imagine (Institute of molecular genetics and genetic engineering)
Not a member yet
3088 research outputs found
Sort by
Present and future of next-generation sequencing application for rare diseases
Get PDFSvaka bolest čija je učestalost manja od 1 u 2000 ljudi definiše se kao retka bolest. Iz tog razloga, broj retkih
bolesti je veliki. Do sada je opisano preko 6000 različitih retkih bolesti. Preko 80% retkih bolesti ima genetičku
osnovu i to je razlog zašto su znanja iz molekularne biologije od neprocenjivog značaja za
istraživanje molekularne osnove retkih bolesti, postavljanje tačne dijagnoze i razvoj inovativnih terapeutika.
Cilj ovog rada je da objasni važnost otkrivanja molekularno-genetičke osnove retkih bolesti i da prikaže
desetogodišnje iskustvo primene sekvenciranja nove generacije u Srbiji (2014.-2023.) u tu svrhu. U
prethodnom periodu za istraživanje retkih bolesti korišćeni su sekvenciranje kliničkog egzoma, sekvenciranje
kompletnog egzoma i sekvenciranje kompletnog genoma. Takođe, date su i perspektive za budućnost
gde će genomika biti kompletirana tehnologijom sekvenciranja dugačkih fragmenata i
komplementirana upotrebom transkriptomike, proteomike, metabolomike i drugih „omika“.Any disease found in less than 1 person out of 2000 people is defined as a rare disease. For this reason, the
number of rare diseases is high. Over 6,000 different rare diseases have been described so far. More than
80% of rare diseases have a genetic basis, and this is the reason why knowledge of molecular biology is invaluable
for research into the molecular basis of rare diseases, establishing an accurate diagnosis and developing
innovative therapeutics. The aim of this paper is to explain the importance of discovering the
molecular genetic basis of rare diseases and to present the ten-year experience of applying new generation
sequencing in Serbia (2014-2023) for this purpose. During this period, clinical exome sequencing,
complete exome sequencing and complete genome sequencing were used for research of rare diseases.
In the future, it is expected that genomics, which until now was based mainly on the technology of shortread
fragments, will be broaden with the long-reads sequencing technology, and complemented by the
use of transcriptomics, proteomics, metabolomics and other omics.Rad je rezultat naučne aktivnosti Centra za genetičku dijagnostiku
retkih bolesti IMGGI
Structure, function and regulation of aquaporin gene expression during drought in plants
Get PDFPovećanje prosečnih godišnjih temperatura iz godine u godinu za posledicu ostavlja sve izraženije sušne
sezone. Suša nepovoljno utiče na rastenje i razviće biljaka, uzrokujući velike ekonomske gubitke na globalnom
nivou. Efekti suše ispoljavaju se kako na morfološkom, tako i na fiziološkom, biohemijskom i molekularnom
nivou organizacije biljaka. Izlaganje biljaka suši narušava normalan transport vode kroz ćelije
što se odražava i na zastupljenost i funkciju kanala za vodu – akvaporina, na membranama. Akvaporini su
transmembranski proteini koji formiraju kanale za prolazak vode i drugih molekula kroz ćelijske membrane.
Ispoljavaju veoma značajnu ulogu u prilagođavanju protoka vode kroz ćelije shodno fiziološkom stanju.
S obzirom na to, poslednjih godina velika pažnja posvećena je ulozi akvaporina pri odgovorima biljaka
na dejstvo suše i drugih abiotičkih stresogenih faktora koji utiču na narušavanje vodnog režima biljaka.
Istraživanja su usmerena ka praćenju promena u ekspresiji gena za akvaporine, zastupljenosti akvaporina
na membranama i uticaju na usvajanje, transport i odavanje vode u atmosferu. U ovom radu predstavljene
su analize strukture i regulacije ekspresije gena za akvaporine, kao i naučna istraživanja u proteklih
deset godina o promenama u ekspresiji gena za akvaporine kod biljaka izlaganih suši. Poseban akcenat
stavljen je na rezultate bioinformatičkih analiza akvaporina kod hortikulturne vrste Impatiens walleriana,
i njihovu ekspresiju pri suši i rehidrataciji.The increase in average annual temperatures from year to year results in pronounced dry seasons. Drought
adversely affects the plants growth and development, causing large economic losses on a global scale.
The effects of drought are manifested both at the plant morphological, as well at the physiological, biochemical
and molecular levels. Exposure of plants to drought disrupts the normal water transport through
the cells, which is reflected in the presence and function of water channels - aquaporins, on the membranes.
Aquaporins are transmembrane proteins that form channels for the water, and other molecules
flow through cell membranes. They play a very important role in adjusting the water flow through the
cells according to the physiological state. In view of this, in recent years much attention has been paid to
the role of aquaporins in plant responses to drought and other abiotic stress factors, which affect the disruption
of the water regime of plants. Researches are aimed at monitoring changes in the expression of
genes for aquaporins, the presence of aquaporins on membranes and the influence on the absorption,
transport and release of water into the atmosphere. This paper presents analyzes of the structure and regulation
of aquaporin gene expression, as well as scientific research over the past ten years on changes in
aquaporin gene expression in plants exposed to drought. Special emphasis was placed on the results of
bioinformatic analyzes of aquaporins in the horticultural species Impatiens walleriana, and their expression
during drought and rehydration
Identification of AGP genes of plants using machine learning methods
Get PDFArabinogalaktanski proteini (AGP) su ekstenzivno glikozilovani proteini ćelijskog zida koje karakteriše velika
raznolikost primarne strukture i širok spektar uloga tokom rastenja i razvića biljaka. Identifikacija sekvenci
koje kodiraju ove proteine na osnovu homologije otežava činjenica da su to proteini sa neuređenom
strukturom (engl. „intrinsically disordered proteins“). Da bi se poboljšao način za identifikaciju i analizu sekvenci
AGP u cilju daljeg ispitivanja ekspresije ovih gena u različitim eksperimentalnim uslovima, primenjen
je pristup koji koristi upravo neuređenost ovih proteina, tj. prisustvo nekarakteristične aminokiseline
hidroksiprolina. Model za predviđanje verovatnoće hidroksilacije prolina na osnovu lokalne sekvence proteina
inkorporiran je u ragp R paket uz brojne druge alate koji omogućavaju analize proteinskih sekvenci.Arabinogalactan proteins (AGPs) are extensively glycosylated cell wall proteins characterised by high diversity
of primary structure and a wide array of functions in plant growth and development. AGPs are intrinsically
disordered proteins, which hinders their homology-based identification. To improve the
methodology for identification and analysis of hydroxyproline-rich glycoprotein (HRGP) sequences for further
monitoring of AGP expression under different experimental conditions, a new approach was developed
using the main feature of HRGPs, the presence of the uncharacteristic amino acid hydroxyproline. A
model for predicting the hydroxylation probability of proline based on the local protein sequence has
been incorporated into the R package the ragp, together with a number of diverse tools that allow the
analysis of protein sequences
Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај
Get PDFIntroduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor.Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе
Probiotički potencijal sojeva Enterococcus faecium izolovanih iz mlečnih proizvoda sa područja Zapadnog Balkana
Get PDFOne of the major genera of the lactic acid bacteria family, Enterococcus sp., has a controversial status, reflected in the fact that enterococci are utilized as starter cultures and probiotics, in addition to being known to cause nosocomial infections. The qualified presumption of the safety list and the widely acknowledged safe status for Enterococcus species are absent. Rich sources of Enterococcus faecium species with possible probiotic characteristics can be found in artisanal dairy products, typically made from raw milk. To further understand the probiotic potential and health-promoting effects, this study looked at the presence of virulence factors and adhesion properties of En. faecium isolated from artisanal dairy products from Western Balkan countries
Efekat imunostimulišućeg soja roda Limosilactobacillus kod pacova sa kolitisom izazvanim trinitrobenzensulfonatom (TNBS)
Get PDFThe aim of the study was to test the potential of immunostimulating Limosilactobacillus fermentum BGHI14 strain to reduce the damage of colon tissue in rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Wistar rats were treated with L. fermentum BGHI14 in the regime of preventive, therapeutic and continuous treatment 22 days prior to and/or 7 days after the administration of TNBS. After sacrifice, the colon tissue samples were taken for RNA isolation, gene expression analysis, histopathological analysis, and malondialdehyde measurement. Judging from the body weights, histopathological scores, malondialdehyde levels and transcription of IL-1β and Tight junction protein 1 (Tjp-1) coding genes, preventive and therapeutic treatment proved to be the most protective in the applied conditions. On the other hand, continuous treatment did not affect the intensity of tissue damage. Considering these results, we discussed the possible mechanisms which might stand behind the protective action of immunostimulating probiotic bacteria in the case of mucosal barrier damage.Cilj ovog istraživanja je bio da se ispita potencijal imunostimulišućeg soja Limosilactobacillus fermentumBGHI14 da smanji oštećenje tkiva debelog creva kod pacova sa kolitisom izazvanim 2,4,6-trinitrobenzensulfonskom kiselinom (TNBS). Pacovi Wistar soja su tretirani sojem L. fermentumBGHI14 u režimu preventivnog, terapijskog i kontinuiranog tretmana 22 dana pre i/ili 7 dana nakon primene TNBS. Nakon žrtvovanja, uzorci debelog creva su sakupljeni za izolaciju RNK, analizu ekspresije gena, histopatološke analize i merenje malondialdehida. Na osnovu telesnih težina pacova, histopatološih rezultata, nivoa malondialdehida i transkripcije IL-1β citokina i proteina tesnih međućelijskih veza (Tjp-1), preventivni i terapijski tretman su se pokazali kao najefikasniji u primenjenim uslovima. S druge strane, kontinuirano lečenje nije uticalo na intenzitet oštećenja tkiva. Uzimajući u obzir ove rezultate, razmotreni su mogući mehanizmi koji stoje iza zaštitnog delovanja imunostimulišućih probiotičkih bakterija u slučaju oštećenja mukozne barijere
Essential oil of Origanum minutiflorum exhibits anti-inflammatory and antioxidative effects in human bronchial cells and antimicrobial activity on lung pathogens
No full textIntroductionOregano essential oil (OEO) is one of the most widely used essential oils worldwide due to its huge therapeutic benefits. Nevertheless, data on the effects of the endemic species Origanum minutiflorum, also known as wild or Turkish oregano, is scarce. On the other hand, various chronic lung diseases, characterised by persistent inflammation, oxidative stress, and common bacterial infections, do not have effective pharmacological therapy. Hence, the aim of this study is to examine the effects of wild oregano essential oil (WOEO) on human bronchial epithelial cells and lung pathogens.MethodsWe provided a detailed chemical composition of WOEO using GC-MS and GC-FID analysis. Anti-inflammatory effects of WOEO were analysed using the qRT-PCR and ELISA methods, while antioxidative properties were examined by using the dichlorofluorescein assay in BEAS-2B cells. Antibacterial activity was tested on lung pathogens by using the agar diffusion assay.ResultsThe major constituents of WOEO, analysed in this study, were carvacrol, linalool, p-cymene, γ-terpinene, and (E)-caryophyllene. We found that treatment with WOEO attenuated LPS-induced IL8 gene expression and hydrogen peroxide-induced oxidative stress in BEAS-2B cells. Moreover, WOEO showed an inhibitory effect on pathogenic bacteria Acinetobacter baumannii and highly resistant Klebsiella pneumoniae commonly seen in healthcare-associated pneumonia.ConclusionOur work presents new insights into the anti-inflammatory, antioxidative, and antimicrobial properties of WOEO which may be used as a simple and local treatment in various chronic lung diseases
Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches
No full textAcute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it’s used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML
Evaluation of Post-Larval Diets for Indoor Weaned Largemouth Bass (Micropterus salmoides)
Get PDFThis study aimed to evaluate different commercial diets (Otohime C1, Aller Futura (AF), Biomar Inicio Plus (BIP)) and one experimental feed (EF) in terms of their effectiveness as post-larval diets for indoor weaned largemouth bass, LMB (Micropterus salmoides). Key variations in the content of nutritive values were monounsaturated fatty acid (MUFA) and highly unsaturated FA (HUFA) ω3. Fish were fed with one of four tested diets from the 33rd to the 40th day post-hatch (DPH). Biometric indices, digestive enzyme-specific activities, thyroid hormone status, and mRNA expression of genes coding for skeleton, neuron, and muscle growth were analyzed. The lowest skeletal deformity rate and highest survival among the treatments were seen in BIP-fed fish. Dietary lipids, with an appropriate balance between MUFA and polyunsaturated FA (PUFA), alongside amino acid balance, were shown to be the main contributors to the growth of the skeleton and/or fish survival. On the other hand, fish growth is correlated with fish digestive capacity and feed moisture percent rather than feed quality. Unexpectedly, BIP-fed fish were attributed with the lowest expression of skeleton differentiation markers, which may reflect the sacrifice of scale and/or cranium growth at the expense of somatic growth. This study highlights the role of non-marine ingredients in the nutrition of post-larval LMB.Preanalyzed data:[https://imagine.imgge.bg.ac.rs/handle/123456789/2764
Precision medicine and COVID-19: Importance of host genome profiling
Get PDFIntroduction: The clinical picture and the course of the disease in COVID-19 patients, caused by coronavirus SARS-CoV-2, vary from asymptomatic to fatal outcome. As the same agent cause the disease, the
individual genomic profile of the patient could contribute to better understanding of this phenomenon.
The current knowledge about genetic markers responsible for a wide range of clinical pictures, as well
as possible application of individualized treatment, will be presented.
Methods: Variantsin genesresponsible for predisposition and response to SARS-CoV-2 infection, pharmacogenetic variantsrelated to drugs used in the treatment of COVID-19, nutrigenetic markersin genes
relevant for the metabolism of the micronutrients(vitamin D,selenium and zinc) were investigated using
GWAS, PCR and sequencing. Genotype data were extracted from database previously obtained using
TruSight One Gene Panel (Illumina).
Results: Eleven pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment and
10 variants affecting the structure and/or function of proteinsimportant forsusceptibility and resistance
to SARS-CoV-2 infection were identified. Several variants in genes related to micronutrients were associated with severe COVID-19. Moreover, GWAS detected a significant genetic signal associated with
COVID-19 related pneumonia.
Conclusion: Multidisciplinary approach, modern sequencing technologies, comprehensive studies with
well-characterized patients’groups, as well as the design of robust bioinformatics tools, enable identification of novel human genetic markers associated with COVID-19. Newly gained knowledge will empower the development of the targeted therapy, as well as the implementation of
nutrigenomics/pharmacogenomics, leading to the application of precision medicine in the treatment of
COVID-19 patients