Sickle cell anaemia

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



Sickle cell is a genetic disorder caused by a missense mutation in the amino acid sequence coding for the haemoglobin gene in red blood cells [1]. The haemoglobin molecule is a tetramer with two alpha subunits and two beta subunits. The mutation occurs in the beta subunit when a valine(V) replaces glutamate(E) in position 6 of the beta subunit, the replacement is referred to as Glu6Val [2].In those who show symptonms of sickle cell anaemia, on the beta globin chain in the sixth amino acid position the base A, which is the second codon for the amino acid, is swapped with a T during transcription of the DNA duplex, causing an A-T —> T -A transgression. This causes a change in the amino acid coded for and hence known as a glu6val or E6V mutation. [3] The mutation occurs on the p arm of chromosome 11 which is an autosome and as mentioned effects the beta subunit.[4] phenylalanine 85 and leucine 88 - which are both non-polar hydrophobic amino acids on the gene - form a socket in which the valine side chain can fuse. This is possible because valine is also hydrophobic unlike glutamate and so form sticky ends with the hydrophobic leucine and phenylalanine, thus resulting in a polymerisation of the molecule which alters the tetramer structure of haemoglobin. The mutation is known as HbS, the normal haemoglobin is referred to as HbA.

Effects of the HbS Mutation

When red blood cells with the wildtype form of the gene (HbA) are subjected to low oxygen concentration the haemoglobin in the cell remains fully functional. However, in cells with the HbS mutation the haemoglobin polymerizes in environments where oxygen concentration is low. The haemoglobin polymers are responsible for the change in red blood cell shape; the cells become long, sickle shaped and fragile. The sickle cells do not deliver oxygen to tissues with the same efficiency as normal blood cells, and they often get caught in small blood vessels leading to blockages. This causes extreme pain and leads to damage of major organs such as the brain, heart, kidneys and muscles [5]. Due to the stress placed on the heart to move the sickled cells around the body, it is often seen that people with sickle cell disease have issues with hypertension. It can result in death and is present in one third of adults with sickle cell disease. [6]As a result of the rapid breakdown of red blood cells, a jaundice like yellowing of the eyes and skin can occur. [7]The solubility of deoxyhaemoglobin also decreases. [8] 


Sickle cell is a recessive autosomal disorder, therefore two defected genes are needed (SS) for sickle cell anaemia. If one parent was 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, a form of heterozygous advantage. 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.[9] This means that in a carrier 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, so 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. It has been predicted that those who have sickle-cell trait may have a 20% increase in fitness over those in the population without sickle-cell trait in areas where malaria is common[10]. HbS is hence thought to be reccessive for SCD, but dominant for Malaria resistance [11]. 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 Hballele favouring the survival of its carriers [12].


  1. Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195
  2. • Page 524, Hartl, D. L. and Ruvolo, M., 2012, Genetics: Analysis Of Genes And Genomes, Eighth Edition, Burlington: Jones and ; Bartlett Learning
  3. Ruvolo, D.H. and M., 2011. Genetics 8E: Analysis of Genes and Genomes Intl Version, Jones and Bartlett Learning, LLC. page 520-525
  4. U.S National Library of medicine, 2009
  5. Essentials of Genetics 6th Edition. William S. Klug, Michael R. Cummings, Charlotte A. Spencer. Peterson International Edition, pg 7
  8. Berg,M.J., Tymoczko, J.L. and Stryer L. (2012) Biochemistry. 7th ed. p.216.
  9. Bruce Alberts et al.,(2009) Essential Cell Biology, 3rd edition, Newyork:Garlands Science
  10. Gelehrter, T. D., Collins, F. S. and Ginsburg, D., 1998. Principles of Medical Genetics. p.51
  11. Daniel L.Hartl and Elizabeht W.Jones (2009) Genetics: Analysis of Genes and Genomes,p.513-515
  12. Biochemistry 6th edition Jeremy M. Berg, John L Tymoczko, Lubert Stryer pg 195-196
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