Fluorescent In Situ Hybridization to Diagnose Down Syndrome

A New Technique Used to Diagnose Down's Syndrome

Young female scientist working in the lab. Nicola Tree

FISH stands for fluorescent in situ hybridization. FISH testing, or FISH analysis as it is sometimes referred to, is a relatively new cytogenetic technique that allows a cytogeneticist to determine how many copies of a particular chromosome are present without having to go through all of the steps involved in producing a karyotype. For example, FISH analysis can quickly tell you how many number 21 chromosomes are present, but it cannot tell you anything about the structure of those chromosomes.

How It Works

FISH testing is usually done on the same samples as a karyotype - blood, amniocytes or a chorionic villi sample. A FISH test is done using a fluorescent probe that binds to certain specific chromosomes. These fluorescent probes are made of DNA specific to certain chromosomes and are tagged with a fluorescent dye. The cells used in the FISH analysis don’t have to be grown or cultured (which can take 7 to 10 days), so the results of a FISH analysis are available much faster than the results of a karyotype.

Typically, a sample is obtained and sent to the laboratory and the chromosomes are isolated on a slide. The probes are then placed on the slide and allowed to hybridize (or find their match) for about 12 hours. Because the probes are made of DNA, they will bind to the “matching” DNA of their specific chromosome. For example, a probe made of DNA specific to chromosome 21 will bind to any number 21 chromosome that is present.

After hybridization (or sticking), the slide is examined under a special microscope that can see fluorescent images. By counting the number of fluorescent signals, a cytogeneticist can determine how many of a specific chromosome are present. For example, a person without Down syndrome will have two fluorescent signals corresponding to their two number 21 chromosomes.

A person with trisomy 21 will have three fluorescent signals corresponding to their three number 21 chromosomes. Typically, cytogeneticists will use probes for the 13, 18, 21, X and Y chromosomes. These are the chromosomes that can result in trisomies for humans.

Diagnosing Down Syndrome

Although it doesn’t look at the actual structure of the chromosomes analyzed, FISH analysis can tell you how many copies of a particular chromosome are present. In Down syndrome, the cytogeneticist uses probes for the number 21 chromosome. If there are three fluorescent signals seen under the microscope, then the diagnosis of Down syndrome is made.

How Does FISH Testing Differ from a Karyotype?

FISH analysis only tells you that certain chromosomes are present and how many of them are present. For example, a typical FISH analysis will tell you how many 13, 18, 21, X and Y chromosomes are present in an amniotic fluid sample. FISH analysis will not give you information about every chromosome nor will it give you information about the actual structure of the chromosomes.


The main advantage of FISH analysis is that it can provide information about certain chromosomes quickly. For example, in three to four days, it can tell how many copies of a number 21 chromosome a particular person may have.

In contrast, a traditional karyotype can take up to two weeks.


The main disadvantage of FISH analysis compared to karyotyping is that FISH analysis gives you less information about all of the chromosomes being studied. For example, a typical prenatal FISH test will tell you how many number 13, 18, 21, X and Y chromosomes are present (i.e., whether there are two copies or three) but will not give you any information about any of the other chromosomes or any information about the actual structure of chromosomes.

What to Ask Your Doctor

  • Does the laboratory you use do FISH testing?
  • Does my insurance cover the cost of FISH testing?
  • How reliable is FISH testing for Down syndrome?
  • How long will it take to get FISH results (from my amnio or CVS)?
  • Does the lab also do a full karyotype?
  • How long does it take to get the results of the karyotype?

Bottom Line

FISH analysis has the benefit of providing rapid, but limited information, about a fetus’s chromosomes. It is very good at answering the question - “Does my baby have trisomy 21?” but it provides limited information about other structural chromosome abnormalities such as translocations and deletions.



American College of Obstetricians and Gynecologists (ACOG). Screening for Fetal Chromosomal Abnormalities. ACOG Practice Bulletin, number 77, January 2007.

National Human Genome Research Institute. Fluorescence In Situ Hybridization (FISH), 2008.