Allele frequency distributions of Apo BVNTR locus in Cukurova, Turkey

WOS: 000251002300010PubMed ID: 16981218The highly polymorphic minisatellites contain a variable number of tandemly repeated (VNTR) DNA sequences. They are extremely useful and informative markers to study genetic variation among human populations. We have analysed the allele frequency distribution at the highly polymorphic apolipoprotein B (Apo B) VNTR locus in order to obtain the population data for the Cukurova region in Turkey by using the polymerase chain reaction and polyacrylamide gel electrophoresis. We observed 10 different alleles and 21 genotypes in a sample of 100 unrelated individuals. The allele frequencies ranged from 0.01 to 0.4, with an expected heterozygosity of 0.69 for the Apo B locus. Alleles 37 (frequency = 0.4) and 35 (frequency = 0.17) were the most common in the Cukurova population. There was a significant deviation from the Hardy-Weinberg equilibrium (HWE) for genotype frequencies (chi(2) = 29.12; df = 1; p = 0.000). This study possesses novelty as it is the first DNA polymorphism study conducted at the Cukurova population using an Apo B minisatellite locus. Copyright (C) 2006 John Wiley & Sons, Ltd

Hemoglobinopathies in the Cukurova Region and Neighboring Provinces

WOS: 000375483800005PubMed ID: 26984585To contribute to the creation of a mutation map of the region, we aimed to determine the mutation spectrum of thalassemias and abnormal hemoglobins (Hbs) in the Cukurova region and surrounding provinces. In this study, a total of 8135 samples from Adana, Hatay, Mersin, Konya and Kayseri provinces between 1993 and 2014 were analyzed. Complete blood cell (CBC) counts and Hb typing were carried out using automatic cell counters, cellulose acetate membrane electrophoresis and high performance liquid chromatography (HPLC), respectively. For the molecular analyses, genomic DNA was extracted using both manual and automated DNA extraction devices. Determination of Hb mutations were done by microarray, restriction fragment length polymorphism (RFLP), amplification refractory mutation system (ARMS) and gap-polymerase chain reaction (gap-PCR) methodologies. Samples were analyzed for abnormal Hb and thalassemia mutations. Out of 8135 samples, 1382 were observed to be carrying Hb mutations. It was identified that 826 mutation carriers included abnormal Hbs with a frequency of 59.7%, 416 carriers included beta-thalassemia (beta-thal) mutations with a frequency of 30.7% and 136 carriers included alpha-thalassemia (alpha-thal) mutations with a frequency of 9.9%. In this study, the most frequently observed abnormal Hb in the region was Hb S [beta 6(A3)Glu -> Val (GTG>GAG), HBB: c.20T>A], whereas the most commonly observed mutations were the IVS-I-110 (G>A) (HBB: c.93-21G>A) point mutation in beta-thal and the 3.7kb deletion in alpha-thal .DPTTurkiye Cumhuriyeti Kalkinma Bakanligi [2005K120320-E]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TAG 0758]; Cukurova University Research Fund, Adana, Turkey [TF2012D7]; [TF2008LTP14]; [TF2006YL9]; [SBE2004D4]; [SBE2002YL1]; [TF2001U32]; [SBE99D2]; [TF 9522]; [TFE 94-4]In this article, findings from the studies titled 'Establishing the infrastructure of the new methods to be used in the diagnosis of hemoglobinopathies: microarray and bioinformatics,' project no. 2005K120320-E by DPT, 'Screening of beta thalassemic gene frequency and determination of mutation focuses in Cukurova,' project no. TAG 0758 by TUBITAK, 'Determination of miRNA expression levels by RT-PCR in sickle cell anemia cases,' project no. TF2012D7 from the Cukurova University Research Fund, Adana, Turkey, 'Typing of the hemoglobinopathies and informing study in high schools in the region of Hatay-Samandag,' project no. TF2008LTP14, 'Determination of hemoglobinopathies with microarray method,' project no. TF2006YL9, 'Determination of abnormal hemoglobin and thalassemia mutation types of Konya region,' project no. SBE2004D4, 'Typing of beta-thalassemia mutations of Anamur region,' project no. SBE2002YL1, 'Screening of thalassemic mutations in Kayseri region,' project no. TF2001U32, 'The analysis of the mutations that cause the deficiency of alpha thalassemia and G6PD enzyme at the molecular level,' project no. SBE99D2, 'The typing of alpha thalassemia deletions by PCR method in the Cukurova region,' project no. TF 9522 and 'Determination of alpha thalassemia mutations at the molecular level in the Cukurova region,' project no. TFE 94-4, have been utilized. In this study, Dr. S. Yuzbasioglu Ariyurek, Dr. S. Menziletoglu Yildiz, Associate Professor A. Erdinc Yalin, Dr. F. Guzelgul and Professor Dr. K. Aksoy (Department of Medical Services and Technics, Vocational School of Health Services, Cukurova University, Adana; Department of Biochemistry, Faculty of Pharmacy, Mersin University, Mersin and Department of Medical Biochemistry, Faculty of Medicine, Cukurova University, Adana, Turkey) were involved in carrying out the experiments and in writing this article

Diagnostic Performance of Erythropoietin and Erythropoietin Receptors Levels in Children with Attention Deficit Hyperactivity Disorder

Objective: Attention deficit hyperactivity disorder (ADHD) is a heterogeneous, highly heritable, a common childhood neurobehavioural disorder resulting from complex gene-gene and gene-environment interactions. The erythropoietin (Epo)/erythropoietin receptors (EpoR) system turned out to have additional important functions in nonhematopoietic tissue. In this study, we aimed to investigate the levels of Epo and and EpoR, and also their diagnostic values in children with ADHD. Methods: A total of 70 children were included in the study, 35 drug-naive patients with ADHD (age: 6−12 years; male/female: 20/15) and 35 healthy controls (age: 6−12 years; male/female: 22/13). Serum Epo and EpoR levels was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Results: The results indicated that the levels of Epo decreased in patients with ADHD compared to control (p < 0.05). On the other hand, EpoR levels increased in these patients (p < 0.05). Furthermore, the ratio of Epo/EpoR was significantly lower in ADHD patients than controls (p < 0.05). Receiver operator characteristic curve analysis showed high diagnostic performance for Epo and EpoR, areas under curve were 0.980 and 1.000, respectively. Conclusion: This is the first report to investigate the association between serum Epo and EpoR levels in ADHD patients. Our results indicated that Epo may play a role in the etiology of ADHD, and Epo therapy may be beneficial in these disorders if given in addition to the routine treatment of children with ADHD. Furthermore, our results reveal possible diagnostic value of Epo and EpoR

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium