Genethics article update: April 2014
Spring is finally here and brings with it a new raft of articles. As always, the presentation of an article is neither and implicit or explicit reflection of our views on quality nor is it an endorsement of a particular view.
Stuart
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Kaye, J; Kanellopoulou, N; Hawkins, N; Gowans, H; Curren, L; Melham, K. CAN I ACCESS MY PERSONAL GENOME? THE CURRENT LEGAL POSITION IN THE UK. MEDICAL LAW REVIEW, 22 (1):64-86; 10.1093/medlaw/fwt027 WIN 2014
This paper discusses the nature of genomic information, and the moral arguments in support of an individuals right to access it. It analyses the legal avenues an individual might take to access their sequence information. The authors describe the policy implications in this area and conclude that, for now, the law appears to strike an appropriate balance, but new policy will need to be developed to address this issue.
Whitfield, S. Weighing Up the Risks: The Challenge of Studying ‘Risk’ in Empirical Research. IDS BULLETIN-INSTITUTE OF DEVELOPMENT STUDIES, 45 (2-3):7-17; SI 10.1111/1759-5436.12079 MAR 2014
Studying multifaceted risks that are simultaneously and differently perceived and experienced presents significant challenges, but gaining insight into multiple realities and rationalities is crucial for achieving effective and collaborative governance. This article describes the challenges of a recent study that looked at how different actors, ranging from smallholder farmers to international biotechnology development projects, weigh up the risks associated with the uncertain future of maize agriculture in Kenya. It presents personal reflections on a 12-month experience of applying a multi-sited, ethnographic research approach in Kenya and the UK, in an attempt to observe the creation, perception and experience of risks. The article demonstrates the importance of history, knowledge, social and institutional settings, trust and politics in the ways that risks are created, perceived and experienced by these different actors, and argues for the necessity of engaging with these highly contextualised processes at individual, local and institutional levels.
Tozzo, P; Caenazzo, L; Parker, MJ. Discovering misattributed paternity in genetic counselling: different ethical perspectives in two countries. JOURNAL OF MEDICAL ETHICS, 40 (3):177-181; 10.1136/medethics-2012-101062 MAR 2014
Misattributed paternity or ‘false’ paternity is when a man is wrongly thought, by himself and possibly by others, to be the biological father of a child. Nowadays, because of the progression of genetics and genomics the possibility of finding misattributed paternity during familial genetic testing has increased. In contrast to other medical information, which pertains primarily to individuals, information obtained by genetic testing and/or pedigree analysis necessarily has implications for other biologically related members in the family. Disclosing or not a misattributed paternity has a number of different biological and social consequences for the people involved. Such an issue presents important ethical and deontological challenges. The debate centres on whether or not to inform the family and, particularly, whom in the family, about the possibility that misattributed paternity might be discovered incidentally, and whether or not it is the duty of the healthcare professional (HCP) to disclose the results and to whom. In this paper, we consider the different perspectives and reported problems, and analyse their cultural, ethical and legal dimensions. We compare the position of HCPs from an Italian and British point of view, particularly their role in *genetic* counselling. We discuss whether the Oviedo Convention of the Council of Europe (1997) can be seen as a basis for enriching the debate.
Couture, V; Dubois, MA; Drouin, R; Moutquin, JM; Bouffard, C. Strengths and pitfalls of Canadian gamete and embryo donor registries: searching for beneficent solutions. REPRODUCTIVE BIOMEDICINE ONLINE, 28 (3):369-379; 10.1016/j.rbmo.2013.10.020 MAR 2014
For the gamete and embryo donation community, it is well recognized that the implementation of a gamete and embryo donor registry (GEDR) represents a good initiative to ensure the best possible health conditions for donor-conceived individuals. Be they national, institutional or independent, GEDR can play a major role in the transmission of health-related *genetic* and medical information. However, from a bioethical analysis standpoint, GEDR raise many questions regarding the extent of their beneficent nature. Based on the recent Canadian GEDR aborted attempt, this article will focus on bioethical issues and paradoxes that can impact the wellbeing of donor-conceived individuals, half-siblings, donors and parents. On one hand, the implementation of a GEDR can be ethically justified as a beneficent action towards lessening harm associated with the transmission of hereditary disease and increasing the effectiveness of preventive and therapeutic approaches. On the other hand, examined through the concept of nonpaternalistic beneficence, GEDR challenge us to recognize beneficiaries’ free agency, as well as the importance to transmit reliable and pertinent information. Ultimately, beyond an individualistic application of the principle of beneficence, socioethics invite us to consider consistency with societal values as a prerequisite for achieving a common good. (C) 2013, Reproductive Healthcare Ltd.
Bonython, W; Arnold, B. Disclosure ‘downunder’: misadventures in Australian genetic privacy law. JOURNAL OF MEDICAL ETHICS, 40 (3):168-172; 10.1136/medethics-2012-101067 MAR 2014
Along with many jurisdictions, Australia is struggling with the unique issues raised by genetic information in the context of privacy laws and medical ethics. Although the consequences of disclosure of most private information are generally confined to individuals, disclosure of genetic information has far-reaching consequences, with a credible argument that genetic relatives have a right to know about potential medical conditions. In 2006, the Privacy Act was amended to permit disclosure of an individual’s genetic information, without their consent, to genetic relatives, if it was to avoid or mitigate serious illness. Unfortunately, additional amendments required for operation of the disclosure amendment were overlooked. Public Interest Determinations (PIDs)-delegated legislation issued by the privacy commissioner-have, instead, been used to exempt healthcare providers from provisions which would otherwise make disclosure unlawful. This paper critiques the PIDs using documents obtained under the Freedom of Information Act-specifically the impact of both the PIDs and the disclosure amendment on patients and relatives-and confidentiality and the procedural validity of subordinate laws regulating medical privacy.
Middleton, A; Bragin, E; Morley, KI; Parker, M for the DDD Study. Online questionnaire development: Using film to engage participants and then gather attitudes towards the sharing of genomic data. SOCIAL SCIENCE RESEARCH, 44 211-223; 10.1016/j.ssresearch.2013.12.004 MAR 2014
How can a researcher engage a participant in a survey, when the subject matter may be perceived as ‘challenging’ or even be totally unfamiliar to the participant? The Genomethics study addressed this via the creation and delivery of a novel online questionnaire containing 10 integrated films. The films documented various ethical dilemmas raised by genomic technologies and the survey ascertained attitudes towards these. Participants were recruited into the research using social media, traditional media and email invitation. The film-survey strategy was successful: 11,336 initial hits on the survey website led to 6944 completed surveys. Participants included from those who knew nothing of the subject matter through to experts in the field of genomics (61% compliance rate), 72% of participants answered every single question. This paper summarises the survey design process and validation methods applied. The recruitment strategy and results from the survey are presented elsewhere. (c) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Berger, VK; Baker, VL. Preimplantation Diagnosis for Single Gene Disorders. SEMINARS IN REPRODUCTIVE MEDICINE, 32 (2):107-113; 10.1055/s-0033-1363552 MAR 2014
Preimplantation genetic diagnosis (PGD) allows patients who are carriers or who are affected by genetic diseases to select unaffected embryos for transfer before becoming pregnant. The practice of PGD is evolving with rapid advances in technology and biopsy methods. Testing for a specific gene mutation can be performed in combination with 24-chromosome aneuploidy screening. Several unique applications of PGD are reviewed, including exclusion diagnosis for couples from Huntington disease families, testing for fragile X premutations, and human leukocyte antigen matching for stem cell donor siblings. Although PGD for single gene mutations allows patients to gain information about their embryos and perhaps avoid a difficult decision about whether or not to terminate an ongoing pregnancy, this technique also provides for much ethical debate encompassing the well-being of the prospective couple, embryo, child, and people in the community affected by the diseases being screened.
Hall, AE; Chowdhury, S; Pashayan, N; Hallowell, N; Pharoah, P; Burton, H. What ethical and legal principles should guide the genotyping of children as part of a personalised screening programme for common cancer? JOURNAL OF MEDICAL ETHICS, 40 (3):163-167; 10.1136/medethics-2012-101079 MAR 2014
Increased knowledge of the gene-disease associations contributing to common cancer development raises the prospect of population stratification by genotype and other risk factors. Individual risk assessments could be used to target interventions such as screening, treatment and health education. Genotyping neonates, infants or young children as part of a systematic programme would improve coverage and uptake, and facilitate a screening package that maximises potential benefits and minimises harms including overdiagnosis. This paper explores the potential justifications and risks of genotyping children for genetic variants associated with common cancer development within a personalised screening programme. It identifies the ethical and legal principles that might guide population genotyping where the predictive value of the testing is modest and associated risks might arise in the future, and considers the standards required by population screening programme validity measures (such as the Wilson and Jungner criteria including cost-effectiveness and equitable access). These are distinguished from the normative principles underpinning predictive genetic testing of children for adult-onset diseases-namely, to make best-interests judgements and to preserve autonomy. While the case for population-based genotyping of neonates or young children has not yet been made, the justifications for this approach are likely to become increasingly compelling. A modified evaluative and normative framework should be developed, capturing elements from individualistic and population-based approaches. This should emphasise proper communication and genuine parental consent or informed choice, while recognising the challenges associated with making unsolicited approaches to an asymptomatic group. Such a framework would be strengthened by complementary empirical research.
Serre, JL; Leutenegger, AL; Bernheim, A; Fellous, M; Rouen, A; Siffroi, JP. Does anonymous sperm donation increase the risk for unions between relatives and the incidence of autosomal recessive diseases due to consanguinity? HUMAN REPRODUCTION, 29 (3):394-399; 10.1093/humrep/det452 MAR 2014
In France gamete donation and notably sperm donation are anonymous. It has been claimed that anonymous artificial insemination by donor (AID) could highly contribute to an increase in the level of consanguinity and the incidence of autosomal recessive diseases, due to the unions between offspring of anonymous donors, unaware of their biological kinship, with the special case of unions between half-siblings. The actual incidence of consanguinity due to AID was compared with that resulting from the two other main sources of consanguinity and recessive diseases, i.e. voluntary unions between related individuals or inadvertent unions between the offspring of a common unknown male ancestor (false paternity). From these data, we estimated that expected unions in France between half sibs per year are 0.12 between offspring of sperm donors (1.2 every 10 years) and 0.5 between offspring of common male ancestors through false paternity (5 every 10 years). More generally, the inadvertent unions between false paternity offspring are roughly four times more frequent than those resulting from anonymous AID. We estimated that in the future, when AID has been in practice for several generations, out the 820 000 annual births in France, respectively, 6 and 25 births will be consanguineous through an unknown common ancestor related to anonymous AID and to a false paternity, both of which are negligible when compared with the 1256 children born from first-degree cousins. About 672 children per year are born with a recessive genetic disease due to the panmictic risk and additional affected cases due to consanguinity would be 34.54 for first-cousin offspring, 0.33 for offspring of individuals related due to false paternity and 0.079 for offspring of individuals related due to anonymous AID. Anonymous AID would therefore be responsible for 0.46% of consanguineous births and for 0.01% of recessive diseases. Therefore, the effect of anonymous AID on half-sibling unions, consanguinity and recessive disease incidence can be regarded as marginal.
Sexton, A; Rawlings, L; Jenkins, M; Winship, I. Predictive Genetic Testing of a Bone Marrow Recipient-Ethical Issues Involving Unexpected Results, Gender Issues, Test Accuracy, and Implications for the Donor. JOURNAL OF GENETIC COUNSELING, 23 (1):33-37; 10.1007/s10897-013-9643-x FEB 2014
We present a case where an apparently straightforward Lynch syndrome predictive genetic test of DNA from a blood sample from a woman yielded an unexpected result of X/Y chromosome imbalance. Furthermore, it demonstrates the complexities of genetic testing in people who have had bone marrow transplants. This highlights the potential for multiple ethical and counselling challenges, including the inadvertent testing of the donor. Good communication between clinics and laboratories is essential to overcome such challenges and to minimise the provision of false results.
Bunnik, EM; Schermer, MHN; Janssens, ACJW. Naming and framing in genomic testing. TRENDS IN MOLECULAR MEDICINE, 20 (2):63-65; 10.1016/j.molmed.2013.11.001 FEB 2014
What’s in a name? Terminology has the power to shape the ethical and regulatory debate surrounding commercially offered genomic testing. This article discusses the normative effects of naming and framing, and proposes that the medical frame, with its focus on the reduction of harm, should be used in the evaluation and regulation of predictive genomic testing.
Galluzzi, G; Noriega, IL. Conservation and Use of Genetic Resources of Underutilized Crops in the Americas-A Continental Analysis. SUSTAINABILITY, 6 (2):980-1017; 10.3390/su6020980 FEB 2014
Latin America is home to dramatically diverse agroecological regions which harbor a high concentration of underutilized plant species, whose genetic resources hold the potential to address challenges such as sustainable agricultural development, food security and sovereignty, and climate change. This paper examines the status of an expert-informed list of underutilized crops in Latin America and analyses how the most common features of underuse apply to these. The analysis pays special attention to if and how existing international policy and legal frameworks on biodiversity and plant genetic resources effectively support or not the conservation and sustainable use of underutilized crops. Results show that not all minor crops are affected by the same degree of neglect, and that the aspects under which any crop is underutilized vary greatly, calling for specific analyses and interventions. We also show that current international policy and legal instruments have so far provided limited stimulus and funding for the conservation and sustainable use of the genetic resources of these crops. Finally, the paper proposes an analytical framework for identifying and evaluating a crop’s underutilization, in order to define the most appropriate type and levels of intervention (international, national, local) for improving its status.
Guo, G; Fu, Y; Lee, H; Cai, T; Harris, KM; Li, Y. Genetic Bio-Ancestry and Social Construction of Racial Classification in Social Surveys in the Contemporary United States. DEMOGRAPHY, 51 (1):141-172; 10.1007/s13524-013-0242-0 FEB 2014
Self-reported race is generally considered the basis for racial classification in social surveys, including the U.S. census. Drawing on recent advances in human molecular genetics and social science perspectives of socially constructed race, our study takes into account both genetic bio-ancestry and social context in understanding racial classification. This article accomplishes two objectives. First, our research establishes geographic genetic bio-ancestry as a component of racial classification. Second, it shows how social forces trump biology in racial classification and/or how social context interacts with bio-ancestry in shaping racial classification. The findings were replicated in two racially and ethnically diverse data sets: the College Roommate Study (N = 2,065) and the National Longitudinal Study of Adolescent Health (N = 2,281).
BURT, C. H. and SIMONS, R. L. (2014), PULLING BACK THE CURTAIN ON HERITABILITY STUDIES: BIOSOCIAL CRIMINOLOGY IN THE POSTGENOMIC ERA. Criminology. doi: 10.1111/1745-9125.12036
Unfortunately, the nature-versus-nurture debate continues in criminology. Over the past 5 years, the number of heritability studies in criminology has surged. These studies invariably report sizeable heritability estimates (∼50 percent) and minimal effects of the so-called shared environment for crime and related outcomes. Reports of such high heritabilities for such complex social behaviors are surprising, and findings indicating negligible shared environmental influences (usually interpreted to include parenting and community factors) seem implausible given extensive criminological research demonstrating their significance. Importantly, however, the models on which these estimates are based have fatal flaws for complex social behaviors such as crime. Moreover, the goal of heritability studies—partitioning the effects of nature and nurture—is misguided given the bidirectional, interactional relationship among genes, cells, organisms, and environments. This study provides a critique of heritability study methods and assumptions to illuminate the dubious foundations of heritability estimates and questions the rationale and utility of partitioning genetic and environmental effects. After critiquing the major models, we call for an end to heritability studies. We then present what we perceive to be a more useful biosocial research agenda that is consonant with and informed by recent advances in our understanding of gene function and developmental plasticity.
Meloni, M. (2014), How biology became social, and what it means for social theory. The Sociological Review. doi: 10.1111/1467-954X.12151
In this paper I first offer a systematic outline of a series of conceptual novelties in the life-sciences that have favoured, over the last three decades, the emergence of a more social view of biology. I focus in particular on three areas of investigation: (1) technical changes in evolutionary literature that have provoked a rethinking of the possibility of altruism, morality and prosocial behaviours in evolution; (2) changes in neuroscience, from an understanding of the brain as an isolated data processor to the ultrasocial and multiply connected social brain of contemporary neuroscience; and (3) changes in molecular biology, from the view of the gene as an autonomous master of development to the ‘reactive genome’ of the new emerging field of molecular epigenetics. In the second section I reflect on the possible implications for the social sciences of this novel biosocial terrain and argue that the postgenomic language of extended epigenetic inheritance and blurring of the nature/nurture boundaries will be as provocative for neo-Darwinism as it is for the social sciences as we have known them. Signs of a new biosocial language are emerging in several social-science disciplines and this may represent an exciting theoretical novelty for twenty-first social theory.
Egalite N, Jaitovich Groisman I, Godard B. (2014) Genetic Counseling Practice in Next Generation Sequencing Research: Implications for the Ethical Oversight of the Informed Consent Process. Journal of Genetic Counseling, 10.1007/s10897-014-9703-x
The potential for next generation sequencing research (NGS) to generate individual genetic results could have implications for the informed consent process and the provision of genetic counseling. We undertook a content analysis of informed consent templates and guidelines produced by Canadian institutional review boards, purposively sampling documents used by researchers to obtain consent from participants in genetics studies. Our goal was to examine the extent to which the informed consent documents addressed genetic counseling and the return of individual genetic results. Our analysis reveals that the majority of informed consent documents did not mention genetic counseling while several did not mention the return of results. We found differences in the ways in which documents addressed availability of counseling, eligibility criteria for referral to a genetic counselor, genetic counselor involvement, provision of services to family members of participants and incidental findings. From an ethical standpoint, consent documents should provide appropriate information so that participants may make an informed decision about their participation in research. The need to ensure adequate counseling for study populations in an NGS research context will necessarily involve adapting values that underlie care in genetic counseling practice. If the interests of research participants are to be truly promoted, the drafting and review of informed consent documents should give proper due to genetic counseling.
Might M, Wilsey M. The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated. Genetics in Medicine, 2014
Rabeharisoa V, Callon M, Marques Filipe A, Arriscado Nunes J, Paterson F, and Vergnaud F. From ‘politics of numbers’ to ‘politics of singularisation’: Patients’ activism and engagement in research on rare diseases in France and Portugal. BioSocieties advance online publication 31 March 2014; doi: 10.1057/biosoc.2014.4
This article investigates how the engagement of patients’ organisations (POs) in research relates to the dynamics of their activism in the area of rare diseases. It traces back how certain concerned families and groups elaborated rareness as an issue of equity and social justice, gave shape to what we call a ‘politics of numbers’ for stating the fact of rare diseases as a major public health problem, and promoted patients’ critical involvement in biomedical and therapeutic research as a solution for mainstreaming rare diseases in regular health systems. It then studies three Portuguese and three French POs, which point to the limits of the epidemiological notion of rareness for capturing the compounded and intersecting nature of the bio-psycho-social make-up of their conditions. It finally shows how these critics progressively lead to the emergence of an alternative politics, which we call a ‘politics of singularisation’. At the core of this politics stands a collective and ongoing profiling of conditions and patients, whose similarities and differences relates to the ubiquity of biological pathways and diseases categories. Our contention is that this ‘politics of singularisation’ not only pictures a politics of illnesses which questions the rationale for nosological classifications, but also, and consequently, affects the making of social links by suggesting the simultaneous identification of individual patients and constitution of collectives to which they partake while asserting their specificities.
Brown DM, Alphey LS, McKemey A, Beech C, James AA. Criteria for Identifying and Evaluating Candidate Sites for Open-Field Trials of Genetically Engineered Mosquitoes. Vector Borne Zoonotic Dis. 2014 Apr 1. [Epub ahead of print]
Recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. It is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. One of these challenges is having a set of criteria for selecting collaborators and sites for efficacy and safety field trials that combine rigorous science with good ethical and legal practices. Specific site-selection criteria were developed in four categories-Scientific, Regulatory, Community Engagement, and Resources-in anticipation of open-field releases of a transgenic mosquito strain designed to suppress populations of the dengue vector mosquito, Aedes aegypti. The criteria are derived from previous published material, discussions, and personal experiences with the expectation of providing guidance to laboratory scientists for addressing the conceptual and operational considerations for identifying partner researchers and countries with whom to collaborate. These criteria are not intended to be prescriptive nor can they be applied to every circumstance where genetic approaches are proposed for deployment. However, we encourage those involved in the discovery phase of research to consider each criterion during project planning activities, and where appropriate, incorporate them into a “go/no-go” decision-making process for further development and testing of the technologies.
Wallace SE, Gaye A, Shoush O, Burton PR. Protecting Personal Data in Epidemiological Research: DataSHIELD and UK Law. Public Health Genomics. 2014 Mar 28. [Epub ahead of print]
Background: Data from individual collections, such as biobanks and cohort studies, are now being shared in order to create combined datasets which can be queried to ask complex scientific questions. But this sharing must be done with due regard for data protection principles. DataSHIELD is a new technology that queries nonaggregated, individual-level data in situ but returns query data in an anonymous format. This raises questions of the ability of DataSHIELD to adequately protect participant confidentiality. Methods: An ethico-legal analysis was conducted that examined each step of the DataSHIELD process from the perspective of UK case law, regulations, and guidance. Results: DataSHIELD reaches agreed UK standards of protection for the sharing of biomedical data. All direct processing of personal data is conducted within the protected environment of the contributing study; participating studies have scientific, ethics, and data access approvals in place prior to the analysis; studies are clear that their consents conform with this use of data, and participants are informed that anonymisation for further disclosure will take place. Conclusion: DataSHIELD can provide a flexible means of interrogating data while protecting the participants’ confidentiality in accordance with applicable legislation and guidance. © 2014 S.
McGuire AL(1), Knoppers BM, Zawati MH, Clayton EW. Can I be sued for that? Liability risk and the disclosure of clinically significant genetic research findings. Genome Res. 2014 Mar 27. [Epub ahead of print]
Genomic researchers are increasingly faced with difficult decisions about whether, under what circumstances, and how to return research results and significant incidental findings to study participants. Many have argued that there is an ethical, maybe even a legal obligation to disclose significant findings under some circumstances. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research. However, there is no explicit legal duty to disclose in the United States. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care. This paper discusses liability risks associated with the disclosure of significant research findings for investigators in the United States.
Strong KA, Zusevics KL, Bick D, Veith R. Views of Primary Care Providers Regarding the Return of Genome Sequencing Incidental Findings. Clin Genet. 2014 Mar 27. doi: 10.1111/cge.12390. [Epub ahead of print]
Sequencing of the entire exome or genome is increasingly used in clinical practice. Debate continues, however, regarding which incidental findings (IFs) should be returned and who should be involved in those decisions. Previous empirical research regarding stakeholder attitudes to the return of IFs has primarily involved genetics professionals; non-genetics health professionals have not been widely surveyed. Given this, a survey regarding return of IFs was administered at the Best Practices in Pediatrics Conference following an educational presentation on genetics terminology and genetic condition examples. A total of 258 participants completed the survey. Of particular note, respondents who were positively disposed to sequencing did not always report wanting to learn about IFs, even if actionable. This is noteworthy given recent American College of Medical Genetics and Genomics guidelines recommending particular actionable IF be returned “without reference to patient preference”. This study’s findings are important because they provide insight regarding the attitudes to the return of genome sequencing results for an important professional group, primary care providers. Ultimately, as likely gatekeepers to referrals for this technology, their opinions about the test will be key to its successful deployment.
Lallier LE, McMeel O, Greiber T, Vanagt T, Dobson AD, Jaspars M. Access to and use of marine genetic resources: understanding the legal framework. Nat Prod Rep. 2014 Mar 26. [Epub ahead of print]
With the adoption of the Nagoya Protocol in 2010, an additional legal instrument under the Convention on Biological Diversity (1992), the legal landscape surrounding the access to and utilization of genetic resources will change. This is likely to impact working procedures for scientists, turning pre-existing ethics into legal obligations. The aim of this article is to inform scientists on the global access and benefit-sharing framework which has been set by the Convention on Biological Diversity and its Nagoya Protocol, focusing specifically on their application to marine genetic resources for which the United Nations Convention on the Law of the Sea (1982) also has relevance.
Machini K, Douglas J, Braxton A, Tsipis J, Kramer K. Genetic Counselors’ Views and Experiences with the Clinical Integration of Genome Sequencing. J Genet Couns. 2014 Mar 28. [Epub ahead of print]
In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors- one third of whom currently offer WES/WGS-participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counselling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of WES/WGS into the clinical setting (molecular/clinical genetics, counseling and bioethics) and suggested that counseling aids (to assist them when explaining aspects of these tests to patients) and webinars focused on WES/WGS (for genetic counselors and other health care professionals) would be useful educational tools. Future research should permit us to further enhance our knowledge of pitfalls and benefits associated with the introduction of these powerful technologies in patient care and to further explore the roles and opportunities for genetic counselors in this rapidly evolving field.
Knoppers BM(1), Sénécal K, Borry P, Avard D. Whole-genome sequencing in newborn screening programs. Sci Transl Med. 2014 Mar 26;6(229):229cm2. doi: 10.1126/scitranslmed.3008494.
The availability of whole-genome sequencing (WGS) is likely to change the practice of population screening programs such as newborn screening (NBS). This Commentary raises key ethical, legal, and social issues surrounding WGS in NBS and suggests a need for deliberation regarding the policy challenges of introducing sequencing in such programs. Any change in the goals of NBS programs should be discussed carefully and should represent the best interests of the child.
Khan AI, Capps BJ, Sum MY, Kuswanto CN, Sim K. Informed Consent for Human Genetic and Genomic Studies: A Systematic Review. Clin Genet. 2014 Mar 19. doi: 10.1111/cge.12384. [Epub ahead of print]
As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies which examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and wellbeing of genetic research participants.
van Schendel RV, Kleinveld JH, Dondorp WJ, Pajkrt E, Timmermans DR, Holtkamp KC, Karsten M, Vlietstra AL, Lachmeijer AM, Henneman L. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur J Hum Genet. 2014 Mar 19. doi: 10.1038/ejhg.2014.32. [Epub ahead of print]
Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance.European Journal of Human Genetics advance online publication, 19 March 2014; doi:10.1038/ejhg.2014.32.
Murray TH. Genetics. Stirring the simmering “designer baby” pot. Science. 2014 Mar 14;343(6176):1208-10. doi: 10.1126/science.1248080.
Solomon BD. Incidentalomas in genomics and radiology. N Engl J Med. 2014 Mar 13;370(11):988-90. doi: 10.1056/NEJMp1310471.
Manolio TA, Green ED. Leading the way to genomic medicine. Am J Med Genet C Semin Med Genet. 2014 Mar;166(1):1-7. doi: 10.1002/ajmg.c.31384. Epub 2014 Mar 11.
The National Human Genome Research Institute, in close collaboration with its research community, is pursuing an ambitious research agenda to facilitate and promote the implementation of genomics in clinical care. Since 2011, research programs utilizing next-generation sequencing in the management of cancer and other multigenic conditions, workup of undiagnosed conditions, and evaluation of disorders of the newborn period have been initiated, along with projects identifying clinically actionable variants and exploring the ethical and social implications of reporting these findings. Several genomic medicine symposia and other consultations have helped to shape these research initiatives and develop educational materials for physicians and others working to implement the use of genomic findings in clinical care. These efforts provide a valuable complement to the highly successful basic genomics research enterprise that has at last enabled the transition of genomics from the bench to the bedside.
Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA, Chaib H, Merker JD, Goldfeder RL, Enns GM, David SP, Pakdaman N, Ormond KE, Caleshu C, Kingham K, Klein TE, Whirl-Carrillo M, Sakamoto K, Wheeler MT, Butte AJ, Ford JM, Boxer L, Ioannidis JP, Yeung AC, Altman RB, Assimes TL, Snyder M, Ashley EA, Quertermous T. Clinical interpretation and implications of whole-genome sequencing. JAMA. 2014 Mar 12;311(10):1035-45. doi: 10.1001/jama.2014.1717.
Comment in
JAMA. 2014 Mar 12;311(10):1017-9.
IMPORTANCE: Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication. OBJECTIVES: To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings. DESIGN, SETTING, AND PARTICIPANTS: An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings. MAIN OUTCOMES AND MEASURES: Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up. RESULTS: Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross κ, 0.52; 95% CI, 0.40-0.64), and reclassified 69% of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in hereditary breast and ovarian cancer. Physician review of sequencing findings prompted consideration of a median of 1 to 3 initial diagnostic tests and referrals per participant, with fair interrater agreement about the suitability of WGS findings for clinical follow-up (Fleiss κ, 0.24; P < 001). CONCLUSIONS AND RELEVANCE: In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine.
Williams MS. Genomic medicine implementation: Learning by example. Am J Med Genet C Semin Med Genet. 2014 Mar;166(1):8-14. doi:10.1002/ajmg.c.31394. Epub 2014 Mar 10.
Genomic Medicine is beginning to emerge into clinical practice. The National Human Genome Research Institute’s Genomic Medicine Working Group consists of organizations that have begun to implement some aspect of genomic medicine (e.g., family history, systematic implementation of Mendelian disease program, pharmacogenomics, whole exome/genome sequencing). This article concisely reviews the working group and provides a broader context for the articles in the special issue including an assessment of anticipated provider needs and ethical, legal, and social issues relevant to the implementation of genomic medicine. The challenges of implementation of innovation in clinical practice and the potential value of genomic medicine are discussed. © 2014 Wiley Periodicals, Inc.
Burke W, Evans BJ, Jarvik GP. Return of results: Ethical and legal distinctions between research and clinical care. Am J Med Genet C Semin Med Genet. 2014 Mar;166(1):105-11. doi: 10.1002/ajmg.c.31393. Epub 2014 Mar 10.
The return of individual results to research participants has been vigorously debated. Consensus statements indicate that researchers and bioethicists consider the return of research results most appropriate when the findings are clinically relevant. Even when clinical utility is the motivator, however, the return of individual research results is not equivalent to clinical care. There are important differences in the domains of research and medical care, both from a legal standpoint and in terms of the ethical responsibilities of clinicians and researchers. As a corollary, researchers risk promoting a therapeutic misconception if they create quasi-clinical settings for return of clinically relevant research results. Rather, efforts should be focused on clarity in the provision of research results, appropriate caveats and, most important, appropriate referrals when the results may be helpful to consider in medical care.
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