Sentence outline:
Sickle cell anemia and malarial resistance

Abstract: Sickle cell anemia is a genetic disease that slightly alters the structure of hemoglobin, the oxygen carrying protein in red blood cells. This modified hemoglobin, when not carrying oxygen, tends to clump with other deoxygenated hemoglobin, deforming red blood cells and causing blood to clot throughout the body. The disease is prevalent in Africa where incidence of malaria is high because sickle cell anemia imparts some resistance to malaria. Because the United States does not have a problem with malaria, the incidence of sickle cell anemia has decreased in the African-American population.
  1. The direct cause of sickle cell anemia is genetic.
  2. A small genetic change in hemoglobin both causes sickle cell anemia and protects against malaria.
  3. Normal hemoglobin (N hemoglobin) and sickle cell hemoglobin (S hemoglobin) differ by only two amino acids, the basic building block of proteins.

    Sickle cell mechanism [added subhead]

  4. When in deoxygenated form, N hemoglobin has two patches of uncharged amino acids exposed to its surface, but S hemoglobin has four such patches.
  5. Because deoxygenated S hemoglobin has four uncharged regions exposed, instead of two as in the N form, it clumps into long chains.

    How sickle cell protects against malaria. [added subhead]

  6. While in the red blood cell, the malarial parasite induces N and S hemoglobin to go to the deoxygenated form through a mechanism known as the Bohr effect.2,3
  7. The malarial parasite can not live in a sickled red blood cell for two reasons.

    Why does sickle cell gene persist? [added subhead]

  8. If people with genes for S hemoglobin are debilitated or even die, how has the disease been perpetuated?
  9. Since sickle cell anemia is only advantageous in regions where incidence of malaria is high, it occurs less often in populations rarely exposed to malaria.
  10. The relationship between malaria and sickle cell anemia is undeniable: both biochemical evidence and demographic evidence support the theory that sickle-cell anemia imparts malarial resistance.

References

Multiple references to whole book, e.g., Ref. 1, deny reader easy access to where cited claims can be found. Paper is a little thin on references.

1. M. I. Barnhart, Sickle Cell. (Upjohn, Kalamazoo, 1979).

2. M. D. Young and G. R. Coatney, in Human Malaria, edited by F. R. Moulton (Science Press Printing Company, Lancaster, 1941), pp. 25-29.

3. W. Jarra, in Malaria and the Red Cell, edited by David Evered and Julie Whelan (Pitman, London, 1983), pp. 137-152.

4. S. Edelstein, The Sickled Cell. (Harvard University Press, Cambridge, 1986).