Whole Genome Sequencing and its Revolutionary Role in Reproduction

Introduction: Whole Genome Sequencing and the Future of Reproduction

Whole Genome Sequencing is defined as the process of determining the complete order of nucleotides in an organism's DNA, including both coding and non-coding regions, which provides a comprehensive understanding of an individual's genetic makeup MedlinePlus Genetics.

Whole Genome Sequencing is expected to revolutionize the field of pregnancy and reproduction. Noura S. Siddiqui, founder and CEO of Orchid Biotech, predicts that comprehensive embryonic screening within In Vitro Fertilization (IVF) procedures will become the optimal approach to reproduction. She emphasizes that this advanced genomic approach can significantly reduce pregnancy-related risks.

Orchid Biotech offers whole genome sequencing for embryos before implantation in IVF. Analyzing the DNA of multiple embryos provides parents with a significant opportunity to reduce the likelihood of their children developing inherited diseases. Siddiqui discussed this topic with Dr. George Church, a leading figure in genomics and professor of genetics at Harvard Medical School, during the WIRED Health Summit.

Impact of Genome Sequencing on Genetic Diseases

It is estimated that 4% of the world's population suffers from diseases caused by a single gene mutation. According to Siddiqui, these monogenic diseases can be entirely avoided through embryo screening.

In addition, nearly half of the world's population suffers from chronic diseases with a genetic basis. By screening five embryos before implanting one, the genetic component of this risk can be mitigated by 30% in the worst-case scenarios and 80% in the best-case scenarios.

Orchid's website explains that the precise risk reduction percentage depends on several factors, including disease prevalence, the number of embryos analyzed, and the extent to which the screened genetic variants impact disease likelihood.

Cost-Effectiveness and Expert Opinions

Church, an investor in Orchid, believes that the embryo screening offered by the company is one of the most cost-effective medical technologies.

The first Human Genome Project cost $3 billion, but the cost of genome sequencing has significantly decreased since then. Whole genome sequencing at Orchid costs several thousand dollars per embryo.

Church views this as a ten-fold return on investment, noting that a significant portion of healthcare costs and psychological and family problems could be resolved this way.

Personal Experience and Types of Diseases Screened

Siddiqui has used this technology to screen her own embryos. She recounted her mother's story, who suffered from blindness in adulthood due to a genetic change in her genome. She said, "Fortunately, all the embryos were negative for that."

She added, "The other thing that is very common in most South Asian families is a high risk of heart disease and diabetes. And that's what we really focus on."

The blindness Siddiqui described is monogenic, meaning it is caused by a single genetic change. Among known monogenic diseases, "95% have no treatment, let alone a cure," Siddiqui stated.

But many other conditions, such as schizophrenia, bipolar disorder, or heart disease, are polygenic, resulting from the cumulative effect of many genetic variants. For these conditions, genetic risk scores can determine the risk of developing the disease and can be calculated for both adults and embryos. Orchid's embryo tests look for both types of diseases.

Reducing Genetic Risks and Ethical Considerations

Siddiqui said about polygenic conditions: "In a normal IVF cycle, you can get a risk reduction of between 30 to 80 percent using the models available today."

"Even if we limit it to the worst-case scenarios, i.e., parents at high risk, the percentage drops from 80% to about 55%." She added that this can be a greater reduction than what can be achieved by high-risk patients taking medication.

However, critics argue that using genetic risk scores to select embryos raises significant ethical concerns, by stigmatizing preventable diseases, and represents a form of eugenics. It is also, at present, an expensive technology available only to a few.

In almost all cases, whole genome sequencing provides information, but also uncertainty. Church had his genome sequenced and mentioned that he suffers from dyslexia, narcolepsy, and cholesterol problems. He said, "Some of them were clear in my genome, and some are still not entirely clear."

For adults considering sequencing their genome, the prospect of what they might discover can be unsettling – but not everything discovered needs to be disclosed.

Church said: "You can enter into a contract with your doctor, essentially stating, 'Don't tell me certain things I don't want to know.' You can categorize things that have no cure."

He also suggested that you could request to withhold information disclosed to you if diseases that were previously untreatable become treatable.

Genome Sequencing for Newborns: Between Benefit and Concern

But there was one group whose genome Church was not enthusiastic about sequencing: newborns.

He said, "It's kind of too late for very early diseases, and too early for late-onset diseases." He noted that these latter cases have very few treatments. "It's a recipe for anxiety more than anything else."