Prenatal Whole Genome Sequencing: Just Because We Can, Should We?

Hastings Center Report

Volumn 42, Issue 4, 2012, Pages 28-40

  Donley, Greer ^a   Hull, Sara Chandros ^a   Berkman, Benjamin E ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; DNA SEQUENCE; ETHICS; FEMALE; GENETIC COUNSELING; GENETIC SCREENING; GENETICS; HEALTH CARE POLICY; HUMAN; HUMAN GENOME; PRACTICE GUIDELINE; PREGNANCY; PRENATAL DIAGNOSIS; UNITED STATES;

FEMALE; GENETIC COUNSELING; GENETIC TESTING; GENOME, HUMAN; HEALTH POLICY; HUMANS; PRACTICE GUIDELINES AS TOPIC; PREGNANCY; PRENATAL DIAGNOSIS; SEQUENCE ANALYSIS, DNA; UNITED STATES;

EID: 84865297917     PISSN: 00930334     EISSN: 1552146X     Source Type: Journal    
DOI: 10.1002/hast.50     Document Type: Article

References (42)

1. E.R. Mardis, "The Impact of Next-Generation Sequencing Technology on Genetics, " Trends in Genetics 24, no. 3 (2008): 133-41; W.G. Feero, A.E. Guttmacher, and F.S. Collins, "Genomic Medicine-an Updated Primer, " New England Journal of Medicine 362 (2010): 2001-2011; G. Carr, "Biology 2.0: A Special Report on the Human Genome, " The Economist, July 17, 2010.
2. Common problems that have been enumerated range from the complexities of informed consent to the availability of genetic counseling resources and the difficulties in maintaining privacy. See T. Caulfield et al., "Research Ethics Recommendations for Whole-Genome Research: Consensus Statement, " PLoS Biology 6, no. 3 (2008): e73; J.A. Robertson, "The $1, 000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals, " American Journal of Bioethics 3, no. 3 (2003): 35-42; A.L. McGuire, T. Caulfield, and M.K. Cho, "Research Ethics and the Challenge of Whole-Genome Sequencing, " Nature Reviews Genetics 9, no. 2 (2008): 152-56; K. Ormond et al., "Challenges in the Clinical Application of Whole-Genome Sequencing, " Lancet 375 (2010): 1749-51.
3. B. Wilfond and K. Nolan, "National Policy Development for the Clinical Application of Genetic Diagnostic Technologies: Lessons from Cystic Fibrosis, " Journal of the American Medical Association 270 (1993): 2948-54.
4. The American College of Genetics and Genomics recently issued a policy statement regarding clinical application of whole genome sequencing. While it does conclude that whole genome sequencing "should not be used at this time as an approach to prenatal screening, " this recommendation is not explored in any detail. American College of Medical Genetics and Genomics, "Points to Consider in the Clinical Application of Genomic Sequencing, " May 15, 2012, at http://www.acmg.net/StaticContent/PPG/Clinical_Application_of_Genomic_Sequencing.pdf.
5. Although these kinds of concerns have been raised about the implementation of novel screening technologies for newborns, given the unique timing of prenatal testing and the massive scope of whole genome sequencing, we believe that this technology will produce distinct ethical concerns as well. See B.A. Tarini, "The Current Revolution in Newborn Screening: New Technology, Old Controversies, " Archives of Pediatric and Adolescent Medicine 161, no. 8 (2007): 767-72.
6. W. Burke et al., "Genetic Screening, " Epidemiologic Reviews 33 (2011): 148-64.
7. L.B. Weinstein, "Selected Genetic Disorders Affecting Ashkenazi Jewish Families, " Family and Community Health 30, no. 1 (2007): 50-62.
8. See B.K. Rothman, The Tentative Pregnancy: How Amniocentesis Changes the Experience of Motherhood (New York: W.W. Norton, 1993); L. Remennick, "The Quest for the Perfect Baby: Why Do Israeli Women Seek Prenatal Genetic Testing?" Sociology of Health and Illness 28, no. 1 (2006): 21-53.
9. A. Hall, A. Bostanci, and C.F. Wright, "Non-Invasive Prenatal Diagnosis Using Cell-Free Fetal DNA Technology: Applications and Implications, " Public Health Genomics 13, no. 4 (2010): 246-55.
10. J.O. Kitzman et al., "Noninvasive Whole-Genome Sequencing of a Human Fetus, " Science Translational Medicine 4, no. 137 (2012): 137ra76, DOI: 10.1126/scitranslmed.3004323.
11. Of course, clinical norms and practices related to genetic testing are constantly evolving, and some practitioners have recently begun offering tests that do not fall within the category of diagnostic tests for serious medical conditions. For example, the BRCA genes, which are not diagnostic, have already been incorporated into some prenatal genetic screening panels. Despite these recent developments, we maintain that the vast majority of data generated by whole genome sequencing will represent new categories of information that are not currently available.
12. E.D. Green and M.S. Guyer, "Charting a Course for Genomic Medicine from Base Pairs to Bedside, " Nature 470 (2011): 204-213.
13. A.L. McGuire and J.R. Lupski, "Personal Genome Research: What Should the Participant Be Told?" Trends in Genetics 26, no. 5 (2010): 199-201; Ormond, "Challenges in the Clinical Application of Whole-Genome Sequencing."
14. See P. Sebastiani et al., "Retraction of Sebastiani et al., " Science 333 (2011): 404.
15. Green and Guyer, "Charting a Course for Genomic Medicine from Base Pairs to Bedside"; R.R. Sharp, "Downsizing Genomic Medicine: Approaching the Ethical Complexity of Whole-Genome Sequencing by Starting Small, " Genetics in Medicine 13, no. 3 (2011): 191-94.
16. S.C. Hull and K. Prasad, "Reading between the Lines: Direct-to-Consumer Advertising of Genetic Testing, " Hastings Center Report 31, no. 3 (2001): 33-35.
17. We acknowledge that the cost of sequencing is only part of the total cost of having the test performed. Other nontrivial factors include the cost of analysis and genetic counseling. We expect these factors to play a role in affordability for consumers, but ultimately to decrease over time.
18. For example, the costs of various prenatal screening tests vary widely. As a reference, however, the Ashkenazi Jewish panel (screening for three to nine conditions) ranged in cost from $200-$2, 082 in 2005. See J.R. Leib et al., "Carrier Screening Panels for Ashkenazi Jews: Is More Better?" Genetics in Medicine 7, no. 3 (2005): 185-90; Mardis, "The Impact of Next-Generation Sequencing Technology on Genetics"; Carr, "Biology 2.0."
19. Illumina, "Illumina Reduces Price of Whole Human Genome Sequencing through Illumina Genome Network, " May 2011, at http://investor.illumina.com/phoenix.zhtml?c=121127&p=irol-newsArticle&ID=1561106&highlight=; Illumina, "Illumina Announces Bold Steps to Accelerate the Adoption of Individual Genome Sequencing, " June 2011, http://investor.illumina.com/phoenix.zhtml?c=121127&p=irol-newsArticle&ID=1572084.
20. Rothman, The Tentative Pregnancy; Remennick, "The Quest for the Perfect Baby."
21. N. Wade, "Disease Cause is Pinpointed with Genome, " New York Times, March 10, 2010; Carr, "Biology 2.0."
22. These categories at times bleed into each other and may not form an exhaustive list, however.
23. One might be skeptical that such uncertain or nonmedical results would actually be shared with a parent who chooses to engage in prenatal whole genome sequencing. However, without a clear commitment discouraging such disclosures, we cannot assume that this information will be withheld from all or most parents. This might be of a particular concern in this category given that this information might be disseminated to parents whether or not the parents were initially interested in receiving it. See E.A. Ostrander, H.J. Huson, and G.K. Ostrander, "Genetics of Athletic Performance, " Annual Review of Genomics and Human Genetics 10 (2009): 407-429; J.R. Garcia et al., "Associations between Dopamine D4 Receptor Gene Variation with Both Infidelity and Sexual Promiscuity, " PLoS One 5, no. 11 (2010): e14162, DOI: 10.1371/journal.pone.0014162; K.E. Burdick et al., "Genetic Variation in DTNBP1 Influences General Cognitive Ability, " Human Molecular Genetics 15, no. 10 (2006): 1563-68.
24. F. Hathaway, E. Burns, and H. Ostrer, "Consumers' Desire Towards Current and Prospective Reproductive Genetic Testing, " Journal of Genetic Counseling 18, no. 2 (2009): 137-46.
25. D.H. Taylor et al., "Genetic Testing for Alzheimer's and Long-Term Care Insurance, " Health Affairs 29, no. 1 (2010): 102-8; K. Lawson et al., "Adverse Psychological Events Occurring in the First Year after Predictive Testing for Huntington's Disease, " Journal of Medical Genetics 33, no. 10 (1996): 856-62; E. Almqvist et al., "A Worldwide Assessment of the Frequency of Suicide, Suicide Attempts, or Psychiatric Hospitalization after Predictive Testing for Huntington Disease, " American Journal of Human Genetics 64, no. 5 (1999): 1293-94; M. Konrad, "Predictive Genetic Testing and the Making of the Pre-Symptomatic Person: Prognostic Moralities Amongst Huntington's-Affected Families, " Anthropology and Medicine 10, no. 1 (2003): 23-49; K. Quaid and M. Wesson, "Exploration of the Effects of Predictive Testing for Huntington Disease on Intimate Relationships, " American Journal of Medical Genetics 57, no. 1 (1995): 46-51; A. Codori, R. Hanson, and J. Brandt, "Self-Selection in Predictive Testing for Huntington's Disease, " American Journal of Medical Genetics 54, no. 3 (1994): 167-73; M. Bloch et al., "Predictive Testing for Huntington Disease in Canada: The Experience of Those Receiving an Increased Risk, " American Journal of Medical Genetics 42, no. 4 (1992): 499-507; T.R. Wahlin et al., "High Suicidal Ideation in Persons Testing for Huntington's Disease, " Acta Neurologica Scandinavica 102, no. 3 (2000): 150-61; M.W. Shaw, "Testing for the Huntington Gene: A Right to Know, a Right Not to Know, or a Duty to Know, " American Journal of Medical Genetics 26 (1987): 243-46.
26. Committee on Bioethics, "Ethical Issues with Genetic Testing in Pediatrics, " Pediatrics 107, no. 6 (2001): 1451-55.
27. S.E. Fisher, "Genetic Susceptibility to Stuttering, " New England Journal of Medicine 362 (2010): 750-52.
28. Future work might further subdivide this category, but that level of analysis is beyond the scope of this paper.
29. Other important goals might be to eliminate certain health conditions, prepare for a child with special needs, or improve health outcomes for the child.
30. Only a portion of these fifty-six disease-associated variants rose to a level of clinical significance that justifies returning the results to the subjects. B.D. Solomon et al., "Incidental Medical Information in Whole-Exome Sequencing'" Pediatrics (in press).
31. One cause of parental anxiety is that some genetic information discovered in the child may have implications for the health status of the parents. This will likely not be expected and could add additional stress. Though this already happens with current prenatal genetic testing, the amount of information will make these kinds of discoveries more common. Rothman, The Tentative Pregnancy.
32. N. Adler et al., "Psychological Responses after Abortion, " Science 248 (1990): 41-44; R.B. Black, "A 1 and 6 Month Follow-Up of Prenatal Diagnosis Patients Who Lost Pregnancies, " Prenatal Diagnosis 9, no. 11 (1989): 795-804.
33. S.R. Leuthner et al., "The Impact of Abnormal Fetal Echocardiography on Expectant Parents' Experience of Pregnancy: A Pilot Study, " Journal of Psychosomatic Obstetrics and Gynecology 24, no. 2 (2003): 121-29; A.-K. Larsson et al., "Parents' Experiences of an Abnormal Ultrasound Examination-Vacillating between Emotional Confusion and Sense of Reality, " Reproductive Health 7 (2010): 10.
34. Though a small number of well-informed parents might choose to make such controversial reproductive choices, we maintain that it would be paternalistic to restrict the technology as a whole. Many other sanctioned prenatal practices-such as learning the sex of the child via ultrasound-run the risk of leading to similarly controversial termination decisions.
35. L. Went, "Ethical Issues Policy Statement on Huntington's Disease Molecular Genetics Predictive Test. International Huntington Association. World Federation of Neurology, " Journal of Medical Genetics 27, no. 1 (1990): 34-38.
36. S. Puri, "I Know It's a Girl and I Need Your Help to Get It Out of Me, " in Slate August 2, 2011, at http://www.slate.com/articles/double_x/doublex/2011/08/i_know_its_a_girl_and_i_need_your_help_to_get_it_out_of_me.html.
37. R. Rosenthal and L. Jacobson, "Pygmalion in the Classroom, " Urban Review 3, no. 1 (1968): 16-20.
38. P.S. Harper and A. Clarke, "Should We Test Children for 'Adult' Genetic Diseases?" Lancet 335 (1990): 1205-6; R. Andorno, "The Right Not to Know: An Autonomy Based Approach, " Journal of Medical Ethics 30, no. 5 (2004): 435-39; J. Beckwith and J. King, "The XYY Syndrome: A Dangerous Myth, " New Science 64, no. 923 (1974): 474-76; M. Everett, "Can You Keep a (Genetic) Secret? The Genetic Privacy Movement, " Journal of Genetic Counseling 13, no. 4 (2004): 273-91; Robertson, "The $1, 000 Genome."
39. The argument for restricting parental access is not based on the belief that children cannot handle medical information. In fact, there have been some studies that demonstrate children's ability to understand their medical situation. Rather, restricting parental access is intended to protect a person's ability to decide as an adult that they do not want to know their genetic information. See P. Alderson, K. Sutcliffe, and K. Curtis, "Children's Competence to Consent to Medical Treatment, " Hastings Center Report 36, no. 6 (2006): 25-34; V.A. Miller, D. Drotar, and E. Kodish, "Children's Competence for Assent and Consent: A Review of Empirical Findings, " Ethics and Behavior 14, no. 3 (2004): 255-95.
40. Some have argued that requiring children to wait until adulthood to receive certain genetic tests creates a bias toward children who prefer not to know their genetic information in the future, as opposed to children who reach adulthood wishing that they had learned their genetic information in childhood. The preferences of the latter group, it is argued, are not upheld in this paradigm. Though we agree that this is a valid concern, we endorse the current standard of care because we think the potential for harm is greater for people whose decision is removed compared to people whose decision is delayed.
41. We acknowledge that guidelines are not binding, and that they are not always followed precisely. Nevertheless, they represent an important articulation of widely accepted norms and serve as a touchstone that shapes the standard of care.
42. Though termination is theoretically the largest infringement on the autonomy of a fetus, we are concerned in this article with the autonomy of already born children. Hence, we are setting aside the complicated question whether fetuses have interests and simply address whether giving parents access to certain prenatal information could harm the interests of the child after it is born.