Cytogenetics is the branch of genetics that studies human chromosomes in order to detect alterations in their number or structure. It is used to diagnose genetic syndromes, investigate the causes of recurrent miscarriage, guide oncological treatments and confirm prenatal findings.
At Ambar Lab we explain what tests are available, when they are requested and how the results are interpreted. We are a laboratory based in Esplugues de Llobregat (Barcelona), founded in 2012 by a team of biology professionals with more than 20 years of prior experience in a reference laboratory. We offer more than 3,000 clinical tests.
What is cytogenetics?
Cytogenetics is the biomedical discipline that analyses chromosomes — the structures containing our DNA — in order to identify chromosomal abnormalities that cause diseases or affect reproductive health. Each human cell contains 46 chromosomes organised into 23 pairs; any excess, loss or rearrangement may have clinical consequences.
This speciality combines microscopy, cell culture and molecular techniques to produce a large-scale “snapshot” of the genome. Unlike sequencing, which reads specific letters of DNA, chromosomal analysis detects changes on the scale of millions of bases: trisomies, monosomies, deletions, duplications and translocations.
Classical cytogenetics vs. molecular cytogenetics
Classical cytogenetics (also known as conventional cytogenetics) uses an optical microscope to visualise stained chromosomes in metaphase. This is the traditional karyotype technique.
Molecular cytogenetics, on the other hand, uses fluorescent probes or DNA microarrays to detect alterations much smaller than the human eye can see. This category includes FISH and array CGH techniques.
What is a cytogenetic study used for?
A cytogenetic analysis is used to diagnose or rule out diseases caused by chromosomal aberrations. Its main applications fall into four areas: reproduction, prenatal diagnosis, onco-haematology and paediatrics.
Chromosomopathies are more common than people realise. According to data published by the NIH, approximately 50% of first-trimester spontaneous miscarriages show a chromosomal alteration detectable by karyotype, a figure that rises to 67.8% when high-resolution molecular techniques are used.
Identifying the chromosomal cause provides decisive information: it helps estimate the risk of recurrence in future pregnancies, guides assisted reproduction techniques, adjusts oncological treatment according to genetic markers and confirms the clinical suspicion of a syndrome.
Types of cytogenetic tests
There are three main tests: karyotype, FISH and array CGH/SNP. Each has its own indication, resolution and turnaround time.
Karyotype
The karyotype is the classical test: cells are cultured, arrested during division, stained with G-banding and photographed under the microscope. It allows the 46 chromosomes to be viewed in order and makes it possible to detect aneuploidies (an abnormal number of chromosomes, such as trisomy 21) and major structural rearrangements.
Its resolution is around 5–10 Mb (megabases), so it does not detect microdeletions. It is the reference technique for family studies, recurrent miscarriage and initial diagnosis in children with suspected syndromes.
FISH (fluorescence in situ hybridisation)
The FISH technique (Fluorescence In Situ Hybridisation) uses fluorescently labelled DNA probes to look for specific chromosomal regions. It is rapid (24–48 hours) and highly precise when confirming specific trisomies (13, 18, 21, X, Y) or known microdeletions such as the one associated with DiGeorge syndrome (22q11.2).
It is the test of choice when the aim is to confirm a specific diagnostic suspicion or monitor conditions such as chronic myeloid leukaemia.
Array CGH / array SNP (molecular cytogenetics)
Array CGH (Comparative Genomic Hybridisation) compares the patient’s DNA with reference DNA on a chip containing thousands of probes. It detects gains and losses of genetic material with a resolution of up to 50 kilobases, around 100 times higher than the karyotype.
Array SNP adds information on loss of heterozygosity and consanguinity. Both are now the first-line standard for investigating developmental delay and autism of unknown cause.
When is a cytogenetic analysis recommended?
Genetic diagnosis through cytogenetics is requested in four well-defined clinical scenarios.
In fertility and recurrent miscarriage
Couples with two or more consecutive miscarriages have an indication for karyotype testing in both partners. According to a review published in Nature Medicine of 1,745 cases, 50.4% of the products of conception from spontaneous miscarriages show chromosomal alterations, with aneuploidies being the most frequent cause.
In prenatal diagnosis
When first-trimester combined screening or the non-invasive prenatal test (NIPT) indicates an elevated risk, the finding is confirmed by karyotype or array CGH on amniotic fluid or chorionic villi. Down syndrome (trisomy 21) is the most frequent chromosomopathy: according to the CDC, it affects approximately 1 in every 700 births, and 95% of cases are due to meiotic non-disjunction.
In onco-haematology
Many blood cancers are characterised by specific translocations. The best known example is the Philadelphia chromosome t(9;22), present in more than 95% of chronic myeloid leukaemias according to the American Society of Hematology, which enables treatment decisions to be made using tyrosine kinase inhibitors.
In paediatrics and rare diseases
In children with developmental delay, dysmorphic features or congenital malformations, molecular cytogenetics is the first-line study recommended by international societies. It allows the identification of microdeletions and microduplications responsible for many rare syndromes.
How is the test carried out step by step?
The process combines a straightforward sample collection with rigorous technical processing. These are the five steps followed by any cytogenetic study in the laboratory:
1. Sample collection. Biological material is obtained according to the clinical case: peripheral blood (lithium heparin tube), bone marrow, amniotic fluid, chorionic villi or miscarriage tissue.
2. Cell culture. The sample is incubated for 48–72 hours under controlled temperature and nutrient conditions in order to stimulate cell division and obtain active chromosomes.
3. Metaphase arrest. Colchicine is added to halt mitosis at the moment of maximum chromosomal condensation, when chromosomes are visible and can be analysed under the microscope.
4. Staining or hybridisation. The specific technique is applied according to the test: G-banding for the karyotype, fluorescent probes for FISH or fluorochrome labelling for array CGH.
5. Analysis and report. A specialist practitioner examines at least 20 metaphases (in the case of the karyotype) or the data generated by the microarray and issues a validated clinical report following ISCN nomenclature.
The turnaround time varies depending on the technique: 48 hours for urgent FISH, 7–10 days for a karyotype on blood and 10–21 days for array CGH.
How is a cytogenetic result interpreted?
The report is drafted following ISCN (International System for Human Cytogenomic Nomenclature). A normal female karyotype is expressed as 46,XX; a male karyotype with trisomy 21 is expressed as 47,XY,+21.
It is useful to be familiar with some key terms. A trisomy is the presence of three copies of a chromosome instead of two (for example, trisomy 21 = Down syndrome). A monosomy is the absence of a chromosome from a pair (45,X = Turner syndrome). A deletion involves the loss of a chromosomal fragment, while a translocation is an exchange of material between two chromosomes. Mosaicism refers to the coexistence of two or more cell lines with different karyotypes in the same individual.
Important: the result must always be interpreted by a medical geneticist or the specialist who requested the test.
Advantages of the cytogenetic study at Ambar Lab
Ambar Lab has experts in genetic diagnosis and a multidisciplinary team of specialists. The differentiating advantages of carrying out your cytogenetic analysis with us include ENAC accreditation under the UNE-EN ISO 15189 standard for clinical laboratories, a complete portfolio that brings karyotype, FISH, array CGH and array SNP together under one roof, and rapid turnaround times with results in 7–10 days for a standard karyotype. In addition, all our reports include clinical advice: a geneticist reviews every case before it is issued.
Frequently asked questions about cytogenetics
Does a cytogenetic test hurt?
No. For most studies, only a conventional blood draw is required. Only invasive prenatal tests (amniocentesis, chorionic villus sampling) require an ultrasound-guided puncture.
How long does a karyotype result take?
Between 7 and 10 working days for peripheral blood. Cell culture is the step that takes up most of the time.
Can cytogenetics detect all genetic diseases?
No. It detects large or medium-sized chromosomal alterations, but not single-point mutations. For those, exome sequencing or gene panels are used.
Is a karyotype the same as an array CGH?
No. The karyotype views chromosomes under the microscope and detects large changes. Array CGH analyses DNA with a resolution around 100 times higher and reveals microdeletions invisible to the microscope.
Is cytogenetics performed on embryos before implantation?
Yes, this is called Preimplantation Genetic Diagnosis (PGT-A) and is carried out during IVF cycles to select chromosomally normal embryos.
Does the National Health System cover the cytogenetic study?
Under established clinical indications (prenatal diagnosis with elevated risk, leukaemias, suspected syndrome), yes. Outside these indications, it is usually carried out privately.
Do you need to have a cytogenetic study?
At Ambar Lab we support you from sample collection through to the interpretation of the report. Request information with no obligation and our clinical team will guide you towards the most appropriate test for your case.
