Genetic mutations can occur through changes in DNA base sequences or large chromosomal alterations. There are two main types of mutations - chromosomal mutations, which involve changes in large chromosome structures like translocations or deletions, and gene mutations, such as point mutations that change single DNA bases. Point mutations can be further divided into nonsense, missense, silent, and frameshift subtypes depending on their effects on protein sequences. Frameshift mutations caused by insertion or deletion of bases can alter reading frames and change all subsequent amino acids. Suppressor mutations in tRNA molecules allow decoding of altered codons to suppress effects of mutations. Mutations provide a mechanism for genetic change and often result in beneficial new genes and functions that enable organism adaptation

1. Genetic Mutations
Atif Hassan Khirelsied Ph.D
Faculty of Medicine
International University of AfricaInternational University of Africa

2. MutationsMutationsMutationsMutations
• The mutation is defined as a permanentThe mutation is defined as a permanent
inheritable change in DNA base sequence.

3. Types of mutationsTypes of mutations
• Chromosomal aberrations
• Gene mutations

4. Chromosomal mutationsChromosomal mutationsChromosomal mutationsChromosomal mutations
• Large sections of chromosomes can be
altered or shifted leading to changes in thealtered or shifted, leading to changes in the
way the genes on them are expressed.

5. Chromosomal mutations include:Chromosomal mutations include:Chromosomal mutations include:Chromosomal mutations include:
• Translocation
• Inversion
• Deletion
• Non‐disjunction.Non disjunction.

6. Chromosomal translocationsChromosomal translocationsChromosomal translocationsChromosomal translocations
• The interchange of large segments of DNA
between two different chromosomes.
• This can change expression of genes if a gene
is at the translocation break‐point or if it is
reattached a new promoter region. p g

7. Chromosomal inversionsChromosomal inversionsChromosomal inversionsChromosomal inversions
• Occur when a region of DNA flips its
orientation with respect to the rest of theorientation with respect to the rest of the
chromosome.
• This can lead to the same problems as• This can lead to the same problems as
translocations.

8. Chromosomal deletionChromosomal deletionChromosomal deletionChromosomal deletion
• A large regions of a chromosome may be• A large regions of a chromosome may be
deleted, leading to loss of some genes.

9. Chromosomal nonChromosomal non disjunctiondisjunctionChromosomal nonChromosomal non‐‐disjunctiondisjunction
S ti h l t k f• Sometimes a chromosome can lose track of
where it is supposed to go in cell division.
• One of the daughter cells will end up with• One of the daughter cells will end up with
more or less than its share of DNA.

10. • When a new cell gets less or more than its
share of DNA it will have problems with geneshare of DNA, it will have problems with gene
dosage.
• Extra or too few copies of the gene, alters theExtra or too few copies of the gene, alters the
cell physiology.

11. Gene mutationsGene mutationsGene mutationsGene mutations
• Point mutations are single base pair g p
changes.
–Substitution
–Deletion
Addi i–Addition

12. b i i iBase substitution mutations
• Transition mutations result from theTransition mutations result from the
exchange of one purine, or pyrimidine, for
another purine or pyrimidineanother purine, or pyrimidine.
• Transversion mutations result from the
exchange of a purine for a pyrimidine orexchange of a purine for a pyrimidine or
visa versa.

13. Effects of point mutationsEffects of point mutationsEffects of point mutationsEffects of point mutations
• Nonsense mutation
Mi t ti• Missense mutation
• Silent mutation

14. U A AU A A
(Termination codon)
Nonsense
mutation
Silent
mutation
U C A
(codon for serine)(codon for serine)
U C U
Missense
mutation U C U
(codon for serine)
mutation
C C A
(codon for proline)
C C A

15. Nonsense mutationNonsense mutationNonsense mutationNonsense mutation
• A nonsense mutation creates a stop codon
h i l i dwhere none previously existed.
• This shortens the resulting protein, possibly
remo ing essential regionsremoving essential regions.

16. MissenseMissense mutationmutationMissenseMissense mutationmutation
i i h h d f h• A missense mutation changes the code of the
mRNA.
• If AGU is changed to AGA the protein will haveIf AGU is changed to AGA, the protein will have
an arginine instead of serine.
• This may alter the shape or properties of the
protein.

17. MissenseMissense MutationsMutations
PartiallyPartially
AcceptableAcceptable acceptableacceptable
UnacceptableUnacceptable

18. Silent mutationsSilent mutationsSilent mutationsSilent mutations
• A silent mutation has no effect on protein
sequence.
• If an AGU was changed to an AGC, the
ld ll h hprotein would still have the appropriate
serine at that position.

19. FrameFrame‐‐shift mutations.shift mutations.
Deletions or insertions of oneDeletions or insertions of one
or two bases

20. FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.
• Deletions or insertions of any number of
bases from the coding sequence of the gene g q g
will alter the reading frame.
• Deletion or insertion of three bases or
multiples of three will omit or add an amino
acids.acids.

21. FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.
• For example, given the coding sequence
and its corresponding protein : p g p
AGA UCG ACG UUA AGCAGA UCG ACG UUA AGC
A S Th L SArg ‐ Ser ‐ Thr ‐ Leu ‐ Ser

22. FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.
•• The insertion of a The insertion of a CC base pair between bases base pair between bases
6 6 and and 7 7 would result in the following new would result in the following new gg
code.code.
AGAAGA UCGUCG CCACAC GUUGUU AAGAAG CCAGAAGA UCGUCG CCACAC GUUGUU AAGAAG CC
ArgArg SerSer HisHis ValVal LysLysArg Arg ‐‐ Ser Ser ‐‐ His His ‐‐ Val Val ‐‐ LysLys

23. Addition of base
RNAmRNA
U C A U C C U A U G G C U 3’‐End5’‐End
Ser Tyr Gly
Addition of U
Ser
U
U C A C C U A U G G C U 3’‐End5’‐End
Ser Pro Met Ala
Deletion of C
C
’ d
Ser
U C A C U A U G G C U
Leu Trp
5’‐End 3’‐End
Deletion of base

24. FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.
• Amino acids beyond the insertion point will be
changed, producing altered non functional
protein
• The frame shift may generate a stop codon which
ld t l d th t iwould prematurely end the protein.

25. Suppressor mutationsSuppressor mutations
• Is a mutation that occurs in the anticodon
regions of tRNA molecules.
• Mutated tRNA are capable of decoding altered• Mutated tRNA are capable of decoding altered
codons, therefore, suppress the effects of
t ti i th t i dimutations in the protein‐coding genes.

26. Mutations are beneficial !Mutations are beneficial !
• Provide a mechanism of change at the DNA
level
Of l i b fi i l d• Often result in beneficial new genes and
functions.
E bl th i t d t t h i• Enable the organism to adapt to a changing
environment.