Analiza polimorfizama gena za APOE, BDNF, BCHE i KIBRA i njihova korelacija sa memorijskim sposobnostima u populaciji studenata

Memorija predstavlja sposobnost privremenog ili trajnog skladi[tenja i priyivanja informacija ste;enih iskustvom ili aktivnim u;enjem i ima multifaktorsku osnovu...Human memory represents the capability of temporary or permanent storage and retrieval of information..

Influence of methylenetetrahydrofolate reductase gene polymorphism C677T on the risk of recurrent spontaneous abortions

Introduction: Spontaneous abortion (SA) is a frequent obstetric complication. Up to 15% of pregnancies end by spontaneous abortion in the first trimester. Five percent of women have two, and 1-2% of women have more than three abortions. The risk of spontaneous abortion is influenced by variety of genetic and environmental factors. Enzyme methylenetetrahydrofolate reductase (MTHFR) is primarily involved in homocysteine remethylation to the methionine. Gene polymorphism C677T in the MTHFR gene causes enzyme thermolability which leads to hyperhomocysteinemia, that might increase the risk of developing placental thrombosis and spontaneous abortion. Aim: The aim of our study was to determine whether the MTHFR C677T polymorphism is associated with the increased risk of SA. Material and methods: This study included 157 women who had at least two unexplained spontaneous abortions and 135 healthy women with at least one child, without previous SA. Detection of MTHFR C677T polymorphism genotypes was performed by PCR-RFLPs method. Investigation of differences between genotype and allele frequencies, in the group of women with SA and the control group, was completed using the x2 test. Results: In the group of patients with recurrent spontaneous abortions, 58 of them had CC genotype (36.94%), 74 had CT genotype (47.13%), and 25 had TT genotype (15.92%). In the control group, 59 of them had CC genotype (43.07%), 55 had CT genotype (40.74%), and 21 had TT genotype (15.56%). The frequency of C allele in the group of patients was 60.51%, and T allele 39.49%; while the frequencies in the control group were 64.07% and 35.93%, respectively. The difference in the genotype (p=0.470) and allele (p=0.393) frequency between the two groups of patients was statistically insignificant. Conclusion: Our results do not show any influence of the analyzed polymorphism on SA

Uporedna analiza duplikacija i delecija u genu za distrofin u grupi bolesnika sa distrofinopatijom iz Srbije

Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44-60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers.Uvod/Cilj. Dišenova mišićna distrofija (DMD) i njegova alelna forma, Bekerova mišićna distrofija (BMD), su Xvezane nasledne bolesti od kojih obolevaju muškarci, a karakteriše ih progresivna mišićna i kardiopulmonalna slabost, posebno kod DMD kao težeg oblika bolesti. Ove bolesti nastaju kao posledica mutacija u genu za distrofin, a najčešće su prisutne intragenske delecije i duplikacije (80%). Novonastalu mutaciju ima1/3 bolesnika, a procenjeno je da su 2/3 majki nosioci. Cilj rada je bio da se analizira učestalost duplikacija u odnosu na delecije u genu za distrofin kod bolesnika sa distrofinopatijom, kao i da se ispita efekat dobijenih mutacija na fenotip kod probanda i utvrdimo status nosioca kod ženskih srodnika probanda sa duplikacijama. Metode. Studijom je bilo obuhvaćeno 22 DMD i 35 BMD nesrodnih bolesnika i šest ženskih srodnika probanda kod kojih su bile otkrivene duplikacije. Za otkrivanje ili potvrdu mutacije, kod probanda i ženskih nosioca, korišćene su metode: lančana reakcija polimerazom (PCR) i višestruko umnožavanje vezanih sondi (MLPA), prema datom protokolu. Rezultati. Kod probanda je nađeno 34 (59,6%) velikih delecija (najčešće su bili zahvaćeni egzoni 44-60) i 6 velikih duplikacija (10,5%) kod 4 DMD i 2 BMD bolesnika. Takođe, duplikacije su nađene kod 3 od 4 (75%) testirane majke. Distribucija duplikacija je bila heterogena, obuhvatala je N-terminalni i štapićasti region i uključivala je veći broj egzona, osim kod jednog DMD bolesnika koji je imao duplikaciju egzona 2. Odstupanje od Monakovog pravila je bilo prisutno kod 9,5% DMD probanda, odnosno kod 15,8% BMD probanda, to jest kod 12,5% slučajeva. Zaključak. Kod 57 DMD/BMD probanda nađeno je 59,6% velikih delecija i 10,5% velikih duplikacija. Najčešće je bio zahvaćen štapićasti domen u DMD genu. Odstupanje od Monakovog pravila je bilo prisutno u 12,5% DMD/BMD slučajeva. Tri od četiri ispitane majke probanda su bile potvrđene kao nosioci

NPM1 gene mutations in children with Myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are rare in children and only a few studies have analyzed their molecular mechanisms. The NPM1 gene encodes for nucleophosmin (NPM) which regulates hematopoiesis. Mutations in exon 12 of the NPM1 cause the nucleophosmin cytoplasmic dislocation and disrupt its functions. We have analyzed mutations of the NPM1 gene in archival bone marrow samples from 17 children with MDS and detected, in one patient, transition C to T in codon 293. To the best of our knowledge, this is the first analysis of NPM1 mutations in childhood MDS and the very first missense mutation of the NPM1 gene reported so far

Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients

Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).This is the peer-reviewed version of the article: Vejnović, D.; Milić, V.; Popović, B.; Damnjanović, T.; Maksimović, N.; Bunjevački, V.; Krajinović, M.; Novaković, I.; Damjanov, N.; Jekić, B. Association of C35T Polymorphism in Dihydrofolate Reductase Gene with Toxicity of Methotrexate in Rheumatoid Arthritis Patients. Expert Opinion on Drug Metabolism & Toxicology 2019, 15 (3), 253–257. [https://doi.org/10.1080/17425255.2019.1563594

Supplementary data for the article: Izrael-Živković, L.; Beškoski, V.; Rikalović, M.; Kazazić, S.; Shapiro, N.; Woyke, T.; Gojgić-Cvijović, G.; Vrvić, M. M.; Maksimović, N.; Karadžić, I. High-Quality Draft Genome Sequence of Pseudomonas Aeruginosa San Ai, an Environmental Isolate Resistant to Heavy Metals. Extremophiles 2019, 23 (4), 399–405. https://doi.org/10.1007/s00792-019-01092-w

Supplementary material for: [https://doi.org/10.1007/s00792-019-01092-w]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3705

Introduction to Molecular genetic diagnostics

Molecular genetic testing is part of modern medical practice. DNA tests are an essential part of diagnostics and genetic counseling in single gene diseases, while their application in polygenic disorders is still limited. Pharmacogenetics studies DNA variants associated with variations in drug efficacy and toxicity, and tests in this field are being developed rapidly. The main method for molecular genetic testing is the polymerase chain reaction, with a number of modifications. New methods, such as next generation sequencing and DNA microarray, should allow simultaneous analysis of a number of genes, even whole genome sequencing. Ethical concerns in molecular genetic testing are very important, along with legislation. After molecular genetic testing, interpretation of results and genetic counseling should be done by professionals. With the example of thrombophilia, we discuss questions about genetic testing, its possibilities and promises