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

Applied Genomics in the Clinic

"Applied genomics in the Clinic" was organised in Istanbul on 17-19 October 2012. The main aim of the workshop was to get an overview of the state of the art of applied genomics in the clinical context in accession and candidate countries, as well as new members, to share best practices in EU and to evaluate these in the light of a public health perspective. There is a clear divide behind the genomic services offered in a country and the awareness among research scientists of the available genomic applications and the future impact of genomic technologies on health services and clinical approaches. In all countries there are a number of common obstacles that delay penetration of genomic technologies in clinical applications : lack of recognised experts ( medical genetics HAS to be recognised as a medical specialty) lack of a regulatory framework that involves political determination of decision makers, lack of common databases on methods and experts, lack of ongoing education for physicians and most importantly reimbursement of testing. Stronger connections and collaborations with the EU for research and technology transfer will function as a leverage for these countries in adopting genomic tools and harmonising the quality of healthcare services they offer. It is very important to establish recognized objective state of the art guidelines for application of genomic technologies in clinical practice. Such guidelines adopted by countries will form the basis of reimbursement policies at national and cross border levels. In addition establishing reliable, not for profit, open access databases for building reference datasets for correct and efficient interpretation of complex data generated by advanced genomic technologies will speed up adoption of the technology in the clinic.JRC.I.1-Chemical Assessment and Testin

Methylenetetrahy-drofolate Reductase Gene Polymorphism in Patients Receiving Hemodialysis

Methylenetetrahydrofolate Reductase (MTHFR) is key enzyme in metabolism of homocysteine. Homozygotes for mutation (TT genotype) have hyperhomocysteinemia, risk factor for atherosclerosis development. The aim of the study was to find out distribution of genotype frequencies of C677T MTHFR among patients on maintenance hemodialysis. Possible association of alleles and genotypes of C677T polymorphism of the MTHFR gene with age of onset, duration of dialysis and cause of kidney failure was studied also. Cross-sectional study includes 80 patients from Clinic of Hemodialysis KUCS in Sarajevo. In order to perform genotyping, isolated DNA was analyzed by RFLP-PCR and gel-electrophoresis. From total of 80 patients, 42.5% (n=24) were female, 57.5% (n=46) were male, mean age 54.59±1.78 years and duration of dialysis 79.92±6.32 months. Genotype distribution was: CC 51.2% (n=41), CT 37.5% (n=30) and TT 11.2% (n=9). Patients with wild-type genotype have longer duration of dialysis in month (87.1 ± 63.93) comparing to TT genotype patients (67.06 ± 39.3), with no statistical significance. T allele frequency was significantly higher in group of vascular and congenital cause of kidney failure (Pearson X2 =6.049, P<0.05) comparing to inflammation etiology group. Genotype distribution results are within the results other studies in Europe. Obtained results indicate that C677T polymorphism is not associated with onset, duration and cause of kidney failure in our hemodialysis population. There is an association of T allele of the MTHFR gene and vascular and congenital cause kidney failure

Methylenetetrahy-drofolate Reductase Gene Polymorphism in Patients Receiving Hemodialysis

Methylenetetrahydrofolate Reductase (MTHFR) is key enzyme in metabolism of homocysteine. Homozygotes for mutation (TT genotype) have hyperhomocysteinemia, risk factor for atherosclerosis development. The aim of the study was to find out distribution of genotype frequencies of C677T MTHFR among patients on maintenance hemodialysis. Possible association of alleles and genotypes of C677T polymorphism of the MTHFR gene with age of onset, duration of dialysis and cause of kidney failure was studied also. Cross-sectional study includes 80 patients from Clinic of Hemodialysis KUCS in Sarajevo. In order to perform genotyping, isolated DNA was analyzed by RFLP-PCR and gel-electrophoresis. From total of 80 patients, 42.5% (n=24) were female, 57.5% (n=46) were male, mean age 54.59±1.78 years and duration of dialysis 79.92±6.32 months. Genotype distribution was: CC 51.2% (n=41), CT 37.5% (n=30) and TT 11.2% (n=9). Patients with wild-type genotype have longer duration of dialysis in month (87.1 ± 63.93) comparing to TT genotype patients (67.06 ± 39.3), with no statistical significance. T allele frequency was significantly higher in group of vascular and congenital cause of kidney failure (Pearson X2 =6.049, P<0.05) comparing to inflammation etiology group. Genotype distribution results are within the results other studies in Europe. Obtained results indicate that C677T polymorphism is not associated with onset, duration and cause of kidney failure in our hemodialysis population. There is an association of T allele of the MTHFR gene and vascular and congenital cause kidney failure

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

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

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

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