1) Because of molecular changes within the sickled cell, oxygen-carrying capacity of the blood is greatly reduced.
2) Because of their peculiar shape, greater rigidity, and tendency to stick together, sickle cells clog smaller vessels in the circulatory system-the arterioles and capillaries, in particular-preventing the blood from delivering oxygen and nutrients, and removing carbon dioxide and wastes from tissues.
This disease was reported for the first time by a Chicago-based cardiologist James B. Herrick in 1910. It was recognized to be the result of a genetic mutation, inherited according to the Mendelian principle of incomplete dominance. Initially, it was not clear what the actual defect was, that caused the sickling. Various experiments indirectly narrowed down the site of the defect to the hemoglobin molecule. The most direct evidence that mutation affected the hemoglobin molecule came from electrophoretic analysis, a method to separate complex mixtures of large molecules by means of an electric current on a gel. When hemoglobin from people with severe sickle cell anemia, the sickle cell trait, and normal red blood cells was subjected to electrophoresis.
It was clear that hemoglobin molecules of people with sickle cell anemia migrated at a different rate, and thus ended up at a different place on the gel, from the hemoglobin of normal people. What was even more interesting was the observation that individuals with the sickle cell trait had about half normal and half sickle-cell hemoglobin, each type making up 50% of the contents of any red blood cell.
To confirm this latter conclusion, the electrophoretic profile of people with the sickle cell trait could be duplicated simply by mixing sickle cell and normal hemoglobin together and running them independently on an electrophoretic gel. These results fit perfectly with an interpretation of the disease as inherited in a simple Mendelian fashion showing incomplete dominance. Here, then, was the first verified case of a genetic disease that could be localized to a defect in the structure of a specific protein molecule. Sickle cell anemia thus became the first in a long line of what have come to be called molecular diseases. Thousands of such diseases (most of them quite rare), including over 150 mutants of hemoglobin alone, are now known.
Tags: Bio Technology, Bio Genetics, Proteins