Publications by authors named "Parvin Shariati"

18 Publications

  • Page 1 of 1

Isolation of Novel Probiotic and Strains From Human Salivary and Fecal Sources.

Front Microbiol 2020 4;11:597946. Epub 2020 Dec 4.

Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Probiotics are non-pathogenic microorganisms that can interact with the gastrointestinal microbiota. They have numerous beneficial health effects that include enhancement of the host immune response, antiallergic, antimicrobial, anti-cancer, and anti-inflammatory properties. Probiotics are capable of restoring the impaired microbiome of a dysbiotic gut. They can be isolated from different environments. However, it is frequently suggested that probiotics for human use should come from human sources. The objective of this study was to isolate and characterize novel probiotic strains from the saliva and feces of healthy human individuals. To meet the criteria for probiotic attributes, the isolates were subjected to numerous standard morphological and biochemical tests. These tests included Gram staining, catalase tests, antibiotic susceptibility testing, hemolytic and antagonistic evaluation, tolerance tests involving temperature, NaCl levels, pH and bile salts, adherence ability assays, and genotypic characterization involving 16S rRNA gene sequencing. From 26 saliva and 11 stool samples, 185 microbial strains were isolated. Based on morphological and biochemical characteristics, 14 potential probiotic candidates were selected and identified genotypically. The new strains belonged to , and . The selected strains were non-hemolytic, showed high tolerance to low pH and bile salts, and strong adherence abilities. Furthermore, the strains displayed a wide range of antimicrobial activities, particularly against antibiotic-resistant pathogens such as methicillin resistant (MRSA). Moreover, five of the selected isolates demonstrated antiproliferative features against human colon cancer cell line (Caco-2). The results of this investigation confirm the diversity of microbial populations in the human gut and saliva, and since these strains are of human origin, they will highly likely display maximal activities in food and drugs set for human use. Hence, the new strains of this study require additional experiments to assess their health-promoting effects.
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http://dx.doi.org/10.3389/fmicb.2020.597946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746552PMC
December 2020

Potential Diagnostic Systems for Coronavirus Detection: a Critical Review.

Biol Proced Online 2020 1;22:21. Epub 2020 Sep 1.

Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Abstract: Currently there are no effective anti-viral drugs for SARS-CoV-2, so the primary line of defense is to detect infected cases as soon as possible. The high rate of contagion for this virus and the highly nonspecific symptoms of the disease (Coronovirus disease 2019, (Covid-19)) that it causes, such as respiratory symptoms, cough, dyspnea, fever, and viral pneumonia, require the urgent establishment of precise and fast diagnostic tests to verify suspected cases, screen patients, and conduct virus surveillance. Nowadays, several virus detection methods are available for viral diseases, which act on specific properties of each virus or virus family, therefore, further investigations and trials are needed to find a highly efficient and accurate detection method to detect and prevent the outcomes of the disease. Hence, there is an urgent need for more and precise studies in this field. In this review, we discussed the properties of a new generation of coronaviruses (SARS-CoV-2) following routine virus detection methods and proposed new strategies and the use of potential samples for SARS-CoV-2 detection.

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http://dx.doi.org/10.1186/s12575-020-00134-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462115PMC
September 2020

Antibiotic hypersensitivity in MRSA induced by special protein aggregates.

Int J Biol Macromol 2019 Sep 2;137:528-536. Epub 2019 Jul 2.

Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address:

Emergence of multidrug-resistant bacteria is a major global concern. According to WHO, methicillin-resistant Staphylococcus aureus (MRSA) is a threatening pathogen resistant to a wide spectrum of antibiotics. Herein, to overcome drug resistance in MRSA, we successfully integrated traditional antibacterial methods but with a novel trick that included use of hen egg-white lysozyme's special aggregates generated by fibrillization. The minimum inhibitory concentration of oxacillin (Ox) for MRSA declined from 600 μM to <20 μM when using aggregates. Scanning and transition electron micrographs showed completely disrupted cells when treated with aggregated protein/Ox (20 μM). The assisting role of aggregates to induce antibiotic hypersensitivity was continuous and stable, but sub-inhibitory antibiotic concentration (20 μM) was required again after 8 h. Investigations regarding mechanism of antibiotic hypersensitivity revealed that aggregates were oligomers but not mature fibrils. Furthermore, reactive oxygen species levels rose significantly after treating bacteria with aggregated protein/Ox. Study of resistance mechanisms indicated that in response to wall structure alterations, mecA expression dropped significantly in the presence of aggregated protein/Ox (20 μM) relative to Ox (20 μM). This observation can be a breakthrough in finding alternatives where antibiotic dosage can be significantly reduced, thereby preventing emergence of new multidrug-resistant bacteria.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.001DOI Listing
September 2019

Novel cyanide electro-biodegradation using in aqueous solution.

J Environ Health Sci Eng 2018 Dec 21;16(2):99-108. Epub 2018 May 21.

1School of Mining, College of Engineering, University of Tehran, Tehran, Iran.

Background: Electro-biodegradation is a novel technique for cyanide degradation in aqueous solutions. Many physical, chemical, and biological methods have been developed and used to treat cyanide degradation. The biological methods are more environmentally-friendly and economically cost-effective when compared to other techniques, however, the process reaction time period is much longer and the efficiency is lower.

Methods: In this research, the bacterial strain, ATCC 7061, was tested for the first time to introduce the Cyanide Electro-biodegradation technique. By using a direct current power supply, electrons were generated in an electro-biodegradation cell containing culture media at free cyanide concentrations of 100 to 500 mg/l, under alkaline conditions.

Results: Experimental tests showed that when electrons were added and bacteria were inoculated into the aqueous media containing 100, 200, 300, 400 and 500 mg/l of free cyanide, the cyanide degradation efficiency increased from 16.2, 21.6, 29.5, 38.7 and 44.5% to 98.6, 99.3, 99.7, 99.8 and 99.7%, in 36, 72, 137, 233 and 301 h, respectively. The results show that by adding electrons, the process reaction time decreases and cyanide degradation efficiency increases significantly.

Conclusions: The results presented here demonstrate for the first time the importance and the significance of the electro-biodegradation technique in the efficient degradation and removal of cyanide present in aqueous solutions.
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http://dx.doi.org/10.1007/s40201-018-0289-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277327PMC
December 2018

Practical evaluation of 11 de novo assemblers in metagenome assembly.

J Microbiol Methods 2018 08 25;151:99-105. Epub 2018 Jun 25.

Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address:

Next Generation Sequencing (NGS) technologies are revolutionizing the field of biology and metagenomic-based research. Since the volume of metagenomic data is typically very large, De novo metagenomic assembly can be effectively used to reduce the total amount of data and enhance quality of downstream analysis, such as annotation and binning. Although, there are many freely available assemblers, but selecting one suitable for a specific goal can be highly challenging. In this study, the performance of 11 well-known assemblers was evaluated in the assembly of three different metagenomes. The results obtained show that metaSPAdes is the best assembler and Megahit is a good choice for conservative assembly strategy. In addition, this research provides useful information regarding the pros and cons of each assembler and the effect of read length on assembly, thereby helping scholars to select the optimal assembler based on their objectives.
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http://dx.doi.org/10.1016/j.mimet.2018.06.007DOI Listing
August 2018

Stability and Antimicrobial Activity of Nisin-Loaded Mesoporous Silica Nanoparticles: A Game-Changer in the War against Maleficent Microbes.

J Agric Food Chem 2018 Apr 11;66(16):4233-4243. Epub 2018 Apr 11.

Center for Nanomedicine and Theranostics, DTU Nanotech , Technical University of Denmark (DTU) , Ørsteds Plads , 2800 Kongens Lyngby , Denmark.

Antimicrobial agents, such as nisin, are used extensively in the food industry. Here, we investigated various approaches to load nisin onto mesoporous silica nanoparticles (MSNs, 92 ± 10 nm in diameter), to enhance its stability and sustained release. The morphology, size, and surface charge of the as-prepared nanoparticles were analyzed using scanning transmission electron microscopy, dynamic light scattering, and ζ potential measurement. Nisin was either physically adsorbed or covalently attached to the variously functionalized MSNs, with high loading capacities (>600 mg of nisin g of nanoparticles). The results of antibacterial activity analysis of nisin against Staphylococcus aureus showed that, despite the very low antibacterial activity of nisin covalently conjugated onto MSNs, the physical adsorption of nisin onto the unfunctionalized nanoparticles enhances its antimicrobial activities under various conditions, with no significant cytotoxicity effects on mouse fibroblast L929 cells. In conclusion, MSNs can be recommended as suitable carriers for nisin under various conditions.
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http://dx.doi.org/10.1021/acs.jafc.7b05492DOI Listing
April 2018

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

Expert Rev Clin Immunol 2017 12 23;13(12):1173-1188. Epub 2017 Oct 23.

a Chemical Injuries Research Center , Baqiyatallah University of Medical Sciences , Tehran , Iran.

Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.
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http://dx.doi.org/10.1080/1744666X.2017.1389646DOI Listing
December 2017

Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate.

Avicenna J Med Biotechnol 2015 Jul-Sep;7(3):113-20

Department of Biology, Payame-Noor University, Tehran, Iran.

Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli).

Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transformed by the encoding gene for FPPS (ispA) under the control of either the trc or P BAD promoters.

Results: Over-expression of ispA under the control of P BAD promoter led to a relative increase in CoQ 10 production only in recombinant E. coli Br although induction by arabinose resulted in partial reduction of CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains. Over-expression of ispA under the control of stronger trc promoter, however, led to a severe decrease in CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains, as reflected by reductions from 629±40 to 30±13 and 564±28 to 80±14 μg/g Dried Cell Weight (DCW), respectively. The results showed high level of FPP reduces endogenous CoQ 8 production as well and that CoQs are produced in a complimentary manner, as the increase in production of one decreases the production of the other.

Conclusion: The reduction in CoQ 10 production can be a result of Dds inhibition by high FPP concentration. Therefore, more effort is needed to verify the role of intermediate metabolite concentration and to optimize production of CoQ 10 .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508334PMC
August 2015

Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients.

Biochim Biophys Acta 2015 Oct 26;1851(10):1383-93. Epub 2015 Jul 26.

Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address:

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive inflammatory condition that has been linked to the dysregulation of many metabolic pathways including lipid biosynthesis. How lipid metabolism could affect disease progression in smokers with COPD remains unclear. We cross-examined the transcriptomics, proteomics, metabolomics, and phenomics data available on the public domain to elucidate the mechanisms by which lipid metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO) signaling network utilizing active/inactive, and functional/dysfunctional lipid-mediated signaling pathways to explore how lipid-metabolism could promote COPD pathogenesis in smokers. SpLiCO was further utilized to investigate signal amplifiers, distributers, propagators, feed-forward and/or -back loops that link COPD disease severity and hypoxia to disruption in the metabolism of sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations for dependency of molecules identified several important nodes in the network with modular regulatory and signal distribution activities. Our systems-based analyses indicate that arachidonic acid is a critical and early signal distributer that is upregulated by the sphingolipid signaling pathway in COPD, while hypoxia plays a critical role in the elevated dependency to glucose as a major energy source. Integration of SpLiCo and clinical data shows a strong association between hypoxia and the upregulation of sphingolipids in smokers with emphysema, vascular disease, hypertension and those with increased risk of lung cancer.
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http://dx.doi.org/10.1016/j.bbalip.2015.07.005DOI Listing
October 2015

Enzymatic production of biodiesel from microalgal oil using ethyl acetate as an acyl acceptor.

J Oleo Sci 2015 ;64(1):69-74

School of Chemical Engineering, College of Engineering, University of Tehran.

Microalgae have become an important source of biomass for biodiesel production. In enzymatic transesterification reaction, the enzyme activity is decreased in presence of alcohols. The use of different acyl acceptors such as methyl/ethyl acetate is suggested as an alternative and effective way to overcome this problem. In this study, ethyl acetate was used for the first time in the enzymatic production of biodiesel by using microalga, Chlorella vulgaris, as a triglyceride source. Enzymatic conversion of such fatty acids to biodiesel was catalyzed by Novozym 435 as an efficient immobilized lipase which is extensively used in biodiesel production. The best conversion yield of 66.71% was obtained at the ethyl acetate to oil molar ratio of 13:1 and Novozym 435 concentration of 40%, based on the amount of oil, and a time period of 72 h at 40℃. The results showed that ethyl acetate have no adverse effect on lipase activity and the biodiesel amount was not decreased even after seven transesterification cycles, so ethyl acetate has a great potential to be substituted for short-chain alcohols in transesterification reaction.
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http://dx.doi.org/10.5650/jos.ess14103DOI Listing
October 2015

Association of CTLA-4 gene 49A/G polymorphism with the incidence of type 1 diabetes mellitus in the Iranian Kurdish population.

Pak J Biol Sci 2013 Dec;16(24):1929-35

Kurdistan Diabetes Center, Tohid hospital, Sanandaj, Iran.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) has an inhibitory function on T cells and is critical for the induction of peripheral tolerance. CTLA-4 +49 G allele affects the CTLA-4 function and has been reported to be correlated with a higher risk of various autoimmune diseases including type 1 diabetes (T1D). The present study was conducted to investigate the association between the polymorphism of the CTLA-4 exon 1+49 A/G and susceptibility to TID and type 2 diabetes (T2D) in Kurds living in Iranian Kurdistan. The+49 A/G polymorphism was analyzed in 60 patients with T1D, 56 patients with T2D and 107 control subjects using PCR Single-strand Conformation Polymorphism (SSCP) and restriction fragment length polymorphism methods. All studied populations (T1D, T2D and Controls) were in Hardy-Weinberg equilibrium (p, 0.39, 0.94 and 0.89, respectively). Both+49 G allele (p = 0. 015, OR = 1.86) and +49 A/G genotype frequencies (p = 0. 012, OR = 2.31) were significantly higher in T1D patients than control. There was significant over-representation of the G allele in female T1D patients. No significant differences in +49 G allele and +49 A/G genotype frequencies were found between T2D and control subjects. SSCP analysis did not show new mutation in the amplified segment. The results of this study indicate that CTLA-4+49 A/G gene polymorphism confers genetic susceptibility to T1D but not T2D in the Kurdish population living in Iranian Kurdistan and women carrying the +49 G allele are at greater risk of getting T1D than men having the G allele.
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http://dx.doi.org/10.3923/pjbs.2013.1929.1935DOI Listing
December 2013

Characterization of a lipase from a newly isolated Pseudomonas sp.

Iran J Microbiol 2013 Dec;5(4):422-7

Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background And Objectives: Lipases are valuable biocatalysts which are widely used in the detergent, food, dairy and pharmaceutical industries. The aims of the present study included the isolation of a lipase-producer from industrial zones and the partial characterization of the enzyme.

Materials And Methods: A number of bacteria were isolated from sites related to the oil industries. An isolate forming a halo zone in a selective medium (TW agar) was then selected and grown on a medium suitable for the production of lipase. The isolate was subsequently identified by the 16S rRNA sequencing method, and its enzyme activity was measured by a spectrophotometer using pNPP as a substrate.

Results: The selected isolate was identified by the molecular method as Pseudomonas sp. Its extracellular lipase activity was 41.5 ± 1.4 U/ml, and the high affinity of this enzyme for the substrate was indicated by the kinetic parameters of Km and Vm, which were estimated by the the Lineweaver-Burk plot as 0.77 mM and 49.5 U/ml, respectively. Activation energy of lipase calculated from the Arrhenius plot was found to be 20.78 kJ/mol, and a temperature coefficient (Q10) of 4.39 indicated the high catalytic activity of the enzyme and the temperature dependence of the enzymatic reaction.

Conclusion: The results demonstrated that the indigenous isolate could have potential applications in many relevant industries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385172PMC
December 2013

Targeting acetate kinase: inhibitors as potential bacteriostatics.

J Microbiol Biotechnol 2013 Nov;23(11):1544-53

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Despite the importance of acetate kinase in the metabolism of bacteria, limited structural studies have been carried out on this enzyme. In this study, a three-dimensional structure of the Escherichia coli acetate kinase was constructed by use of molecular modeling methods. In the next stage, by considering the structure of the catalytic intermediate, trifluoroethanol (TFE) and trifluoroethyl butyrate were proposed as potential inhibitors of the enzyme. The putative binding mode of these compounds was studied with the use of a docking program, which revealed that they can fit well into the enzyme. To study the role of these potential enzyme inhibitors in the metabolic pathway of E. coli, their effects on the growth of this bacterium were studied. The results showed that growth was considerably reduced in the presence of these inhibitors. Changes in the profile of the metabolic products were studied by proton nuclear magnetic resonance spectroscopy. Remarkable changes were observed in the quantity of acetate, but other products were less altered. In this study, inhibition of growth by the two inhibitors as reflected by a change in the metabolism of E. coli suggests the potential use of these compounds (particularly TFE) as bacteriostatic agents.
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http://dx.doi.org/10.4014/jmb.1305.05026DOI Listing
November 2013

Apoptosis and reduced cell proliferation of HL-60 cell line caused by human telomerase reverse transcriptase inhibition by siRNA.

Acta Haematol 2010 14;124(2):72-8. Epub 2010 Jul 14.

Department of Hematology-Immunology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: The close correlation between telomerase activity and human telomerase reverse transcriptase (hTERT) expression has made hTERT to be considered as a selective molecular target for human cancer therapy. In this study, the ability of short-interfering RNA (siRNA) to downregulate hTERT expression and its correlation with cell growth and apoptosis in the promyelocytic cell line HL-60 was evaluated.

Materials And Methods: hTERT siRNA was designed and transfected to HL-60. hTERT mRNA expression, cell proliferation and apoptotic cells were measured.

Results And Conclusion: The results indicated that hTERT siRNA resulted in 97.2 ± 0.6% downregulation of the hTERT mRNA content; inhibition of the cell proliferation rate was about 52.8 ± 2.3% and the apoptotic index of cells was 30.5 ± 1.5%. hTERT plays an essential role in cell proliferation and control of the viability of leukemic cells, thus promising the development of drugs for leukemia.
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http://dx.doi.org/10.1159/000314960DOI Listing
October 2010

Mitochondrial tRNALeu/Lys and ATPase 6/8 gene variations in spinocerebellar ataxias.

Neurodegener Dis 2009 5;6(1-2):16-22. Epub 2008 Nov 5.

Research and Sciences Campus, Azad University, Tehran, Iran.

Background: The spinocerebellar ataxias (SCA) comprise a heterogeneous group of severe late-onset neurodegenerative diseases that are promoted by the expansion of a tandem-arrayed DNA sequence that modifies the primary structure of the protein.

Methods: Genomic DNA of 20 patients affected with SCAs was extracted from peripheral blood and screened for deletions in mitochondrial DNA (mtDNA). Sequencing of tRNA(Leu), tRNA(Lys), cytochrome oxidase II, ATPase 6/8 and NADH dehydrogenase I (NDI) genes belonging to mtDNA from patients with SCAs was also carried out to detect the presence of variations.

Results: We identified cytosine-adenine-guanine (CAG) trinucleotide repeat expansions in 20 patients. Seven of these patients had at least one nucleotide change in mtDNA. In such cases, 5 nucleotide variations resulted in amino acid changes with two novel variations T8256G and G9010A.

Conclusion: SCA patients showed high levels of mtDNA variations in lymphocytes. It can be proposed that the SCA gene proteins (Ataxins) are involved in the complicated intracellular mechanisms that affect cellular organelles and their components, such as the mitochondrial genome. The instability of CAG repeats in polyglutamine diseases such as SCAs and Huntington's disease might be a causative factor in mtDNA variation or possible damage.
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http://dx.doi.org/10.1159/000170885DOI Listing
February 2009

Variation of DAT1 VNTR alleles and genotypes among old ethnic groups in Mesopotamia to the Oxus region.

Hum Biol 2008 Feb;80(1):73-81

Medical Genetic Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Variation of a VNTR in the DAT1 gene in seven ethnic groups of the Middle East was used to infer the history and affinities of these groups. The populations consisted of Assyrian, Jewish, Zoroastrian, Armenian, Turkmen, and Arab peoples of Iran, Iraq, and Kuwait. Three hundred forty subjects from these seven ethnic groups were screened for DAT1. DAT1 VNTR genotyping showed 3, 6, 7, 8, 9, 10, 11, and 12 alleles in the samples. Analysis of these data revealed differentiation and relationship among the populations. In this region, which covers an area of 2-2.5 million km2, the influence of geography and especially of linguistic characteristics has had potentially major effects on differentiation. Religion also has played a major role in imposing restrictions on some ethnic groups, who as a consequence have maintained their community. Overall, these ethnic groups showed greater heterogeneity compared to other populations.
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http://dx.doi.org/10.3378/1534-6617(2008)80[73:VODVAA]2.0.CO;2DOI Listing
February 2008

Investigation of tRNA(Leu/Lys) and ATPase 6 genes mutations in Huntington's disease.

Cell Mol Neurobiol 2008 Nov 2;28(7):933-8. Epub 2008 Apr 2.

Science & Research Unit, Azad University, Tehran, Iran.

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats which code for glutamine in the HD gene product, huntingtin. Huntingtin is expressed in almost all tissues, so abnormalities outside the brain can also be expected. Involvement of nuclei and mitochondria in HD pathophysiology has been suggested. In fact mitochondrial dysfunction is reported in brains of patients suffering from HD. The tRNA gene mutations are one of hot spots that can cause mitochondrial disorders. In this study, possible mitochondrial DNA (mtDNA) damage was evaluated by screening for mutations in the tRNA(leu/lys) and ATPase 6 genes of 20 patients with HD, using PCR and automated DNA sequencing. Mutations including an A8656G mutation in one patient were observed, which may be causal to the disease. Understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could potentially be important for the development of therapeutic strategies in HD.
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http://dx.doi.org/10.1007/s10571-008-9261-6DOI Listing
November 2008

Huntington's disease and mitochondrial DNA deletions: event or regular mechanism for mutant huntingtin protein and CAG repeats expansion?!

Cell Mol Neurobiol 2007 Nov 20;27(7):867-75. Epub 2007 Oct 20.

Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, PO Box 14155-6343, Tehran, Iran.

The mitochondrial DNA (mtDNA) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as Huntington's disease (HD). Research studies were conducted to determine the possible levels of mitochondrial defect (deletion) in HD patients and consideration of interaction between the expanded Huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. To determine mtDNA damage, we investigated deletions based in four areas of mitochondrial DNA, in a group of 60 Iranian patients clinically diagnosed with HD and 70 healthy controls. A total of 41 patients out of 60 had CAG expansion (group A). About 19 patients did not show expansion but had the clinical symptoms of HD (group B). MtDNA deletions were classified into four groups according to size; 9 kb, 7.5 kb, 7 kb, and 5 kb. We found one of the four-mtDNA deletions in at least 90% of samples. Multiple deletions have also been observed in 63% of HD patients. None of the normal control (group C) showed mtDNA deletions. The sizes or locations of the deletions did not show a clear correlation with expanded CAG repeat and age in our samples. The study presented evidence that HD patients had higher frequencies of mtDNA deletions in lymphocytes in comparison to the controls. It is thus proposed that CAG repeats instability and mutant Htt are causative factor in mtDNA damage.
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http://dx.doi.org/10.1007/s10571-007-9206-5DOI Listing
November 2007