CHROMOSOME ABNORMALITIES
Genomic abnormalities that are large enough to
be detected by the examination of chromosomes by
microscopy are usually referred to as chromosome
abnormalities. Numerical chromosome abnormali-
ties include polyploidy and aneuploidy. Polyploidy
means an abnormal multiple of the number of
chromosomes; diploidy is normal, triploidy and
tetraploidy are abnormal and, therefore, polyploid.
Ployploidy is almost always lethal
in utero
, resulting
in spontaneous abortion. Aneuploidy refers to the
presence of an extra copy of a chromosome,
trisomy, or the absence of a copy of a chromosome,
monosomy. Aneuploidy frequently results in sponta-
neous abortion but live birth and even a near-normal
life span are possible. The aneuploid conditions
most frequently encountered clinically are listed in
Table 10.1
The structural abnormalities involving one
chromosome include deletions, inversions, duplica-
tions, ring chromosomes, and isochromosomes. A
ring chromosome arises when the end of each arm of
a chromosome has been deleted and the arms have
joined at the sites of the deletions. Isochromosomes
are the result of abnormal centromere division in
which there is duplication of one arm of the
chromosome and deletion of the other.
Insertions and translocations are structural
abnormalities that involve two, and sometimes more,
chromosomes. An insertion occurs when part of one
chromosome is inserted into another, nonhomolo-
gous chromosome. A reciprocal translocation
consists of the exchange of chromosomal material
between two nonhomologous chromosomes so that
two translocation chromosomes are formed. A
Robertsonian translocation consists of the fusion of
two acrocentric chromosomes at the centromere with
loss of the short arms of both so that a single translo-
cation chromosome is formed. Acrocentric chromo-
somes have their centromeres located far from the
center of the chromosome; the short arms are very
short, consisting of stalks with satellites at the end.
The acrocentric chromosomes are 13, 14, and 15
(group D) and 21 and 22 (group G).
Chromosome analysis
There are two methods currently in use for
chromosome analysis, G-banding and fluorescence
in situ
hybridization. G-banding refers to Giemsa
staining of chromosomes in their condensed state.
The cells that are used for this analysis are periph-
eral blood lymphocytes, which form the overwhelm-
ing majority of the mitotically active cells in
peripheral blood. An anticoagulated blood specimen
is added to tissue culture medium and incubated in
the presence of phytohemagglutinin. The phytohem-
agglutinin agglutinates the red cells from the speci-
men and stimulates the lymphocytes to divide. A
microtubule inhibitor, such as colchicine, is also
added to the medium to arrest the mitotic cells in
metaphase. Alternatively, the mitotic cells can be
arrested in prometaphase. The cells are harvested,
lysed with hypotonic buffers, fixed, and mounted on
cover slips. Following gentle trypsinization, the
chromosomes are stained with Giemsa. The Giemsa
staining results in a banding pattern that is character-
istic for each chromosome (Figure 10.1). Meta-
phase chromosomes produce approximately 350 to
550 bands per haploid set, prometaphase chromo-
somes produce approximately 850 bands, and
mechanically stretched metaphase chromosomes
produce upwards of 1400 bands (Claussen
et al.
1994). The bands are caused by alternating portions
of the chromosome that are darkly stained by
Giemsa (G-bands) and lightly stained by Giemsa
(R-bands). There is believed to be an underlying
structural explanation for the banding pattern. The
usual explanation is that G-bands contain DNA that
is rich in AT base pairs and R-bands contain DNA
Genetic Disease
10-1
Table 10.1
Most Frequent Abnormalities of Chromosome Number
Abnormality
Chromosome Disorder
trisomy
21
Down syndrome
X XXY
Klinefelter syndrome
Y XYY
XYY syndrome
monosomy
X XO
Turner syndrome
Chapter 10
GENETIC DISEASE
© 2001 Dennis A. Noe
