The Ethics of Large-Scale Genomic Research

Background: With the outbreak of high throughput next-generation sequencing (NGS), the biological research of drug discovery has been directed towards the oncology and infectious disease therapeutic areas, with extensive use in biopharmaceutical development and vaccine production. Method: In this review, an effort was made to address the basic background of NGS technologies, potential applications of NGS in drug designing. Our purpose is also to provide a brief introduction of various Nextgeneration sequencing techniques. Discussions: The high-throughput methods execute Large-scale Unbiased Sequencing (LUS) which comprises of Massively Parallel Sequencing (MPS) or NGS technologies. The Next geneinvolved necessarily executes Largescale Unbiased Sequencing (LUS) which comprises of MPS or NGS technologies. These are related terms that describe a DNA sequencing technology which has revolutionized genomic research. Using NGS, an entire human genome can be sequenced within a single day. Conclusion: Analysis of NGS data unravels important clues in the quest for the treatment of various lifethreatening diseases and other related scientific problems related to human welfare.

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‘CTRL’: an online, Dynamic Consent and participant engagement platform working towards solving the complexities of consent in genomic research

European Journal of Human Genetics ◽

10.1038/s41431-020-00782-w ◽

2021 ◽

Author(s):

Matilda A. Haas ◽

Harriet Teare ◽

Megan Prictor ◽

Gabi Ceregra ◽

Miranda E. Vidgen ◽

...

Keyword(s):

Large Scale ◽

Genomic Medicine ◽

International Standards ◽

Security And Privacy ◽

Genomic Research ◽

Return Of Results ◽

Future Research ◽

Design And Development ◽

Participant Engagement ◽

Dynamic Consent

AbstractThe complexities of the informed consent process for participating in research in genomic medicine are well-documented. Inspired by the potential for Dynamic Consent to increase participant choice and autonomy in decision-making, as well as the opportunities for ongoing participant engagement it affords, we wanted to trial Dynamic Consent and to do so developed our own web-based application (web app) called CTRL (control). This paper documents the design and development of CTRL, for use in the Australian Genomics study: a health services research project building evidence to inform the integration of genomic medicine into mainstream healthcare. Australian Genomics brought together a multi-disciplinary team to develop CTRL. The design and development process considered user experience; security and privacy; the application of international standards in data sharing; IT, operational and ethical issues. The CTRL tool is now being offered to participants in the study, who can use CTRL to keep personal and contact details up to date; make consent choices (including indicate preferences for return of results and future research use of biological samples, genomic and health data); follow their progress through the study; complete surveys, contact the researchers and access study news and information. While there are remaining challenges to implementing Dynamic Consent in genomic research, this study demonstrates the feasibility of building such a tool, and its ongoing use will provide evidence about the value of Dynamic Consent in large-scale genomic research programs.

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Attitudes to the return of incidental and targeted genomic findings obtained in a high-risk pediatric cancer versus an inherited genetic condition research setting.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.10066 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 10066-10066

Author(s):

Conrad Vincent Fernandez ◽

Nada Jabado ◽

Kym Boycott ◽

David Malkin ◽

Eric Bouffet ◽

...

Keyword(s):

Pediatric Cancer ◽

Large Scale ◽

Health Impact ◽

Genomic Research ◽

Childhood Onset ◽

Genetic Condition ◽

Chi Square ◽

Research Results ◽

Pediatric Cancer Patients ◽

Almost All

10066 Background: The disclosure of clinically significant, validated incidental and target findings to participants in genomic research is often recommended. There have been no reports on whether attitudes of parents differ if these findings emerge from an acquired pediatric cancer versus an inherited genetic condition setting. Methods: Parents in 3 large-scale projects [Canadian Pediatric Cancer Genome Consortium (CPCGC), the Finding of Rare Genes Canada Consortium (FORGE) and the Orphan Diseases: identifying Genes and Novel Therapeutics to Enhance Treatment Project (IGNITE)] were surveyed using a mailed, validated 29-item questionnaire. Two reminders were sent. Analysis was by descriptive and Chi-square statistics. Results: Response rate: 64% (n=307/480). 40% were > 50 yrs age; more than half had a grade 12 education. 86 were parents of poor risk pediatric cancer patients and 221 were parents or individuals with rare inherited conditions. Most stated a very strong or strong right to genomic research results, irrespective if from the target condition (97%) or incidental (86%). 70% wish genetic counselling pre- and post-research testing; an additional 20% were uncertain what this entails. Almost all indicated that genomic research for childhood onset conditions should occur, regardless of whether therapy existed (99%) or not (91%). A few indicated that they would not want incidental results showing an untreatable fatal condition (17%). Most want results, even if these suggest susceptibility to multiple conditions (87%) or are of uncertain health impact (84%). Most felt a right to genomic research that showed a serious condition in siblings, whether treatable (94%) or not (89%). 74% strongly support that results discovered after death of the proband be shared with family. Conclusions: Parents of children in both cancer and inherited rare conditions genomic research do not differ in indicating a strong right and desire to receive research results, even if they are of uncertain impact, of childhood onset, or after death of the proband. Clear delineation of what will or will not be offered from genomic research should be established at the time of consent.

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Ethical and public policy challenges for pharmacogenomics

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2014.16.4/egershon ◽

2014 ◽

Vol 16 (4) ◽

pp. 567-574 ◽

Cited By ~ 5

Keyword(s):

Psychiatric Disorders ◽

Large Scale ◽

Ethical Issues ◽

De Novo ◽

Correct Choice ◽

Genomic Research ◽

Drug Metabolizing Enzyme ◽

Increased Risk ◽

Number Variation ◽

Metabolizing Enzyme

It is timely to consider the ethical and social questions raised by progress in pharmacogenomics, based on the current importance of pharmacogenomics for avoidance of predictable side effects of drugs, and for correct choice of medications in certain cancers. It has been proposed that the entire population be genotyped for drug-metabolizing enzyme polymorphisms, as a measure that would prevent many untoward and dangerous drug reactions. Pharmacologic treatment targeting based on genomics of disease can be expected to increase greatly in the coming years. Policy and ethical issues exist on consent for large-scale genomic pharmacogenomic data collection, public vs corporate ownership of genomic research results, testing efficacy and safety of drugs used for rare genomic indications, and accessibility of treatments based on costly research that is applicable to relatively few patients. In major psychiatric disorders and intellectual deficiency, rare and de novo deletion or duplication of chromosomal segments (copy number variation), in the aggregate, are common causes of increased risk. This implies that the policy problems of pharmacogenomics will be particularly important for the psychiatric disorders.

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From single nuclei to whole genome assemblies

10.1101/625814 ◽

2019 ◽

Cited By ~ 3

Author(s):

Merce Montoliu-Nerin ◽

Marisol Sánchez-García ◽

Claudia Bergin ◽

Manfred Grabherr ◽

Barbara Ellis ◽

...

Keyword(s):

Single Cell ◽

Large Scale ◽

Genomic Data ◽

Life Cycles ◽

Genomic Research ◽

Metagenomic Data ◽

Model Organisms ◽

Genomic Study ◽

And Function ◽

Genome Assemblies

SummaryA large proportion of Earth's biodiversity constitutes organisms that cannot be cultured, have cryptic life-cycles and/or live submerged within their substrates1–4. Genomic data are key to unravel both their identity and function5. The development of metagenomic methods6,7 and the advent of single cell sequencing8–10 have revolutionized the study of life and function of cryptic organisms by upending the need for large and pure biological material, and allowing generation of genomic data from complex or limited environmental samples. Genome assemblies from metagenomic data have so far been restricted to organisms with small genomes, such as bacteria11, archaea12 and certain eukaryotes13. On the other hand, single cell technologies have allowed the targeting of unicellular organisms, attaining a better resolution than metagenomics8,9,14–16, moreover, it has allowed the genomic study of cells from complex organisms one cell at a time17,18. However, single cell genomics are not easily applied to multicellular organisms formed by consortia of diverse taxa, and the generation of specific workflows for sequencing and data analysis is needed to expand genomic research to the entire tree of life, including sponges19, lichens3,20, intracellular parasites21,22, and plant endophytes23,24. Among the most important plant endophytes are the obligate mutualistic symbionts, arbuscular mycorrhizal (AM) fungi, that pose an additional challenge with their multinucleate coenocytic mycelia25. Here, the development of a novel single nuclei sequencing and assembly workflow is reported. This workflow allows, for the first time, the generation of reference genome assemblies from large scale, unbiased sorted, and sequenced AM fungal nuclei circumventing tedious, and often impossible, culturing efforts. This method opens infinite possibilities for studies of evolution and adaptation in these important plant symbionts and demonstrates that reference genomes can be generated from complex non-model organisms by isolating only a handful of their nuclei.

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CURRENT ISSUES OF LEGAL REGULATION OF HUMAN GENOME DATABASES CREATING AND FUNCTIONING

The rule-of-law state: theory and practice ◽

10.33184/pravgos-2020.2.12 ◽

2020 ◽

Vol 16 (2) ◽

pp. 134-144

Author(s):

Алексей Чемерис ◽

Владимир Анисимов ◽

Фарит Аминев

Keyword(s):

Human Genome ◽

Genetic Information ◽

Large Scale ◽

Legal Regulation ◽

National Standards ◽

Genomic Research ◽

Genomic Information ◽

Federal Law ◽

Genome Databases ◽

State Organizations

The relevance of the article is due, on the one hand, to the active introduction of genomic research technologies into everyday life and the accumulation of a significant amount of genetic information while providing medical care and other genome screening and sequencing services by private and state organizations. On the other hand, it is relevant due to the beginning of the implementation of large-scale government projects to create an information-analytical system for storing and processing genetic data. In these circumstances, the issues of developing an effective legal regulation of creating and functioning of human genome databases are of particular importance. Aim: to study the requirements of international and national standards for statutory regulation of relations connected to genomic researches, as well as to collecting, processing, storing and using genetic information. Methods: in the study formal logical and general scientific methods of scientific knowledge are used; private scientific (comparative legal, formal dogmatic) methods are used. Results: Based on these requirements, the current national legislation is assessed, an urgent need is defined to adopt a special federal law on the protection of genomic information, which enshrines the necessary rules on procedures for forming relevant databases, the procedure for storing and using the resulting genomic information, as well as the legal regime of the information contained in the database.

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Assessing anthelmintic resistance risk in the post-genomic era: a proof-of-concept study assessing the potential for widespread benzimidazole-resistant gastrointestinal nematodes in North American cattle and bison

Parasitology ◽

10.1017/s0031182020000426 ◽

2020 ◽

Vol 147 (8) ◽

pp. 897-906 ◽

Cited By ~ 1

Author(s):

Russell W. Avramenko ◽

Elizabeth M. Redman ◽

Claire Windeyer ◽

John S. Gilleard

Keyword(s):

Drug Resistance ◽

Large Scale ◽

Anthelmintic Resistance ◽

Low Frequency ◽

Nematode Species ◽

Amplicon Sequencing ◽

Gastrointestinal Nematodes ◽

Genomic Research ◽

Resistance Risk ◽

Benzimidazole Resistance

AbstractAs genomic research continues to improve our understanding of the genetics of anthelmintic drug resistance, the revolution in DNA sequencing technologies will provide increasing opportunities for large-scale surveillance for the emergence of drug resistance. In most countries, parasite control in cattle and bison has mainly depended on pour-on macrocyclic lactone formulations resulting in widespread ivermectin resistance. Consequently, there is an increased interest in using benzimidazole drugs which have been used comparatively little in cattle and bison in recent years. This situation, together with our understanding of benzimidazole resistance genetics, provides a practical opportunity to use deep-amplicon sequencing to assess the risk of drug resistance emergence. In this paper, we use deep-amplicon sequencing to scan for those mutations in the isotype-1 β-tubulin gene previously associated with benzimidazole resistance in many trichostrongylid nematode species. We found that several of these mutations occur at low frequency in many cattle and bison parasite populations in North America, suggesting increased use of benzimidazole drugs in cattle has the potential to result in widespread emergence of resistance in multiple parasite species. This work illustrates a post-genomic approach to large-scale surveillance of early emergence of anthelmintic resistance in the field.

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What Does DNA Tell Us about Past Connections and the Settlement of Sahul?

The Oxford Handbook of the Archaeology of Indigenous Australia and New Guinea ◽

10.1093/oxfordhb/9780190095611.013.11 ◽

2021 ◽

Author(s):

Elizabeth Matisoo-Smith ◽

Anna L. Gosling

Keyword(s):

Indigenous Peoples ◽

Large Scale ◽

Human Impacts ◽

Genomic Research ◽

Community Consultation ◽

Sequencing Technology ◽

Local Fauna ◽

Population Replacement ◽

Scale Population ◽

Early Human

Archaeological evidence indicates that the continent of Sahul has been continuously settled for almost as long as modern humans have lived outside of Africa. The relative isolation of the continent, and the difficulty involved in getting there, have meant that the populations have not been subject to the large-scale population replacement seen in other parts of the world. Recent advances in DNA sequencing technology, including the ability to sequence full genomes in both ancient and modern populations, have revealed that the genomes of the Indigenous peoples of Australia and New Guinea, and the local fauna, can contribute significantly to our understanding of early human migrations from Africa, human impacts on environments, as well as human evolution more broadly. Given the power of genomic data, it is of the utmost importance that genomic research of ancient and modern samples is conducted ethically, with full community consultation and engagement at all stages.

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Unraveling the Roles of Regulatory Genes during Domestication of Cultivated Camellia: Evidence and Insights from Comparative and Evolutionary Genomics

Genes ◽

10.3390/genes9100488 ◽

2018 ◽

Vol 9 (10) ◽

pp. 488 ◽

Cited By ~ 5

Author(s):

Chao Yan ◽

Ping Lin ◽

Tao Lyu ◽

Zhikang Hu ◽

Zhengqi Fan ◽

...

Keyword(s):

Complex Traits ◽

Large Scale ◽

Genetic Alterations ◽

Genomic Research ◽

Economic Traits ◽

Vast Number ◽

Scale Population ◽

Camellia Species ◽

Flower And Fruit Development ◽

Future Work

With the increasing power of DNA sequencing, the genomics-based approach is becoming a promising resolution to dissect the molecular mechanism of domestication of complex traits in trees. Genus Camellia possesses rich resources with a substantial value for producing beverage, ornaments, edible oil and more. Currently, a vast number of genetic and genomic research studies in Camellia plants have emerged and provided an unprecedented opportunity to expedite the molecular breeding program. In this paper, we summarize the recent advances of gene expression and genomic resources in Camellia species and focus on identifying genes related to key economic traits such as flower and fruit development and stress tolerances. We investigate the genetic alterations and genomic impacts under different selection programs in closely related species. We discuss future directions of integrating large-scale population and quantitative genetics and multiple omics to identify key candidates to accelerate the breeding process. We propose that future work of exploiting the genomic data can provide insights related to the targets of domestication during breeding and the evolution of natural trait adaptations in genus Camellia.

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ESC - a comprehensive resource for SARS-CoV-2 immune escape variants

10.1101/2021.02.18.431922 ◽

2021 ◽

Author(s):

Mercy Rophina ◽

Kavita Pandhare ◽

Afra Shamnath ◽

Mohamed Imran ◽

Bani Jolly ◽

...

Keyword(s):

Genetic Variants ◽

Viral Genome ◽

Neutralizing Antibodies ◽

Large Scale ◽

Immune Escape ◽

Spike Protein ◽

Genomic Research ◽

Disease Pathogenesis ◽

Underlying Mechanisms ◽

Gain Access

ABSTRACTEver since the breakout of COVID-19 disease, ceaseless genomic research to inspect the epidemiology and evolution of the pathogen has been undertaken globally. Large scale viral genome sequencing and analysis have uncovered the functional impact of numerous genetic variants in disease pathogenesis and transmission. Emerging evidence of mutations in spike protein domains escaping antibody neutralization is reported. We have a precise collation of manually curated variants in SARS-CoV-2 from literature with potential escape mechanisms from a range of neutralizing antibodies. This comprehensive repository encompasses a total of 532 variants accounting for 146 unique variants tested against 75 antibodies and patient convalescent plasma. This resource enables the user to gain access to an extensive annotation of SARS-CoV-2 escape mutations which we hope would contribute to exploring and understanding the underlying mechanisms of immune response against the pathogen. The resource is available at http://clingen.igib.res.in/esc/.

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