Mutation

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Mutation

• Point Mutations
• Spontaneous
• Depurination
• Deamination
• Oxidatitive damage
• Replication errors
• Trinucleotide repeat expansion and human disease
• Induced
• Base analogs
• Base modifiers
• Base damagers (DNA damage)
• Ames Test for Mutagens (because some mutagens
  carcinogens)

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Spontaneous MutationsDepurination
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Depurination Mutagenesis by SOS-mediated repair
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Spontaneous DeaminationCytosine to Thymine
5 methyl Cs Are hot spots For mutations
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Spontaneous MutationsOxidative damage
G-C to T-A transversions
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Spontaneous Replication Errors Amino to Imino
Cytosine
G-C to A-T and A-T to G-C transitions
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Spontaneous Replication ErrorsKeto to Enol
Thymine
A-T to G-C and G-C to A-T transitions
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Spontaneous Replication ErrorsAmino to Imino
Adenine
A-T to G-C and G-C to A-T transitions
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Spontaneous Replication ErrorsKeto to Enol
Guanine
G-C to A-T and A-T to G-C transitions
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Spontaneous INDEL Mutations insertion or
deletion of one to a few bps
Slippage and mispairing in repeat-rich
sequences hot spots for indel mutations
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Trinucleotide Repeat ExpansionsFragile-X
syndrome
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Induced MutationsBase Analogs 5 BU (5BrdU)
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Induced MutationsBase Analogs 2-AP(2
aminopurine)
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Induced Mutations Base Modifiers EMS and
NG(ethylmethansulfonate and nitrosoquanidine)
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Induced Mutations Intercalating
Drugs(intercalating dyes)
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Induced MutationsUV Light
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Experimental Test for Mutagensthe Ames Test
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Induced MutationsAFB1 and G-C to T-A
transversions
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Example Results of the Ames Test
TA100 requires a missense TA1538 requires a
frame shift
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Summary of Spontaneous and Induced Mutations

• Imino C pairs with A G-C to A-T transition
• A-T to G-C
• Enol T pairs with G A-T to G-C
• G-C to A-T
• Imino A pairs with C A-T to G-C
• G-C to A-T
• Enol G pairs with T G-C to A-T
• A-T to G-C
• Ionized 5 BU pairs with G A-T to G-C
• G-C to A-T
• Protonated 2-AP pairs with C A-T to G-C
• G-C to A-T
• 0-6 ethyl guanine pairs with T G-C to A-T
• Aflatoxin-mediated depurination of G G-C to T-A
  transversion