A karyotype is a standardized picture of an individual’s chromosomes. To create this visual map, scientists isolate a cell, capture an image of the chromosomes during cell division when they are most condensed, and then arrange them in a specific order. The primary purpose of this technique is to screen for large-scale genetic changes, such as missing, extra, or structurally altered chromosomes. These changes may be associated with various developmental or health conditions.
The Visual Map of Chromosomes
The visual representation of the chromosomes, known as the karyogram, is meticulously organized for easy comparison. A typical human karyotype contains 23 pairs of chromosomes: 22 pairs of non-sex chromosomes (autosomes) and one pair of sex chromosomes. These homologous pairs are matched by size, shape, and the pattern of light and dark bands that appear when stained.
The chromosomes are arranged in descending order of size, starting with chromosome 1 and ending with chromosome 22, with the sex chromosomes placed last. This arrangement helps identify missing or extra copies of a particular chromosome. Each chromosome is characterized by a unique banding pattern, created using stains like Giemsa that bind differentially to DNA regions.
Each chromosome has a distinct structure defined by the centromere, the constricted point that divides the chromosome into two arms. The short arm is designated the “p” arm, and the longer arm is the “q” arm. The length ratio of the p and q arms, combined with the detailed banding pattern, allows geneticists to precisely identify every segment.
Understanding Standard Genetic Notation
Interpreting a karyotype report requires understanding the standardized alphanumeric language known as the International System for Human Cytogenomic Nomenclature (ISCN). A normal karyotype lists the total number of chromosomes, followed by the sex chromosomes. For example, a normal male is designated as 46, XY, and a normal female as 46, XX.
When an abnormality is present, the notation specifies the nature and location of the change. The plus sign (+) indicates the gain of an entire chromosome, and the minus sign (-) indicates the loss. For instance, an extra chromosome 21 is written as 47, XX, +21.
Structural changes use specific abbreviations:
- “del” for a deletion (loss of a segment)
- “dup” for a duplication (gain of a segment)
- “inv” for an inversion (a segment flipped and reinserted)
- “t” for a translocation (exchange of material between two different chromosomes)
To pinpoint the exact location of a structural change, the notation uses the chromosome number, the arm (p or q), and a band number. For example, a deletion on the short arm of chromosome 5 might be written as del(5)(p15), identifying the deletion at band 15 of the short arm.
Interpreting Numerical Abnormalities
Numerical abnormalities involve gaining or losing one or more entire chromosomes, a condition called aneuploidy. The most common type is trisomy, where a cell contains three copies of a specific chromosome instead of the usual two homologous copies. Trisomy 21 (47, +21) is a frequently cited example of this numerical gain.
Other recognized trisomies involve chromosomes 18 (47, +18) and 13 (47, +13), which are associated with developmental challenges. The opposite abnormality is monosomy, where only one copy of a particular chromosome is present. Complete monosomy of an autosome is rarely observed in live births as it is often incompatible with development.
Variations in the number of sex chromosomes are also common. Klinefelter Syndrome involves an extra X chromosome (47, XXY). Turner Syndrome is characterized by a single X chromosome in a female (45, X). These numerical changes are simple to identify by counting the total number of chromosomes and observing the extra or missing component.
Interpreting Structural Abnormalities
Structural abnormalities represent rearrangements of genetic material within or between chromosomes, rather than a change in the total count. A deletion occurs when a segment of a chromosome is lost, while a duplication is the presence of an extra copy of a chromosomal segment. Both result in an unbalanced karyotype because the total amount of genetic material is altered.
In an inversion, a chromosomal segment breaks off, flips 180 degrees, and reinserts into the same chromosome. If the inverted segment includes the centromere, it is called a pericentric inversion; otherwise, it is a paracentric inversion. Although an inversion does not change the total amount of genetic material, it can affect gene regulation and cause issues when passed to offspring.
Translocations involve the exchange of genetic material between two non-homologous chromosomes. A reciprocal translocation involves a simple, balanced exchange of segments, often written as $t(A;B)$. A Robertsonian translocation is a specific fusion occurring between two acrocentric chromosomes (13, 14, 15, 21, and 22). In this case, the long arms of the two chromosomes fuse, and the short arms are lost. This often leads to an overall chromosome count of 45, but the individual is typically healthy unless the translocation is passed on in an unbalanced form.