Biology Reference
In-Depth Information
introduced (Caspersson et al. 1970; Drets and Shaw 1971). The most
common technique used today, G-banding, is shown in Figure 5.1. Each of
the chromosomes can be identified by its size, shape, and characteristic
banding pattern. The light and dark bands of each chromosome are num-
bered according to an accepted international standard (Fig. 5.2) (Mitelman
1995). By convention, the chromosomes are ordered essentially from
largest to smallest, with the shorter arm of each chromosome (the p arm)
positioned on top, and the longer q arm below.
When a chromosomal rearrangement such as a translocation or deletion
is described, it is done according to nomenclature guidelines that cite the
chromosome(s) involved and the band where the break is thought to have
occurred (Mitelman 1995). For example, a deletion (del) of chromosomal
material from the long arm of chromosome 14 between bands q22 and q23
is denoted as del(14)(q22q23). A translocation (t) between the short arm
of chromosome 3 from band p24 to the end of the short arm (pter), and the
long arm of chromosome 8 from band q13 to the end of the long arm (qter),
is described as t(3;8)(p24;q13).
2.1 Cytogenetic Causes of Human Disease
Over the course of hundreds of thousands of years of evolution, the human
species has come to maintain a relatively stable karyotype. Gross variation
in the number or structure of human chromosomes severely reduces genetic
fitness. It is estimated that the human complement of 46 chromosomes con-
tains 50,000 to 100,000 genes, with temporal and spatial regulation of each.
With few exceptions, addition or deletion of whole chromosomes (aneu-
ploidy) is incompatible with life. Large subchromosomal deletions or
duplications are similarly lethal, whereas fetuses with small deletions or
duplications may be viable. A large percentage of the DNA that comprises
human chromosomes does not encode proteins, but even small, submicro-
scopic pieces of chromosomes can contain dozens or hundreds of genes.
Chromosomal rearrangements such as translocations can abrogate gene
expression, resulting in multiple congenital anomalies, similar in nature to
an autosomal dominant mutation.
2.1.1 Aneuploidy
The first chromosomal disorders reported to cause human pathology were
aneuploidies. Lejeune et al. reported in 1959 that nine children with “mon-
golism” (Down syndrome, Fig. 5.3) had an additional small chromosome
(now known to be chromosome 21) (Lejeune et al. 1959). In the same year,
a number of sex chromosome aneuploidies were reported, including Turner
syndrome (45,X, Fig. 5.4), in which a female typically has only 45 chromo-
somes, with monosomy X (Ford et al. 1959), and Klinefelter syndrome
(47,XXY), in which a phenotypic male has two X chromosomes and one Y,
