Sickle cell, Biology

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Sickle cell anaemia in man is caused by a defective chain of haemoglobin. The abnormal haemoglobin known as MbS differs from natural haemoglobin (HhA) in one amino acid. A substitutional mutation causes the replacement of glutamic acid by valine in the sixth position from the amino terminal end of the Q chain polypeptide. This is because instead of the triplet GAA or GAG which codes for glutarnic acid in normal chains, the abnormal mRNA has GUA or GUG which codes for valine. IdbS in deoxygenated state precipitates out of solution forming elongate crystals. 'The formation of crystals in turn produces a characteristic deformation of RBCs and the cells acquire a crescent or sickle shape, hence the name sickle cell anaemia. The deformation of red cell weakens the red cell membrane and lyses the cells. The loss of red cells and haemoglobin leads to anaemia and this causes oxygen deficiency to the tissues per unit time. Pt, single substitution, more specifically, replacing the thymine by adenine in the second position of the sixth triplet of the P chain gene triggers a variety of responses that affects several aspects of the pfnysiology of the organism. Individuals who are homozygous (HbSiHbS) for the gene usually die early in life. In heterozygotes some proporrion of red cells lyse periodically but this does not cause any serious harm to the individual and in any case the survival is not affected.


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