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33 Publications visible to you, out of a total of 33
Generation of iPSCs from a Patient with the M694V Mutation in the MEFV Gene Associated with Familial Mediterranean Fever and Their Differentiation into Macrophages.

Abstract (Expand)

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin … protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the MEFV mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type MEFV gene. Keywords: Familial Mediterranean fever; MEFV gene; differentiation; macrophages; patient-specific induced pluripotent stem cells.

Authors: Elena V Grigor'eva, Lana V Karapetyan, Anastasia A Malakhova, Sergey P Medvedev, Julia M Minina, Varduhi H Hayrapetyan, Valentina S Vardanyan, Suren M Zakian, Arsen Arakelyan, Roksana Zakharyan

Date Published: 2024

Publication Type: Journal

Generation of three induced pluripotent stem cell lines (RAUi001-A, RAUi001-B and RAUi001-C) from peripheral blood mononuclear cells of a healthy Armenian individual.

Abstract (Expand)

The study of pathological processes in cells carrying mutations should be carried out in comparison with a healthy control group. Familial Mediterranean fever (FMF), which is caused by a mutation in … the MEFV gene, is predominantly found in people of Armenian nationality with the prevalence of 14–100 per 10000. We have obtained induced pluripotent stem cells (iPSCs) from Armenian healthy patient, which will be included as a control group in the study of this disease. iPSCs rapidly proliferate in colonies of cells with a typical pluripotent-like morphology, have a normal karyotype (46,XX). iPSCs express pluripotency markers (OCT4, SOX2, TRA-1–60, NANOG) and are able to give derivatives of three germ layers.

Authors: Elena V. Grigor’eva, Anastasia A. Malakhova, Lilit Ghukasyan, Varduhi Hayrapetyan, Sofi Atshemyan, Valentina Vardanyan, Suren M. Zakian, Roksana Zakharyan, Arsen Arakelyan

Date Published: 17th Jun 2023

Publication Type: Journal

Molecular Analysis of SARS-CoV-2 Lineages in Armenia

Abstract (Expand)

The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and … Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity. Phylodynamic and transmission analysis allowed to attribute specific clades as well as infer their importation routes. Thus, the first two waves of positive case increase were caused by the 20B clade, the third peak caused by the 20I (Alpha), while the last two peaks were caused by the 21J (Delta) and 21K (Omicron) variants. The functional analyses of mutations in sequences largely affected epitopes associated with protective HLA loci and did not cause the loss of the signal in PCR tests targeting ORF1ab and N genes as confirmed by RT-PCR. We also compared the performance of nanopore and Illumina short-read sequencing and showed the utility of nanopore sequencing as an efficient and affordable alternative for large-scale molecular epidemiology research. Thus, our paper describes new data on the genomic diversity of SARS-CoV-2 variants in Armenia in the global context of the virus molecular genomic surveillance.

Authors: Diana Avetyan, Siras Hakobyan, Maria Nikoghosyan, Lilit Ghukasyan, Gisane Khachatryan, Tamara Sirunyan, Nelli Muradyan, Roksana Zakharyan, Andranik Chavushyan, Varduhi Hayrapetyan, Anahit Hovhannisyan, Shah A. Mohamed Bakhash, Keith R. Jerome, Pavitra Roychoudhury, Alexander L. Greninger, Lyudmila Niazyan, Mher Davidyants, Gayane Melik-Andreasyan, Shushan Sargsyan, Lilit Nersisyan, Arsen Arakelyan

Date Published: 17th May 2022

Publication Type: Journal

Expression of micro-RNAs miR-31, miR-146a, miR-181c and miR-155 and their target gene IL-2 are altered in schizophrenia: a case-control study

Abstract (Expand)

Background: Schizophrenia is a severe psychiatric disorder with a heterogeneous clinical phenotype. The association of interleukins and other cytokines and their receptors with schizophrenia has been … previously reported. Additionally, a number of studies have reported altered mico-RNA (miRNA) expression in schizophrenia and other psychiatric disorders. The aim of our study was to explore the possible association of miR-31, miR-146a, miR-181c and miR-155 with schizophrenia pathogenesis, as well as their link to IL2 gene expression in disease. Methods: For this case-control study, 225 patients with paranoid schizophrenia and 225 sex- and age-matched controls with no family history of schizophrenia were recruited. The expression of studied miRNAs and the IL2 gene was measured using qPCR. DNA samples of all patients and controls were genotyped for IL2 rs2069778 single nucleotide polymorphism (SNP) using PCR with sequence specific primers (PCR-SSP). Statistical analyses include the Mann-Whitney U-test and Fischer’s exact test. Results: All studied miRNAs were over-expressed in schizophrenic patients IL2 gene expression was down-regulated in schizophrenic patients. The IL2 rs2069778 SNP is not associated with schizophrenia but regulates expression of the IL2 gene. Conclusions: Over-expression of studied miRNAs and down-regulation of IL2 gene expression may be considered as genetic risk factors for chronic schizophrenia. Abnormalities in studied miRNA expressions result in the deregulation of the T-cell receptor signaling pathway in schizophrenia.

Authors: Hovsep Ghazaryan, Roksana Zakharyan, Martin Petrek, Zdenka Navratilova, Andranik Chavushyan, Eva Novosadova, Arsen Arakelyan

Date Published: 10th Dec 2019

Publication Type: Journal

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

Abstract (Expand)

Background: Despite the important role of the nerve growth factor in the survival and maintenance of neurons in ischemic stroke, data regarding the relationships between variations in the encoding gene … and stroke are lacking. In the present study, we evaluated the association of the functional polymorphisms in NGF (rs6330) and NGFR (rs2072446 and rs734194) genes with ischemic stroke in an Armenian population. Methods: In total, 370 unrelated individuals of Armenian nationality were enrolled in this study. Genomic DNA samples of patients and healthy controls were genotyped using polymerase chain reaction with sequence-specific primers. Results: The results obtained indicate that the minor allele of rs6330 (Pcorr = 2.4E-10) and rs2072446 (Pcorr = 0.02) are significantly overrepresented in stroke group, while the minor allele of rs734194 (Pcorr = 8.5E-10) was underrepresented in diseased subjects. Single nucleotide polymorphisms in NGF gene (rs6330) and NGFR gene (rs2072446 and rs734194) are associated with the disease. Furthermore, it was shown that the carriage of the NGF rs6330*T minor allele is associated with increased infarct volume and higher risk of recurrent stroke. Conclusions: In conclusion, our findings suggest that the NGF rs6330*T and NGFR rs2072446*T minor alleles might be nominated as a risk factor for developing ischemic stroke and NGFR rs734194*G minor allele as a protective against this disease at least in Armenian population. Keywords: Ischemic stroke, Nerve growth factor, Nerve growth factor receptor, NGF, NGFR, Single nucleotide polymorphism

Authors: Ani Stepanyan, Roksana Zakharyan, Arsen Simonyan, Gohar Tsakanova, Arsen Arakelyan

Date Published: 2nd Mar 2018

Publication Type: Journal

Characterization of BRCA1/2 mutations in patients with family history of breast cancer in Armenia.

Abstract (Expand)

Background. Breast cancer is one of the most common cancers in women worldwide. The germline mutations of the BRCA1 and BRCA2 genes are the most significant and well characterized genetic risk factors … for hereditary breast cancer. Intensive research in the last decades has demonstrated that the incidence of mutations varies widely among different populations. In this study we attempted to perform a pilot study for identification and characterization of mutations in BRCA1 and BRCA2 genes among Armenian patients with family history of breast cancer and their healthy relatives. Methods. We performed targeted exome sequencing for BRCA1 and BRCA2 genes in 6 patients and their healthy relatives. After alignment of short reads to the reference genome, germline single nucleotide variation and indel discovery was performed using GATK software. Functional implications of identified variants were assessed using ENSEMBL Variant Effect Predictor tool. Results. In total, 39 single nucleotide variations and 4 indels were identified, from which 15 SNPs and 3 indels were novel. No known pathogenic mutations were identified, but 2 SNPs causing missense amino acid mutations had significantly increased frequencies in the study group compared to the 1000 Genome populations. Conclusions. Our results demonstrate the importance of screening of BRCA1 and BRCA2 gene variants in the Armenian population in order to identity specifics of mutation spectrum and frequencies and enable accurate risk assessment of hereditary breast cancers. Keywords: BRCA1; BRCA2; breast cancer; mutation screening; targeted exome sequencing.

Authors: Sofi Atshemyan, Andranik Chavushyan, Nerses Berberian, Arthur Sahakyan, Roksana Zakharyan, Arsen Arakelyan

Date Published: 10th Jan 2017

Publication Type: Journal

Transcription Factors in Schizophrenia: A Current View of Genetic Aspects

Abstract (Expand)

Background: Schizophrenia is a polygenic mental disorder with about 80% heritability. Growing evidence indicated that synaptic dysfunctions contribute to SCZ etiopathogenesis. The context and purpose …e of the study: Transcription factors play an important role in the regulation of gene expression. Whereas expression analysis of transcription factor has been performed, studies of their genetic variants are limited. The current review article summarizes data on transcription factors early growth response 3 (EGR3), c-fos transcription (FOS), immune early response 5 (IER5), c-jun (JUN), Nk2 Homeobox 1 (NKX2-1), and transcription factor 4 (TCF4) encoding genes in schizophrenia. Results and main findings: An important role of the mentioned genes in this pathology has been identified. Conclusions: We concluded that the genetic variants of the transcription factor encodng genes might contribute to the assessment of disease susceptibility and can find potential use for the development of genetically-driven diagnostic approaches in the future.

Author: Zakharyan Roksana

Date Published: 30th Dec 2016

Publication Type: Journal

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