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Mutations. Categories of Mutations by Type. Deletions Inversions Insertions Duplications Point mutations Change of a single nucleotide in the DNA Nucleotide change – transition or transversion Single nucleotide insertion Single nucleotide deletion. Categories of Mutations by Affect.

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Mutations

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Mutations l.jpg

Mutations


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Categories of Mutations by Type

  • Deletions

  • Inversions

  • Insertions

  • Duplications

  • Point mutations

    • Change of a single nucleotide in the DNA

      • Nucleotide change – transition or transversion

      • Single nucleotide insertion

      • Single nucleotide deletion


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Categories of Mutations by Affect

  • Regulatory

    • Affect production or steady state levels of gene product

      • promoters, splicing sequences, ribosome binding sites

  • Structural (Coding)

    • Affect actual sequence of gene product

      • point mutations within coding sequence

  • Silent

    • a change in DNA sequence that has no detectable affect on gene expression or gene product function

      • SNP – single nucleotide polymorphisms


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Point Mutations in Coding Sequences

Missense – changes amino acid

Nonsense – creates stop codon

Frameshift – alters remainder of reading frame results in completely different amino acid sequence.


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Base Changes

  • Transitions

    • pyrimidine replaces pyrimidine - C to T or T to C

    • purine replaces purine – G to A or A to G

    • GC changed to A=T or vice versa

    • Most common base change

  • Transversion

    • purine replaces pyrimidine or vice versa

    • G to C or T

    • A to C or T

    • C to G or A

    • T to G or A

    • GC changed to CG or T=A

    • Rare


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Tautomeric Shifts Lead to Transitions

Figure 16.10


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Normal

amino-A = keto-T

amino-C  keto-G

Tautomeric

imino-A = amino-C

amino-A = imino-C

enol-T  keto-G

keto-T  enol-G

Tautomeric Base-Pairing


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Tautomeric Shifts Alter Base-Pairing Specificity


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Tautomer

Figure 16.10


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Modification of Bases by Alkylating Agents

EMS – ethylmethane sulfonate

DMS – Dimethyl sulfonate

ENU - Ethylnitrosourea


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Alkylation Leads to Transitions


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Deamination leads to Transitions


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Oxidative DNA Damage Leads to Transversion Mutations

free radicals


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Intercalation Leads to Insertions/Deletions


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Ionizing Radiation

DNA Damage

VIS


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Shortwave UV (UVA) Causes Thymidine Dimers


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X-rays & γ-rays Cause DNA Strand Breaks


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