Result of a mutation: sickle cell anemia

All manifestations of sickle cell anemia are due
to the substitution of a single nucleotide base in
the !-globin gene. The sickle cell mutation is
the transversion of the second nucleotide base
of codon 6, adenine (A), to thymine (T). This
changes the codon GAG, for glutamic acid, to
GTG, the codon for valine. During the 1950s,
Vernon M. Ingram determined the amino acid
sequence of hemoglobin and found that the
only difference between sickle cell hemoglobin
(HbS) and normal adult hemoglobin (HbA) was
this exchange in the ! chain. This has far-reaching
pathophysiological consequences and explains
all manifestations of the disease. Sickle
cell hemoglobin (HbS) is less soluble than normal
hemoglobin and does not allow normal
erythrocyte distortion. It crystallizes in the
deoxy state and forms small rods. Thus, the
erythrocytes become firm and deform into
sickle cells. Unlike normal erythrocytes, sickle
cells are unable to pass through small arteries
and capillaries. These become clogged and
cause local oxygen deficiency in the tissues,
followed by infection. As a rule, learning disability
due to frequent illness occurs. Defective
erythrocytes are destroyed (hemolysis).
Chronic anemia and its numerous sequelae
such as heart failure, liver damage, and infection
are the result.