Genome-wide sequencing: Ethical considerations

Genome is the collection of genes in every cell of a living organism. It is a code that tells the cells how to behave. Genome sequencing is a method that is used to determine the exact sequence of a certain length of DNA: short piece, specific parts, or the entire genome. The goal of genome sequencing is to decipher what the DNA sequence means and thus to understand how the disparities in genome account for individual differences. While not every difference is consequential, the sum of these differences is responsible for the organism’s specific outlook and behavior - even its probability of getting sick or responding to specific medications. Like most technologies, however, genome sequencing has its ethical challenges.

The major step towards understanding the human genome was pioneered by the Human Genome Project that successfully sequenced the entire genome of a human for the first time in 2003. Since then, the technology has developed to the point that genome-wide sequencing (GWS) (e.g., whole-exome sequencing, whole-genome sequencing) is an emerging approach of personalized medicine that is used in health care for genetic diagnosis of fetuses, children, as well as adults. While multiple serial tests were once required for a person under diagnostic investigation, GWS accomplishes this in a single assay. It requires patients to undergo a standard blood draw that is sent to the laboratory, where molecular analysts, bioinformaticians, and laboratory geneticists analyze the sequenced data. These groups of scientists must collaboratively interpret the sequencing results connecting phenotype to genotype and establish whether identified variants should be considered pathogenic. That can be done only with limited certainty and with the presence of incidental findings.

GWS is subject to many of the same ethical challenges as other genetic tests such as respect for individual autonomy and consent, balancing of harms and benefits, or protecting individual’s confidentiality while also considering the protection of individual’s relatives. What deserves special attention, however, is the concern with uncertainty, incidental findings, and the challenge on professional roles. The key sources of uncertainty lie in errors in genetic analyses, the question of whether genetics determine a patient’s phenotype or how much other factors (e.g. environmental) play a role, as well as in the question of the role of individual variation in a genome. Incidental findings are the results that are unrelated to the original purpose of GWS, but may be relevant to the patients and their genetically related families. Patients and their families should be informed about the possibility and decide if they wish to be informed if incidental findings arise. The presence of incidental findings is especially ethically challenging if the findings involve children, or reveal substantial and immediate potential harms that health interventions can mitigate. Particularly these concerns can present a challenge to health professionals who need to adjust to working and counselling patients based on the non-deterministic statistical data [4]. GWS is thus a technology that takes a huge step towards personalized medicine, but when putting it into practice, one needs to bear in mind its inherent ethical challenges. MS

CADTH/ CA 2019: Genome-Wide Sequencing for Unexplained Developmental Delays and Multiple Congenital Anomalies: A Rapid Qualitative Review. https://www.cadth.ca/sites/default/files/pdf/htis/2019/RC1098_Whole%20Exome%20Sequencing_Final.pdf

CADTH/ CA 2019: Genome-Wide Sequencing: Ethical Considerations. CADTH technology review. https://www.cadth.ca/sites/default/files/hta-he/he0020-genome-wide-sequencing-ethical-considerations.pdf

Robin Z Hayeems, Kym M Boycott, Genome-wide sequencing technologies: A primer for paediatricians, Paediatrics & Child Health, Volume 23, Issue 3, June 2018, Pages 191–197, https://doi.org/10.1093/pch/pxx152

Hashiloni-Dolev, Y, Nov-Klaiman, T, Raz, A. Pandora's pregnancy: NIPT, CMA, and genome sequencing—A new era for prenatal genetic testing. Prenatal Diagnosis. 2019; 39: 859– 865. https://doi.org/10.1002/pd.5495