Sickle Cell Trait and Inheritance Of Sickle Cell
Sickle cell trait (Sicklemia) describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that allele (homozygous).
Those who are heterozygous for the sickle cell allele produce both normal and abnormal hemoglobin (the two alleles are codominant). Sickle cell disease is a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance hemoglobin in the red blood cells. Sickling and sickle cell disease also confer some resistance to malaria. (Schofield and Grau, 2005).
Parasitisation of red blood cells, so that individuals with sickle cell trait (heterozygotes) have a selective advantage in some environment.
INHERITANCE OF SICKLE CELL DISEASE AND TRAIT
Sickle cell is inherited in the autosomal recessive pattern. Sickle cell conditions are inherit from parents in the same way as blood type, hair colour, and texture, eye colour and other physical traits.
The types of hemoglobin a person makes in the red blood cells depend on the hemoglobin genes are inherited from his parents. If one parent has sickle cell anaemia (SS) and the other has sickle cell trait then there is a 50% chance of their child’s having sickle cell trait. When both parents have sickle cell trait a child has a 25% chance of sickle cell disease. (Chrouser, et al, 2011).
Sickle cell gene mutation arose spontaneously in different geographic areas, as suggested by restriction endonuclease analysis. These variants are known as Cameroon, Senegal, Benin, Bantu and Saudi-Asian. Their clinical importance springs from the fact that some of them are associated with HbF levels, examples, Senegal and Saudi-Asian variants tends to have milder disease. (Piel et al, 2007).
In people heterozygous for HbS (carriers of sickling haemoglobin), the polymerization problems are minor, because the normal allele is able to produce over 50% of the haemoglobin.
In people homozygous for HbS, the presence of long chain polymers of HbS distort the shape of the red blood cell from a smooth doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to break within the capillaries. Carriers have symptoms only if they are derived of oxygen (for example while climbing a mountain) or while severely dehydrated. Under normal circumstances, these painful crises occur about 0.8 times per year per patient.
The sickle cell disease occurs when the glutamic acid is replaced by valine to change its structure and function. Valine is hydrophobic, causing the hermoglobin to collapse in on itself occasionally. When enough haemoglobin collapses in on itslet the red blood cells become sickle shaped.
The gene defect is known as mutation of a single nucleotide (A to T) of the Betaglobin gene, which results in glutamic acid being substituted by valine at position 6. Hemoglobin S with this mutation is referred to as Hbs apposed to the normal adult HbA. The genetic disorder is due to the mutation of a single nucleotide, from a CTC to CAC codon on the template strand which is transcribed into a GUG codon.
This is normally a benign mutation causing no apparent effects on the secondary, tertiary or quaternary structure of haemoglobin in conditions of normal oxygen concentration. The deoxy form of haemoglobin exposes a hydrophobic patch on the protein between the E and F helices. The hydrophosic residues of the valine at position 6 of the beta chain in hemoglobin are able to associate with the hydrophobic patch, causing haemoglobin S molecules to aggregate and form fibrous precipitates.
The allele responsible for sickle cell anaemia is autosomal recessive and can be found on the short arm of chromosome 11. A person that receives the defective gene from both father and mother develops the disease.
A person that receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1:4 change of their child developing the disease and 1:2 chance of their child being just a carrier. Since the gene is incompletely recessive, carriers can produce a few sickle red blood cells not enough to cause symptoms but enough to give resistance to malaria.
This does not confer full immunity to malaria. Heterozygotes are still able to contract malaria but their symptoms are generally less severe (Allison, 2009), because of this, heterozygotes have a higher fitness than either of the homozygotes, this is known as heterozygote advantage.