What factors affect single-gene PGD accuracy?

 

What factors affect single-gene PGD accuracy?

Many scenarios can affect the accuracy of single-gene PGD and cause misdiagnosis. Natera’s Parental Support addresses these problems by using a microarray testing platform with Parental Support bioinformatics. The accuracy of Natera’s single-gene PGD testing is usually greater than 99%. 

Scenario

Potential problem

Spectrum solution

Allele drop-out

With PGD testing, the very small amount of DNA available in the embryo biopsy sample needs to be amplified (or copied) many times to make sure that there is enough DNA available for testing. ADO occurs when one copy of a gene (or allele) amplifies and the other copy does not. This can cause a misdiagnosis. For a recessive condition, an unaffected carrier embryo could appear to be affected; for a dominant condition, an affected embryo could appear to be unaffected.

Natera evaluates many informative DNA markers—known as single nucleotide polymorphisms (SNPs)—surrounding the mutation. By evaluating a large number of linked SNPs, we are able to definitively diagnose the embryo, even if there is allele drop-out at the mutation site.

Chromosome recombination 

Chromosome recombination occurs when two copies of the same chromosome in a parent break and then reconnect to the opposite copy. Recombination is a normal occurrence that happens during the formation of the egg and sperm, but it can lead to misdiagnoses with PGD if it occurs near the disease gene.

Looking at linked markers throughout the chromosome enables the detection of chromosome recombination, reducing false-negative and false-positive results.

DNA contamination

Misdiagnosis can occur if non-embryonic DNA is mixed into the sample and tested by mistake.

Natera matches all embryo samples to DNA samples taken from the parents, confirming that the sample is from the embryo and that the embryos belong to those parents. This prevents misdiagnosis due to contamination or sample mix-up.

Extra or missing copies of the chromosome carrying the gene mutation

An extra or missing copy of the chromosome that contains the disease gene can lead to a misdiagnosis.

Before making a single-gene diagnosis, Natera evaluates the entire chromosome carrying the gene mutation to ensure that there are exactly two copies.

Human error

Human errors can result in sample mix-ups or subjective interpretation of results.

Natera matches all embryo samples to DNA samples taken from the parents, confirming that the sample is from the embryo and that the embryos belong to those parents. This prevents misdiagnosis due to contamination or sample mix-up. Natera’s highly accurate and proprietary analysis of results with the Parental Support algorithm eliminates human interpretation error.

 

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