To understand the importance of correct nucleotide sequence and protein structure, look to the example of sickle cell anemia. Sickle cell anemia is a genetic disease caused by a single point mutation, on the beta-globin gene. This single base mutation is from A to T in the triplet codon (GAG GTC) for the sixth amino acid on the beta chain of the hemoglobin molecule. When this mutation occurs, a hydrophobic valine residue is substituted for a negatively charged glutamic acid (normal beta chain). This single base change affects the way the protein transports oxygen, and causes a crippling disease.
Sickle cell anemia is a autosomal recessive disorder. Only homozygotes are affected by the disease. The hemoglobin molecules of these individuals are abnormally shaped -- also called sickle shaped.
Sickle cell anemia causes a distortion of the red blood cells into sickle shapes that consequently slows the blood flow and decreases the amount of oxygen the red cells are able to carry. Sickle cells then tend to become trapped and destroyed in the liver and in the spleen. This results in a shortage of red blood cells -- called anemia -- which causes the patient to be pale, fatigued, and short of breath. Complications such as infection can worsen a patients anemia by speeding up destruction of red blood cells or by reducing red blood cell production. Sickle cell crisis occurs when sickled RBCs become lodged in nearby tissues so that no cells can get through to bring oxygen to them. This lack of oxygen causes severe pain for the patient. Further, a patient in crisis often requires blood transfusions. If treatment is not given, or if it fails, organ failure and death may occur.
Morbidity begins in early childhood, with the appearance of symptoms. Chronic anemia and serious infection are among the most common symptoms. Many states have mandatory screening policies for newborns. Also, midwives and doctors offer at-risk pregnant women screening tests, to look for the trait. Children with sickle cell have a increased risk of infection by polysaccharide-encapsulated infection -- as much as a 400% higher risk than healthy children. The mortality rate for children under age 10 is 1%; the chance of reaching adulthood is 85%.
Sickle Cell Links
One of the best links -- overview of sickle cell.
Emory University Sickle Cell Information Page
March Of Dimes Sickle Cell Information Page
