What Chromosome Is Sickle Cell On?

Sickle cell anemia is a genetic blood disorder resulting from a point mutation on the short arm of chromosome 11. The mutated gene sequence produces inelastic, sickle-shaped red blood cells which are broken down in the capillaries and spleen quicker than they can be replaced by the body. The discovery of sickle cell anemia's underlying cause was a milestone in molecular biology for being the first human genetic disease to have a causal relationship established between a specific protein mutation and the disease's external symptoms.

History

• Sickle cell anemia was first identified by Chicago cardiologist James B. Herrick in 1904, though reports of the disease's symptoms were recorded as early as 1670 in Ghana, Africa. In 1949 Linus Pauling and his colleagues at the California Institute of Technology published "Sickle Cell Anemia, a Molecular Disease," which determined that sickle-cell symptoms were the result of a mutation in the hemoglobin molecule. The hemoglobin gene was isolated on chromosome 11 between 1990 and 2003 during the research conducted by the internationally-funded Human Genome Project.

The Facts

• Sickle cell anemia is an inherited, homozygous disease. To fully express sickle cell anemia an individual must have two copies of the abnormal hemoglobin gene. Individuals with one normal and one abnormal hemoglobin gene are known as sickle cell trait carriers and typically do not express any adverse symptoms. As of 2008 roughly 70,000 people are afflicted by sickle cell anemia in America. Due to the genetic predisposition of certain ethnicities the disease primarily affects African-Americans.

Mechanism

• In sickle cell anemia the abnormal hemoglobin gene is characterized by a single nucleotide polymorphism in the beta-globin chain of hemoglobin. This mutation converts the DNA base pair of adenine to thymine, resulting in the protein expression of valine instead of glutamate at position 6 of the beta-globin chain. Because valine is hydrophobic it readily polymerizes with other hydrophobic areas of the hemoglobin protein to form rigid fibers. These rigid fibers give red blood cells their sickle shape and also account for the loss of red blood cell elasticity.

Symptoms

• Sickle cell anemia produces a range of symptoms that vary from mild to very severe. Anemic symptoms, the body's response to a low blood count, may include dizziness, headaches, shortness of breath and chest pain. Sickle cell anemia patients also experience acute or chronic pain episodes termed sickle cell crises as a result of sickle cell buildup in the lungs, abdomen, joints and bones. Sickle cell anemia can also spur more severe blood-related complications such as splenic crisis, acute chest syndrome, pulmonary arterial hypertension, stroke and multiple organ failure.

Causes

• From the molecular analysis of chromosome structures researchers at the Medical College of Gujarat, India have determined that the hemoglobin gene was mutated several times through no less than four independent mutational events. Three of those mutational events occurred in Africa with a fourth taking place in central India or Saudi Arabia. All of the hemoglobin gene mutational events occurred approximately 70,000 to 150,000 years ago.