Abstract Genetic diseases can result from several environmental factors; however, they primarily result from inherited genes. Genetic diseases are known to occur as a result of an abnormality in an inherited gene. Sickle cell anaemia is one of the most common genetic diseases. This report discusses its pathogenesis and presents classical methods available for its diagnosis. The classical methods identified in this report are haemoglobin electrophoresis, isoelectric focusing, and high-performance liquid chromatography. Finally, the document discusses DNA-based methods used in sickle cell anaemia. The two methods presented in this report are Restriction Fragment Length Polymorphisms and Polymerase Chain Reaction. Introduction Any disease that occurs as a result of an abnormality in one’s genome is classified as a genetic disease. Genetic diseases are acquired through heredity, or gene mutation. Sickle cell anemia is one such genetic disease caused by genetic inheritance 1 . Sickle cell anemia is inherited as an autosomal recessive condition meaning that the gene that contains the disorder can be passed from the parent to either male or female child. However, both parents must have sickle cell genes for the inheriting child to have two sickle cell genes 2. The disease results from mutations that take place in the DNA sequence of a single gene and is therefore classified as a monogenetic disorder. Thus, it is a disorder of the blood and occurs as a result of inherited abnormal hemoglobin. The analogous nature of hemoglobin may cause red blood cells to rip apart. This leads to a reduction in the number of red blood cells as hemolysis continues, resulting into anaemia. The disease is the most widespread among the inherited blood anaemias and majorly affects Africans and African Americans. Pathogenesis of sickle cell anaemia The β-globin chain of hemoglobin undergoes the process of mutation and this causes the replacement of valine, a type of a hydrophobic amino acid, by hydrophilic amino acids 3 . The β-globin is located at the diminutive side of chromosome 11 4 . In this case, haemoglobin S (HbS) is formed by an alliance between “2 mutant β-globin subdivisions and 2 wild-type α-globin subdivisions forms” 4 .in case of low oxygen, the nonexistence of a polar amino acid at the sixth position of the β-globin chain increases the polymerisation of non-covalent haemoglobin. This deforms red blood cells into a sickle shape, and as a result, reduces their elasticity. This reduction in red blood cell elasticity is most important in the pathophysiology of sickle-cell anaemia. The elasticity of normal red blood cells facilitates their deformation thereby enabling their passage through capillaries. However, in sickle-cell anaemia, low-oxygen condition enhances red blood cell sickling. Continuous sickling damages the cell membrane. The condition becomes worse since the cells can no longer regain their original shape even when normal oxygen condition is returned. Consequently, the red blood cells attain rigidity which is difficult to deform while passing through thin capillaries. This causes vessel occlusion, as well as, ischaemia. Ischemia is a restriction within the blood supply which leads to dysfunction of tissue or vasoconstriction. A high number of white