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CASE FILES: BIOCHEMISTRY
subdivided into three categories; silent, missense, and nonsense. Silent
mutations do not affect the translated mRNA or final protein product—
thus the name
silent.
The genetic code is degenerate, which means that most
amino acids are encoded by several different codons or triplets of DNA/RNA
bases. Therefore, it is possible to switch a single base but not alter the result-
ing protein product (Table 13-1a). The sickle cell trait is a result of a missense
mutation. This type of point mutation actually does alter the protein prod-
uct. In the case of sickle cell hemoglobin, an adenine is replaced by a thymine,
causing a hydrophilic glutamic acid to be replaced with a hydrophobic valine
in the resulting protein (Table 13-1b). In a nonsense mutation, the mutation
brings about a premature stop in the gene of interest because the altered
codon now represents a stop codon (Table 13-1c). These are commonly seen
in muscular dystrophies and some cystic fibrosis cases. Aminoglycosides are
currently being used to treat premature stop codons as they affect the
translational accuracy of transfer ribonucleic acids (tRNAs), thereby allowing
recognition of incorrect codons including the stop codon. Ultimately, the
translation machinery reads through the premature stop codon because of
altered amino acid insertion by the tRNAs and produces full-length protein
instead of a truncated protein or degraded mRNA.
Table 13-1a
EXAMPLES OF MUTATIONAL EVENTS
SILENT MUTATION
GENETIC CODE
SILENT MUTATION ENCOUNTERED
CODON
AMINO ACID
CODON
AMINO
ACID
MUTANT
CODON
AMINO
ACID
GCC
Alanine
GC
C
Alanine
GC
T
Alanine
GCT
Alanine
GCA
Alanine
GCG
Alanine
Table 13-1b
MISSENSE MUTATION
P-Chain of normal hemoglobin
GTG
Gly
CAC
His
CTG
Leu
ACT
Thr
CCT
Pro
G
A
G
Glu
GAG
Glu
A missense mutation found in
P-chain of sickle cell hemoglobin
GTG
Gly
CAC
His
CTG
Leu
ACT
Thr
CCT
Pro
G
T
G
Val
GAG
Glu
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