Our genetic instruction manual is organized within the cell nucleus in chromosomes. Genetic disorders can often be traced to alterations in these structures. The karyotype is a powerful diagnostic tool that provides a snapshot of an individual’s entire set of chromosomes, allowing scientists to visually scan for large-scale genetic clues. This technique is used in medical genetics to detect chromosomal abnormalities that result in various syndromes and health conditions.
Visualizing the Genome
A karyotype is an organized picture of a person’s chromosomes, captured during cell division when they are most condensed and visible. Cells, often collected from a blood sample, are cultured and treated to stop them in the metaphase stage. This stage is chosen because the chromosomes are tightly coiled, making them easiest to analyze under a microscope.
The chromosomes are then stained, most commonly with a Giemsa dye in a process called G-banding. This creates a distinct pattern of light and dark stripes along each chromosome’s length. These unique banding patterns are specific to each chromosome, acting like a barcode that aids in identification. The resulting images are arranged into a standardized format, pairing homologous chromosomes and ordering them by size (chromosome 1 to chromosome 22), with the sex chromosomes (X and Y) placed last. This visual arrangement, sometimes called a karyogram, allows for the assessment of the entire genome for structural or numerical changes.
Clues from Chromosome Quantity
The most straightforward clue a karyotype reveals is an abnormality in the total number of chromosomes. The normal human cell contains 46 chromosomes, arranged in 23 pairs. A deviation from this number is known as aneuploidy, indicating the presence of an extra or missing chromosome.
An extra chromosome is termed a trisomy, meaning three copies of a specific chromosome exist instead of two. The most recognized example is Trisomy 21, commonly known as Down Syndrome, where an individual has three copies of chromosome 21. Trisomy 18 (Edwards Syndrome) and Trisomy 13 (Patau Syndrome) are other severe conditions resulting from an extra copy of those autosomes.
Alternatively, the absence of a chromosome is called a monosomy. Monosomy of an entire autosome is typically lethal, but monosomy of a sex chromosome is survivable. Turner Syndrome, for instance, is characterized by a female having only one X chromosome (45,X). Extra sex chromosomes also present as numerical abnormalities, such as Klinefelter Syndrome (47,XXY) or Triple X Syndrome (47,XXX).
Clues from Chromosome Arrangement
Beyond counting, the karyotype is highly effective at detecting alterations in the physical structure of individual chromosomes. The specific G-banding patterns allow analysts to see if a piece of a chromosome is missing, duplicated, or moved. The total chromosome count may be the normal 46, but the internal arrangement is visibly incorrect.
A deletion occurs when a segment of a chromosome is lost, resulting in a shorter chromosome with a missing block of banding. Cri-du-chat syndrome is a well-known condition caused by a deletion on the short arm of chromosome 5. Conversely, a duplication involves an extra copy of a chromosome segment, making that chromosome longer than its pair.
Translocations are visible rearrangements where a piece of one chromosome breaks off and attaches to a different, non-homologous chromosome. This exchange can be balanced (no genetic material is lost or gained) or unbalanced (leading to a gain or loss of material). Inversions are structural changes where a segment of a chromosome breaks off, flips around, and reattaches, appearing as a reversed banding pattern within the chromosome arm.
Limitations of Karyotype Analysis
While robust for large-scale changes, karyotype analysis has limitations in resolution. The technique relies on visually identifying changes in stained chromosomes under a microscope, meaning only larger alterations are noticeable. Karyotyping generally has a resolution limit of about 5 to 10 megabases (Mb) of DNA.
The test is ineffective for detecting small genetic changes, such as point mutations (a change in a single DNA base pair). Very small deletions or duplications (microdeletions or microduplications) are too small to be seen using this method. Subtle forms of mosaicism—where an individual has two or more cell lines with different genetic makeups—can also be missed if the percentage of abnormal cells is low.
A normal karyotype therefore does not rule out all genetic disorders. This prompts the use of complementary, higher-resolution tests like DNA sequencing or chromosomal microarray analysis when a small-scale anomaly is suspected.