the person’s life. Clinical Application 14.1 (p. 530) discusses
a pleiotropic disorder that left its mark on American history,
porphyria variegata.
Genetic Heterogeneity
The same phenotype resulting from the actions of different
genes is called
genetic heterogeneity
ik het
ı˘-te). For example, the nearly 200 forms of hereditary
deafness are each due to impaired actions of a different gene.
Different genes affect different aspects of hearing.
Genetic heterogeneity occurs when genes encode differ-
ent enzymes that catalyze the same biochemical pathway,
or encode different proteins that are part of the pathway.
For example, eleven biochemical reactions lead to blood clot
formation. Clotting disorders may result from mutations in
the genes that specify any of the enzymes that catalyze these
reactions, leading to several types of bleeding disorders.
A couple was arrested on suspicion of child abuse because their
toddler suF
ered repeated broken bones. Tests for the gene known
to cause osteogenesis imperfecta, “brittle bone disease,” which can
break bones even in a fetus, revealed that the parents were wild type.
They were found guilty. However, discovery of a second gene that
causes osteogenesis imperfecta enabled them to be tested again, for
this gene, and they were exonerated. Their child had inherited a rare
form of the disease.
Distinguish between penetrance and expressivity.
What is pleiotropy?
What is genetic heterogeneity?
Most if not all characteristics and disorders considered
“inherited” refl
ect input from the environment as well as
genes. Characteristics molded by one or more genes plus
the environment are termed
multifactorial traits
or com-
plex traits.
Traits determined by more than one gene are termed
Most polygenic traits are also influenced by
the environment. Eye color is an example of a trait that is
as close to purely polygenic as we know. Usually, several
genes each contribute to differing degrees toward molding
an overall phenotype. A polygenic trait, with many degrees
of expression because of the input of several genes, is said
to be continuously varying. Height, skin color, and eye color
are polygenic traits
gs. 24.7, 24.8,
Although the expression of a polygenic trait is continu-
ous, we can categorize individuals into classes and calcu-
late the frequencies of the classes. When we do this and
Most genotypes vary somewhat from person to person, due
to the effects of the environment and other genes. Even iden-
tical twins may not exhibit the symptoms of an inherited
illness in the exact same way. The terms penetrance, expres-
sivity, and pleiotropy are used to describe some of these dis-
tinctions of genotype.
Penetrance and Expressivity
Some disease-causing allele combinations are
which means that everyone who inherits a par-
ticular genotype has some symptoms. A genotype is
pletely penetrant
if some individuals do not express the
associated phenotype. Polydactyly, having extra ±
ngers or
toes, is incompletely penetrant (see ± g. 7.46). Some people
who inherit the autosomal allele have more than ±
ve dig-
its on a hand or foot, yet others known to have the allele
(because they have an affected parent and child) have ten
± ngers and ten toes.
The penetrance of a gene is described numerically. If
80 of 100 people who have inherited the dominant poly-
dactyly allele have extra digits, the allele is 80% penetrant.
However, incomplete penetrance is dif±
cult to detect because
it describes the absence of a phenotype.
A phenotype is
variably expressive
if the symptoms
vary in intensity in different people—which is nearly always
the case. One person with polydactyly might have an extra
digit on both hands and a foot; another might have two extra
digits on both hands and both feet; a third person might have
just one extra ±
ngertip. Penetrance refers to the all-or-none
expression of a genotype in an individual; expressivity refers
to the severity of a phenotype. Polydactyly is both incom-
pletely penetrant and variably expressive.
A single genetic disorder can produce several symptoms, a
phenomenon called
o-tro-pe). Family mem-
bers who have different symptoms can appear to have differ-
ent illnesses.
Pleiotropy is seen in genetic diseases that affect a single
protein found in different parts of the body. This is the case
for Marfan syndrome, an autosomal dominant defect in an
elastic connective tissue protein called ±
brillin. The protein's
abundance in the lens of the eye, in the bones of the limbs,
± ngers, and ribs, and in the aorta explains the symptoms of
lens dislocation, long limbs, spindly ± ngers, and a caved-in
chest. The most serious symptom is a life-threatening weak-
ening in the aorta wall, which sometimes causes the vessel to
suddenly burst. If the weakening is found early, a synthetic
graft can be used to patch that part of the vessel wall, saving
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