for bachelor level student.

1. Mutation
Binaya Tamang
UCMS-TH

2. Introduction
Any sudden change occurring in hereditary material is called as
mutation
• For e.g., Changes in the nucleotide sequence of DNA
Can happen at any time:
• miosis of cell division,
• during DNA replication,
• or anytime if DNA is damaged by mutagens
Change in phenotype may be seen: DNA mRNA  protein(
enzyme, structural protein, antibody, receptor etc.)

3. Mutagens
Simply: mutation + generating mutagens
TWO types
1. Chemical
a. Base analogs: 5-bromouracil
b. Alkylating agents: Ethyl methyl sulfonate, nitrogen mustards
c. Acridine dyes
d. Intercalating agents (Ethidium Bromide)
e. Reactive oxygen species
2. Physical/ Radiation
a. Ionizing ( X-ray, ⍺-ray, β-ray, 𝛾-ray)
b. Non Ionizing –UV rays
Thymine dimers

4. Classified based upon
Site ( gene or chromosome) imp
Tissue origin ( somatic or germinal)
Cause ( spontaneous or induced)
Out come ( Silent, missense , Nonsense, frameshift)imp

5. On the basis of site
Two type: a) Gene /point. and b) chromosomal mutation
Gene mutation
1. Due to
1. Substitution
2. Deletion
3. Insertion
Lets describe each type
 Substitution:
• Transition: same class base is replaced by same type (e.g. purine by
purine or pyrimidine by pyrimidine)
• Transversions : one class of base is replaced by another class ( e.g.
purine by pyrimidine or vice versa)

6. Insertions & deletions:
• Insertion : Addition of one or more nucleotide base pair in a gene.
(Huntington's chorea, Duchenne muscular dystrophy)
• Deletion: Removal of one of more nucleotide pair more nucleotide pair.
( alpha thalassemia , hemophilia , cystic fibrosis)

7. If change is seen in only a single nucleotide point
mutation.
Point mutation: Includes the deletion, insertion, or substitution of ONE
nucleotide in a gene
• Best e.g. is Sickle Cell disease  one nucleotide substitution
• Occurs in the hemoglobin gene.

8. All these changes in gene can show effect  another
base of classification
Based on effect
due to substitution of single base/point
mutation.
• Missense mutation
• Silent mutation
• Nonsense mutation
due to insertion or deletion of one or
more nucleotides ( point + > 1 base )
• Frame shift mutation
• Lets explain each type
a) Missense mutation: a base is substituted 
alters a codon in the mRNA  a different
amino acid ( missense)
• E.g. HbS or sickle- cell hemoglobin

9. Silent and Non-sense mutation
b) Silent mutation: a base is changed but due to degeneracy of the codon,
same amino acid coded mutation is silent and no effect on phenotype.
c) Nonsense mutation : changes a sense codon into a nonsense codon or stop
codon (UAG,UAA,UGA).
• Nonsense mutation early in the mRNA  premature termination of
translation.
• protein is shorter than usual most likely nonfunctional

10. Frame shift mutation
Occurs when bases of not multiple of 3
are added or deleted.
It changes the reading frame of codon.
Like of sentence THE CAT ATE RAT
If one “C” is added in front of CAT, the
reading frame will be like
THE CCA TAT ERA T… ( reading
frame is shifted which changes the
sentence)
Results:
• Totally different amino acids
sequence OR
• Truncated protein due to termination
codon.
E.g crohn’s dis, Tay-Sachs dis

11. 2. Chromosomal/ large scale mutation :
a) Morphological: changes in chromosome structure
• Deletion
• Duplication
• Inversion
• Translocation
b) Numerical : changes in chromosome number (n)
• Euploidy
• Polyploidy
• Aneuploidy

12. Deletion: a seg. of a chr is deleted
Duplication: a seg. of a chr is duplicated
Inversion: a seg get cut & attached
inversely (180 o)
Translocation: a seg of chr get attached to
different chr.
Morphological: changes in chr. structure

13. Numerical : changes in chr. number
Euploidy: no. of Chr changes by a set (n)
• n haploid
• 2ndiploid
• 3ntriploid
• Many time polyploid
Aneuploidy: no of chr changes by (∓)1 or (∓) 2 in individual
chromosome.
 Human: 2n (diploid). Lets take 12th chr.
• Out of 2 , If one chromosome is lost monosomy: 2n-1
• Out of 2 , If both chromosomes are lost nullisomy: 2n-2
• Similarly, if one is added Trisomy: 2n+1
• If two are added  tetrasomy: 2n+2.
• E.g, Down’s syndrome( trisomy 21), patau syndrome (trisomy 13), Edward
syndrome (trisomy 18)

14. Other classification
Based on tissue of origin
• Somatic: vegetative  doesn't transmit to next generation. E.g. Skin
cancer
• Germinal  gametic or reproductive cell  transmitted to next
generation.
Cause of mutation
• Spontaneous: spontaneously or naturally with out any intervention of
any chemical mutagens. Eg. Methylation followed by deamination
of cytosine.Very slow process
• Induced: due to treatment with either a chemical or physical agent
called mutagens. E.g X- rays causing mutation in cereals

15. Mutation and Polymorphism
Mutation: Rare Genetic change ( Less than 1%)
• Alter the function of the protein or the Enzyme.
• May occur on average 1 on every 106 base pairs.
Polymorphism: is common variation (greater than 1%)
• no change in function or small effect
• occur on average one every 200-1000 base Pairs.
Polymorphism is change with no effect in the phenotype.

16. 🙏👋👋 Thank you