Chromosomal microarray analysis (XMA) is a high-tech method for assessing the karyotype for the presence of certain mutations associated with an increase in the number of DNA copies (duplication), or with the loss of part of the genetic material (deletion). Such anomalies often cause hereditary diseases, so CMA is an important diagnostic tool in modern medicine. Typically, this technology is used to check the genotype of the fetus, as well as newborns and children.
General characteristics of the method
Microarray chromosome analysis is otherwise called molecular karyotyping. The method is based on the technology of DNA hybridization with genetic markers (previously known specific nucleotide sequences) embedded in a carrier (matrix). The study allows to analyzemany sections of chromosomes and identify the presence of structural rearrangements (abberations) associated with a lack or excess of genetic material.
The method is not designed to detect point mutations in genes, but it has a higher resolution than traditional karyotyping. CMA can detect submicroscopic changes that play an important role in the pathogenesis of various diseases, including congenital anomalies and mental retardation.
The meaning of molecular karyotyping
The main purpose of CMA is to identify small additional (microduplication) or missing (microdeletion) fragments of genetic information relative to a standard sample. These deviations are called copy number variations (CNV).
The prefix "micro" means that this technology is aimed at detecting very small changes. However, CMA is also suitable for detecting major chromosomal anomalies, such as various aneuploidies (Down syndrome, Patau, etc.). However, the study is not able to determine changes within a single gene.
In addition to microdeletions and microduplications, analysis reveals the genetic identity of large parts of chromosomes, which may indicate:
- blood relationship of the child's parents;
- obtaining both copies of chromosomes from only one parent.
With XMA you can also detecttranslocations, but only if they are not balanced.
Chromosomal microarray analysis is not a way to decode a genotype or a method to detect any genes. This study is only aimed at comparing the amount of genetic material in the chromosomes of the patient with the control. After the discovery of CNV, the laboratory determines which genes were contained there and, based on this, interprets the result. Copy number variants play an important role in the pathogenesis of various diseases, but their presence does not always lead to any abnormalities.
Research purpose
Chromosomal microarray analysis is done to check if the baby has CNVs that could be the cause:
- autism;
- global stunting;
- mental retardation;
- various birth defects;
- convulsions;
- unusual physical features (dysmorphisms);
- congenital anomalies.
The study also determines the presence or absence of numerical chromosomal abnormalities (Down Syndrome, etc.).
There are 2 main reasons for doing an XMA test:
- prophylactic - checking the child's genome for microdeletions or microduplications;
- diagnostic - performed to establish the genetic causes of various disorders that may be associated with CNV.
Sometimes, to clarify the results of the study, a check of the genome of the parents is carried out.
According to the international standard and recommendations of several medical communities,XMA is a level 1 test designed for individuals with congenital anomalies, autism, or developmental disabilities of unknown origin.
Numerous reviews of chromosomal microarray analysis confirm its important diagnostic value. The method allows you to find the genetic causes of problems in a child when there are no common and fairly obvious chromosomal disorders (such as Down syndrome). Sometimes CMA, on the contrary, helps to exclude the presence of chromosomal disorders in children with developmental problems. Such results are considered favorable, since acquired defects are correctable, while genetic disorders cannot be corrected.
Method technology
XMA allows you to simultaneously analyze a large number of different DNA fragments, each of which corresponds to a specific genetic marker printed on the matrix. The latter is a subject stack covered in thousands of such probes.
2 types of DNA are used for the test:
- patient;
- standard (corresponds to the normal human genome).
Genetic material is applied to the matrix, where the hybridization reaction between the probes and their corresponding sample fragments takes place. That is, sequences from identical sections of chromosomes are combined with each other.
A special device separately evaluates the degree of hybridization of each probe with the control and with the prototype. In normalcase, it should be the same. If any fragment of the patient contains an excess of genetic material, the device gives a green signal, and if there is a deficiency, it is red.
Thus, all regions of the genome for which the matrix contains markers are evaluated. Instrument signals are captured by the scanner and processed by the computer.
XMA types
There are 3 types of chromosomal microarray analysis:
- targeted;
- standard;
- extended.
Their main difference lies in the resolution, which is regulated by the number of DNA markers used. This parameter is otherwise called the density of the matrix. In the target analysis, it is the lowest (350 thousand markers). This is the most accessible and cheapest type of test that detects the most common microdeletions and microduplications. It is used to confirm known specific syndromes associated with CNV.
Standard HMA uses 750,000 markers that test all clinically significant regions of the human genome. This test detects not only common CNVs, but also chromosomal abnormalities that cause undifferentiated syndromes. The same function, but much more informative, is performed by extended chromosomal microarray analysis. It represents the deepest study of the genome with a matrix containing 2.67 million DNA markers.
XMA Efficiency
XMA is a modern and very effective way to detect chromosomal abnormalities. before for themdetection used the standard cytogenetic method, which consisted of a visual inspection of the patient's chromosomes. In comparison, the resolution of molecular karyotyping is 1000 times higher and allows you to find the smallest changes that could not be detected before. This increased the diagnostic yield by 10. In addition, CMA does not require pre-culture of cells and allows you to analyze many regions of chromosomes at the same time.
The usefulness of molecular karyotyping for a particular patient depends on:
- of the selected type of analysis (advanced, targeted or standard);
- correct assessment of the result;
- equipment and a set of DNA chips (markers built into the matrix) that a particular laboratory uses.
The name of one of the highest quality medical genetic centers where you can perform chromosomal microarray analysis is "Genomed". Reviews about this institution describe it as a high-level medical organization with modern technological equipment that allows for a wide range of different genetic tests, including quite rare ones. For XMA in "Genomed" (Moscow, Podolskoe highway, 8) sets of DNA markers from the leading manufacturing company are used.
