Cytogenetic testing involves examining chromosomes, structures within our cells that contain our DNA. These tests analyze the number and arrangement of chromosomes to identify changes associated with various health conditions. Chromosomes carry thousands of genes that influence growth, development, and overall function. By studying these organized packages of DNA, medical professionals can detect abnormalities that may lead to genetic disorders or other health concerns.
Types of Cytogenetic Analysis
One method in cytogenetics is karyotyping, which provides a visual representation of an individual’s chromosomes. Cells are collected, grown in a laboratory, and treated to stop division when chromosomes are most condensed. Stained to reveal banding patterns, they are then photographed and arranged by size and shape into a karyogram. Karyotyping identifies large-scale changes, such as extra or missing chromosomes, or significant structural rearrangements like large deletions or translocations. This technique has a resolution limited to detecting changes larger than about 5 million base pairs.
Another technique is Fluorescence In Situ Hybridization (FISH), which uses fluorescently labeled probes to target specific DNA sequences on chromosomes. These probes bind to complementary sequences, causing targeted regions to light up under a special microscope. FISH can detect smaller deletions, duplications, or rearrangements that might be missed by conventional karyotyping, providing more detailed information about specific gene locations or copy numbers. It can be applied to both dividing and non-dividing cells, offering flexibility in analysis.
Chromosomal Microarray Analysis (CMA) offers a higher resolution view of the genome compared to karyotyping and FISH. It scans chromosomes for tiny missing or extra DNA pieces, known as copy number variants. CMA uses a microchip platform with thousands of probes to compare a patient’s DNA to a reference sample, identifying imbalances that can be as small as a few thousand base pairs. While CMA is effective at detecting these submicroscopic deletions and duplications, it does not identify balanced rearrangements, where DNA is rearranged but no material is gained or lost.
Medical Applications of Cytogenetic Testing
Cytogenetic testing plays a role in various medical situations, providing insights into genetic conditions across different life stages. In prenatal diagnosis, tests screen for chromosomal abnormalities in the developing fetus. They can detect conditions like Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), or Patau syndrome (Trisomy 13), especially when maternal screening tests or ultrasounds show unusual findings. This allows expectant parents and their healthcare providers to understand potential genetic conditions before birth.
Postnatal diagnosis uses cytogenetic testing in children who exhibit developmental delays, intellectual disabilities, or multiple congenital anomalies. Identifying a chromosomal cause provides families with answers and guides medical management. These tests can uncover genetic reasons for various symptoms, including growth issues, neurological concerns, or distinct physical features.
Cytogenetic testing is used in oncology to diagnose and guide treatment for certain cancers, particularly leukemias and lymphomas. Cancer cells often acquire chromosomal changes, such as specific translocations or gene amplifications, which can influence how the cancer behaves and responds to therapy. Detecting these acquired genetic alterations helps classify the type of cancer, estimate its prognosis, and inform decisions about targeted treatments.
They are also applied in fertility and reproductive health. Couples experiencing recurrent pregnancy loss or infertility may undergo cytogenetic analysis to identify underlying chromosomal rearrangements that could affect conception or lead to miscarriages. In some cases, testing can reveal balanced translocations in a parent that, while not causing symptoms in them, can result in unbalanced chromosomal abnormalities in their offspring.
The Testing Process and Sample Requirements
Cytogenetic analysis requires a biological sample containing cells with intact chromosomes. The type of sample collected depends on the patient’s age and the reason for testing. For unborn babies, samples are obtained through procedures like amniocentesis or chorionic villus sampling (CVS). Amniocentesis collects amniotic fluid containing fetal cells, usually between 15 and 20 weeks. CVS takes a tissue sample from the placenta, reflecting the baby’s genetic makeup, usually between 10 and 13 weeks.
For children and adults, the most common sample is a blood sample, from which white blood cells (lymphocytes) are used for analysis. A simple blood draw is usually sufficient. In some cases, like investigating blood cancers or specific genetic conditions, a bone marrow sample may be collected. This involves a procedure where a small amount of marrow is taken from the hip bone. Cheek swabs can also provide cells for some types of cytogenetic tests.
Interpreting Test Results
A normal cytogenetic test result indicates an individual has the expected 46 chromosomes and normal structure. For females, this is represented as 46,XX, and for males, 46,XY, signifying 22 pairs of non-sex chromosomes (autosomes) and one pair of sex chromosomes. These results suggest that no large-scale numerical or structural chromosomal abnormalities were detected by the specific test performed.
Abnormal results fall into two main categories: numerical and structural abnormalities. Numerical abnormalities involve too many or too few whole chromosomes. Examples include trisomy, where there is an extra copy of a chromosome (e.g., Trisomy 21 in Down syndrome), or monosomy, where a chromosome is missing (e.g., Monosomy X in Turner syndrome). These changes alter the overall amount of genetic material and can impact development.
Structural abnormalities involve changes in the organization of one or more chromosomes. This includes deletions (missing segments) or duplications (repeated segments). Translocations (pieces reattaching to other chromosomes) or inversions (reversed segments) are also structural changes. The impact of these structural changes varies depending on the specific chromosome involved and the size of the alteration. Interpreting these complex test results requires specialized expertise and should always be discussed with a healthcare provider or genetic counselor to understand the health implications.