Before embarking on a discussion of chromosomal aberrations, it is appropriate to review karyotyping as the basic tool of the cytogeneticist. A karyotype is a photographic representation of a stained metaphase spread in which the chromosomes are arranged in order of decreasing length. A variety of techniques for staining chromosomes has been developed. With the widely used Giemsa stain (G banding) technique, each chromosome set can be seen to possess a distinctive pattern of alternating light and dark bands of variable widths (
Fig. 7.13 ). The use of banding techniques allows identification of each chromosome, and can detect and localize structural abnormalities large enough to produce changes in banding pattern (described later).
In humans, the normal chromosome count is 46 (i.e., 2n = 46). Any exact multiple of the haploid number (n) is called euploid. Chromosome numbers such as 3n and 4n are called polyploid. Polyploidy generally results in a spontaneous abortion. Any number that is not an exact multiple of n is called aneuploid. The chief cause of aneuploidy is nondisjunction of a homologous pair of chromosomes at the first meiotic division or a failure of sister chromatids to separate during the second meiotic division. The latter also may occur during mitosis in somatic cells, leading to the production of two aneuploid cells. Failure of pairing of homologous chromosomes followed by random assortment (anaphase lag) also can lead to aneuploidy. When nondisjunction occurs at the time of meiosis, the gametes formed have either an extra chromosome (n + 1) or one less chromosome (n − 1). Fertilization of such gametes by normal gametes would result in two types of zygotes: trisomic, with an extra chromosome (2n + 1), or monosomic (2n − 1). Monosomy involving an autosome is incompatible with life, whereas trisomies of certain autosomes and monosomy involving sex chromosomes are compatible with life. These, as we shall see, are associated with variable degrees of phenotypic abnormality. Mosaicism is a term used to describe the presence of two or more populations of cells with different complements of chromosomes in the same individual. In the context of chromosome numbers, postzygotic mitotic nondisjunction would result in the production of a trisomic and a monosomic daughter cell; the descendants of these cells would then produce a mosaic. As discussed later, mosaicism affecting sex chromosomes is common, whereas autosomal mosaicism is not.
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Fig. 7.13 G-bandedkaryotypefromanormalmale(46,XY).AlsoshownisthebandingpatternoftheX-chromosomewithnomenclatureofarms,regions,bands,andsubbands.(Karyotype courtesy of Dr. Stuart Schwartz, Department of Pathology, University of Chicago, Chicago, Illinois.) 2 3 2211112323456781 3 3 4 2 2 2 1 1 1 2 2 3 3 X-CHROMOSOME 1 1 Arm Region Band Sub-band p q 1 1 6 13 19 20 21 22 X Y 14 15 16 17 18 7 8 9 10 11 12 2 3 4 5 1 2
Structural changes in the chromosomes typically result from chromosomal breakage followed by loss or rearrangement of material. Such changes usually are designated using a cytogenetic shorthand in which p (French, petit) denotes the short arm of a chromosome, and q, the long arm. Each arm is then divided into numbered regions (1, 2, 3, and so on) from centromere outward, and within each region the bands are numerically ordered (