Background: After the first genome had been sequenced in 2003 with an international project, Huma... more Background: After the first genome had been sequenced in 2003 with an international project, Human Genome Project, the 1000 Genomes Project also revealed the analysis of 1092 and 2504 genomes respectively. Whole exome sequencing of human samples was reported to detect approximately 20,000-30,000 SNV and indel calls on average. It is very important to choose the best tool that suits the related study. Methods: In this study, it is aimed to demonstrate the results of an in-house method (SELIM) for variant prioritization of WES data without using in-silico methods. Results: By this method, the annotated data have been decreased by 7.4-13.8 times (mean=10.9). Conclusion: By the initiation of 1.000.000 genome project, powerful databases are needed. In this respect, SELIM is an in-house workflow that can easily be used for simplifying the annotated data without using any insilico methods.
Network modeling analysis in health informatics and bioinformatics, Aug 10, 2019
Whole exome sequencing (WES), workflow consists of the following steps: raw data quality assessme... more Whole exome sequencing (WES), workflow consists of the following steps: raw data quality assessment, pre-processing, alignment, post-processing, variant calling, annotation, and prioritization. WES of human samples was reported to detect approximately 20,000-30,000 SNV and indel calls on average. Therefore, it is very important to choose the best tool that suits the related study. In this study, we aimed to upgrade our previous in-house variant prioritization method to analyse WES data without using in silico methods. By this method, the annotated data have been decreased by means of 52.3 times. Therefore, we both established a successful WES workflow for increasing the diagnostic rate of patients with reducing the raw data. Recently, we are also building a web-based workflow to help the users from all over the world.
International Journal of Human Genetics, Feb 8, 2014
Historically, Punjab has served a major passage way for human migration to Indian subcontinent an... more Historically, Punjab has served a major passage way for human migration to Indian subcontinent and has influenced the genetic structure of extant populations in Punjab. Therefore, Punjabi population possesses an exclusive genetic profile primarily due to the many migratory events in this region which caused an extensive range of genetic diversity. Hence, the present study is an attempt to understand the effect of these influences on genetic differentiation, diversity a nd popula tion structure of Punjab. Genetic polymorphism at five highly polymorphic short tandem repeat loci (STR) is studied in four endogamous population groups of Punjab, India. The studied groups included Jat Sikh, Majbi Sikh, Brahmin and Ramdasia to evaluate their significance in human identification and genetic study. All selected groups practice endogamy and a total of 358 individuals belonging to these four endogamous groups were studied for five highly polymorphic with greater power of exclusion STR loci: THO1, TPOX, D7S820, CSF1PO and vWA. The highest observed heterozygosity was found in Ramdasia population for almost all the markers except vWA which had highest observed heterozygosity among Majbi Sikh population group. In this study, the average sub-ethnic differentiation (Fst) among the four populations of northwest Punjab was 0.0821. The marker with the highest contribution to interpopulation genetic difference was obser ved to be vWA.
Limited number of researches exist on the relationship between PPARGC1A gene polymorphism (rs8192... more Limited number of researches exist on the relationship between PPARGC1A gene polymorphism (rs8192678) and affects the athletic performance. Thus, the present study aims to decipher any possible association of the rs8192678 polymorphism in the PPARGC1A gene with the competitive performances of Turkish elite track and field athletes. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/sedentary with the ages of 18-35 voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the personal best (PB) of the athletes. Whole exome sequencing (WES) was performed by the genomic DNA sample isolated from blood of the participants. The association between rs8192678 polymorphism and PB was examined by one-way analysis of covariance (ANCOVA) with the adjustment of sex and sport experience. According to the results, there were not any significant deviation between the wi...
The aim of the study was to identify genetic variants associated with personal best scores in Tur... more The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10−7) in genotype–phenotype and case–control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional va...
The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its ... more The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its effect on elite athletes’ performance. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/ physically inactive, aged 18–35, voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the athletes’ personal best (PB). Whole exome sequencing (WES) was performed by the genomic DNA isolated from the peripheral blood of the participants. Sports type, sex, and competitive performance were chosen as the parameters to compare within and between the groups by linear regression models. The results showed no statistically significant difference between the CC, TC, and TT genotypes within and between the groups (p > 0.05). Additionally, our results underlined that there were no statistically significant differences for the association of rs2228570 polymorphism with PBs...
Yapılan araĢtırmanın amacı, anjiyotensinojen (AGT) rs699 gen polimorfizminin futbolcular ve sedan... more Yapılan araĢtırmanın amacı, anjiyotensinojen (AGT) rs699 gen polimorfizminin futbolcular ve sedanter bireyler arasında genotip ve allel dağılımlarının incelenmesidir. Materyal & Metot: Yapılan araĢtırmaya 52 futbolcu ve 106 sedanter birey olmak üzere toplam 158 katılımcı gönüllü olarak dahil edilmiĢtir. Genomik DNA, kullanıcı protokolüne göre Invitrogen DNA Ġzolasyon Kiti (Invitrogen, ABD) kullanılarak oral epitel hücrelerden izole edilmiĢtir. Genotipleme iĢlemi ger ek zamanlı Polimeraz Zincir Reaksiyonu (Rt-PCR) metodu ile ger ekleĢtirilmiĢtir. Bulgular: Gruplar, genotip ve allel bakımından karĢılaĢtırıldıklarında istatistiksel olarak anlamlı bir farklılık tespit edilmemiĢtir (sırasıyla X 2 =1.774, p=0.438, X 2 = .993, p=0.465). AraĢtırmada hem sporcularda hem de kontrol grubunda CT genotipinin ve C allel taĢıyıcılığının daha fazla olduğu tespit edilmiĢtir. Sonuç: Literatür bilgileri de dikkate alındığında hem futbolcuların hem de kontrol grubunun sürat, gü ve kuvvet branĢlarına daha yatkın oldukları söylenebilir. Benzer araĢtırmaların elit seviyede performans gösteren ok sayıda futbolcu gruplarının üzerinde analiz edilmesini öneririz.
... Personal Authors, Ergun, Mehmet Ali (Gazi University Faculty of Medicine, Besevler, Ankara,Tu... more ... Personal Authors, Ergun, Mehmet Ali (Gazi University Faculty of Medicine, Besevler, Ankara,Turkey), E-mail: [email protected] ... QF-PCR can rapidly and accurately diagnose sex chromosome status and imbalances, reducing maternal anxiety and aiding in efficient ...
Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "... more Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal dysgenesis primarily affect the gonads. Genetic alterations in ten unrelated females with complete 46, XY gonadal dysgenesis (GD) were analyzed using an Array 2.7 M platform with whole genome coverage. The analysis result suggested that the most significant region maps to chromosome 8q24.3 which were previously reported by another independent study with a similar patient cohort and this region being probable candidate related to complete 46, XY GD.
BACKGROUND Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorde... more BACKGROUND Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as first-tier genetic tests. This study's first aim was to determine the clinical usefulness of CMAs in children diagnosed with ASD in a Turkish population. The second aim was to describe the CNVs and clinical phenotypes of children with ASD. METHODS AND RESULTS This was a single-center retrospective cross-sectional study. Data were obtained from the medical records of children with ASD followed at Gazi University Hospital, (Ankara, Turkey). The sample consisted of 47 ASD cases (mean age: 60.34 ± 25.60 months; 82.9% boys). The diagnostic yield of the CMAs was 8.5%. Four pathogenic CNVs were identified: 9p24.3p24.2 deletion, 15q11-q13 duplication, 16p11.2 deletion, and 22q13.3 deletion. Also, four variants were found at 2q36.3, 10p11.21, 15q11.2, and Xp11.22, which were classified as variants of uncertain significance (VUS). CONCLUSIONS The TRAP12 and PARD3 genes in CNVs classified as VUS may be worth investigating for autism. The initial identification of both clinical and biological markers can facilitate monitoring, early intervention, or prevention and advance our understanding of the neurobiology underlying ASD.
Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that partic... more Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that participate in overlapping clinical features with autism spectrum disorders (ASDs). It has been reported that in addition to common mutations or deletions, individuals with chromosomal duplications including either the MECP2 or UBE3A loci show clinical features related to those of MECP2 duplication syndrome, AS, or ASDs. Here we report a 10-year--10-months old male patient having overlapping clinical features of MECP2 duplication syndrome, AS and ASDs. He had mental retardation, lack of speech and developmental delay, and also dysmorphic features such as plagiocephaly, retrognathia, hyperextensible joints in fingers and elbows, broad great toe and three different sizes of cafe au laits. The X-ray revealed compound craniosynostosis and the cranial MRI at 10 years showed delayed myclination. Due to his clinical features, we performed molecular karyotyping and found numerous genomic alterations. Two of these genomic alterations including duplications of chromosome Xq28 and 15qll.2ql3.l1 were found to be compatible with his clinical findings. According to methylation analysis, duplicated UBE3A gene found to be not methylated. The present case study may contribute to a better definition and an improved comprehension of the overlapping pathways of MECP2 and UBE3A.
Journal of the Turkish-German Gynecological Association, Sep 1, 2011
An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic vill... more An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic villus biopsy specimen of a balanced reciprocal translocation carrier mother. This was a 3:1 segregation of the unbalanced product of the balanced maternal 8:9 translocation. The chromosomes of the carrier of the balanced reciprocal translocation pair with their matching homologous segments at meiosis I, a quadrivalent figure is formed and chromosomes segregate from this configuration. Increased nuchal tranaslucency was also determined on fetal sonography at the 13 rd week of gestation. The final karyotype was 47,X Y,+der(8)t(8;9)(q11.2;p22) mat, and the parents were informed about this tertiary trisomy. After genetic counseling, the parents decided to terminate the pregnancy. The presented case is a reminder of the probability of the unbalanced products of the 3:1 segregation, rather than the common 2:2 segregation.
Isolated partial duplication of the long arm of chromosome 11 is very rare. The main features are... more Isolated partial duplication of the long arm of chromosome 11 is very rare. The main features are dysmorphic facial features, pre/postnatal growth retardation, speech delay, mental retardation, hypotonia, microcephaly, and cardiac, vertebral, limb and genital anomalies. In this case, we report a patient with partial trisomy of 11q13.5 → qter due to a de novo rearrangement consisting of the whole X chromosome and part of chromosome 11; 46,X,der(X)(Xqter → Xp22.33::11q13.5 → 11qter). Additional findings were a separated clavicle, lacrimal duct stenosis and prenatally detected renal hypoplasia. SNP array results revealed a duplication between 11q13.5 and 11qter, measuring 58 Mb, from nucleotide 76,601,607 to 134,926,021. As a result, molecular karyotyping could be performed in such cases in order to establish a definite phenotype-genotype correlation using conventional or molecular cytogenetics techniques.
Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA ... more Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA at any stage of the mitotic cycle. Analysis of sister chromatid exchange (SCE) has come into use as a sensitive DNA-damage indicator. We investigated the SCE rates in radiology technologists who are occupationally and chronically exposed to ionizing radiation. The study included 39 radiology technologists and 35 sex- and age-matched healthy controls. There was a statistically significant difference in the SCE frequency between radiology technologists and controls (p&lt;0.0001). Additionally, previous SCE data of 10 radiology technologists were compared with current results regarding radiation exposure time. There was statistically significant difference between previous and current SCE values (p=0.005). The significant increase in the frequency of SCE in radiology technologists emphasizes the importance of radiation-protection procedures in order to minimize radiation exposure and avoid possible genotoxic effects. Comparison of two studies that measured SCE values of radiology technologists after 8 years also suggests that the genotoxic effect is reversible. In conclusion, radiation is still an important mutagenic agent despite improvements in daily working hours and conditions.
Genetic Testing and Molecular Biomarkers, Aug 1, 2018
Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascu... more Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascular systems, is caused by heterozygous pathogenic variants in FBN1. To date, over 1800 different pathogenic variants have been reported. In the present study, FBN1 sequence analysis was performed in a family and two unrelated patients with MS. Three novel pathogenic variants were detected. Two of these variants [c.6610T&amp;amp;gt;C; p.(Cys2204Arg) and c.1956T&amp;amp;gt;G; p.(Cys652Trp)], which affect a cysteine residue, were associated with MS with ectopia lentis, whereas the mutation causing a premature stop codon [c.2506delA; p.(Ser836ValfsX10)] leads to a classical MS of a milder phenotype. We anticipate that the three novel pathogenic variants identified in this study will provide further support for the clinical relevance of variants in the large FBN1 gene.
Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this ... more Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism. The presented case will contribute to the identification of the genotype-phenotype correlation in chromosome 18 anomalies.
Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha... more Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G polymorphism and CAD, the c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.
Recent studies suggest that copy number variations (CNVs) play a signi cant role in the aetiology... more Recent studies suggest that copy number variations (CNVs) play a signi cant role in the aetiology of ASD. This study aims to investigate CNVs, which are thought to be an important factor in ASD etiology. In addition it was aimed to specify the clinical usefulness of chromosomal microarrays (CMA) in the examination of ASD patients in Turkish population. Of 47 children (60.34±25.60 months; 82.9% boys) with ASD were constructed the sample. The karyotype structure of all participants was found to be normal using conventional cytogenetic methods. DNA obtained from the venous blood samples of the participants was evaluated using SurePrint G3 ISCA V2 CGH 8x60K Array (Agilent Technologies Santa Clara, CA, USA). We have identi ed 8 CNVs, ranging in size from 55 kb to 6.5 Mb in 7 (5 boys) of 47 children with ASD of the 4 of 8 CNVs were classi ed as pathogenic, which were 9p24.3p24.2 deletion in 3 Mb size, 15q11-q13 duplication in 6.5 Mb size, 16p11.2 deletion in 598 kb size and 22q13.3 deletion in 55 kb size. According to results has been demonstrated that diagnostic yield of CMA in Turkish children with ASD was 8.5%. Our results indicate that CNVs contribute a part to the genetic aetiology of Turkish children with ASD. In accordance with the literature, these results emphasize the clinical importance of CMA to investigate the aetiology of ASD.
Background: After the first genome had been sequenced in 2003 with an international project, Huma... more Background: After the first genome had been sequenced in 2003 with an international project, Human Genome Project, the 1000 Genomes Project also revealed the analysis of 1092 and 2504 genomes respectively. Whole exome sequencing of human samples was reported to detect approximately 20,000-30,000 SNV and indel calls on average. It is very important to choose the best tool that suits the related study. Methods: In this study, it is aimed to demonstrate the results of an in-house method (SELIM) for variant prioritization of WES data without using in-silico methods. Results: By this method, the annotated data have been decreased by 7.4-13.8 times (mean=10.9). Conclusion: By the initiation of 1.000.000 genome project, powerful databases are needed. In this respect, SELIM is an in-house workflow that can easily be used for simplifying the annotated data without using any insilico methods.
Network modeling analysis in health informatics and bioinformatics, Aug 10, 2019
Whole exome sequencing (WES), workflow consists of the following steps: raw data quality assessme... more Whole exome sequencing (WES), workflow consists of the following steps: raw data quality assessment, pre-processing, alignment, post-processing, variant calling, annotation, and prioritization. WES of human samples was reported to detect approximately 20,000-30,000 SNV and indel calls on average. Therefore, it is very important to choose the best tool that suits the related study. In this study, we aimed to upgrade our previous in-house variant prioritization method to analyse WES data without using in silico methods. By this method, the annotated data have been decreased by means of 52.3 times. Therefore, we both established a successful WES workflow for increasing the diagnostic rate of patients with reducing the raw data. Recently, we are also building a web-based workflow to help the users from all over the world.
International Journal of Human Genetics, Feb 8, 2014
Historically, Punjab has served a major passage way for human migration to Indian subcontinent an... more Historically, Punjab has served a major passage way for human migration to Indian subcontinent and has influenced the genetic structure of extant populations in Punjab. Therefore, Punjabi population possesses an exclusive genetic profile primarily due to the many migratory events in this region which caused an extensive range of genetic diversity. Hence, the present study is an attempt to understand the effect of these influences on genetic differentiation, diversity a nd popula tion structure of Punjab. Genetic polymorphism at five highly polymorphic short tandem repeat loci (STR) is studied in four endogamous population groups of Punjab, India. The studied groups included Jat Sikh, Majbi Sikh, Brahmin and Ramdasia to evaluate their significance in human identification and genetic study. All selected groups practice endogamy and a total of 358 individuals belonging to these four endogamous groups were studied for five highly polymorphic with greater power of exclusion STR loci: THO1, TPOX, D7S820, CSF1PO and vWA. The highest observed heterozygosity was found in Ramdasia population for almost all the markers except vWA which had highest observed heterozygosity among Majbi Sikh population group. In this study, the average sub-ethnic differentiation (Fst) among the four populations of northwest Punjab was 0.0821. The marker with the highest contribution to interpopulation genetic difference was obser ved to be vWA.
Limited number of researches exist on the relationship between PPARGC1A gene polymorphism (rs8192... more Limited number of researches exist on the relationship between PPARGC1A gene polymorphism (rs8192678) and affects the athletic performance. Thus, the present study aims to decipher any possible association of the rs8192678 polymorphism in the PPARGC1A gene with the competitive performances of Turkish elite track and field athletes. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/sedentary with the ages of 18-35 voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the personal best (PB) of the athletes. Whole exome sequencing (WES) was performed by the genomic DNA sample isolated from blood of the participants. The association between rs8192678 polymorphism and PB was examined by one-way analysis of covariance (ANCOVA) with the adjustment of sex and sport experience. According to the results, there were not any significant deviation between the wi...
The aim of the study was to identify genetic variants associated with personal best scores in Tur... more The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10−7) in genotype–phenotype and case–control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional va...
The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its ... more The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its effect on elite athletes’ performance. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/ physically inactive, aged 18–35, voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the athletes’ personal best (PB). Whole exome sequencing (WES) was performed by the genomic DNA isolated from the peripheral blood of the participants. Sports type, sex, and competitive performance were chosen as the parameters to compare within and between the groups by linear regression models. The results showed no statistically significant difference between the CC, TC, and TT genotypes within and between the groups (p > 0.05). Additionally, our results underlined that there were no statistically significant differences for the association of rs2228570 polymorphism with PBs...
Yapılan araĢtırmanın amacı, anjiyotensinojen (AGT) rs699 gen polimorfizminin futbolcular ve sedan... more Yapılan araĢtırmanın amacı, anjiyotensinojen (AGT) rs699 gen polimorfizminin futbolcular ve sedanter bireyler arasında genotip ve allel dağılımlarının incelenmesidir. Materyal & Metot: Yapılan araĢtırmaya 52 futbolcu ve 106 sedanter birey olmak üzere toplam 158 katılımcı gönüllü olarak dahil edilmiĢtir. Genomik DNA, kullanıcı protokolüne göre Invitrogen DNA Ġzolasyon Kiti (Invitrogen, ABD) kullanılarak oral epitel hücrelerden izole edilmiĢtir. Genotipleme iĢlemi ger ek zamanlı Polimeraz Zincir Reaksiyonu (Rt-PCR) metodu ile ger ekleĢtirilmiĢtir. Bulgular: Gruplar, genotip ve allel bakımından karĢılaĢtırıldıklarında istatistiksel olarak anlamlı bir farklılık tespit edilmemiĢtir (sırasıyla X 2 =1.774, p=0.438, X 2 = .993, p=0.465). AraĢtırmada hem sporcularda hem de kontrol grubunda CT genotipinin ve C allel taĢıyıcılığının daha fazla olduğu tespit edilmiĢtir. Sonuç: Literatür bilgileri de dikkate alındığında hem futbolcuların hem de kontrol grubunun sürat, gü ve kuvvet branĢlarına daha yatkın oldukları söylenebilir. Benzer araĢtırmaların elit seviyede performans gösteren ok sayıda futbolcu gruplarının üzerinde analiz edilmesini öneririz.
... Personal Authors, Ergun, Mehmet Ali (Gazi University Faculty of Medicine, Besevler, Ankara,Tu... more ... Personal Authors, Ergun, Mehmet Ali (Gazi University Faculty of Medicine, Besevler, Ankara,Turkey), E-mail: [email protected] ... QF-PCR can rapidly and accurately diagnose sex chromosome status and imbalances, reducing maternal anxiety and aiding in efficient ...
Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "... more Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal dysgenesis primarily affect the gonads. Genetic alterations in ten unrelated females with complete 46, XY gonadal dysgenesis (GD) were analyzed using an Array 2.7 M platform with whole genome coverage. The analysis result suggested that the most significant region maps to chromosome 8q24.3 which were previously reported by another independent study with a similar patient cohort and this region being probable candidate related to complete 46, XY GD.
BACKGROUND Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorde... more BACKGROUND Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as first-tier genetic tests. This study's first aim was to determine the clinical usefulness of CMAs in children diagnosed with ASD in a Turkish population. The second aim was to describe the CNVs and clinical phenotypes of children with ASD. METHODS AND RESULTS This was a single-center retrospective cross-sectional study. Data were obtained from the medical records of children with ASD followed at Gazi University Hospital, (Ankara, Turkey). The sample consisted of 47 ASD cases (mean age: 60.34 ± 25.60 months; 82.9% boys). The diagnostic yield of the CMAs was 8.5%. Four pathogenic CNVs were identified: 9p24.3p24.2 deletion, 15q11-q13 duplication, 16p11.2 deletion, and 22q13.3 deletion. Also, four variants were found at 2q36.3, 10p11.21, 15q11.2, and Xp11.22, which were classified as variants of uncertain significance (VUS). CONCLUSIONS The TRAP12 and PARD3 genes in CNVs classified as VUS may be worth investigating for autism. The initial identification of both clinical and biological markers can facilitate monitoring, early intervention, or prevention and advance our understanding of the neurobiology underlying ASD.
Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that partic... more Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that participate in overlapping clinical features with autism spectrum disorders (ASDs). It has been reported that in addition to common mutations or deletions, individuals with chromosomal duplications including either the MECP2 or UBE3A loci show clinical features related to those of MECP2 duplication syndrome, AS, or ASDs. Here we report a 10-year--10-months old male patient having overlapping clinical features of MECP2 duplication syndrome, AS and ASDs. He had mental retardation, lack of speech and developmental delay, and also dysmorphic features such as plagiocephaly, retrognathia, hyperextensible joints in fingers and elbows, broad great toe and three different sizes of cafe au laits. The X-ray revealed compound craniosynostosis and the cranial MRI at 10 years showed delayed myclination. Due to his clinical features, we performed molecular karyotyping and found numerous genomic alterations. Two of these genomic alterations including duplications of chromosome Xq28 and 15qll.2ql3.l1 were found to be compatible with his clinical findings. According to methylation analysis, duplicated UBE3A gene found to be not methylated. The present case study may contribute to a better definition and an improved comprehension of the overlapping pathways of MECP2 and UBE3A.
Journal of the Turkish-German Gynecological Association, Sep 1, 2011
An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic vill... more An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic villus biopsy specimen of a balanced reciprocal translocation carrier mother. This was a 3:1 segregation of the unbalanced product of the balanced maternal 8:9 translocation. The chromosomes of the carrier of the balanced reciprocal translocation pair with their matching homologous segments at meiosis I, a quadrivalent figure is formed and chromosomes segregate from this configuration. Increased nuchal tranaslucency was also determined on fetal sonography at the 13 rd week of gestation. The final karyotype was 47,X Y,+der(8)t(8;9)(q11.2;p22) mat, and the parents were informed about this tertiary trisomy. After genetic counseling, the parents decided to terminate the pregnancy. The presented case is a reminder of the probability of the unbalanced products of the 3:1 segregation, rather than the common 2:2 segregation.
Isolated partial duplication of the long arm of chromosome 11 is very rare. The main features are... more Isolated partial duplication of the long arm of chromosome 11 is very rare. The main features are dysmorphic facial features, pre/postnatal growth retardation, speech delay, mental retardation, hypotonia, microcephaly, and cardiac, vertebral, limb and genital anomalies. In this case, we report a patient with partial trisomy of 11q13.5 → qter due to a de novo rearrangement consisting of the whole X chromosome and part of chromosome 11; 46,X,der(X)(Xqter → Xp22.33::11q13.5 → 11qter). Additional findings were a separated clavicle, lacrimal duct stenosis and prenatally detected renal hypoplasia. SNP array results revealed a duplication between 11q13.5 and 11qter, measuring 58 Mb, from nucleotide 76,601,607 to 134,926,021. As a result, molecular karyotyping could be performed in such cases in order to establish a definite phenotype-genotype correlation using conventional or molecular cytogenetics techniques.
Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA ... more Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA at any stage of the mitotic cycle. Analysis of sister chromatid exchange (SCE) has come into use as a sensitive DNA-damage indicator. We investigated the SCE rates in radiology technologists who are occupationally and chronically exposed to ionizing radiation. The study included 39 radiology technologists and 35 sex- and age-matched healthy controls. There was a statistically significant difference in the SCE frequency between radiology technologists and controls (p&lt;0.0001). Additionally, previous SCE data of 10 radiology technologists were compared with current results regarding radiation exposure time. There was statistically significant difference between previous and current SCE values (p=0.005). The significant increase in the frequency of SCE in radiology technologists emphasizes the importance of radiation-protection procedures in order to minimize radiation exposure and avoid possible genotoxic effects. Comparison of two studies that measured SCE values of radiology technologists after 8 years also suggests that the genotoxic effect is reversible. In conclusion, radiation is still an important mutagenic agent despite improvements in daily working hours and conditions.
Genetic Testing and Molecular Biomarkers, Aug 1, 2018
Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascu... more Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascular systems, is caused by heterozygous pathogenic variants in FBN1. To date, over 1800 different pathogenic variants have been reported. In the present study, FBN1 sequence analysis was performed in a family and two unrelated patients with MS. Three novel pathogenic variants were detected. Two of these variants [c.6610T&amp;amp;gt;C; p.(Cys2204Arg) and c.1956T&amp;amp;gt;G; p.(Cys652Trp)], which affect a cysteine residue, were associated with MS with ectopia lentis, whereas the mutation causing a premature stop codon [c.2506delA; p.(Ser836ValfsX10)] leads to a classical MS of a milder phenotype. We anticipate that the three novel pathogenic variants identified in this study will provide further support for the clinical relevance of variants in the large FBN1 gene.
Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this ... more Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism. The presented case will contribute to the identification of the genotype-phenotype correlation in chromosome 18 anomalies.
Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha... more Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G polymorphism and CAD, the c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.
Recent studies suggest that copy number variations (CNVs) play a signi cant role in the aetiology... more Recent studies suggest that copy number variations (CNVs) play a signi cant role in the aetiology of ASD. This study aims to investigate CNVs, which are thought to be an important factor in ASD etiology. In addition it was aimed to specify the clinical usefulness of chromosomal microarrays (CMA) in the examination of ASD patients in Turkish population. Of 47 children (60.34±25.60 months; 82.9% boys) with ASD were constructed the sample. The karyotype structure of all participants was found to be normal using conventional cytogenetic methods. DNA obtained from the venous blood samples of the participants was evaluated using SurePrint G3 ISCA V2 CGH 8x60K Array (Agilent Technologies Santa Clara, CA, USA). We have identi ed 8 CNVs, ranging in size from 55 kb to 6.5 Mb in 7 (5 boys) of 47 children with ASD of the 4 of 8 CNVs were classi ed as pathogenic, which were 9p24.3p24.2 deletion in 3 Mb size, 15q11-q13 duplication in 6.5 Mb size, 16p11.2 deletion in 598 kb size and 22q13.3 deletion in 55 kb size. According to results has been demonstrated that diagnostic yield of CMA in Turkish children with ASD was 8.5%. Our results indicate that CNVs contribute a part to the genetic aetiology of Turkish children with ASD. In accordance with the literature, these results emphasize the clinical importance of CMA to investigate the aetiology of ASD.
Uploads
Papers by Mehmet Ergun