PGT-SR (preimplantation genetic testing for structural rearrangements) is a test developed for carriers of chromosome rearrangements

Chromosome rearrangements are formed when one or more pieces of chromosomes, the structures that contain an individual’s genetic material, find themselves in an altered position. For example, one common type of rearrangement, called a ‘translocation’, occurs when there is an exchange of materials between two chromosomes.

Approximately 1 in 500 people carry a chromosome rearrangement. People who have a balanced chromosome rearrangement in their cells are usually healthy, but they are at increased risk of producing pregnancies where the fetus has pieces of chromosome lost or duplicated. This loss or duplication of parts of a chromosome often leads to miscarriage, or the birth of children with disabilities.

PGT-SR (preimplantation genetic testing for structural rearrangements) is a test developed for carriers of chromosome rearrangements, which examines embryos produced using IVF technology in an attempt to distinguish embryos that are normal or balanced for the structural rearrangement from those that have pieces of chromosome missing or duplicated. Only embryos predicted to be normal/balanced are transferred to the uterus and consequently the risks of a miscarriage or abnormal pregnancy are reduced.

Translocations

Translocations

Fragments of two chromosomes are broken and exchanged. In this case the exchange does not involve any gene gain or loss for that chromosome, they continue functioning normally.
Fragments of two chromosomes are broken and exchanged. In this case there is a gene loss/gain in the chromosomes resulting from unbalanced chromosome material in the genome.
Robertsonian translocations are the most common type of structural rearrangements wherein a certain type of chromosome (acrocentric) fuses with another such chromosome resulting in a long chromosome. Such translocations may result in a loss or gain of either of the fused chromosomes when dividing in egg or sperm cell.
Fragments from two different chromosomes have been exchanged. After producing sperm or eggs, part of one chromosome has been lost (light green) while part of the other has been duplicated (dark green). This results in loss/gain of certain genes located on the chromosomes involved in the translocation: the rearrangement is said to be ‘unbalanced’. End-to-end fusion of two acrocentric chromosomes (which only have one arm). Increased risk of loss or duplication during formation of sperm and eggs, leading to high risk of trisomy and monosomy for the chromosomes involved. A portion of one of the chromosomes is lost, meaning that the genes that were in the affected area are deleted.

Deletions

A breakage in the DNA sequence can result in a loss or deletion of a chromosome fragment.

Duplication

Duplication is when a segment of a chromosome is doubled-up, meaning there will be extra copies of the genes in the affected region.

Insertion

Insertion is when a fragment of a chromosome is detached from its original place and inserted into another chromosome.

Inversions

When two breaks occur on the same chromosome, and the resulting fragment rotates before inserting back into the chromosome, this leads to ‘inversions’. When eggs or sperm are produced, the normal and inverted copies of the chromosome come together and exchange pieces. The presence of the inversion can result in a proportion of the gametes to lose parts of the affected chromosome, while duplicating other areas.

What are the benefits of PGT-[SR]Seq?

The transfer of embryos with the correct number of chromosomes is associated with:

Who should consider PGT-[SR]Seq?

PGT-SR is for couples where one partner is known to carry a balanced structural rearrangement. Types of rearrangement that can be tested include Robertsonian or reciprocal translocations and pericentric or paracentric inversions.

Juno Genetics’ PGT-SR technology uses next-generation sequencing in order to provide the best possible accuracy rates (exceeding 95%). The highly-validated test assesses thousands of sites on each chromosome, measuring the amount of DNA at each point in order to calculate the number of chromosomes. In many cases, this analysis is supplemented by analyzing variations in the DNA sequence, known as single nucleotide polymorphisms (SNPs), further enhancing the accuracy of the test.

logo PGTSR
PROCESS
Case feasibility assessed by Juno
IVF
5-10 days
Biopsy and embryo vitrification
Sample sent to Juno Genetics
PGT[SR]Seq
Transfer of normal embryos
Case feasibility assessed by Juno
IVF
5-10 days
Biopsy and embryo vitrification
Sample sent to Juno Genetics
PGT[SR]Seq
Transfer of normal embryos

A detailed description of the PGT[SR]Seq method and its requirements is given in the Juno Genetics User Manual. In brief, Juno can undertake a new PGT[SR]Seq case once a genetic report describing the chromosomal rearrangement has been received and a Juno scientist has confirmed that PGT[SR]Seq is technically possible. A completed Requisition Form, formally requesting PGT[SR]Seq and providing relevant information concerning the patients, is also required. Rarely, PGT[SR]Seq is not technically possible. For this reason, patients should not begin a cycle until Juno has reviewed the patient’s genetic report and confirmed that PGT[SR]Seq is feasible.

RESOURCES

Clinical documentation

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