Bioinformatics search for genetic markers of socially significant diseases in promoters of human genes DOI Open Access

Published: July 6, 2022

Language: Английский

Transcription Factors as Important Regulators of Changes in Behavior through Domestication of Gray Rats: Quantitative Data from RNA Sequencing DOI Open Access
Dmitry Oshchepkov, И. В. Чадаева, R. V. Kozhemyakina

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12269 - 12269

Published: Oct. 14, 2022

Studies on hereditary fixation of the tame-behavior phenotype during animal domestication remain relevant and important because they are both basic research applied significance. In model animals, gray rats Rattus norvegicus bred for either an enhancement or reduction in defensive response to humans, first time, we used high-throughput RNA sequencing investigate differential expression genes tissue samples from tegmental region midbrain 2-month-old showing tame aggressive behavior. A total 42 differentially expressed (DEGs; adjusted p-value < 0.01 fold-change > 2) were identified, with 20 upregulated 22 downregulated compared rats. Among them, three encoding transcription factors (TFs) detected: Ascl3 was upregulated, whereas Fos Fosb brains brain. Other DEGs annotated as associated extracellular matrix components, transporter proteins, neurotransmitter system, signaling molecules, immune system proteins. We believe that these encode proteins constitute a multifactorial determining behavior which have been artificially selected. demonstrated several structural subtypes E-box motifs—known binding sites many developmental TFs bHLH class, including ASCL subfamily TFs—are enriched set promoters rats’. Because ASCL3 may act repressor target other hypothesize TF gene indicates longer neurogenesis (as rats), is sign neoteny domestication. Thus, our shows new function ASCL3: it play most role behavioral changes animals.

Language: Английский

Citations

11

Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression DOI Open Access
Д. А. Рассказов, И. В. Чадаева,

Ekaterina Sharypova

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8684 - 8684

Published: Aug. 4, 2022

Synthetic targeted optimization of plant promoters is becoming a part progress in mainstream postgenomic agriculture along with hybridization cultivated plants wild congeners, as well marker-assisted breeding. Therefore, here, for the first time, we compiled all experimental data—on mutational effects proximal on gene expression—that could find PubMed. Some these datasets cast doubt both existence and uniqueness sought solution, which unequivocally estimate promoter mutation expression when are grown under various environmental conditions during their development. This means that inverse problem study ill-posed. Furthermore, found data vitro interchangeability human TATA-binding proteins allowing application Tikhonov’s regularization, making this well-posed. Within frameworks, created our Web service Plant_SNP_TATA_Z-tester then determined limits its applicability using those solution. We confirmed (of mutations expression) predicted by correlate statistically significantly study. Lastly, exemplified an to agriculturally valuable promoters.

Language: Английский

Citations

10

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases DOI Open Access

С. Г. Шихевич,

И. В. Чадаева,

Bato Khandaev

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3996 - 3996

Published: Feb. 16, 2023

Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine helps understand how, why, when, what ARDs one can develop depending their genetic background. Within this mainstream paradigm, we wanted find out whether the known ARD-linked DEGs available PubMed reveal a molecular marker that will serve purpose anyone’s any tissue at time. We sequenced periaqueductal gray (PAG) tame aggressive rats, identified rat-behavior-related DEGs, compared them homologous animal DEGs. analysis yielded statistically significant correlations between behavior-related ARD-susceptibility-related fold changes (log2 values) expression these DEG homologs. found principal components, PC1 PC2, corresponding half-sum half-difference log2 values, respectively. With linked ARD humans used as controls, verified components. only common for ARDs: an excess Fcγ receptor IIb suppressing immune cell hyperactivation.

Language: Английский

Citations

5

Human_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use cases DOI Creative Commons

S. V. Filonov,

N. L. Podkolodnyy, O. A. Podkolodnaya

et al.

Vavilov Journal of Genetics and Breeding, Journal Year: 2023, Volume and Issue: 27(7), P. 728 - 736

Published: Dec. 11, 2023

It was previously shown that the expression levels of human genes positively correlate with TBP affinity for promoters these genes. In turn, single nucleotide polymorphisms (SNPs) in gene can affect DNA and, as a consequence, expression. The Institute Cytology and Genetics SB RAS (ICG) has developed method predicting based on three-step binding mechanism: (1) slides along DNA, (2) stops at site, (3) TBP-promoter complex is fixed due to helix bending. showed high correlation theoretical predictions measured values during repeated experimental testing by independent groups researchers. This model served base other ICG web services, SNP_TATA_Z-tester SNP_TATA_Comparator, which make statistical assessment SNP-induced change promoter help predict changes may be associated genetic predisposition diseases or phenotypic features organism. this work, we integrated into database information about SNPs obtained automatic extraction from various heterogeneous data sources, well estimates using their effect wild-type SNPs. We have Human_SNP_TATAdb used annotation identification candidate SNP markers diseases. results genome-wide analysis are presented, including distribution respect number transcripts, affecting TBP-DNA positions within promoters, patterns linking promoter, specificity site characteristics promoters. its statistically related important functional classification study differential

Language: Английский

Citations

5

Animal Models of Hypertension (ISIAH Rats), Catatonia (GC Rats), and Audiogenic Epilepsy (PM Rats) Developed by Breeding DOI Creative Commons

M. A. Ryazanova,

В. С. Плеканчук, О. И. Прокудина

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(7), P. 1814 - 1814

Published: June 24, 2023

Research into genetic and physiological mechanisms of widespread disorders such as arterial hypertension well neuropsychiatric other human diseases is urgently needed in academic practical medicine the field biology. Nevertheless, studies have many limitations pose difficulties that can be overcome by using animal models. To date, for purposes creating models pathologies, several approaches been used: pharmacological/chemical intervention; surgical procedures; technologies transgenic animals, knockouts, or knockdowns; breeding. Although some these are good certain research aims, they drawbacks, greatest being a strong perturbation (in biological system) that, along with expected effect, exerts side effects study. Therefore, investigating pathogenesis disease, obtained selection target trait high value this approach allows creation model “natural” manifestation pathology. In review, three rat described: ISIAH rats (arterial hypertension), GC (catatonia), PM (audiogenic epilepsy), which developed breeding Laboratory Evolutionary Genetics at Institute Cytology (the Siberian Branch Russian Academy Sciences).

Language: Английский

Citations

4

Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection DOI Open Access
Anton Bogomolov, Sergey Filonov, И. В. Чадаева

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9010 - 9010

Published: May 19, 2023

Atherosclerosis is a systemic disease in which focal lesions arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development atheroma (atherogenesis) narrows blood vessels, reduces supply leads to cardiovascular diseases. According World Health Organization (WHO), diseases leading cause death, has been especially boosted since COVID-19 pandemic. There variety contributors atherosclerosis, including lifestyle factors genetic predisposition. Antioxidant diets recreational exercises act as atheroprotectors can retard atherogenesis. search for molecular markers atherogenesis atheroprotection predictive, preventive personalized medicine appears be most promising direction study atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis atheroprotection. hub regulating these processes found ancient. silico analysis all 5112 SNPs their promoters revealed 330 candidate SNP markers, statistically significantly change affinity TATA-binding protein (TBP) promoters. These made us confident that natural selection acts against underexpression At same time, upregulation one promotes health.

Language: Английский

Citations

2

RatDEGdb: a knowledge base of differentially expressed genes in the rat as a model object in biomedical research DOI Creative Commons
И. В. Чадаева,

S. V. Filonov,

Karina Zolotareva

et al.

Vavilov Journal of Genetics and Breeding, Journal Year: 2023, Volume and Issue: 27(7), P. 794 - 806

Published: Dec. 11, 2023

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) rat as model object is collection published data on gene expression strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other afflictions. current release contains information 25,101 DEGs representing 14,320 unique that change transcription levels 21 tissues 10 genetic 11 diseases based 45 original scientific papers. RatDEGdb novel that, unlike any database, it offers manually curated annotations rats with use independent clinical equal changes homologous revealed people pathologies. put were annotated their homologs affected people. In its release, 94,873 such for 321 836 959 papers found PubMed. may be interesting first all to geneticists, molecular biologists, physicians, advisors well experts biopharmaceutics, bioinformatics personalized genomics. publicly available at https://www.sysbio.ru/RatDEGdb.

Language: Английский

Citations

2

A Principal Components Analysis and Functional Annotation of Differentially Expressed Genes in Brain Regions of Gray Rats Selected for Tame or Aggressive Behavior DOI Open Access
И. В. Чадаева, R. V. Kozhemyakina,

С. Г. Шихевич

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4613 - 4613

Published: April 23, 2024

The process of domestication, despite its short duration as it compared with the time scale natural evolutionary process, has caused rapid and substantial changes in phenotype domestic animal species. Nonetheless, genetic mechanisms underlying these remain poorly understood. present study deals an analysis transcriptomes from four brain regions gray rats (Rattus norvegicus), serving experimental model object domestication. We gene expression profiles hypothalamus, hippocampus, periaqueductal matter, midbrain tegmental region between tame domesticated aggressive revealed subdivisions differentially expressed genes by principal components that explain main part variance. Functional (in DAVID (Database for Annotation, Visualization Integrated Discovery) Bioinformatics Resources database) allowed us to identify describe key biological processes can participate formation different behavioral patterns seen two groups rats. Using STRING- DB (search tool recurring instances neighboring genes) web service, we built a association network. engaged broad network interactions have been identified. Our offers data on whose levels change response artificial selection behavior during

Language: Английский

Citations

0

Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma DOI Open Access

Karina Zolotareva,

Polina A. Dotsenko,

N. L. Podkolodnyy

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12802 - 12802

Published: Nov. 28, 2024

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise Mediterranean diet can alleviate In this work, we first time estimated phylostratigraphic age indices (PAIs) all 153 POAG-related human genes in NCBI Gene Database. allowed us separate them into two groups: that appeared before after phylum Chordata, is, ophthalmologically speaking, camera-type eye evolved. Next, genes’ promoters, silico predicted 3835 candidate SNP markers significantly change TATA-binding protein (TBP) affinity these promoters and, through molecular mechanism, expression levels genes. Finally, verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, GeneMANIA—as well as ClinVar database. It was concluded POAG likely be a symptom self-domestication syndrome, downside being civilized.

Language: Английский

Citations

0

Literature Review: Biomedical Information of Animal Treadmill Speed Control Using Proportional Integral Derivative Controller DOI Creative Commons

Cut Nanda Nurbadriani,

Melinda Melinda,

Roslidar Roslidar

et al.

Green Intelligent Systems and Applications, Journal Year: 2024, Volume and Issue: 4(2), P. 109 - 119

Published: Dec. 12, 2024

The use of treadmill exercise in cardiovascular research played a vital role assessing heart health and determining appropriate regimens for patients. Before applying these to humans, experiments on animals, such as white rats or mice, were conducted simulate human responses. A specialized designed experimental animals was required determine doses based individual abilities. This process involved controlling the speed, which generated by conveyor driven DC motor. motor speed regulated through PID (Proportional Integral Derivative) control, while encoder sensors monitored motor’s rotation limit switch determined duration. article reviewed design implementation systems used animal-based research, focusing control using controllers. Previous studies that contributed development discussed, with an emphasis precise mechanisms conditions tailored subject's system also incorporated accurately adjust track duration, ensuring alignment physiological capabilities test subjects. Furthermore, this review explored potential advancing systems, offering insights into how technology could support medical experts optimal rats. These developments helped bridge gap between applications, facilitating improved outcomes.

Language: Английский

Citations

0