The role of gene expression in evolutionary adaptation has been a subject of debate for over 40 years.cis‐regulation of transcription has been proposed to be the primary source of morphological novelty in evolution, though this is based on only a handful of examples. Recently the first genome‐wide studies of gene expression adaptation have been published, giving us an initial global view of this process. Systematic studies such as these will allow a number of key questions currently facing the field (...) of gene expression evolution to be addressed. (shrink)

Madole & Harden's assertion that the effects derived from within-family genome-wide association studies (GWASs) and from randomized controlled trials (RCTs) are equivalent is misleading. GWASs are substantially more “non-unitary, non-uniform, and non-explanatory” than RCTs. While the within-family GWAS bring us closer to identifying genetic causes, whether it will change behavioral genetics into a causal science is an open question.

Higher states of consciousness in which the human mind can transcend the boundaries of logic and reason are envisioned as natural to the experience and potential growth of every human being. So far they have been mostly monitored by electrophysiological methods. In this study we were particularly interested in discovering the molecular transcriptional basis of higher states of consciousness. In addition to phenomenological reports of meditators who participated in this study the generated higher states of consciousness were also EEG recorded. (...) We assessed the whole genome gene expression analysis of long-term meditators in four separate trials and detected significant differential gene expression in association with higher states of consciousness. The number of differently expressed genes as well as high proportion of genes themselves differed between meditators. Despite this, gene ontology enrichment analysis found significant biological and molecular processes shared among meditators’ higher state of consciousness. (shrink)

Polygenic scores (PGSs) have several limitations. They are confounded with environmental effects on behavior and cannot be used to study how mutations affect brain function and behavior. For this, mutations with large effects, which often arise in only one geographical population are needed. Genome-wide association studies (GWASs), commonly used for identifying mutations, have difficulty detecting these mutations. A strategy that overcomes this challenge is discussed.

The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC cytidine (...) deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. “clustered”) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome‐wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators. (shrink)

Whether, and to what degree, do patents granted on human genes cast a shadow of uncertainty over genomics and its applications? Will owners of patents on individual genes or clusters of genes sue those performing whole-genome analyses on human samples for patent infringement? These are related questions that have haunted molecular diagnostics companies and services, coloring scientific, clinical, and business decisions. Can the profusion of whole-genome analysis methods proceed without fear of patent infringement liability?Whole-genome sequencing is proceeding apace. Academic centers (...) have been performing whole-genome and -exome sequencing in research for at least five years, and academic clinical laboratories with national reach have been doing sequencing for clinical applications for almost as long. Companies have also been offering WGS and WES as a clinical service for a few years now. So far as we know, no one has been sued for infringement of “gene patents” for performing WGS. (shrink)

We address Turkheimer’s argument that genome-wide association studies of behaviors and psychiatric traits will fail to produce coherent explanations. We distinguish two major sources of potential i...

A recent analysis of the genomes of Darwin's finches revealed extensive interspecies allele sharing throughout the history of the radiation and identified a key locus responsible for morphological evolution in this group. The radiation of Darwin's finches on the Galápagos archipelago has long been regarded as an iconic study system for field ecology and evolutionary biology. Coupled with an extensive history of field work, these latest findings affirm the increasing acceptance of introgressive hybridization, or gene flow between species, as a (...) significant contributor to adaptive evolution. Here, we review and discuss these findings in relation to both classical work on Darwin's finches and contemporary work showing similar evolutionary signatures in other biological systems. The continued unification of genomic data with field biology promises to further elucidate the molecular basis of adaptation in Darwin's finches and well beyond. (shrink)

In this article we examine the “phenotype” concept in light of recent technological advances in Genome-Wide Association Studies . By observing the technology and its presuppositions, we put forward the thesis that at least in this case genotype and phenotype are effectively coidentifled one by means of the other. We suggest that the coidentiflcation of genotype-phenotype couples in expression-based GWAS also indicates a conceptual dependence, which we call “co-deñnition.” We note that viewing these terms as codeflned runs against possible expectations, (...) viz., that genotypes and phenotypes could ultimately be expressed independently from one another. In addition, the co-definition of genotypes and phenotypes in this context emphasizes the correlative character of both genotypes and phenotypes in GWAS. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, (...) some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, (...) some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in clinical reproductive (...) applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. (...) Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates. (shrink)

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical and (...) a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)

From the earliest days of the Human Genome Project, the holy grail of genomics was the ability to perform whole-genome sequencing quickly, accurately, and relatively inexpensively so that the benefits of genomics would be widely available in clinical settings. Although the mythical $1,000 genome sequence seemed elusive for many years, next-generation sequencing technologies and other recent advances clearly indicate that inexpensive whole-genome sequencing is at hand.Whole-genome sequencing has demonstrable value in elucidating the genetic etiology of rare disorders, in identifying atypical (...) variants in common diseases, in determining pharmacogenomically appropriate drugs and dosages, in performing tumor genome sequencing, and in aiding other clinical applications for the diagnosis and treatment of individuals who are symptomatic or whose family health history places them at substantial risk. Undoubtedly, the clinical applications of wholegenome sequencing will increase in the future. (shrink)

Genomic research can reveal ‘unsolicited’ or ‘incidental’ findings that are of potential health or reproductive significance to participants. It is widely thought that researchers have a moral obligation, grounded in the duty of easy rescue, to return certain kinds of unsolicited findings to research participants. It is less widely thought that researchers have a moral obligation to actively look for health-related findings. This paper examines whether there is a moral obligation, grounded in the duty of easy rescue, to actively hunt (...) for genomic secondary findings. We begin by showing how the duty to disclose individual research findings can be grounded in the duty of easy rescue. Next, we describe a parallel moral duty, also grounded in the duty of easy rescue, to actively hunt for such information. We then consider six possible objections to our argument, each of which we find unsuccessful. Some of these objections provide reason to limit the scope of the duty to look for secondary findings, but none provide reason to reject this duty outright. We argue that under a certain range of circumstances, researchers are morally required to hunt for these kinds of secondary findings. Although these circumstances may not currently obtain, genomic researchers will likely acquire an obligation to hunt for secondary findings as the field of genomics continues to evolve. (shrink)

Genome editing in livestock could potentially be used in ways that help resolve some of the most urgent and serious global problems pertaining to livestock, including animal suffering, pollution, antimicrobial resistance, and the spread of infectious disease. But despite this potential, some may object to pursuing it, not because genome editing is wrong in and of itself, but because it is the wrong kind of solution to the problems it addresses: it is merely a ‘technological fix’ to a complex societal (...) problem. Yet though this objection might have wide intuitive appeal, it is often not clear what, exactly, the moral problem is supposed to be. The aim of this paper is to formulate and shed some light on the ‘technological fix objection’ to genome editing in livestock. I suggest that three concerns may underlie it, make implicit assumptions underlying the concerns explicit, and cast some doubt on several of these assumptions, at least as they apply to the use of genome editing to produce pigs resistant to the Porcine Reproductive and Respiratory Syndrome and hornless dairy cattle. I then suggest that the third, and most important, concern could be framed as a concern about complicity in factory farming. I suggest ways to evaluate this concern, and to reduce or offset any complicity in factory farming. Thinking of genome editing’s contribution to factory farming in terms of complicity, may, I suggest, tie it more explicitly and strongly to the wider obligations that come with pursuing it, including the cessation of factory farming, thereby addressing the concern that technological fixes focus only on a narrow problem. (shrink)

Evidence for recombination suppression has been identified in linkage studies of several unstable DNA diseases. Also sex‐specific changes in recombination frequency have been detected at the loci of Huntington's disease and myotonic dystrophy. It can be hypothesized that meiotic recombination is regulated by genome‐wide genomic imprinting and that changes in meiotic recombination imply the presence of the genomic imprinting defect. If aberrant recombination at the locus of trinucleotide repeat expansion is verified, new theoretical and experimental opportunities will arise in (...) studies on the role of genomic imprinting in the unstable DNA diseases. (shrink)

BackgroundObtaining informed consent for participation in genomic research in low-income settings presents specific ethical issues requiring attention. These include the challenges that arise when providing information about unfamiliar and technical research methods, the implications of complicated infrastructure and data sharing requirements, and the potential consequences of future research with samples and data. This study investigated researchers’ and participants’ parents’ experiences of a consent process and understandings of a genome-wide association study of malaria involving children aged five and under in Mali. (...) It aimed to inform best practices in recruiting participants into genomic research.MethodsA qualitative rapid ethical assessment was undertaken. Fifty-five semi-structured interviews were conducted with the parents of research participants. An additional nine semi-structured interviews were conducted with senior research scientists, research assistants and with a member of an ethics committee. A focus group with five parents of research participants and direct observations of four consent processes were also conducted. French and translated English transcripts were descriptively and thematically coded using OpenCode software.ResultsParticipants’ parents in the MalariaGEN study had differing understandings of the causes of malaria, the rationale for collecting blood samples, the purposes of the study and the kinds of information the study would generate. Genomic aspects of the research, including the gene/environment interaction underlying susceptibility or resistance to severe malaria, proved particularly challenging to explain and understand.ConclusionsThis study identifies a number of areas to be addressed in the design of consent processes for genomic research, some of which require careful ethical analysis. These include determining how much information should be provided about differing aspects of the research and how best to promote understandings of genomic research. We conclude that it is important to build capacity in the design and conduct of effective and appropriate consent processes for genomic research in low and middle-income settings. Additionally, consideration should be given to the role of review committees and community consultation activities in protecting the interests of participants in genomic research. (shrink)

Madole & Harden argue that the Mendelian reshuffling of genes and genomes is analogous to randomised controlled trials. We are not convinced by their arguments. First, their recipe for meeting the demands on randomised experiments is inherently inconsistent. Second, disequilibrium across chromosomes conflicts with their assumption of statistical independence. Third, the genome-wide association study (GWAS) method has many pitfalls, including low repeatability.

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. (shrink)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)

Circadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: (...) essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)

Broad genome-wide testing is increasingly finding its way to the public through the online direct-to-consumer marketing of so-called personal genome tests. Personal genome tests estimate genetic susceptibilities to multiple diseases and other phenotypic traits simultaneously. Providers commonly make use of Terms of Service agreements rather than informed consent procedures. However, to protect consumers from the potential physical, psychological and social harms associated with personal genome testing and to promote autonomous decision-making with regard to the testing offer, we argue that current (...) practices of information provision are insufficient and that there is a place – and a need – for informed consent in personal genome testing, also when it is offered commercially. The increasing quantity, complexity and diversity of most testing offers, however, pose challenges for information provision and informed consent. Both specific and generic models for informed consent fail to meet its moral aims when applied to personal genome testing. Consumers should be enabled to know the limitations, risks and implications of personal genome testing and should be given control over the genetic information they do or do not wish to obtain. We present the outline of a new model for informed consent which can meet both the norm of providing sufficient information and the norm of providing understandable information. The model can be used for personal genome testing, but will also be applicable to other, future forms of broad genetic testing or screening in commercial and clinical settings. (shrink)

BackgroundGenome-wide association studies (GWAS) provide a powerful means of identifying genetic variants that play a role in common diseases. Such studies present important ethical challenges. An increasing number of GWAS is taking place in lower income countries and there is a pressing need to identify the particular ethical challenges arising in such contexts. In this paper, we draw upon the experiences of the MalariaGEN Consortium to identify specific ethical issues raised by such research in Africa, Asia and Oceania.DiscussionWe explore ethical (...) issues in three key areas: protecting the interests of research participants, regulation of international collaborative genomics research and protecting the interests of scientists in low income countries. With regard to participants, important challenges are raised about community consultation and consent. Genomics research raises ethical and governance issues about sample export and ownership, about the use of archived samples and about the complexity of reviewing such large international projects. In the context of protecting the interests of researchers in low income countries, we discuss aspects of data sharing and capacity building that need to be considered for sustainable and mutually beneficial collaborations.SummaryMany ethical issues are raised when genomics research is conducted on populations that are characterised by lower average income and literacy levels, such as the populations included in MalariaGEN. It is important that such issues are appropriately addressed in such research. Our experience suggests that the ethical issues in genomics research can best be identified, analysed and addressed where ethics is embedded in the design and implementation of such research projects. (shrink)

The variation in genome size and basic chromosome number was analyzed in the wide range of angiosperm plants. A divergence of monocots vs. dicots (eudicots) genome size distributions was revealed. A similar divergence was found for annual vs. perennial dicots. The divergence of monocots vs. dicots genome size distributions holds at different taxonomic levels and is more pronounced for species with larger genomes. Using nested analysis of variance, it was shown that putative constraints on genome size variation are not only (...) stronger in dicots as compared to monocots but in the former they start to operate already at the family level, whereas in the latter they do so only at the order level. At the same time, variation in basic chromosome number is constrained at the order level in both groups. Higher basic chromosome numbers were found in perennial plants as compared to the annual ones, which can be explained by their need for a higher genetic recombination as compensation for the longer life-cycles. A negative correlation was found between genome size and basic chromosome number, which can be explained as a trade-off between different recombination mechanisms. (shrink)

Genes are functional cell segments of DNA within an organism, as well as basic physical units of biological inheritance, which have consequences for human dignity and public interest. Genes and genetic material (DNA strands of nucleotides, genetically altered plants and animals e.g., see Appendix B) are patentable. In the US and around the globe, governments grant genetic patents for new, non-obvious, and useful gene inventions. A wide range of interest groups such as religious leaders, scientists, biotech pharmaceuticals, medical practitioners, health (...) care providers, venture capitalists, medical patients and persons have interests in defining what is subject to patents. Yet, it is at least questionable that genetic inventions, and the ownership of discoveries of gene mutations leading to possible diseases, should be subject to influence by interest groups. Although some genes (cDNA) are currently legally patentable, the question in this examination is whether gene patents should be legally and morally justified. In this work I examine whether gene patents should legally and morally be justified, given the principles of biomedical ethics such as human Beneficence /Autonomy and Justice. I argue that gene patenting is not justifiable, and I consider what can be done to create a system that delivers access to genetic information in the current genetic Intellectual Patent system. This interdisciplinary work is more complex than whether bio-science researchers and corporate entities should hold gene patents, or differentiating the legal question of whether genes are an invention or a discovery in the human genome. Mere responses to these questions would not ultimately solve the genetic justice problem. The justification for genetic appropriation is more complexity, since it is grounded in axiological claims about human dignity and public interest set in an ever changing biomedical/biogenetic technology. To address this complexity, I will draw upon the ideas of “the capability approach” to genetic justice found in the work of Nussbaum and Sen. This work is an interdisciplinary examination of the proper appropriation of natural genetic material and its impact on human dignity. It is argued that genetic material and information should be accessible to all, via heath care, for example. We must look to new ways to achieve genetic justice that promote human flourishing as a public good. (shrink)

In the future, the Human Genome Project could eventually open the way to perhaps the determination of the complete wiling diagram of the human brain. This kind of progress may move neuroscience forward into the next level of understanding of human neurophysiology, development and behavior. The next crucial step would be to know, exactly what are the function of this genes, and why its lack or alteration causes a certain disease. Although, genomic has in some way contributed to almost every (...) aspects of neurobiology, the results are both significant and troubling.One of the areas, where HGP will contribute to neuroscience is the mapping of qualitative or complex traits. Complex traits like appearence, intelligence and personality are likely to be affected by hundreds or thousands of different genes, rather than one or a few. On the other hand, the complex organisms are not just the simple result of the sum of their genes, nor do genes alone build the different part of organism or influence behaviour by themselves. In spite of the wide variety of misunderstanding, misinterpretation or possible misusing of these new genetic information, this sort of research may eventually lead to useful practical medical results for humans. This information can contribute to work out therapies to treat learning and memory disorders, neurological disorders like Alzheimer's disease, afflicting more and more people in an increasingly ageing population. Genetics believe, there are 3000 to 4000 hereditary diseases. Gene therapy could one day cure some of them, but only when all the details of their genetic basis are known. Biomedicine in the next century will probably have a completely new role in society based on the beginnings inherent in the HGP.There is a general agreement, that modern neuroscience raises important ethical concerns that not have been adequately addressed either by scientists themselves or by the bioethics community. Some scientists interpreted the rapid progress in neuroscience as additional conformation for a materialist account of human nature, resulting in an attack on traditional belief systems. There is a clear tension between the widely held believes and the intellectual views of many scientists. (shrink)

Whole genome sequencing is quickly becoming more affordable and accessible, with the prospect of personal genome sequencing for under $1,000 now widely said to be in sight. The ethical issues raised by the use of this technology in the research context have received some significant attention, but little has been written on its use in the clinical context, and most of this analysis has been futuristic forecasting. This is problematic, given the speed with which whole genome sequencing technology is likely (...) to be incorporated into clinical care. This paper explores one particular subset of these issues: the implications of adopting this technology in the prenatal context without a good understanding of when and how it is useful. Prenatal whole genome sequencing differs from current prenatal genetic testing practice in a number of ethically relevant ways. Most notably, whole genome sequencing would radically increase the volume and scope of available prenatal genetic data. The wealth of new data could enhance reproductive decision‐making, promoting parents' freedom to make well‐informed reproductive decisions. We argue, however, that there is potential for prenatal whole genome sequencing to alter clinical practice in undesirable ways, especially in the short term. We are concerned that the technology could (1) change the norms and expectations of pregnancy in ways that complicate parental autonomy and informed decision‐making, (2) exacerbate the deleterious role that genetic determinism plays in child rearing, and (3) undermine children's future autonomy by removing the option of not knowing their genetic information without appropriate justification. (shrink)

There is ongoing controversy as to whether the genome is a representing system. Although it is widely recognised that DNA carries information, both correlating with and coding for various outcomes, neither of these implies that the genome has semantic properties like correctness or satisfaction conditions, In the Scope of Logic, Methodology, and the Philosophy of Sciences, Vol. II. Kluwer, Dordrecht, pp. 387–400). Here a modified version of teleosemantics is applied to the genome to show that it does indeed have semantic (...) properties – there is representation in the genome. The account differs in three respects from previous attempts to apply teleosemantics to genes. It emphasises the role of the consumer of representations. It rejects the standard assumption that genetic representation can be used to explain the course of an organism’s development. And it identifies the explanatory role played by representational properties of the genome. A striking consequence of this account is that other inheritance systems could also be representational. Thus, a version of the parity thesis is accepted. However, the criteria for being an inheritance system are demanding, so semantic properties are not ubiquitous. (shrink)

Broad genome‐wide testing is increasingly finding its way to the public through the online direct‐to‐consumer marketing of so‐called personal genome tests. Personal genome tests estimate genetic susceptibilities to multiple diseases and other phenotypic traits simultaneously. Providers commonly make use of Terms of Service agreements rather than informed consent procedures. However, to protect consumers from the potential physical, psychological and social harms associated with personal genome testing and to promote autonomous decision‐making with regard to the testing offer, we argue that (...) current practices of information provision are insufficient and that there is a place – and a need – for informed consent in personal genome testing, also when it is offered commercially. The increasing quantity, complexity and diversity of most testing offers, however, pose challenges for information provision and informed consent. Both specific and generic models for informed consent fail to meet its moral aims when applied to personal genome testing. Consumers should be enabled to know the limitations, risks and implications of personal genome testing and should be given control over the genetic information they do or do not wish to obtain. We present the outline of a new model for informed consent which can meet both the norm of providing sufficient information and the norm of providing understandable information. The model can be used for personal genome testing, but will also be applicable to other, future forms of broad genetic testing or screening in commercial and clinical settings. (shrink)

High‐capacity sequencing technologies have dramatically reduced both the cost and time required to generate complete human genome sequences. Besides expanding our knowledge about existing diversity, the nature of these technologies makes it possible to extend knowledge in yet another dimension: time. Recently, the complete genome sequence of a 4,000‐year‐old human from the Saqqaq culture of Greenland was determined to 20‐fold coverage. These data make it possible to investigate the population affinities of this enigmatic culture and, by identifying several phenotypic traits (...) of this individual, provide a limited glimpse into how these people may have looked. While undoubtedly a milestone in ancient DNA research, the cost to generate an ancient genome, even from such an exceptionally preserved specimen, remains out of reach for most. Nonetheless, recently developed DNA capture methods, already applied to Neanderthal and fossil human mitochondrial DNA, may soon make large‐scale genome‐wide analysis of ancient human diversity a reality, providing a fresh look at human population history. (shrink)

The generation of patterns and the diversity of cell types in a multicellular organism require differential gene regulation. At the heart of this process are enhancers or cis‐regulatory modules (CRMs), genomic regions that are bound by transcription factors (TFs) that control spatio‐temporal gene expression in developmental networks. To date, only a few CRMs have been studied in detail and the underlying cis‐regulatory code is not well understood. Here, we review recent progress on the genome‐wide identification of CRMs with chromatin (...) immunoprecipitation of TF‐DNA complexes followed by microarrays (ChIP‐on‐chip). We focus on two computational approaches that have succeeded in predicting the expression pattern driven by a CRM either based on TF binding site preferences and their expression levels, or quantitative analysis of CRM occupancy by key TFs. We also discuss the current limits of these methods and highlight some of the key problems that have to be solved to gain a more complete understanding of the structure and function of CRMs. (shrink)

Many areas of genetic research, genetic forensics and genetic essentialism are treated in public sphere debate as suspicious and problematic or are subject to waves of moral panic. In cultural theory, likewise, strong critiques of the genetic essentialism emerge as part of a broader critical assessment of the discourses of the biological sciences and the assertion of a connection between genes and human behavior. However, the scientific and popular claim to the existence of a “gay gene” is not treated in (...) the same way, and has been widely celebrated both within lesbian/gay culture and more broadly in liberal-humanist speech. This essay suggests that it is not enough to presume that this is a result of the extension of essentialism into new popular understandings of human biology. Rather, this essay examines five reasons which have made the popular acceptance of a “gay gene” tenable: the dominance of “gay personage” arguments, the continued influence of early sexology, the suspicion of psychological and constructionist approaches to lesbian/gay sexualities, the effectiveness of genetic essentialism in“ethnic rights” political approaches and the continued centrality of “fixed subjecthood” in contemporary western culture. (shrink)

Implicit God-like and ghost-in-the-machine metaphors underlie much current thinking about genomes. Although many criticisms of such views exist, none have succeeded in substituting a different, widely accepted view. Viewing the genome with its protein packaging as a brain gets rid of Gods and ghosts while plausibly integrating machine and information-based views. While the ‘wetware’ of brains and genomes are very different, many fundamental principles of how they function are similar. Eukaryotic cells are compound entities in which case the nuclear genome (...) might best be thought of more as a government than simply as a brain. (shrink)

The use of genome-wide association studies in medical research and the increased ability to share data give a new twist to some of the perennial ethical issues associated with genomic research. GWAS create particular challenges because they produce fine, detailed, genotype information at high resolution, and the results of more focused studies can potentially be used to determine genetic variation for a wide range of conditions and traits. The information from a GWA scan is derived from DNA that is a (...) powerful personal identifier, and can provide information not just on the individual, but also on the individual's relatives, related groups, and populations. Furthermore, it creates large amounts of individual-specific digital information that is easy to share across international borders. This paper provides an overview of some of the key ethical issues around GWAS: consent, feedback of results, privacy, and the governance of research. Many of the questions that lie ahead of us in terms of the next generation sequencing methods will have been foreshadowed by GWAS and the debates around ethical and policy issues that these have created. (shrink)

The Human Genome Project is an expensive, ambitious, and controversial attempt to locate and map every one of the approximately 100,000 genes in the human body. If it works, and we are able, for instance, to identify markers for genetic diseases long before they develop, who will have the right to obtain such information? What will be the consequences for health care, health insurance, employability, and research priorities? And, more broadly, how will attitudes toward human differences be affected, morally and (...) socially, by the setting of a genetic “standard”? The compatibility of individual rights and genetic fairness is challenged by the technological possibilities of the future, making it difficult to create an agenda for a “just genetics.” Beginning with an account of the utopian dreams and authoritarian tendencies of historical eugenics movements, this book’s nine essays probe the potential social uses and abuses of detailed genetic information. Lucid and wide-ranging, these contributions will interest bioethicists, legal scholars, and policy makers. Essays: “The Genome Project and the Meaning of Difference,” Timothy F. Murphy “Eugenics and the Human Genome Project: Is the Past Prologue?,” Daniel J. Kevles “Handle with Care: Race, Class, and Genetics,” Arthur L. Caplan “Public Choices and Private Choices: Legal Regulation of Genetic Testing,” Lori B. Andrews “Rules for Gene Banks: Protecting Privacy in the Genetics Age,” George J. Annas “Use of Genetic Information by Private Insurers,” Robert J. Pokorski “The Genome Project, Individual Differences, and Just Health Care,” Norman Daniels “Just Genetics: A Problem Agenda,” Leonard M. Fleck “Justice and the Limitations of Genetic Knowledge,” Marc A. Lappé. (shrink)

Public opinion can affect the adoption of genome editing technologies. In food production, genome editing can be applied to a wide range of applications, in different species and with different purposes. This study analyzed how the public responds to five different applications of genome editing, varying the species involved and the proposed purpose of the modification. Three of the applications described the introduction of disease resistance within different species, and two targeted product quality and quantity in cattle. Online surveys in (...) Canada, the US, Austria, Germany and Italy were carried out with a total sample size of 3698 participants. Using a between-subject design, participants were confronted with one of the five applications and asked to decide whether they considered it right or wrong. Perceived risks, benefits, and the perception of the technology as tampering with nature were surveyed and were complemented with socio-demographics and a measure of the participants’ moral foundations. In all countries, participants evaluated the application of disease resistance in humans as most right to do, followed by disease resistance in plants, and then in animals, and considered changes in product quality and quantity in cattle as least right to do. However, US and Italian participants were generally more positive toward all scenarios, and German and Austrian participants more negative. Cluster analyses identified four groups of participants: ‘strong supporters’ who saw only benefits and little risks, ‘slight supporters’ who perceived risks and valued benefits, ‘neutrals’ who showed no pronounced opinion, and ‘opponents’ who perceived higher risks and lower benefits. This research contributes to understanding public response to applications of genome editing, revealing differences that can help guide decisions related to adoption of these technologies. (shrink)

Background: Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrolment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study. Methods: The study used a rapid assessment incorporating multiple qualitative methods (...) including in depth interviews, focus group discussions and observations of consent processes. Differences between verbal information provided during community engagement processes, and consent processes during the enrolment of cases and controls were identified, as well as the factors influencing the tailoring of such information. Results: MalariaGEN participants and field staff seeking consent were generally satisfied with their understanding of the project and were familiar with aspects of the study relating to malaria. Some genetic aspects of the study were also well understood. Participants and staff seeking consent were less aware of the methodologies employed during genomic research and their implications, such as the breadth of data generated and the potential for future secondary research.Moreover, trust in and previous experience with the Navrongo Health Research Centre which was conducting the research influenced beliefs about the benefits of participating in the MalariaGEN study and subsequent decision-making about research participation. Conclusions: It is important to recognise that some aspects of complex genomic research may be of less interest to and less well understood by research participants and that such gaps in understanding may not be entirely addressed by best practice in the design and conduct of consent processes. In such circumstances consideration needs to be given to additional protections for participants that may need to be implemented in such research, and how best to provide such protections.Capacity building for research ethics committees with limited familiarity with genetic and genomic research, and appropriate engagement with communities to elicit opinions of the ethical issues arising and acceptability of downstream uses of genome wide association data are likely to be important. (shrink)

Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrolment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study.

New advances in genomics changed the research landscape significantly in the last few years. The power and significance of already existing tissue collections is enhanced by their growing size, and all over the world national projects aim to connect with each other at the international level, calling for integrated and common regulations in the transnational research field. The post genomics era faces problems that are partially different from those within the classical bioethical framework. The challenge is to find new ways (...) to deal with regulations in order to facilitate research without frustrating personal rights. Informed Consent has been the center of this wide debate. We propose a model for rethinking consent in an open-time/open-goal framework suitable to genomics research. Consensus becomes more than a single legal step and goes more in the direction of a participated governance mechanism, a circular open process of communication which the IC sheet signature is just one instance of. This approach provides a governance framework based on different levels of consensus and participation that already contains mechanisms to resolve conflicts between different instances and to protect both the interest of research and the rights of participants. (shrink)

The development of improved methods for genome‐wide association studies (GWAS) for genetics of quantitative traits has been an active area of research during the last 25 years. This activity initially started with the use of mixed linear model (MLM), which was variously modified. During the last decade, however, with the availability of high throughput next generation sequencing (NGS) technology, development and use of pangenomes and novel markers including structural variations (SVs) and k‐mers for GWAS has taken over as a (...) new thrust area of research. Pangenomes and SVs are now available in humans, livestock, and a number of plant species, so that these resources along with k‐mers are being used in GWAS for exploring additional genetic variation that was hitherto not available for analysis. These developments have resulted in significant improvement in GWAS methodology for detection of marker‐trait associations (MTAs) that are relevant to human healthcare and crop improvement. (shrink)

Many scientists and doctors hope that affordable genome sequencing will lead to more personalized medical care and improve public health in ways that will benefit children, families, and society more broadly. One hope in particular is that all newborns could be sequenced at birth, thereby setting the stage for a lifetime of medical care and self‐directed preventive actions tailored to each child's genome. Indeed, commentators often suggest that universal genome sequencing is inevitable. Such optimism can come with the presumption that (...) discussing the potential limits, cost, and downsides of widespread application of genomic technologies is pointless, excessively pessimistic, or overly cautious. We disagree. Given the pragmatic challenges associated with determining what sequencing data mean for the health of individuals, the economic costs associated with interpreting and acting on such data, and the psychosocial costs of predicting one's own or one's child's future life plans based on uncertain testing results, we think this hope and optimism deserve to be tempered.In the analysis that follows, we distinguish between two reasons for using sequencing: to diagnose individual infants who have been identified as sick and to screen populations of infants who appear to be healthy. We also distinguish among three contexts in which sequencing for either diagnosis or screening could be deployed: in clinical medicine, in public health programs, and as a direct‐to‐consumer service. Each of these contexts comes with different professional norms, policy considerations, and public expectations. Finally, we distinguish between two main types of genome sequencing: targeted sequencing, where only specific genes are sequenced or analyzed, and whole‐exome or whole‐genome sequencing, where all the DNA or all the coding segments of all genes are sequenced and analyzed.In a symptomatic newborn, targeted or genome‐wide sequencing can help guide other tests for diagnosis or for specific treatment that is urgently needed. Clinicians use the infant's symptoms (or phenotype) to interrogate the sequencing data. These same complexities and uncertainties, however, limit the usefulness of genome‐wide sequencing as a population screening tool. While we recognize considerable benefit in using targeted sequencing to screen for or detect specific conditions that meet the criteria for inclusion in newborn screening panels, use of genome‐wide sequencing as a sole screening tool for newborns is at best premature. We conclude that sequencing technology can be beneficially used in newborns when that use is nuanced and attentive to context. (shrink)

Lockdowns and quarantines have been implemented widely in response to the COVID-19 pandemic. This has been accompanied by a rise in interest in the ethics of ‘passport’ systems that allow low-risk individuals greater freedoms during lockdowns and exemptions to quarantines. Immunity and vaccination passports have been suggested to facilitate the greater movement of those with acquired immunity and who have been vaccinated. Another group of individuals who pose a low risk to others during pandemics are those with genetically mediated resistances (...) to pathogens. In this paper, we introduce the concept of genomic passports, which so far have not been explored in the bioethics literature. Using COVID-19 as an illustrative example, we explore the ethical issues raised by genomic passports and highlight differences and similarities to immunity passports. We conclude that, although there remain significant practical and ethical challenges to the implementation of genomic passports, there will be ways to ethically use them in the future. (shrink)