In a normal person,
- RBCs contain Hb molecules.
- One Hb molecule contains 4 polypeptide chains.
- 2 alpha & 2 beta chains.
- A particular gene is responsible for the formation of 2 beta chains.
- It is situated on the short limb of 11th chromosome.
- In a particular beta chain, 6th amino acid is the hydrophilic glutamic acid.
- Glutamic acid is responsible for the polarization of a particular oxygen molecule to bind with the Hb molecule.
- The bound oxygen molecule is then transported in the RBC to supply the body cells.
In an anaemic patient,
- Beta globin gene is affected (point mutation).
- It is responsible for the formation of affected beta chains.
- Normal 2 alpha chains & 1 beta chain combine with the affected beta chain to form an abnormal Hb molecule called sickle cell haemoglobin (Hbs).
- So, 6th amino acid of the affected beta chain is not the glutamic acid but hydrophobic amino acid called valine.
- The oxygen molecules cant bind with the valine.
- Then the total number of oxygen molecules that can bind with a Hb molecule become less.
- So, the body cells prone to ischemia.
- In low oxygen concentrations (ex – high altitude), absence of the polar amino acid at the 6th position of beta chain promotes non covalent polymerization of Hb molecules.
- Hb molecules become aggregated.
- Aggregated Hb molecules become precipitated.
- Due to the precipitate, RBCs loss their membrane elasticity.
- RBCs distort their shape due to loss of membrane elasticity.
- This process is called sickling.
- Sickle cells are rapidly removed from the circulation because they are non reversible with high oxygen concentrations.
- Autosomal recessive disease.
- Inherited by consanguineous marriages.
- Both males & females are affected.
- The trait is shown when both genes are recessive (homozygous).
- Heterozygous females are carries.
- They do not show the disease (asymptomatic).
- But they transmit this gene to their children.
- There is a 1-in-4 chance of their child developing the disease & 1-in-2 chance of their child is being just a carrier.
- Heterozygous individuals are moderately resistant to the malarial infection.
- Severe anaemia