Frequency of Main Western-Euroasian mtDNA Haplogroups and Paleolithic and Neolithic Lineages in the Genetic Structure of Population of Northeastern Bosnia

Mitochondrial DNA (mtDNA) variations were analyzed in a sample of 245 individuals of Bosnian-Herzegovinian population from the area of ​​ Northeastern Bosnia (also known as Tuzla region). Haplogroup affiliation was determined using RFLP method (Restriction Fragment Length Polymorphism) analyzing haplogroup-specific markers of mtDNA coding region, characteristic for the main Western-Eurasian haplogroups. Additional analyses of two sequenced hypervariable segments (HVSI and HVSII) of mtDNA control region were performed in order to identify U subhaplogroups. The study revealed that 95.51% of the analyzed individuals belonged to the typical Western-Eurasian haplogroups: H, I, J, K, T, U, V, W or X. The most frequent haplogroup in the analyzed population was the haplogroup H (52.65%) which, due to its increased frequency, represents a marking haplogroup of the population of Northeastern Bosnia. The results of intergroup genetic analysis showed that Bosnian-Herzegovinian population is genetically closer to previously studied populations of Herzegovinians (part of Bosnia and Herzegovina), Slovenians and Croats in relation to other neighboring populations located in Southeastern Europe. Our study also suggests that population genetic structure of Tuzla region is dominated by mutations that are classified as „Paleolithic”. These mutations were probably brought to the area of Northeastern Bosnia through waves of prehistoric and historic migrations, but the impact of any pre-Neolithic, Neolithic or some ,,later,, migrations, with a slightly lower contribution to the genetic structure of this population, also can-not be neglected

Overview of Human Population-Genetic Studies in Bosnia and Herzegovina during the Last Three Centuries: History and Prospective

Modern Bosnia and Herzegovina is a multi-ethnic and multi-religion country, with a very stormy history. Certain archaeological findings indicate continuous population of its territory since the Paleolithic. In time, vast number of different factors jointly influenced fascinating diversity of local human populations. A great number of small, more or less isolated, indigenous populations, make this area quite attractive for population-genetic surveys of different levels and approaches. Austro-Hungarian military physicians conducted the very first known bio-anthropological analyses of Bosnia-Herzegovina population at the end of the 19th century. Thus, the first step towards resolving the genetic structures of local B&H human populations was made. The studies that followed (conducted throughout most of the 20th century) were primarily based on the observation of various phenotypic traits. This stage was followed by the examination of various cytogenetic and fundamental DNA based molecular markers. The efforts undertaken over the last three centuries revealed »human genetic treasure« in Bosnia and Herzegovina. However, even now, after all the studies that were conducted, many interesting features remain to be discovered and described within the existing local human populations

Lessons learned - resolving the enigma of genetic factors in IBS

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi) genetic research and provides a vision on how to address and improve (epi) genetic approaches in this complex disorder in the future.This is the peer reviewed version of the paper: Gazouli, M., Wouters, M. M., Kapur-Pojskić, L., Bengtson, M.-B., Friedman, E., Nikčević, G., Demetriou, C. A., Mulak, A., Santos, J., & Niesler, B. (2016). Lessons learned—Resolving the enigma of genetic factors in IBS. Nature Reviews Gastroenterology & Hepatology, 13(2), 77–87. [https://doi.org/10.1038/nrgastro.2015.206]Published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/977

Assessment of relatedness between neurocan gene as bipolar disorder susceptibility locus and schizophrenia

Large scale genetic association meta-analyses showed that neurocan (NCAN) gene polymorphism rs1064395 is susceptibility locus for bipolar disorder. These studies also included patients with bipolar disorder originated from Bosnia and Herzegovina. Followed by theory of shared genetic elements between bipolar disorder and schizophrenia susceptibility, other studies explored several genetic factors with schizophrenia vulnerability as well. In this work, authors investigated the association between previously confirmed bipolar disorder genetic risk factor-neurocan with schizophrenia in a population sample of Bosnia and Herzegovina. Ethical aspects of this research were assessed by Ethics Committee of Clinical Center University of Sarajevo. Blood samples for DNA extraction were taken from the total of 86 patients and healthy individuals who previously signed informed consent. Genotyping for rs 1064395 was done using direct sequencing method. A case-control analysis of common genetic polymorphism within neurocan gene and schizophrenia status in a consecutively sampled patient cohort have been done using Fisher-exact test with odds-ratio calculation. No statistically significant allele and genotype association with disease status was found (p>0.05). Our finding supports the fact that large-scale genetic association studies approach need to be employed when detecting the variants with small additive effect in phenotypes with complex ethiology

Association of dopamine receptor gene polymorphism and psychological personality traits in liability for opioid addiction

There is a clear evidence that same psychoactive substance may cause various individual physiological reactions in same environmental conditions. Although there is a general attitude on equal liability to opioid addiction, latest genetic analysis findings imply there are certain quantifiable factors that could lead to elevated individual liability towards development of opioid addiction. The goal of this study was to investigate association of certain personality traits and genetic factors (separately and in combination) with heroin addiction. Total of 200 individuals participated in the study: 100 patients on Metadone Maintenance Treatment (MMT) and 100 age and sex matched healthy volunteers. All were medically examined, interviewed and psychologically evaluated using Eysenck personality questionnaire (EPQ) and genotyped for DRD2 (rs1800497) using PCR-RFLP method. Overrepresentation of certain personality traits (neuroticism, psychoticism and extraversion/intraversion), together with environemental risk factors such as: upbringing within incomplete families and familial history of psychotropic substances abuse, are associated with high-risk development of opioid addiction

Posttraumatic stress disorder among women after the war in Sarajevo: a rationale for genetic study.

An exposure to extreme trauma events leads to posttraumatic stress disorder (PTSD) in up to 14-50% of war survivors. Recent findings suggest that genetic factors could play a certain role in PTSD development. In order to illustrate this possibility, we present results of a pilot study on gender specific sample of Sarajevo civilians immediately after the war cessation. During the period 1992-1995, Sarajevo civilians experienced continuous life threatening events with a great risk of developing PTSD in such conditions. Our study included 100 women adjusted to same socio-demographic characteristics. All women were interviewed using Harvard Trauma Questionnaire (HTQ) and divided into two groups (domestic and returnees) according to exposure length to extreme war life events of six or forty-three months. Above 50% of total analysed sample fulfilled criteria for PTSD. Regarding duration in trauma exposure no significant difference between these two groups were found. The only significant predictor found was physical abuse (p>0.01) that still cannot explain why some women develop PTSD while others not. Several years after the war, PTSD frequencies are decreased and disorder became chronic and more severe. However, the PTSD prevalence remains high when compared to general population rates. Therefore, Sarajevo population being exposed for almost four years to extreme war life events represents unique model for comparative research on PTSD etiology within the light of latest findings in molecular genetics of PTSD

Investigation of Ivs14+1G>A Polymorphism of Dpyd Gene in a Group of Bosnian Patients Treated with 5-Fluorouracil and Capecitabine

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14+ 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation

Lessons learned - resolving the enigma of genetic factors in IBS

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi)genetic research and provides a vision on how to address and improve (epi)genetic approaches in this complex disorder in the future.status: publishe

Lessons learned - resolving the enigma of genetic factors in IBS

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi) genetic research and provides a vision on how to address and improve (epi) genetic approaches in this complex disorder in the future.Peer-reviewed manuscript: [https://imagine.imgge.bg.ac.rs/handle/123456789/1625

Current state and prospects of biotechnology in Central and Eastern European countries. Part II: new and preaccession EU countries(CRO, RO, B&H, SRB)

Innovation holds the potential for economic prosperity. Biotechnology (BT) has proved to be a viable vehicle for the development and utilization of technologies, which has brought not only advances to society, but also career opportunities to nation-states that have enabling conditions. In this review, we assess the current state of BT-related activities within selected new and preaccession EU countries (NPA) of CEE region namely Croatia, Romania, Bosnia and Herzegovina and Serbia, examining educational programs, research activity, enterprises, and the financing systems. The field of BT covers a broad area of activities, including medical, food and agriculture, aquaculture or marine, environmental, biofuels, bioinformatics, and many others. Under the European Commission (EC), member-states are to set their Research and Innovation Strategies for Smart Specialization (RIS3), to identify priorities or strengths in order to develop knowledge intensive economies. As the four countries highlighted in this review are in the early stages of implementing RIS3 or have not yet fully formulated, it presents an opportunity to learn from the successes and failures of those that have already received major structural funds from the EC. A critical point will be the ability of the public and private sectors' actors to align, in the implementation of RIS3 as new investment instruments emerge, and to concentrate efforts on a few select target goals, rather than distribute funding widely without respect to a long-term vision