Mutation
The hereditary material of life
That affects the
behavior and physiology
of all living things
Introduction
DNA
Gene
Chromosome
Codons
Codon Amino Acid
GCA Alanine
Corresponds to
There is a total of 64 codons in humans
1 codon “AUG” encodes methionine that
starts the transcription of protein
60 codons encodes the 20 different amino
acid synthesized inside human body
3 codons that stops protein synthesis and
are known as “stop codons”
TGA TAA TAG
Different types of proteins are built
according to the sequence and type of
amino acids used as building material.
Mutation occurs when an organism’s
DNA undergoes a change or an alteration
in its sequence.
Different types of mutations exist,
corresponding to different types of
alterations.
A mutation degree depends on type of
mutation, its location and the number of
genes involved.
Types of Mutations
Mutations
Small scale Large scale
“Affects a single gene” “Affects an entire chromosome”
Such as;
Duplication
Sequence mutation
(Point Mutation) Deletion
Frame-shift mutation Inversion
Translocation
S. Scale M
A) Sequence mutation (Point Mutation)
Substitution
Substitution Inversion
Normal Gene Mutant Gene
GGTCTCCTCACGCCA GGTCACCTCACGCCA
CCAGAGGAGUGCGGU CCAGUGGAGUGCGGU
Pro-Glu-Glu-Cys-Gly Pro-Val-Glu-Cys-Gly
Cont. Substitution
Substitution
Transition
Transition Transversion
Pyrimidine to Pyrimidine
T C
Purine to Purine
A G
Cont. Substitution
Transversion
Purine to Pyrimidine and vice versa
A T
T A
G C
C G
A T
Sequence mutation
B) Inversion
Normal Gene Mutant Gene
GGTCTCCTCACGCCA GGTCCTCTCACGCCA
CCAGAGGAGUGCGGU CCAGGAGAGUGCGGU
Pro-Glu-Glu-Cys-Gly Pro-Gly-Glu-Cys-Gly
Cont. S. scale M
Frame-shift mutation
Deletion Insertion
Frame-shift mutations affect the number
of base pairs in the gene unlike Point
mutations.
Cont. S. scale M
Effects of small scale mutations:
Missense Mutation
Mutation yields either good or bad change to the living
creature
Neutral / Silent Mutation
Mutation yields no change to the living creature
Nonsense mutation
Mutations yields an incomplete protein with no function
Facts
Mutation and Cell division
Meiosis Mitosis
Gametes Somatic cells
( meiotic cells); (mitotic cells)
sperm and egg cells body cells
A normal human cell is called Diploid cell, containing (23
pairs) of chromosomes.
(22 pair) of these chromosomes are known as Autosomes,
and they are the same in both males and females.
The (23rd pair) of these chromosomes are the sex
chromosomes.
Males have the (23rd pair) as Y and X chromosomes ,while
females have them as 2 copies of the X chromosome.
Mutations can occur during either meiosis or mitosis, but
only undergo “Autosomal inheritance” during meiosis.
Large scale Mutations
Duplication:
A gene which is a part of a
chromosome is copied
twice during replication.
It leads to an
over-expression of the
duplicated gene.
Cont. L. scale M
Deletion:
A gene which is a part of a chromosome is
deleted during replication
Cont. L. scale M
Inversion:
A whole gene is flipped around and re-inserted into a
chromosome.
There are two types;
1-Paracentric
2-Pericentric
Cont. L. scale M
Cont. L. scale M
Translocation:
A segment of DNA from one chromosome is moved to
another non-homologous chromosome.
Translocation can be balanced
or unbalanced.
Unbalanced translocation
leads to miscarriage or an
abnormal child
Translocation can be
reciprocal or
non-reciprocal.
Robertsonian Translocation
It is a rare form of chromosomal translocation that, in
humans, generally occurs in the five acrocentric
chromosome pairs (13, 14, 15, 21 and 22).
It is responsible for some genetic disorders
Disorders and Diseases associated
with DNA mutation
Down syndrome
It is a result of the presence
of 3rd copy of chromosome
No.21 in a person.
It causes both mental and
physical retardation.
It is caused by
Non-Disjunction mutation.
Non-Disjunction
mutation
Klinefelter’s Syndrome
It is also caused by
Non-Disjunction mutation.
A result of extra X
chromosome in
males
Turner’s Syndrome
It is also caused by
Non-Disjunction mutation.
A result of missing
X chromosome in
females, instead of
having XX chromosome.
Cri-du-chat Syndrome
It is an example of Deletion mutation
Cri-du-chat syndrome results
when a piece of chromosome
No.5 is missing
Infants with this condition
often have a high pitched cry
that sounds like that of a cat
Patau Syndrome
An example of Robertsonian translocation
It is a result of extra
partial part of
chromosome No.13 in
human body cells, the
disorder is known as
Trisomy 13 or Trisomy
D.
Patau syndrome can
also be a result of
a whole extra chromosome No.13 in body cells.
Sickle cell disease;
An example of Point mutation.
In which the codon responsible for forming the
hydrophilic amino acid glutamic acid (GAG) to be
replaced with the hydrophobic amino acid Valine
(GTG) at the 16 position.
The Beta-globin gene is found on the short arm of
chromosome 11.
Cystic fibrosis:
An example of Frame-shift mutation.
It happens when 3 bases responsible for the formation
of the amino acid Phenylalanine are deleted at the 508th
position on the protein.
The mutation is in the gene cystic fibrosis
transmembrane conductance regulator (CFTR)
CTFR gene encodes phenylalanine a membrane-based
protein that functions in transporting chloride ions
across the membrane.
Thus chloride transportation is defective and leads to
excessive water build up in the cell and mucus secreting
glands produce a thicker than normal mucus which is
characteristic symptom of CF.
Genetic Vocabulary
Alleles: different versions (sequences) of a gene.
Genotype: the complete set of alleles for all genes carried
by an individual.
Phenotype: observable trait specified by the genotype.
Wild type: standard reference genotype (Most common
allele for a certain trait).
Euploidy: "true" ploidy, meaning two members of each
homologous pair.
Aneuploidy: "not true" ploidy, meaning more or fewer
members than two of each homologous pair.
Dominant Allele & Recessive Allele
Diploid organisms have two copies of each gene
A recessive mutant allele must be present in two copies
(be homozygous) to cause a phenotype in a diploid
organism to be observable
In contrast, a dominant mutant allele needs to be present
in only one copy (heterozygous) in a diploid organism for
the phenotype to be observable.
Most recessive alleles cause gene inactivation and
phenotypic loss of function.
Some dominant alleles change or increase activity
causing a gain of function.
However, a dominant effect can be caused by gene
inactivation if two copies of the gene are needed for
proper function (haplo-insufficiency).
Identifying Dominant mutations
Identifying Recessive mutations
Mutation types
Morphological mutations
Affect the visible properties of an organism.
Lethal mutations:
Affect viability of the organism
Conditional mutations:
They cause a mutant phenotype only under restrictive
conditions, but cause a wild-type phenotype under
permissive conditions (e.g. temperature sensitive)
Biochemical mutations:
They are identified by the loss or change of some
biochemical function of the cells, typically resulting in an
inability to grow and proliferate.
Loss-of-function mutations:
Also known as “Null mutations”, they are usually
recessive, however in some cases they are dominant.
This means that the single remaining wild-type allele is
unable to provide the amount of gene product needed for
the cells and the organism to be wild type.
Gain-of-function mutations
They result in a new function added to a gene. The
phenotype will be expressed in the heterozygote.
Forward mutation
It is a mutation which changes wild type to mutant, while
reverse mutation changes mutant to wild type and restore
its function.
Suppressor mutation (Intragenic / Intergenic mutation)
It changes the codon of an already mutated codon, which
results in restoring function, thus it hides the effect of
another mutation.
Mechanisms of Gene Mutation:
1-Spontaneous mutations
wobble-pairing
Additions and deletions
Mechanisms of Gene M.
2- Induced Mutations:
A)Chemical Mutagens
a)Base Analogs
Similar to normal bases,
incorporated into DNA
during replication.
Some cause mis-pairing
(e.g., 5-bromouracil), which
act like cytosine, but not all
are mutagenic.
b)Base modifying Agents
They act at any stage of the cell cycle.
Example of base modifying agents are; (Deaminating
agents, Hydroxylating agents and Alkylating agents).
I)Deamination
Amino group is removed from a base (C => U); if not
replaced U pairs with A in next round of replication
(CG => TA).
Prokaryote DNA contains small amounts of 5-
Methylcytosine(5MC); deamination of 5MC produces T
(CG => TA).
Regions with high levels of 5MC are mutation hot
spots.
II) Depurination
It is common;
A or G are removed and replaced with a random base.
C) Intercalating agents:
Examples: Proflavin, ethidium bromide
3- Radiation:
Can cause breaks in DNA
Can cause crosslinking of
pyrimidines (especially T-T
dimmers)
Ionizing radiation has a
cumulative effect and kills
cells at high doses
DNA repair mechanisms
Enzyme-based repair mechanisms prevent and repair
mutations and damage to DNA in prokaryotes and
eukaryotes.
Types;
1-DNA polymerase proofreading;
3’-5’ exonuclease activity corrects errors during the process
of replication.
2-Photoreactivation (also called light repair); Photolyase
enzyme is activated by UV light (320-370 nm) and splits
abnormal base dimers apart.
3-Demethylating DNA repair enzymes;
Repair DNAs damaged by alkylation.
4-Nucleotide excision repair (NER);
Damaged regions of DNA unwind and are removed by
specialized proteins; new DNA is synthesized by DNA
polymerase.
5-Methyl-directed mismatch repair;
Removes mismatched base regions not corrected by DNA
polymerase proofreading. Sites targeted for repair are
indicated in E. coli by the addition of a methyl (CH3)
group at a GATC sequence
Genetic diseases associated with defects
in DNA repair systems
Xeroderma Pigmentosum
It is a result of defects in
nucleotide-excision repair
It is characterized by freckle-
like spots on skin, sensitivity to
sunlight and predisposition to
skin cancer.
No cure, only sunlight protection is used.
Cockayne syndrome
It is also a result of defects in nucleotide-excision repair
it is characterized by;
1-Dwarfism,
2-Sensitivity to sunlight,
3-Deafness,
4-Premature aging and
intellectual disability.
Trichothodystrophy
Another genetic disease resulting
from defects in nucleotide-
excision repair
It is characterized by;
1-Brittle hair,
2-Skin abnormalities,
3-Short stature,
4-Immature sexual development and characteristic facial
features.
Hereditary non-polyposis colon cancer
It is a result of defects in mismatch repair
It is a predisposition to colon cancer
Conclusion
“Mutation is a double-
edged sword”
“It can lead a living creature either
to its demise or its evolution”
Thank You
For
Listening