A karyotype is an organized profile of an individual’s chromosomes, providing a visual map of the entire genetic complement. This powerful tool involves microscopically examining the number, size, and shape of these structures to identify genetic variations. Karyotyping offers a comprehensive, genome-wide screen for abnormalities that can cause developmental disorders, infertility, or cancer. By providing a standardized view of the 23 pairs of human chromosomes, it serves as a foundational diagnostic method in medical genetics.
The Basic Function of Karyotyping
Karyotyping begins by collecting a sample of dividing cells, typically from blood, bone marrow, or amniotic fluid, and then culturing them in a laboratory setting. Technicians must arrest the cell division process at metaphase, the stage where chromosomes are most condensed and clearly visible. The chromosomes are then stained, most commonly using Giemsa banding, which produces a unique pattern of dark and light transverse bands along each chromosome arm.
The distinctive banding pattern allows for precise identification and pairing of chromosomes. The stained chromosomes are photographed and then arranged in a standardized format called a karyogram. They are organized into homologous pairs, ordered numerically from chromosome 1 down to chromosome 22, followed by the sex chromosomes (X and Y). This standardized arrangement makes it possible to immediately spot any deviations from the normal 46-chromosome pattern.
Diagnosing Conditions Caused by Aneuploidy
A frequent application of karyotyping is the detection of aneuploidy, which refers to having an abnormal number of chromosomes. These numerical errors, involving the gain or loss of entire chromosomes, are easily visible on the karyogram. Karyotyping provides confirmation for conditions resulting from an extra copy of an autosome, which are a major cause of birth defects and developmental delays.
A classic example is Trisomy 21 (Down syndrome), where a third copy of chromosome 21 is present. Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are lethal conditions caused by an extra copy of chromosomes 18 and 13. Karyotyping can accurately diagnose these conditions, often prenatally.
Karyotyping is the standard for confirming sex chromosome aneuploidies. Turner syndrome presents as a monosomy, with only a single X chromosome (XO), while Klinefelter syndrome is characterized by an extra X chromosome in males (XXY). These numerical abnormalities are apparent on the karyogram, making the technique a highly reliable initial diagnostic method for these syndromes.
Detecting Complex Structural Changes
Beyond counting chromosomes, karyotyping visualizes complex structural rearrangements within or between chromosomes. These changes include deletions, where a segment is missing, and duplications, where a segment is repeated. These issues cause an imbalance in genetic material, leading to various developmental disorders.
The technique is particularly useful for identifying translocations, which involve the exchange of segments between non-homologous chromosomes. A balanced translocation, where genetic material is rearranged but no net gain or loss occurs, often results in a phenotypically healthy carrier. However, these balanced carriers face a higher risk of producing gametes with unbalanced translocations, which can lead to recurrent miscarriage or the birth of a child with a severe genetic condition.
Karyotyping can detect inversions, where a chromosome segment has been flipped 180 degrees, which can interfere with proper pairing during meiosis. While newer methods offer higher resolution, karyotyping remains suited for detecting balanced structural rearrangements. This is because it provides a visual image of the entire chromosome architecture, showing the position of the material rather than just the amount. This visual integrity is crucial for genetic counseling regarding reproductive risk.
Assessing Somatic Mutations in Oncology
Karyotyping shifts its focus from inherited disorders to acquired mutations when applied in oncology, helping to classify and predict the behavior of cancers. Cancer cells frequently exhibit highly abnormal and chaotic karyotypes, including multiple numerical changes (polyploidy) and marker chromosomes. Analyzing these complex somatic changes is a powerful tool for cancer diagnosis and prognosis.
A clinically significant example is the Philadelphia chromosome, a reciprocal translocation between chromosome 9 and chromosome 22, designated t(9;22). This structural rearrangement, visible via karyotype, creates the BCR-ABL1 fusion gene. Its presence is the defining characteristic in over 90% of chronic myeloid leukemia (CML) cases.
Its presence not only confirms the diagnosis but also guides therapeutic decisions, as it indicates responsiveness to specific targeted drug therapies. Karyotyping maintains its importance as a versatile diagnostic platform, providing a snapshot of chromosomal health from prenatal screening to monitoring acquired genetic chaos in a tumor.