Sequence Variation

Question 1

What’s Synonymous base substitution?

What are the 2 types of Nonsynonymous base substitution?

What’s Insertion and Deletion?

What’s happens if an insertion or deletion is in a multiple of 3 or not?

Answer 1

• Silent mutation where a single base change doesn’t change the amino acid, due to degeneracy
• • Missense - single substitution changes the amino acid
  • Nonsense - single substitution makes it into a stop codon, which prematurely stops translation (Shortened protein)
• ≥1 bases, which can change the whole sequence = loss/gain of amino acids
• • If a multiple of 3, its IN-FRAME
  • If it isn’t, it’s FRAMSHIFT

Question 2

How can mutation cause loss of function?

How does this relate to certain conditions?

Answer 2

• • Reduced activity/stability = Hypomorph
  • Complete loss of the protein = Amorph (Null allele)
• • In Sickle cell anaemia and CF, which are recessive, 1 healthy copy of gene is enough to produce a healthy amount of protein
  • In Haploinsufficiency, which is dominant, loss of 1 allele is enough to cause a problem due to a lack of protein

Question 3

How can mutation cause gain of function?

How does this relate to certain conditions?

What is a dominant negative?

Answer 3

• ↑Gene expression, New function for protein
• In Achondroplasia (dominant), a mutant allele produces a damaging mutant protein
• Mutant allele produce protein that interferes with the intended, correct role

Question 4

Germline vs Somatic mutation?

Answer 4

Germline - mutation in every body cell - Can be passed down

Somatic - only affects non-germline cells -Can’t be passed down