Cytogenetics is a field of biology dedicated to the study of chromosomes, the organized structures within cells that contain a person’s genetic information. This discipline investigates the number, structure, and inheritance of chromosomes. Through specialized laboratory techniques, cytogenetics helps understand how changes in these structures can impact health and development. It provides insights into their role in various biological processes.
Chromosomes and Their Basic Study
Chromosomes are thread-like structures inside the nucleus of animal and plant cells, carrying genetic information as DNA. Humans have 46 chromosomes arranged in 23 pairs: 22 autosomes and one pair of sex chromosomes (XX for females, XY for males). Each chromosome contains hundreds to thousands of genes, which are DNA segments providing instructions for building and maintaining an organism.
The basic study of chromosomes involves creating a karyotype, an organized profile of a person’s chromosomes. To prepare a karyotype, cells, commonly from blood samples, are cultured and stimulated to divide. At metaphase, when chromosomes are condensed and visible, their division is arrested. Cells are then treated with a hypotonic solution to swell and spread the chromosomes, followed by fixation to preserve their structure.
Prepared cells are then dropped onto glass slides and stained, typically using G-banding, which produces a unique pattern of light and dark bands on each chromosome. These banding patterns allow scientists to identify individual chromosomes and detect structural changes. The chromosomes are then photographed and arranged in a standardized order by size and centromere position, creating the complete karyotype for analysis.
How Cytogenetics Diagnoses Conditions
Cytogenetics plays an important role in diagnosing various health conditions by identifying numerical or structural abnormalities in chromosomes. These abnormalities can involve an extra chromosome, a missing chromosome, or rearrangements where parts of chromosomes are duplicated, deleted, or moved. Such changes help link specific chromosomal patterns to recognized genetic disorders.
One common application is diagnosing constitutional disorders, which are present from birth. For example, Down syndrome is caused by an extra copy of chromosome 21 (Trisomy 21). Turner syndrome, affecting females, results from the absence of all or part of one X chromosome (45,X). Klinefelter syndrome, affecting males, involves an extra X chromosome (47,XXY).
Cytogenetics is also important in oncology for identifying chromosomal changes associated with different types of cancer. Many cancers are characterized by specific chromosomal translocations, where segments of two different chromosomes swap places. For instance, chronic myeloid leukemia (CML) is identified by the Philadelphia chromosome, resulting from a reciprocal translocation between chromosome 9 and chromosome 22 [t(9;22)]. This rearrangement creates a fusion gene that drives cancer progression.
Advanced Cytogenetic Methods
Beyond traditional karyotyping, advanced cytogenetic techniques provide higher resolution and allow for the detection of smaller, more subtle chromosomal changes. These methods offer enhanced diagnostic capabilities, particularly when conventional banding techniques may not reveal the abnormality. They target specific chromosomal regions or analyze the entire genome for imbalances.
One such technique is Fluorescence In Situ Hybridization (FISH), which uses fluorescently labeled DNA probes that bind to specific DNA sequences on chromosomes. Under a fluorescent microscope, these probes illuminate particular regions, allowing detection of very small deletions, duplications, or translocations not visible with standard karyotyping. FISH can also count specific chromosomes or assess gene amplification.
Chromosomal Microarray Analysis (CMA), also known as array CGH, is another advanced method that detects very small gains or losses of chromosomal material across the entire genome. This technique compares a patient’s DNA to a reference DNA sample, identifying regions where the patient has too much or too little genetic material. CMA offers a much higher resolution than traditional karyotyping, enabling the detection of submicroscopic imbalances that can cause developmental delays, intellectual disabilities, or other medical conditions.