Download Gene Mutations

Gene Mutations
Gene Mutations
O A mutation is a permanent change in the
DNA sequence of a gene.
O Any change in this sequence is likely to
change the message transcribed into
mRNA which will in turn alter the amino
acid sequence causing a change in the
structure and function of the protein
being coded for.
Gene Mutations
O If a nucleotide is added, deleted
or changed the sequence of
codons in the transcribed mRNA
is changed and therefore the
resulting chain of amino acids is
altered.
1. POINT MUTATIONS
O Are single nucleotide base changes in a
gene’s DNA sequence. This type of
mutation can change the gene’s protein
product in the following ways:
O Normal Line of Un-Mutated DNA:
Normal DNA TAC TGC ACC GGT ACT
mRNA
AUG ACG UGG CCA UGA
protein
met thr try
pro stop
Missense mutations
O Missense mutations are point mutations
that result in a single amino acid change
within the protein.
Mutated DNA TAC TGC AAC GGT ACT
mRNA
AUG ACG UUG CCA UGA
protein
met
thr leu pro stop
O LEU CHANGED FROM TRY
O For example, in
sickle-cell disease,
the 20th nucleotide
of the gene for the
beta chain of
hemoglobin found on
chromosome 11 is
changed from the
codon GAG (for
glutamic acid) to
GUG (which codes
valine), so the 6th
amino acid is
incorrectly
substituted.
Nonsense mutations
O Nonsense mutations are point mutations
that create a premature “translation stop
signal” (or “stop” codon), causing the
protein to be shortened.
Mutated DNA TAC TGC ATC GGT ACT
mRNA
AUG ACG UAG CCA UGA
protein
met
thr STOP
O STOP CHANGED FROM TRY
O Nonsense Mutations for
cystic fibrosis have been
found in almost 1000
combinations. Each of
these mutations occurs in
a huge gene that encodes
a protein (of 1480 amino
acids) called the cystic
fibrosis transmembrane
conductance regulator
(CFTR). Unlike a missence
mutation in sickle cell
anemia, it can be various
mutations that cause
cystic fibrosis.
O Ex: The substitution of a T
for a C at nucleotide 1609
converted a glutamine
codon (CAG) to a STOP
codon (TAG). The protein
produced by this patient
had only the first 493
amino acids of the normal
chain of 1480 and could
not function.
Silent mutations
O Silent mutations are point mutations that do not cause amino
acid changes within the protein.
Mutated DNA TAC TGA ACC GGT ACT
mRNA
AUG ACU UGG CCA UGA
protein
met thr try
pro
stop
O THR still codes for THR
O There is no example of a silent mutation because it does not
affect the organisms phenotype.
2. FRAMESHIFT
MUTATIONS
O Result in a shift of the “reading frame”
during protein translation.
O There are two different types
Insertion Mutations
O Insertion mutations add one or more DNA
bases which changes the grouping of
nucleotide bases into codons.
O Frameshifts often create new STOP codons
and thus generate nonsense mutations. Just
as well as the protein would probably be too
garbled to be useful to the cell.
Mutated DNA
mRNA
protein
TAC TAG CAC CGG TAC
AUG AUC GUG GCC AUG
met iso
val ala met
T
A
O A base inserted at the 5th spot, shifting all the bases
down.
Deletion Mutations
O Deletion mutations remove one or more
DNA bases which changes the grouping of
nucleotide bases into codons.
Mutated DNA TAC TGC CCG GTA CT
mRNA
AUG ACG GGC CAU GA
protein
met thr gly his
O 13th base is removed, eliminating 1 amino
acid.
O Cri du chat syndrome, also known as
chromosome 5p deletion syndrome, is a rare
genetic disorder due to a missing part of
chromosome 5. Its name is a French term (catcry or call of the cat) referring to the
characteristic cat-like cry of affected children
due to problems with the larynx and nervous
system. About 1/3 of children lose the cry by
age 2.
O Other symptoms of cri du chat syndrome
may include:
O feeding problems because of difficulty
swallowing and sucking.
O low birth weight and poor growth.
O severe cognitive, speech, and motor delays.
O behavioral problems such as hyperactivity,
aggression, tantrums, and repetitive
movements.
O unusual facial features which may
change over time.
O excessive drooling.
Introns and Exons
O Exons – segments of DNA that code
for amino acids that will become part
of a protein.
O Exons are not found next to each
other. They are separated by sections
of DNA called introns.
O Introns – segments of DNA that do not code for
amino acids of a protein.
O When a gene is transcribed, both the introns
and exons are made into RNA.
O The introns must then be cut out and the
remaining exon pieces must be joined together.
O Before this happens, two other strings of
nucleotides are added to the ends of the RNA.
One is called a cap and the other is called a tail.