MD1006: Sickle Cell Anaemia essay PDF

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Essay for sickle cell anaemia...

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Hundreds of variants of human hemoglobin are known, with about 95% resulting from a single amino acid substitution. Many show no clinical effects, while others cause serious abnormalities. A well-known example is HbS, which causes sickle cell disease. In HbS, glutamate in the 6th position of the  -chain of HbA (normal adult hemoglobin) has been replaced by valine. (a)

Describe the molecular structural basis of sickle-cell anemia.

Sickle-cell anemia (SCA) arises when someone carries both copies of a recessive gene to produce a mutated form of HbA, Hemoglobin S (HbS). Hb molecules form large fibrous aggregates. These fibers extend across RBCs. This distorts their biconcave shape. They become crescent or sickle-shaped. These distorted cells clog up small capillaries and reduce blood flow, leading to symptoms such as painful swelling in extremities. Poor blood flow leads to increased chances of strokes and bacterial infections.

(1) HbS substitution decreases the solubility of deoxyhaemoglobin. Hbs causes a single amino acid in the β chain of haemoglobin to be replaced. A valine residue in position six on the β chain replaces a glutamate residue. People who suffer with SCA exhibit this mutation on both β chains of the mutated haemoglobin molecule (HbS). The substituent valine residue is found on the surface of the T-state molecule. This nonconservative substitution gives HbS its sticky hydrophobic patch, replacing the polar glutamate residue. The hydrophobic patch reacts with another hydrophobic area formed by Phe 85 and Val 88 on the other β chain. This causes the aforementioned aggregation of large fibers. (2) HbS doesn’t significantly affect the properties of oxyhaemoglobin. Aggregation doesn’t occur when HbS is oxygenated because the molecule changes from the T form to the R form. In the R form, the Phe 85 and Val 88 residues are tucked away inside the oxygenated Hb assembly. The surface valine residue of HbS is benign if it is not exposed to a partner on the other β chain. This means that the properties of oxygenated HbS are similar to oxygenated HbA. (b) Despite being such a life-threatening disease, why is the HbS gene still relatively prevalent in certain regions of the African continent? Give a brief answer (= no more than ten sentences). The HbS gene is still prevalent because heterozygous genotypes (HbA / HbS) have increased immunity to malaria without showing any of the symptoms of sickle cell anaemia (heterozygous advantage)

The heterozygous condition causes the phenotype known as sickle cell trait. These people show some resistance to Plasmodium falciparum, the parasite causing malaria. These parasites live in red blood cells but they cannot live in the sickle-shaped cells. Malaria outbreaks are common in Africa. Those with heterozygous advantage are most likely to survive and reproduce, passing on the recessive gene....