Vavilovskii Zhurnal Genetiki i Selektsii最新文献

{"title":"Reconstruction of gene regulatory networks from single cell transcriptomic data.","authors":"M A Rybakov, N A Omelyanchuk, E V Zemlyanskaya","doi":"10.18699/vjgb-24-104","DOIUrl":"https://doi.org/10.18699/vjgb-24-104","url":null,"abstract":"<p><p>Gene regulatory networks (GRNs) - interpretable graph models of gene expression regulation - are a pivotal tool for understanding and investigating the mechanisms utilized by cells during development and in response to various internal and external stimuli. Historically, the first approach for the GRN reconstruction was based on the analysis of published data (including those summarized in databases). Currently, the primary GRN inference approach is the analysis of omics (mainly transcriptomic) data; a number of mathematical methods have been adapted for that. Obtaining omics data for individual cells has made it possible to conduct large-scale molecular genetic studies with an extremely high resolution. In particular, it has become possible to reconstruct GRNs for individual cell types and for various cell states. However, technical and biological features of single-cell omics data require specific approaches for GRN inference. This review describes the approaches and programs that are used to reconstruct GRNs from single-cell RNA sequencing (scRNA-seq) data. We consider the advantages of using scRNA-seq data compared to bulk RNA-seq, as well as challenges in GRN inference. We pay specific attention to state-of-the-art methods for GRN reconstruction from single-cell transcriptomes recruiting other omics data, primarily transcription factor binding sites and open chromatin profiles (scATAC-seq), in order to increase inference accuracy. The review also considers the applicability of GRNs reconstructed from single-cell omics data to recover and characterize various biological processes. Future perspectives in this area are discussed.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 8","pages":"974-981"},"PeriodicalIF":0.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of autistic personality traits with the EEG scores in non-clinical subjects during the facial video viewing.","authors":"A N Savostyanov, D A Kuleshov, D I Klemeshova, M S Vlasov, A E Saprygin","doi":"10.18699/vjgb-24-108","DOIUrl":"https://doi.org/10.18699/vjgb-24-108","url":null,"abstract":"<p><p>A software information module of the experimental computer platform \"EEG_Self-Construct\" was developed and tested in the framework of this study. This module can be applied for identification of neurophysiological markers of self-referential processes based on the joint use of EEG and facial video recording to induce the brain's functional states associated with participants' personality traits. This module was tested on a group of non-clinical participants with varying degrees of severity of autistic personality traits (APT) according to the Broad Autism Phenotype Questionnaire. The degree of individual severity of APT is a quantitative characteristic of difficulties that a person has when communicating with other people. Each person has some individual degree of severity of such traits. Patients with autism are found to have high rates of autistic traits. However, some individuals with high rates of autistic traits are not accompanied by clinical symptoms. Our module allows inducing the brain's functional states, in which the EEG indicators of people with different levels of APT significantly differ. In addition, the module includes a set of software tools for recording and analyzing brain activity indices. We have found that relationships between brain activity and the individual level of severity of APT in non-clinical subjects can be identified in resting-state conditions following recognition of self-referential information, while recognition of socially neutral information does not induce processes associated with APT. It has been shown that people with high scores of APT have increased spectral density in the delta and theta ranges of rhythms in the frontal cortical areas of both hemispheres compared to people with lower scores of APT. This could hypothetically be interpreted as an index of reduced brain activity associated with recognition of self-referential information in people with higher scores of autistic traits. The software module we are developing can be integrated with modules that allow identifying molecular genetic markers of personality traits, including traits that determine the predisposition to mental pathologies.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 8","pages":"1018-1024"},"PeriodicalIF":0.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Root cap border cells as regulators of rhizosphere microbiota.","authors":"N A Omelyanchuk, V A Cherenko, E V Zemlyanskaya","doi":"10.18699/vjgb-24-99","DOIUrl":"https://doi.org/10.18699/vjgb-24-99","url":null,"abstract":"<p><p>A rhizosphere (a narrow area of soil around plant roots) is an ecological niche, within which beneficial microorganisms and pathogens compete with each other for organic carbon compounds and for the opportunity to colonize roots. The roots secrete rhizodeposits into the rhizosphere, which include border cells, products of root cell death and liquids secreted by living cells (root exudates). Border cells, which have their name due to their location in the soil next to the root (at the border of the root and soil), represent terminal differentiation of columella and adjacent lateral root cap cells. Border cells can detach from the root cap surface both as single cells and as cell layers. Border cells are constantly supplied to the soil throughout plant life, and the type and intensity of border cells' sloughing depend on both plant species and soil conditions. Currently, data on the factors that control the type of border cells' release and its regulation have been described in different plant species. Border cells are specialized for interaction with the environment, in particular, they are a living barrier between soil microbiota and roots. After separation of border cells from the root tip, transcription of primary metabolism genes decreases, whereas transcription of secondary metabolism genes as well as the synthesis and secretion of mucilage containing these metabolites along with extracellular DNA, proteoglycans and other substances increase. The mucilage that the border cells are embedded in serves both to attract microorganisms promoting plant growth and to protect plants from pathogens. In this review, we describe interactions of border cells with various types of microorganisms and demonstrate their importance for plant growth and disease resistance.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 8","pages":"918-926"},"PeriodicalIF":0.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor TCF4: structure, function, and associated diseases.","authors":"R R Savchenko, N A Skryabin","doi":"10.18699/vjgb-24-85","DOIUrl":"https://doi.org/10.18699/vjgb-24-85","url":null,"abstract":"<p><p>Our understanding of human genes - particularly their structure, functions, and regulatory mechanisms - is still limited. The biological role of approximately 20 % of human proteins has not been established yet, and the molecular functions of the known part of the proteome remain poorly understood. This hinders progress in basic and applied biological and medical sciences, especially in treating hereditary diseases, which are caused by mutations and polymorphic variants in individual genes. Therefore, it is crucial to comprehend the mechanisms of protein functioning to address this problem. This further emphasizes the importance of investigating gene functions and molecular pathogenetic pathways associated with single-gene inherited diseases. This review focuses on the TCF4 gene that encodes a transcription factor crucial for nervous system development and functioning. Pathogenic variants in this gene have been linked to a rare genetic disorder, Pitt-Hopkins syndrome, and TCF4 polymorphic variants are associated with several socially significant diseases, including various psychiatric disorders. The pathogenetic mechanisms of these conditions remain unexplored, and the knowledge about TCF4 upregulation and its target genes is limited. TCF4 can be expressed in various isoforms due to the complex structure and regulation of its gene, which complicates the investigation of the protein's functions. Here, we consider the structure and functions of the TCF4 transcription factor. We discuss its potential target genes and the possible loss-of-function pathogenetic mechanisms identified in animal and cellular models of Pitt-Hopkins syndrome. The review also examines the advantages and limitations of potential therapies for Pitt-Hopkins syndrome that are based on TCF4 dosage compensation or altering the activity of TCF4 target genes.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"770-779"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed cytogenetic analysis of three duck species (the northern pintail, mallard, and common goldeneye) and karyotype evolution in the family Anatidae (Anseriformes, Aves).","authors":"V R Beklemisheva, K V Tishakova, S A Romanenko, D A Andreushkova, V A Yudkin, E А Interesova, F Yang, M A Ferguson-Smith, A S Graphodatsky, A A Proskuryakova","doi":"10.18699/vjgb-24-84","DOIUrl":"https://doi.org/10.18699/vjgb-24-84","url":null,"abstract":"<p><p>Galliformes and Anseriformes are two branches of the Galloanserae group, basal to other Neognathae. In contrast to Galliformes, Anseriformes have not been thoroughly researched by cytogenetic methods. This report is focused on representatives of Anseriformes and the evolution of their chromosome sets. Detailed cytogenetic analysis (G-banding, C- banding, and fluorescence in situ hybridization) was performed on three duck species: the northern pintail (Anas acuta, 2n = 80), the mallard (A. platyrhynchos, 2n = 80), and the common goldeneye (Bucephala clangula, 2n = 80). Using stone curlew (Burhinus oedicnemus, 2n = 42, Charadriiformes) chromosome painting probes, we created homology maps covering macrochromosomes and some microchromosomes. The results indicated a high level of syntenic group conservation among the duck genomes. The two Anas species share their macrochromosome number, whereas in B. clangula, this number is increased due to fissions of two ancestral elements. Additionally, in this species, the presence of massive heterochromatic blocks in most macroautosomes and sex chromosomes was discovered. Localization of clusters of ribosomal DNA and telomere repeats revealed that the duck karyotypes contain some microchromosomes that bear ribosomal RNA genes and/or are enriched for telomere repeats and constitutive heterochromatin. Dot plot (D-GENIES) analysis confirmed the established view about the high level of syntenic group conservation among Anatidae genomes. The new data about the three Anatidae species add knowledge about the transformation of macro- and sex chromosomes of Anseriformes during evolution.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"759-769"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of AZFс Y chromosome microdeletions and association with spermatogenesis in Russian men from the general population.","authors":"L V Osadchuk, G V Vasiliev, M K Ivanov, M A Prasolova, M A Kleshchev, A V Osadchuk","doi":"10.18699/vjgb-24-86","DOIUrl":"https://doi.org/10.18699/vjgb-24-86","url":null,"abstract":"<p><p>The Y chromosome contains a set of genes with testis-specific expression that are responsible for the development of testes and spermatogenesis, and it is the most important target in the search for genetic causes of male infertility. Most of these genes are located in the \"azoospermia factor\" AZF locus (regions AZFa, AZFb, and AZFc) on the long arm of the Y chromosome. Microdeletions of the Y chromosome, leading to the removal of the entire AZF locus as well as one or more regions (complete deletions), are one of the leading causes of spermatogenesis impairment and infertility. However, the role of partial AZFc deletions (gr/gr, b2/b3, b1/b3) in spermatogenesis failure is unclear, and their impact on spermatogenesis varies between populations. The aim of the present study was to assess the frequency of various types of AZFc microdeletions and to search for associations with spermatogenesis parameters in men of Slavic ethnicity from the general Russian population (n = 700, average age 25.8 years). To identify AZF microdeletions, the presence/absence of 15 STS markers was analyzed using multiplex real-time polymerase chain reaction. Age, weight, height, and the volume, concentration, total count, proportion of motile and morphologically normal spermatozoa in the ejaculate were recorded for all participants. In the studied sample, 19.9 % (139/700) of men were found to have AZFc microdeletions, of which 16.7 % (117/700) were carriers of a partial b2/b3 deletion, 3.0 % (21/700) had a partial gr/gr deletion, and 0.14 % (1/700) had a complete b2/b4 deletion. Neither AZFa nor AZFb microdeletions nor other types of AZF deletions were detected. The overall frequency of all types of AZFc deletions, as well as each type of partial microdeletion, b2/ b3 and gr/gr, did not differ in the groups of azoospermia, severe oligozoospermia (≤5.0 mill/ml), oligozoospermia (5.0 < SC <16.0 mill/ml), and normal sperm concentration (≥16.0 mill/ml). Comparison of semen parameters in groups with different types of partial AZFc deletions and the control group (without deletions) also did not reveal significant differences. Thus, partial AZFc microdeletions b2/b3 and gr/gr do not have a significant impact on spermatogenesis in Slavic men. It is suggested that in Slavs, partial AZFc microdeletions b2/b3 and gr/gr are fixed in Y haplogroups N3 and R1a, respectively, and their negative impact on spermatogenesis is balanced by other genetic factors. The higher frequency of partial AZFc deletions (19.7 %) in Slavs compared to European populations (7.3 %) established in our study may be explained by the widespread distribution of these Y haplogroups in the Slavic population of Russia.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"780-791"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenetic features of intergeneric amphydiploids and genome-substituted forms of wheat.","authors":"E D Badaeva, R O Davoyan, N A Tereshchenko, E V Lyalina, S A Zoshchuk, N P Goncharov","doi":"10.18699/vjgb-24-80","DOIUrl":"https://doi.org/10.18699/vjgb-24-80","url":null,"abstract":"<p><p>Synthetic intergeneric amphydiploids and genome-substituted wheat forms are an important source for transferring agronomically valuable genes from wild species into the common wheat (Triticum aestivum L.) genome. They can be used both in academic research and for breeding purposes as an original material for developing wheat-alien addition and substitution lines followed by translocation induction with the aid of irradiation or nonhomologous chromosome pairing. The chromosome sets and genome constitutions of allopolyploids are usually verified in early hybrid generations, whereas the subsequent fate of these hybrids remains unknown in most cases. Here we analyze karyotypes of five hexa- (2n = 6x = 42) and octoploid (2n = 8x = 56) amphydiploids of wheat with several species of the Aegilops, Haynaldia, and Hordeum genera, and six genome-substituted wheat-Aegilops forms, which were developed over 40 years ago and have been maintained in different gene banks. The analyses involve C-banding and fluorescence in situ hybridization (FISH) with pAs1 and pSc119.2 probes. We have found that most accessions are cytologically stable except for Avrodes (genome BBAASS, a hexaploid genome-substituted hybrid of wheat and Aegilops speltoides), which segregated with respect to chromosome composition after numerous reproductions. Chromosome analysis has not confirmed the presence of the N genome from Ae. uniaristata Vis. in the genome-substituted hybrid Avrotata. Instead, Avrotata carries the D genome. Our study shows that octoploid hybrids, namely AD 7, AD 7147 undergo more complex genome reorganizations as compared to hexaploids: the chromosome number of two presumably octoploid wheat-Aegilops hybrids were reduced to the hexaploid level. Genomes of both forms lost seven chromosome pairs, which represented seven homoeologous groups and derived from different parental subgenomes. Thus, each of the resulting hexaploids carries a synthetic/hybrid genome consisting of a unique combination of chromosomes belonging to different parental subgenomes.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"716-730"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular genetic and morphological characteristics of Micractinium thermotolerans and M. inermum (Trebouxiophyceae, Chlorophyta) from pyroclastic deposits of the Kamchatka Peninsula (Russia).","authors":"R Z Sushchenko, V Yu Nikulin, V B Bagmet, A Yu Nikulin","doi":"10.18699/vjgb-24-79","DOIUrl":"https://doi.org/10.18699/vjgb-24-79","url":null,"abstract":"<p><p>During the study of algal diversity in pyroclastic deposits of the Kamchatka Peninsula, Chlorella-like green algae strains VCA-72 and VCA-93 were isolated from samples collected from along the Baydarnaya river bed on the Shiveluch volcano in 2018 and at the outlet of thermal vapors along the edge of the caldera on the southern slope of the Gorely volcano in 2020. Identification of the strains was carried out within the framework of an integrative approach using microscopic and molecular genetic methods, including preliminary taxon identification, obtaining nucleotide sequences of the small subunit and the internal transcribed spacer rRNA, reconstruction of phylogenetic trees and secondary structures of the ITS1 and ITS2 rRNA regions. On the phylogenetic tree, strain VCA-93 was clustered in the Micractinium thermotolerans species clade. No differences were found when comparing the helical domain models of ITS1 and ITS2 in M. thermotolerans. Strain VCA-72 occupied a basal position in the M. inermum clade. The secondary structure patterns of the helices of strain VCA-72 were generally similar to those of M. inermum, but intraspecific variability was noted, mainly due to substitutions in the apical and lateral loops. Five hCBC substitutions were found in the helical regions of the studied M. inermum strains, while no CBC substitutions were found. A detailed analysis of morphology and life cycle allowed us to identify the characteristics of the cells in aging cultures: their size was significantly higher than in vegetative ones and they were pear-shaped, oval, and ellipsoidal with a shallow, wide constriction in the center. In addition, cells with colorless lipid droplets were detected in aging cultures of both species. The ability to synthesize and accumulate lipids indicates the great potential of the strains for the production of biodiesel fuel. A review of the habitats of previous and new findings allowed us to note the ecological plasticity of the studied species. The results obtained complement the information on the biogeography of the species: this is the first record of M. inermum for the territory of Russia, and that of M. thermotolerans, for the Kamchatka Peninsula.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"706-715"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the primary structure and production of recombinant poly(ADP-ribose)polymerase 1 of long-lived Heterocephalus glaber.","authors":"K N Naumenko, A R Nurislamov, K D Nazarov, V S Fishman, A A Popov, I O Petruseva, A N Evdokimov, O I Lavrik","doi":"10.18699/vjgb-24-77","DOIUrl":"https://doi.org/10.18699/vjgb-24-77","url":null,"abstract":"<p><p>DNA repair is a most important cellular process that helps maintain the integrity of the genome and is currently considered by researchers as one of the factors determining the maximum lifespan. The central regulator of the DNA repair process is the enzyme poly(ADP-ribose)polymerase 1 (PARP1). PARP1 catalyzes the synthesis of poly(ADP-ribose) polymer (PAR) upon DNA damage using nicotinamide adenine dinucleotide (NAD+) as a substrate. This polymer covalently attaches to PARP1, which leads to its dissociation from the complex with damaged DNA and stimulation of the repair process. Despite intensive research on PARP1, its properties as an isolated protein have not been practically studied in mammals that demonstrate a long maximum lifespan, such as, for example, the naked mole rat (Heterocephalus glaber). High activity of DNA repair systems is observed in the cells of the naked mole rat, which ensures their high resistance to oxidative stress, as well as to genotoxic effects. The revealed features may be due to the high activity of PARP1 in the cells of the naked mole rat; however, this issue remains poorly understood and, thus, requires more detailed research, including one with the use of isolated protein PARP1 of the naked mole rat, the isolation and characterization of which have not been carried out before. In the present work, the amino acid sequence of PARP1 of the naked mole rat is compared with the amino acid sequences of orthologous proteins of other mammals. In contrast to human PARP1, 13 evolutionarily conservative amino acid substitutions in various functional domains of the protein have been identified in the amino acid sequence of naked mole rat PARP1. Using the cDNA of the naked mole rat's Parp1 gene, a vector was created for the expression of the target protein in Escherichia coli cell culture. For the first time, a detailed description of the procedure for the expression and purification of the recombinant protein PARP1 of the long-lived naked mole rat is presented. In addition, poly(ADP-ribose)polymerase activity of the obtained protein was evaluated. The results presented in this paper are the basis for further detailed characterization of the properties of purified recombinant naked mole rat PARP1.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"688-695"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene.","authors":"E V Grigor'eva, A A Malakhova, E S Yarkova, J M Minina, Y V Vyatkin, J A Nadtochy, E A Khabarova, J A Rzaev, S P Medvedev, S M Zakian","doi":"10.18699/vjgb-24-76","DOIUrl":"https://doi.org/10.18699/vjgb-24-76","url":null,"abstract":"<p><p>Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the development of the disease, to identify targets for therapeutic intervention and to test potential drugs to prevent neuronal death. Analysis of exome sequencing data from a 46-year-old patient with a clinical diagnosis of Parkinson's disease revealed the presence of the pathological variant c.2013T>G (rs63750756) in the MAPT gene, which is associated with frontotemporal dementia with parkinsonism-17. By reprogramming the patient's peripheral blood mononuclear cells, we obtained induced pluripotent stem cells (iPSCs). Two iPSC lines were characterised in detail. Reprogramming was performed by transfection with non-integrating episomal vectors expressing the OCT4, SOX2, KLF4, LIN28, L-MYC and mp53DD proteins. The iPSC lines ICGi052-A and ICGi052-B proliferate stably, form colonies with a morphology characteristic of human pluripotent cells, have a normal diploid karyotype (46,XX), express endogenous alkaline phosphatase and pluripotency markers (OCT4, NANOG, SSEA-4 and TRA-1-60) and are able to differentiate into derivatives of three germ layers: ento-, ecto- and mesoderm. The iPSC lines obtained and characterised in detail in this work represent a unique tool for studying the molecular genetic mechanisms of the pathogenesis of frontotemporal dementia with parkinsonism-17, as well as for testing potential drugs in vitro.</p>","PeriodicalId":44339,"journal":{"name":"Vavilovskii Zhurnal Genetiki i Selektsii","volume":"28 7","pages":"679-687"},"PeriodicalIF":0.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}