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BIO20 DNA Mutation PDF
BIO20 DNA Mutation PDF
DNA MUTATION
MUTATIONS
Mutation is the alteration in the gene sequence.
Hereditary (mutation on the germline)
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Point Mutation
A. Substitution mutation
single-base mutations, substitution of one or more
nucleotides by the same number of different
nucleotides.
Transition Transversion
purine to purine purine to pyrimidine (vice-versa)
A G A C G C
pyrimidine to pyrimidine A T G T
C T
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deletion of G at
codon 4
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Consequence of Deletion:
FRAMESHIFT MUTATION – a shift in the reading
frame, which produces a non-functional protein
Frameshift Mutation
Cystic Fibrosis is caused by a mutation in the gene
cystic fibrosis transmembrane conductance regulator
(CFTR).
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Spontaneous Mutation
SPONTANEOUS MUTATION
likely mutations that occur because of the following:
Induced Mutation
INDUCED MUTATION
are mutations that were acquired from the environment
(environmental factors).
Physical Agents
- mutagens in the form of high energy radiation
UV Radiation – leads to the formation of dimers which
can block DNA replication or interfere with base pairing.
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UV Radiation
Induced Mutation
Physical Agents
- mutagens in the form of high energy radiation
X-rays
– leads to single and double-stranded DNA
breakage or may lead to formation of hydroxyl radicals
from water.
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Induced Mutation
Chemical and Mutagens
Base Analogues
-have similar structures to the DNA bases which
undergo tautomerism enabling to cause tautomer
mispairing
Example: 5-bromouracil
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Induced Mutation
Base Analog: 5-
Bromouracil
5-BrU induces a point
mutation via base
substitution. This base
pair will change from
an A-T to a G-C or
from a G-C to an A-T
after a number of
replication cycles
Induced Mutation
Alkylating agents
-adds a methyl or ethyl group to a base
- the largest class of potential mutagens present in man’s
environment
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Induced Mutation
Alkylating agent: N-nitrosoamine
When N-nitrosamine is in the liver, it is metabolized by liver enzymes to
form alkylating agents which can attack guanine. If alkylation occurs, an
apurinic site is produced. During replication, an apurinic site may be
ignored resulting in a deletion in the daughter strand or a base selected at
random and place in the daughter strand.
Induced Mutation
Deaminating agents
-removes amino groups from a base
Example: Sodium nitrite (used as preservative, color enhancer
and color fixative bacon, smoked fish, tocino, etc.)
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Induced Mutation
When ingested, NaNO2 is converted to nitrous acid in acidic
conditions. HNO2 removes functional groups from Adenine,
Guanine and Cytosine. Like deamination of adenine, will result in
the formation of hypoxanthine, a base analogue of guanine.
Induced Mutation
When ingested, NaNO2 is converted to nitrous acid in acidic
conditions. HNO2 removes functional groups from Adenine,
Guanine and Cytosine. Like deamination of adenine, will result in
the formation of hypoxanthine, a base analogue of guanine.
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Induced Mutation
Intercalating agents
- contains a cyclic system that can interact with the bases of the
DNA
Examples:
Benzene (an organic solvent)
Benzo-a-pyrene (cigarette smoke, coal tar, automobile exhaust,
charbroiled food)
Aflatoxin (metabolic product of molds in peanuts, oils and grains)
Induced Mutations
Intercalating Agents
It physically binds to the bases by inserting itself between adjacent base pairs
because of its planar structure. This affects the opening of the DNA during
replication or transcription.
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Induced Mutations
Benzo(a)pyrene inserted
between base pairs
Induced Mutation
Viral agents
some viruses contain oncogenes which can be
activiated once they have inserted their DNA in the
host’s genome.
When virus insert their DNA into the host’s genome,
the sequence of the bases of the host DNA may be
altered or certain destructive genes can be
activated.
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References:
Voet, Voet and Pratt, Principles of Biochemistry 3 rd
ed. Wiley Publication (2008).
Lodish H, Berk A, Zipursky SL, et al. Molecular Cell
Biology, 5th edition. New York: W. H. Freeman;
(2004).
Barnum, S., Biotechnology, Wadsworth – Thomson
Publishing Co. (1998).
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