Genetics and Genomics
often results in mental retardation, indicating that many
genes affect brain function. Sex chromosome aneuploidy is
less severe. Extra genetic material is apparently less danger-
ous than missing material, and this is why most children
born with the wrong number of chromosomes have an extra
one, called a
so-me), rather than a missing one,
Aneuploid conditions have historically been named for
the researchers or clinicians who identiF
ed them, but today
chromosome designations are preferred because they are
more precise. Down syndrome, for example, refers to a dis-
tinct set of symptoms usually caused by trisomy 21. It is the
most common autosomal aneuploid. However, the syndrome
may also arise from one copy of chromosome 21 exchanging
parts with a different chromosome in a gamete and the fertil-
ized ovum receiving excess chromosome 21 material. This
is a type of chromosomal aberration called a
Knowing whether an individual has trisomy 21 or transloca-
tion Down syndrome is important, because the probability
of trisomy 21 recurring in a sibling is about 1 in 100, but the
chance of translocation Down syndrome recurring is consid-
erably greater. Clinical Application 24.2 takes a closer look
at trisomy 21.
Trisomies 13 and 18 are the next most common auto-
somal aneuploids and usually result in miscarriage. An infant
with trisomy 13 has an underdeveloped face, extra and fused
ngers and toes, heart defects, small adrenal glands, and a
cleft lip or palate. An infant with trisomy 18 suffers many
of the problems seen in trisomy 13, plus a peculiar position-
ing of the F
ngers and ﬂ aps of extra abdominal skin called a
indicates the rarity of trisomies 13, 18, and
21 and that it is rarer still for an affected newborn to survive
infancy. Trisomies of the other autosomes do not develop
beyond the embryonic period.
Sex chromosome aneuploids are less severely affected
than are autosomal aneuploids. XO syndrome (Turner syn-
drome) affects 1 in 2,000 newborn girls, but these represent
only 1% of XO conceptions. Often the only symptom is a lag
in sexual development, and with hormone supplements, life
can be fairly normal, except for infertility.
About 1 in every 1,000 to 2,000 females has an extra X
chromosome in each cell, a condition called triplo-X. Often
the only associated characteristics are great height and men-
strual irregularities. Males with an extra X chromosome have
XXY syndrome (Klinefelter syndrome). Like XO females,
many XXY males typically do not realize they have an
unusual number of chromosomes until they encounter fertil-
ity problems and their chromosomes are checked. Associated
characteristics are sexual underdevelopment (rudimen-
tary testes and prostate glands and no pubic or facial hair),
growth of breast tissue, long limbs, and large hands and feet.
XXY syndrome affects 1 in every 500 to 2,000 male births.
One male in 1,000 has an extra Y chromosome, called
XYY syndrome, or Jacobs syndrome. Until 1974, the extra
chromosome was linked to criminal behavior, because the
Which chromosomes and genes determine sex?
What are the three functional classes of genes on the Y chromosome?
Why do X-linked recessive conditions appear most commonly in
How can gender aF
ect gene expression?
Deviations from the normal human chromosome number of 46
produce syndromes because of the excess or deF cit of genes.
Rearrangement of chromosomes, such as an inversion of a sec-
tion of a chromosome, or two nonhomologous chromosomes
exchanging parts, may also cause symptoms. This may hap-
pen if the rearrangement disrupts a vital gene or if it results
in “unbalanced” gametes that contain too little or too much
genetic material. Chromosome number abnormalities may
involve single chromosomes or entire sets of chromosomes.
The most drastic upset in chromosome number is an entire
extra set, a condition called
results from formation of a diploid, rather than a normal
haploid, gamete. ±or example, if a haploid sperm fertilizes a
diploid egg, the fertilized egg is
with three copies of
each chromosome. Most human polyploids cease developing
as embryos or fetuses, but occasionally an infant survives for
a few days, with many anomalies. Eight cases of tetraploidy
(4 copies of each chromosome) have been reported. One such
child, at age 26 months, had severe delayed growth and devel-
opment, a small head with tiny features, and a heart defect.
Some organs normally have a few polyploid cells, with
no adverse effects on health. Liver cells, for example, may be
tetraploid or even octaploid (8 chromosome sets). Polyploidy
is common in ﬂ owering plants and is seen in some insects,
but it is rare in vertebrates.
A normal chromosome number is termed
Cells missing a chromosome or having an extra one are
u-ploid). Aneuploidy results from a meiotic
(f g. 24.12)
In normal meiosis, pairs of homologous chromosomes sepa-
rate, and each of the resulting gametes contains only one
member of each pair. In nondisjunction, a chromosome pair
fails to separate, either at the F rst or at the second meiotic
division, producing a sperm or egg that has two copies of a
particular chromosome or none, rather than the normal one
copy. When such a gamete fuses with its mate at fertiliza-
tion, the resulting zygote has either 47 or 45 chromosomes,
instead of the normal 46.
Symptoms that result from aneuploidy reflect which
chromosome is missing or extra. Autosomal aneuploidy