C Y T O G E N E T I C S


Fluorescent IN SITU Hybridization (FISH)      Spanish Version


Fluorescent IN SITU Hybridization (FISH) is a relatively new technology utilizing fluorescently labeled DNA probes to detect or confirm gene or chromosome abnormalities that are generally beyond the resolution of routine Cytogenetics. The sample DNA (metaphase chromosomes or interphase nuclei) is first denatured, a process that separates the complimentary strands within the DNA double helix structure. The fluorescently labeled probe of interest is then added to the denatured sample mixture and hybridizes with the sample DNA at the target site as it reanneals (or reforms itself) back into a double helix. The probe signal can then be seen through a fluorescent microscope and the sample DNA scored for the presence or absence of the signal.


Metaphase FISH

FISH can be used in metaphase cells to detect specific microdeletions beyond the resolution of routine Cytogenetics or identify extra material of unknown origin. It can also help in cases where it is difficult to determine from routine Cytogenetics if a chromosome has a simple deletion or is involved in a subtle or complex rearrangement. In addition, metaphase FISH can detect some of the specific chromosome rearrangements seen in certain cancers.

The number of microdeletion syndromes diagnosed by FISH is expanding rapidly. The sensitivity of these tests in every case is better than routine Cytogenetics but depends on the particular syndrome. In some syndromes, the probe is specific for the defective gene as in Williams Syndrome where a deletion has been shown in the elastin gene in 96% of individuals with a firm diagnosis. In other syndromes such as Prader-Willi/Angelman, the etiology of the syndrome is heterogeneous and microdeletions compose only a portion of the cases (60%).


Microdeletion Syndromes Currently Diagnosable with FISH

  • Cri-du-Chat

  • Miller-Dieker Syndrome

  • Smith-Magenis Syndrome

  • Steroid Sulfatase Deficiency

  • DiGeorge/Velo-Cardio-Facial/CATCH-22/Shprintzen Syndrome
  • Kallman Syndrome

  • Williams Syndrome

  • Wolf-Hirschhorn

  • Prader-Willi/Angelman Syndrome


Interphase FISH

FISH can be used in interphase cells to determine the chromosome number of one or more chromosomes as well as to detect some specific chromosome rearrangements that are characteristic for certain cancers. The primary advantage of interphase FISH is that it can be performed very rapidly if necessary, usually within 24 hours, because cell growth is not required.

A good example is the Aneuploid Screen test which is performed on amniotic fluid cells when there is a strong clinical indication for one of the common trisomies. The sample nuclei are denatured and hybridized with DNA probes for chromosomes 13, 18, 21, X, and Y and results usually obtained within 24 hours. Routine Cytogenetics is included with an Aneuploid Screen to confirm the results or detect any abnormalities not detected by interphase FISH.


Click on the following links to see some FISH examples:


Basic Cytogenetics | Cytogenetics Information Site