by Lime Red Tetrahedron

Created on: June 23, 2010

Sickle-cell anemia is the direct result of a base-point mutation (substitution_ involving the 17th nucleotide of the B-globin gene, near the end of chromosome 11. This gene contains one incorrect nucleotide base, which translates into one incorrect amino acid in the B-globin chain (one of the polypeptides that form the quaternary structure of hemoglobin) causing a conformational change. As the quaternary structure of hemoglobin is changed, its properties change quite dramatically. The normally-globular (fairly round) hemoglobin molecule becomes a more rigid, long molecule. This translates into the sickle-shape observed in the blood cells of those with this disease.

Normally, the B-globin has the following amino acid sequence:

. . . - threonine - proline - glutamate - glutamate - . . .

The base-point mutation changes this sequence to the following:

. . . - threonine - proline - valine - glutamate - . . .

Each red blood cell can carry a great deal of oxygen (O2) due to the large amount of hemoglobin each cell contains. With normal hemoglobin, erythrocytes form their normal donut-like shape. However, the rod-like sickle-cell hemoglobin stacks in the red blood cell in such a way as to render the cell more rigid, lending it the characteristic sickle shape. The shape of the sickle-cell erythrocytes causes the symptoms of the disease, such as pain and blockage of capillaries, arteries and veins.

It is thought that sickle-cell anemia evolved in human populations in which malaria is prevalent, as the sickle-cells afford the afflicted with a good deal of resistance against the malaria parasite, plasmodium. The parasite has difficulty attaching to the sickle cells as compared to normal erythrocytes, allowing the individual to survive unaffected. In those homozygous for sickle-cell anemia, all erythrocytes are sickle cells, causing widespread complications and an extremely shortened life expectancy. However, those heterozygous for the condition have some sickle cells and some unaffected erythrocytes, allowing them to avoid many of the complications of the disease, all the while enjoying a resistance to plasmodium. Thus, historically, there has been a selective advantage associated with this condition.

In modern times, where antibiotics can easily deal with most parasites and infections, the advantage to having even partial sickle-cell anemia is nonexistent. Treatment of this condition mostly relies upon preventing the blockage of arteries, veins and capillaries, and prescribing pain medication to make the condition tolerable. Because the cause is genetic, there is no cure for sufferers. However, prospective parents can be screened for the condition, allowing them to make an informed decision before having a child.

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