The document discusses the nature and types of mutations, highlighting their occurrence in somatic and germline cells and the potential for hereditary transmission. It categorizes mutations based on transmission stability, molecular alterations, effects on encoded proteins, and functional impacts, such as loss or gain of function. Examples of mutations include substitutions, insertions, deletions, and the implications of dynamic mutations related to genetic disorders.

1. TYPES OF MUTATION
Dr. A. T. Sharma
Assist. Professor
Nanded Pharmacy College, Nanded

2. Introduction
• The permanent change in sequence of
nucleotides.
• May occur in somatic cells or germ line cells
• Mutation in somatic cells does not pass to future
generations while mutation in germ line cells may
be passed to future generations
• Mutation may be in coding sequences (hereditary
disorder or disease) or in non-coding sequences
• Mutation may occur due exposure to mutagenic
agents and errors through DNA replication and
repair

3. Mutagens
• Anything that causes a mutation (a change in the DNA
of a cell).
• DNA changes caused by mutagens may harm cells and
cause certain diseases, such as cancer.
• Examples of mutagens include radioactive substances,
x-rays, ultraviolet radiation, and certain chemicals.
Types of Mutation
Based on transmission: Depending upon transmission
from one generation to generation, mutation can be
classified in to –
• Stable/fixed mutations: Mutation transferred
unaltered (unchanged)
• Unstable/dynamic mutations: Mutation undergo
variations as they pass on to families

4. Stable/fixed mutations: Classified on the basis of the
particular molecular alterations at the DNA level as –
• Substitution: Replacement of a single nucleotide by
another.
- Two kinds of substitutions –
- Transition: Replacement by the identical nucleotide.
E.g. a pyrimidine for a pyrimidine (C for T or vice versa) or
a purine for a purine ( A for G or vice versa)
- Transversion: Replacement by the different nucleotide
• Insertion: Addition of one or two or more nucleotides
in to a gene.
- If insertion in coding sequence and includes one, two
or nucleotides which are not multiple of three, it will
interrupt the reading structure.

5. • Deletion: Complete loss of one or more nucleotides
- If insertion in coding sequence and includes one,
two or nucleotides which are not multiple of three, it
will interrupt the reading structure.
• Duplication: Doubling of one or more nucleotides.

7. Unstable / dynamic mutations:
Contain triplet replication sequences which,
in affected persons, arise in enlarged copy
number as compared to the overall
population.
• Repeats of three nucleotides increase in
copy numbers until they cross the
threshold above which they become
unstable.
• Defective proteins, change in regulation
of gene expression, synthesis of toxic
RNA, chromosomal instability.
• Triplet increase or expansion has been
recognized the mutational origin for
number of different single gene disorders
known as trinucleotide repeat disorders.
• Larger the expansion, faster the onset
and more is the severity of disease.
• Mechanism is unknown.

8. Based on the effect on the encoded protein:
Depending upon the basis of effect on the
polypeptide sequence of the encoded protein, two
classes as -
Synonymous or silent mutation: A mutation does
not change the polypeptide product of the gene
• A single base-pair substitution, particularly at
third position of a codon, produces a codon
coding for the same amino acid – no change in
properties of the protein.
Non-synonymous mutations: A mutation leading to
change in the encoded polypeptide
• Abnormal protein function

10. • Occurs in one of the three main ways:
- Missense: A single base-pair substitution
resulting in coding for different amino acid and
production of a changed protein.
- May or may not disturb protein function
Conservative substitution: Mutation coding for a
chemically similar amino acid and hence no effect
on protein function
Non-conservative substitution: Mutation coding
for a chemically dissimilar amino acid and hence
effect on protein structure – complete loss or
reduction of biological activity

11. - Nonsense: A substitution of base-pair leading to the
generation of one of the stop codons – results in premature
termination of translation of a peptide chain – reduces the
biological activity of the protein.
- Frameshift: Insertion or deletion of nucleotides not in a
multiple of three disturbing the interpretation of frame
- Usually insert premature STOP codons (along with large
number of amino acid changes, effect on protein structure)
- Reading of codon is changed, STOP codon may not be read or
may be added later or earlier site
- Protein produced may be unusually short, abnormally long
and/or contain wrong amino acids – nonfunctional protein
- Severe genetic diseases like Tay-Sachs disease, familial
hypercholesterolemia

12. Frameshift mutation

13. Based on functional effects of mutations on the
protein: The mutations effect can appear as any of
the following:
Loss-of-function mutations (Inactivating
mutations): Mutations that result in the gene
product having less or no function (being partially
or wholly inactivated). When the allele has a
complete loss of function (null allele), it is often
called an amorph or amorphic mutation.
• Loss of function mutations are generally
recessive.
• E.g. a nonsense mutation that causes polypeptide
chain termination during translation.

14. Gain-of-function (Activating mutations): Mutations
that change the gene product such that its effect
gets stronger (enhanced activation) or even is
superseded by a different and abnormal function.
• When the new allele is created,
a heterozygote containing the newly created
allele as well as the original, will express the new
allele (dominant phenotypes).
• Hypermorph (increased gene expression) and
neomorph (novel function).
• E.g. Loss of growth control as in oncogenes

15. Thank You…!!!
(Disclaimer: The images and diagrams in this presentation have
been downloaded from the google source. I am grateful to all the
publishers & the google.)