The consequences of mutations in

Your Favorite Gene (YGF)

Exon 1 Intron 1 Exon 2

-200
UAS TATA ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
5’ UTR 3’ UTR 0
0

mRNA

Transcription Unit
 The consequences of mutations in
NON CODING regions of Your Favorite Gene (YGF)-
Promoter

Exon 1 Intron 1 Exon 2

-200
UAS
TATA ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
5’ UTR 3’ UTR 0
Mutations in the Promoter
0
•Reduce or abolish transcription of
mRNA resulting in no protein or
reduced amount of normal or wildtype
protein mRNA
•Mutations in the TATA may alter the
+1 site resulting in a new
transcription start site. This may
decrease the stability of the mRNA Transcription Unit
resulting in less wt mRNA and
therefore less wt protein.
 The consequences of mutations in
NON CODING regions of Your Favorite Gene (YGF)-
Terminator

Exon 1 Intron 1 Exon 2

-200
UAS
TATA
ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
5’ UTR 3’ UTR 0
Mutations in the 3’ UTR/Terminator
0
•3’ Untranslated region- may
decrease the stability of the mRNA
resulting in less wt mRNA and
therefore less wt protein. mRNA
•Terminator sequence- will result in
longer mRNA which may decrease
the stability of the mRNA resulting in
less wt mRNA and therefore less wt Transcription Unit
protein.
 The consequences of mutations in
NON CODING regions of Your Favorite Gene (YGF)-
5’ UTR

Exon 1 Intron 1 Exon 2

-200
UAS
TATA
ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
5’ UTR 3’ UTR 0
Mutations in the 5’ UTR
0
•5’ Untranslated region-(Shine
Delgarno or Kokak sequence)
binding of the ribosome will be
abolished; no translation but mRNA
normal mRNA! No protein formed!

Transcription Unit
 The consequences of mutations in
NON CODING regions of Your Favorite Gene (YGF)-
Introns and Splice Junctions

Exon 1 Intron 1 Exon 2

-200
UAS
TATA
ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
Mutations in the Intron 3’ UTR 0
5’ UTR
5’, 3’ splice junctions or Branch 0
point -this will result in the abnormal
splicing causing an abnormal
mRNA- upon translation, the exon 1
sequences will be normally translated mRNA
but a frame shift will occur when the
intron sequences are translated.
Other intron sequences- should
Transcription Unit
not alter splicing resulting in
normal mRNA and Protein
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-

Exon 1 Intron 1 Exon 2

-200
UAS
TATA
ATGCCcggaaaGUGA
+ +
1 1
Promoter
Coding sequence 0
5’ UTR 3’ UTR 0
Mutations in the coding 0
sequences-
•These mutations alter the quality
of the protein mRNA
•mRNA regulation, abundance and
size is normal Transcription Unit
•The coding sequence is altered so
that the protein amino acid
sequence is changed!
mRNA
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-

mRNA

We use special terms to refer to the type of mutation that

alters the quality of the protein.

These terms only refer to mutations in the CODING

SEQUENCE! Not mutations in the promoter or
terminators.!
The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-
full length protein& functional

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

Silent THE ONE BIG FLY HAD ONE RED EYE

A silent mutation alters the DNA sequence but still codes for the
same amino acid so the resulting protein is identical.

CUU vs CUA both code for the same amino acid Leucine.
The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-full length protein but
nonfunctional

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

THI ONE BIG FLY HAD ONE RED EYE
CONSERVATIVE MISSENSE - REPLACE LIKE AMINO ACID
FOR LIKE AMINO ACID, CHARGED FOR CHARGED,
HYDROPHOBIC FOR HYDROPHOBIC.
NONCONSERVATIVE MISSENSE- REPLACE UNLIKE AMINO
ACID FOR UNLIKE AMINO ACID. An example is Sickle cell
anemia where a glutamic acid is replaced with valine .
THQ ONE BIG FLY HAD ONE RED EYE
The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)
Temperature sensitive

mRNA

Some missense mutations are temperature sensitive:

They show no phenotype at normal temperature
(permissive) but show a phenotype at the restricted
temperature (usually elevated)
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)
Temperature sensitive

How does this happen?

At 37°C The wildtype protein has a normal
at 37°C
stucture and has 100% activity. WT protein 100%
At 42°C, the interactions causing the wt structure
are weakened and the protein has a slight
structural change resulting in 85% activity. at 45°C
At 37°C, due to the amino acid substitution WT protein 85%
(missense mutation), the mutant has an altered
structure rsulting in a decrease in activity to 60 % at 37°C
of wildtype. The mutant may have a slight
phenotype such as slow growth Mut protein 60%

At 42°C, the interactions causing the mutant

structure are weakened and the protein has a
structural change resulting in 10% activity. This
at 45°C
activity is insufficient to allow the protein to Mut protein 10%
function and results in strong phenotype (no
growth and the process stops.)
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)- Shortened protein

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

NONSENSE THE ONE BIG stop
a codon is replaced with a stop codon.Shortened
protein; Function depends on how much of the wildtype amino acids
remain.
FRAMESHIFT THE ONE QBI GFL YHA DON
Insertions or deletions that are not multiples of 3 alter the reading frame.
The amino acid sequence after the frameshift is garbage and often a
stop codon is encountered that shortens the polypeptide. Function
depends on how much of the wildtype amino acid sequence remains
before the shift.
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

DUPLICATION THE ONE BIG FLY FLY HAD ONE RED EYE
A duplication repeats a portion of the coding sequence. If it is in
multiples of 3 it does not alter the code but will add an additional amino
acid. Depending on what aa is added and where it is in the tertiary
structure will dictate the consequences of a single aa insertion.
 The consequences of mutations in CODING regions of
Your Favorite Gene (YGF)-

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

EXPANDING THE ONE BIG FLY FLY HAD ONE RED EYE
THE ONE BIG FLY FLY FLY HAD ONE RED EYE
THE ONE BIG FLY FLY FLY FLY HAD ONE RED EYE

An expanding mutation expands with each generation. Since these are

usually triplets, it adds additional amino acids to the protein. Expansion
beyond a threshold are associated with a series of diseases- including
Fragile X syndrome and Huntington’s Disease.