Module 9 - Effects of DNA mutation

Question 1

Point mutations

Answer 1

One base is replaced by another: can be either transition (purine-purine or pyrimidine-pyrimidine) or transversion (purine-pyrimidine)

This can occur due to base analogues or tautomers

Question 2

Insertion mutation

Answer 2

Occurs as nucleotdies are inseted into the nucleotide sequences

This can occur due to intercalating agents (ethidium bromide)

Question 3

Deletion mutations

Answer 3

The deletion of a base pair

Question 4

Inversion mutations

Answer 4

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

Question 5

Synonymous mutations

Answer 5

Have no effect on the amino acid sequence (UUA and UUG both produce leucine)

Also called a silent mutation

Question 6

Non-synonymous mutations

Answer 6

Changes the amino acid sequence

Also called a missense mutation

Question 7

Nonsense mutations

Answer 7

Changes a codon for an amino acid into a stop sequence

Question 8

Readthrough mutations

Answer 8

Changes a stop sequence into an amino acid sequence

Question 9

Frameshift mutations

Answer 9

Shifts the reading frame which causes multiple changes to successive amino acids

Question 10

Suppressive mutations

Answer 10

In second site reversion, a second mutation restores the correct amino acid sequence, though the nucleotide sequence is still altered

Question 11

Monogenic disorders

Answer 11

Caused by defects in a single gene, roughly 6,000 of them

Most common - inherited breast cancer
Second most common - cystic fibrosis (~1/2500 born with CF each year in the UK)

Question 12

CFTR gene

Answer 12

Cystic fibrosis transmembrane regulator genes

CFTR protein is a chloride channel on the cell surface and is responsible for the proper balance of salt and water within a cell and outside the cell

If this gene is mutated and dysfunctional, the water and salt balance is messed up and thick mucous is produced and excessive salt is lost during perspiration

Question 13

The most common form of cystic fibrosis mutation

Answer 13

Due to the deletion of three nucleotides which removes a codon for phenylalanine (F), the 508th/1480 amino acid in the polypeptide.

This causes the polypeptide to be made but not into the surface of the membrane.

Called ΔF508 or F508del, causes 68% of cases

Question 14

The second most common form of cystic fibrosis mutation

Answer 14

Changes a glycine (G) at position 542 into a stop codon (X)

Nonsense mutation, forming G542X

2.5% of cases

Question 15

The third most common form of cystic fibrosis mutation

Answer 15

Changes a glycine (G) at position 551 to an aspartic acid (D)

Non-synonymous point mutation (Missense mutation), forming G551D

1.5% of cases

Question 16

Orkambi

Answer 16

Made up of Ivacaftor and Lumacaftor.

Has been shown to be effective in people with cystic fibrosis with the F508del mutation.

Question 17

Lumacaftor

Answer 17

Improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature CFTR protein to the cell surface

Question 18

Ivacaftor

Answer 18

CFTR potentiator that facilitates increased chloride ion transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface

Question 19

haploinsufficiency

Answer 19

Occurs when only one copy of a gene is functional, causing too little protein to be produced

Question 20

Alagille syndrome

Answer 20

An example of haploinsufficiency

It results in heart abnormalities and liver problems from abnormal bile ducts

the gene codes for the CD339 (JAG1) protein which is involved in cell-to-cell signaling during embryo development

Question 21

How being a carrier may affect the possible effect of a disease?

Answer 21

With some human genes, being a carrier gives a predisposition to disease:

Retinoblastoma, retinal cancer, is an example:
Sporadic retinoblastoma is rare and randomly occurs throughout the population; however, familial retinoblastoma is more common in affected families

If someone in the family has only one functional copy of the retinal tumour-resistant gene

Question 22

Trisomy

Answer 22

Caused by having three copies of a chromosome

Question 23

Monosomy

Answer 23

Caused by having one copy of a chromosome

Trisomy 7 - bone marrow underdeveloped: high chance of leukaemia

Question 24

Chromosome translocation

Answer 24

Occurs as part of one chromosome moves to another chromosome

A common form - chromosome 22 and chromosome 9 exchange segments (this can cause leukaemia)

Question 25

The Philadelphia chromosome: how it causes leukaemia?

Answer 25

The abl gene stimulates cell division after being switched on by a second messenger after it is activated by extracellular signals

If the second messenger is translocated to another chromosome, then the abl gene is not regulated and it is constantly activated and cell replication is continuous