Cytogenetics is a specialized field at the intersection of classical genetics and cell biology, focusing on the study of chromosomes. These thread-like structures, found within the cell nucleus, are the carriers of an organism’s deoxyribonucleic acid (DNA). The discipline examines the number, structure, and behavior of chromosomes to understand how they relate to cell function and heredity.
The primary goal of cytogenetic analysis is to detect and characterize chromosomal abnormalities that may lead to disease or developmental issues. By visualizing the genetic blueprint, scientists link changes in the physical organization of DNA to clinical outcomes. This information is used across various medical specialties to inform diagnosis, prognosis, and treatment decisions.
The Role of Chromosomes
Chromosomes are the central subject of cytogenetics because they contain the vast majority of an organism’s genetic information. Each chromosome is a complex of DNA coiled around structural proteins, primarily histones. This organization ensures that DNA can be accurately replicated and distributed during cell division.
A normal human cell contains 46 chromosomes, organized into 23 pairs. Twenty-two pairs are autosomes, and the final pair consists of the sex chromosomes (XX or XY). Cytogenetics identifies two main categories of aberrations: numerical and structural changes.
Numerical abnormalities, or aneuploidy, involve having an extra or missing copy of an entire chromosome. For instance, having three copies of a chromosome instead of two is known as a trisomy. These changes are most commonly caused by errors during cell division, specifically nondisjunction.
Structural abnormalities involve rearrangements within or between chromosomes, though the total number remains 46. These include translocations (segments swapping places), deletions (missing pieces), and inversions (flipped segments). While some structural changes are balanced, others result in a loss or gain of genetic material, severely impacting development.
Essential Laboratory Techniques
The visualization and analysis of chromosomes require specialized laboratory techniques. The foundational method is the G-banded karyotype. This process involves culturing cells and treating them with a mitotic inhibitor to arrest them at the metaphase stage of division.
G-Banded Karyotype
At metaphase, chromosomes are condensed and distinct. Cells are stained using Giemsa dye, which produces G-bands—a reproducible pattern unique to each chromosome pair. A karyotype is created by digitally arranging the resulting images by size and banding pattern. This allows detection of large-scale structural rearrangements or numerical errors, though resolution is limited to changes spanning several million base pairs of DNA.
Fluorescence In Situ Hybridization (FISH)
To detect smaller changes, Fluorescence In Situ Hybridization (FISH) is employed. This technique uses small, fluorescently tagged DNA probes designed to bind only to a specific target sequence on the chromosome. When viewed under a fluorescent microscope, the probe’s location lights up, allowing for the detection of microdeletions, microduplications, or specific gene fusions. FISH can be performed on non-dividing cells, but it is limited to looking for the specific change for which the probe was designed.
Chromosomal Microarray Analysis (CMA)
The highest-resolution technique for detecting copy number changes across the entire genome is Chromosomal Microarray Analysis (CMA). CMA compares the patient’s DNA to a reference sample to detect subtle gains (duplications) or losses (deletions) of genetic material. CMA can identify changes smaller than the resolution of a karyotype. While highly effective at detecting unbalanced changes, CMA cannot detect balanced structural rearrangements, such as translocations, which require physical visualization.
Cytogenetics in Medical Diagnosis
The diagnostic power of cytogenetics is applied across the lifespan, addressing congenital conditions, reproductive challenges, and acquired diseases. A long-standing application is in prenatal diagnosis, using fetal cells obtained through amniocentesis or chorionic villus sampling. This screens for constitutional disorders in the developing fetus.
Prenatal and Constitutional Diagnosis
Prenatal cytogenetics routinely confirms or rules out common numerical abnormalities like Trisomy 21 (Down syndrome) or Turner syndrome. Results provide crucial information for managing pregnancy and preparing for care. For couples with recurrent miscarriage, testing can reveal a balanced translocation in a parent, which often leads to non-viable pregnancies.
For children and adults, cytogenetics diagnoses constitutional disorders that manifest after birth, such as unexplained developmental delays or intellectual disability. Analysis of a peripheral blood sample looks for an underlying chromosomal cause. Identifying a specific aberration, like a microdeletion syndrome, provides a clear diagnosis and allows for targeted medical management and genetic counseling.
Cancer Cytogenetics
A major area is cancer cytogenetics. Unlike constitutional disorders, cancer involves acquired chromosomal changes that occur only in tumor cells, driving growth and progression. Identifying these specific abnormalities classifies the cancer type, predicts its behavior, and guides treatment selection.
A classic example is the Philadelphia chromosome, a reciprocal translocation between chromosomes 9 and 22, which is diagnostic for Chronic Myelogenous Leukemia (CML). Identifying this rearrangement is tied to the use of targeted therapy drugs. Cytogenetic analysis remains a tool for determining prognosis and monitoring treatment effectiveness, particularly in hematological malignancies.