Effects of Mutations I - Lecture 19

Question 1

What are point mutations?

Answer 1

One base pair is replaced with another

Question 2

What is a transition point mutation?

Answer 2

○ Purine to purine (A <-> G)
○ Pyrimidine to pyrimidine (C <-> T)

Question 3

What is a transversion point mutation?

Answer 3

○ Purine to pyrimidine or vice versa
○ (A or G <-> T or C)

Question 4

What is an insertion mutation?

Answer 4

One or more base pairs are inserted

Question 5

What is a deletion mutation?

Answer 5

One or more base pairs are deleted

Question 6

What is an inversion mutation?

Answer 6

Two or more base pairs are excised and reinserted in the opposite orientation

Question 7

What are the different effects of point mutations?

Answer 7

○ Synonymous mutations (silent mutation) - no effect on the amino acid sequence
○ Non-synonymous mutations (missense mutation) - changes the amino acid sequence
○ Nonsense mutation - changes a codon for an amino acid into a stop codon
○ Readthrough mutation - changes a stop codon to a codon for an amino acid

Question 8

What are the effects of insertion and deletion mutations?

Answer 8

○ Frameshift mutations - changes the reading frame:
- Insertion = extra amino acids are added
- Deletion = truncated protein

Question 9

What are suppressive mutations?

Answer 9

○ Reverses the effect of a mutation
○ In second site reversion: a second mutation restores the correct amino acid sequence though the nucleotide sequence is still altered

Question 10

What are monogenic disorders?

Answer 10

Inherited genes caused by defects in individual genes

Question 11

What does the CFTR gene do?

Answer 11

Codes for CFTR protein that is a chloride channel which is responsible for proper balance of salt and water within and outside the cell

Question 12

What does a mutation in the CFTR gene cause?

Answer 12

A dysfunction of the salt and water balance leading to thick mucous and excessive loss of salt in the sweat

Question 13

What is the most common mutation that causes cystic fibrosis?

Answer 13

○ Deletion of three nucleotides
○ Removes a codon for phenylalanine which is the 508th amino acid in the polypeptide (ΔF508)
○ CFTR protein is still made but does not get to the cell surface

Question 14

What are the other mutations that can cause cystic fibrosis?

Answer 14

○ Nonsense mutation
○ Non-synonymous point mutation

Question 15

How does a nonsense mutation cause cystic fibrosis?

Answer 15

○ Changes to a glycine at position 542 to a stop codon (G542X)
○ CFTR protein is not made and causes the mRNA to be degraded

Question 16

How does a non-synonymous point mutation cause cystic fibrosis?

Answer 16

○ Changes a glycine at position 551 to an aspartic acid (G551D)
○ CFTR protein is made and get to the cell surface but works at only 4% of the normal rate

Question 17

What is the treatment for cystic fibrosis?

Answer 17

○ Orkambi is made up of Ivacaftor and Lumacrofter
○ Treatment effective in people with two copies of the F508del mutation

Question 18

What does the CFTR Lumacrofter do?

Answer 18

Facilitates the processing and trafficking of CFTR to increase the amount of CFTR at the cell surface

Question 19

What does the CFTR Ivacrofter do?

Answer 19

Potentiates the channel-open probability of CFTR at the cell surface