Saturday, April 25, 2020

Sickle Essays - Hemoglobins, Fetal Hemoglobin, Sickle Cell Trait

Sickle Cell Anemia We feel that this report looks a lot better single-spaced. A Brief History of Sickle Cell Disease Sickle Cell Disease in African Tradition Sickle cell disease has been known to the peoples of Africa for hundreds, and perhaps thousands, of years. In West Africa various ethnic groups gave the condition different names: Ga tribe: Chwechweechwe Faute tribe: Nwiiwii Ewe tribe: Nuidudui Twi tribe: Ahotutuo Sickle Cell Disease in the Western Literature Description of Sickle Cell Disease In the western literature, the first description of sickle cell disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual red cells that were "sickle shaped". Relationship of Red Cell Sickling to Oxygen In 1927, Hahn and Gillespie showed that sickling of the red cells was related to low oxygen. Deoxygenation and Hemoglobin In 1940, Sherman (a medical student at Johns Hopkins) noted a birefringence of deoxygenated red cells, suggesting that low oxygen altered the structure of the hemoglobin in the molecule. Protective Role of Fetal Hemoglobin in Sickle Cell Disease Janet Watson, a pediatric hematolist in New York, suggested in 1948 that the paucity of sickle cells in the peripheral blood of newborns was due to the presence of fetal hemoglobin in the red cells, which consequently did not have the abnormal sickle hemoglobin seen in adults. Abnormal Hemoglobin in Sickle Cell Disease Using the new technique of protein electrophoresis, Linus Pauling and colleagues showed in 1949 that the hemoglobin from patients with sickle cell disease is different than that of normals. This made sickle cell disease the first disorder in which an abnormality in a protein was known to be at fault. Amino Acid Substitution in Sickle Hemoglobin In 1956, Vernon Ingram, then at the MRC in England, and J.A. Hunt sequenced sickle hemoglobin and showed that a glutamic acid at position 6 was replaced by a valine in sickle cell disease. Using the known information about amino acids and the codons that coded for them, he was able to predict the mutation in sickle cell disease. This made sickle cell disease the first known genetic disorder. Preventive Treatment for Sickle Cell Disease Hydroxyurea became the first (and only) drug proven to prevent complications of sickle cell disease in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, which was completed in 1995. How Does Sickle Cell Cause Disease? The Mutation in Hemoglobin Sickle cell disease is a blood condition primarily affecting people of African ancestry. The disorder is caused by a single change in the amino acid building blocks of the oxygen-transport protein, hemoglobin. This protein, which is the component that makes red cells "red", has two subunits. The alpha subunit is normal in people with sickle cell disease. The ?-subunit has the amino acid valine at position 6 instead of the glutamic acid that is there normally. The alteration is the basis of all the problems that occur in people with sickle cell disease. The schematic diagram shows the first eight-of the 146 amino acids in the ?-globin subunit of the hemoglobin molecule. The amino acids of the hemoglobin protein are represented as a series of linked, colored boxes. The lavender box represents the normal glutamic acid at position 6. The dark green box represents the valine in sickle cell hemoglobin. The other amino acids in sickle and normal hemoglobin are identical. The molecule, DNA (deoxyribonucleic acid), is the fundamental genetic material that determines the arrangement of the amino acid building blocks in all proteins. Segments of DNA that code for particular proteins are called genes. The gene that controls the production of the ?-subunit of hemoglobin is located on one of the 46 human chromosomes (chromosome #11). People have twenty-two identical chromosome pairs (the twenty-third pair is the unlike X and Y-chromosomes that determine a person's sex). One of each pair is inherited from the father, and one from the mother. Occasionally, a gene is altered in the exchange between parent and offspring. This event, called mutation, occurs extremely infrequently. Therefore, the inheritance of sickle cell disease depends totally on the genes of the parents. If only one of the ?-globin genes is the "sickle" gene and the other is normal, the person is a carrier. The condition is called sickle cell trait. With a few rare exceptions, people with sickle cell trait are completely normal. If both ?-globin genes code for the sickle protein, the person has sickle cell disease. Sickle cell disease is determined at conception, when a person

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