DNA mutations

Question 1

Types of DNA mutations?

Answer 1

Duplication (Of gene or part of gene)
Deletions (Of whole gene or some exons)
Mutations within regulatory sequence
Mis-sense mutation
Non-sense mutation
Splice site mutation
Expansion of tri-nucleotide repeat

Question 2

What is in frame deletion?

Answer 2

A complete codon is removed thus only one amino acid is lost. Less catastrophic. Reading frame isn’t altered. Results in a milder disease - later onset death typically

Question 3

What is out of frame deletion?

Answer 3

A base is lost so frame shifts to the right
Disrupts the protein e.g. duchenne muscular dystrophy. Reading frame is changed.
Can cause quite catastrophic effects - early mortality

Question 4

What is splice site mutation?

Answer 4

Intron is not spliced due to base changes and so enzymes doesn’t recognise splicing site.
Sequence of intron is translated and proteins are synthesised.

Question 5

What is a nonsense mutation?

Answer 5

Changes codon to stop codon, due to out of frame deletion.
Results in - incomplete, non functional protein
eg. Duchenne’s muscular dystrophy.

Question 6

What is mis sense mutation?

Answer 6

Mutation in which single base change, changes codon for different amino acid.
Can result in silent mutation and a non functional protein
eg. Sickle cell disease CAG replaced with CTG.

Question 7

What is expansion of a tri-nucleotide repeat?

Answer 7

Codon is repeated several times, in the beginning of the sequence.
Normal repeat range - 15-20
If no. of repeats is 36+ leads to development of Huntington’s Disease
More no. of repeats leads to earlier onset.

Question 8

What is allelic heterogeneity?

Answer 8

Lots of different variants in one gene e.g. cystic fibrosis

Question 9

What is locus heterogeneity?

Answer 9

Variants in different genes give the same clinical condition e.g. hypertrophic cardiomyopathy

Question 10

Explain dominant variants:

Answer 10

Manifest the disease phenotype in the heterozygous state i.e. the condition occurs if there is one variant and one normal allele

Question 11

Explain recessive variants:

Answer 11

Manifest disease in homozygous state i.e. there have to be variants in both alleles.
The majority of pathogenic variants are recessive.

Question 12

Mechanisms of dominance?

Answer 12

Do we need to know this?