Mutations are errors in the genotype that create new alleles
and can result in a variety of genetic disorders. In order for a
mutation to be inherited from one generation to another, it must
occur in sex cells, such as eggs and sperm, rather than in somatic
cells. The best way to detect whether a genetic disorder exists
is to use a karyotype, a photograph of the chromosomes
from an individual cell, usually lined up in homologous pairs, according
Some human genetic illnesses are inherited in a Mendelian
fashion. The disease phenotype will have either a clearly dominant
or clearly recessive pattern of inheritance, similar to the traits
in Mendel’s peas. Such a pattern will usually only occur if the
disease is caused by an abnormality in a single gene. The mutations
that cause these diseases occur in genes on the autosomal
chromosomes, as opposed to sex-linked diseases, which we
cover later in this chapter. (Be careful not to confuse autosomal
chromosomes with somatic cells; autosomal chromosomes are the chromosomes
that determine bodily characteristics and exist in all cells,
both sex and somatic.)
A Mendelian genetic illness initially arises as a new
mutation that changes a single gene so that it no longer produces
a protein that functions normally. Some mutations, however, result
in an allele that produces a nonfunctional protein. A disease resulting
from this sort of mutation will be inherited in a recessive fashion:
the disease phenotype will only appear when both copies of the gene
carry the mutation, resulting in a total absence of the necessary
protein. If only one copy of the mutated allele is present, the
individual is a heterozygous carrier, showing no signs of the disease
but able to transmit the disease gene to the next generation. Albinism
is an example of a recessive illness, resulting from a mutation
in a gene that normally encodes a protein needed for pigment production
in the skin and eyes. The pedigree shown below diagrams
three generations of a hypothetical family affected by albinism.
The pedigree demonstrates the characteristic
features of autosomal recessive inheritance. The parents
of an affected individual usually show no signs of disease, but
both must at least be heterozygous carriers of the disease gene.
Among the offspring of two carriers, 25 percent will have the disease,
50 percent will be carriers, and 25 percent will be noncarriers.
No offspring produced by a carrier and a noncarrier will have the
disease, but 50 percent will be carriers. Although not shown in
this pedigree, offspring produced by two individuals who have the
disease in their phenotype, which means both parents are recessive
homozygous, will all develop the disease.
Many recessive illnesses occur with much greater frequency
in particular racial or ethnic groups that have a history of intermarrying
within their own community. For example, Tay-Sachs disease is especially
common among people of Eastern European Jewish descent. Other well-known
autosomal recessive disorders include sickle-cell anemia and cystic
Usually, a dominant phenotype results from the presence
of at least one normal allele producing a protein that functions
normally. In the case of a dominant genetic -illness, there is a mutation
that results in the production of a protein with an abnormal and
harmful action. Only one copy of such an allele is needed to produce
disease, because the presence of the normal allele and
protein cannot prevent the harmful action of the mutant protein.
If a recessive mutation is like a car with an engine that cannot
start, a dominant mutation is like a car with an engine that explodes.
A spare car will solve the problem in the first case, but will do
nothing to protect the garage in the second case.
Huntington’s disease, which killed folksinger Woody Guthrie,
is a dominant genetic illness. A single mutant allele produces an
abnormal version of the Huntington protein; this abnormal protein
accumulates in particular regions of the brain and gradually kills
the brain cells. By middle age, this progressive brain damage produces
severely disturbed physical movements, loss of intellectual functions,
and personality changes. The pedigree shown below diagrams three
generations of a hypothetical family with Huntington’s disease.
This pedigree demonstrates the characteristic
features of autosomal dominant inheritance. Notice that
all affected individuals have at least one parent with the disease.
Unlike recessive inheritance, there is no such thing as a carrier:
the disease will affect all heterozygous individuals.
Among the offspring of an affected heterozygote and an unaffected
person, 50 percent will be affected and 50 percent will be unaffected.
None of the children born to two unaffected individuals will have
the disease. (Although not shown in this pedigree, homozygous dominant
mutations often produce very severe cases of the disease, because
the amount of the abnormal protein is doubled and the normal protein
is entirely absent.)
Recessive and dominant characteristics result from the
mutation of a single gene. Some genetic disorders result from the
gain or loss of an entire chromosome. Normally, paired homologous
chromosomes separate from each other during the first division of
meiosis. If one pair fails to separate, an event called nondisjunction,
then one daughter cell will receive both chromosomes and the other
daughter cell will receive none. When one of these gametes joins
with a normal gamete from the other parent, the resulting offspring
will have either one or three copies of the affected chromosome,
rather than the usual two.
A single chromosome contains hundreds to thousands of
genes. A zygote with three copies of a chromosome (trisomy), instead
of the usual two, generally cannot survive embryonic development.
Chromosome 21 is a major exception to this rule; individuals with
three copies of this small chromosome (trisomy 21) develop the genetic
disorder called Down syndrome. People with Down syndrome show at
least mild mental disabilities and have unusual physical features
including a flat face, large tongue, and distinctive creases on
their palms. They are also at a much greater risk for various health
problems such as heart defects and early Alzheimer’s disease.
The absence of one copy of a chromosome (monosomy) causes
even more problems than the presence of an extra copy. Only monosomy
of the X chromosome (discussed below) is compatible with life.
Polyploidy occurs when a failure occurs during
the formation of the gametes during meiosis. The gametes produced
in this instance are diploid rather than haploid. If fertilization
occurs with these gametes, the offspring receive an entire extra
set of chromosomes. In humans, polyploidy is always fatal, though
in many plants and fish it is not.
Sex Chromosomes and Sex-Linked Traits
Dominant and recessive illnesses occur with equal frequency
in males and females. This is because the genes involved are located
on autosomes, which are the same in both genders. Many physical
traits, however, obviously do differ between the two genders. In
addition, gender dramatically affects the inheritance of certain
traits and illnesses that have no obvious connection to sexual characteristics.
These sex-linked traits are controlled by genes located
on the sex chromosomes. Humans have 46 chromosomes, including 44
autosomes (nonsex chromosomes) and the two sex chromosomes, which
can be either X or Y. The autosomes come in 22 homologous pairs,
present in both males and females. Females also possess a homologous
pair of X chromosomes, while males have one X chromosome and one
Y chromosome (the master gene for “maleness” is located on the Y
chromosome). All eggs have an X chromosome, so the sex of a child
is determined at the time of fertilization by the type of sperm.
If the fertilizing sperm carries an X chromosome, the child will
be female; if it carries a Y chromosome, the child will be male.
The X chromosome is much larger than the tiny Y chromosome, and
most of the genes on the X chromosome do not have a homologous counterpart
on the Y.
Genes on autosomes will always be present in two copies:
one inherited from the maternal parent, the other from the paternal
parent. The traits controlled by such autosomal genes will be generally
unaffected by gender and will follow Mendelian patterns of inheritance
(with the exceptions noted in previous sections). In contrast, genes
on the X chromosome (X-linked genes) are present in two copies in
females but only one copy in males. Female offspring will inherit
one copy of an X-linked gene from each parent, but male offspring
must inherit the Y chromosome from their father and therefore always inherit
only the maternal allele of any X-linked gene. For example, color
blindness and hemophilia are sex-linked disorders. The mutated gene
that causes these disorders is recessive and exists on the X chromosome.
In order for a female, who is XX, to have a phenotype that is color
blind or hemophiliac, both of her parents have to have the recessive
gene. But since males have only one X chromosome inherited from
their mother, if their mother expresses the recessive mutation,
that trait will automatically be expressed in the
male child’s phenotype, since the male has no other gene to assert
dominance over the recessive mutation.
The pedigree shown below diagrams three generations of
a hypothetical family affected by hemophilia A.
This pedigree demonstrates many of the characteristic
features of X-linked recessive inheritance. Heterozygous females
are carriers who do not express the disease. In contrast, all males
with the mutated allele will express the disease; there are no male
carriers. Affected males will transmit the mutated allele to none
of their sons but to all of their daughters, who will then all be
carriers. Heterozygous females will transmit the disease to one-half
of their sons, and one-half of their daughters will be carriers.
Affected males generally have an unaffected father and a mother
who is a carrier; 50 percent of their maternal uncles will have