Essentials of Anatomy and Physiology

59

BOX3–2 GENETIC DISEASE—SICKLE-CELL ANEMIA

Normal hemoglobin

Normal red blood cells (RBCs)

Sickle red blood cells

Sickle

hemoglobin

(HbS)

Deo

xyg

enatio

n

α

β

β

α

Iron in heme

Box Figure 3–B Structure of hemo-

globin A and sickle-cell hemoglobin and

their effect on red blood cells.

Agenetic diseaseis a hereditary disorder, one
that may be passed from generation to generation.
Although there are hundreds of genetic diseases,
they all have the same basis: a mistake in DNA.
Because DNA makes up the chromosomes that are
found in eggs and sperm, this mistake may be
passed from parents to children.
Sickle-cell anemia is the most common genetic
disorder among people of African descent and
affects the hemoglobin in red blood cells. Normal
hemoglobin, called hemoglobin A (HbA), is a pro-
tein made of two alpha chains (141 amino acids
each) and two beta chains (146 amino acids each).
In sickle-cell hemoglobin (HbS), the sixth amino
acid in each beta chain is incorrect; valine instead of
the glutamic acid found in HbA. This difference
seems minor—only 2 incorrect amino acids out of
more than 500—but the consequences for the per-
son are very serious.
HbS has a great tendency to crystallize when
oxygen levels are low, as is true in capillaries. When
HbS crystallizes, the red blood cells are deformed
into crescents (sickles) and other irregular shapes.

These irregular, rigid red blood cells clog and rup-

ture capillaries, causing internal bleeding and

severe pain. These cells are also fragile and break up

easily, leading to anemia and hypoxia (lack of oxy-

gen). Treatment of this disease has improved

greatly, but it is still incurable.

What has happened to cause the formation of

HbS rather than HbA? Hemoglobin is a protein; the

gene for its beta chain is in DNA (chromosome 11).

One amino acid in the beta chains is incorrect,

therefore, one triplet in its DNA gene must be, and

is, incorrect. This mistake is copied by mRNA in the

cells of the red bone marrow, and HbS is synthe-

sized in red blood cells.

Sickle-cell anemia is a recessive genetic disease,

which means that a person with one gene for HbS

and one gene for HbA will have “sickle-cell trait.”

Such a person usually will not have the severe

effects of sickle-cell anemia, but may pass the gene

for HbS to children. It is estimated that 9% of

African-Americans have sickle-cell trait and about

1% have sickle-cell anemia.