A genetic disease is a hereditary disorder, one that may be passed from generation to generation. Although there are hundreds of genetic diseases, they all have the same basis: a mistake in DNA. Because DNA makes up the chromosomes that are found in eggs and sperm, this mistake may be passed from parents to children. Sickle-cell anemia is the most common genetic disorder among people of African descent and affects the hemoglobin in red blood cells. Normal hemoglobin, called hemoglobin A (HbA), is a protein made of two alpha chains (141 amino acids each) and two beta chains (146 amino acids each). In sickle-cell hemoglobin (HbS), the sixth amino acid in each beta chain is incorrect; valine instead of the glutamic acid found in HbA. This difference seems minor—only 2 incorrect amino acids out of more than 500—but the consequences for the person are very serious.
HbS has a great tendency to crystallize when oxygen levels are low, as is true in capillaries. When HbS crystallizes, the red blood cells are deformed into crescents (sickles) and other irregular shapes. These irregular, rigid red blood cells clog and rupture capillaries, causing internal bleeding and severe pain. These cells are also fragile and break up easily, leading to anemia and hypoxia (lack of oxygen). Treatment of this disease has improved greatly, but it is still incurable. What has happened to cause the formation of HbS rather than HbA? Hemoglobin is a protein; the gene for its beta chain is in DNA (chromosome 11). One amino acid in the beta chains is incorrect, therefore, one triplet in its DNA gene must be, and is, incorrect. This mistake is copied by mRNA in the cells of the red bone marrow, and HbS is synthesized in red blood cells.
Sickle-cell anemia is a recessive genetic disease, which means that a person with one gene for HbS and one gene for HbA will have “sickle-cell trait.” Such a person usually will not have the severe effects of sickle-cell anemia, but may pass the gene for HbS to children. It is estimated that 9% of African-Americans have sickle-cell trait and about 1% have sickle-cell anemia.