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    Analysis of the Population Genetic Structure of Hb D-Los Angeles [?121 (GH4) Glu?Gln GAA?CAA] in Denizli, Turkey; Genetic Diversity, Historical Demography and Estimation of the Mutation Rates Based on Haplotype Variation
    (Wiley, 2016) Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol O.
    Objective: Understanding the genetic origin of the Hb D-Los Angeles hemoglobin may elucidate population interactions such as movements, migrations, and environmental effects on mutation mechanisms in human biology throughout history. Our study aimed to understand the genetic origin of Hb D-Los Angeles based on haplotype data, observed in the Denizli province of Turkey. Methods: We studied DNA samples from 40 unrelated patients with abnormal hemoglobin Hb D-Los Angeles and 59 unrelated healthy subjects from our DNA bank. Possible associated haplotypes, HWE, genetic diversity and population differentiation, population genetic structure analysis and historical-demographic analysis for the two populations were determined by Arlequin ver. 3.5. Results: Molecular diversity results from the two populations show that both populations are genetically similar as far as development and expansion during the historical period. Historical gene flow results show high gene flow between the two populations. SSD and rg tests failed to reject the null hypothesis of population expansion which is consistent with unimodal distribution. Our estimated tau values show that the average time since the demographic expansion for normal and Hb D-Los Angeles populations ranged from approximately 42,000-38,000 ybp, respectively. Conclusions: Our data suggest that the Hb D-Los Angeles population originated within the normal population in Denizli, Turkey. Our results support the hypothesis that the Hb D-Los Angeles mutation may have originated in the Mediterranean area, independent from other populations such as India and China. The evaluation of such data may contribute valuable information to anthropological, paleoclimatic, archaeological, and phylogeographical approaches to human biology throughout the historical period. (C) 2015 Wiley Periodicals, Inc.
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    Associations of IL-17 and IL-17 receptor polymorphisms with Behcet's disease in Denizli Province of Turkey
    (Springer, 2023) Arikan, Sanem; Oztuerk, Onur; Duygulu, Seniz; Atalay, Erol Omer; Atalay, Ayfer
    Although the etiopathogenesis of Behcet's disease is not known, studies conducted in different populations show that it is a multifactorial disease that is thought to develop as a result of the interaction of environmental and genetic factors. IL-17 is thought to induce the neutrophilic inflammation and the tissue damage mediated by immune response in patients. Polymorphisms in the gene region encoding IL-17 and IL-17R molecules may play a critical role in the pathogenesis of the disease and contribute to the elucidation of disease mechanism. We aimed to show the association of IL-17A, IL-17F, and IL-17RC polymorphisms and haplotypes in Behcet's disease patients and its clinical features. We genotyped IL-17A (rs4711998 (A/G), rs8193036 (C/T), rs2275913 (A/G), rs3819025 (A/G), rs8193038 (A/G), rs3804513 (A/T), rs1974226 (C/T), rs3748067 (C/T)); IL-17F (rs763780 (T/C), rs2397084 (T/C)); and IL-17R (IL-17RC) (rs708567 (C/T)) polymorphisms in 88 patients with Behcet's disease and 133 healthy controls using PCR-RFLP-based approach. The results of our study showed that polymorphisms of IL-17A, rs8193036 (C/T), rs3819025 (G/A), rs3804513 (A/T), IL-17F rs2397084 (T/C), and IL-17RC rs708567 (C/T) are associated with the susceptibility to the BD. When the haplotype distributions of all loci of IL-17Aand IL-17A/IL-17F together were examined and in contrast to the data obtained from the controls, the GTGGAACC (27.84%) and GTGGAACCTT (25.57%) have the highest frequencies. In conclusion, the allele and genotype frequency differences of the IL-17A, IL-17F, and IL-17R and haplotype frequencies between Behcet's disease and controls indicate that the genetic structure of Behcet's disease may be different.
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    Comparative analysis of hemoglobin S and normal populations based on ?-Globin Like Gene Cluster Haplotype Variation in Denizli, Turkey; Historical- Geographical perspectives and mutation age estimation
    (Inonu University School of Medicine Department of Biophysics, Malatya, 2017) Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol Omer
    Öz: Aim: Our study aimed to understand the genetic origin of Hb S based on comparative analysis with normal population haplotype data in the Denizli province of Turkey. Material and Methods: We performed data obtained from previously published articles. We studied DNA samples from 12 unrelated patients with heterozygous abnormal hemoglobin S (Hb S) and 59 unrelated healthy subjects from published articles. The association of population genetic parameters such as haplotypes, diversity, differentiation, HWE and demographic analysis for two populations were performed by latest version of the Arlequin software (ver. 3.5). Results: Our results show that normal and Hb S populations have different genetic parameters based on haplotype diversity through the history. The obtained results are highly associated with frequency haplotype [+ ---+ + +] (20.8%) in the Hb S population and the Mediterranean haplotype I [+ ----+ +] (14.4%) in the Normal population. According to historical population growth and mutation age parameter of ? values for normal and Hb S populations dated approximately 42,000 to 26,000 ybp, respectively. Conclusions: Historically, two populations exhibit different genetic parameters and unimodal growth distribution. Our results are consistent with the Hb S mutation which occured in this region about 26,000 years ago.
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    Comparative analysis of hemoglobin S and normal populations based on β-Globin Like Gene Cluster Haplotype Variation in Denizli, Turkey; Historical-Geographical perspectives and mutation age estimation )
    (2017) Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol Omer
    Aim: Our study aimed to understand the genetic origin of Hb S based on comparative analysis with normal population haplotype data in the Denizli province of Turkey. Material and Methods: We performed data obtained from previously published articles. We studied DNA samples from 12 unrelated patients with heterozygous abnormal hemoglobin S (Hb S) and 59 unrelated healthy subjects from published articles. The association of population genetic parameters such as haplotypes, diversity, differentiation, HWE and demographic analysis for two populations were performed by latest version of the Arlequin software (ver. 3.5). Results: Our results show that normal and Hb S populations have different genetic parameters based on haplotype diversity through the history. The obtained results are highly associated with frequency haplotype [+ ---+ + +] (20.8%) in the Hb S population and the Mediterranean haplotype I [+ ----+ +] (14.4%) in the Normal population. According to historical population growth and mutation age parameter of τ values for normal and Hb S populations dated approximately 42,000 to 26,000 ybp, respectively. Conclusions: Historically, two populations exhibit different genetic parameters and unimodal growth distribution. Our results are consistent with the Hb S mutation which occured in this region about 26,000 years ago
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    Estimating the age of Hb G-Coushatta [22(B4)GluAla] mutation by haplotypes of -globin gene cluster in Denizli, Turkey
    (Wiley, 2018) Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol O.
    BackgroundHb G-Coushatta variant was reported from various populations' parts of the world such as Thai, Korea, Algeria, Thailand, China, Japan and Turkey. In our study, we aimed to discuss the possible historical relationships of the Hb G-Coushatta mutation with the possible migration routes of the world. For this purpose, associated haplotypes were determined using polymorphic loci in the beta globin gene cluster of hemoglobin G-Coushatta and normal populations in Denizli, Turkey. MethodsWe performed statistical analysis such as haplotype analysis, Hardy-Weinberg equilibrium, measurement of genetic diversity and population differentiation parameters, analysis of molecular variance using F-statistics, historical-demographic analyses, mismatch distribution analysis of both populations and applied the test statistics in Arlequin ver. 3.5 software program. ResultsThe diversity of haplotypes has been shown to indicate different genetic origins for two populations. However, AMOVA results, molecular diversity parameters and population demographic expansion times showed that the Hb G-Coushatta mutation develops on the normal population gene pool. Our estimated values showed the average time since the demographic expansion for normal and Hb G-Coushatta populations ranged from approximately 42,000 to 38,000 ybp, respectively. ConclusionOur data suggest that Hb G-Coushatta population originate in normal population in Denizli, Turkey. These results support the hypothesis that the multiple origin of Hb G-Coushatta and indicate that mutation may have been triggered the formation of new variants on beta globin haplotypes.
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    The IL-8 Gene Polymorphisms in Behcet's Disease Observed in Denizli Province of Turkey
    (Taylor & Francis Inc, 2016) Atalay, Ayfer; Arikan, Sanem; Ozturk, Onur; Oncu, Mustafa; Tasli, Mehmet Levent; Duygulu, Seniz; Atalay, Erol Omer
    Behcet's disease is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration and uveitis with unknown pathogenesis. IL-8, a proinflammatory cytokine, has been found increased in the active stage of BD. DNA samples were obtained from 88 patients with BD and 112 healthy control subjects in Denizli province of Turkey. All genotyping experiments of SNPs in IL-8 gene were performed using polymerase chain reaction-restriction fragment polymorphism. We found that IL-8 -845 T > C and -738 T > A sites are non-polymorphic. There were no differences in the polymorphisms of IL-8 + 396 G/T, + 781 C/T, and + 1633 C/T sites except IL-8 -251 T > A in between patients and healthy controls. Analysis of IL-8 polymorphisms indicates that the distribution of frequencies seems to be associated with -251 T > A and gender, -251 T > A and erythema nodosum, -251 T > A and ocular involvement, + 781 C > T and erythema nodosum, + 396 G > T and pathergy positivity, and + 1633 C > T and papulopustular lesion. We demonstrated that the frequencies of IL-8 haplotypes were significantly different with BD patients than control group. We found that the distribution of IL-8 haplotypes was significantly different with genital ulcers, ocular involvement, positive pathergy test, erythema nodosum, papulopustular lesions, and arthritis with BD patients than healthy control individuals. Our study suggests that IL-8 gene polymorphisms may affect susceptibility to BD and increase the risk of developing disease. In order to confirm and assess the association of IL-8 and other cytokine gene polymorphisms in the pathophysiology of BD, large cohort studies are needed.
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    Time estimations by network of beta globin gene cluster haplotypes linked with Hb D-Los Angeles [?121 (GH4) Glu ? Gln GAA ? CAA] mutation in the world populations
    (Wiley, 2018) Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol O.
    Background beta-Globin gene cluster haplotypes associated with the Hb D-Los Angeles mutation have been reported in many different locations in different populations including Italy, Iran, Thailand, Belgium, Mexico, Holland, and Turkey. In this study, we have identified genetic relationships and formation periods between the haplotypes reported in the world regarding the Hb D-Los Angeles. Methods We comparatively analyzed the RFLP (restriction fragment length polymorphism) data in Denizli region and world populations using Arlequin 3.5 statistical software program. The data obtained from the Arlequin software were then entered into the Phylogenetic Network software to calculate the age estimates and to discover possible links between the haplotypes. Results We observed the frequencies of the beta-globin gene haplotypes for the seven polymorphic restriction sites around the world and calculated the estimated time of haplotypes using Network software on the basis of ancestral haplotypes. We performed the phylogenetic network analysis of the haplotypes linked with Hb D-Los Angeles mutation by processing the data of frequency and age estimations with Network software. Conclusion Our period of time results suggests that HAP1 was formed before modern human migration to Asia and/or independent origin of the Hb D-Los Angeles mutation from other populations. Considering that the population in Denizli region started the Hb D-Los Angeles mutation past about 40,000 years ago, it can be said that HAP1, HAP15, and HAP21 belong to the gene pool with an external effect. Our period of time results of HAP6 is compatible with published dating results.