More information about Preimplantation Genetic Diagnosis (PGD) for single gene disorders
PGD, or preimplantation genetic diagnosis, is a laboratory test used to examine one cell or several cells from an embryo for a specific genetic disease. To test the embryos a biopsy is performed on a single blastomere cell on Day 3 of development, or a trophectoderm biopsy of several cells from a blastocyst is performed on Day 5. Prior to embryo testing DNA samples are collected from both parents. These samples are needed to develop the single gene testing specific to the mutation in the family. It is also possible that DNA from additional family members will be requested (usually saliva samples). Depending on the single gene disorder and the specific mutations involved, it may take 2-8 weeks for Natera to develop the PGD test after all DNA samples have been received.
The single gene testing is performed by either Polymerase Chain Reaction (PCR) with gene sequencing and linkage analysis, or by linkage analysis alone. PCR with sequencing allows the lab to directly see if the genetic change, or mutation, is present in the embryo cell tested. Linkage analysis uses a set of genetic markers located around the mutation in question to determine which copy of a gene the embryos include. Natera’s linkage testing is unique in that it uses an average of 35 linked markers surrounding the mutation in question versus 2-6 like most PGD technologies. The accuracy of Natera’s PGD for a single gene disorder is typically greater than 99%.
Parental Support™ Technology from Natera
Parental Support™, Natera’s breakthrough technology, is the most accurate and comprehensive technology available to perform PGD. Single gene PGD is particularly prone to misdiagnosis, which can occur for many reasons. The main problems experienced are:
- Allele Drop Out (ADO) when the section of the DNA containing the gene mutation does not copy correctly and a mutation may be missed
- Chromosome recombination
- DNA contamination from non-embryonic DNA mixed into the sample
- Extra or missing copies of the chromosome carrying the gene mutation
- Human error
Natera’s Parental Support wards off these problems by using a microarray testing platform with Parental Support bioinformatics.
- To address allele drop out, Natera evaluates approximately 35 small areas of DNA called ‘markers’ that surround the mutation, compared with the 2 to 6 markers typically examined by other PGD methods. Multiple tightly linked markers with Parental Support enables precision by reducing false negatives and false positives. Natera matches all embryo samples to DNA samples taken from the parents, confirming that the DNA being tested is from the embryo, and that the embryos belong to the parents, to prevent misdiagnosis due to contamination or sample mix up.
- Natera evaluates the entire chromosome carrying the gene mutation to make sure there are exactly two copies before making a diagnosis on gene status.
Two different options for Single Gene Testing
Natera can also test for all chromosome abnormalities at the same time that single gene PGD is performed. Natera offers two options for single gene PGD:
- Single Gene Testing PLUS 24 Chromosome Aneuploidy Screening*
- Single Gene Testing PLUS Trisomy 21 Aneuploidy Screening
*The 24 Chromosome Aneuploidy Screening also includes aneuploidy testing for chromosome 21.
Patients may wish to consider Single Gene Testing PLUS 24 Chromosome Aneuploidy Screening if they:
- Are of advanced maternal age (35 or older)
- Have had previously failed IVF cycles
- Have experienced recurrent miscarriages
Screening for chromosome abnormalities, or aneuploidy, may increase the chance for healthy embryo implantation, decrease the chance of miscarriage, and reduce the chance of having a child with a chromosome problem. Parental Support uses a state-of-the-art SNP microarray to screen all 24 chromosomes from a single blastomere from a Day 3 biopsy, or from several cells from a Day 5 biopsy. It then compares information from the cell(s) with genetic information gathered by the parents and possibly other family members, along with genetic information learned from the human genome project, which increases the accuracy of the results.
Results are reported for all 24 chromosomes plus the single gene condition with a turn around time of 5 business days. A frozen embryo transfer (FET) is required.
While Natera can test for single gene disorders and aneuploidy (including Trisomy 21, or Down syndrome) at the same time, it is not possible to test for all potential causes of birth defects or genetic diseases. In order to perform PGD for a single gene disorder, Natera must know the exact DNA mutation(s) that are responsible for the disorder in the family first.
Preimplantation Genetic Diagnosis in the IVF Cycle
PGS for aneuploidy from Natera can be performed on Day 3 after fertilization, when one blastomere cell is removed from each developing embryo. PGS can also be performed on day 5 using a technique called blastocyst biopsy. These samples are then sent to Natera’s CLIA-certified laboratory in San Carlos, California.
With both day 3 and day 5 biopsies, embryos are frozen until test results are returned after 5 business days; they are then thawed and transferred in a later frozen embryo transfer (FET) IVF cycle.