Sickle cell anemia, hemoglobin abnormality

Our blood contains the complex protein hemoglobin, which carries oxygen from the lungs to other parts of the body. In the genetic disease known as sickle-cell anemia, hemoglobin molecules are abnormal and have a lower solubility, especially in their unoxygenated form. Consequently, as much as 85% of the hemoglobin in red blood cells crystallizes out of solution. 

Fig. 5. At the left, molecules of normal hemoglobin or of oxygenated sickle-cell-anemia hemoglobin are shown, with random orientations, and at about the average distance apart characteristic of red-cell contents. At the right long strings of molecules of deoxygenated sickle-cell-anemia hemoglobin are shown, assuming the parallel orientation characteristic of the nematic liquid crystals that presumably form within the red cells in the venous blood of patients with sickle-cell anemia, and twist the red cells into the abnormal shape characteristic of the disease.

Since the discovery of sickle-cell anemia hemoglobin 14 years ago some scores of other abnormal human hemoglobins have been discovered. These abnormal hemoglobins are associated with many different diseases. 

Mlcrochromatographlc Methods During the past two years rapid. Inexpensive, miniaturized column chromatographic methods for the separation of hemoglobins have been developed These methods are designed for the qualitative detection and quantitative determination of hemoglobins In normal and abnormal conditions and cover the quantitation of Hb-A2 the detection of Hb-S, Hb-C other abnormal Hbs differentiation of various conditions In adults and the detection of hemoglobinopathies especially sickle cell anemia at birth (27, 28, 29, 30) ... 

The most common abnormal hemoglobin in the United States is hemoglobin S (HbS). Two genes for HbS result in sickle cell disease (SCD) or sickle cell anemia, which occurs in 0.3% of African Americans. One gene for HbS results in sickle cell trait, which occurs in 8% of African Americans. Hemoglobin C, another abnormality, occurs in 2% to 3% of African Americans. 

Hemoglobinopathies have traditionally been defined as a family of dis orders caused by production of a structurally abnormal hemoglobin molecule, synthesis of insufficient quantities of normal hemoglobin, or, rarely, both. Sickle-cell anemia (HbS), hemoglobin C disease (HbC), and the thalassemia syndromes are representative hemoglobinopathies that can have severe clinical consequences. The first two conditions result from production of hemoglobin with an altered amino acid sequence, whereas the thalassemias are caused by decreased produc tion of normal hemoglobin. 

The change of a single base in the DNA sequence for normal hemoglobin can encode for the abnormal hemoglobin, giving rise to sickle cell anemia. Which base in the codon for glu in DNA is replaced to give the codon(s) for val (See Exercises 79 and 101.)... 

There are many kinds of amino acid substitutions that may produce abnormal hemoglobins besides that found in sickle cell anemia, but these conditions will not be elaborated upon here. 

Singer, H., Chemoff, A. I., and Singer, L., Studies on abnormal hemoglobin. I. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation. Blood 6, 413-428 (1951). 

In sickle cell anemia, the hemoglobin molecule (HbS) is abnormal. If the P chains of normal hemoglobin (HbA) and HbS have the N-terminal sequences shown below and the chains otherwise are the same, which of the following statements is TRUE ... 

A. Diseases related to abnormal hemoglobin Sickle cell anemia results from a point mutation (GAG to GTG) that causes valine to replace glutamate at position 6 in the P-globin chain. In hemoglobin Wayne, deletion of a base causes a frameshift that produces the wrong sequence of amino acids in the chain beyond position 127. 

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