type alleles has the normal number of receptors. The asso-
ciated phenotypes parallel the number of receptors—those
with two mutant alleles develop severe disease as children,
individuals with one mutant allele may become ill in young
or middle adulthood, and people with two wild type alleles
do not develop this type of hereditary heart disease.
Different alleles that are both expressed in a heterozygote
For example, two of the three alleles of the
gene, which determines ABO blood type, are codominant (see
± g. 14.21). The
gene encodes the enzymes that place the A
and B antigens on red blood cell surfaces. The three alleles are
. People with type A blood may be either genotype
type B corresponds to
type AB to
type O to
alleles are codominant.
To Chapter 14, Blood Groups and Transfusions,
Distinguish between autosomes and sex chromosomes.
Distinguish between genotype and phenotype.
Distinguish between wild type and mutant alleles.
How do the modes of transmission of autosomal recessive and
autosomal dominant inheritance diF
Distinguish between incomplete dominance and codominance.
Certain recessive alleles that cause illness remain in a population
because carriers are protected against another condition, such as an
infectious disease. ±or example, in carriers of sickle cell disease (see
g. 4.24), not enough red blood cells are deformed to block circula-
tion under normal atmospheric conditions, but enough are sickle
shaped to keep out malaria parasites. Carriers for sickle-cell disease
and certain other inherited anemias do not easily contract malaria. If
they do contract malaria, the symptoms are mild.
An example of an autosomal dominant condition is
Huntington disease (HD). Symptoms usually begin in the
late thirties or early forties and include loss of coordination,
uncontrollable dancelike movements, behavioral changes and
cognitive decline. Figure 24.5 shows the inheritance pattern
for HD. If one parent has the mutant allele, half of his or her
gametes will have it. Assuming the other parent does not have
a mutant allele, each child conceived has a 1 in 2 chance of
inheriting the gene and, eventually, developing the condition.
Most of the 3,000 or so known human inherited disorders
are autosomal recessive. These conditions tend to produce
symptoms early, even before birth. Autosomal dominant
conditions often begin to cause symptoms in adulthood.
These disorders remain in populations because people have
children before they know that they have inherited the ill-
ness. For some autosomal dominant disorders, genetic tests
can reveal that a disease-causing genotype has been inher-
ited, even before symptoms begin. Clinical Application 24.1
explores how a genetic counselor can help families under-
stand the implications of different modes of inheritance.
Gene therapy, still experimental, alters, replaces, silences, or aug-
ments a gene’s function to prevent, delay, or improve speci²
toms. In humans gene therapy targets only aF
ected somatic cells and
therefore cannot be transmitted to the next generation. A gene ther-
apy for an inherited bleeding disorder provides genes that encode
cient, inactive, or missing clotting factors. Delivering gene ther-
apy is challenging. To treat C±, for example, a wild type copy of the
C±TR gene is inhaled; for muscular dystrophy, a wild type dystrophin
gene is implanted in muscle. Many gene therapies deliver healing
genes in viruses, which themselves can cause problems.
Different Dominance Relationships
Most genes exhibit complete dominance or recessive-
ness. Interesting exceptions are incomplete dominance and
the heterozygous pheno-
type is intermediate between that of either homozygote. For
example, in familial hypercholesterolemia (FH), a person
with two disease-causing alleles completely lacks LDL (low-
density lipoprotein) receptors on liver cells that take up cho-
lesterol from the bloodstream
(F g. 24.6)
. A person with one
disease-causing allele (a heterozygote) has half the normal
number of cholesterol receptors. Someone with two wild
Incomplete dominance appears in the plasma
cholesterol levels of heterozygotes and homozygotes for familial
hypercholesterolemia (±H). This condition is one of many that increase the
cholesterol level in the blood, raising the risk of developing cardiovascular
disease. The photograph shows cholesterol deposits on the elbow of a
young man who is a homozygote for the disease-causing allele.
Plasma cholesterol (milligrams/deciliter)