Lecture 9 - Mutations, Genetic Diseases and DNA Repair

Question 1

Variations at a locus in two alleles that occur at a frequency greater than that expected from recurring mutations are generally termed:

Answer 1

DNA polymorphisms

Question 2

The ___________ polymorphism refers to differences in alleles at loci containing different numbers of tandemly repeated runs of a simple sequence.

Answer 2

Variable number of tandem repeat (VNTR) polymorphism

*Note: includes microsatellite and minisatellite DNA polymorphisms

Question 3

In which type of mutation is the protein missing part or all of an exon sequence?

Answer 3

RNA splicing mutation

Question 4

Sickle cell anemia results from what type of mutation?

Answer 4

Missense mutation (Glu -> Val)

Question 5

What are two types of mutations caused by splicing errors?

Answer 5

1. Alteration of conserved splice signals

2. Direct activation of cryptic splice sites

Question 6

Mutations that alter conserved splice signals - at splice donor or splice acceptor sequences - can have what two results?

Answer 6

1. Intron retention (where there is failure of splicing; intron not excised)
2. Exon skipping (where spliceosome brings together splice donor and acceptor sites of nonneighboring exons)

Question 7

A mutation can ______________ by changing its sequence so that it becomes more like the consensus splice donor or acceptor sequence.

Answer 7

directly activate a cryptic splice site

Question 8

Xeroderma Pigmentosum is an inherited disease that leads to a phenotype of skin cancer, photosensitivity, and neurological abnormalities. What DNA repair process is affected (and defected) in XP?

Answer 8

nucleotide excision repair

Question 9

The BRCA-2 mutation is associated with a phenotype of breast and ovarian cancer. What process is affected in this mutation?

Answer 9

homologous recombination repair

Question 10

What are 4 primary sources of mutations?

Answer 10

1. Spontaneous alteration of nucleotides
2. Chemical modifications of bases
3. Radiation damage
4. Polymerase errors during replication

Question 11

About 3% of C nucleotides in vertebrate DNA are methylated to help control gene expression. When these are accidentally deaminated, what nucleotide do they form?

Answer 11

They form the natural nucleotide T (which would be paired with a G on the opposite strand, forming a mismatched base pair).

Question 12

What are the 4 major mechanisms of DNA repair?

Answer 12

1. Nucleotide excision repair (NER)
2. Base excision repair (BER)
3. Mismatch repair
4. Double-strand DNA break repair

Question 13

Which type of “end-joining” is more difficult to accomplish in double-strand DNA break repair?

Answer 13

Homologous end-joining

Question 14

Which type of “end-joining” is more precise in achieving double-strand DNA break repair?

Answer 14

Homologous end-joining

Question 15

Which is NOT a disease linked to trinucleotide expansions?
A. Huntington's disease
B. Fragile X Syndrome
C. Xeroderma Pigmentosum
D. Myotonic dystrophy
E. Friedreich's ataxia

Answer 15

C. Xeroderma Pigmentosum - this is caused by a defective nucleotide excision repair (NER) process

Question 16

Mutations in the XPD helicase, a component of TFIIH, can result in what phenotype?

Answer 16

Premature aging

Question 17

Which statement about hemoglobin genes and thalassemia is correct?

A. Normal individuals inherit two copies of the a-globin gene, one from each parent.

B. a-thalassemias are sex-linked because the a-chain genes are on the X-chromosome.

C. a-thalassemias vary in severity with the location of the mutation within the a-chain genes.

D. Most a-thalassemias involve deletions of a-chain genes owing to non-homologous crossover.

Answer 17

D.

Question 18

Severe B-thalassemia may not become clinically apparent until a child is several months old because:

A. Newborn oxygen needs are minimal.
B. The gamma to beta-globin switch is not complete until several months after birth.
C. Overexpression of zeta-globin accounts for the missing chain.
D. Elevated hemoglobin A2 compensates for the missing B-globin chain.

Answer 18

B.