The pattern of inheritance is often determined by studying the
history of a trait among a group of relatives. As an example,
a pedigree in which a rare autosomal-dominant condition is
transmitted through four generations is shown in Fig. 7. The
mutant allele is located on an autosome; the affected individu-
als are heterozygous. Because one of the two alleles at this
gene locus is altered by mutations and each of the two alleles
has a 50% probability of being transmitted to a child (Fig. 6,
cross no. 2), each child has a 50% risk of being affected. Because
this mutation is autosomal, it is transmitted independently
of the sex chromosomes, and the risk of being affected is not
influenced by the sex of the parents or child.
In some dominant conditions, the harmful phenotype may not
be expressed in a gene carrier (this is called incomplete pen-
etrance), or clinical signs may vary in severeness among carriers
(this is called variable expressivity). Penetrance and expressivity
may be influenced by other genetic factors, including the sex of
the affected person; in other instances, the constitution of the
"normal" allele has been implicated. Environmental conditions
may occasionally be important. In most cases, however, the
reasons are unknown.
Inheritance also can occur in an autosomal-recessive manner. A
pedigree for albinism, that is, with an autosomal-recessive trait,
is shown in Fig. 8. The affected individuals (IV, 2 and 6) have
two mutant alleles (one from each parent), and they are homo-
zygous for the albinism gene. Hence, their unaffected parents
(III, 4 and 5) must both be heterozygous for this allele. The
probability of two individuals having the same allele increases
when some of their genes come from a common ancestor (that
is, when they are relatives). An increase of matings between
relatives (for example, first cousins) in comparison with the
population average is characteristic for rare autosomal-reces-
sive diseases.
Finally, X-linked modes of inheritance occur when the mutant
allele is located on the X chromosome. The most important
X-linked mode of inheritance is the recessive one (Fig. 9). Here,
the males (referred to as hemizygotes, having only one allele)
are affected because they have no normal allele. The female
heterozygotes, on the other hand, will be unaffected because
the one normal allele is sufficient for maintaining function. A
Human Genetics (continued)
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Fig. 6 Examples of mendelian crosses using two alleles, A and A'.
(Copyright © McGraw Hill)
Fig. 7 Typical pedigree pattern of a rare autosomal-dominant trait: classical achondroplastic
dwarfism. Individuals with this anomaly, caused by a defect in bone growth, have extremely
short arms and legs, but are otherwise normal. I–IV are generations; shaded individuals
manifest the trait.
(Copyright © McGraw Hill)
Fig. 8 Typical pedigree pattern of a rare autosomal-recessive trait: albinism.
(Copyright © McGraw Hill)
