Gene Mutations

Question 1

Define mutation

Answer 1

Change in DNA sequence

Question 2

Define gene mutation.

Answer 2

Mutation within a gene affecting nucleotide sequence

Question 3

Distinguish somatic vs germ-line mutations.

Answer 3

Somatic:
-body cells
-not inherited
-can cause cancer

Germ-line:
-gametes
-inherited
-passes to offspring

Question 4

What is a transition?

Answer 4

Purine <-> purine or pyrimidine <-> pyrimidine substitution

Question 5

What is a transversion?

Answer 5

Purine <-> pyrimidine substitution

Question 6

Define silent (synonymous) mutation.

Answer 6

Codon change -> same amino acid (genetic code redundancy)

Question 7

Define missense mutation.

Answer 7

Codon change -> different amino acid

Question 8

Conservative vs non conservative substitution?

Answer 8

Conservative -> similar chemistry -> mild effect

Non conservative -> different chemistry-> likely functional disruption

Question 9

Define nonsense mutation.

Answer 9

Codon -> premature stop codon -> truncated protein

Question 10

Define frame shift mutation.

Answer 10

Insertion/deletion not multiple of 3 -> altered reading frame -> usually nonfunctional protein

Question 11

How do regulatory mutations affect genes?

Answer 11

Occur in promoter/regulatory sites
Alter TF or RNA pol binding
Can decrease, abolish, or enhance transcription

Question 12

Cause of spontaneous mutations?

Answer 12

DNA replication
DNA polymerase slipping
Tautomeric shifts

Question 13

What causes trinucleotide repeat disorders?

Answer 13

DNA Polymerase slippage -> repeat expansion
Example: Huntington’s disease
Normal:~28 CAG
Disease:>36 CAG

Polyglutamine expansion

Question 14

What are tautomeric shifts?

Answer 14

Rare base forms (amino<->imino, keto<->enol)
Incorrect base pairing -> mutation

Question 15

Two types of transposable elements?

Answer 15

1. DNA transposons (use transposase)
2. Retrotransposons (RNA intermediate + reverse transcriptase)

Question 16

How do transposons cause mutation?

Answer 16

Insert into gene -> insertion mutation -> premature termination

Question 17

Examples of induced mutagens?

Answer 17

Base analogs (5-bromouracil)
Alkylating agents (EMS)
Intercalating agents (ethidium bromide)
UV light (thymine dimers)
X-rays / gamma rays

Question 18

How do intercalating agents cause mutation?

Answer 18

Insert between base pairs -> distort helix -> frameshift mutations

Question 19

What is photoreactive repair?

Answer 19

Photolysis cleaves thymine dimers (present in bacteria, not humans)

Question 20

What is base excision repair?

Answer 20

DNA glycosylase removes base
AP endonuclease cuts backbone
DNA polymerase fills gap
DNA ligaments seals

Question 21

What is nucleotide excision repair (NER)?

Answer 21

Removes bulky lesions (e.g. thymine dimers)
Excision of short DNA segment
DNA polymerase + ligase repair

Question 22

What disease is caused by defective NER?

Answer 22

Xeroderma pigmentosum
Extreme UV sensitivity -> skin cancer

Question 23

DNA repair gene mutations linked to cancer?

Answer 23

BRCA2 -> breast cancer
MSG2, MLH1 -> colorectal cancer