Hemoglobinopathies (2,3,4,5,6)

Question 1

What makes up the structure of haemoglobin?

a. Four alpha globin chains
b. Four alpha and four beta globin chains
c. Two alpha and two beta globin chains
d. Four myoglobin subunits

Answer 1

c. Two alpha and two beta globin chains

Question 2

What is true about myoglobin?

a. It aids oxygen diffusion into the lungs
b. It decreases the solubility of oxygen
c. It has a low affinity for oxygen
d. It demonstrates Michaelis Menten kinetics

Answer 2

d. It demonstrates Michaelis Menten kinetics

Question 3

• Leghemoglobins are the most primitive oxygen binding proteins and found primarily in bacteria.

Answer 3

F

Question 4

• Hemocyanin is a copper containing O2 transporter whilst Hemoerythrin is a O2 transporter lacking heme.

Answer 4

T

Question 5

• The deoxygenated state of haemoglobin is also called the T state whilst the oxygenated form is called the R state.

Answer 5

T

Question 6

What is true about the divergence of globin genes?

a. α and β globin are close together on chromosome 11, suggesting a recent divergence
b. β, γ and δ are less similar to each other than α
c. The most recent divergence occurred between β and δ and they only differ in 10/146 positions
d. α globin was the last globin to diverge

Answer 6

c. The most recent divergence occurred between β and δ and they only differ in 10/146 positions

Question 7

What can somatic cell hybrids not be used for?

a. Gene mapping
b. Inducing totipotency via ES cells
c. Complementation
d. Dominance studies

Answer 7

b. Inducing totipotency via ES cells

Question 8

What is aminopterin?

a. A cancer drug that blocks the de novo DNA synthesis pathway
b. An enzyme that is required to produce DNA via the salvage pathway
c. A substrate for Thymidine Kinase required for DNA synthesis
d. A compound that converts HGPRT+ to HGPRT-

Answer 8

a. A cancer drug that blocks the de novo DNA synthesis pathway

Question 9

• Each globin protein contains one alpha subunit from the alpha gene.

Answer 9

F

Question 10

• The majority of globin protein is α2β2.

Answer 10

T

Question 11

• There are four alpha globin genes in the haploid genome.

Answer 11

F

Question 12

• Mutations to βglobin can be detrimental to the foetus.

Answer 12

F

Question 13

What is not a feature of Heriditary Methemoglobinemia?

a. Suffers are protected from malaria
b. It results in a ferric haem (Fe3+) which won’t reversibly bind O2
c. It can arise due to an AA change in a globin near haem
d. It can be due to a mutation in MetHb reductase

Answer 13

a. Suffers are protected from malaria

Question 14

What is the role of MetHb reductase?

a. It converts Fe2+ to Fe3+ in order to oxygenate tissue
b. It is responsible for a Hb Lepore phenotype
c. It converts Fe3+ to Fe2+ which can bind oxygen
d. It leads to Heriditary Methemoglobinemia when overactive

Answer 14

c. It converts Fe3+ to Fe2+ which can bind oxygen

Question 15

What are the molecular genetics of Sickle Cell Anaemia?

a. A mutation in the LCR leads to the over production of alpha globin
b. A single AA change causes a change from polar glutamic acid to non-polar valine in beta globin
c. A frame shift mutation results in an early stop codon and truncated globin proteins which aggregate
d. A single AA change causes a change from negatively charged glutamic acid to positively charged lysine

Answer 15

b. A single AA change causes a change from polar glutamic acid to non-polar valine in beta globin

Question 16

What is not a consequence of sickle cell anaemia?

a. RBCs accumulate in the liver and the organ becomes enlarged
b. RBCs are destroyed and this results in anaemia
c. RBCs clump together and can result in local blood supply failure
d. Dilation of the heart can lead to heart failure

Answer 16

a. RBCs accumulate in the liver and the organ becomes enlarged

Question 17

In general, what is thalassemia?

a. Chronic deficiency of alpha globin chains
b. An excess of beta globin and alpha globin chains
c. The disease that results when gamma globin production is not replaced by beta globin production in the foetus
d. Quantitative abnormalities of haemoglobin

Answer 17

d. Quantitative abnormalities of haemoglobin

Question 18

What is linkage disequilibrium?

a. The term to describe the high rate of people diagnosed with both sickle cell anaemia and thalassemia
b. Alleles at separate loci associated with each other higher frequency than expected by chance
c. When alleles on the same chromosome are so far apart they do not form an association with each other
d. Linkage between two separate loci grows over time and many generations

Answer 18

b. Alleles at separate loci associated with each other higher frequency than expected by chance

Question 19

What is false about thalassemia?

a. Alpha thalassemia can result in inclusion bodies with β4
b. Beta thalassemia leads to the precipitation of insoluble α4
c. β4 tetramers are absent in those with Alpha thalassemia
d. Beta thalassemia can often result in RBC degradation in the marrow and spleen

Answer 19

c. β4 tetramers are absent in those with Alpha thalassemia

Question 20

• Hb Lepore and anti Lepore arise due to unequal crossover during meiosis.

Answer 20

T

Question 21

• Countries where malaria is prevalent have a low level of sickle cell anaemia.

Answer 21

F

Question 22

• HbS migrates more slowly than HbA during gel electrophoresis as it is missing a charge.

Answer 22

T

Question 23

• People who are homozygous for Sickle Cell Anemia thrive because plasmodium has trouble parasitising their RBCs and they can survive easily as half their cells are non-sickle.

Answer 23

F

Question 24

What is the phenotype of someone with two functional Alpha-genes?

a. Wildtype
b. HbH disease
c. Alpha thalassemia trait
d. Hb Barts Hydrops Fetalis

Answer 24

c. Alpha thalassemia trait

Question 25

What makes up the Beta thalassemia phenotypes?

a. Asymptomatic heterozygotes are thalassemia intermedia
b. β+ and β(0) heterozygotes are thalassemia major
c. Those with one mild allele and concurrent alpha-thal or HPFH are thalassemia minor
d. Those with Thalassemia intermedia have symptoms, but don’t need transfusions

Answer 25

d. Those with Thalassemia intermedia have symptoms, but don’t need transfusions

Question 26

What is false about B+ thal caused by a G to A mutation at position 110?

a. The protein product is normal as 18 bases are added to the coding sequence and 18 is divisible by 3
b. The alternative splicing pathway is favoured 90% of the time
c. The mutation within the intron results in a frame shift mutation in the coding sequence
d. The mutation results in a new splice acceptor site being created within the first intron

Answer 26

a. The protein product is normal as 18 bases are added to the coding sequence and 18 is divisible by 3

Question 27

What is FALSE about Haemoglobin E?

a. The causative mutation is found in the coding sequence of the Beta globin gene
b. A single base change leads to a Glu to Lys substitution and creation of HbE
c. The mutation results in a new donor site which impacts splicing and leads to a short exon 1
d. The mutation occurs within the first intron and leads to an extra splice site in the Beta globin gene

Answer 27

d. The mutation occurs within the first intron and leads to an extra splice site in the Beta globin gene

Question 28

• Deletions are the primary cause of both alpha and beta thalassemia.

Answer 28

F

Question 29

• It is possible to be born with zero functioning alpha genes.

Answer 29

F

Question 30

• Northern blots are more specifc than dot-blot hybridisation.

Answer 30

T

Question 31

• Globin chains are present in β+ and absent in β(0) individuals.

Answer 31

T

Question 32

• β globin mRNA is absent in all β(0) individuals.

Answer 32

F

Question 33

What demonstrates that there are additional regulatory sites for B-thal?

a. The Beta globin gene is turned off in mouse erythroleukemia cells
b. DNAase hypersensitive sites can be identified and correspond to regions of closed chromatin
c. Hybridisation of mouse erythroleukemia cells and human fibroblasts results in human beta globin production
d. Hybridisation of mouse erythroleukemia cells and human fibroblasts leads to the down regulation of all globin genes

Answer 33

c. Hybridisation of mouse erythroleukemia cells and human fibroblasts results in human beta globin production

Question 34

What can happen if the beta globin gene promoter is deleted?

a. Alpha globin will accumulate and the foetus will die
b. Delta globin will be produced in adult tissue
c. Gamma globin synthesis does not cease due to a lack of competition
d. The delta and epsilon globin genes are not spliced out of mRNA transcripts

Answer 34

c. Gamma globin synthesis does not cease due to a lack of competition

Question 35

Which gene expression modifier is matched to its correct description?

a. KLF1 directly activates HDAC
b. HDAC activates BCLIIA which activates HBG
c. KLF 2 and 4 activate HBB expression
d. KLF1 activates HBB expression through BCLIIA

Answer 35

d. KLF1 activates HBB expression through BCLIIA

Question 36

What is false about globin regulation at the level of transcription?

a. MYB and KLF1 regulate each other
b. MicroRNAs can influence gamma and beta expression directly or through MYB
c. MYB is an oncogenic transcription factor
d. BCLIIA is often repressed by the action of microRNAs

Answer 36

d. BCLIIA is often repressed by the action of microRNAs

Question 37

What is not a possible treatment for thalassemia?

a. Molecularly targeting and deleting the gamma globin promoter
b. Recurrent transfusions
c. Gene therapy
d. HDAC inhibitors and short chain fatty acids that inhibit histone demethylation

Answer 37

a. Molecularly targeting and deleting the gamma globin promoter

Question 38

• The type of globin produced is due to competition between promoters.

Answer 38

T

Question 39

• Full expression of a gene is still possible in the absence of the LAR.

Answer 39

F