## Sickle cell aneamia

Sickle cell anaemia is a disease that is caused by a substitution mutation in the DNA sequence which results in a change to the morphology (shape) of red blood cells. Haemoglobin is a molecule in the red blood cell that is required to bind oxygen to deliver it around the body. A healthy human produces haemoglobin A, which is composed of two α- and two β-subunits, with each subunit encoded by a different gene. The essence of this disease is the substitution of a single nucleotide in the gene for haemoglobin A, resulting in sickle-shaped red blood cells containing haemoglobin S instead of red blood cells with the classic sponge shape containing haemoglobin A. These two haemoglobins differ at the DNA level only by a single substitution of thymine for adenine, which results in the original amino acid, glutamic acid, being replaced by valine, consequently haemoglobin A is changed to haemoglobin S (Figure 5.5). The consequence of this change is the altered properties of the sickle-shaped blood cells. Normal shaped red blood cells are able to move through even the smallest blood vessels, whereas in sickle cell anaemia the cells change shape, becoming crescent, or sickle, shaped. Sickle cells block the blood vessels and prevent oxygen from reaching the organs and tissues. Sickle cell anaemia is a recessive disease, meaning that two mutant alleles of the same gene are required for symptomatic expression. In recessive homozygotes, i.e., individuals carrying both mutant versions of the gene, severe haemolytic anaemia (a low number of red blood cells) with frequent mortality develops by the age of 20. In heterozygotes (individuals carrying one normal and one mutant copy of the gene), the symptoms of the disease are less severe and manifest mainly in stressful situations, resulting in a reduced quality of life.