PGT-M: Preimplantation genetic testing for monogenic disorders

Preimplantation genetic testing is performed prior to embryo transfer, which... 

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is intended for couples, who are at risk of transmitting a severe genetic disease to their offspring, which is caused by a defect of a single gene in one of the parents,

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allows to choose the „healthy“ embryo without specific genetic defect

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is performed in RepromedaLab since 2004, thus for the longest time out of all assisted reproduction centres in Czechia

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s performed on the 5th day after fertilization by collecting several cells from the developing embryo

Ing. Tomáš Kocur, MBA

Business Director

+420 774 973 680

What is PGT-M?

Preimplantation genetic testing for monogenic disorders (PGT-M), previously Preimplantation genetic diagnosis (PGD), is intended for couples, who are at risk of transmitting a severe genetic disease to their offspring, which is caused by a defect of a single gene in one of the parents. 

 

 

What is Karyomapping?

Karyomapping is a universal method combining Preimplantation genetic testing for monogenic disorders (PGT-M) with Preimplantation genetic testing for aneuploidies (PGT-A) in examined embryos within a single test and therefore allows to choose euploid embryo without genetic defect with the highest implantation potential.

Who is Karyomapping suitable for?

Karyomapping is designed for all the couples with a known genetic defect in a family, who are planning a pregnancy and want to ensure the birth of a healthy baby. Karyomapping could be applied to all the Mendelian disorders with autosomal dominant, autosomal recessive and X-linked type of heredity.

What is necessary to know before Karyomapping?

Prior to IVF treatment with Karyomapping, it is necessary to know the causal mutation responsible for a particular genetic disease in a family. For a successful analysis, we need to examine DNA of embryos and both parents, as well as a reference sample with a known genotype for a causal mutation. The typical example for the autosomal recessive disease would be Cystic Fibrosis, with both parents being healthy carriers of a mutation and a reference sample being their child with diagnosed Cystic Fibrosis.  

In certain situations, Karyomapping can be performed without a reference sample (de-novo mutations). In such case, there is an additional step of direct mutation analysis in embryos. This, along with the linkage analysis, can reliably detect which embryos do not carry any genetic defect. 

 

How does it work?

Karyomapping uses more than 300.000 polymorphic sequences (SNPs) equally distributed along the whole genome for indirect diagnostics of monogenic disorders. Analysis of those sequences results in a so-called karyomap, which visualizes haplotype layout of all chromosomes including crossing-overs in the examined embryo. In the first step, informative SNPs are identified, which allows determining all four parental haplotypes (two paternal marked as P1 and P2 and two maternal marked as M1 and M2). Those haplotypes represent four parental chromosomes.

 

Informative SNPs are subsequently compared with the genotype of a reference sample and allow to determine a „phase“ that represents, which out of four parental chromosomes the reference sample inherited. In the example above, with both parents being carriers for Cystic Fibrosis and the reference sample is their child suffering from Cystic Fibrosis, it could be identified which parental haplotypes are tied with causal mutations. In the last step, those haplotypes are compared to the reference sample and examined embryos. If the embryo has the same haplotypes as a reference sample, based on an indirect analysis supported by dozens of informative SNPs around the mutation, we can predict that embryo inherited both mutated alleles for Cystic Fibrosis.

 

What are the benefits of Karyomapping?

One of the main benefits of Karyomapping is its versatility. Thanks to equal distribution of informative SNPs across the whole genome it allows a diagnostics for any genetic disease with a known causal mutation. Therefore there is no need to optimize the whole procedure for each individual family, which would be very time consuming (a couple of months) and examination is typically done within several weeks. Another advantage is the simultaneous detection of aneuploidies in examined embryos, which tremendously increases the chance for a successful treatment.