Genetic Research Research Articles

Cystic fibrosis management in pediatric population—from clinical features to personalized therapy

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

Genome-wide sequencing in children with epilepsy and developmental disorders

The progress of genetic diagnostic methods and a significant improvement in the quality of next-generation sequencing (NGS) have led to a revolution in the study of the genetics of epilepsy. Genome-wide sequencing (PSG) is the «gold standard» in genetic research in epilepsy.Material and methods. Genome-wide sequencing was performed in 168 probands aged from 1 month to 18 years with a suspected diagnosis of genetic epilepsy. PSG was prescribed to patients who, alongside with epilepsy, had delayed intellectual/speech development and/or motor disorders and behavioral disorders.Results. According to the results of PSG, genetic variants related to the phenotype of the disease were detected in 137 out of 168 (81.5%) children, variations in the number of DNA copies were noted in 14 out of 168 (8.3%) patients. Variants with unclear clinical significance were described in 35 of 137 (25.54%). In the remaining 102 out of 137 (74.45%) patients, the identified causative genetic variants were described as probably pathogenic and pathogenic. Monogenic developmental and epileptic encephalopathies (DEE) were detected in 37/137 or 27% of all patients, while the spectrum of these genetic encephalopathies was extremely wide (from DEE type 1 to DEE type 97). In 52/137 (37.9%) children, the presence of a specific genetic syndrome outside the framework of the DEE, classified in OMIM, was confirmed.Conclusion. The results confirm the high informative value of genome-wide sequencing in a group of children with a combination of epilepsy, intellectual, speech, motor and behavioral disorders. In most cases, the results allow either to prescribe a genotype-oriented symptomatic (less often pathogenetic) treatment, or rationally justify the tactics of further observation and examination, as well as to increase the effectiveness of medical and genetic counseling. The authors express their sincere gratitude to the Charity foundation for medical and social genetic aid projects «Life Genome” for assistance in conducting genome-wide sequencing of most of the described patients.

A framework for the integration of development and evolution: The forgotten legacy of James Meadows Rendel

The historical challenges to bridge the gaps between developmental biology and population or statistical genetics under the explanatory dominance of the Modern Evolutionary Synthesis during the 20th century have been thoroughly documented. However, although several attempts to integrate these fields have been made, most have been deemed unsuccessful. As an example of those efforts, in this paper I discuss the work of James Meadows Rendel, a student of J. B. S. Haldane and disciple of Conrad Hal Waddington. I present his largely forgotten or unrecognized, but innovative, ideas about canalization and the role of development in phylogeny as a valuable piece to connect these fields that could still have important ramifications for today's evolutionary biology. In fact, it is expected that the legacy of J. M. Rendel will be rediscovered, and more importantly, incorporated and extended by future researchers, in light of the growth of evolutionary developmental biology in the last decades. What is more, this case offers a chance to critically revisit standard historiographies about the dichotomy between developmental and population genetics research frameworks in 20th century biology.

Features of determining the subspecies status of honey bees (Apis mellifera) based on morphometric wing indicators of drones

As of today, in Ukraine, there are no opportunities to conduct genetic research on a sufficient scale to identify the composition of the genomes of honey bees. Wing morphometrics of drones is a readily available alternative for obtaining information about the approximate composition of DNA. The goal of the work was to formulate the principles of the main stages of research and illustrate the procedure for obtaining morphometric data, methods of their processing, and possibilities for interpreting the obtained results. In the package of statistical data processing application programs Statistica, the classification of 2,147 drone wings obtained from 6 apiaries of Zhytomyr, Mykolaiv, and Kyiv regions was carried out according to eight indices: Ci, Dbi, Disc.sh, Pci, Ri, Ci.3, Ci.2.1, and Ci.2.2. We propose a method for obtaining morphometric wing standards of bees based on studying a significant number of bee colonies from various apiaries in specific regions of Ukraine. Using a two-stage methodology, three datasets were formed and recommended for use as standards: one for the local population of Ukrainian bees and two for populations of the A.m.mellifera subspecies distributed in the Polissia region. We analyzed the reliability of results in determining the taxonomic affiliation of bees was analyzed. Using the example of a single bee colony, a detailed procedure is demonstrated to identify taxonomic affiliation through utilization of the obtained standards. It has been demonstrated that in case of reliable identification of standards belonging to specific subspecies, it is possible to predict the likely composition of chromosomal sets in the genomes of drones, queens, and worker bees partially corresponding to the wing phenotype.

A fine-scale genetic map of the Japanese population.

Genetic maps are fundamental resources for linkage and association studies. A fine-scale genetic map can be constructed by inferring historical recombination events from the genome-wide structure of linkage disequilibrium-a non-random association of alleles among loci-by using population-scale sequencing data. We constructed a fine-scale genetic map and identified recombination hotspots from 10 092 551 bi-allelic high-quality autosomal markers segregating among 150 unrelated Japanese individuals whose genotypes were determined by high-coverage (30×) whole-genome sequencing, and the genotype quality was carefully controlled by using their parents' and offspring's genotypes. The pedigree information was also utilized for haplotype phasing. The resulting genome-wide recombination rate profiles were concordant with those of the worldwide population on a broad scale, and the resolution was much improved. We identified 9487 recombination hotspots and confirmed the enrichment of previously known motifs in the hotspots. Moreover, we demonstrated that the Japanese genetic map improved the haplotype phasing and genotype imputation accuracy for the Japanese population. The construction of a population-specific genetic map will help make genetics research more accurate.

Development and Characterization of Fifteen Polymorphic Microsatellite Loci for Rare and Endangered Species within Luciobarbus Heckel, 1843 Genus in the Aral Basin and Their Conservation Application

Biodiversity conservation entails not only the preservation of specific taxa but also genetic diversity. Despite the crucial role of molecular data in freshwater fish conservation management, there is a scarcity of information regarding the genetic diversity of Luciobarbus Heckel, 1843 (Actinopterygii, Cyprinidae) populations in the Aral system. Therefore, the primary aim of this study was to provide genetic information on two native species of the Luciobarbus genus found in the Aral system: L. conocephalus (Kessler, 1872) and L. brachycephalus (Kessler, 1872). These species, like many others in the Aral system, confront the imminent threat of extinction due to system alterations. However, genetic studies on these species at the nuclear level are challenging because Luciobarbus is an allotetraploid genus. Consequently, genetic investigations thus far have focused mainly on sequencing mitochondrial genes due to their haploid nature. This study has successfully developed fifteen new polymorphic microsatellite loci, which can prove to be valuable for population genetics, conservation, and other pertinent research on these species.

Gilles de la Tourette syndrome as a rare co-morbidity of Klinefelter syndrome.

Klinefelter syndrome (47, XXY) is the most common sex chromosome aneuploidy. In addition to male hypergonadotropic hypogonadism, a wide range of neurodevelopmental disorders, anxiety and affective symptoms have been reported in a substantial proportion of cases. We document the rare case of a 43-year-old man diagnosed with Klinefelter syndrome and co-morbid Gilles de la Tourette syndrome. He presented with multiple motor and vocal tics since adolescence, as well as anxiety and affective symptoms as his main tic-exacerbating factors. Tic severity was rated as marked (Yale Global Tic Severity Scale score of 78/100), and recommendations for the treatment of both tics and psychiatric co-morbidities were formulated. Neurodevelopmental tics in the context of Klinefelter syndrome have been previously documented in three cases only. Gilles de la Tourette syndrome is 3-4 times more common in males than females and its etiological factors include multiple genetic components (genetic heterogeneity). Our case report widens the spectrum of neurodevelopmental disorders observed in the context of Klinefelter syndrome and contributes to genetic research on the role of the X chromosome in the pathophysiology of tic disorders.

Joint extraction of wheat germplasm information entity relationship based on deep character and word fusion

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model’s capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production.

Advances in DNA Extraction Techniques: A Comprehensive Review of Methods and Applications

The extraction of DNA is a fundamental process in molecular biology, underpinning a wide range of applications from genetic research to forensic science and medical diagnostics. This review aims to explore the latest advancements in DNA extraction techniques, highlighting their principles, applications, and suitability for various types of biological samples. Traditional DNA extraction methods, such as phenol-chloroform and ethanol precipitation, have served as the backbone of DNA isolation for decades. However, these techniques often involve hazardous chemicals and can be time-consuming. Recent advancements have focused on developing safer, faster, and more efficient methods, with a focus on automation and scalability. Innovations such as magnetic bead-based extraction, silica column purification, and specialized kits have greatly simplified the process, allowing for high-throughput applications in clinical and research settings. In addition to these technical improvements, new approaches have emerged to address specific challenges, such as extracting DNA from degraded or trace samples, as seen in forensic investigations, or isolating cell-free DNA for non-invasive prenatal testing and cancer diagnostics. Moreover, microfluidic devices and lab-on-a-chip technologies are transforming the landscape by enabling DNA extraction from minute samples with minimal reagent consumption. This review discusses the principles underlying these advanced techniques, their benefits and limitations, and the specific contexts in which they excel. It also considers future trends, including further automation, integration with sequencing platforms, and the potential for point-of-care applications. By examining the current state of DNA extraction technology, this review aims to provide researchers and practitioners with a comprehensive guide to the best methods for their specific needs.

Application of Developmental Regulators for Enhancing Plant Regeneration and Genetic Transformation.

Establishing plant regeneration systems and efficient genetic transformation techniques plays a crucial role in plant functional genomics research and the development of new crop varieties. The inefficient methods of transformation and regeneration of recalcitrant species and the genetic dependence of the transformation process remain major obstacles. With the advancement of plant meristematic tissues and somatic embryogenesis research, several key regulatory genes, collectively known as developmental regulators, have been identified. In the field of plant genetic transformation, the application of developmental regulators has recently garnered significant interest. These regulators play important roles in plant growth and development, and when applied in plant genetic transformation, they can effectively enhance the induction and regeneration capabilities of plant meristematic tissues, thus providing important opportunities for improving genetic transformation efficiency. This review focuses on the introduction of several commonly used developmental regulators. By gaining an in-depth understanding of and applying these developmental regulators, it is possible to further enhance the efficiency and success rate of plant genetic transformation, providing strong support for plant breeding and genetic engineering research.

Influence of Climate Change Adaptation Policies on Sheep Farming Viability in Australia

Purpose: The aim of the study was to analyze the influence of climate change adaptation policies on sheep farming viability in Australia. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: Climate change adaptation policies in Australia have significantly influenced the viability of sheep farming in recent years. Research indicates that the implementation of targeted adaptation measures, such as improved pasture management and water conservation strategies, has helped mitigate the adverse impacts of climate change on sheep farming viability. Studies have shown that farms adopting these policies have experienced higher survival rates of livestock and increased profitability compared to those without such measures. Additionally, government support programs aimed at assisting sheep farmers in implementing climate adaptation strategies have been instrumental in enhancing the resilience of the sector. Unique Contribution to Theory, Practice and Policy: Adaptation theory in environmental economics, resilience theory & theory of planned behavior (TPB) may be used to anchor future studies on analyze the impact of climate change on wheat yields in Australia. The enhancement of breeding programs focuses on practical genetic advancements to create drought and heat-resistant sheep varieties, addressing direct climate impacts on livestock. By advocating for government and industry funding for genetic research, the recommendations influence policy towards investing in long-term solutions for climate resilience.

The mitochondrial genome of an important edible insect species, the African palm weevil (Rhynchophorus phoenicis)

The African palm weevil (Rhynchophorus phoenicis) is a species of high economic importance in sub-Saharan Africa, both as a culturally traditional edible insect and as an agricultural pest. Here we provide a de novo assembly and annotation for the mitochondrial genome of this species from whole-genome sequence data. The mitogenome was AT-rich and 17,161bp in length, containing 13 protein-coding, 22 transfer RNA, and two ribosomal RNA genes. Phylogenetic reconstruction showed the African palm weevil to cluster within the genus Rhynchophorus and the weevil tribe Rhynchophorini. This mitogenome will be important for future genetic research into this emerging edible insect species.

Application of Genomic Medicine in Africa: 14th Conference of the African Society of Human Genetics and the 2nd International Congress of the Moroccan Society of Genomics and Human Genetics, Rabat, Morocco 2022.

The 14th African Society of Human Genetics (AfSHG) Morocco Meeting and 2nd International Congress of the Moroccan Society of Genomics and Human Genetics (SM2GH), held in Rabat, Morocco, from December 12 through 17, 2022, brought together 298 attendees from 23 countries, organized by the AfSHG in collaboration with the SM2GH. The conference's overarching theme was "Applications of Genomics Medicine in Africa," covering a wide range of topics, including population genetics, genetics of infectious diseases, hereditary disorders, cancer genetics, and translational genetics. The conference aimed to address the lag in the field of genetics in Africa and highlight the potential for genetic research and personalized medicine on the continent. The goal was to improve the health of African populations and global communities while nurturing the careers of young African scientists in the field. Distinguished scientists from around the world shared their recent findings in genetics, immunogenetics, genomics, genome editing, immunotherapy, and ethics genomics. Precongress activities included a 2-day bioinformatics workshop, "NGS Analysis for Monogenic Disease in African Populations," and a Young Investigators Forum, providing opportunities for young African researchers to showcase their work. The vast genetic diversity of the African continent poses a significant challenge in investigating and characterizing public health issues at the genetic and functional levels. Training, research, and the development of expertise in genetics, immunology, genomics, and bioinformatics are vital for addressing these challenges and advancing genetics in Africa. The AfSHG is committed to leading efforts to enhance genetic research, coordinate training, and foster research collaborations on the continent.

Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3′ UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.

РОЛЬ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ МЕТОДОВ ИССЛЕДОВАНИЙ В ЭТИОПАТОГЕНЕЗЕ ОСТЕОМИЕЛИТА ЧЕЛЮСТЕЙ

The subject of the study is the importance of molecular genetic research methods in the study of the etiopathogenesis of osteomyelitis of the jaws. The purpose of the work is to provide up-to-date information to researchers, dental surgeons, and maxillofacial surgeons on the possibilities of molecular genetic research in identifying bacterial pathogens in osteomyelitis of the jaws, as well as to reflect genetic markers of pathogenicity factors for a number of the main causative agents of the disease. Methodology. International scientific databases PubMed, ScienceDirect, Scopus, Cochrane Collaboration, Elsevier, as well as electronic catalogs eLIBRARY.RU and CyberLeninka.ru were used. Results. A review of publications demonstrated that S. aureus and S. Epidermidis dominate the etiological spectrum of causative agents of bone tissue infections. The participation of these microorganisms is determined by a whole range of pathogenicity factors. Toxins and Panton-Valentine leukocidin (PVL) genes play a major role in the pathogenesis of osteomyelitis and disease progression. It has been shown that the pathogenic bacteria Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are capable of inducing differentiated production of cytokines. The most attention has been attracted to E. faecium, which exhibits multidrug resistance to a wide range of antibiotics. The proportion of infections mediated by S. epidermidis and S. Saprophyticus is, on average, about 25% of cases. The proportion of representatives of gram-negative flora Escherichia, Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia, Serratia reaches 23% of cases. Pathogenic nosocomial strains of P. aeruginosa are also involved in the formation of chronic inflammation in osteomyelitis. According to the results of published studies, more than a third of cases of chronic osteomyelitis are mediated by microbial associations, which are dominated by S. aureus, S. epidermidis and, less commonly, E. faecalis. Conclusions. The use of PCR analysis to identify the causative agents of osteomyelitis and gene amplification using specific primers has a huge advantage over routine microbiological tests, being an informative method for studying the pathogenicity factors of the main pathogens. The high importance of molecular genetic methods in the study of the etiopathogenesis of osteomyelitis of the jaws requires their widespread use in the clinic of surgical dentistry and maxillofacial surgery to successfully solve complex problems in the rehabilitation of patients with this disease.

Pangenome analyses of Clostridium butyricum provide insights into its genetic characteristics and industrial application

Clostridium butyricum is a Gram-positive anaerobic bacterium known for its ability to produce butyate. In this study, we conducted whole-genome sequencing and assembly of 14C. butyricum industrial strains collected from various parts of China. We performed a pan-genome comparative analysis of the 14 assembled strains and 139 strains downloaded from NCBI. We found that the genes related to critical industrial production pathways were primarily present in the core and soft-core gene categories. The phylogenetic analysis revealed that strains from the same clade of the phylogenetic tree possessed similar antibiotic resistance and virulence factors, with most of these genes present in the shell and cloud gene categories. Finally, we predicted the genes producing bacteriocins and botulinum toxins as well as CRISPR systems responsible for host defense. In conclusion, our research provides a desirable pan-genome database for the industrial production, food application, and genetic research of C. butyricum.

Specificities and commonalities of the Planctomycetes plasmidome.

Plasmids, despite their critical role in antibiotic resistance and modern biotechnology, are understood in only a few bacterial groups in terms of their natural ecological dynamics. The bacterial phylum Planctomycetes, known for its unique molecular and cellular biology, has a largely unexplored plasmidome. This study offers a thorough exploration of the diversity of natural plasmids within Planctomycetes, which could serve as a foundation for developing various genetic research tools for this phylum. Planctomycetes plasmids encode a broad range of biological functions and appear to have coevolved significantly with their host chromosomes, sharing many homologues. Recent transfer events of insertion sequences between cohabiting chromosomes and plasmids were also observed. Interestingly, 64% of plasmid genes are distantly related to either chromosomally encoded genes or have homologues in plasmids from other bacterial groups. The planctomycetal plasmidome is composed of 36% exclusive proteins. Most planctomycetal plasmids encode a replication initiation protein from the Replication Protein A family near a putative iteron-containing replication origin, as well as active type I partition systems. The identification of one conjugative and three mobilizable plasmids suggests the occurrence of horizontal gene transfer via conjugation within this phylum. This comprehensive description enhances our understanding of the plasmidome of Planctomycetes and its potential implications in antibiotic resistance and biotechnology.

The release of ‘LCP 85‐384’ and its contribution to the Louisiana sugar industry

The release of ‘LCP 85‐384’ and its contribution to the Louisiana sugar industry

Understanding the Spread of Insecticide Resistance through Population Genetic Approach: A Review

This review discusses the application of the population genetic approach in elucidating the deployment of insecticide resistance to mosquito vectors. Although there have been a lot of scientific work describing population genetic research and insecticide resistance, a study focusing on the spread of insecticide resistance using the population genetic approach needs to be done. Population genetics explains how a population is diverse in response to fitness and the cost of environmental factors. Thus, readers can relate this process to how insecticides spread in the population. Additionally, some fundamental mechanisms of insecticide resistance are also covered. As successive reproduction of advantageous phenotypic traits, such as resistance depends on many factors including continuous pressure, recombination rate, migration rate, genetic drift, and so on. Currently, genome-wide association studies involve chromosome-wide SNPs in which recombination hotspots occur or microsatellite flanking region of resistance gene target in which the fixation process can potentially serve as a suitable marker for elucidating the deployment. The information provided in this review to facilitate how the susceptible individual still exists despite the predominance of resistant individuals and how the resistance reverts to the vulnerable state.

Understanding the determinants of sweet taste liking in the African and East Asian ancestry groups in the U.S.-A study protocol.

The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E).