Sickle Cell Disease SCD (aka Sickle Cell Anemia) is a genetic disorder in humans that results from a defect in the human hemoglobin molecule. Such defect is characterized by the formation of hard, sticky, sickle-shaped red blood cells, in contrast to the biconcave-shaped red blood cells (RBCs) found in “normal” individuals. The mode of inheritance of the SCD has been shown to be autosomal recessive.
Structural characterization: Human hemoglobin is a protein consisting of two pairs of identical polypeptide units, each encoded by a different family of genes: two alpha-globin genes (HBA) and two beta-globin genes (HBB).  The alpha-globin genes are located on chromosome 16 and the beta-globin genes are located on chromosome 11.
Functional Characterization: Human hemoglobin is the component of red blood cells (RBCs) that transports oxygen from the lungs to the rest of the body. When hemoglobin is deoxygenated in the tissues, it undergoes a conformational change and picks up carbon dioxide (a waste product of respiration) that it then exchanges for more oxygen in the lungs, thus continuing the cycle.  In the case of the normal or wild type hemoglobin protein, the original conformation is restored when the hemoglobin comes into contact with more oxygen. However, mutant or sickle cell hemoglobin gets stuck in the deoxygenated conformation and is therefore unable to bind oxygen again. Often the hard, inflexible, sickle-shaped RBCs aggregate together and form fibrous threads. The fibrous threads of sickled red blood cells are unable to pass through the narrow capillaries of the circulatory system, which leads to a reduced amount of blood flow to certain parts of the body. This leads to intense pain, along with a variety of associated problems.
Sequence characterization: The SCD mutation occurs in the HBB gene for one of the beta-globin chains of hemoglobin; specifically, as a glutamic acid-to-valine substitution at the sixth residue of the beta-globin polypeptide chain, click here to see figure. Since the mutation occurs at a single site, it is then referred to as single-point mutation. A set of three nucleotides in a messenger RNA (mRNA) sequence is called a codon and each codon specifies a single amino acid, which is added to a growing protein chain.  The substitution of a single nucleic acid base in the mRNA sequence causes a different amino acid to be inserted into one of the beta globin chains. Thus, instead of a glutamic acid at the sixth position in the beta-globin protein sequence, a person with SCD contains the amino acid valine instead.  As will be explained later in the tutorial this valine substitution is responsible for the clumping together of hemoglobin molecules and for the resulting symptoms of SCD.
Target genes: Human hemoglobin, messenger RNA, beta-globin (HBB), chromosome 11. click here to see full record

Source:
Paul S. Frenette and George F. Atweh. Sickle cell disease: old discoveries, new concepts, and future promise. Journal of Clinical Investigation v.117(4); April 2, 2007 pp 850-858.