ACC
glu val pro glu thr

Frameshift by Base Deletion

The removal of one or more nucleotide in the DNA
sequence
The effect is worse when the insertion is not in the
multiple of three
The change of all amino acid at and after the point of
mutation
Normal code: GAG-GUU-CCU-AAA-CCU

glu

Deletion

val

pro

lys

pro

: GAG-UUC-CUA-AAC-CU
glu

phe

leu

asn

Why deletion of one base pair in any part of the DNA strand
can be lethal compared to the substitution of one base pair?
It causes frame shift mutation
When the deletion starts in the middle of a codon, it shifts the
reading frame by one base
Frame shift mutations cause gene to be read in the different
three base groups
From the mutation point, it disrupts the coding sequence of
amino acid
Changes in codons result in changes in amino acid sequence
and different polypeptide is produced
As a result, different protein is produced
Lead to non-functional protein
The effect is usually harmful to human