Deck 13: The Treatment of Genetic Disease

Question 1

What is the effect of RNAi on its target?

A) Increased protein translation
B) Transcriptional inhibition
C) Transcriptional upregulation
D) Degradation of target RNA
E) Stabilization of target RNA

Answer 1

Degradation of target RNA

Question 2

In theory, cell transplantation using embryonic stem cells derived by nuclear transplantation will avoid what complication that is associated with transplantation?

A) Immune rejection of the transplanted tissue
B) Necrosis of tissue in donor before transplant
C) Long hospital stays
D) Need for bone marrow ablation in bone marrow recipients
E) Complicated surgeries

Answer 2

Immune rejection of the transplanted tissue

Question 3

What is the likely explanation when individuals with cystathionine-synthase deficiency do not respond to treatment by cofactor supplementation?

A) They have a dominant negative mutation
B) They have a recessive mutation
C) They lack residual cystathionine synthase activity
D) The level of vitamin supplementation required to stimulate their cystathionine synthase is toxic
E) The cofactor binding site is mutated

Answer 3

They lack residual cystathionine synthase activity

Question 4

Why is Duchenne muscular dystrophy (DMD) a technically difficult disease to treat with gene therapy?

A) The DMD gene is too repetitive
B) It will be difficult to target the vector to enough myocytes to be therapeutic
C) DMD uses multiple promoters in different cell types
D) DMD has complicated alternative splicing patterns
E) B and C

Question 5

The first successful cure of a genetic disease by gene therapy was achieved in a patient with which disorder?

A) Sickle cell disease
B) β thalassemia
C) Krabbe disease
D) Gaucher disease
E) X-linked severe combined immunodeficiency

Question 6

Treatment of familial hypercholesterolemia with cholestyramine results in which of the following?

A) Increased expression of the normal allele of the low-density lipoprotein (LDL) receptor gene
B) Decreased expression of the mutant allele of the LDL receptor gene
C) Binding and sequestration of the mutant LDL receptor
D) Enhanced efficiency of the normal LDL receptor pool
E) Compensatory expression of other lipoprotein receptors

Question 7

What modification lead to increased success of enzyme replacement therapy for Gaucher disease?

A) Removal of phosphate groups to improve targeting to central nervous system
B) Removal of terminal sugars to increase uptake by macrophages
C) Removal of phosphate groups to increase protein half-life
D) Addition of polyethylene glycol to increase protein half-life
E) Addition of terminal sugars to increase uptake by macrophages

Question 8

What is the mechanism of decitabine treatment for sickle cell disease?

A) Incorporation of decitabine into DNA causes γ-globin promoter hypermethylation
B) Incorporation of decitabine into DNA causes γ-globin promoter hypomethylation
C) Incorporation of decitabine into RNA increases γ-globin translation
D) Incorporation of decitabine into RNA decreases γ-globin translation
E) Incorporation of decitabine into HbS increases its function

Question 9

How does curcumin treatment lead to a normalization of chloride transport in mice with the cystic fibrosis transmembrane conductance regulator (CFTR) DF508 mutation?

A) It causes skipping of the mutated codon
B) It is a cofactor for the CFTR protein
C) It prevents retention and degradation of CFTR in the endoplasmic reticulum
D) It prevents transport of the mutant CFTR to the lysosome
E) It inhibits the proteasome

Question 10

Which of the following is a major limitation of retroviruses for use as gene therapy vectors?

A) Small size of inserts they can accommodate
B) Hard to propagate
C) They cannot integrate into host DNA without cell division
D) Vector construction is difficult
E) Likelihood of unregulated virus replication

Question 11

To what source of hematopoietic stem cells are recipients generally more tolerant of histoincompatibility?

A) Unrelated bone marrow
B) Blood transfusion
C) Placental cord blood
D) Bone marrow from a first-degree relative
E) Transfusion of white blood cell component only

Question 12

How might gentamicin be a therapy for individuals with a nonsense mutation in CFTR?

A) It causes misincorporation of an amino acid at the nonsense codon
B) It is a cofactor for the CFTR protein
C) It prevents retention and degradation of CFTR in the endoplasmic reticulum
D) It causes upregulation of the CFTR gene
E) It prevents transport of the mutant CFTR to the lysosome

Question 13

What severe side effect was observed in one gene therapy trial for X-linked severe combined immune deficiency (SCID)?

A) Graft rejection
B) Graft-versus-host disease
C) A malignant lymphoproliferative disorder
D) Worsening of the SCID phenotype
E) Liver failure

Question 14

Current guidelines recommend which dietary guidelines for management of phenylketonuria (PKU)?

A) Complete removal of phenylalanine (Phe) from diet beginning as soon as possible and lasting through childhood
B) Complete removal of Phe from diet beginning as soon as possible and lasting throughout life
C) Low Phe diet beginning as soon as possible and lasting through childhood
D) Low Phe diet beginning as soon as possible and lasting throughout life
E) Low Phe diet beginning as soon as possible and lasting through childhood or when a woman is pregnant

Question 15

Approximately 50% of patients with homocystinuria caused by cystathionine-synthase deficiency respond to treatment with which vitamin, the precursor to this enzyme's cofactor?

A) Vitamin A
B) Vitamin B₆
C) Vitamin B₁₂
D) Vitamin C

Question 16

Polyethylene glycol modification of adenosine deaminase for enzyme replacement therapy has which of the following effects?

A) Enhances the catalytic activity of the enzyme
B) Reduces likelihood of eliciting a neutralizing antibody response to the protein
C) Enhances cofactor binding of the enzyme
D) Stabilizes the protein conformation
E) All of the above

Question 17

New approaches to therapy of sickle cell disease and β thalassemia are aimed at increasing expression of which gene?

A) ( $\beta$ ) globin
B) ( $\alpha$ ) globin
C) Fetal hemoglobin
D) Hemoglobin S (HbS)
E) Hemoglobin E (HbE)

Question 18

Why is insertional inactivation of an essential gene not likely to be an important risk in retroviral-mediated gene therapies?

A) The number of essential genes is fairly low
B) The gene therapy vectors do not lead to insertion of exogenous DNA into the host genome
C) The vectors are engineered to insert the exogenous DNA into introns
D) The likelihood of the same essential gene being inactivated in a significant number of host cells is small
E) The exogenous DNA is designed to be spliced out of the host gene's transcripts and should not interfere with expression of the host genes