Deck 11: The Molecular Basis of Genetic Disease

Question 1

The hemoglobin E (HbE) allele of b globin, which is associated with reduced production of the b-globin chain, occurs at a very high frequency in which region?

A) Europe
B) South America
C) Sub-Saharan Africa
D) The Middle East
E) Southeast Asia

Answer 1

Southeast Asia

Question 2

Which of the following types of mutations can cause a loss of function to the protein?

A) Missense
B) Nonsense
C) Frameshift
D) Splice site
E) Any of the above

Answer 2

Any of the above

Question 3

Why can a-globin mutations have an effect earlier in life than b-globin mutations?

A) There are fewer $\alpha$ -globin genes
B) The $\beta$ -like globin hemoglobin F (HbF) is produced during fetal development and $\beta$ globin predominates only after birth
C) Fewer $\alpha$ globins are in each hemoglobin molecule
D) More $\alpha$ globins are in each hemoglobin molecule
E) Mutations in the $\alpha$ -globin genes prevent proper developmental expression of other globin genes

Answer 3

The $\beta$ -like globin hemoglobin F (HbF) is produced during fetal development and $\beta$ globin predominates only after birth

Question 4

Which clinical phenotype is associated with an imbalance in the production of the a- and b-globin chains?

A) Hemophilia
B) Hemolytic anemia
C) Sickle cell anemia
D) Thalassemia
E) Polycythemia

Question 5

At which stage can a mutation disrupt the normal production of a protein?

A) Translation of polypeptide
B) Protein folding
C) Posttranslational modification
D) Subcellular localization
E) Any of the above

Question 6

Which of the following is the most common effect of a disease causing mutation on a protein?

A) Loss of function
B) Gain of function
C) Heterochronic expression
D) Ectopic expression
E) Dominant negative

Question 7

Why is hydrops fetalis largely restricted to Southeast Asia?

A) Dietary differences between populations affect expressivity of the phenotype
B) The type of malaria present in this area
C) Two α-globin alleles are commonly deleted in cis in this population
D) ( $\alpha$ -)Thalassemia carrier status is most common in this population
E) A compensating hemoglobinopathy is less common in this population

Question 8

Which clinical phenotype is associated with a b-chain mutation that locks the hemoglobin into the relaxed state, which has a high affinity for oxygen?

A) Hemophilia
B) Hemolytic anemia
C) Sickle cell anemia
D) Thalassemia
E) Polycythemia

Question 9

What is the effect of deletion of the locus control region for the b-globin gene cluster?

A) Loss of fetal hemoglobin expression
B) Reduced expression of hemoglobin
C) Absent expression of all of the hemoglobin genes in the cluster
D) Overexpression of all of the hemoglobin genes in the cluster
E) Inappropriate expression of fetal and embryonic hemoglobin after birth

Question 10

In addition to mutations in a globin, a thalassemia can result from mutations in which of the following genes?

A) ( $\beta$ ) globin
B) ( $\gamma$ ) globin
C) (XIST)
D) (ATRX)
E) A or B

Question 11

Four sites associated with what type of DNA conformation are important for the regulatory control of b globin expression by the locus control region (LCR)?

A) Open chromatin conformation
B) Closed chromatin conformation
C) DNA hairpin
D) DNA break
E) DNA loop

Question 12

A transition between which two hemoglobin molecules occurs around the time of birth?

A) ( $\alpha$ to $\beta$ )
B) ( $\alpha$ to $\gamma$ )
C) ( $\beta$ to $\gamma$ )
D) ( $\gamma$ to $\beta$ )
E) ( $\varepsilon$ to $\gamma$ )