Sickle cell anemia is a genetic disease that affects more than 70,000 Americans. The disease is caused by the production of abnormal hemoglobin, which is able to connect to itself and make long chains. As a result, red blood cells lose their flexibility and become deformed, adopting the hard, bowed shape that gives them a sickle appearance. Red blood cells with the distorted shape cannot enter the small blood vessels of the body, so organs and tissues become starved for oxygen. These blood cells also are targeted for early degradation, causing anemia.
Hemoglobin Type S
There are several known mutations in the beta-hemoglobin gene, symbolized as Hb, that cause this disease. The most prevalent sickle cell mutation is symbolized by HbS. This mutation is a single change in the DNA sequence and occurs near the beginning of the Hb gene. Because of this change, when the DNA sequence is used to make the hemoglobin protein, a single substitution occurs at the sixth position of the protein sequence.
Sickle cell anemia is inherited in a recessive manner, meaning that two mutant copies of the Hb gene, one from each parent, must be present for the disease to manifest. In order for a person to develop sickle cell anemia, he inherits at least one copy of HbS; the other copy of the Hb gene also must be a mutant form of beta-hemoglobin. An individual with two copies of HbS usually develops more severe sickle cell anemia.
Hemoglobin Type C
A different mutation of the beta-hemoglobin gene is known as HbC. This is also a single change in the DNA sequence that affects a protein subunit of beta-hemoglobin. A person with an HbC version of the gene and HbS as the other copy of the gene will develop sickle cell anemia.
Hemoglobin Types D, E and O
There are three other mutations of the Hb gene--HbD, HbE and HbO--that will cause sickle cell anemia when it is inherited from one parent and a copy of the HbS version is inherited from the other parent. These mutations are significantly rarer in the general population.
Beta-Thalassemia
Beta-thalassemia is a condition in which less beta-hemoglobin is produced. There are several distinct mutations that lead to beta-thalassemia, each occurring in the regulatory region controlling the use of that gene. As with the other mutant variants of beta-hemoglobin, there must be a copy of the HbS version of the gene from one parent as well as a beta-thalassemia version of the gene from the other parent for sickle cell anemia to occur. In this case, not enough beta-hemoglobin is made from the beta-thalassemia version of the gene to compensate for the HbS abnormal hemoglobin.
