FISH (Fluorescence In Situ Hybridization)
Definition
A laboratory technique used to detect and show the location of a specific DNA sequence on a chromosome. The person's set of chromosomes is fixed onto a slide; a small piece of DNA labeled with a fluorescent dye (a probe) is added. The probe finds and binds to the matching sequence on the chromosome, and where the probe has bound is seen under a special microscope.
Purpose
Diagnosis of genetic conditions, gene mapping, identification of chromosome abnormalities, and cross-species chromosome comparison. In the clinic, it is a targeted test used when a specific microdeletion or duplication syndrome is suspected.
Results
The expected number of signals is seen at the region the probe binds. A missing signal suggests a deletion, an extra signal suggests a duplication, and a signal appearing on an unexpected chromosome suggests a rearrangement or translocation.
Risks and Limitations
FISH only finds what you are looking for. It is a targeted test: it shows only the region the probe was designed for. For this reason it is not suitable for screening purposes unless suspicion points to a specific syndrome.
Chromosomal microarray (CMA) is a broader, higher-resolution primary test; FISH is a more focused approach. According to an international consensus statement, in people with developmental delay/intellectual disability, autism spectrum disorder, or multiple congenital anomalies, the diagnostic yield of CMA is 15 to 20%, while that of G-banded karyotyping is about 3%.
Conversely, truly balanced rearrangements and low-level mosaicism generally cannot be detected by array methods, and in these cases karyotype and FISH retain their value. The consensus recommends reserving karyotype for cases with a clear chromosomal syndrome (e.g., Down syndrome), a family history of a rearrangement, or a history of recurrent miscarriage.