Karyomapping is a robust modern molecular-genetic array-based examination of variants in the DNA sequence. The so-called "indirect" genetic diagnosis, which is the basis for PGT-M examination, is based on the unicity of a set of these variants in each individual. As it is an examination of the entire genome, in addition to examining any monogenic disease, it also allows for an indicative screening examination of the quantitative changes of all chromosomes (PGT-A).
Principle of the Karyomapping method
The method is based on the comparison of DNA of the embryonal samples and DNA of the couple and a reference family member collected within SET-UP. DNA is extracted from the collected samples and in addition, the whole genome amplification (WGA of the MDA type) is performed in embryonal samples. The examination itself is performed on a special type of microchip (SNParray) that is able to detect at the same time large number of selected single-nucleotide polymorphisms of the whole genome. A particular combination of SNP in the area of the gene causing a particular monogenic disease distinguishes the individuals (family members, embryos) and both their alleles of this gene (haplotypes). By comparing the found haplotypes with the family tree information of the examined family the haplotypes associated with the presence of the respective mutation (i.e. carrying a risk for the condition) are then determined. In some cases which however occur very rarely it is necessary to use Karyomapping in combination with direct detection of the mutation. The method is universal and enables examination of any known monogenic disease. Another advantage includes a significant reduction of complexity and decrease of the preparation phase of the examination (SET-UP).
Limitations of the Karyomapping method
PGD for a familial monogenic disease (PGT-M) cannot exclude any other disease or congenital defect of the foetus which are not caused by mutation in the respective gene. Karyomapping cannot detect the de novo mutations in the embryonal DNA.
Karyomapping, as a method primarily intended for elimination of a monogenic disease, does not provide detection of random aneuploidies to the level comparable with aCGH or NGS. Screening of aneuploidies using Karyomapping is only an additional examination that can increase success of therapy by means of selection of the most promising embryo and is offered charge-free
Genetic analysis and consultation
2019/08/27 IVF Zentren Prof. Zech – Pilsen, RNDr. Martina Hrubá, Ph.D.