Genetic Variation

Question 1

What are the 5 types of single-gene mutations?

Answer 1

1. Base-pair substitutions
2. Insertions and deletions
3. Duplications
4. Control and structural types
5. Unusual types

Question 2

Describe base-pair substitution mutations. What are the three basic types?

Answer 2

This type of mutation is a chance in one base pair.

1. Silent mutation - occurs in the third (wobble) position resulting in no change in amino acids
2. Missense mutation - changes in codon from one amino acid to another
3. Nonsense - changes in codon results in a stop codon and premaure truncation of the protein

Question 3

Describe insertion or deletion as a single-gene mutation.

What is a frameshift mutation? What is likely a result of this?

Answer 3

This results in bases added to or removed from the sequence.

Large ones can disrupt more than one gene, and small ones can change the sequence.

When a number of bases is added or deleted, that is not a multiple of three, this results in a frameshift mutation. This changes the “reading frame” which results in a completely different amino acid. Premature truncation is likely.

Question 4

When non-coding DNA has mutations what could be effected that would effect mRNA expression?

What could be effected that effects processing and protein sequence?

Answer 4

mRNA expression could be effected by changes to promoters, enhancers, and silencers.

mRNA processing and sequence could be effected by changes to splice sites.

Question 5

What do most splice sites start and end with?

Answer 5

Introns typically start with GT and end with AG

Question 6

What could result from splice site mutations?

Answer 6

Cryptic sites can become functional, exon skipping can occur.

The donor or acceptor can mutate

Question 7

What are three types of other mutations?

Answer 7

1. Duplications
2. Transposons
3. Expanded repeats

Question 8

Describe duplication mutations.

Answer 8

Large regions of DNA, sometimes whole genes duplicated.

Can effect gene function and gene dosage

Question 9

Describe transposon mutation.

Answer 9

Transposons are mobile genetic elements that can insert in or near a gene which alters expression

Question 10

Describe expanded repeats as mutations

Answer 10

Expanded repeats consist of trinucleotides, a run of one amino acid.

When this number increases to a certain threshold this can disrupt function.

Question 11

What are the different ways that mutations effect function of genes?

Answer 11

1. Loss of function - protein has no activity
2. Gain of function - protein has new or greater activity

Question 12

What is a polymorphism?

Give an example.

Answer 12

A gene with mutliple forms with frequency >1% and no deleterious effects.

Blood groups are a good example. ABO system and Rh system

Question 13

What are the different types of hemoglobin mutations and examples?

Answer 13

1. Structural mutations - change in proteins
   ex: Sickle cell anemia (glutamate 6->valine)
2. Control of expression
   ex: thalassemias, or persistence of fetal hemoglobin

Question 14

Describe thalassemias? What type of mutation is this? Which cell does it attack? What are clinical presentations?

Answer 14

Thalassemias are a hemoglobin mutation effecting control of expression. This results in a defect of either alpha- or beta-globin. With excess of one type of globin tetramers form of the other subunit. Precipitation causes damage to RBCs which then have shorter lifespans. This causes anemia and often splenomegaly.

Question 15

What are three types of mutagens that can cause mutation? What is the molecular mutation caused by this?

Answer 15

1. Ionizing radiation - creating reactive radicals

this reacts with bases causing double-stranded breaks

2. Nonionizing radiation - shift of electrons causing reactions

Ex: pyrimidine dimers formed by UV

3. Chemicals - base analogs insert, react, change

Deamination reactions convert C to U

Question 16

What are three factors that influence the rate of mutation of a gene?

Answer 16

1. Size (larger size, larger target)
2. Age at reproduction (longer time, more mutation)
3. “hot spots” (CpG dimers)

Question 17

Explain CpG dimer “hot spots”

Answer 17

An area of human DNA that is especially prone to mutation. This is because CpG dimers are typically methylated. If a methylated C is deaminated this becomes a T. Then through mismatched repair the opposite strand is converted to an A to match

Question 18

What is the major role of DNA repair?

Answer 18

to prevent mutation

Question 19

What is an example of a mutation that effects more than one base?

Answer 19

Pyrimidine dimers

Question 20

Describe xeroderma pigmentosum. What defect causes this? What are these individuals sensitive to?

Answer 20

Mutations in skin cells with photosensitivity. Disorders of DNA repair in which the nucleotide excision repair is inhibited. Unable to repair pyrimidine dimers.