Genetic screening will empower families

Whole-exome screening: could it be a powerful tool for neonatal and lifelong health? Written by Rachel Westphal.

If you could know, from the day you were born, your risk of developing certain diseases, would you want to?

With the increasing affordability of genetic screening options, these tests have the potential to become powerful tools, empowering people towards lifelong health. In particular, whole-exome screening, which focuses on parts of the genome that can give more indication of disease risk, should become a part of routine neonatal healthcare.

Targeted testing

Some genetic tests look at all the genetic information in an organism, but whole-exome screening focuses on an important subset of the DNA. The exome is like the building instructions for putting amino acids together into a protein. If the instructions are wrong, the amino acid sequence can change and result in an abnormally-shaped protein, often causing health problems or diseases.

Whole-exome screening provides people with the power to understand their health like never before. It provides more data more quickly than other types of genetic testing, such as the multi-step process of testing for one potential genetic disease at a time. A trial screening reported on over 1,000 genetic conditions, a number that will only increase as genetic data is illuminated by new knowledge.

A simple procedure

Neonatal whole-exome screening would also be straightforward to implement. In one trial, neonates under 42 days of age were successfully tested with whole-exome screening. The trial demonstrated it could be done routinely alongside the heel prick test, only a blood or saliva sample is needed, and results take just a few weeks.

Furthermore, the cost of whole-exome screening starts at around £300, less than a third of the price of sequencing the entire genome. Although whole-genome sequencing is more powerful and may someday even be cheaper, for now whole-exome sequencing is more efficient as the exome is home to about 85% of genetic variations that cause disease.

Improving lives

Take the case of Turner syndrome. This genetic disorder in females can lead to infertility and a shortening of life expectancy by more than 10 years, particularly because 22% of patients are diagnosed only after age 12. With earlier detection, interventions such as surgery, hormone treatment, and hearing aids can be implemented in a timely manner. If neonatal whole-exome screening were widely implemented, there would be similar benefits for many other diseases.

Some people would prefer not to know their odds of getting a host of potentially deadly diseases and might resent the fact they had no say in the matter as a baby. However, some patients who have undergone exome screening as adults thought it was a positive experience. 

Michelle Ewy participated in a Mayo Clinic exome study and discovered she carried the BRCA2 mutation, significantly increasing her risks of breast and ovarian cancers. Since she did not know of a family history of these cancers, she was not previously aware of her risk. After genetic counselling, she decided to opt for surgery to remove her breasts and ovaries to limit her risk of disease. 

Another participant in the study, Damask Grinnell, also discovered a risk of breast cancer. She said, “I think it’s better to know now and to be able to do all these preventative things.” Personally, if I could know my risk for a disease and be able to detect and intervene early, I would prefer taking that risk to not knowing at all.

The law will need to protect genetic information, to ensure data is stored safely and protected from breaches and is not misused by commercial interests. Unfortunately, genetic data used in the wrong way could lead to discrimination. For example, life insurance policies above £500,000 can discriminate based on a genetic testing result.

Finally, counselling should become a mandatory accompaniment to genetic testing to ensure the results are properly understood. Genetic testing is not determinative: environmental factors and diet also influence risk of disease. As such, whole-exome screening provides a limited but useful assessment of risk. Parents (and later the child) must be well-informed about these nuances.

In summary, whole-exome screening will empower families and clinicians to anticipate risk of disease to detect and intervene early. This screening method is efficient, cost-effective, and powerful. When adopted with proper counselling and protection of genetic data, it can be a successful testing programme.

Rachel Westphal (she/her) is a Medical Law and Ethics LLM student. (Twitter: @ichbinrachelw)

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