Genetic Knowledge Research Articles

Genetics and genomics in healthcare: The future is now.

Genetics and genomics in healthcare: The future is now.

Genetics in the NICU: Nurses' Perceived Knowledge and Desired Education

Background Many infants admitted to the neonatal intensive care unit (NICU) have genetic conditions. Previous research has shown that gaps exist in the genetics knowledge of nurses and that they lack comfort applying genetics information to clinical practice. Studies assessing the knowledge or comfort of NICU nurses with genetics have not previously been completed. Method A total of 122 NICU nurses completed a survey assessing perceived knowledge of genetics, comfort with clinical scenarios involving genetics, and desired genetics education. Results Perceived knowledge and overall comfort were correlated with highest degree received, how prepared a nurse felt by the genetics education received in their training, and having a close relationship with someone with a genetic condition. Almost all respondents (96%, n = 117) desired additional genetics education. Conclusion Gaps exist in the genetics knowledge of neonatal nurses in our cohort, and their overall comfort working with clinical scenarios involving genetics was low. There is significant interest in additional genetics education. [J Contin Educ Nurs. 2023;54(1):16-24.].

Understanding cancer predisposition in Singapore: What's next.

Knowledge of an underlying genetic predisposition to cancer allows the use of personalised prognostic, preventive and therapeutic strategies for the patient and carries clinical implications for family members. Despite great progress, we identified six challenging areas in the management of patients with hereditary cancer predisposition syndromes and suggest recommendations to aid in their resolution. These include the potential for finding unexpected germline variants through somatic tumour testing, optimal risk management of patients with hereditary conditions involving moderate-penetrance genes, role of polygenic risk score in an under-represented Asian population, management of variants of uncertain significance, clinical trials in patients with germline pathogenic variants and technology in genetic counselling. Addressing these barriers will aid the next step forward in precision medicine in Singapore. All stakeholders in healthcare should be empowered with genetic knowledge to fully leverage the potential of novel genomic insights and implement them to provide better care for our patients.

Bacillus velezensis S141, a soybean growth-promoting bacterium, hydrolyzes isoflavone glycosides into aglycones.

Bacillus velezensis S141, a plant growth-promoting rhizobacteria (PGPR), was isolated from a soybean field in Thailand. Previous studies demonstrated that S141 enhanced soybean growth, stimulating nodulation for symbiotic nitrogen fixation with soybean root nodule bacteria, including Bradyrhizobium diazoefficience USDA110. Isoflavone glycosides are produced in soybean roots and hydrolyzed into their aglycones, triggering nodulation. This study revealed that S141 efficiently hydrolyzed two isoflavone glycosides in soybean roots (daidzin and genistin) to their aglycones (daidzein and genistein, respectively). However, S141, Bacillus subtilis 168, NCIB3610, and B. velezensis FZB42 hydrolyzed isoflavone glucosides into aglycones. A BLASTp search suggested that S141 and the other three strains shared four genes encoding β-glucosidases corresponding to bglA, bglC, bglH, and gmuD in B. subtilis 168. The gene inactivation analysis of B. subtilis 168 revealed that bglC encoded the major β-glucosidase, contributing about half of the total activity to hydrolyze isoflavone glycosides and that bglA, bglH, and gmuD, all barely committed to the hydrolysis of isoflavone glycosides. Thus, an unknown β-glucosidase exists, and our genetic knowledge of β-glucosidases was insufficient to evaluate the ability to hydrolyze isoflavone glycosides. Nevertheless, S141 could predominate in the soybean rhizosphere, releasing isoflavone aglycones to enhance soybean nodulation.

Deep learning - cancer genetics and application of deep learning to cancer oncology

Arguably the human body has been one of the most sophisticated systems we encounter but until now we are still far from understanding its complexity. We have been trying to replicate human intelligence by way of artificial intelligence but with limited success. We have discovered the molecular structure in terms of genetics, performed gene editing to change an organism’s DNA and much more, but their translatability into the field of oncology has remained limited. Conventional machine learning methods achieved some degree of success in solving problems that we do not have an explicit algorithm. However, they are basically shallow learning methods, not rich enough to discover and extract intricate features that represent patterns in the real environment. Deep learning has exceeded human performance in pattern recognition as well as strategic games and are powerful for dealing with many complex problems. High-throughput sequencing and microarray techniques have generated vast amounts of data and allowed the comprehensive study of gene expression in tumor cells. The application of deep learning with molecular data enables applications in oncology with information not available from clinical diagnosis. This paper provides fundamental concepts of deep learning, an essential knowledge of cancer genetics, and a review of applications of deep learning to cancer oncology. Importantly, it provides an insightful knowledge of deep learning and an extensive discussion on its challenges. The ultimate purpose is to germinate ideas and facilitate collaborations between cancer biologists and deep learning researchers to address challenging oncological problems using advanced deep learning technologies.

Genetic Knowledge: a Gift or a Curse?

The origins of genetic research in the molecular era are discussed along with the prospects for development of the system of the values underlying their legal regulation. Heredity and variability are included into a historically defined worldview as socially significant values respectively occupying alternate leading positions in archaic and modern societies. The article substantiates a connection between ideas about heredity and variability and the social structure, institutions and social practices of the two main types of the pre-molecular era societies. The article also discusses the significance of pre-scientific ideas concerning blood as a special substance ensuring biological, social and legal inheritance in the system of social action of the archaic society. Analysis is given to the conceptual foundations of the strategy of overcoming the ‘right of blood’ in modern societies, where the value of heredity is replaced by the value of variability to serve as a value-system basis for development and progress. Examples of coexisting worldviews and values inherent in both archaic and modern forms that still interact in present-day societies are presented and generalized. The example of the parascientific blood-type theory prevalent in today’s Japan is used to illustrate the ability of collective consciousness to integrate scientific ideas into deep underlying layers of pre-scientific thinking. The postmodern mixture of worldviews and values gives rise to ambiguity and uncertainty with regard to values in the era of discovery of the genetic mechanism of inheritance, creating additional difficulties for rule-makers (legislators) in course of forming a system for the legal regulation of genetic research. Finding a balance between prohibitions and permissions in the corpus of laws and by-laws regulating genetic knowledge development is all the more important given that the demarcation between representing and intervening in the research carried out by molecular biologists is losing its certainty (definiteness) even faster than in the physics of the microworld, let alone other subject areas of the modern science. Bioethics, which is currently providing a philosophical basis for the legal regulation of genetic research, requires theoretical elaboration and conceptualization. As one of the substantiation options, the article proposes the concept of supplementing instrumental rationality with social communication put forward by Jürgen Habermas within the framework of his theory of communicative action

Rs7537605 polymorphism in VAV3 gene and rs28665122 polymorphism in SEPS gene are not associated with Hashimoto's thyroiditis in North-East Algerian population.

Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disease which leads, in most cases, to hypothyroidism. HT is also classified as a multifactorial disease, which is caused by an interaction between genetic and environmental factors. Current knowledge of HT genetics is still very limited, especially in Algerian population. We wanted to investigate the association of two single-nucleotide polymorphisms (SNPs) inside VAV3 and SEPS genes with HT in Algerian population. We conducted a case-control study that included 100 HT cases and 126 healthy controls that were recruited from three private endocrinology clinics. Two SNPs, rs7537605 and rs28665122 inside VAV3 and SEPS genes were genotyped using real-time polymerase chain reaction (real-time PCR). Binary logistic regression model was used to test the association of selected SNs with HT and linear regression model was used to test association of these SNPs with thyroid peroxidase antibodies (TPOAb) levels. Binary logistic regression results revealed no allelic association of the minor allele A between Hashimoto's thyroiditis cases and healthy controls (P=0.896) for the rs7537606 in VAV3 gene. The same observation was reported for the AA (P=0.477), AG (P=0.752) genotypes and for the genotypic models: dominant (P=1.0) and recessive (P=0.555). Also, there was no significant difference in the TT (P=0.230), TC (P=0.717) and allelic distribution of the minor allele T (P=0.859), and the combined models: TT + TC (P=1.0), TC + CC (P=0.138) between patients and controls for the rs28665122 polymorphism of the SEPS1 gene. This is the first genetic study that investigated the genetic association of rs7537605 and rs28665122 inside VAV3 and SEPS genes in Algerian population. Our results suggest that these two SNPs may not be involved in the pathogeneses of HT since we found no association between them and HT/TPOAb levels. Further research that will include larger sample size is required.

A Method of Teaching Genetics Based on the Use of Genotoxic Studies

The purpose of this study is to give students the opportunity to develop their genetic knowledge, linking them with important problems of society. Interactive research-based teaching methods are widely used in genetic education. This allows you to determine the degree of interest of the student in the subject. A special place in teaching genetics is occupied by laboratory work. Laboratory work arouses interest, allowing students to engage in science using research methods. Modern students should learn how to use scientific models, calculate appropriate mathematical approaches and statistics to solve problems, as well as manage and integrate data. Given the importance of genetics for society, in this article we decided to focus on hemotoxins, an urgent problem at the present time. Having developed the Ames test, one of the test systems for determining genotoxicity, we focused on the features of teaching genetics. Laboratory experience helps students to control the influence of the surrounding world from hemotoxins, various factors on the processes of pollution, mutation, inheritance and, conducting the experiment, to understand mistakes, interpret the data obtained, draw the right conclusions. In this regard, interactive methods were used to consolidate the theoretical knowledge of students in the form of practice: cumulative brainstorming, minute reflection.

Past, present, and future of genetic strategies to control tolerance to the main fungal and oomycete pathogens of grapevine.

The production of high-quality wines is strictly related to the correct management of the vineyard, which guarantees good yields and grapes with the right characteristics required for subsequent vinification. Winegrowers face a variety of challenges during the grapevine cultivation cycle: the most notorious are fungal and oomycete diseases such as downy mildew, powdery mildew, and gray mold. If not properly addressed, these diseases can irremediably compromise the harvest, with disastrous consequences for the production and wine economy. Conventional defense methods used in the past involved chemical pesticides. However, such approaches are in conflict with the growing attention to environmental sustainability and shifts from the uncontrolled use of chemicals to the use of integrated approaches for crop protection. Improvements in genetic knowledge and the availability of novel biotechnologies have created new scenarios for possibly producing grapes with a reduced, if not almost zero, impact. Here, the main approaches used to protect grapevines from fungal and oomycete diseases are reviewed, starting from conventional breeding, which allowed the establishment of new resistant varieties, followed by biotechnological methods, such as transgenesis, cisgenesis, intragenesis, and genome editing, and ending with more recent perspectives concerning the application of new products based on RNAi technology. Evidence of their effectiveness, as well as potential risks and limitations based on the current legislative situation, are critically discussed.

TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels.

Anesthesia with propofol is frequently associated with hypotension. The TRPA1 gene contributes to the vasodilator effect of propofol. Hypotension is crucial for anesthesiologists because it is deleterious in the perioperative period. We tested whether the TRPA1 gene polymorphisms or haplotypes interfere with the hypotensive responses to propofol. PCR-determined genotypes and haplotype frequencies were estimated. Nitrite, nitrates, and NOx levels were measured. Propofol induced a more expressive lowering of the blood pressure (BP) without changing nitrite or nitrate levels in patients carrying CG+GG genotypes for the rs16937976 TRPA1 polymorphism and AG+AA genotypes for the rs13218757 TRPA1 polymorphism. The CGA haplotype presented the most remarkable drop in BP. Heart rate values were not impacted. The present exploratory analysis suggests that TRPA1 genotypes and haplotypes influence the hypotensive responses to propofol. The mechanisms involved are probably other than those related to NO bioavailability. With better genetic knowledge, planning anesthesia with fewer side effects may be possible.

Detection of Homologous Loci in Sheep and Cattle

Background: The study of the homology of loci between different species has allowed the improvement of specific genetic knowledge and the development of several fundamental concepts. Thanks to this method, Wright discovered the correspondence between a gene and an enzyme (Wright, 1917). In ruminants, this correspondence between loci of different species has been demonstrated for a very long time (Lauvergne, 1979). In fact, the objective of this work was, initially, to use microsatellites recommended for sheep (FAO, 2011) for the amplification of bovine DNA to show that these loci are homologous and, then, to study the genetic diversity and population structure of three groups of each of the two species in Tunisia. Methods: In this study, we used three microsatellite markers (OarFCB304, OarFCB193 and MAF209) to verify whether they can be amplified in both sheep and cattle. For that, we considered 28 samples of sheep species from 3 different populations and 17 samples of cattle belonging to three breeds. The data obtained were also used to study their genetic diversity and population structure. Result: We have demonstrated the existence of microsatellite regions common to sheep and cattle. Regarding genetic diversity, we observed a heterozygous deficiency in all the studied breeds. Nei’s genetic distances were greater between breeds of cattle than between breeds of sheep.

NIAGADS Alzheimer’s Genomics Database: version GRCh38

AbstractBackgroundThe Alzheimer’s Genomics Database (GenomicsDB) is an interactive knowledgebase for Alzheimer's disease (AD) genetics that offers a platform for data sharing, discovery, and analysis to accelerate research on AD and AD related dementias (ADRD). The resource provides unrestricted access to GWAS summary statistics datasets, variant annotations, and meta‐analysis results deposited at the NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). Here we introduce an updated version of the GenomicsDB, now mapped against the latest human genome assembly, GRCh38.MethodThe GenomicsDB allows users to interactively mine AD/ADRD summary statistics datasets or visually inspect them and compare with annotated variant tracks and GRCh38 aligned functional genomics tracks from the FILER functional genomics repository (Kuksa et al. 2022). Available tracks include key AD datasets from large‐scale sequencing projects such as IGAP (Lambert et al. 2013; Kunkle et al. 2019) and the ADGC (e.g., Naj et al. 2011) that have been lifted over from earlier genome builds. Available annotated variants include those from the AD Sequencing Project’s (ADSP) Release3 WGS, called from nearly 17k samples. All variants reported in the GenomicsDB are annotated using an assembly specific version of ADSP annotation pipeline (Butkiewicz et al. 2018). The GenomicsDB provides a REST API for programmatic access. Supported queries return complete annotations for single or bulk lookups of GenomicsDB entries (genes, variants, genomic loci) and ranged queries of datasets as JSON documents.ResultThe GenomicsDB currently hosts >70 datasets and reports >150 million annotated variants from the ADSP and 23 AD/ADRD GWAS studies, mapped to GRCh38. Keeping up with community standards allows this resource to provide ongoing support for AD/ADRD research by making it possible to integrate AD/ADRD relevant `omics datasets generated by the ADSP and others who have adopted GRCh38 as their reference genome.ConclusionThe NIAGADS Alzheimer’s Genomics Database v. GRCh38 (www.niagads.org/genomics) provides an up‐to‐date and accessible platform that facilitates unrestricted sharing of genetic knowledge underpinning AD/ADRD. To best serve our user community, NIAGADS will continue to provide the GRCh37.p19 version of the Alzheimer’s Genomics Database (including programmatic access) in archival format.

CONOCIMIENTO SOBRE GENÉTICA Y CONFIANZA EN PRUEBAS GENÉTICAS EN UNA CIUDAD DE TAMAÑO MEDIO EN ARGENTINA

Public attitudes about genetics appear to depend on the local context. We analyzed survey responses obtained in 2015 from 293 residents of Luján, a city in the province of Buenos Aires, Argentina, who self-assessed their knowledge about genetics and their trust in genetic tests. The survey integrated a larger research project for which consenting adult participants shared demographic and genealogical information and provided saliva samples for genetic ancestry analyses. Participants reported little knowledge but high trust in genetic testing when questioned about knowledge and trust. Well-known media stories of DNA-based forensic genetic investigations to identify the victims of state repression during the military dictatorship may have contributed to the high self-assessment of their genetic knowledge expressed by some participants, regardless of educational attainment. Our analysis provides information that could be used as a baseline to begin unraveling the current level of public trust in genetics in a region of the Global South where genetic testing has become widespread, but people’s knowledge of and trust in genetics remain poorly studied. Key words: genetic tests, knowledge, public attitudes, trust

What is New in Pediatric Orthopaedic: Basic Science.

An understanding of musculoskeletal basic science underpins most advancements in the field of orthopaedic surgery. Knowledge of biomechanics, genetics, and molecular pathways is integral to the understanding of the pathophysiology of disease and guides novel treatment options to improve patient outcomes. The purpose of this review is to provide a comprehensive and current overview of musculoskeletal basic science relevant to pediatric orthopaedic surgery. Comprehensive Pubmed database searches were performed for all English language articles published between January 2016 and November 2021 using the following search terms: basic science, pediatric orthopaedics, fracture, trauma, spine, scoliosis, DDH, hip dysplasia, Perthes, Legg-Calve-Perthes, clubfoot, and sports medicine. Inclusion criteria focused on basic science studies of pediatric orthopaedic conditions. Clinical studies or case reports were excluded. A total of 3855 articles were retrieved. After removing duplicates and those failing to meet our inclusion criteria, 49 articles were included in the final review. A total of 49 papers were selected for review based on the date of publication and updated findings. Findings are discussed in the subheadings below. Articles were then sorted into the following sub-disciplines of pediatric orthopaedics: spine, trauma, sports medicine, hip, and foot. With this review, we have identified many exciting developments in pediatric orthopaedic trauma, spine, hip, foot, and sports medicine that could potentially lead to changes in disease management and how we think of these processes. Level V.

Inclusion body myositis: from genetics to clinical trials

Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies and is characterized by a slowly progressive disease course with asymmetric muscle weakness of predominantly the finger flexors and knee extensors. The disease leads to severe disability and most patients lose ambulation due to lack of curative or disease-modifying treatment options. Despite some genes reported to be associated with hereditary IBM (a distinct group of conditions), data on the genetic susceptibility of sporadic IBM are very limited. This review gives an overview of the disease and focuses on the current genetic knowledge and potential therapeutic implications.

Early Signs of the Effects of Forest Fragmentation on the Genetic Diversity and Structure of the Threatened Ecuadorian Tree Ocotea rotundata (Lauraceae)

The diversity of genetic resources is essential to cope with environmental changes. However, despite forests play a crucial role in mitigating changes, genetic knowledge has scarcely been used for forest conservation. In this study, we used nuclear microsatellites to understand the patterns of genetic diversity and population genetic structure in Ocotea rotundata van der Werff (Lauraceae), an endemic Ecuadorian tree, highly affected by habitat changes and fragmentation. Our results show high levels of genetic diversity, except in one population. The level of genetic differentiation between populations was low and genetic clusters showed no apparent spatial pattern. In fact, a high degree of genetic admixture was found between most populations. Migration rates were asymmetric but overall high, except in one population, where outgoing gene dispersal was limited. Nevertheless, allelic fixation values suggested a general deficit in heterozygotes, probably due to an increase in the levels of mating between close relatives. Although long-lived organisms, such as trees, can often accumulate a surprising amount of genetic diversity, the results found here could be an early sign of a decline in the diversity of O. rotundata. These findings provide baseline information on genetic resources to support future restoration programs to mitigate the impacts of changes in O. rotundata populations.

CRISPR-Cas9 Technology for the Creation of Biological Avatars Capable of Modeling and Treating Pathologies: From Discovery to the Latest Improvements.

This is a spectacular moment for genetics to evolve in genome editing, which encompasses the precise alteration of the cellular DNA sequences within various species. One of the most fascinating genome-editing technologies currently available is Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and its associated protein 9 (CRISPR-Cas9), which have integrated deeply into the research field within a short period due to its effectiveness. It became a standard tool utilized in a broad spectrum of biological and therapeutic applications. Furthermore, reliable disease models are required to improve the quality of healthcare. CRISPR-Cas9 has the potential to diversify our knowledge in genetics by generating cellular models, which can mimic various human diseases to better understand the disease consequences and develop new treatments. Precision in genome editing offered by CRISPR-Cas9 is now paving the way for gene therapy to expand in clinical trials to treat several genetic diseases in a wide range of species. This review article will discuss genome-editing tools: CRISPR-Cas9, Zinc Finger Nucleases (ZFNs), and Transcription Activator-Like Effector Nucleases (TALENs). It will also encompass the importance of CRISPR-Cas9 technology in generating cellular disease models for novel therapeutics, its applications in gene therapy, and challenges with novel strategies to enhance its specificity.

Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis

Limited studies have been conducted to identify and validate multiple sclerosis (MS) genetic loci associated with disability progression. We aimed to identify MS genetic loci associated with worsening of disability over time, and to develop and validate ensemble genetic learning model(s) to identify people with MS (PwMS) at risk of future worsening. We examined associations of 208 previously established MS genetic loci with the risk of worsening of disability; we learned ensemble genetic decision rules and validated the predictions in an external dataset. We found 7 genetic loci (rs7731626: HR 0.92, P = 2.4 × 10–5; rs12211604: HR 1.16, P = 3.2 × 10–7; rs55858457: HR 0.93, P = 3.7 × 10–7; rs10271373: HR 0.90, P = 1.1 × 10–7; rs11256593: HR 1.13, P = 5.1 × 10–57; rs12588969: HR = 1.10, P = 2.1 × 10–10; rs1465697: HR 1.09, P = 1.7 × 10–128) associated with risk worsening of disability; most of which were located near or tagged to 13 genomic regions enriched in peptide hormones and steroids biosynthesis pathways by positional and eQTL mapping. The derived ensembles produced a set of genetic decision rules that can be translated to provide additional prognostic values to existing clinical predictions, with the additional benefit of incorporating relevant genetic information into clinical decision making for PwMS. The present study extends our knowledge of MS progression genetics and provides the basis of future studies regarding the functional significance of the identified loci.

Clinical practice guidelines for Fragile X syndrome

Fragile X syndrome (FXS) is the most common monogenic form of inherited intellectual disability and autism spectrum disorder (ASD). More than 99% of individuals with FXS are caused by the unstable expansion of CGG repeats located within the 5'-untranslated region of the FMR1 gene. The clinical features of FXS include various degrees of cognitive deficit, physical, behavioral and psychiatric problems. Early treatment and prevention from having further affected children can be guided by molecular genetic testing of the FMR1 gene. The following guideline has combined the relevant research, guidelines and consensus worldwide, and summarized the genetic knowledge and clinical treatment for FXS in order to achieve a standardized diagnosis, treatment and prevention for patients and families affected by this disease.

Exploring People's Knowledge of Genetics and Attitude towards Genetic Testing: A Cross-Sectional Study in a Population with a High Prevalence of Consanguinity.

This study investigated people's knowledge of genetics, attitudes toward genetic testing, and views on consanguinity. This cross-sectional study utilized a validated questionnaire modified from published studies to collect data on people's knowledge of genetics and attitudes about genetic testing among 1008 respondents from various Saudi Arabian regions. Using SPSS software version 26, data were analyzed using a t-test, ANOVA, and multivariate analysis. p-values of <0.05 were considered statistically significant. About 59.9% of the participants had sufficient knowledge of genetics, and around 50% had a favorable attitude toward genetic testing. Knowledge of genetics is significantly correlated (p ≤ 0.001) with a positive attitude toward genetic testing. Gender, age, level of education, marital status, family income, and family history were significantly correlated with respondents' understanding of genetics. Gender, family income, residence, and family history were associated with attitudes toward genetic testing at a 0.05 level of significance. There is a need to strengthen peoples' knowledge of genetics and attitudes toward genetic testing through diverse educational programs and healthcare strategies. Impetus on how to disseminate genetic information on consanguinity and transmission of diseases should be prioritized in regions where consanguineous marriages are high.