Genetics & Applications https://genapp.ba/editions/index.php/journal <p><strong>Genetics &amp; Applications</strong> (G&amp;A) is the official journal of the Institute for Genetic Engineering and Biotechnology (<a title="INGEB" href="http://www.ingeb.unsa.ba" target="_blank" rel="noopener">www.ingeb.unsa.ba</a>), University of Sarajevo (<a href="http://www.unsa.ba/">http://www.unsa.ba/</a>). It is envisaged as an open access international journal issued twice a year in print and electronic (online) format, publishing peer-reviewed articles of novel and significant discoveries in the fields of basic and applied genetics. Special issues or supplements may also be produced from time to time upon agreement with the Editorial Board.</p> <p>Topics covered within Genetics and Applications (G&amp;A) include: </p> <p>Molecular genetics, Cytogenetics, Plant genetics, Animal genetics, Human genetics, Medical genetics, Forensic genetics, Population and evolutionary genetics, Conservation genetics, Genomics and functional genomics, Genetic engineering and biotechnology and Bioinformatics.</p> <p>Authors are encouraged to submit complete, unpublished, original works that are not under review in any other journals. Acceptable papers are those that gather and disseminate fundamental knowledge in all areas of genetics.</p> Institute for Genetic Engineering and Biotechnology, University of Sarajevo en-US Genetics & Applications 2566-2937 <p><a href="http://creativecommons.org/licenses/by-sa/4.0/" rel="license"><img style="border-width: 0;" src="https://i.creativecommons.org/l/by-sa/4.0/88x31.png" alt="Creative Commons License" /></a><br />This work is licensed under a <a href="http://creativecommons.org/licenses/by-sa/4.0/" rel="license">Creative Commons Attribution-ShareAlike 4.0 International License</a>.</p> <p><sup>©</sup>Genetics &amp; Applications, The Official Publication of the Institute for Genetic Engineering and Biotechnology, University of Sarajevo</p> The Mitochondrial landscape of the Konjuh and Majevica mountains of northeastern Bosnia: The view in the context genetic and demographic history https://genapp.ba/editions/index.php/journal/article/view/148 <p>This study is the first report on the mtDNA profile of human settlements of the Konjuh and Majevica mountains of northeastern Bosnia. The aims of this study were: a) determination of mitochondrial genetic structure of populations of the Konjuh and Majevica mountains of northeastern Bosnia; b) detection of trace of ancient of mtDNA variations; and c) assessment of genetic relations with other Bosnian and Herzegovina populations and neighboring populations from the Balkan region. The genetic structure of populations of Konjuh and Majevica is shaped by western Eurasian maternal signals, which may trace their ancestry to the Paleolithic, pre-Neolithic and Neolithic. Especially interesting is the feature of the Neolithic expansion in this area. This applies especially to the presence of the pre-Neolithic lineages HV*and N1a in northeastern Bosnia, which can indicate an early settlement of this region of Bosnia by pre-Neolithic populations from the Middle East. This region abounds with resources of salt sites, which might suggest in favor of the thesis that the early-Neolithic colonists needed a safe source of salts so as to settle in the Balkan area. The populations of mountains of northeastern Bosnia indicate elements of the local population history, but they do not show strict genetic closure in relation to the neighboring populations of the Balkans. This may be a consequence of the population size, degree of geographic isolation and events of migration.</p> Irma Mujkić Adisa Ahmić Lejla Lasić Emir Halilović Alen Ismailović Naris Pojskić Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-05 2022-12-05 6 2 18 30 10.31383/ga.vol6iss2ga02 In silico prediction of the inhibitory effect of phytochemical components extracted from Knautia sarajevensis on the main protease of SARS-CoV-2 virus https://genapp.ba/editions/index.php/journal/article/view/152 <p>Essential role in replication and transcription of coronavirus makes the main protease of SARS-CoV-2 a great traget for drug design. The aim of this study was to predict structural interactions of compounds isolated from the Bosnian-Herzegovinian endemic plant <em>Knautia sarajevensis</em> (G. Beck) Szabó against the 3CLpro of SARS-CoV-2 virus. The three-dimensional crystal structure of SARS-CoV-2 main protease was retrieved from the RCSB Protein Data Bank and the three-dimensional structures of isolated compounds were obtained from the PubChem database. Active site was predicted using PrankWeb, while the preparation of protease and compounds was performed using AutoDock Tools and OpenBabel. Molecular docking was carried out using AutoDock Vina. Structural interactions are visualised and analyzed using PyMOL, LigPlus and UCSF Chimera. Apigenin, kaempferol, myricetin and quercetin showed the highest binding affinity for SARS-CoV-2 main protease and formed significant hydrogen bonds with the given protein. Results obtained in this study are in accordance with previous studies and showed that these compounds could potentially have antiviral effects against SARS-CoV-2. These findings indicate that <em>K. sarajevensis</em> could be potentially utilized as an adjuvant in the treatment of coronavirus disease 2019, but further pharmacological studies are required in order to prove the potential medicinal use of the plant.</p> Tarik Corbo Merima Miralem Abdurahim Kalajdzic Naris Pojskic Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-06 2022-12-06 6 2 31 40 10.31383/ga.vol6iss2ga03 Investigation of the Relationship between IL-6, IL-6R and CXCL5 Polymorphisms and Obesity in Denizli Province of Turkey https://genapp.ba/editions/index.php/journal/article/view/150 <p>Obesity and its effects on increasing morbidity and mortality have reached the level of an epidemic with a high frequency in modern populations. <em>IL-6</em> released from adipose tissue is known to trigger the chronic inflammation in obesity. <em>CXCL5</em>, which mediates the activation and migration of neutrophils, has been found at high levels in obese subjects. In our study, we aimed to investigate the possible effects of <em>IL-6</em>, <em>IL-6R</em> and <em>CXCL5</em>, polymorphisms and haplotypes on the development of obesity. We studied <em>IL-6</em>, rs2069827 (-1363, G/T), rs1800797 (-597, G/A), rs1800796 (-572, G/C) and rs1800795 (-174, G/C), <em>IL-6R</em> rs4845617 (-183, G/A), rs2228145 (+48892, A/C) and <em>CXCL5</em> rs352046 (-156, G/C) polymorphic sites in 60 obesity patients and 59 healthy controls. For genotyping we used PCR-RFLP based approach. The <em>IL-6 </em>rs1800796, rs1800795 and <em>IL-6R</em> rs4845617 G allelles could be the possible genetic factors responsible for obesity. We found similar results in female obese group. The results indicated that there was no association between obesity and other SNPs (rs2069827, rs1800797, and rs1800795 and rs2228145) and <em>CXCL5</em>, rs352046. The results of <em>IL-6</em> and <em>IL-6R</em> haplotype analysis by global differentiation test showed that haplotypes may have different distributions between obese and controls. Our results showed that polymorphisms and possible haplotypes in <em>IL-6</em> and <em>IL-6R</em> genes, which have an important role in inflammation, may affect the development of obesity. This study points out the necessity of investigating the possible effects of gene polymorphisms of other cytokines and their receptors in the development of obesity in larger populations.</p> Sanem Arikan Kerime Demirel Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-07 2022-12-07 6 2 41 50 10.31383/ga.vol6iss2ga04 In vivo cytogenotoxicity testing of isotretinoin by the micronucleus assay in the blood of male Sprague-Dawley rats Isotretinoin is cytotoxic and genotoxic https://genapp.ba/editions/index.php/journal/article/view/151 <p>Isotretinoin (ISO), one of vitamin A-derived retinoids, is comparatively the most widely prescribed drug in acne vulgaris pathogenesis. Despite its excellent therapeutic success, the systemic use of this drug showed undesirable serious side effects such as teratogenesis, oxidative stress, and genotoxicity. The uses of retinoids in cancer therapy are limited due to severe adverse reactions. This has led the scientific community to ask for further studies qualifying ISO features and comparing their efficacy and safety. The purpose of this study was to evaluate the cytogenotoxicity of multiple oral doses (5, 10, 15, and 20 mg/kg, daily for seven consecutive days) of ISO in male Sprague-Dawley rats. The micronucleus assay was used to investigate genotoxicity biomarkers such as the percentage of micronucleated polychromatic erythrocytes (%MNPCEs) and the percentage of aberrant cells (%Abc). Another goal was to test the cytotoxicity of the drug by measuring the ratio between PCEs and normochromatic erythrocytes (NCEs) (PCEs/NCEs). In comparison with the control, the three cytogenetic endpoints: %MNPCEs, P/N, and %Abc significantly (P ≤ 0.0017) dose-dependent increase. This suggested genotoxicity and cytotoxicity of the tested ISO doses. Therefore, the therapeutic uses of ISO should be restricted to a very narrow range border. Further studies are needed to shed more light on the safety profile of ISO therapy.</p> Ahmad Khalil Hasan Abo Siam Mai Daradkeh Amneh Alrabie Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-08 2022-12-08 6 2 51 60 10.31383/ga.vol6iss2ga05 Preliminary assessment of genetic gain through the selection of different pedunculate oak populations in provenance test https://genapp.ba/editions/index.php/journal/article/view/154 <p>The distribution of pedunculate oak in Bosnia and Herzegovina is important in connecting the southern and eastern provenances of the Balkan Peninsula with provenances from Central Europe. However, due to over-exploitation, pedunculate oak is almost extinct in Bosnia and Herzegovina. This research aims to determine the heredity and production potential of the pedunculate oak from 28 provenances in the Bosnian-Herzegovinian provenance test through the genetic gain of thickness and height growth. The results will be used in selection of best provenances in terms of genetic gain. For this research, height and root collar diameter of pedunculate oak plants in Bosnian-Herzegovinian provenance tests were measured in 2012, 2016 and 2020. The provenance test was established in 2009. It contains 28 provenances from Bosnia and Herzegovina. Heredity and selection differential were assessed using analysis of variance. Possible genetic gain if using five best and one best provenance were determined. The results of the genetic gain for height obtained using data from 2012 and 2020 were low. The results obtained for 2016 indicate that the genetic gain for height, using five best provenances would be 7.62%, and using the best provenance 9.98%. Results of the genetic gain for root collar diameter obtained for 2016 and 2020 were low. For 2012, the genetic improvement using five best provenances would be 4.28%, and using the best provenance 6.32%. The results indicate that by selecting the best provenances of pedunculate oak and their propagation, we can achieve a significant increase in plant height and thickness, i.e., the yield of wood mass. As research concerns juvenile material, it is necessary to continue systematic monitoring, to determine the actual heredity and genetic age, when the trees reach their physiological maturity, and when the annual value oscillations become uniform.</p> Dalibor Ballian Mirzeta Memišević Hodžić Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-14 2022-12-14 6 2 61 69 10.31383/ga.vol6iss2ga06 Analysis of cytogenetic aberrations in a bone marrow of patients with malignant head and neck lymphadenopathies - A single center experience https://genapp.ba/editions/index.php/journal/article/view/157 <p>Cytogenetic testing plays a major role in the diagnosis of different types of lymphadenopathies, assessment of survival prognosis, but also in the selection of adequate therapeutic strategies. Reports on aggressive head and neck lymphomas combining (cyto)genetics with pathology are rare, also lacking in Bosnia and Herzegovina. The aim of this retrospective study was to provide all chromosome aberrations data recorded in the group of patients diagnosed with malignant head and neck lymphadenopathy, and to analyze advantages and disadvantages of bone marrow (BM) cytogenetics analysis. Out of 819 patients who underwent cytogenetic analysis of BM in five years’ time spread, chromosomal abnormalities were analysed in 54 karyotypes of patients with clinically suspected head and neck lymphadenopathy. We recorded 66,6% Non-Hodgkin lymphoma, 26% Hodgkin lymphoma, 3,7% Acute lymphoblastic leukemia and 3,7% Chronic lymphocytic leukemia. Chromosomal abnormalities in the karyotype were detected in 32 (59.2%) of a total of 54 patients. A normal karyotype was observed in 14 (26%) patients. In 8 (14.8%) subjects, it was not possible to perform cytogenetic analysis. The results of this research are representative in a term of the karyotype characteristics of patients with head and neck lymphoma. This is the first work of its kind in Bosnia and Herzegovina and will continue through a multicenter study in order to characterise the diagnostic and prognostic significance of cytogenetic abnormalities in lymphoma patients.</p> Semir Mešanović Amila Krašić Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-15 2022-12-15 6 2 70 78 10.31383/ga.vol6iss2ga07 RNA Sequencing indicates gene expression changes in Silene sendtneri seeds after seed priming with silicic acid https://genapp.ba/editions/index.php/journal/article/view/160 <p>To improve our understanding of the molecular mechanisms underlaying seed priming, RNA transcriptome analysis was performed using primed and non-primed seeds of <em>Silene sendtneri</em>. Seed priming was performed by submergence in 1% silicic acid for 24h at 4°C, followed by rinsing with sterilised water and desiccation to original moisture content. <em>Silene sendtneri</em> is a species with no sequenced genome and annotation of <em>de novo</em> assembly of transcriptome was done against several species. Gene ontology (GO) analysis indicated that genes related to heavy metal transporters and heat shock proteins are differentially expressed after priming with silicic acid. Within these gene categories, genes such as heavy metal-associated isoprenylated plant protein 26-like (log2fold -8.79) were downregulated, while others such as heavy metal ATPase 5 (log2fold 6.46), heat shock factor protein HSF30-like isoform X1 (log2fold 5.98) were upregulated.</p> Erna Karalija Arnela Demir Jelena Samardžić Adisa Parić Sabina Dahija Felice Contaldi Federico Martinelli Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-20 2022-12-20 6 2 79 88 10.31383/ga.vol6iss2ga08 CRISPR/Cas9-mediated targeted mutagenesis of FAD2-1 gene for oleic acids composition in sunflower https://genapp.ba/editions/index.php/journal/article/view/159 <p>Sunflower (<em>Helianthus annuus</em> L.) is the most widespread plant used for production of oil among all oilseeds cultivated in Turkey in terms of agricultural area and production. Sunflower with high oleic acid content is always desirable because of benefits on health and industrial use. The enzyme <em>FAD2-1</em> catalyzes the conversion of oleic acid to linoleic acid in sunflower. The fatty acid composition can be enhanced by gene editing of <em>FAD2-1</em> gene by CRISPR/Cas9 technique which has been applied recently as a new breeding technique to improve productivity and enhance sustainability in agriculture. Hence, CRISPR/Cas9 genome editing systems were utilized to knockout the <em>FAD2-1</em> gene in order to increase production of oleic acid content. For this purpose, two low oleic sunflower genotypes were transformed with two sgRNA that target <em>FAD2-1</em> gene. sgRNA expression cassettes were assembled into the binary vector by Golden Gate assembly in a single reaction which is followed by <em>A. tumefaciens</em>-mediated transformation and <em>in vitro</em> germination. Putatively transformed shoots were selected with <em>A. tumefaciens</em>-mediated the optimized kanamycin concentration (100 mg/L) in the medium. The challenges of transformation of sunflower were summarized and possible solutions were proposed. This study indicated that sunflower still can be modified by CRISPR/Cas9 genome editing system to develop high oleic sunflower.</p> Yagmur Zeynep Uslu Buse Nur Ural Nicat Cebrailoglu Yildiz Aydın Yelda Ozden Ciftci Ahu Altinkut Uncuoglu Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-12-21 2022-12-21 6 2 89 102 10.31383/ga.vol6iss2ga09 Overview of current approaches in cancer immunotherapy and personalized opportunities for future aspect https://genapp.ba/editions/index.php/journal/article/view/149 <p>Cancer refers to a group of diseases characterized by a rapid and uncontrolled proliferation of cells in the body after undergoing a series of structural variations. Non-specific methods such as surgery, radiotherapy, and chemotherapy are used widely in cancer treatment. Recently, there is a special focus on specific methods such as immunotherapy that targets certain parts of the patient’s immune system. New treatment options are needed in this respect because nonspecific methods are insufficient in curing the disease, do not increase patient's survival, and healthy cells are damaged as well as cancer cells. Immunotherapy has less toxicity, fewer side effects during treatment, and is a patient-specific individualized treatment modality. Due to the fact that human tumors occur with a combination of genetic and epigenetic changes, cancer cells manage to recognize immunity and escape subsequent destruction. The main goal of cancer immunotherapy is to reactivate the immune system to neutralize tumor cells. Immunotherapy has many advantages such as preventing the side effects of chemotherapy/radiotherapy, avoiding metastases, and targeting cancer stem cells. The main treatment methods used in cancer immunotherapy, are cancer vaccines, adoptive cell therapy, cytokines, and monoclonal antibodies. In this review, we outline some of the main strategies in cancer immunotherapy and discuss the progress in personalized cancer therapy.</p> Ceyda Durmaz Berrin Erdag Copyright (c) 2022 Genetics & Applications https://creativecommons.org/licenses/by-nc-sa/4.0 2022-11-30 2022-11-30 6 2 1 17 10.31383/ga.vol6iss2ga01