Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent pediatric leukemia; it can be defined according to chromosomic and genomic data. Cytogenetic analyses and determination of chromosomal numbers (such as hypo- or hyperdiploidy) and/or specific chromosomal rearrangements are basic for ALL classification and treatment. Even though cure rates of childhood ALL are at ~95%, pharmacogenetic aspects are of raising importance. Material and Methods: We have analyzed the literature for ALL subtypes, corresponding therapy options, and pharmacogenetic implications. Results: Data for ALL subtypes such as B-ALL, T-ALL, Ph-like ALL, DS-ALL, ETP-ALL, BCR-ABL1-like ALL are presented here. The gene polymorphism which lead to metabolizability of 6-MP are ITPA variants (94C>A) and IVS2+21A>C, in conjunction with TPMT (238G>C, TPMT*3B 460G>A and *3C 719A>G and NUDT15 (415C>T). For methotrexate metabolism gene polymorphisms are found for gene MTHFR as C677T and A1298C. Conclusion: In the last decade in many hospital laboratories, pharmacogenetic aspects gain more and more importance. Application of many molecular biology methods provided progress in treatment and diagnosis of ALL patients. Combination therapy is proposed as an alternative to single drug treatments.

Systemic lupus erythematosus (SLE) is a disease associated with an impaired autoimmune response; the immune system attacks erroneously own tissues, which leads to inflammation, tissue damage and complement activation. The latter plays a pivotal role in SLE pathology, as complement level is suited as histological marker for disease diagnoses and management. Besides, environmentally factors have been highlighted and their significant contribution for individual genetic predisposition has been pointed out. Here complement factors, their activity and their ability to modify DNA with histone proteins are reviewed; known gene mutations involved in SLE, and new therapeutic approaches suggested for SLE are discussed and summarized, as well.

Mucopolysaccharidosis type IIIB (MPS IIIB), also known as Sanfilippo syndrome type B, is a metabolic disease caused by mutations in both alleles of the NAGLU gene encoding for the enzyme α-N-acetylglucosaminidase. A malfunction of this enzyme causes  inability to degrade heparan sulfate, which leads to accumulation of glycosaminoglycans in the cells. MPS IIIB is associated with different symptoms such as neurodegeneration, extreme hyperactivity, sleeping problems, aggressive behavior, reduced fear, and cognitive  deterioration. The condition is by now not curable. Here we describe a patient with MPS IIIB diagnosed at the age of 5 presenting with communication problems, motor dysfunctions, and speech and sleeping problems.Standard biochemical tests for neurodegenerative disorders and DNA analyses including NAGLU mutation screening were performed. We also did some psychological tests assessing the patient's communication skills and behavior. The patient was heterozygote for two mutations in the gene NAGLU (Y140C and Ser169fs). Thus, he suffered from MPS IIIB due to two mutations in the disease-causing gene.The patient presented with clear signs and symptoms of MPS IIIB with at least one of the two mutations affecting the α-N-acetylglucosaminidase protein function severely. Here we report the combination of a well-known and previously unreported mutation in the NAGLU gene; this could be dependent on geographical origin of the patient, which needs to be clarified by molecular studies of more MPS IIIB patients from Southeast Europe.

Systemic lupus erythematosus (SLE) is a disease associated with an impaired autoimmune response; the immune system attacks erroneously own tissues, which leads to inflammation, tissue damage and complement activation. The latter plays a pivotal role in SLE pathology, as complement level is suited as histological marker for disease diagnoses and management. Besides, environmentally factors have been highlighted and their significant contribution for individual genetic predisposition has been pointed out. Here complement factors, their activity and their ability to modify DNA with histone proteins are reviewed; known gene mutations involved in SLE, and new therapeutic approaches suggested for SLE are discussed and summarized, as well.

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:

Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.

The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation.

Aim Chromosome translocations are considered as one of the most severe forms of genome defects. Because of the clinical significance of chromosome translocations and scarce data on the incidence of sporadic translocations in population of Bosnia and Herzegovina, we aimed to report sporadic translocation frequencies in samples karyotyped in our laboratory. Methods The study group consisted of 108 samples. Whole blood was cultivated in complete medium for 72 hours with the thymidine application at 48th hour to synchronize the cell culture. Metaphases were arrested by colcemid 60 minutes before harvesting. Following hypotonic treatment, cells were fixed and cell suspension was dropped on coded slides. Dried slides were subjected to conventional GTG (G-banding with trypsin-Giemsa) banding and analyzed under 1000x magnification in the accordance with ISCN (International System for Human Cytogenetic Nomenclature) and E.C.A. Cytogenetic Guidelines and Quality Assurance. Results The incidence of all detected sporadic translocations was 27.81 x 10-4 per metaphase. The incidence of sporadic translocations involving chromosomes 7 and 14, being considered as the most frequent sporadic translocations of the human karyotype in phytohaemagglutinin (PHA) stimulated lymphocytes, was 15.89 x 10-4 per metaphase. The most frequent breakpoints were 7p21, 14q11 and 14q21. Other detected sporadic translocation breakpoints were: 1q25, 3p22, 7p13, 7q11.22, 7q33, 14q23 and 19q13.4. Conclusion Higher incidence of sporadic translocations compared to the similar studies was registered. Since potential explanations for this issue are smaller sample size and higher exposure of examined population to genotoxic agents, further monitoring of sporadic translocation incidences is recommended.

This paper provides an overview of the seven possible hand-related traits, with an idea to estimate the statistical phenotypic association between them. The traits observed in this study were: midphalangeal hair, Hitchhiker’s thumb, extensibility of proximal joint of thumb, digital index, nail shape, crooked fifth finger and hand clasping. The mentioned characteristics were observed in 7431 unrelated subjects, with approximately equal gender distribution. For each case, three groups were formed: total, male and female. The subjects were evenly distributed throughout Bosnia and Herzegovina’s various geographical regions, and they properly represent the country’s national and ethnic composition. The Chi-squared test was used to determine the statistical significance of the association between these traits, while Fisher’s exact test was utilized as an extra test to analyze the association between each pair of observed features. Also, Chi-squared test was applied for observing differences in the frequencies of the phenotypic characteristics of the hand between the genders. Following traits were shown to have a statistically significant association: midphalangeal hair-Hitchhiker’s thumb, midphalangeal hair – digital index, midphalangeal hair – nail shape, midphalangeal hair – crooked fifth finger, Hitchhiker’s thumb- extensibility of proximal joint of thumb, digital index – nail shape, digital index -crooked fifth finger, midphalangeal hair – hand clasping, crooked fifth finger – hand clasping. Analysis of differences in the frequencies of the observed phenotypic traits of the hand according to the genders showed statistical significance for D, Dht, Ref and Lf.

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.