Mod 9- Effects Of DNA Mutations

Question 1

What are the effects of mutations on the information content of a gene?

Answer 1

Mutations can alter the information content by changing the sequence of nucleotides, potentially affecting gene expression and function.

This includes point mutations, insertions, deletions, and other types of mutations.

Question 2

Define point mutation.

Answer 2

One base pair is replaced with another (one base pair changes)

This can be classified into transitions and transversions.

Question 3

What is a transition mutation?

Answer 3

A mutation where a purine is replaced by another purine (A ↔ G) or a pyrimidine is replaced by another pyrimidine (T ↔ C).

Question 4

What is a transversion mutation?

Answer 4

A mutation where a purine is replaced by a pyrimidine or vice versa (A or G ↔ T or C).

Question 5

What occurs during an insertion mutation?

Answer 5

One or more base pairs are inserted into the DNA sequence.

Question 6

What occurs during a deletion mutation?

Answer 6

One or more base pairs are deleted from the DNA sequence.

Question 7

Define inversion mutation.

Answer 7

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

Question 8

What is a synonymous mutation?

Answer 8

A mutation that has no effect on the amino acid sequence, also called a silent mutation.

Silent mutations also include those in intergenic (non-coding) regions

Question 9

What is a non-synonymous mutation?

Answer 9

A mutation that changes the amino acid sequence, also known as a missense mutation.

Question 10

What is a nonsense mutation?

Answer 10

A mutation that changes a codon for an amino acid into a stop codon.

this is detrimental

Question 11

What is a readthrough mutation?

Answer 11

A mutation that changes a stop codon to a codon for an amino acid.

This could change its function

Question 12

What is a frameshift mutation?

Answer 12

A mutation that changes the reading frame, altering all downstream codons.

Question 13

What are suppressive mutations?

Answer 13

Mutations that can reverse the effects of an earlier mutation, such as second site reversion.

In a second site reversion, a second mutation restores the correct amino acid sequence (but the sequence is still altered)

Question 14

What are monogenic disorders?

Answer 14

Inherited diseases caused by defects in individual genes.

Question 15

What is one of the most common monogenic disorders in the UK?

Answer 15

Cystic Fibrosis.

Question 16

What does the cystic fibrosis transmembrane regulator (CFTR) gene do?

Answer 16

It directs the synthesis of the CFTR protein, which is a chloride channel responsible for the proper balance of salt and water within a cell.

Question 17

What is the most common mutation in CFTR among UK patients?

Answer 17

ΔF508 or F508del (68% of cases), which is a deletion of three nucleotides.

Question 18

What does the ΔF508 mutation remove?

Answer 18

A codon for phenylalanine (F), which is the 508th amino acid in the polypeptide.

This means the CFTR protein is still made but doesn’t get to the cell surface/membrane

Question 19

What is the second commonest CFTR mutation?

Answer 19

G542X (2.5% of cases), which is a nonsense mutation that changes glycine (G) at position 542 to a stop codon (X).

This causes the CFTR protein to not be made and the abnormal position of the stop codon causes the mRNA to be degraded

Question 20

What is the third commonest CFTR mutation?

Answer 20

G551D (1.5% of cases), a non-synonymous point mutation (missense mutation) that changes glycine (G) at position 551 to aspartic acid (D).

The CFTR protein is made and gets to the cell surface but works at only 4% of the normal rate

Question 21

What is the treatment for Cystic Fibrosis?

Answer 21

Orkambi = made up of Ivacaftor (opens channel) and Lumacaftor (facilitates processing and trafficking of CFTR to get to cell surface)

Treatment is effective in people with CF who have 2 copies of the F508del mutation

Question 22

What are mutations important for in organisms?

Answer 22

Evolution and diversity of organisms

Some mutations may also cause disease.

Question 23

What are monogenic disorders?

Answer 23

Inherited diseases caused by defects in individual genes.

Question 24

What does phenotype refer to?

Answer 24

Biological characteristics.

Question 25

What does it mean that most organisms are diploid?

Answer 25

They have two copies of each chromosome and gene.

Question 26

What are alleles?

Answer 26

Alternate forms of a gene.

Question 27

What is haploinsufficiency?

Answer 27

A condition where a mutation in just one gene causes disease.

Question 28

What is an example of a disorder caused by haploinsufficiency?

Answer 28

Mandibulofacial Dysostosis Guion Almeida type (MFDGA).

Question 29

What is a common result of large deletion mutations?

Answer 29

Diseases such as deletion of about 500 kb from the X chromosome.

Question 30

What is trisomy?

Answer 30

Three copies of a chromosome.

Question 31

What condition is caused by trisomy of chromosome 21?

Answer 31

Down syndrome.

Question 32

What is monosomy?

Answer 32

Where one chromosome is missing.

Question 33

What does a chromosome translocation involve?

Answer 33

Part of one chromosome becomes attached to another chromosome E.g. the exchange of segments between chromosome 9 and 22

Question 34

What is the Philadelphia chromosome?

Answer 34

- A common cause of leukemia associated with the bcr-abl gene - A normal abl gene codes for the abl protein = stimulates cell division in response to signals from outside the cell - Second messengers controlled by the external signals interact to switch on the abl gene when the abl protein is needed - When mutated, the control region is lost so second messengers have no effect - Gene is switched on all the time - Cell division is uncontrolled

Question 35

What happens when the bcr-abl gene is switched on all the time?

Answer 35

Cell division becomes uncontrolled.

Question 36

True or False: Not all human mutations are harmful.

Answer 36

True.

Question 37

What is the Apolipoprotein A-I 'Milano' variant associated with?

Answer 37

R173C missense mutation Low prevalence of cardiovascular disease in carriers of this mutation

Question 38

What mutation is associated with high bone density?

Answer 38

- G171V missense mutation in LDL-Receptor–Related Protein 5 (LRP5) - Associated with high bone density and less broken bones in carriers of this mutation - LRP5 regulates Wnt signalling which is an essential pathway for bone development

Question 39

What is the relationship between red hair and pain sensitivity?

Answer 39

Individuals with red hair often require more anaesthesia due to a loss of MC1R function.

Question 40

What is a characteristic of natural short sleepers?

Answer 40

Lifelong short sleep with no obvious adverse outcomes.

Question 41

What mutation is associated with natural short sleep?

Answer 41

Missense mutation in DEC2 (DEC2-P384R) Mutant DEC2 causes increased expression of the wake promoting peptide Orexin

Question 42

Effects of mutations on the cystic fibrosis gene

Answer 42

Mutation in CFTR causes a dysfunction of the salt and water balance leading to thick mucous and excessive loss of salt in the sweat

Question 43

What is MFDGA?

Answer 43

- a craniofacial disorder caused by haploinsufficiency of RNA splicing factor EFTUD2 - part of U5 snRNP = defective RNA splicing of pre-mRNAs required for development

Question 44

Example of where being a carrier gives a predisposition to a disease

Answer 44

- Retinoblastoma = cancer of the retina - Sporadic retinoblastoma is rare and occurs throughout the population - Familial retinoblastoma is more common in affected families - RB is a tumour suppressor gene

Question 45

Example of monsomy

Answer 45

Monosomy 7 = one copy of chromosome 7 missing Leads to bone marrow failure and high risk of leukemia