Mutations-2

Dr Surekha Bhat
Professor in Biochemistry
 Learning objectives
At the end of this lecture, students should be able to:
1.List the types of genetic mutations
2.Explain the phenotypic changes associated with TNR
expansion in coding and non coding regionshe different
types of point mutation with examples
3.Explain and compare frame-shift mutations with in-
frame mutations
4.Explain trinucleotide repeat expansion mutations and
their unique features
 Types of genetic mutations

•Point mutation
•Frameshift mutation
•Inframe mutation
•Trinucleotide repeat expansion mutation
 1. Point mutation
• Mutation due to a single base change
Based on the type of change:
A. Transition mutation:
Purine replaces purine or pyrimidine replaces pyrimidine
B. Transversion:
Purine replaces pyrimidine or vice versa
Based on the effects of mutation:
A. Silent mutation
• Changed codon codes for the same amino acid
• Therefore the mutation will not be known (silent)
Eg. UCA → UCU
(Serine) (Serine)
B. Missense mutation
• Changed codon codes for a different amino acid
C. Nonsense mutation
• Mutation converts the original codon to stop codon
• Leads to premature termination of translation
 2. Frameshift mutation
• Insertion or deletion mutation
• Causes a change in the reading frame downstream of insertion
or deletion
 3. In-frame mutation
• Insertion or deletion mutation in multiples of 3
• No major change in reading frame; loss or gain of amino acid/s
in the mutated polypeptide
 Trinucleotide repeat expansion
• Normally, triplets in some areas of the DNA repeat
over and over (tandem repeats)
• Number of tandem repeats vary from individual to
individual (polymorphic)
• If tandem triplet repeats expand, it is called
trinucleotide repeat (TNR) expansion
• Results in too many copies of the triplet → protein
structure/function/level affected
• TNR expansion is dynamic in nature (unstable and
increases in size with generation)
• If expansion reaches a threshold, a genetic disease can
result
 Trinucleotide repeat:
a type of short tandem repeat

CAG

7 repeats

8 repeats
 Unusual Aspects of Inheritance
of Trinucleotide Repeat Disorders
1. Anticipation
2. Expansion takes place both in somatic and
germ cells
3. Parent-of-origin effects
4. Skewed X-inactivation
5. Methylation effects
6. Incomplete penetrance
7. Variable expressivity
8. Premutation alleles