16. Mutations (a)

Question 1

What is the most common form of sequence variation in the human genome?

Answer 1

Single-base substitutions, aka single nucleotide polymorphisms (SNPs/snips).

Question 2

What is the most common SNP?

Answer 2

C to T changes.

Question 3

What is a mis sense mutation?

Answer 3

One amino acid is substituted by another, normally by a single base change.

Question 4

What is a silent mutation?

Answer 4

A single base substitution which does not substitute the amino acid.

Question 5

What is a nonsense mutation?

Answer 5

An amino acid codon is mutated to a stop codon.

Question 6

What is a frame shift mutation?

Answer 6

The reading frame of the mRNA is altered in some way.

Question 7

What are conservative missense mutations?

Answer 7

A change in amino acids that is tolerated in non-critical regions of proteins.

Question 8

How are premature termination codons created?

Answer 8

By a gain or loss of bases not in multiples of 3 base pairs so there is a frameshift.

Question 9

What Mechanism protects against premature termination codons?

Answer 9

mRNAs with PTCs are degraded by nonsense mediated decay (NMD) so little or no protein is produced.

Question 10

What will happen to a mutation at an intron splice site that means an exon of multiple 3 base pairs is skipped?

Answer 10

The mRNA will be shortened but remain in frame.

Question 11

What will happen to a mutation at an intron splice site that means an exon not of multiple 3 base pairs is skipped?

Answer 11

The mRNA is shortened and will contain a frameshift and a PTC. This leads to NMD.

Question 12

What can cause base changes?

Answer 12

Sequence changes in DNA replication (rare tautomeric forms with altered base-pairing or DNA strand slippage in replication), chemicals (direct alteration of bases or disruption of DNA base stacking) or exposure to radiation (uv light or radioactive substances).

Question 13

What is a tautomeric shift?

Answer 13

When a proton in a base changes position briefly and then moves back. When the proton is in the moved state, some forms behave as an altered template during DNA replication so it bonds to the wrong base.

Question 14

What are the anomalous base-pairing from tautomeric forms?

Answer 14

A=C and G-=T.

Question 15

How can slippage occur during replication?

Answer 15

Either the newly synthesised strand loops out and results in addition of one nucleotide on the new strand. Or the template strand loops out and results in omission of one nucleotide on the new strand.

Question 16

What happens in chemical mutagen base changes?

Answer 16

Nitrous acid replaces amino groups with keto groups, so there is conversion of one base to another, e.g. cytosine to uracil and therefore base pairs with adenine.
Ethyl methane sulphonate (EMS) removes purine rings and apurinic sites can be paired with any base in replication.

Question 17

What is an example of base stacking mutagens?

Answer 17

2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic aromatic amine food mutagen in cooked meats and cigarette smoke condensates. It districts DNA base packing and causes single base deletions at GC base pairs.

Question 18

How does IQ work to cause base mutations?

Answer 18

Intercalation of a molecule of IQ forces the bases further apart on one DNA strange. This leads to misreading by DNA polymerase and deletion of a single base.

Question 19

How can exposure to radiation be reduced?

Answer 19

Avoiding flying and x-Rays, other than that though, it is impossible to avoid radiation as it’s all around us.

Question 20

What are the positive effects of UV light?

Answer 20

Exposure to UVB induces production of vitamin D in the skin.

Question 21

What are the negatives to UV exposure?

Answer 21

Over exposure to UVB causes sunburn and some forms of skin cancer. UVA, UVB and UVC can damage collagen fibres and lead to skin ageing. UVA and UVB destroy vitamin A in skin.

Question 22

What does UV light photons cause, in terms of base pairing?

Answer 22

Cause adjacent thymine bases to base pair with each other. These diners often resolve spontaneously in photo reactivation but not always - basis of UV light damage.

Question 23

What are some DNA repair processes?

Answer 23

Proof reading, polymerase detects the mis paired 3’ base in the newly synthesised strand and corrects these errors 99% of the time.
Nucleotide mismatch repair, enzymes detect mismatched bases in new strand and replace them. A patch of DNA sequence is replaced (not just the mutation).
Excision repair.

Question 24

What can failure of DNA repair mechanisms result in?

Answer 24

Cancer. Certain genes are in charge of encoding mismatch repair enzymes. If they are damaged, mutations aren’t repaired as much and this can lead to cancer.

Question 25

What 6 new characteristics are required in a cell to form tumours?

Answer 25

Divide independently of external growth signals, ignore external anti-growth signals, avoid apoptosis, divide indefinitely, stimulate sustained angiogenesis and invade tissues to establish secondary tumours.

Question 26

What are oncogenes?

Answer 26

Retro viruses that contain genes that can transform cells to a cancerous phenotype.

Question 27

What are human proto-oncogenes?

Answer 27

The human counterpart to the viral oncogenes that perform a range of cell cycle control functions. Key amino acid substitutions activate them into dominantly acting cancer causing oncogenes.

Question 28

What determines the consequences of a mutation?

Answer 28

The type of mutation and its location.