A new kind of examination called “molecular karyotype” has nowadays almost replaced classical karyotype, used for the detection of various chromosomal abnormalities. Molecular karyotype (or array Comparative Genomic Hybridization – aCGH) is a modern technique which can detect chromosomal abnormalities with much higher precision than classical karyotype.
Array CGH is a technique of high sensitivity and precision. This examination can discover deviations from the normal number of chromosomes and quantitative chromosomal changes of a smaller size, such as microdeletions and microduplications. In such cases, only a small part- and not the whole chromosome- is absent or is duplicated.
This method can discover much smaller chromosomal changes (at an analysis range of 3-10 Mb) compared to what classical karyotype can find (segments smaller than ~4Mb). Of course, the small size of these mutations does not mean that these changes are less important. Such small alterations in the total quantity of the genetic material are considered responsible for various genetic syndromes, related with congenital anomalies, mental retardation, psychokinetic retardation, autism, etc.
Besides the detailed diagnosis, the molecular karyotype has plenty of other advantages. It is an examination which does not require cell culture, fact that makes the diagnostic method faster. In addition, this technique can provide us information for the whole genome, because it does not focus only on a particular side of the chromosomes, as conventional cytogenetic techniques (FISH) do. Therefore, now it is possible to discover genetic changes, that otherwise could not be found.
However, despite the pros, molecular karyotype has also its cons. The limitations of the method are related with the inadequate detection of balanced translocations (when two non-homologous chromosomes “exchange” parts) and inversions (when a chromosomal segment is reversed, resulting in rearrangement with opposite orientation), the inability to spot point mutations, to discover cases of polyploidy, or cases of mosaicism in a small rate (less than 10-15%). When it is considered necessary, the results of the molecular karyotype can be supplemented with a classical karyotype analysis.
Molecular karyotype is an analysis, which can be performed during the fertility examination of a couple, during the prenatal testing and during the second trimester of the pregnancy (after amniocentesis or trophoblast biopsy). In addition, molecular karyotype is a technique used also for embryo examination for preimplantation genetic testing (PGT), in cases of IVF. The examination can be performed with peripheral blood sample in the adults. In cases of PGT, the embryo is biopsied so that blastomeres can be taken for testing. In any case, the genetic lab performs DNA isolation from the obtained cells, which then is analyzed with the use of the microarray platform (CGH arrays).