Genetic Technologies Research Articles

The Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance.

Functional annotation and interpretation of genetic variants are a critical step in genetic diagnosis, as it may lead to personalized therapeutic options and genetic counseling. While the number of confirmed pathogenic genetic variants in an individual is relatively low, the number of variants of uncertain significance (VOUS) can be considerably higher, increasing the number of potential carriers of genetic disorders. Thus, reducing uncertainty and assessing the real effect of VOUS are crucial for clinical and medical genetics. In this study, we evaluated the efficacy of genetic screening technologies in accurately predicting pathogenic variants and their corresponding disease prevalence in a cohort of over 6000 healthy individuals involved in assisted reproduction programs. Using data from 305 genes associated with recessive disorders, we determined the frequency of carriers of pathogenic variants and VOUS in our dataset and compared the predicted prevalence based on this information with reported population prevalence data. The higher predicted prevalence in some disorders when considering VOUS suggests a mostly benign effect.

Transhumanism, Human Moral Enhancement, and Virtues

Moral transhumanism is a project that aims to enhance human beings by using modern technology in a morally beneficial way. This article discusses the problems and ethical dilemmas raised by transhumanism, notably whether (moral) virtues may be enhanced in the proposed manner. To achieve this end, moral transhumanism primarily proposes the use of genetic technology and pharmacology. Regarding moral virtues, the article suggests that sensitivity to reasons is a fundamental feature of human moral cognition. Enhancing moral virtues would diminish this sensitivity or assign it a superfluous role while jeopardizing the person’s autonomy and self-determination.

A duty to enhance? Genetic engineering for the human Mars settlement.

Humans living off-world will face numerous physical, psychological and social challenges and are likely to suffer negative health effects due to their lack of evolutionary adaptation to space environments. While some of the necessary adaptations may develop naturally over many generations, genetic technologies could be used to speed this process along, potentially improving the wellbeing of early space settlers and their offspring. With broad support, such a program could lead to significant genetic modification of off-world communities, for example, to limit radiation damage on body systems or prevent bone and muscle loss in reduced gravity conditions. Given the extreme stressors of living off-world, and the need to have a healthy workforce to support a fledgling human settlement, those in favour of using genetic technologies to enhance settlers might even claim there is a moral imperative to protect their health in the face of the unique threats of space travel, especially for children born in settlements who did not take on these risks voluntarily. For some, this might simply be an extension of procreative beneficence. However, ethical concerns arise regarding the risks of embracing a eugenicist agenda and the potential impacts on the rights of future settlers to refuse such genetic enhancements for themselves or their children.

Deepening Root Inputs: Potential Soil Carbon Accrual From Breeding for Deeper Rooted Maize.

Breeding annual crops for enhanced root depth and biomass is considered a promising intervention to accrue soil organic carbon (SOC) in croplands, with benefits for climate change mitigation and soil health. In annual crops, genetic technology (seed) is replaced every year as part of a farmer's fixed costs, making breeding solutions to climate change more scalable and affordable than management approaches. However, mechanistic understanding and quantitative estimates of SOC accrual potentials from crops with enhanced root phenotypes are lacking. Maize is the highest acreage and yielding crop in the US, characterized by relatively low root biomass confined to the topsoil, making it a suitable candidate for improvement that could be rapidly scaled. We ran a 2-year field experiment to quantify the formation and composition (i.e., particulate (POM), coarse and fine mineral-associated organic matter (chaOM and MAOM, respectively) of new SOC to a depth of 90 cm from the decomposition of isotopically labeled maize roots and exudates. Additionally, we used the process-based MEMS 2 model to simulate the SOC accrual potential of maize root ideotypes enhanced to either shift root production to deeper depths or increase root biomass allocation, assuming no change in overall productivity. In our field experiment, maize root decomposition preferentially formed POM, with doubled efficiency below 50 cm, while root exudates preferentially formed MAOM. Modeling showed that shifting root inputs to deeper layer or increasing allocation to roots resulted in a deterministic increase in SOC, ranging from 0.05 to 0.15 Mg C ha-1 per year, which are at the low end of the range of published SOC per hectare annual accrual estimates from adoption of a variety of crop management practices. Our analysis indicates that for maize, breeding for increasing root inputs as a strategy for SOC accrual has limited impact on a per-hectare basis, although given that globally maize is produced on hundreds of millions of hectares each year, there is potential for this technology and its effect to scale. For maize-soy system that dominates US acres, changes in the overall cropping system are needed for sizable greenhouse gas reductions and SOC accrual. This study demonstrated a modeling and experimental framework to quantify and forecast SOC changes created by changing crop root inputs.

The TOR signalling pathway in fungal phytopathogens: A target for plant disease control.

Plant diseases caused by fungal phytopathogens have led to significant economic losses in agriculture worldwide. The management of fungal diseases is mainly dependent on the application of fungicides, which are not suitable for sustainable agriculture, human health, and environmental safety. Thus, it is necessary to develop novel targets and green strategies to mitigate the losses caused by these pathogens. The target of rapamycin (TOR) complexes and key components of the TOR signalling pathway are evolutionally conserved in pathogens and closely related to the vegetative growth and pathogenicity. As indicated in recent systems, chemical, genetic, and genomic studies on the TOR signalling pathway, phytopathogens with TOR dysfunctions show severe growth defects and nonpathogenicity, which makes the TOR signalling pathway to be developed into an ideal candidate target for controlling plant disease. In this review, we comprehensively discuss the current knowledge on components of the TOR signalling pathway in microorganisms and the diverse roles of various plant TOR in response to plant pathogens. Furthermore, we analyse a range of disease management strategies that rely on the TOR signalling pathway, including genetic modification technologies and chemical controls. In the future, disease control strategies based on the TOR signalling network are expected to become a highly effective weapon for crop protection.

Histiocytosis Advancements Parallel Ophthalmic Innovations. The LXXXI Edward Jackson Memorial Lecture

PurposeTo highlight innovations in ophthalmic oncology through histiocytosis advancements. DesignPerspective and retrospective review. MethodsThe literature outlining the recent advancements in histiocytosis and ocular oncology were reviewed and combined with trial data and personal recollection. Intersections between these two fields were discussed. ResultsThe understanding of genetic mutations in disease—both in which cells they occur and the timing of mutation development—has expanded in tandem for the fields of ophthalmic oncology and histiocytosis. Similarly, advancements in diagnostic and treatment technology in one field can help patients in the other. For example, in one study, cell-free DNA testing reliably detected mutations in 14 of 18 (78%) patients with suspected histiocytosis. This technique has also been used in ophthalmic oncology as an alternative to invasive biopsy to avoid the risk of tumor externalization, vision impairment, and other side effects. These and other advancements, have allowed both fields to utilize targeted agents to successfully treat diseases with an actionable mutation; or deliver more targeted chemotherapy via the intraarterial technique. ConclusionsThe explosion of molecular genetics technology and targeted therapies has revolutionized cancer treatment, including histiocytosis and ophthalmic oncology. Recent progress in both fields has shown how these seemingly disparate areas have many intersections, and this speaks to the collaborative spirit that is inherent in clinical research.

Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.

Advances in genetic technologies and disease modeling have greatly accelerated the pace of introducing and validating molecular-genetic contributors to disease. In dystonia, there is a growing convergence across multiple distinct forms of the disease onto core biological processes. Here, we discuss two of these, the endosome-autophagosome-lysosome pathway and the integrated stress response, to highlight recent advances in the field. Using these two pathomechanisms as examples, we further discuss the opportunities that molecular-genetic grouping of dystonias present to transform dystonia care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Genetic and other omics-based information in the most-cited recent clinical trials

Abstract Introduction Since the genomic revolution, the utilization of genetic and omics technologies has undergone considerable expansion within clinical studies, employed in design, analysis, and interpretation. Methods A recent study of Siena et al. developed a database containing the 600 most cited clinical trials published from 2019 to 2022. Building on this database, the aim of our study is to assess how frequently genetic and other omics-based information has been used in the design, analysis, results or conclusion of these recent influential trials. Results 132 out 600 (22%) trials used genetic or other omics. These trials were more likely to be oncology trials (76%vs34%), having industry funding (59%vs47%), and having industry authors (75%vs54%) than others. Overall, genetics and genomics were present in 75% of the trials (100/132), and oncology was the predominant medical field (76%, n = 101). The prevailing use was detection of specific mutations (n = 99), often (n = 60) used as eligibility criterion. These mutations were mostly somatic (n = 85), while 14 were germline. Other applications included transcriptomics (20.4%), proteomics (10.6%), metabolomics (8.3%) and metagenomics (8.3%). 36 studies (27%) employed multiple applications. Genetics or other omics were used in 10% of the studies (14/132) for randomization stratification and in 63% (83/132) to conduct subgroup analysis. Among the latter, in 48% (40/83) the presence of a somatic mutation was significantly associated with the investigated health outcomes, while germline mutation or other omics only in the 12% (10/83). In the trials conclusions, authors addressed the relevance of the genetic or omics information in 62.1% (82/132) of the trials. Conclusions A sizeable proportion of the most-cited clinical trials use genetics or omics-based information, but the large majority pertains to cancer mutations in oncology trials. Use of genetics and omics needs to become more common in other clinical trial fields. Key messages • Genetic profiling and omics applications should be incorporated into trial design. • Genomic research is mostly oncology related and it needs to be expanded to other medical fields.

N-glycosylation of the envelope glycoprotein I is essential for the proliferation and virulence of the duck plague virus

Duck plague virus (DPV) causes the highly pathogenic duck plague, and the envelope glycoprotein I (gI), as one of the key virulence genes, has not yet had its critical virulence sites identified through screening. This study used reverse genetics technology to target the gI, specifically within the DPV genome. Four DPV mutants with gI N-glycosylation site mutations were designed and constructed, and these mutant strains were successfully rescued. Our results confirmed that three asparagine residues of gI (N69, N78, and N265) are N-glycosylation sites, and western blot analysis substantiated that glycosylation at each predicted N-glycosylation site was compromised. The deglycosylation of gI leads to the protein misfolding and subsequent retention in the endoplasmic reticulum (ER). The subsequent deglycosylated gI is carried into the Golgi apparatus (GM130) in the interaction of gE. Compared to the parental virus, the mutated virus shows a 66.3% reduction in intercellular transmission capability. In ducks, the deglycosylation of gI significantly reduces DPV replication in vivo, thereby weakening the virulence of DPV. This study represents the first successful creation of a weak DPV virus strain by specific mutation at the N-glycosylation site. The findings provide a foundational understanding of DPV pathogenesis and form the basis for developing live attenuated vaccines against the disease.

Academic Digest of the Center for Legal Support of Bioeconomics and Genetic Technologies of Kutafin Moscow State Law University (MSAL)

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Future prospects and challenges in developing saline-tolerant banana

Banana (Musa spp.) is an essential fruit with high economic value worldwide. One of the main environmental constraints in banana cultivation is abiotic stress on marginal land caused by salinity stress. This salinity stress can significantly reduce banana productivity and even cause plant death. Global climate change due to warming and reduced rainfall has increased the number of agricultural areas affected by salinity. This review article will describe current knowledge of biodiversity and various biological responses when banana plants are exposed to saline stress. This article also mentions the challenges in the banana breeding program with the current development of plant breeding and genetic engineering technology that could be used to create saline-tolerant banana accessions, its prospects, and the societal controversy underlying this technology. Thus, the information presented in this article could be a reference in the saline-tolerant banana breeding program.

CRISPR-Cas systems in enterococci.

Enterococci are members of the microbiota of humans and other animals. They can also be found in the environment, associated with food, healthcare infections, and hospital settings. Due to their wide distribution, they are inserted in the One Health context. The selective pressure caused by the extensive use of antimicrobial agents in humans, animals, and agriculture has increased the frequency of resistance to various drugs among enterococcal species. CRISPR-Cas system, an important prokaryotic defense mechanism against the entry of mobile genetic elements, may prevent the acquisition of genes involved in antimicrobial resistance and virulence. This system has been increasingly used as a gene editing tool, which can be used as a way to recognize and inactivate genes of interest. Here, we conduct a review on CRISPR systems found in enterococci, considering their occurrence, structure and organization, mechanisms of action and use as a genetic engineering technology. Type II-A CRISPR-Cas systems were shown to be the most frequent among enterococcal species, and the orphan CRISPR2 was the most commonly found system (54.1%) among enterococcal species, especially in Enterococcus faecalis. Distribution of CRISPR systems varied among species. CRISPR systems had 1 to 20 spacers, with size between 23 and 37bp and direct repeat sequences from 25 to 37bp. Several applications of the CRISPR-Cas biotechnology have been described in enterococci, mostly in vitro, using this editing tool to target resistance- and virulence-related genes.

Current status for utilization of cold resistance genes and strategies in wheat breeding program.

Low temperature chilling is one of the major abiotic stresses affecting growth and yield of Triticum aestivum L. With global climate change, the risk of cold damage in wheat production has increased. In recent years, with the extensive research on wheat chilling resistance, especially the development of genetic engineering technology, the research on wheat chilling resistance has made great progress. This paper describes the mechanism of wheat cold damage, including cell membrane injury, cytoplasmic concentration increased as well as the imbalance of the ROS system. Mechanisms of cold resistance in wheat are summarised, including hormone signalling, transcription factor regulation, and the role of protective enzymes of the ROS system in cold resistanc. Functions of cloned wheat cold resistance genes are summarised, which will provide a reference for researchers to further understand and make use of cold resistance related genes in wheat. The current cold resistant breeding of wheat relies on the agronomic traits and observable indicators, molecular methods are lacked. A strategy for wheat cold-resistant breeding based on QTLs and gene technologies is proposed, with a view to breeding more cold-resistant varieties of wheat with the deepening of the research.

Etika Pengobatan/Rekayasa Genetik dalam Islam sebagai Implikasi untuk Terapi Gen dan Teknologi DNA serta Tantangan Kontemporer

Gene therapy offers the potential for treating genetic diseases and improving quality of life, but it also raises significant ethical challenges, including issues of genetic manipulation and eugenics. By identifying fundamental principles of Islamic ethics, this study explores how genetic technology can be integrated within an appropriate moral context. Through literature analysis and scholarly perspectives, this article highlights the need for dialogue among scientists, medical practitioners, and religious communities to establish guidelines for the use of this technology. The findings indicate that a balance between technological innovation and the preservation of Islamic ethical values is essential to ensure that scientific advancements provide benefits without violating moral principles. The article also recommends further research to explore the practical applications of gene therapy within the framework of Islamic ethics.

Alteplase vs. Tenecteplase: An In-depth Analysis of Their Relative Effectiveness in Treating Acute Ischaemic Stroke.

Dear Editor, Stroke stands as the second-leading cause of death worldwide [1, 2]. Each year, over 12 million individuals are impacted by stroke, resulting in approximately 6.5 million fatalities [1]. Stroke globally ranks as the third-leading factor causing a combination of death and disability [2]. Every year, around seven hundred thousand individuals in the United States undergo an Acute Ischemic Stroke (AIS), making up 85% of all stroke cases [2]. New treatments like intravenous thrombolysis and mechanical thrombectomy have cut mortality by 10% compared to older methods, enhancing long-term disability prevention rates following Acute Ischemic Stroke [2]. Alteplase is the sole FDA-approved thrombolytic drug in AIS within the first 4.5 hours. Despite its potential for disability-free recovery, its usage is constrained by a brief time window and adverse effects, notably a 6% risk of symptomatic bleeding. In addition, its fibrinolytic efficacy is limited, achieving vascular reopening in less than half of the patients, and can cause cytotoxicity to the already hypoxic brain with resultant cerebral edema [2]. Tenecteplase (TNK), a modified variant of alteplase, has improved features including greater fibrin selectivity and longer half-life and is given as a single bolus instead of an infusion, thanks to genetic recombinant technology [3]. Numerous studies have supported TNK's efficacy over alteplase in treating AIS. In 2016, Bruce C.V. Campbell and colleagues demonstrated that, according to the analysis of modified Rankin scale scores, tenecteplase exhibited a more favorable overall functional outcome compared to alteplase [4]. A dosage of 0.25 mg/kg of tenecteplase emerges as a promising alternative to replace alteplase as the preferred treatment for patients with AIS occurring within 4.5 hours due to TNK's superior early neurological recovery rates and comparable safety outcomes [3]. Despite gathering evidence from experimental trials indicating TNK's advantages over alteplase for AIS, the use of TNK at a dosage of 0.4 mg/kg appears to pose safety concerns when compared to alteplase [3]. Bruce C.V. Campbell and his fellow researchers revealed in their study that in spite of the beneficial effects of TNK relative to alteplase, there was no significant variation in the speed of recovery to independent function. Notably, they found no discernible distinction in the occurrence of intracranial hemorrhage [4]. ---Continue

Genetics, emotion and care: Navigating future reproductive decisions in families of children with rare genetic conditions.

Little is known regarding the future reproductive decision-making of parents of children with rare genetic conditions. Our research draws on data from an online survey and qualitative photo-elicitation interviews with families living with Noonan Syndrome. We demonstrate how genetic knowledge and prenatal genetic testing become embedded in reproductive practices. Yet the idea of using selective genetic technologies to influence reproductive outcomes remains highly emotive. Our analysis reveals that for these parents, the rationalities of reproduction, although technologised and biomedicalised, remain centred on caring for their disabled child. Genetic subjectivities become entangled with responsibilities of care-giving and emotion tied to the realities of living with disability. We argue that for these parents, reproductive decisions are relational and affective, situated within families and communities and shaped by access to emotional, financial, physical and temporal resources. Our findings provide new insights into the ontologies of selective genetic technologies and reproductive governance in families living with disability.

Screening and stability verification of reference genes in Botrytis cinerea ZX2 fermentation

Botrytis cinerea, an airborne plant pathogen, holds the potential to synthesize sesquiterpenes, which have been used for the industrial production of abscisic acid. Previously, through our genetic technology, we obtained strain ZX2, whose main product 1´,4´-trans-ABA-diol is physiologically active in plants. In this study, 50 L of fed fermentation was carried out with ZX2 strain to study the stability of expression of TUA, TUB, ATC, EF-1, GAPDH, UCE and GTP genes. Four kinds of software (GeNorm, NormFinder, BestKeeper and Delta Ct) were used to analyze the expression stability of candidate genes, and finally the best reference gene was screened by RefFinder. Based on the results, the ACT was the most stable gene. It was used to normalize the expression levels of two genes related to 1´,4´-trans-ABA-diol production (hmgr and bcaba3) when fed-batch fermentation. Guide the selection of appropriate internal reference genes during the fermentation process to accurately quantify the relative transcription levels of target genes in B.cinerea ZX2.

Application of Genetic Research Techniques in Myopia Research

The rapid development of genetic research techniques has provided new perspectives and tools for the study of myopia. This paper reviews several key genetic technologies, including genome sequencing, gene editing technologies, genetic association studies, and epigenetic technologies, and explores their applications in myopia research. Through genome sequencing, researchers can identify genetic variations associated with myopia; gene editing technologies offer powerful tools to explore gene functions and their impact on myopia; genetic association studies help reveal genes and genetic markers related to myopia; and epigenetic technologies provide insights into how environmental factors influence the genetic mechanisms underlying myopia. Despite significant achievements, current research faces challenges such as data complexity, ethical issues, and technical limitations. Future advancements in technology and research are expected to continue expanding the application of genetic techniques in myopia research, offering new strategies and methods for the prevention and treatment of myopia.

Validating a novel genetic technology for hybrid maize seed production under management practices associated with resource‐poor farmers in Zimbabwe

Validating a novel genetic technology for hybrid maize seed production under management practices associated with resource‐poor farmers in Zimbabwe