Mutation

1. GENE MUTATIONS
DR.K.SHWETA

2. • Is it mutation?

3. Specific Learning Objectives
• Define mutation
• Classification of mutations
• Example for each type of mutation
• What are mutagens?
• Manifestation of mutations
• Ame`s test

4. What Are Mutations?
• Changes in the nucleotide sequence of
DNA
• May occur in somatic cells (aren’t passed to
offspring)
• May occur in gametes (eggs & sperm) and
be passed to offspring

6. Are Mutations Helpful or Harmful?
• Mutations happen
regularly
• Almost all mutations are
neutral
• Chemicals & UV
radiation cause
mutations
• Many mutations are
repaired by enzymes

8. Are Mutations Helpful or Harmful?
• Some type of skin
cancers and leukemia
result from somatic
mutations
• Some mutations may
improve an organism’s
survival (beneficial)

9. Types of Gene Mutations
• Include:
–Point Mutations
–Substitutions
–Insertions
–Deletions
–Frameshift

11. Point Mutation
• Change of a single
nucleotide
• Includes the deletion,
insertion, or substitution
of ONE nucleotide in a
gene

13. Point Mutation
• Sickle Cell disease is
the result of one
nucleotide
substitution
• Occurs in the
hemoglobin gene

14. SUBSTITUTION
• Transition- replacement of purine by another
purine
• Transversion- purine is changed to pyrimidine

15. DELETION
a) Large gene deletions- eg: alpha-thalassemia
hemophilia
b) Deletion of codon- eg: cystic fibrosis
508th phenylalanine missing in CFTR protein
c) Deletion of single base- frameshift effect

16. INSERTION
Single base addition- frameshift effect
Trinucleotide expansion- Huntington`s chorea
CAG trinucleotides repeated 30-300 times
Duplications- unequal crossing over of
chromosomes during meiosis

17. EFFECTS OF MUTATIONS
Silent mutation
Mis-sense but acceptable
Mis-sense partially acceptable
Mis-sense unacceptable
Nonsense
Frameshift
conditional

18. Silent mutation
• Point mutation
• Mutation is silent; no effect on phenotype
• Eg- CUA mutated to CUC - LEUCINE

19. Mis-sense acceptable
• Hemoglobin A molecule- 67th aminoacid in
betachain is valine (GUU)
Point mutation
GCU-alanine
Hb Sydney

20. Mis-sense partially acceptable
• Aminoacid substitution affects functional
properties of protein
• Eg: sickle cell anemia- GAG to GUG
• GLUTAMATE to VALINE

21. Mis-sense Unacceptable
• Single aminoacid substitution produces
nonfunctional protein and is incompatible
with life
• Eg: HbM- Histidine (CAU) to tyrosine (UAU) in
alpha chain leads to methemoglobinemia

22. Nonsense terminator
• UAC- Tyrosine mutated to terminator codon
(UAA or UAG)
• Premature termination of protein
• Functional activity is lost- beta thalassemia

23. Frame shift mutation
Addition or deletion of bases
Reading frame shifts – completely irrelevant
protein with altered aminoacid sequence
Thalassemia, premature termination, run on
polypepetide

24. Mutations
• Frameshift Mutations – shifts the
reading frame of the genetic
message so that the protein may
not be able to perform its
function.
– Insertion
• THE FAT CAT ATE THE RAT
• THE FAT HCA TAT ETH ERA T
– Deletion
• THE FAT CAT ATE THE RAT
• TEF ATC ATA TET GER AT
H
H

26. Amino Acid Sequence
Changed

27. Conditional mutation
• Spontaneous mutations are conditional
• Manifested only when circumstances are
appropriate
• Combination of antitubercular drugs to
overcome resistance

29. Chromosome Mutation
Animation