is avoided to a certain degree. However, inactivation is not
complete; therefore, individuals with trisomies [for example,
XXY (Klinefelter syndrome), XXX (triple-X syndrome), or XYY]
or monosomies (XO; Turner syndrome) often show abnormal
sexual development, intelligence, or behavior.
Diseases with mendelian inheritance
In contrast to chromosomal aberrations, the genetic defects in
hereditary diseases with simple, mendelian modes of inheri-
tance cannot be recognized by microscopic examination; as
a rule, they must be inferred more indirectly from the pheno-
type and the pattern of inheritance in pedigrees (Fig. 5). The
defects are found in the molecular structure of the DNA. Often,
one base pair only is altered, although sometimes more com-
plex molecular changes (such as deletions of some bases or
abnormal recombination) are involved. Approximately 1% of
all newborns have, or will develop during their lives, a heredi-
tary disease showing a simple, mendelian mode of inheritance.
In medical genetics, a condition is called dominant if the
heterozygotes deviate in a clearly recognizable way from the
normal homozygotes, in most cases by showing an abnormal-
ity. Because such dominant mutations are usually rare, almost
no homozygotes are observed and their clinical condition is
typically unknown. In exceptional instances, homozygotes for
dominant conditions have been described; they have usually
shown more severe clinical signs than the heterozygotes.
In Fig. 6, there are four mendelian crosses for one pair of al-
leles, A and A'. Cross no. 2, the backcross between the normal
homozygote and the heterozygote, which leads to 1:1 seg-
regation, is found most commonly in autosomal-dominant
inheritance. Crosses 3 and 4 are extremely rare because homo-
zygotes for an abnormal allele are usually rare. In autosomal-
recessive inheritance, backcrosses between normal homo-
zygotes and heterozygotes (cross no. 2) are also common;
however, because heterozygotes are normal phenotypically,
such crosses will go unnoticed in most instances. The most
common cross leading to homozygous, clinically affected off-
spring is the intercross between two heterozygotes, AA', which
results in 1:2:1 segregation.
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 indi-
viduals 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 indepen-
dently of the sex chromosomes, and the risk of being affected
is not influenced by the sex of the parents or child.
Human Genetics (continued)
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Fig. 5 Some common symbols used for the presentation of human pedigrees.
(Copyright © McGraw Hill)
