Vladislav Sergeevitch Baranov

• Professor
• Russian Academy of Sciences

A new approach to understanding hereditary and multifactorial diseases, based on the integration of the results of a comprehensive study of their pathogenomics with the involvement of mathematical and bioinformatic analyzes, has made it possible to revise the initial provisions of predictive medicine in accordance with the rules of modern "precisio...

Spinal muscular atrophy is a progressive motor neuron disorder caused by deletions or point mutations in the SMN1 gene. It is not known why motor neurons are particularly sensitive to a decrease in SMN protein levels and what factors besides SMN2 underlie the high clinical heterogeneity of the disease. Here we studied the methylation patterns of ge...

Uterine leiomyoma (UL) is one of the most highly prevalent gynecological diseases, which is a benign tumor that develops in the myometrium. Although the main reason for the development of UL is hormonal imbalance, a considerable role in its pathogenesis is played by genetic factors that affect the manifestation and severity of the disease. Currentl...

BACKGROUND: Uterine leiomyoma and endometriosis are the most common gynecological diseases in women of reproductive age. A number of data indicate that there are common elements in the pathogenesis of these hyperproliferative conditions. This article is devoted to comparative analysis of the role of the WNT4, HOXA10 and TWIST1 genes in the developm...

The present study investigates telomere length (TL) in dividing chorionic cytotrophoblast cells from karyotypically normal and abnormal first trimester miscarriages and ongoing pregnancies. Using Q-FISH, we measured relative TLs in the metaphase chromosomes of 61 chorionic villous samples. Relative TLs did not differ between karyotypically normal s...

The human lifespan is strongly influenced by telomere length (TL) which is defined in a zygote—when two highly specialised haploid cells form a new diploid organism. Although TL is a variable parameter, it fluctuates in a limited range. We aimed to establish the determining factors of TL in chromosomes of maternal and paternal origin in human tripl...

Clinical tests based on whole-genome sequencing are generally focused on a single task approach, testing one or several parameters, although whole-genome sequencing (WGS) provides us with large data sets that can be used for many supportive analyses. In spite of low genome coverage, data of WGS-based non-invasive prenatal testing (NIPT) contain ful...

In the present study, we aimed to check whether uterine leiomyomas (ULs) with an apparently normal karyotype in vitro comprise “hidden” cell subpopulations with numerical chromosome abnormalities (heteroploid cells). A total of 32 ULs obtained from 32 patients were analyzed in the study. Each UL was sampled for in vivo and in vitro cytogenetic stud...

Hypothesis/Aims of study: Disorders of the hemostatic system continue to occupy one of the leading places in the structure of the causes of infertility and miscarriage. While being associated with reproductive losses, hemostatic disorders are a significant link in the pathogenesis of placenta-associated pregnancy complications. The consumption of p...

Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing...

This chapter discusses modern data on zygote nucleus formation, its further development in blastomeric cells, at cleavage stages, at compaction, and during primary differentiation into trophectoderm cells and inner cell mass. Also new insights based on cytogenetic, molecular genetic/cytogenomic data, and epigenetic mechanisms of embryo development...

Efficient and specific delivery of nucleic acid (NA) therapeutics to tumor cells is extremely important for cancer gene therapy. Various therapeutic strategies include delivery of DNA-therapeutics such as immunostimulatory or suicide genes and delivery of siRNA-therapeutics able to silence expression of cancer-related genes. Peptides are a promisin...

Since the very first publications on preimplantation genetic testing, researchers have faced a serious problem — a high mosaicism level in the preimplantation human embryos obtained by means of in vitro fertilization cycles. The nature of this mosaicism and its high impact on embryo development draws attention to this issue. In this research we stu...

Objectives In March 2020, the World Health Organization declared that an infectious respiratory disease caused by a new severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, causing coronavirus disease 2019 (COVID-19)] became a pandemic. In our study, we have analyzed a large publicly available dataset, the Genome Aggregation Database (gnomA...

Objectives: In March 2020, the World Health Organization declared that an infectious respiratory disease caused by a new severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, causing coronavirus disease 2019 (COVID-19)] became a pandemic. In our study, we have analyzed a large publicly available dataset, the Genome Aggregation Database (gnom...

Spinal muscular atrophy (SMA) is a genetic disease, which characterized by the degeneration of motor neurons in the spinal cord and further striated muscle atrophy. The research of the processes in diseased neurons is complicated due to the impossibility of obtaining them safely from patients. Thus, we generated SMA type III induced pluripotent ste...

Duchenne muscular dystrophy (DMD) is a severe and rapidly progressive hereditary muscular disease with X-linked recessive inheritance, occurring mainly in males. A complete loss of dystrophin resulted from out-of-frame deletion mutations in the DMD gene leads to Duchenne muscular dystrophy. DMD induced pluripotent stem cells (iPSCs) are a suitable...

Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors i...

MicroRNAs (miRNAs) are a class of small noncoding RNAs that play an important role in the mRNA regulation translation and degradation. Recent studies uncovered the implication of miRNA in the development of preeclampsia (PE)—a common and potentially fatal complication in pregnancy. This review provides an analysis of the current knowledge on miRNA...

The goal of the research is to study the effect of KE peptide on telomere length of PHA-stimulated blood lymphocytes of young and middle-aged men. 11 blood lymphocyte samples were enrolled in the analysis. Relative telomere length was measured using fluorescence in situ hybridization with DNA-probes specific to telomere sequences of human chromosom...

We review recent studies dealing with the molecular genetics and basic results of omics analysis of uterine leiomyoma (LM)—a common benign muscle tumor of the uterus. Whole genome studies of LM resulted in the discovery of many new gene nets and biological pathways, including its origin, transcriptomic, and epigenetic profiles, as well as the impac...

We studied the effect of peptide AEDG on telomere length and mitotic index of PHA-stimulated blood lymphocytes from young (18-22 years, N=5) and middle-aged (49-54 years, N=6) men. In the younger age group, no significant changes in the mitotic index were detected, while in the middle-aged group, a decrease in this parameter was found in one case....

We report on the phenotype and the reproductive history of an adult female patient with an unbalanced karyotype: 8p23 and 18p11.3 terminal deletions and 8p22 duplication. The indication for karyotyping of the 28-year-old patient was a structural rearrangement in her miscarriage specimen: 45,ХХ,der(8;18)t(8;18)(p23;p11.3). Unexpectedly, the patient...

In recent years, noninvasive prenatal testing (NIPT) for fetal chromosomal abnormalities has come into wide use. NIPT allows detection of fetal chromosomal abnormalities without invasive sampling of fetal material: by analyzing cell-free fetal DNA in maternal blood. Here, we report on the pilot results of using NIPT at the D.O. Ott Research Institu...

The present study reports on the frequency and the spectrum of genetic variants causative of monogenic diabetes in Russian children with non‑type 1 diabetes mellitus. The present study included 60 unrelated Russian children with non‑type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were screened using whole‑exome seque...

Experimental embryology achievements in the century resulted in the birth of the first child conceived artificially. Besides its obvious social significance, the successful solution of the “test-tube babies” provided also the unique chance for direct inspection of human embryos growing in vitro at their earlier stages. New technologies applied for...

Background: Wilson's disease (WD) is a rare inherited disorder caused by mutations in the ATP7B gene resulting in copper accumulation in different organs. However, data on ATP7B mutation spectrum in Russia and worldwide are insufficient and contradictory. The objective of the present study was estimation of the frequency of ATP7B gene mutations in...

Background: Incorrect epigenetic modifications of the human genome may result in epigenetic disorders, thus, highlighting the necessity of studying chromosome epigenetic patterns in human development. Aim of the study: A comparative analysis of acetylated histone H3K9 (AcH3K9) patterns in human metaphase chromosomes from the lymphocytes of adults...

Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-pathways, and some others. Introduction of small i...

Background In the conditions of dynamic development diagnostic capabilities and understanding of the pathogenetic mechanisms of diabetes, the main task of clinicians is the earliest possible verification of the type of diabetes. New diagnostic methods such as whole-exome sequencing allow to finally verify the type of diabetes mellitus and are of sp...

Hypothesis/aims of study. Endometriosis is one of the most pressing problems of gynecology. Clarifying the expression of the estrogen receptor (ESR1) and the progesterone receptor (PGR) genes and polymorphisms in the aromatase (CYP19A1) gene in endometriosis will expand the understanding of the pathogenesis of the disease and the causes of resistan...

In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introduce aberrant epigenetic regulation as a possible pathway to chro...

Methylation profiles of CpG islands within the SLC23A2, CDK2AP1, and DYNC1H1 genes and their association with spinal muscular atrophy (SMA) severity were studied. High clinical heterogeneity of SMA suggests the existence of different factors modifying SMA phenotype with gene methylation as a plausible one. The genes picked up in our earlier genome‐...

5-hydroxymethylcytosine (5hmC) is an oxidative derivative of 5-methylcytosine (5mC). Recent studies have revealed a sharp difference in the levels of 5hmC in 2 opposite DNA strands of a given chromosome and a chromosome-wide cell-to-cell variability in mammalian cells. This asymmetric 5hmC distribution was found in cultured cells, which may not ful...

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletion or mutation in SMN1 gene. SMA human induced pluripotent stem cells (iPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. We generated iPSCs from a SMA type I patient and SMA type II patient by using non-integrat...

Development of gene therapy for endometriosis requires inhibition of vascularization in endometrial lesions. We have previously developed CXCR4 receptor-targeted siRNA carrier L1 and observed efficient RNAi-mediated down-regulation of VEGFA gene expression in endothelial cells followed by decrease in VEGFA protein production and inhibition of cell...

The progress of genomic technologies has led to an increased understanding of the role of spermatozoa and spermioplasm RNA complex which is associated with male fertility. In this review, information about functional role of spermatozoal RNA such as messenger RNA and different types of noncoding RNAs is discussed. Data on the relationship between s...

Here, we determined basic differentially expressed genes in endometrial lesions compared to eutopic endometrium of the patients with endometriosis (EM). Endometrial biopsy and tissue sampling were performed in ten women with pelvic EM and nine controls at their mid-secretory phase. NGS of mRNA combined with bioinformatic analysis and complemented b...

The immunofluorescent study of genomic distribution of 5-formylcytosine and 5-carboxylcytosine in human preimplantation development – from the zygote up to the blastocyst stage – suggests a timeline of epigenetic reprogramming of the chromatin regions with different structure and functions.

Current problems and some future perspectives of molecular genetic study of connective tissue diseases (CTDs) are reviewed. The corresponding clinical manifestation and mode of heritable disorders of connective tissue (HDCT) inheritance are subdivided into inherited, mostly monogenic, forms and mixed or multifactorial dysplasia of connective tissue...

For over 100 years, endometriosis, as a chronic, estrogen-dependent, inflammatory, heritable disease affecting approximately 5–10% of women in reproductive age has been the focus of clinicians and scientists. In spite of numerous environmental, genetic, epigenetic, endocrine, and immunological studies, our knowledge of endometriosis is still fragme...

Background. Very little research has been devoted to the studying fertility problem in nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. It is difficult to draw definitive conclusions regarding the need for glucocorticoid therapy in NCAH women based on limited data. Therefore, evaluating fertility in patients with...

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene. Being a monogenic disease, it is characterized by high clinical heterogeneity. Variations in penetrance and severity of symptoms, as well as clinical discrepancies between affected family members can result from modifier genes influence on disease manife...

In connection with the ambiguity in the interpretation of the results of stimulation tests in congenital hypopituitarism, children need to search for molecular genetic markers of the disease. Molecular genetic analysis in patients with congenital hypopituitarism (genes GH1, GHRH, GHRHR,BTK, GHSR, PROP1, POU1F1, HESX1, LHX3, LHX4, SOX3, SOX2, OTX2,...

In this review, we summarize the data on 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine— cytosine modifications which are produced by TET-mediated oxidation of 5-methylcytosine in DNA. We show the biochemistry of modified cytosine, as well as methods for its global and location analysis. We also highlight the milestones in the ev...

Background: Preeclampsia (PE) is the most common complication of pregnancy that remains to be a major cause of maternal and fetal mortality. Prediction and early diagnosis of PE would allow for timely initiation of preventive therapy. According to recent studies of ACVR2A gene polymorphism is associated with PE, but it is still unclear whether thes...

Condensation: Chromothripsis involving chromosomes 1, 3, 13 in a large solitary non-recurrent MED12-mutation negative uterine fibroid is associated with novel pathways of leiomyoma-specific pathogenesis.

Clinical manifestations of heterogeneity of growth hormone deficiency when definitive results of hormonal stimulus test determines the need to search for molecular genetic markers of the disease to form personalized therapeutic algorithms. Molecular genetic analysis in patients with congenital hypopituitarism was carried out by new-generation seque...

The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensati...

Using immunofluorescence with specific antibodies, we analyzed DNA hydroxymethylation in uncultured cells from 25 human uterine leiomyomas considering the menstrual cycle phase during surgery and the presence of MED12 gene mutations. It was found that each tumor node had specific DNA hydroxymethylation level that did not depend on the presence of m...

Результаты молекулярно-генетических исследований свидетельствуют о возможном участии грелина в патогенезе некоторых форм низкорослости. Однако при изолированной соматотропной недостаточности мутации в гене рецептора грелина являются редкой причиной данного заболевания. В статье описан случай обнаружения методом секвенирования нового поколения (NGS)...

The aim of study was to determine feasible changes of placental miRNAs expression profiles revealed by next generation sequencing (NGS) in pregnancies with GDM complicated or not with PE. Out of 27 miRNAs, studied expression was significantly different (FDR < 0.05) only for his-miR-45a. Comparative analysis of revealed reliable differences in expre...

We performed immunofluorescent analysis of DNA hydroxymethylation and methylation in human testicular spermatogenic cells from azoospermic patients and ejaculated spermatozoa from sperm donors and patients from infertile couples. In contrast to methylation which was present throughout spermatogenesis, hydroxymethylation was either high or almost un...

Evolution of prenatal diagnostic service (PDS) in Russia is briefly outlined. It has started in the middle of 1960s, when it was mainly treated as a part of medical genetic counselling (period 1). In 1993 PDS was officially approved by the Federal Ministry of Health Care as a new clinical service. For many years, 1993–2000 (period 2), the infrastru...

Advantages and drawbacks of noninvasive prenatal testing (NIPT) of chromosomal anomalies are briefly reviewed. Material supply, employment issues, financial and management problems in European countries and in Russia are discussed. Many problems are rising under implementation of this new method into the clinical practice.

Aims To study the possible association of catechol-O-methyltransferase (COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids. Methods The COMT Val158Met allele and genotype frequencies were compared between age-matched w...

In this chapter, the protocol of combined immunofluorescence detection of 5-methylcytosine and its oxidative derivatives and FISH is given. This approach can be applied on fixed preparations of human chromosomes and nuclei. Human PHA-stimulated adult and fetal lymphocytes, uncultured tissues comprising spontaneously dividing cells, such as chorion,...

In this review, we summarize data on 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine – cytosine modifications which are produced by TET-mediated oxidation of 5-methylcytosine in DNA. We show the biochemistry of modified cytosine as well as methods for its global and location analysis. We also highlight the milestones in the evoluti...

Uterine leiomyomas (ULs) are common benign tumors affecting women of different ethnicities. A large proportion of UL has mutations in MED12. Multiple and solitary ULs usually manifest with different severities, suggesting that their origin and growth pattern may be driven by different molecular mechanisms. Here, we compared the frequency and the sp...

Induced pluripotent stem cells (iPSCs) give the possibility for disease modeling, drug and toxicology screening and development of the new therapeutic approaches. Directed differentiation of iPSCs into specialized cell types represents a unique tool in order to study and model certain diseases, which affects specific type of cells, in vitro. One of...

Pre-eclampsia (PE) is a complication of pregnancy that affects 5‑8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal morta...

Some novel molecular and cell methods implicated into assistant reproductive technology and prenatal diagnostics are reviewed. Special attention is paid to new generation sequencing (NGS) technique, arrayCGH, genome editing (CRISPR/Cas9 method), cell and gene therapy of embryos as well as to non-Invasive prenatal diagnostics and preconception testi...

Endometriosis (EM) and uterine leiomyoma (UL) are two most frequent benign tumors of monoclonal origin affecting about 30% of all women in their reproductive age. Modern molecular technologies have made a tremendous impact in understanding both disorders. Here is the first comparative analysis of molecular mechanisms underlying development of EM an...

Analysis of variations in DNA structure using a low-density microarray technology for routine diagnostic in evidence-based medicine is still relevant. In this work the applicability of 3-D macroporous monolithic methacrylate-based platforms for detection of different pathogenic genomic substitutions was studied. The detection of nucleotide replacem...

HLA-G is a nonclassical MHC class Ib molecule predominantly expressed in cytotrophoblasts and also under pathological conditions in chronically inflamed and malignant tissues. Polymorphisms of the HLA-G gene, some of which are functionally important, may potentially affect both the coding and noncoding regions of this gene. Using the PCR method we...

Modern molecular approaches to prenatal diagnostic of inherited diseases are briefly reviewed. Advantages and limitations of molecular methods for analysis of chromosomal anomalies (QF-PCR, aCGH, NGS) are considered in line with conventional prenatal karyotyping. The special attention is paid to efficacy, limitations and diagnostic options of nonin...

In 2009-2010, 98 patients diagnosed with the coronary heart disease, but without the expressed metabolic violations, decompensated conditions and diseases were surveyed. Patients of 60-90 years were divided by age into two groups: younger than 75 years--47 people; 75 years and older--51; there were 41 women and 57 men; the ratio between women and m...

Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases an...

Genotype and allele frequencies of uncoupling proteins 2 and 3 genes (UCP2 and UCP3) and peroxisome proliferator-activated receptors genes (PPARA, PPARD and PPARG) were studied in 206 residents of the siege and in 139 individuals of more than 69 years old (control group). Studied polymorphisms included UCP2 (Ala55Val), UCP3 (C-55T), PPARA (G/C), PP...

Spinal muscular atrophy (SMA) is a monogenic neurodegenerative disorder subdivided into four different types. Whole genome methylation analysis revealed 40 CpG sites associated with genes that are significantly differentially methylated between SMA patients and healthy individuals of the same age. To investigate the contribution of methylation chan...

Purpose. The wide range of the factors promoting emergence of GLD and also specificity of racial features of this disease testify to importance of studying of the genetic reasons of hereditary predisposition to development of GLD. Design/methodology/approach. PCR-RFLP analysis of the studied polymorphism of genes associated with the formation metho...

We report the sequential changes in 5-hydroxymethylcytosine (5hmC) patterns in the genome of human preimplantation embryos during DNA methylation reprogramming. We have studied chromosome hydroxymethylation and methylation patterns in triploid zygotes and blastomeres of cleavage-stage embryos. Using indirect immunofluorescence, we have analyzed the...

In this review, we summarize data on 5-hydroxymethylcytosine—a modification of cytosine with a recently discovered epigenetic effect. We discuss the biochemical mechanisms of 5-hydroxymethylcytosine generation and further modification in the mammalian genome, analyze the role of 5-hydroxymethylcytosine in the epigenetic reprogramming during mammali...

Analysis of ABCB4 gene in young women with cholelithiasis and relative story of gallstone disease was performed by NGS sequencing. The discovered “risk alleles” of this gene and their adverse haplotypes testify to ABCB4 participation in the development of cholelithiasis.

Background: Success in gene therapy greatly depends on the efficiency of nucleic acid delivery. Important features of the carriers for gene delivery should include an enhanced transfection ability, targeting of specific receptors and low toxicity. In the present study, we characterized CXCR4-targeted cross-linking peptides modified with an N-termi...

The overview represents the recent most conspicuous findings in aging studies. It includes new data on the whole genome association studies (GWAS) in big cohort of centenaries, recently found mutation protecting from Alzheimer disease, discovery of hypothalamus as a command center of human aging, very important data on the negative effect of common...