Lecture 23: DNA Mutation

Question 1

What is a mutation?

Answer 1

Mutation: physical change in the genetic material

• a mutation within a DNA region encoding a protein (gene) may cause an abnormal protein to be produced.
• mutations may cause small or large changes. Large changes impact many proteins
• a mutated protein may have an insignificant to severe effect

Question 2

Mutations are rare, why?

Answer 2

DNA is a very stable molecule:

• DNA helix and supercoiling provide geometric tightness
• normally consists of 2 complementary strands (a mutation can be repaired by proof reading DNA polymerase at the time of replication
• the nucleotide bases lie protected inside the sugar phosphate backbone

Question 3

Mutation effect is rare (location dependant)

Answer 3

Extragenic (not located in a gene) mutations
-don’t effect protein sequence
Intragenic (within a gene) mutations
-may affect the organism (through changed protein sequence)
-may not affect the organism
A) redundancy if code
B) mutation may be in a non-coding region
C) multiple copy or suppressor genes may mask the effect of the mutation.

Question 4

Frequency of mutation:

Answer 4

About one mutation in every million to every billion replicants of a cell

Question 5

Causes of mutations

Answer 5

1. Spontaneous mutations:
   - damage (from an unknown case) may occur at any time in any cell.
   - mutations result when damaged genes are replicated without repair
   - such mutations occur frequently in organisms with short generation times, such as viruses or bacteria
2. Induced mutations:
   - result of exposure to mutagens (agents that increase rate of mutation)
   - can be purposely induced eg X-rays etc
   - natural mutagens eg cosmic rays, UV light
   - human created mutagens (eg asbestos, nuclear fall out)

Question 6

Somatic vs germinal mutations

Answer 6

Somatic mutations:

• mutations in the body cells of an organism excluding those which produce eggs or sperm
• may effect entire developmental process of organism or
• may be localised to a particular region
• somatic mutations may result in unusual cell growth

Germinal:

• mutations in gamete cells
• can be passed to offspring
• may not effect parents but can create genetic disorders in offspring

Question 7

Types of mutations.
Ie
Gross mutations
Point mutations

Answer 7

1. Gross mutations:
   A) change in chromosomal structure:
   -insertion/ deletion (INDEL)
   -duplication of a nucleotide segment
   -inversion (180 degree rearrangement of segment within a chromosome)
   -translocation (movement if a segment to another region)
   B) change in chromosomal number:
   -polyploidy (change in entire chromosome set) more than 2 chromosome sets
   -aneuploidy (change within the chromosome set) ie chromosome addition or deletion. Eg Down syndrome
2. Point mutations:
   -changes made by substituting a single base with another or by adding or deleting one or more adjacent nucleotides
   Eg sickle cell anaemia
   Types of point mutations
   A) transition, b) transversion and c) INDEL

Question 8

Transition point mutation

Answer 8

Mutations involving the substitution of a:

1. Purine with a purine eg A G
2. Pyrimidine with a pyrimidine eg C T

Question 9

Transversion point mutation

Answer 9

Mutations involving the substitution of a: 
1. Purine by a pyrimidine 
A  C or T
G  C or T
2. Pyrimidine by a purine 
C  G or A
T  G or A

Question 10

INDEL Mutation

Answer 10

Insertion-deletion of bases

• may affect a single base (point mutation) up to a large number of bases (even a chromosome)
• the most common mutation that causes severe cystic fibrosis only a single codon
• small effect at DNA level that may have profound effect on the protein (ie frameshift mutation).

Question 11

Expanding genes

Answer 11

Some genes have repeated base sequences and the number of these may increase each generation.
Expanding genes are responsible for increasingly severe cases of
-muscular dystrophy (CTG repeats)
-huntingtons disease
-fragile X syndrome:
-6-50 CGG repeats in an unaffected individual
-50-200 CGG repeats in a carrier
-more than 200 repeats in an affected individual

Question 12

Mutations and their effect on proteins

Answer 12

1. Frameshift mutation: additions or deletions that change the reading frame (ie effect on coding region)
   - may result in devestating mutation since the entire amino acid sequence may change after mutation.
2. Missence mutation: (substitution of a different amino acid for the original) refer to slide 20
3. Nonsense mutation: results in the insertion of a stop codon
4. Silent mutations: don’t change the protein sequence

Question 13

Effect on the phenotype of the cell

Answer 13

Non-lethal mutations: no effect on phenotype
-redundancy of the genetic code reduces the chance that point mutations alter specified amino acids.

Lethal mutations: lead to the death of cell or host