Sickle cell anemia is a heritable disease affecting hemoglobin, the molecule in red blood cells responsible for carrying oxygen throughout the body. The presence of an abnormal hemoglobin protein causes red blood cells to take on a stiff, curved shape like a farm implement called a sickle, which does not allow them to pass through small capillaries and leads to oxygen deprivation and tissue damage. The abnormal hemoglobin also breaks down more quickly than usual. Individuals with sickle cell anemia generally have a reduced life expectancy of 40 to 50 years.
Sickle Cell Trait
Sickle cell anemia is caused by a single mutation in the beta-hemoglobin (Hb) gene. The normal DNA sequence for the beta-hemoglobin gene is called HbA, while the sickle cell causing version is called HbS. This form of the gene is also referred to as the sickle cell trait. The mutation in HbS allows the beta-hemoglobin protein to form long chains under stressful conditions. Red blood cells containing the HbS form of the protein lose their elasticity and take on the stiff sickle shape. The disease is inherited in a recessive manner, which means that an affected individual has two copies of the HbS gene, one inherited from each of his parents. This is denoted as HbSS. Carriers of the sickle cell trait are called HbAS because one copy of the gene is the normal HbA form and one is the HbS form. Carriers usually do not suffer from symptoms because they make enough healthy beta-hemoglobin that the disease does not arise. However, they can pass the trait on to their children.
Other Hemoglobin Mutations
Usually sickle cell anemia is caused by two HbS genes, one from each parent, but sometimes the combination of HbS from one parent and another Hb mutation from the other parent will also lead to the disease. The HbC version of the gene has a different mutation in the DNA sequence and also leads to sickling. People with HbS as one copy of the gene and HbC as the other are HbSC; because these individuals do not have a normal HbA copy of the gene they develop the disease. In a similar manner, individuals with HbS as one copy and HbD, HbE or HbO versions of the gene as the other also develop sickle cell anemia; these occurrences of sickle cell anemia are rarer. Beta-thalassemia is another disease caused by mutations that reduce the amount of beta-hemoglobin made. Individuals with one HbS gene and a beta-thalassemia mutation of Hb also do not make enough healthy beta-hemoglobin to compensate for the HbS mutation and exhibit the disease.
Genetic Advantage of Sickle Cell Trait
The Sickle Cell Disease Association of America and the Centers for Disease Control and Prevention estimate that 1,000 children a year are born with sickle cell anemia and that over 70,000 Americans have this disease. The reason why this deleterious disease remains prevalent in the world population is that the presence of one mutant copy of the beta-hemoglobin gene offers an advantage: some mutant forms of beta-hemoglobin give resistance to malaria. The shortened life span of red blood cells carrying mutant beta-hemoglobin prevents the malaria parasite from fully maturing and so reduces the strength of the infection. Beta-thalassemia has also been linked to reduced infection by malaria. The advantage of being a carrier and thus being less susceptible to malaria is why sickle cell mutations are still prevalent despite the severity the disease.
