Frequently Asked Questions

Which sequencers are supported by ⓖSEQ?

ⓖSEQ has been tested to run successfully in our own lab, and client labs across the world, on Illumina?s MiSeq, and on the Ion Torrent S5. See our whitepaper for more information on validation. We are interested in expanding ⓖSEQ to work on additional sequencer types, when a client requests it.

Does my clinic need to have a sequencer for me to use ⓖSEQ?

No. Your clinic may request a free biopsy kit (you must provide and respond to us on your official email address affiliated with your clinic, and describe your title at this clinic). Once the kit arrives, follow the instructions to send your embryo biopsies to the Genomic Prediction Clinical Lab in New Jersey, USA. You will get a ⓖSEQ report on your embryo biopsies within a few days of their arrival.

What are the benefits of using ⓖSEQ over other aneuploidy screens?

ⓖSEQ can match all of the features of the market dominant PGT-A solution: VeriSeq, including comprehensive chromosome screening (CCS). In addition, ⓖSEQ has ultra-high throughput (48 samples per sequencing run, compared to VeriSeq’s 24), single-step library prep (see the lab video - ⓖSEQ’s single-step lab prep takes 4 hours, rather than the 1.5 days of VeriSeq). In addition, ⓖSEQ has the ability to detect abnormalities which older methods such as VeriSeq cannot detect, such as polyploidy (whole genome trisomy), sample contamination (DNA from two embryos, or from the embryo and the lab technician), and even some instances of sample mislabeling. ⓖSEQ’s industry-leading data analysis techniques makes ⓖSEQ faster, broader, and more accurate than other, less advanced PGT-A products. Aside from all of this, our report is generated and email delivered automatically, with superior data detail, LIMS utility, and user interface (see video section). Our final advantage is that we are interested in adapting software, user interface, and research projects to your particular clinic. Learn more in this video.

If I want to try ⓖSEQ on my own sequencer, how do I order a free ⓖSEQ Kit? What does it include?

A ⓖSEQ trial kit includes the reagents required for preparing 48 samples for a single ⓖSEQ assay (specifically, six 8-strip tubes containing the master mix), as well as a number of 3d printed tools, and the documents required (protocol, manifest, sample sheet. The ⓖSEQ kit will look like this, and your clinic may request your free kit here (you must provide and respond to us on your official email address affiliated with your clinic, and describe your title at this clinic, as well as your sequencer setup).

When will EPⓖT be available?

EPⓖT will be available in 2018. Genomic Prediction’s Chief Science Officer, Dr. Nathan Treff, will present our validation study at ASRM (American Society for Reproductive Medicine) in October, titled “Validation of simultaneous preimplantation genetic testing (PGT) for aneuploidy, monogenic, and polygenic disorders”.

What is the difference betwen ⓖSEQ and EPⓖT?


Genomic Sequence
Quantification


Expanded Pre-Implantation
Genomic Testing

Fully Automated Report

Chromosome Abnormalities

Monogenic Disorders

Polygenic Disorders

Next Generation Sequencing

Microarray Technology

Number of disorders

Neanderthal Ancestry

Available for Adults

Available for Embryos

Available Now

Fully Automated Report

Chromosome Abnormalities

Monogenic Disorders

Polygenic Disorders

Next Generation Sequencing

Microarray Technology

Number of disorders

Neanderthal Ancestry

Available for Adults

Available for Embryos

Available Now

order of dozens

Learn More


Expanded Pre-Implantation
Genomic Testing

Fully Automated Report

Chromosome Abnormalities

Monogenic Disorders

Polygenic Disorders

Next Generation Sequencing

Microarray Technology

Number of disorders

Neanderthal Ancestry

Available for Adults

Available for Embryos

Available Now

100 - 1000

2018

Learn More

Which disease traits will EPⓖT screen against?

The following is a list of genomic predictors which may be available in our report. The predictors are developed using machine learning techniques on large genomic data sets, and validated on populations which are different from the population used in training. Our predictors improve as more data become available for training and testing. The actual disease risks which are included in our report may change over time.


Type 1 Diabetes

Type 2 Diabetes

Coronary Artery Disease

Atrial Fibrillation

Breast Cancer

Prostate Cancer

Hypothyroidism

Intellectual Disability (ID)

Idiopathic Short Stature (ISS)

Inflammatory Bowel Disease

Chronic Kidney Disease

Prostate Cancer

Malignant Melonoma

Basal Cell Carcinoma

Testicular cancer

Basal Cell Carcinoma

Hypertension

Hypertension (resistive)

Heart Attack

Ovarian Cancer

Schizophrenia

Does EPⓖT screen non-disease traits?

We provide risk scores for traits related to disease risk, but not for purely cosmetic traits. We want to provide improved health and well-being to IVF families.

Is it any different to look at 1000 places in the genome related to breast cancer risk, than it is to look at a single place - such as the BRCA1 gene - which affects breast cancer risk?

Fundamentally, polygenic screening is no different from monogenic screening. In both cases, you are stacking the odds, and reducing risk. The only difference is that polygenic predictors perform better than monogenic ones.

Improving genotype information quality and validation for the decisions being made provides benefit to IVF families, but it can only reduce risk, never remove it entirely. Much as screening against BRCA1 does not guarantee a life free of breast cancer, choosing the embryo among a dozen with the smallest breast cancer risk across the entire genome will not guarantee a life free of breast cancer. It only reduces the risk of breast cancer - albeit far more than the more primitive technologies of the past have been able to.

What screening in the past has been done which is similar to your EPⓖT, and what are the bioethics norms of the reproductive field?

While the PGT-A and PGT-M (pre-implantation genetic testing for aneuploidy and monogenic disease, respectively) aspects of our product are similar to existing products, the PGT-P (pre-implantation genetic testing for polygenic disease) aspect of our product is entirely new and unique. No other product in history has ever offered anything like PGT-P, our EPⓖT is the first to provide polygenic scoring across the entire genome of the embryo. This entirely novel concept has only recently been made possible by progress on the bleeding edge of scientific advance.

The American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) provides some pertinent bioethical framework, which serves to guide testing of human embryos.

ASRM and SART do not distinguish between monogenic and polygenic disease risk; in part because essentially all disease risk is polygenic in nature, as most scientists readily comprehend. Virtually all disease risks which are popularly described as monogenic are, at a deeper level of understanding, of course polygenic, due to the interconnected nature of gene expression across the human genome.

There is a formal bioethics position on this general subject, recently updated in 2018, written by the Ethics Committee of the American Society for Reproductive Medicine.

A key phrase from the paper:

PGD for adult-onset conditions is ethically justified when the condition is serious and no safe, effective interventions are available. It is ethically allowed for conditions of lesser severity or penetrance. The Committee strongly recommends that an experienced genetic counselor play a major role in counseling patients considering such procedures.

As mentioned above, a salient example is the case of genetic breast cancer susceptibility, the "Breast Cancer Risk" trait. Many locations in the human genome affect the polygenic trait of “Breast Cancer Risk”. The example which the bioethicists focus upon in the paper is the BRCA1 gene. The presence of a correctly identified BRCA1 variant does not predict with certainty that an individual will ever develop cancer. Rather, this is a single SNP, affecting a highly polygenic trait named Breast Cancer Risk. The ASRM Ethics Committee deliberates that the benefit of reduced cancer risk is difficult to simply compare to the potential negatives induced by PGT (damage to/destruction of the embryo, incorrect genotyping resulting in transfer of an embryo with BRCA1, etc), and must be weighed in consultation with a genetic counselor. However, PGT for BRCA1 is ultimately inferred to be ethically permissible. Of course, PGT for BRCA1 is widely practiced among members of SART, but not yet using a comprehensive, polygenic panel for the Breast Cancer Risk trait.

However, even simply selecting against several Breast Cancer Risk variants simultaneously - for example, BRCA1 and BRCA2 - is itself an expansion upon the premise inherent in selecting against just BRCA1 alone. It is key to understand that what is being screened against is not “BRCA”, but it is the polygenic trait of Breast Cancer Risk, which is affected by BRCA1, BRCA2, and many other genetic loci besides. There are many labs in the world, adherent to the ASRM Ethics Committee guidelines, who already offer to screen against both BRCA1 and BRCA2.

Likewise, the Myriad panel is an example of testing for many Breast Cancer Risk associated loci, albeit in adults (not in embryos).

A different disease example which is famously stochastic, but merely monogenic, is Torsion Dystonia. TD is primarily controlled by a single location in the genome, and has 30% of what is called “penetrance”. This means that if you have the genetic variant which is said to cause the disease, you get the disease 30% of the time. Nobody can reliably improve that prediction further; and in fact, there are well studied cases of Dystonia where monozygous twins (identical twins, with identical genetics, and growing up in the same household) have discordant disease phenotypes. The stochastic nature of the correlation between genotype and phenotype appears, for the time being, to be inherent and irreducible. Nonetheless, Torsion Dystonia has for decades likewise been a target for PGT, as has been the case for many other, similarly stochastic disease traits. This is why PGT for some variants affecting disease risk is justified, when the condition is serious and no safe, effective interventions are available. And this is why screening against conditions of even lesser severity or penetrance is commonplace in the field. One can never entirely avoid the element of chance, but one can weigh the dice against the most obvious 1's and 2's on the dice roll.

More generally, we adhere to the SART guidelines for moving innovation to practice.

What statistical certainty is needed for a prediction to be actionable?

This is something which the individual clinician / genetic counselor must advise and decide upon, as they already do for PGT-A and PGT-M.

How can different disease risks be weighed against one another?

This must again require genetic counseling and deliberation by the clinician / genetic counselor. It should not be left to a mathematical formula.

© Genomic Prediction, 2018