Mutations

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Mutations
R.C. Gupta Professor and Head Dept. of
Biochemistry National Institute of Medical
Sciences Jaipur, India
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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EMB-RCG
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Point mutations
E M B - R C G
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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(No Transcript)
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Silent mutations
Substitution of 3rd base may not change
the meaning of codon due to degeneracy
E M B - R C G
For example, GGC ? GGG will not change the
meaning (both are codons for glycine)
Mutations which do not change the code
words are known as silent mutations
EMB-RCG
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Mis-sense
mutations
The base substitution changes the code word
E M B - R C G
EMB-RCG
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Effect depends upon structures of the
substituted and the original amino acids
If structures of new and original amino
acids are similar, effect may be minimal
E M B - R C G
EMB-RCG
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Some areas of a protein molecule are
critical to its function
E M B - R C G
If substitution occurs in a critical area,
the effect will be severe
EMB-RCG
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E M B - R C G
EMB-RCG
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Acceptable mis-sense mutations
Haemoglobin Hikari is an example of acceptable
mis-sense mutation
Lysine at position 61 in the ß-chain is
substituted by asparagine
E M B - R C G
This mutant haemoglobin is capable of normal
functioning
EMB-RCG
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Partially acceptable mis-sense mutations
Haemoglobin S (HbS) is an example of
partially acceptable mis-sense mutation
Substitution of Glu by Val at position six
of b-chain partially impairs the functioning
E M B - R C G
HbS functions normally at high oxygen tension but
gets precipitated at low oxygen tension
EMB-RCG
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Effect of haemoglobin S
RBC at normal oxygen tension
RBC at low oxygen tension
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Unacceptable mis-sense mutations
Haemoglobin MBoston is an example of
unacceptable mis-sense mutation

Histidine at position 58 of a
chain is replaced by tyrosine
E M B - R C G
This makes Hb MBoston incapable of
combining with oxygen
EMB-RCG
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Nonsense mutations
E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Frameshift mutations
Frameshift mutations occur due to insertion
or deletion of bases
Insertion or deletion of one or two bases
changes the reading frame
E M B - R C G
The resulting protein has a garbled amino
acid sequence distal to mutation
Such proteins are generally non-functional
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Deletion or addition
THE CAT SAW THE DOG THE CAT RAN
Deletion of H after the first letter
TEC ATS AWT HED OGT HEC ATR AN
Insertion of H after the first letter
THH ECA TSA WTH EDO GTH ECA TRA
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E M B - R C G
Conversely, a stop codon may be changed
into a sense codon
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E M B - R C G
EMB-RCG
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Suppressor mutations
E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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E M B - R C G
EMB-RCG
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Suppressor mutation