Sickle Cell Anemia Research Paper

Introduction - sickle cell anemia
The first suggestion that genes might provide the information for all proteins came from Linus Pauling's lab at Caltech. He and his student Harvey Itano studied hemoglobin, the protein in red blood cells that transports oxygen from the lung to metabolically active tissues, like muscle, where it is needed. In particular, they focused on the hemoglobin of people with sickle-cell disease, also known as sickle-cell anemia, a genetic disorder common in Africans, and therefore among African Americans as well. The red blood cells of sickle-cell victims tend to become deformed, assuming a distinctive "sickle" shape under the microscope, and the resulting blockages in capillaries can be horribly painful, even lethal.
A molecule of hemoglobin is an 2 2 tetramer; that is, it consists of two identical chains and two identical chains. Hemoglobin is contained in the erythrocytes (red blood cells;Greek:erythros, red kytos, a hollow vessel) of which it forms 33% by weight in normal individuals, a concentration that is nearly the same as it has in the crystalline state. In every cycle of their voyage through the circulatory system, the erythrocytes, which are normally flexible biconcave disks,must squeeze through capillary blood vessels smaller in diameter than they are. In individuals with the inherited disease sickle-cell anemia, many erythrocytes assume an irregular crescentlike shape under conditions of low oxygen concentration typical of the capillaries. This “sickling” increases the erythrocytes’ rigidity, which hinders their free passage through the capillaries. The sickled cells therefore impede the flow of blood in the capillaries such that,in a sickle-cell “crisis,” the blood flow in some areas may be completely blocked, thereby giving rise to extensive tissue damage and excruciating pain. Moreover, individuals with sickle-cell anemia suffer from severe hemolytic anemia (a condition characterized by red cell destruction) because the increased mechanical fragility of their erythrocytes halves the normal 120-day lifetime of these cells. The devastating effects of this
Pauling and his co-workers subsequently demonstrated, through electrophoretic studies, that normal human hemoglobin (HbA) has an anionic charge that is around two units more negative than that of sickle-cell hemoglobin. In 1956, Vernon Ingram developed the technique of fingerprinting peptides in order to pinpoint the difference between HbA and HbS.

center6985 Fig: oxyhemoglobin and deoxyhemoglobin center18923000 Ingram’s fingerprints of HbA and HbS revealed that their alpha subunits are identical but that their beta subunits differ by a vari- ation in one tryptic peptide. Sequencing studies eventually indicated that this difference arises from the re- placement of the Glu beta 6 of HbA (the Glu in the sixth posi- tion of each beta chain) with Val in HbS (Glu beta 6 S Val),thus accounting for the charge difference observed by Pauling. This was the first time an inherited disease was shown to arise from a specific amino acid change in a protein.
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Single-Base Mutation Associated with Sickle-Cell Anemia Sequence for Wild-Type Hemoglobin
GTG CAC CTG ACT CCT GAG GAG AAG TCT GCC GTT ACT
Val His Leu Thr Pro Glu Glu Lys Ser Ala Val