Sickle cell anaemia

Sickle cell anaemia is an autosomal recessive disorder, which leads to deformation of the shape of the red blood cells, which then prevent the cells being able to travel through small blood vessels. This then deprives organs and tissues of oxygen. Sufferers experience a lot of pain, referred to as a crisis and the condition can lead to other serious medical problems.

Genetics  

Sickle cell is an genetic disorder caused by a mutation in the amino acid sequence coding for the haemoglobin gene . This mutation is caused by a hydrophobic valine (V) replacing glutamic acid  otherwise known as glutamate (E)in position 6 of the beta haemoglobin chain. Hence sickle cell is denoted as E6V .The new valine lies on the surface of the T-state molecule, this new hydrophobic patch interacts with Leucine in position 8 another hydrophobic patch on the haemoglobin, which initiates aggregation. The aggregates form long fibres which stiffen the normally flexible red blood cells . This leads to distortion of the red blood cells and leads to capillary occlusion, preventing the delivery of oxygen to body tissues. The mutation is known as HbS, the normal haemoglobin is referred to as HbA.

Inheritance   

Sickle cell is a recessive autosomal disorder, therefore two defected genes are needed (SS) for sickle cell anaemia. If one parents were to be a carrier of the gene, (SA), each child would have a 25% chance of inheriting two sickle cell genes, 25% chance of inheriting two normal genes, and 50% chance of becoming a carrier like the parents. 

Sickle-Cell Trait

When people carry both the HbB gene and the mutated HbS gene they are said to have sickle-cell trait. They are relatively unaffected by the symptoms associated with sickle cell anaemia, however they can pass the HbS mutation onto their offspring. The interesting point here is that people with sickle-cell trait are resisitant to malaria. The reason for this higher resistance is because the plasmodium falciparum parasite that is responsible for malaria grows poorly in sickled cells. This means that a proportion of the parasite will affect the sickled cells rather than the normal red blood cells. A high proportion of the parasite attempting to grow in Sickled cells will not survive, hence there will be a lower concentration of P.falciparum to affect the normal cells and this gives the carrier a higher probability of surviving the attack. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance.

The lethal nature of malaria and its prevalance in West Africa goes towards explaining the prevalance of the HbS allele in West African populations (1 in 100 West Africans being Sickle Cell Anaemia sufferers), due to  the presence of the HbS allele favouring the survival of its carriers .