Genetic Control Mechanisms Research Articles

Morphological and molecular aspects of lung development.

Healthy breathing relies on normal morphological and functional development of the lung. This includes different prenatal and postnatal developmental stages. Depending on species and postnatal behavior as nest escapers or nest squatters, the duration of individual developmental phases and the state of differentiation of the lungs at birth differ. However, the sequence and morphology of the lung developmental stages are similar in all mammals, so knowledge gained from animal models about development-specific genetic control and regulatory mechanisms can be translated in principle to the human lung. Functional lung development comprises the maturation of the surfactant system, which is closely linked to the morphological development of the pulmonary acini. Although a number of reviews are found in the literature, a presentation that integrates the morphological and molecular regulatory mechanisms is missing. Therefore, the aim of this article was to provide an up-to-date comprehensive review of the main morphological steps and regulatory mechanisms of lung development, including clinical aspects related to developmental disorders.

A 5.2-kb insertion in the coding sequence of PavSCPL, a serine carboxypeptidase-like enhances fruit firmness in Prunus avium.

Fruit firmness is an important trait in sweet cherry breeding because it directly positively influences fruit transportability, storage and shelf life. However, the underlying genes responsible and the molecular mechanisms that control fruit firmness remain unknown. In this study, we identified a candidate gene, PavSCPL, encoding a serine carboxypeptidase-like protein with natural allelic variation, that controls fruit firmness in sweet cherry using map-based cloning and functionally characterized PavSCPL during sweet cherry fruit softening. Genetic analysis revealed that fruit firmness in the 'Rainier' × 'Summit' F1 population was controlled by a single dominant gene. Bulked segregant analysis combined with fine mapping narrowed the candidate gene to a 473-kb region (7418778-7 891 914 bp) on chromosome 6 which included 72 genes. The candidate gene PavSCPL, and a null allele harbouring a 5244-bp insertion in the second exon that completely inactivated PavSCPL expression and resulted in the extra-hard-flesh phenotype, were identified by RNA-sequencing analysis and gene cloning. Quantitative RT-PCR analysis revealed that the PavSCPL expression level was increased with fruit softening. Virus-induced gene silencing of PavSCPL enhanced fruit firmness and suppressed the activities of certain pectin-degrading enzymes in the fruit. In addition, we developed functional molecular markers for PavSCPL and the Pavscpl5.2-k allele that co-segregated with the fruit firmness trait. Overall, this research identified a crucial functional gene for fruit firmness. The results provide insights into the genetic control and molecular mechanism of the fruit firmness trait and present useful molecular markers for molecular-assisted breeding for fruit firmness in sweet cherry.

Novel multiple gynoecium genotype in sorghum (Sorghum bicolor L.)

A novel fodder sorghum ( L.) genotype (EC484238) with multiple gynoecium has been Sorghum bicoloridentified at ICAR-IGFRI, Jhansi for the first time in India. The floral microscopic study of this novel genotyperevealed that female mega-gametophyte produced multiple gynoecium ranging from two to six, instead of one as in normal sorghum genotypes with bi-feathery stigma on each ovary. These multiple ovaries succeeded to produce viable twin or triplet seeds per spikelet per panicle. The twin and triple seed ratio ranged from 97-99% and 1-3%, respectively per panicle. This unique sorghum genotype might be a homeobox mutant which could shed light on the genetic regulation and control mechanisms governing the development of floral str ucture in sorghum as well as in other grasses of the Poaceae family. Multi-ovary sorghum has the obvious advantage of the increased number of seeds per panicle, thereby potentially increasing the seed yield. The novel genotype might be used in future fodder sorghum breeding programmes and will have more significance for the development of dual purpose fodder sorghum

Determination of the melanin and anthocyanin content in barley grains by digital image analysis using machine learning methods.

The pigment composition of plant seed coat affects important properties such as resistance to pathogens, pre-harvest sprouting, and mechanical hardness. The dark color of barley (Hordeum vulgare L.) grain can be attributed to the synthesis and accumulation of two groups of pigments. Blue and purple grain color is associated with the biosynthesis of anthocyanins. Gray and black grain color is caused by melanin. These pigments may accumulate in the grain shells both individually and together. Therefore, it is difficult to visually distinguish which pigments are responsible for the dark color of the grain. Chemical methods are used to accurately determine the presence/ absence of pigments; however, they are expensive and labor-intensive. Therefore, the development of a new method for quickly assessing the presence of pigments in the grain would help in investigating the mechanisms of genetic control of the pigment composition of barley grains. In this work, we developed a method for assessing the presence or absence of anthocyanins and melanin in the barley grain shell based on digital image analysis using computer vision and machine learning algorithms. A protocol was developed to obtain digital RGB images of barley grains. Using this protocol, a total of 972 images were acquired for 108 barley accessions. Seed coat from these accessions may contain anthocyanins, melanins, or pigments of both types. Chemical methods were used to accurately determine the pigment content of the grains. Four models based on computer vision techniques and convolutional neural networks of different architectures were developed to predict grain pigment composition from images. The U-Net network model based on the EfficientNetB0 topology showed the best performance in the holdout set (the value of the "accuracy" parameter was 0.821).

A body map of super-enhancers and their function in pig.

Super-enhancers (SEs) are clusters of enhancers that act synergistically to drive the high-level expression of genes involved in cell identity and function. Although SEs have been extensively investigated in humans and mice, they have not been well characterized in pigs. Here, we identified 42,380 SEs in 14 pig tissues using chromatin immunoprecipitation sequencing, and statistics of its overall situation, studied the composition and characteristics of SE, and explored the influence of SEs characteristics on gene expression. We observed that approximately 40% of normal enhancers (NEs) form SEs. Compared to NEs, we found that SEs were more likely to be enriched with an activated enhancer and show activated functions. Interestingly, SEs showed X chromosome depletion and short interspersed nuclear element enrichment, implying that SEs play an important role in sex traits and repeat evolution. Additionally, SE-associated genes exhibited higher expression levels and stronger conservation than NE-associated genes. However, genes with the largest SEs had higher expression levels than those with the smallest SEs, indicating that SE size may influence gene expression. Moreover, we observed a negative correlation between SE gene distance and gene expression, indicating that the proximity of SEs can affect gene activity. Gene ontology enrichment and motif analysis revealed that SEs have strong tissue-specific activity. For example, the CORO2B gene with a brain-specific SE shows strong brain-specific expression, and the phenylalanine hydroxylase gene with liver-specific SEs shows strong liver-specific expression. In this study, we illustrated a body map of SEs and explored their functions in pigs, providing information on the composition and tissue-specific patterns of SEs. This study can serve as a valuable resource of gene regulatory and comparative analyses to the scientific community and provides a theoretical reference for genetic control mechanisms of important traits in pigs.

Characterization of a novel dominant mutation BrCRSL conferring curled rod-shaped leaves in Chinese cabbage

Leaf morphogenesis requires precise genetic control and hormone regulation to develop into ideal plant architectures. Leaf flattening is an adaptive trait to obtain efficient photosynthesis, for which the leaf adaxial–abaxial polar establishment is of great importance. Herein, a novel leaf morphological mutant, curled rod-shaped leaf (crsl), was isolated and characterized from Chinese cabbage (Brassica rapa L. ssp. pekinensis) EMS-induced population. The leaves in crsl were slender and rod-shaped, with the abaxial side folded upwards and the distal side curled downwards, the mesophyll cells were loosely arranged, and the epidermal morphology was opposite on the adaxial and abaxial surface. Genetic analysis revealed that the curled rod-shaped leaf mutant phenotype was controlled by a dominate nuclear gene, named BrCRSL. MutMap and Kompetitive Allele Specifc PCR (KASP) genotyping demonstrated that BraA02g016100.3C was the most likely candidate for BrCRSL. Compared with the wild-type, a non-synonymous SNP mutation (C to T) occurred in the 8th exon of BraA02g016100.3C in crsl. BraA02g016100.3C is orthologous of Arabidopsis thaliana MAB1 (AT5G50850), which encodes a putative mitochondrial PDH E1β subunit protein and contributes to PIN-dependent auxin transport in organ development. The amino acid substitution from proline (P) to leucine (L) is conserved among the homologous proteins of BraA02g016100.3C. ​The crsl mutant exhibited abnormal auxin metabolism, primarily manifested by high level of L-tryptophan (TRP) accumulation that is the precursor of IAA biosynthesis. Furthermore, the expression of a wide range of leaf adaxial/abaxial polarity-related genes was affected in crsl. Our results contribute to a better understanding of the genetic control mechanism underlying leaf morphogenesis in Chinese cabbage and provide new insights into the auxin-related leaf axial growth.

Genetic control of a sex-specific piRNA program

Sexually dimorphic traits in morphologies are widely studied,1,2,3,4 but those in essential molecular pathways remain largely unexplored. Previous work showed substantial sex differences in Drosophila gonadal piRNAs,5 which guide PIWI proteins to silence selfish genetic elements, thereby safeguarding fertility.6,7,8 However, the genetic control mechanisms of piRNA sexual dimorphism remain unknown. Here, we showed that most sex differences in the piRNA program originate from the germ line rather than the gonadal somatic cells. Building on this, we dissected the contribution of sex chromosomes and cellular sexual identity toward the sex-specific germline piRNA program. We found that the presence of the Y chromosome is sufficient to recapitulate some aspects of the male piRNA program in a female cellular environment. Meanwhile, sexual identity controls the sexually divergent piRNA production from X-linked and autosomal loci, revealing a crucial input from sex determination into piRNA biogenesis. Sexual identity regulates piRNA biogenesis through Sxl, and this effect is mediated, in part, through chromatin proteins Phf7 and Kipferl. Together, our work delineated the genetic control of a sex-specific piRNA program, where sex chromosomes and sexual identity collectively sculpt an essential molecular trait.

Fine mapping and causal gene identification of a novel QTL for early flowering by QTL-seq, Target-seq and RNA-seq in spring oilseed rape

A novel quantitative trait locus for early flowering in spring oilseed rape, BnaC08cqDTF, was mapped to an 86-kb region on chromosome C08, and its causal gene, CRY2, was uncovered. Days to flowering is a very important agronomic and adaptive trait of Brassica napus oilseed rape (AACC, 2n = 38). We previously identified BnaC08cqDTF as a novel candidate quantitative trait locus (QTL) for early flowering in spring oilseed rape. Here, we present fine mapping of the locus and a study of its causal gene. Initial mapping was performed by QTL sequencing of DNA pools of BC3F2 plants with extreme flowering times derived from crosses between the spring-type cv. No. 4512 (early flowering) and cv. No. 5246 (late flowering), along with fine mapping by target sequencing of the BC3F2 and BC4F2populations.Fine mapping narrowed down BnaC08cqDTF to an 86-kb region on chromosome C08. The region harbored fifteen genes. After comparative analyses of the DNA sequences for mutation between A and C syntenic regions and detected by RNA-seq and qRT-PCR between the two parents, we found that BnaC08G0010400ZS harbors an A/G nonsynonymous mutation in exon 3. This single nucleotide polymorphism (SNP) haplotypewas alsocorrelated with early flowering ina 256 accession panel. BnaC08G0010400ZS is a homolog of the AT1G04400 gene (CRY2) in Arabidopsis. The analyses of transgenic Arabidopsis verified that BnaC08G0010400ZS is responsible for early flowering. Our results contribute to a better understanding of the genetic control mechanism of early flowering in spring Brassica napus and will promote the breeding for early mature varieties.

Field Resistance to Rose Rosette Disease as Determined by Multi-Year Evaluations in Tennessee and Delaware

Rose rosette disease (RRD) caused by the rose rosette emaravirus (RRV) and transmitted by the eriophyid mite Phyllocoptes fructiphilus (Pf), both native to North America, has caused significant damage to roses over the last several decades. As cultural and chemical control of this disease is difficult and expensive, a field trial was established to systematically screen rose germplasm for potential sources of resistance. One hundred and eight rose accessions representing the diversity of rose germplasm were planted in Tennessee and Delaware, managed to encourage disease development, and evaluated for symptom development and viral presence for three years. All major commercial rose cultivars were susceptible to this viral disease to varying levels. The rose accessions with no or few symptoms were species accessions from the sections Cinnamomeae, Carolinae, Bracteatae, and Systylae or hybrids with these. Among these, some were asymptomatic; they displayed no symptoms but were infected by the virus. Their potential depends on their ability to serve as a source of viruses. The next step is to understand the mechanism of resistance and genetic control of the various sources of resistance identified.

Superior Clone Selection in a Eucalyptus Trial Using Forest Phenotyping Technology via UAV-Based DAP Point Clouds and Multispectral Images

The quantitative, accurate and efficient acquisition of tree phenotypes is the basis for forest “gene-phenotype-environment” studies. It also offers significant support for clarifying the genetic control mechanisms of tree traits. The application of unmanned aerial vehicle (UAV) remote sensing technology to the collection of phenotypic traits at an individual tree level quantitatively analyses tree phenology and directionally evaluates tree growth, as well as accelerating the process of forest genetics and breeding. In this study, with the help of high-resolution, high-overlap, multispectral images obtained by an UAV, combined with digital elevation models (DEMs) extracted from point clouds acquired by a backpack LiDAR, a high-throughput tree structure and spectral phenotypic traits extraction and a genetic selection were conducted in a trial of Eucalyptus clones in the State-owned Dongmen Forest Farm in the Guangxi Zhuang Autonomous Region. Firstly, we validated the accuracy of extracting the phenotypic parameters of individual tree growth based on aerial stereo photogrammetry point clouds. Secondly, on this basis, the repeatability of the tree growth traits and vegetation indices (VIs), the genetic correlation coefficients between the traits were calculated. Finally, the eucalypt clones were ranked by integrating a selection index of traits, and the superior genotypes were selected and their genetic gain predicted. The results showed a high accuracy of the tree height (H) extracted from the digital aerial photogrammetry (DAP) point cloud based on UAV images (R2 = 0.91, and RMSE = 0.56 m), and the accuracy of estimating the diameter at breast height (DBH) was R2 = 0.71, and RMSE = 0.75 cm. All the extracted traits were significantly different within the tree species and among the clones. Except for the crown width (CW), the clonal repeatability (Rc) of the traits were all above 0.9, and the individual repeatability values (Ri) were all above 0.5. The genetic correlation coefficient between the tree growth traits and VIs fluctuated from 0.3 to 0.5, while the best clones were EA14-15, EA14-09, EC184, and EC183 when the selection proportion was 10%. The purpose of this study was to construct a technical framework for phenotypic traits extraction and genetic analysis of trees based on unmanned aerial stereo photography point clouds and high-resolution multispectral images, while also exploring the application potential of this approach in the selective breeding of eucalypt clones.

Wheat end-use quality: State of art, genetics, genomics-assisted improvement, future challenges, and opportunities.

Wheat is the most important source of food, feed, and nutrition for humans and livestock around the world. The expanding population has increasing demands for various wheat products with different quality attributes requiring the development of wheat cultivars that fulfills specific demands of end-users including millers and bakers in the international market. Therefore, wheat breeding programs continually strive to meet these quality standards by screening their improved breeding lines every year. However, the direct measurement of various end-use quality traits such as milling and baking qualities requires a large quantity of grain, traits-specific expensive instruments, time, and an expert workforce which limits the screening process. With the advancement of sequencing technologies, the study of the entire plant genome is possible, and genetic mapping techniques such as quantitative trait locus mapping and genome-wide association studies have enabled researchers to identify loci/genes associated with various end-use quality traits in wheat. Modern breeding techniques such as marker-assisted selection and genomic selection allow the utilization of these genomic resources for the prediction of quality attributes with high accuracy and efficiency which speeds up crop improvement and cultivar development endeavors. In addition, the candidate gene approach through functional as well as comparative genomics has facilitated the translation of the genomic information from several crop species including wild relatives to wheat. This review discusses the various end-use quality traits of wheat, their genetic control mechanisms, the use of genetics and genomics approaches for their improvement, and future challenges and opportunities for wheat breeding.

Identification of SNPs and InDels probably associated with the development of spontaneous tumors in radish (<i>Raphanus sativus</i> L.)

Radish (Raphanus sativus L.) is an agronomically important root crop belonging to the Brassicaceae family. A genetic collection of inbred radish lines, which was based on contrasting genetically determined traits including trait ability to develop tumors, was created at St. Petersburg State University in the middle of the 20th century [1]. Full genetics network controlling this trait still remains unclear [2], and elucidation of its mechanisms can help reveal the key regulators of systemic mechanisms that control cell proliferation and differentiation.
 The purpose of this work is to identify single nucleotide polymorphisms (SNPs) and InDels in genes which are candidates for participation in the tumor development process within in the tumor-forming radish line compared to the non-tumor radish line.
 We have assembled the genomes of two lines contrasting in the ability to tumorigenesis, annotated them, aligned sequences per assembly, identified candidate genes and differences in the structure of these genes in contrasting radish lines using bioinformatics tools. Bioinformatics data were confirmed by the sequencing by Sanger method.
 As a result, in the tumor-forming radish line we identified 151 genes with InDels in their coding regions, which led to various variants of frameshift. Moreover, we detected 39 genes with single nucleotide substitutions (SNPs). According to the gene pathway enrichment analysis, the corresponding genes were classified into the several groups.
 Thus, the data obtained will allow us to clarify in more detail the genetic control mechanisms of the tumor development in radish.
 The work was supported by the Ministry of Science and Higher Education of the Russian Federation in accordance with the agreement No. 075-15-2022-322.

Comparative evolutionary dynamics of the 5’cis-regulatory elements (CREs) of miR167 genes in diploid and allopolyploid cotton species

Cotton fiber morphogenesis is tightly regulated by several microRNAs (miRNAs) including miR167 which regulates auxin-signaling through the transcriptional regulation of its target genes during fiber development. To emphasize the evolution of spatiotemporal regulatory attributes of miR167 genes during fiber development, a comparative analysis of 5′cis-regulatory elements (CREs) and coding sequences of miR167 genes from progenitor diploid A2 (G. arboreum), D5 (G. raimondii) species and decedent allopolyploid AD1 (G. hirsutum) and AD2 (G. barbadense) species were performed in an evolutionary framework. Interestingly, different miR167 genes were conserved both in A- and D-subgenomes of AD1 and AD2 species (>90% sequence similarities) and acquired the least variations in gene sequences during allopolyploidy followed by species diversification. However, substantial accumulation of structural variations in 1.5kb long upstream regions exhibited that the regulatory regions had undergone extensive evolutionary changes during cotton evolution in both diploid and allopolyploid species. Several unique CREs could be identified and further classified into development-, light-, organ-, stress- and hormone-responsive motifs with their varied frequencies. Co-expression analyses of miR167 genes and their respective CREs-binding transcription factors (TFs) showed tissue- and developmental stage-specific correlation, especially with bHLH transcription factor (R2 = 0.93) during fiber initiation and elongation stages of AD1 species. The reconstructed gene networks of the most significant predicted TFs with CREs underscored the possible genetic control mechanisms of these factors during fiber development. These observations highlighted that various regulatory motifs were preserved during cotton evolution and may be exploited for future crop improvement programs.

Genetic mapping and physiological analysis of chlorophyll-deficient mutant in Brassica napus L

BackgroundLeaf color mutants have reduced photosynthetic efficiency, which has severely negative impacts on crop growth and economic product yield. There are different chlorophyll mutants in Arabidopsis and crops that can be used for genetic control and molecular mechanism studies of chlorophyll biosynthesis, chloroplast development and photoefficiency. Chlorophyll mutants in Brassica napus are mostly used for mapping and location research but are rarely used for physiological research. The chlorophyll-deficient mutant in this experiment were both genetically mapped and physiologically analyzed.ResultsIn this study, yellow leaf mutant of Brassica napus L. mutated by ethyl methyl sulfone (EMS) had significantly lower chlorophyll a, b and carotenoid contents than the wild type, and the net photosynthetic efficiency, stomatal conductance and transpiration rate were all significantly reduced. The mutant had sparse chloroplast distribution and weak autofluorescence. The granule stacks were reduced, and the shape was extremely irregular, with more broken stromal lamella. Transcriptome data analysis enriched the differentially expressed genes mainly in phenylpropane and sugar metabolism. The mutant was mapped to a 2.72 Mb region on A01 by using BSA-Seq, and the region was validated by SSR markers.ConclusionsThe mutant chlorophyll content and photosynthetic efficiency were significantly reduced compared with those of the wild type. Abnormal chloroplasts and thylakoids less connected to the stroma lamella appeared in the mutant. This work on the mutant will facilitate the process of cloning the BnaA01.cd gene and provide more genetic and physiological information concerning chloroplast development in Brassica napus.

How the lung folds itself: biophysical insights from evolution

Evolution has generated an enormous diversity of biological form. Given this diversity, it is highly likely that every tissue structure that one can imagine has been built by the embryo of one species or another. We are interested in uncovering the physical (mechanical) mechanisms by which epithelial sheets fold themselves into branching tubes in the embryo, and using those mechanisms to engineer tissues in culture. Over the past half century, developmental biologists have identified several biochemical signaling pathways and genetic control mechanisms necessary for tissue morphogenesis. In parallel, biological systems must obey Newton’s laws of motion, and physical forces need to be generated in order to sculpt simple populations of cells into complex tissue forms. Inspired by the evolutionary diversity of embryonic forms, we have combined time‐lapse imaging analysis with computational modeling and engineered tissue models to identify the mechanical forces and downstream signaling pathways that are responsible for generating the diverse architectures of the lungs from birds, mammals, and reptiles. I will describe our recent insights into the different physical mechanisms used to fold the epithelium across these three classes of vertebrates, and possible explanations for the divergence of the avian lung.

Detection of Deregulated miRNAs in Childhood Epileptic Encephalopathies.

The term "epileptic encephalopathy" is used to describe a possible relationship between epilepsy and developmental delay. The pathogenesis of developmental encephalopathies, independent of epilepsy, can be defined by genetic control mechanisms. The aim of this study was to investigate the use of miRNAs as serum biomarkers for the determination and discrimination of epileptic encephalopathies. Whole blood samples obtained from 54 individuals in 2 groups designated as epileptic encephalopathy patients' group (n = 24) and healthy controls (n = 30) were included in this study. The expression levels of 10 miRNAs were determined using qRT-PCR. After the determination of expression levels, the correlation of upregulated miRNA levels and Ki67 index was calculated using Pearson correlation test. The comparison of epileptic encephalopathy patients' group with healthy controls revealed the upregulation of one miRNAs (hsa-miR-324-5p) and downregulation of three miRNAs (hsa-miR-146a-5p, hsa-miR-138-5p, hsa-miR-187-3p). It has been determined that miRNAs with altered expression are an important factor in the formation of epileptic seizures and seizure-induced neuronal death. The fact that processes that play a key role in epiloptogenesis are under the control of miRNAs causes miRNAs to become meta-controllers of gene expression in the brain. We thought that further studies are needed to prove that especially hsa-miR-146a-5p, hsa-miR-138-5p, and hsa-miR-187-3p can be used as epileptic encephalopathy biomarkers. The detection of disease-specific miRNAs could contribute to the development of precision treatments.

New generation genome sequencing methods

Sequencing procedures, which present information related to events in the living metabolism, are performed by genetic methods. Gene structure and genetic control mechanisms can be determined by sequencing methods, as they represent significant contributions to transcriptomic, ecological, and epidemiological studies. Thus, chromosomal abnormalities in living things with a whole genome analysis of different organisms (e.g., plants, bacteria, yeast, fungi, and viruses) are detected quickly, so that clinical disease can be diagnosed with reliable data from biomedical research. The nucleic acid sequencing processes have a history of about fifty years. With the technology developed in recent years, second and third-generation methods, known as next-generation sequencing (NGS), found their rightful place in the sector approximately 15 years ago. New-generation sequencing promotes inexpensive, routine, and comprehensive analyses of the living genome. In general, sequencing methods are separated as first-, second-, and third-generation sequencing methods, with the latter called ‘new-generation sequencing:’ our review focuses on these specific sequencing methods.

Genetic control mechanisms and genetic regulatory systems

Genetic control mechanisms and genetic regulatory systems

Competitive dCas9 binding as a mechanism for transcriptional control

Catalytically dead Cas9 (dCas9) is a programmable transcription factor that can be targeted to promoters through the design of small guide RNAs (sgRNAs), where it can function as an activator or repressor. Natural promoters use overlapping binding sites as a mechanism for signal integration, where the binding of one can block, displace, or augment the activity of the other. Here, we implemented this strategy in Escherichia coli using pairs of sgRNAs designed to repress and then derepress transcription through competitive binding. When designed to target a promoter, this led to 27‐fold repression and complete derepression. This system was also capable of ratiometric input comparison over two orders of magnitude. Additionally, we used this mechanism for promoter sequence‐independent control by adopting it for elongation control, achieving 8‐fold repression and 4‐fold derepression. This work demonstrates a new genetic control mechanism that could be used to build analog circuit or implement cis‐regulatory logic on CRISPRi‐targeted native genes.

On the issue of nongenotoxic cancerogenes

Introduction. Chemical, physical or biological factors that can cause the formation and expansion of cancer cells are diverse in terms of both activity and mechanisms of action, which leads to the complexity of assessing the risk of developing malignant neoplasms. The aim. Discussion of the classification of carcinogens based on their ability to interact with DNA cell and possible mechanisms of genetic control of carcinogenesis processes induced by non-genotoxic carcinogens. Core content. The article draws attention to some controversial points related to the attribution of factors acting on the body to genotoxic or non-genotoxic carcinogens. The terminology used in the literature to describe genotoxic (mutagenic) and carcinogenic factors is presented. The mechanisms of action of non-genotoxic carcinogens are discussed. The important role of experts determining the danger to public health of factors with potential genotoxicity and carcinogenicity is noted. Conclusion. Non-genotoxic carcinogens are capable of inducing malignant growth through mechanisms not associated with direct damage to genetic structures in the cell. However, the realization of carcinogenic effects caused by such factors is determined by various mechanisms of genetic control.