Q11 - Alpha- vs Beta-Thalassemia and AHSP

Theoretical 1 Real exam question - full text reproduced under IBO's CC BY-NC-SA 4.0 license

Protein Structure, Folding & Function Pedigree Analysis & Human Genetic Disorders

Thalassemia, the most common inherited disorder of hemoglobin, is caused by loss or substantial reduction of one of the globin chains. This results in lowered levels of functional hemoglobin and decreased function of red blood cells, which lead to anemia. In alpha-thalassemia, the alpha chain of hemoglobin is not produced in sufficient quantity and consequently, hemoglobin tetramers form that contain only the beta chain. In beta-thalassemia, the beta chain of hemoglobin is not produced in sufficient quantity and the alpha chains form insoluble aggregates that precipitate inside immature red blood cells and prevent differentiation into mature cells. The normal haploid human genome has one beta chain and two alpha chain coding genes. Presence of four alleles for alpha chain compared to two alleles for beta chain in the cells of normal individuals is expected to results in excess amounts of alpha chain and production of alpha aggregates. However, alpha aggregates do not exist in the cells of normal individuals. One mechanism for maintaining alpha chains in soluble form was revealed by the discovery of an 11-kDa protein in red blood cells called alpha-hemoglobin stabilizing protein (AHSP). This protein forms a soluble complex specifically with alpha chain monomers as they are synthesized. The crystal structure of a complex between AHSP and alpha-hemoglobin reveals that AHSP binds to the same face of alpha-globin as does beta-globin and ensures the proper folding of alpha-globin as it is produced. beta-globin displaces AHSP when it is expressed.

Using the information and data, determine which of the statements are true or which are false.

A. Higher incidence of severe beta-thalassemia compared to severe alpha-thalassemia could be explained by difference in copy numbers of alpha and beta genes.

B. alpha-globin/beta-globin ratio is an appropriate marker for screening of beta-thalassemia.

C. alpha-Hemoglobin has a higher affinity for beta-hemoglobin than for AHSP.

D. AHSP deleterious mutations are expected to mimic beta-thalassemia phenotype with respect to alpha- chain aggregation.

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Question reproduced from IBO 2018, Theoretical Paper 1, licensed under CC BY-NC-SA 4.0 - attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)