We examined dermatoglyphics of children in three Albanian and one Roma population sample (collected from 641 individuals from the Albanian populations and 226 individuals from the Roma population of both sexes). We compared Albanian and Roma populations based on four finger (whorl, radial and ulnar loop, and arch) and thirteen palmar traits (pattern frequencies in the Thenar/I interdigital area, II, III, and IV interdigital area, Hypothenar and axial »t« triradius position). The differences between the populations were more evident for palmar traits. In our study the Albanian and the Roma populations showed the best separation when finger and palmar traits are separately analyzed. As expected, the Albanian and the Roma populations separated in statistical analyses of most traits; the main reason for this is the different origins of two ethnic groups. The observed difference also indicates a low level of admixture between the Albanians and the Roma despite them living beside one another for several centuries.

Introduction: The process of protein synthesis is a vital process for all kingdoms of life. The ribosome is a ribonucleoprotein complex that reads the genetic code, from messenger RNA (mRNA) to produce proteins and to tightly regulate and ensure cells growth. The fact that numerous diseases are caused by defect during the ribosome biogenesis is important to understand this pathway. Materials and methods: We have analyzed the literature for ribosome biogenesis and its links with different diseases which have been found. Results and discussion: We have discussed the key aspect of human ribosome biogenesis and its links to diseases. We have also proposed the potential of applying this knowledge to the development of a ribosomal stress-based cancer therapy. Conclusion: Major challenges in the future will be to determine factors which play a pivotal role during ribosome biogenesis. Therefore, more anti-cancer drugs and gene therapy for genetic diseases will be developed against ribosomal biogenesis in the coming years. Graphical abstract:

Abstract Male infertility is caused by spermatogenetic failure, clinically noted as oligoor azoospermia. Approximately 20% of infertile patients carry a genetic defect. The most frequent genetic defect leading to azoospermia (or severe oligozoospermia) is Klinefelter syndrome (47, XXY), which is numerical chromosomal abnormality and Y- structural chromosome aberration. The human X chromosome is the most stable of all human chromosomes. The X chromosome is loaded with regions of acquired, rapidly evolving genes. The X chromosome may actually play an essential role in male infertility and sperm production. Here we will describe X chromosome aberrations, which are associated with male infertility.

Mucopolysaccharidoses (MPSs) are known as rare genetic diseases which are caused by mutation in the enzyme heparin sulfate, which normally leads to degradation and accumulation of glycosaminoglycans in the cells. There are 11 types of MPSs, whereby neuropathy may occur in seven of them (MPS I, II, IIIA, IIIB, IIIC, IIID and VII). Accumulation of degraded heparin sulfate in lysosomes causes cellular dysfunction and malfunction of several organs. However, the exact molecular mechanism how protein degradation and storage leads to cellular dysfunction is not understood, yet. Nonetheless, several genetic and biochemical methods for diagnosis of MPSs are available nowadays. Here we provide an overview on known molecular basis of MPS in general, including enzyme defects and symptoms of MPS; however, the main focus is on MPS type III together with potential and perspective therapy-options.

of the age group of 6–12 years, and 10 patients of the age group of 12–18 years. Conclusions: Data suggest that pediatric cases of COVID-19 in adolescents have more severe symptoms than in the other age groups; however, in general children tend to cope much more easily with the virus than adults.

Introduction: Conventional cytogenetics by the use of standard karyotyping allows the study of numerical and structural chromosomal aberrations. Haematological malignancies include a number of cancer types that originate in the blood cells of the bone marrow or of the lymphatic system. Cytogenetic methods are traditionally used for the sake of diagnosis and prognosis of these diseases. However, with the ever more frequent use of molecular methods in the diagnostic laboratories, the importance of the conventional cytogenetic analysis in the diagnosis of haematological diseases needs to be reassessed. Aim: To evaluate the role of cytogenetic methods in the diagnosis of haematological malignancies. Materials and Methods: A retrospective analysis of cytogenetic findings of 146 patients with various haematological malignancies was performed. All of the findings were made over a period of three years at the Centre for Genetics at the Medical Faculty of the University of Sarajevo in Bosnia and Herzegovina. Microsoft Excel 2019 was used for the analysis and presentation of data in the form of tables and graphs. Results: The results of the present study showed that the use of conventional cytogenetic analysis is a good diagnostic method for 50.68% (74) of patients in whom chromosomal aberrations were detected. Conclusion: Cytogenetics remains the most comprehensive method for assessing chromosomal abnormalities due to its ability to detect clinically relevant aneuploidies and additional cytogenetic abnormalities that cannot be detected by locus-specific assays.

Rheumatoid arthritis is a polygenic disease of unknown etiology, occurs worldwide in both developed and underdeveloped countries and involves all races. The aim of this study is to determine the correlation between hematological parameters (DBC and ESR) and biomarkers of inflammation (CRP) in patients with RA predisposing gene variants HLA-DRB1*04 or HLA-DRB1*03. This study analyzed the results of hematological and biochemical parameters of 33 patients diagnosed with RA, carriers ofgene variants of HLA-DRB1*04 or HLA-DRB1*03, and 33 subjects of control group non-carriers for HLA-DRB1*04 or HLA-DRB1*03. All hematological parameters (DBC) were analyzed on a Beckman Coulter DxH 800 hematology counter. The erythrocyte sedimentation rate was expressed in mm/h. The CRP biochemical test was performed on a Cobas c311 automatic analyzer. In group of RA patients carriers of HLA-DRB1*04 or HLA-DRB1*03 gene variants, the values of HGB and HCTwere significantlylower(p < 0.05) while the values of RDW, RDW-SD, MO, BA, MO#, BA#, ESR and CRP were statistically increased (p < 0.05) from the control group without these variants.

Introduction: Genetic polymorphism is associated with individual responses to medication and susceptibility to diseases, and it represents the basis for individualized medical treatment and drug genomics studies. Genetic variation at CYP2D6 is high, both among populations and among individuals in the same population. Aim: The aim of the study was to investigate the CYP2D6 gene duplication and the non-synonymous single-nucleotide polymorphisms (SNP) 100C>T in the CYP2D6 gene in members of the Bosnian population. Material and Methods: The blood samples were collected from 151 unrelated and healthy donors from Bosnian populations consisted of 94 females and 57 males. Duplex long-range PCR was used to determine whether individuals carrying CYP2D6 gene duplication. The resulting PCR product of 5.1 kb, containing all nine CYP2D6 exons, was used as template for detection of the CYP2D6 100C>T allele by nested PCR. Results: The CYP2D6 gene duplication frequency found in the Bosnian population (2.73%) was related to the frequencies of this allele in other Caucasians. The gene duplication is the result of inheritance of more than two copies of the fully functional CYP2D6 alleles. In contrast, the frequency of the CYP2D6 100C>T variant, with possibly damaging function, in the Bosnian population (15.56%) was significantly higher when compared with the other Caucasians but significantly lower when compared with Asians. Conclusion: CYP2D6 metabolizes many commonly prescribed drugs. Variations in the gene encoding this enzyme have been associated with individual differences in drug metabolism rates. The individuals with multiple CYP2D6 gene copies metabolize drugs more rapidly and therapeutic plasma levels will not be achieved at ordinary drug dosages. The non-synonymous coding SNP (100C>T) were predicted to have damaging effects on the protein function.

Background: The gene for 5,10-methylenetetrahydrofolate reductase (NAD(P)H) or MTHFR gene encodes protein methylenetetrahydrofolate reductase (MTHFR), an enzyme important in folate metabolism. Aim: The aim of this study was to determine the frequencies of 677C>T and 1298A>C polymorphisms in the MTHFR gene of healthy subjects from the population. Material and methods: The blood samples were collected from 164 unrelated and healthy donors from population consisted of 98 females and 66 males. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through Haploview analysis. Results: The frequency of MTHFR 677T allele in the population (32.62%) was in agreement with the frequency of this allele in most other populations, however, the frequency of MTHFR 1298C allele (38.41%) was higher than that reported for most other populations in the world. Haploview analysis showed a relatively strong LD between 677C>T and 1298A>C SNPs with D′ values of 0.87. Conclusion: Regarding the two MTHFR polymorphisms, three of the nine combined genotypes were present in 87.2% of the population. 33.54% subjects were complex heterozygous (677CT/1298AC genotype), 34.15% subjects had 677CC/1298AC and 19.51% of 677CT/1298AA genotype. The subjects with 677TT genotype had a 1298AA or 1298AC genotype while subjects with 1298CC genotype had only 677CC genotype. The subjects with 677CC/1298AA genotype were only 3.05%. We were not found triple 677CT/1298CC and quadruple 677TT/1298CC mutation suggesting decreased viability of embryos with increased numbers of mutant alleles.

Cancer patients in developing and low‐income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14‐month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0–5 months, 6–12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6–12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6–12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib.

The cytokinesis‐block micronucleus cytome (CBMN‐Cyt) assay was developed as a system for evaluating DNA damage, cytostasis, and cytotoxicity. The aim of the present study was to estimate levels of micronuclei (MNi), nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (apoptosis/necrosis), nuclear division index, and nuclear division cytotoxicity index values in the peripheral blood lymphocytes of environmentally exposed subjects to heavy metals from five Bosnian regions, characterized by different exposure to heavy metals. The study was performed using CBMN‐Cyt assay, considering factors, such as age, gender and smoking habits and their possible effects on analyzed parameters. In total, 104 healthy subjects were selected (49.04% females and 50.96% males; average age, 35.41 years; 51.92% smokers and 48.08% nonsmokers). There was significant difference between the frequency of NBUDs in Tuzla as compared to the control group. Furthermore, there was observed a statistically significant difference for the frequency of NPBs between Zenica, Olovo, and Kakanj when compared with the controls. Males showed a significantly higher number of apoptotic cells than females in controls. There were significant differences between smokers and nonsmokers in the frequency of NPBs in controls (higher in nonsmokers) and necrotic cells in Olovo (higher in nonsmokers). The pack years of smoking significantly influenced the number of necrotic cells in controls and the frequency of NBUDs in the overall sample. The results of the present study provide evidence of significantly increased frequency of NPBs and NBUDs in exposed subjects, suggesting that these endpoints are highly sensitive markers for measuring genotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1331–1342, 2015.

Objective: This study investigated the influence of sex and ageing on chromosomal damage and the role of life-style habits on the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) of healthy Bosnian subjects. Materials and Methods: Peripheral blood samples were obtained from 100 healthy, unrelated individuals in Bosnia and Herzegovina during 2010 and 2011. Chromosome preparations were made by dropping and air drying and slides were stained with 10% Giemsa solution (pH 6.8). The cytogenetic analysis was carried out in a cytogenetic laboratory in the Department of Biology of the Faculty of Science in Sarajevo. The category of total structural CAs was sub classified as chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs) while the category of total numerical CAs was sub classified as aneuploid and polyploid mitoses. All statistical analyses were carried out using Microsoft Excel 2010 (Microsoft Corporation) and the Windows Kwikstat Winks SDA 7.0.2 statistical software package (Texa Soft Cedar Hill, Texas). Results: Cytogenetic analysis revealed the average number of structural CAs was 2.84 and of numerical CAs was 9.56. There was a significant increase in the frequency of chromosome-type aberrations (1.92) compared with chromatid-type aberrations (CTAs) (0.92) and a significant increase in the frequency of aneuploid (8.83) compared with polyploid (0.73) mitoses. Significant positive correlations between age and CTAs in human PBLs were also demonstrated. Additional statistical analysis showed that ageing increase number of numerical CAs in lymphocytes of drinkers. The frequency of structural CAs of females exposed to radiation was significantly greater than in males. Analysis indicates the presence of a positive association between CAs and smoking in younger subjects but a negative correlation between aberrant cells frequencies and alcohol in older drinkers. Conclusion: The results of the study support the conclusion that sex and age, together with life-style habits of individuals as confounding factors can affect spontaneous frequency of CAs especially to CTAs in PBLs that are a biomarker of cancer risk.

Introduction: This study was performed to establish a baseline value of micronucleus frequency in buccal cells and to estimate the impact of the most common factors (sex and age, and smoking) on micronucleus and degenerative nuclear alteration frequencies in the sample of healthy Bosnian subjects.Methods: The Buccal Micronucleus Cytome (BMCyt) assay, based on scoring not only micronucleus frequency but also other genome damage markers, dead or degenerated cells, provides a measure of cytotoxic and genotoxic effects.Results: Our results showed the baseline buccal micronucleus frequency was 0.135% or 1.35‰, as well as positive correlations between micronucleus frequencies and formations of degenerative nuclear alterations (nuclear buds, karyolytic and karyorrhectic cells). The number of micronuclei in buccal cells was significantly higher in females than in males. There was positive association between the age and frequency of analysed cytogenetic biomarkers. Buccal cell micronuclei and degenerative nuclear alternations were more frequent among cigarette smokers than non-smokers and significantly higher in female smokers than in male smokers. Cytogenetic damages showed significantly positive correlation between intensity of smoking and the number of nuclear alterations. The years of smoking had a significant influence not only on the number of nuclear alterations but also in micronuclei and nuclear buds in buccal cells.Conclusions: The sex influences the number of micronuclei in human buccal cells. The ageing increased the number of micronuclei and other biomarkers of DNA damage. The cigarette smoking significantly increases the frequencies of micronuclei and nuclear buds, pyknotic, karyolytic and karyorrhectic cells.

ABSTRACT Introduction: Alprazolam is a triazolobenzodiazepine used in panic disorders and other anxiety states. Target organ of Alprazolam is CNS, causing depression of respiration and consciousness. Aim: This study aimed to estimate the genotoxic potential of Alprazolam using Allium cepa test. Methods: Allium cepa is one of the most suitable plants for detecting different types of xenobiotics. The test enables the assessment of different genetic endpoints making possible damage to the DNA of humans to be predicted. Results: Alprazolam induced chromosomal (anaphase bridges, breaks, lagging and stickiness, abnormal spiralisation, multipolarity and polyploidy) and cytological aberrations, especially nuclear alterations (nuclear buds, fragmented nucleus and apoptotic bodies, cells without nucleus, binucleated and micronucleated cells), morphological alterations in shape and size of cells, spindle disturbance and polar deviation in root tip meristem cells of Allium cepa at all tested concentrations. Alprazolam also caused significant inhibition of mitotic index in these cells. Conclusion: These changes in cells are indicators of genotoxic potential of Alprazolam suggesting a need for further in vitro studies on animal and human lymphocytes as well as in vivo studies.