Monthly Digest

  • Informed consent practices for exome sequencing: An interview study with clinical geneticists in the Netherlands
    Original Article
    Wendy Bos, Eline M. Bunnik
    Molecular Genetics & Genomic Medicine, 14 January 2022
    Open Access
    Genomic sequencing is being used more frequently in the clinic, not only by clinical geneticists, but also by other specialists (“mainstreaming”). The use of genomic sequencing gives rise to challenges regarding informed consent, as it can yield more, and more complex results.
    This study maps the informed consent process for exome sequencing in the Netherlands by means of semistructured interviews with 14 clinical geneticists. Interviewees were asked about their strategies for informing patients about exome sequencing and supporting patients in their decision making, about what they think of as essential information elements, about the challenges they experience, and about their preferences for future policy and practice.
    Clinical geneticists typically discuss the following topics: the nature and aim of the test, the possible results (including unsolicited or incidental findings and Variants of Uncertain Significance) of the test and the consequences of those results for the patient and their family members. Some clinical geneticists use a layered approach to informed consent, meaning that they give short and concise information at first, and provide more detailed information depending on the situation or the needs of the patient.
    During pre-test counseling for genomic sequencing, clinical geneticists use various strategies to enhance patient understanding and personalization of the informed consent process. Going forward, layering information may be part of a solution to ethical challenges of informed consent, also in mainstream settings.

  • Functional genomics data: privacy risk assessment and technological mitigation
    Gamze Gürsoy, Tianxiao Li, Mark B. Gerstein
    Perspective | 10 November 2021
    Nature Reviews Genetics
    The generation of functional genomics data by next-generation sequencing has increased greatly in the past decade. Broad sharing of these data is essential for research advancement but poses notable privacy challenges, some of which are analogous to those that occur when sharing genetic variant data. However, there are also unique privacy challenges that arise from cryptic information leakage during the processing and summarization of functional genomics data from raw reads to derived quantities, such as gene expression values. Here, we review these challenges and present potential solutions for mitigating privacy risks while allowing broad data dissemination and analysis.

  • Ethical, legal, and social issues in the Earth BioGenome Project
    Jacob S. Sherkow, Katharine B. Barker, Robert Cook-Deegan, Richard Durbin et al.
    Perspective, Evolution
    PNAS, January 18, 2022 | 119 (4) e2115859119
    The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project’s technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP’s Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not—and cannot—provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP’s work.

  • The Human Pangenome Project: a global resource to map genomic diversity
    Ting Wang, Lucinda Antonacci-Fulton, David Haussler
    Perspective | 20 April 2022
    Nature, Volume 604 Issue 7906, 21 April 2022
    The Human Pangenome Reference Consortium aims to offer the highest quality and most complete human pangenome reference that provides diverse genomic representation across human populations.
    The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene–disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.

  • Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa
    Segun Fatumo, Joseph Mugisha, Opeyemi Soremekun, Allan Kalungi, Richard Mayanja, Christopher Kintu, Ronald Makanga, Ayoub Kakande, Andrew Abaasa, Gershim Asiki, Robert Kalyesubula, Robert Newton, Moffat Nyirenda, Manjinder S Sandhu, Pontiano Kaleebu
    medRxiv, 2022.05.05.22274740; doi:
       The Uganda Genome Resource (UGR) is a well characterised genomic database, with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC) – a population-based open cohort study established in 1989 by the Medical Research Council (MRC) UK in collaboration with the Uganda Virus Research Institute (UVRI).

    In 2011, UGR was launched with genotype data on ∼5000 and whole genome sequence data on ∼2000 Ugandan individuals from 9 ethno-linguistic groups. Leveraging other available platforms at the MRC Uganda such as Biorepository centre for sample storage, Clinical Diagnostic Laboratory Service (CDLS) for sample diagnostic testing, sequencing platform for DNA extraction, Uganda Medical informatics Unit (UMIC) for large-scale data analysis, GPC for additional sample collection, UGR is strategically poised to expand and generate scientific discoveries.

    Here, we describe UGR and highlight the important genetic findings thus far including how UGR is providing opportunities to: (1) discover novel disease susceptibility genetic loci; (2) refine association signals at new and existing loci; (3) develop and test Polygenic Risk Score (PRS) to determine individual’s disease risk; 4) assess how some risk factors including infectious diseases are causally related to non-communicable diseases (NCDs) in Africa; (5) develop research capacity for genomics in Africa; and (6) enhance African participation in the global genomics research arena. Leveraging established research infrastructure, expertise, local genomic leadership, global collaboration and strategic funding, we anticipate that UGR can develop further to a comparable level of European and Asian large-scale genomic initiatives.

  • Participant recall and understandings of information on biobanking and future genomic research: experiences from a multi-disease community-based health screening and biobank platform in rural South Africa
    Authors: Manono Luthuli, Nothando Ngwenya, Dumsani Gumede, Resign Gunda, Dickman Gareta, Olivier Koole, Mark J. Siedner, Emily B. Wong and Janet Seeley
    Research  Open Access
    BMC Medical Ethics, 2022 23:43  Published on: 18 April 2022
    Limited research has been conducted on explanations and understandings of biobanking for future genomic research in African contexts with low literacy and limited healthcare access. We report on the findings of a sub-study on participant understanding embedded in a multi-disease community health screening and biobank platform study known as ‘Vukuzazi’ in rural KwaZulu-Natal, South Africa.
    Semi-structured interviews were conducted with research participants who had been invited to take part in the Vukuzazi study, including both participants and non-participants, and research staff that worked on the study. The interviews were transcribed, and themes were identified from the interview transcripts, manually coded, and thematically analysed.
    Thirty-nine individuals were interviewed. We found that the research team explained biobanking and future genomic research by describing how hereditary characteristics create similarities among individuals. However, recollection and understanding of this explanation seven months after participation was variable. The large volume of information about the Vukuzazi study objectives and procedures presented a challenge to participant recall. By the time of interviews, some participants recalled rudimentary facts about the genetic aspects of the study, but many expressed little to no interest in genetics and biobanking.
    Participant’s understanding of information related to genetics and biobanking provided during the consent process is affected by the volume of information as well as participant’s interest (or lack thereof) in the subject matter being discussed. We recommend that future studies undertaking biobanking and genomic research treat explanations of this kind of research to participants as an on-going process of communication between researchers, participants and the community and that explanatory imagery and video graphic storytelling should be incorporated into theses explanations as these have previously been found to facilitate understanding among those with low literacy levels. Studies should also avoid having broader research objectives as this can divert participant’s interest and therefore understanding of why their samples are being collected.

  • Gene Editing, Animal Disenhancement and Ethical Debates: A Conundrum for Business Ethics?
    N Thomas, A Langridge
    Animals and Business Ethics
    Book Chapter
    Springer. 25 April 2022
    The Palgrave Macmillan Animal Ethics Series. Palgrave Macmillan, Cham.
    Despite the potential of genetic disenhancement to create livestock incapable of pain and thus reduce animal suffering in industrial farming, ethical theorists have rejected disenhancement as intuitively unethical or as part of a broader dismissal of industrial farming. Although criticisms of industrial farming may be valid, the suffering of animals involved still needs to be addressed, and business ethics is specially placed to do so. In this chapter, a brief overview of the related ethical issues of industrial farming and disenhancement are outlined, and practical steps businesses should make to address animal suffering are provided. Explicit Corporate Social Responsibility policies that reflect the interest of animals, workers and consumers as stakeholders should be put in place, which would provide a mechanism to make businesses accountable for genetic modification and animal welfare more generally.

  • Governing Gene Drive Technologies: A Qualitative Interview Study
    de Graeff, Karin R. Jongsma, Jeantine E. Lunshof & Annelien L. Bredenoord
    AJOB Empirical Bioethics, Volume 13, 2022  Issue  2
    Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth.
    A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically.
    Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment.
    The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations.

  • Proceedings of an expert workshop on community agreement for gene drive research in Africa – Co-organised by KEMRI, PAMCA and Target Malaria
    Gates Open Research
    Open Letter metrics AWAITING PEER REVIEW
    [version 1; peer review: awaiting peer review]
    Delphine Thizy, Lea Pare Toe, Charles Mbogo, Damaris Matoke-Muhia, Vincent Pius Alibu, S. Kathleen Barnhill-Dilling, Tracey Chantler, Gershom Chongwe, Jason Delborne, Lydia Kapiriri, Esther Nassonko Kavuma, Sethlomo Koloi-Keaikitse, Ana Kormos, Katherine Littler, Dickson Lwetoijera, Roberta Vargas de Moraes, Noni Mumba, Lilian Mutengu, Sylvia Mwichuli, Silvia Elizabeth Nabukenya, Janet Nakigudde, Paul Ndebele, Carolyne Ngara, Eric Ochomo, Simon Odiwuor Ondiek, Stephany Rivera, Aaron J. Roberts, Rodrick Sambakunsi, Abha Saxena, Naima Sykes, Brian B. Tarimo, Nicki Tiffin, Karen H. Tountas
    Peer Reviewers Invited
    Funders: Bill and Melinda Gates Foundation, Silicon Valley Community Foundation, Open Philanthropy Project
    PUBLISHED 29 Jan 2021
    Gene drive research is progressing towards future field evaluation of modified mosquitoes for malaria control in sub-Saharan Africa. While many literature sources and guidance point to the inadequacy of individual informed consent for any genetically modified mosquito release, including gene drive ones, (outside of epidemiological studies that might require blood samples) and at the need for a community-level decision, researchers often find themselves with no specific guidance on how that decision should be made, expressed and by whom. Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be designed.

  • Genome-edited crops for improved food security of smallholder farmers
    Kevin V. Pixley, Jose B. Falck-Zepeda, Neal Gutterson
    Comment | 07 April 2022
    Nature Genetics, Volume 54 Issue 4, April 2022
       Widespread enthusiasm about potential contributions of genome-edited crops to address climate change, food security, nutrition and health, environmental sustainability and diversification of agriculture is dampened by concerns about the associated risks. Analysis of the top seven risks of genome-edited crops finds that the scientific risks are comparable to those of accepted, past and current breeding methods, but failure to address regulatory, legal and trade framework, and the granting of social license, squanders the potential benefits…

    Many countries are still uncertain about whether to grow and how to regulate genome-edited crop varieties12. Scientific, political and social considerations impact these decisions, which are complicated by the rapidly evolving features of the science and inconsistent use of genome-editing terminology13. For example, genome editing may or may not involve the transitory introduction of foreign DNA sequences, may or may not result in transgenic products, and may or may not generate products that substantially differ from varieties bred through conventional breeding. Precise consistent use of accurate terminology (for instance, as proposed by the National Academies of Sciences Engineering and Medicine14) to transparently explain the process, products, benefits and potential risks and mitigation strategies is essential to build public trust and consistent regulatory oversight of technologies, including genome editing.