JOVANA
Library Glossary Getting Started Three Levels Fields How it works Mission
Join the mission
All guides

Mosaicism and the Tools That See It: FISH

Not every cell in a body need carry the same chromosomes. Mosaicism — two cell populations in one person — explains milder presentations, and FISH is the molecular probe that pinpoints changes the karyotype can miss.

Mosaicism: a body of two populations

So far we have assumed every cell in a person carries the same karyotype. Mosaicism breaks that assumption: it is the presence of two or more genetically different cell populations in one individual, all grown from a single fertilized egg. It arises when an error like nondisjunction happens not in a gamete but after fertilization, during the embryo's own divisions. Every cell descended from the slip-up inherits the change; every cell from the normal lineage does not.

The earlier in development the error occurs, the larger the share of affected cells. This is why mosaic forms of conditions like Down syndrome can present more mildly than the full version: if only a fraction of cells carry the trisomy, the dose imbalance is diluted across the body. A karyotype reports mosaicism by listing both populations, for example 46,XX / 47,XX,+21, with the proportion of each.

FISH: lighting up a target

A karyotype is powerful but limited: it sees whole chromosomes and large bands, so it can miss a microdeletion or fail to identify exactly which chromosomes are involved in a complex rearrangement. FISH — fluorescence in situ hybridization — fills that gap. It uses a short, lab-made stretch of DNA called a probe, matched to one specific region of the genome and tagged with a fluorescent dye. The probe binds only to its matching sequence, so under the microscope that exact spot glows.

  1. Choose a probe matched to the region in question — say, the chromosome 21 region for a suspected trisomy.
  2. Gently denature the cell's DNA so the double strands separate, exposing single strands the probe can read.
  3. Let the fluorescent probe hybridize — bind by base-pairing — to its matching target region.
  4. Count the glowing dots under the microscope: two signals is the expected pair, three flags a trisomy, one flags a deletion or monosomy.

Because FISH targets a precise spot, it can confirm a microdeletion invisible to the karyotype, and it can be read on cells that are not dividing — useful for rapid checks. The two techniques are partners: the karyotype gives the whole-genome overview, and FISH zooms in to answer a pointed question. Together with newer microarray methods, they are how cytogenetics turns an invisible chromosomal change into a visible, countable signal — the thread that has run through this entire track.