A karyotype provides an organized profile of a person’s chromosomes, offering a fundamental tool in genetic analysis. It presents an individual’s complete set of chromosomes, arranged in homologous pairs and ordered by size. This visual representation identifies chromosomal abnormalities that can lead to various genetic conditions.
The Building Blocks of a Karyotype
A karyotype displays all 23 pairs of human chromosomes: 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes (XX for female, XY for male). These chromosomes are arranged by size, with sex chromosomes positioned last. Each chromosome exhibits distinct light and dark bands when stained, allowing for identification and detection of structural changes. Cells for a karyotype are obtained from samples (e.g., blood, amniotic fluid), cultured, and then halted during metaphase when chromosomes are most visible. They are then stained and photographed for analysis.
Reading a Normal Karyotype
A normal karyotype uses standard notation. A normal human karyotype consists of 46 chromosomes arranged in 23 pairs. Represented as “46, XX” for a female and “46, XY” for a male, “46” indicates the total chromosome number. “XX” or “XY” specifies the sex chromosomes, determining biological sex. A normal karyotype indicates all chromosomes are present in correct number and appear structurally sound, without visible deletions, duplications, or rearrangements.
Spotting Chromosomal Variations
Identifying deviations from a normal karyotype involves examining both the number and structure of the chromosomes. Numerical abnormalities, known as aneuploidies, occur when there is an extra or missing chromosome. For example, a trisomy indicates an extra copy of a chromosome, resulting in three copies instead of the usual two, while a monosomy means a chromosome is entirely missing. These numerical changes are detected by counting the total chromosome number and observing if any pair has more or fewer than two chromosomes.
Structural abnormalities involve changes within the chromosomes themselves, altering their banding patterns or overall shape. These can include large deletions, where a segment of a chromosome is missing, or duplications, where an extra segment is present. Inversions occur when a segment of a chromosome is reversed, while translocations involve segments of chromosomes moving to a different, non-homologous chromosome. Karyotyping can reveal these rearrangements by showing altered banding patterns or unusual chromosome sizes and shapes.
Genetic Insights from Karyotypes
Karyotypes provide insights into various genetic conditions by revealing specific chromosomal changes. For instance, Down syndrome, a common genetic condition, is identified by an extra copy of chromosome 21 (Trisomy 21). In such cases, the karyotype would show 47 chromosomes instead of 46, with three copies of chromosome 21. Turner syndrome, affecting females, is characterized by only one X chromosome instead of two, notated as 45, X. Klinefelter syndrome, affecting males, is identified by an extra X chromosome, resulting in a 47, XXY karyotype.
Karyotyping also detects structural abnormalities with clinical relevance. For example, specific translocations, such as the Philadelphia chromosome (between chromosomes 9 and 22), are associated with certain forms of leukemia. Karyotype analysis also investigates recurrent miscarriages, as balanced translocations in parents can lead to unbalanced chromosome sets in offspring.
What Karyotypes Don’t Reveal
While karyotyping is a powerful tool for detecting chromosomal abnormalities, it has certain limitations. Karyotyping can only identify relatively large changes in chromosome number or structure. It cannot detect single gene mutations, which are small changes within a gene’s DNA sequence. Very small deletions or duplications, often referred to as microdeletions or microduplications, may also be beyond the resolution of standard karyotyping.
Epigenetic modifications, which are changes in gene expression without altering the underlying DNA sequence, are not visible through karyotype analysis. For these finer-scale genetic alterations, other tests like DNA sequencing or chromosomal microarray analysis are necessary.