Threatened Species Initiative: Empowering conservation action using genomic resources.

Globally, 15,521 animal species are listed as threatened by the International Union for the Conservation of Nature, and of these less than 3% have genomic resources that can inform conservation management. To combat this, global genome initiatives are developing genomic resources, yet production of a reference genome alone does not conserve a species. The reference genome allows us to develop a suite of tools to understand both genome-wide and functional diversity within and between species. Conservation practitioners can use these tools to inform their decision-making. But, at present there is an implementation gap between the release of genome information and the use of genomic data in applied conservation by conservation practitioners. In May 2020, we launched the Threatened Species Initiative and brought a consortium of genome biologists, population biologists, bioinformaticians, population geneticists, and ecologists together with conservation agencies across Australia, including government, zoos, and nongovernment organizations. Our objective is to create a foundation of genomic data to advance our understanding of key Australian threatened species, and ultimately empower conservation practitioners to access and apply genomic data to their decision-making processes through a web-based portal. Currently, we are developing genomic resources for 61 threatened species from a range of taxa, across Australia, with more than 130 collaborators from government, academia, and conservation organizations. Developed in direct consultation with government threatened-species managers and other conservation practitioners, herein we present our framework for meeting their needs and our systematic approach to integrating genomics into threatened species recovery.

Ethical, legal, and social issues in the Earth BioGenome Project.

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.

CCR5 and Biological Complexity: The Need for Data Integration and Educational Materials to Address Genetic/Biological Reductionism at the Interface of Ethical, Legal, and Social Implications.

In the age of genomics, public understanding of complex scientific knowledge is critical. To combat reductionistic views, it is necessary to generate and organize educational material and data that keep pace with advances in genomics. The view that CCR5 is solely the receptor for HIV gave rise to demand to remove the gene in patients to create host HIV resistance, underestimating the broader roles and complex genetic inheritance of CCR5. A program aimed at providing research projects to undergraduates, known as CODE, has been expanded to build educational material for genes such as CCR5 in a rapid approach, exposing students and trainees to large bioinformatics databases and previous experiments for broader data to challenge commitment to biological reductionism. Our students organize expression databases, query environmental responses, assess genetic factors, generate protein models/dynamics, and profile evolutionary insights into a protein such as CCR5. The knowledgebase generated in the initiative opens the door for public educational information and tools (molecular videos, 3D printed models, and handouts), classroom materials, and strategy for future genetic ideas that can be distributed in formal, semiformal, and informal educational environments. This work highlights that many factors are missing from the reductionist view of CCR5, including the role of missense variants or expression of CCR5 with neurological phenotypes and the role of CCR5 and the delta32 variant in complex critical care patients with sepsis. When connected to genomic stories in the news, these tools offer critically needed Ethical, Legal, and Social Implication (ELSI) education to combat biological reductionism.

An international policy on returning genomic research results.

The Global Alliance for Genomics and Health has approved a policy for the return of clinically actionable genomic research results, the first such policy approved by an international body. The policy acknowledges the potential medical benefits to millions of individuals who are participating in genomics research. It ties the pace of implementation to each country's clinical standards, including for the return of secondary findings, and urges funders to set aside resources to support responsible return.

How to deal with uncertainty in prenatal genomics: A systematic review of guidelines and policies.

Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aimed to provide a comprehensive overview of guidelines available for addressing uncertainty related to prenatal chromosomal microarray (CMA) and ES. Ten uncertainty types associated with prenatal ES and CMA were identified and defined by an international multidisciplinary team. Medline (all) and Embase were systematically searched. Laboratory scientists, clinical geneticists, psychologists, and a fetal medicine specialist screened the papers and performed the data extraction. Nineteen papers were included. Recommendations generally emphasized the importance of trio analysis, clinical information, data sharing, validation and re-analysis, protocols, multidisciplinary teams, genetic counselling, whether to limit the possible scope of results, and when to report particular findings. This systematic review helps provide a vocabulary for uncertainties, and a compass to navigate uncertainties. Prenatal CMA and ES guidelines provide a strong starting point for determining how to handle uncertainty. Gaps in guidelines and recommendations were identified and discussed to provide direction for future research and policy making.

Ethical, Legal, and Social Issues (ELSI) in Clinical Genetics Research.

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies in the context of genetics and genomics research. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research is increasingly relevant in recent years as there has been a greater emphasis on "translational research" that moves genomic discoveries from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of GE3LS research questions or content domains and the methodologies that might be employed in studying them. We conclude with some practical suggestions about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

Sorting Signed Permutations by Intergenic Reversals.

Genome rearrangements are mutations affecting large portions of a genome, and a reversal is one of the most studied genome rearrangements in the literature through the Sorting by Reversals (SbR) problem. SbR is solvable in polynomial time on signed permutations (i.e., the gene orientation is known), and it is NP-hard on unsigned permutations. This problem (and many others considering genome rearrangements) models genome as a list of its genes in the order they appear, ignoring all other information present in the genome. Recent works claimed that the incorporation of the size of intergenic regions, i.e., sequences of nucleotides between genes, may result in better estimators for the real distance between genomes. Here we introduce the Sorting Signed Permutations by Intergenic Reversals problem, that sorts a signed permutation using reversals both on gene order and intergenic sizes. We show that this problem is NP-hard by a reduction from the 3-partition problem. Then, we propose a 2-approximation algorithm for it. Finally, we also incorporate intergenic indels (i.e., insertions or deletions of intergenic regions) to overcome a limitation of sorting by conservative events (such as reversals) and propose two approximation algorithms.

Analogies in Genomics Policymaking: Debates and Drawbacks.

The analogy between genomics and imaging has been an important touchstone in the debate on how secondary findings should be handled in both clinical and research genomics contexts. However, a critical eye is needed to understand whether an analogy like this one provides an adequate basis for policymaking in genomics. Genomics and imaging are undoubtedly similar in certain ways, but whether that similarity is adequate to justify adopting identical policies is a task that requires further analysis. This is highlighted by the fact that secondary findings are produced in other domains of medicine and public health, such as newborn screening programs, routine laboratory panels, and antibiotic sensitivity testing, and that the practices for handling secondary findings in each of these areas are different. These examples demonstrate that medicine has no single comprehensive policy or set of practices for managing secondary findings. Analogies to imaging, newborn screening, routine testing panels, and antibiotic sensitivity testing all lead to different policy options for genomics. In this piece we argue that analogies are a powerful way of driving policy discussions by rendering two different areas of medical practice similar, but an overdependence on a single analogy risks limiting policy discussions in potentially deleterious ways.

Informed Consent for Genetic and Genomic Research.

Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This article addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. © 2020 Wiley Periodicals LLC.

Challenges of Genetic Data Sharing in African Studies.

Data sharing is a valuable aspect of science and required by most funding bodies and journals. However, the national regulatory guidelines of many African nations do not explicitly allow for broad genetic data sharing. Given these restrictions, there is a need to reconsider these policies and propose creative solutions.

The Future of DTC Genomics and the Law.

Direct-to-Consumer ("DTC") genomics has been a controversial topic for over a decade. Much work has been done on the legal issues it raises. This article asks a different question: What will DTC genomics and its legal issues look like in ten to twenty years? After discussing the five current uses of DTC genomics, it describes three current legal issues: medical uses, privacy of genomic information, and privacy in collection and analysis of human DNA. It then suggests that changes in human genomics and how it is used will make the first of those DTC genomics legal issues less important in the future, but that the third will be increasingly significant.

How Can Law and Policy Advance Quality in Genomic Analysis and Interpretation for Clinical Care?

Delivering high quality genomics-informed care to patients requires accurate test results whose clinical implications are understood. While other actors, including state agencies, professional organizations, and clinicians, are involved, this article focuses on the extent to which the federal agencies that play the most prominent roles - the Centers for Medicare and Medicaid Services enforcing CLIA and the FDA - effectively ensure that these elements are met and concludes by suggesting possible ways to improve their oversight of genomic testing.

From Genetics to Genomics: Facing the Liability Implications in Clinical Care.

Health care is transitioning from genetics to genomics, in which single-gene testing for diagnosis is being replaced by multi-gene panels, genome-wide sequencing, and other multi-genic tests for disease diagnosis, prediction, prognosis, and treatment. This health care transition is spurring a new set of increased or novel liability risks for health care providers and test laboratories. This article describes this transition in both medical care and liability, and addresses 11 areas of potential increased or novel liability risk, offering recommendations to both health care and legal actors to address and manage those liability risks.