Molecular Cytogenetics

Homapage / Molecular Cytogenetics

What is molecular cytogenetics?

Molecular cytogenetics combines molecular biology and cytogenetics. It involves the use of a series of techniques referred to as fluorescence in situ hybridization, or FISH.

What is FISH?

In the FISH technique, DNA probes which are labeled with different colored fluorescent tags that are specific for chromosomal regions are hybridized to interphase nuclei or metaphase chromosomes.

What are the advantages of FISH over conventional cytogenetic methods?

The advantage over conventional cytogenetic methods is that it can be applied to the interphase cell. This means that it is not necessary to culture cells to achieve metaphases. Since it is a rapid test and eliminates the need of culturing the cells, this technique is mainly used in prenatal and preimplantation genetic diagnosis (Figure 1 and 2).

 Figure 1: FISH analysis is performed under dark conditions.
Figure 2: Analysis of trophectoderm cells. Images are taken by a camera and stored in archive. 

What kind of samples can be analyzed using FISH?

  • Embryonic cells (Polar Body, Blastomere, Trophectoderm Cells)
  • Sperm
  • Amniotic fluid
  • Peripheral blood
  • Bone Marrow
  • Fetal blood (cord blood of the fetus)
  • Corrionic Villi (CV)
  • Abortus Material
  • Skin 

What are the diagnostic applications of the FISH Technique?

Preimplantation Genetic Diagnosis

  • 5 chromosome Probe Set (13,16,18,21,22) (Figure 3)
  • 9 chromosome Probe set (13,15,16,17,18,21,22,X,Y)
  • Telomeric Centromeric and Locus specific probes (for Translocation carriers) (Figure 4)

Prenatal Genetic Diagnosis

  • 5 chromosome Probe Set (13,16,18,21,22)
  • 9 chromosome Probe set (13,15,16,17,18,21,22,X,Y)
  • Telomeric Centromeric and Locus specific probes (for Translocation carriers)

Sperm FISH Analysis

  • 5 chromosome Probe Set (13,18,21,X,Y)
  • Telomeric Centromeric and Locus specific probes (for Translocation carriers)

Microdeletion Analysis

  • Prader-Willi/Angelman Syndrome
  • DiGeorge Syndrome
  • Williams Syndrome
  • Cri-du-Chat Syndrome
  • 1p36 Microdeletion Syndrome
  • Wolf-Hirschhorn Disease
  • SRY Region


  • Acute Lymphocytic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Multiple Myeloma
  • Myelodisplastic Syndrome
  • Non-Hodgkin’s Lymphoma
  • BCR/ABL t(9;22)
  • PML/RARA t(15;17)
  • AML/ETO t(8;21)
  • IGH/MAF t(14;16)(q32;q23)
  • Inversion (16)
Figure 3: Klinefelter’s Syndrome diagnosed in an embryo, (47,XXY).   Figure 4: FISH analysis with specific probes


What is Sperm FISH?

In the sperm FISH procedure, at least 1000 sperm cells are analysed by FISH technique. Cells can be analyzed for the chromosomes 13,16,18,21,22,X,Y and the aneuploidy and diploidy frequencies are calculated as percentages (Figure 5). Deviations from the normal ranges provide a guide for the estimation of the proportion of normal embryos in preimplantation genetic diagnosis procedures.

Normally each sperm contains 22 autosomal chromosomes and 1 sex chromosome (either X or Y). 

When is sperm FISH an appropriate diagnostic tool?

Sperm FISH is an appropriate diagnostic tool for

  • Severe male infertility cases
  • Repeated implantation failures
  • Recurrent pregnancy losses
  • Male translocation/inversion carriers

What are the advantages of the sperm FISH test?

The sperm FISH test provides a good guide to the frequency of normal or balanced sperm cells in male translocation or inversion carriers. According to our studies, reciprocal translocation carriers have a higher rate of unbalanced sperms compared to robertsonian translocation carriers.

Figure 5: Abnormal sperm containing an excess number of chromosomes.

In addition, the sperm FISH test is a valuable technique for detecting abnormalities such as gonadal mosaicism or de novo chromosomal abnormalities formed during spermatogenesis, which can be the underlying cause of repeated implantation failures or recurrent pregnancy losses.

What are de novo abnormalities?

De novo abnormalities do not come from the parents but occur spontaneously in the genome. They can be mutations or chromosomal rearrangements and can cause gonadal mosaicisms. De novo abnormalities are inheritable once they are formed.