This document discusses DNA mutations and mutagenesis. It defines mutation as a heritable alteration in genetic material and describes the main types of mutations: substitutions, deletions, insertions, and frameshift mutations. It also discusses what causes mutations, including spontaneous mutations from replication errors and induced mutations from exposure to mutagens like chemicals, UV radiation, and ionizing radiation. Mutagens can cause changes in DNA structure like thymine dimers or breaks in the phosphodiester backbone. Learning objectives are to understand the definition of mutation, different types of mutations, and common mutagens.

1. DNA Mutations and
Mutagenesis
MPH
1-19-15

2. Learning Objectives
• By the end of this lecture……….we all should
be able to appreciate:
– The definition of mutation
– Chromosome and gene mutations
– Types of Mutagens

3. Mutation
A heritable alteration or change in the genetic
material.

4. Why mutations occur?
• Spontaneously
• Exposure to mutagens

5. Types of Mutation

6. Types of Mutations

7. Substitution

8. Substitution
• A substitution is the replacement of a single nucleotide by
another.
• Most common type of mutation.
• If substitution involves replacement by the same type of
nucleotide
• Two types:
– Transition: (More frequent)
• A pyrimidine for a pyrimidine (C for T or vice versa)
• A purine for a purine (A for G or vice versa);
– Transversion:
• A pyrimidine by a purine
• A purine for a pyramidine

9. Substitution/Point Mutation

10. Deletion
• Loss of one or more nucleotides.
– Small deletions may lead to frame shift
– Larger deletions may result in partial or complete
gene deletions and may arise through unequal
crossover.

11. Insertion

12. Insertion
• An insertion involves the addition of one or more
nucleotides into
• a gene.
• Small insertions may lead to frame shift.
• Tri-nucleotide repeat sequences
Unstable trinucleotide repeats may be within coding or
non-coding regions of genes and hence vary in their
pathogenic mechanisms

13. Frameshift Mutation

14. Chromosomal Rearrangements

15. Trinucleotide Repeats

16. Trinucleotide repeats

17. Polymorphisms
Sequence variants with no obvious effect upon
phenotype may be termed polymorphisms.

18. Structural Effects of mutations
• Non-synonymous mutations
– Missence
– Nonsence
– Frameshift
• Synonymous mutations

19. Non-synonymous mutations
If a mutation leads to an alteration in the
encoded polypeptide, it is known as a non-
synonymous mutation.

20. Missense Mutations
A single base-pair substitution can result in
coding for a different amino acid and the
synthesis of an altered protein, a so-called
missense mutation.

21. Nonsense Mutations
A substitution that leads to the generation of
one of the stop codons will result in
premature termination of translation of a
peptide chain, or what is termed a
nonsense mutation.

22. Frameshift mutations
If a mutation involves the insertion or deletion
of nucleotides that are not a multiple of
three, it will disrupt the reading frame and
constitute a frameshift mutation.

23. MUTATIONS IN NON-CODING DNA
• In general, mutations in non-coding DNA are
less likely to have a phenotypic effect.
• Exceptions include mutations in promoter
sequences or other regulatory regions that
affect the level of gene expression.
• Mutations in miRNA or siRNA binding sites
within UTRs are also likely to result in disease

24. What causes mutations?
Spontaneous Mutations Mistakes in replication
Induced Mutations Caused by a mutagen
Mutagens
•Chemical
•Physical

25. Radiation can cause mutations

26. Effects of UV Radiation
Thymine dimers
Base pairing on
opposite strand does
not occur
Polymerase skips
during replication
Fortunately
these are
repaired

27. Effect of UV on DNA structure

28. Ionizing radiation
•Any radiation capable of displacing electrons
from atoms or molecules, thereby producing
ions.
•Causes breaks in the phosphodiester
backbone, DNA cannot be replicated unless
repaired
•Some examples are alpha, beta, gamma, and
X-rays
•Causes formation of free radicals, and toxic
oxygen
.