Biology Reference
In-Depth Information
for a complement number of 47 instead of the usual 46 (Jacobs and Strong
1959). Additional sex chromosome aneuploidies, such as 47,XXX, 47,XYY
and other combinations, were also described.
Of all cytogenetic abnormalities observed, aneuploidies are the most
common. They account for greater than 90% of the chromosomally abnor-
mal newborns and spontaneous pregnancy losses (Therman and Susman
1993). The sex chromosome aneuploidies are the only variations in total
chromosome number that can yield a relatively healthy individual. Indeed,
often patients with sex chromosome aneuploidies are ascertained only at
puberty or in adulthood when sexual developmental or reproductive
difficulties arise. Among the autosomal trisomies, only trisomy 21 is
compatible with a relatively long life, but it is characterized by multiple
developmental problems, both physical and mental. Trisomy 21 is the single
most common cause of mental retardation, and has the highest incidence
of any autosomal chromosomal aneuploidy in liveborns (Gardner and
Sutherland 1996). Other autosomal trisomies, such as trisomies 13 and 18,
are seen among liveborns, but these infants have severe mental and physi-
cal handicaps, and rarely survive for more than a year (Therman and
Susman 1993). If these trisomies are found in a mosaic state, where only a
subset of cells in the body has the abnormal number of chromosomes, the
individual may live many years, though a wide spectrum of disabilities, from
very mild to profound will typically be present. Other trisomies or mono-
somies are generally only seen in stillbirths or miscarriages, reflecting the
severity of the chromosomal imbalance on fetal development.
2.1.2 Unique Chromosomal Rearrangements
A variety of chromosomal rearrangements is possible, having been seen in
human karyotypes. A translocation is an exchange of genetic material
between two chromosomes. Translocations can be either balanced or un-
balanced. The term balanced implies an exact exchange of chromosomal
material. Constitutional balanced translocations are usually without clini-
cal significance to an individual. Approximately 1 in 500 newborns are
balanced translocation carriers (Hook and Hammerton 1997). However,
an apparently balanced translocation can also cause gene disruptions or
fusions, resulting in an untoward outcome. For example, studies show that
balanced translocations are five times more frequent in mentally retarded
individuals than in the general population (Funderburk et al. 1977).
The best studied translocations are the acquired translocations found in
various cancers, especially hematological disorders. Perhaps the most well
known translocation in human disease is the “Philadelphia” chromosome
described by Nowell and Hungerford in leukemic cells from patients with
chronic myeloid leukemia (Nowell and Hungerford 1960). Named for the
city in which it was discovered, the Philadelphia chromosome results from
a balanced translocation between chromosomes 9 and 22, t(9;22)(q34;q11).
