Transcript Recombinant DNA Technology

Gene Mutation
Mutation
Mutation: change in DNA sequence
Causes of mutation:
Spontaneous Due to naturallyoccurring errors in
DNA replication
Induced
Due to exposures to
radiation or chemical
mutagens
Spontaneous Mutation
Spontaneous mutation in gene for a blood clotting
factor, leading to hemophilia.
Point Mutations
Point mutation: change in one or a few
DNA nucleotides
Substitution
One nucleotide is replaced
by another
Deletion
One or more nucleotides
are removed
Insertion
One or more nucleotides
are added
Duplication
Nucleotides are repeated
within a gene
Substitutions
Name
Substitution
Transition
ATGC
Purinepurine
Pyrimidinepyrimidine
change to same
type of base
Transversion Purinepyrimidine
change to different Pyrimidinepurine
type of base
Example
ATCG
Examples of Substitutions
Transition
Transversion
3’-T-T-C-5’ 3’-T-C-C-5’ 3’-T-T-C-5’
5’-A-A-G-3’ 5’-A-G-G-3’ 5’-A-A-G-3’
3’-T-G-C-5’
5’-A-C-G-3’
RNA 5’-A-A-G-3’ 5’-A-G-G-3’ 5’-A-A-G-3’
codon
5’-A-C-G-3’
DNA
Top
strand is
template
Amino
Acid
lysine
arginine
lysine
threonine
Effects of Substitutions
on the Protein Sequence
Type
Definition
Example
(codons are shown)
AGG CGG
Arg
Arg
AAA AGA
Synonymous Change to a chemicallySIMILAR AMINO ACID
Lys
Arg
AAA GAA
Missense Change to a chemicallyDIFFERENT AMINO ACID
Lys
Glu
CAG UAG
Nonsense Change to a stop codon,
SHORTENS THE PROTEIN Gln
Stop
Silent
Change to a different codon
for the SAME AMINO ACID
Applying Your Knowledge
The mutation that leads
to Sickle-cell Disease
(HbS) is a
1. Silent Mutation
2. Synonymous mutation
3. Missense Mutation
4. Nonsense Mutation
5. None of these
HbA
HbS
Applying Your Knowledge
The mutation that leads
to the insertion of valine
into HbS is due to a
1. Transition
2. Transversion
3. Both a transition and a
transversion
4. Neither a transition nor a
transversion
HbS
Frameshift Mutations
Frameshift mutation: deletion or insertion of
nucleotide bases, not in multiples of three
Causes a change in the “reading frame” of
codons for the protein sequence
Original Codon Sequence
AAG-ACU-UAC-CAA
Amino acid sequence
Lys---thr---tyr---gln
Frameshift due to insertion AA(A)-GAC-UUA-CCA-A
Amino acid sequence
Lys----asp---leu---pro
Insertions in multiples
of three nucleotides
restore the reading
frame.
Tandem Duplications
Tandem duplications: adjacent or nearby
repeat of part of a gene’s sequence
Charcot-MarieTooth Disease
Repeat of
1.5 million
base pairs
within gene
Disorder of nervous
system that affects
nerves directed to
muscles in hands and
feet.
Causes a numbing of
hands and feet, difficulty
walking
Expanding Triplet Repeats
Expanding Triplet Repeats: increase in number of
a specific trinucleotide within a gene from
generation to generation
Huntington Disease Repeat of CAG triplet leads to
repeat of glutamine in the protein
Huntingtin.
Neurodegenerative disorder
leading to personality changes
and uncontrollable movements.
Expansion of the Trinucleotide Repeat for Huntington’s Disease
Allen
(46,13)
age 50
Jama
(7,18)
Christina
(93,7)
age 26
Andrew
(69,6)
age 37
Joseph
(7,6)
Kristen
(64,22)
age 40
Linda
(6,22)
Ann
Greg
(64,22) (11,19)
age 39
Nathaniel
(72,19)
age 35
Debbie
(13,6)
Paula
(13,12)
Bill
(8,12)
Evan
(not tested)
Applying Your Knowledge
1.
2.
3.
4.
Substitution
Frameshift Mutation
Tandem Duplication
Expanding Triplet Repeat
A. An insertion of one or two nucleotide bases causes
a _____ .
B. Replacing one nucleotide with another causes a
____.
C. A repeat of part of a gene’s sequence in a nearby
region is a ______.
Repair of
DNA
Type of Damage
Repair Mechanism
Ultraviolet Light Causing
Photoreactivation
Thymine-Thymine Dimers
Damage caused by
Excision Repair
chemicals or ultraviolet light
Incorrect base inserted in
Mismatch Repair
new strand during replication
Repairing UV-Damaged DNA
Use of light and
enzymes to
reverse thyminethymine dimers
Use of
enzymes to
remove and
replace region
with thyminethymine dimer
Photoreactivation
Mismatch Repair: Correcting Errors
in DNA Replication
Xeroderma Pigmentosum: Accumulation
of DNA Damage Leads to Skin Cancer
Applying Your Knowledge
1. Mismatch Repair
2. Excision Repair
3. Photoreactivation
A. Method of replacing a DNA region that was
damaged by radiation or chemicals
B. Method that uses white light to repair thyminethymine dimers produced by ultraviolet radiation
C. Method of replacing DNA region where a nucleotide
was incorrectly placed during replication