Describing the number and physical features of chromosomes can reveal abnormalities that underlie genetic diseases. This description is facilitated by special staining techniques that produce a particular banding pattern on each chromosome. State-of-the-art techniques make this approach even more powerful, enabling the detection of individual genes that cause disease.
Some genetic diseases can be detected by looking at the structure and number of chromosomes that form when DNA is compacted during mitosis. Once chromosomes are formed, cytogeneticists halt mitosis and perform the staining. The staining produces a distinct banding pattern that reveals different characteristics such as number, shape, and type of chromosomes. Such a description of an individual’s chromosomes is called a karyotype.
To facilitate karyotyping, an image is taken of the stained chromosomes, and individual chromosomes are identified and cut out from the image. The chromosomes are then arranged in pairs and ordered by size. This layout is called a karyogram. In a human karyogram, the 22 autosomes are labeled 1 through 22, from the largest to the smallest pair. The two sex chromosomes are labeled X or Y. A karyogram makes it easy to spot missing or additional pieces of a chromosome, or a whole extra copy, all of which can underlie genetic diseases.
Marthe Gautier, Jérôme Lejeune, and Raymond Turpin discovered in 1959 that patients with Down syndrome had a third copy of chromosome 21. Down syndrome is therefore also called trisomy 21. People with Down syndrome typically have mild to severe intellectual disability and physical symptoms including delayed growth, but individuals vary widely in the degree to which they are affected. Down syndrome is caused when the copies of chromosome 21 fail to separate into distinct sperm or egg cells during meiosis. The result is a germ cell with 24 chromosomes instead of the usual 23. When such a germ cell fuses with a cell of the other parent during fertilization, the resulting zygote has 47 chromosomes. In a small percentage of Down syndrome cases only an extra piece of chromosome 21 is present, usually fused to a different chromosome.
Cytogeneticists nowadays extract much more information from a karyogram than merely the chromosome number and structure due to advances in molecular biology, chemistry, and instrumentation. The lichen-derived dye that was used in the first cytogenetic studies was replaced by more stable dyes such as Giemsa. Giemsa stains some parts of the DNA strand stronger than others, depending on base composition and chromatin structure. The resulting pattern of staining intensity is called G-banding. This pattern is reproducible and identical for individuals of a species, so abnormalities are easy to spot. There are several methods available to produce banding patterns, which facilitates diagnosis of different chromosomal abnormalities.
