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Application of diagnostic methods and molecular diagnosis of hemoglobin disorders in Khuzestan province of Iran
Fakher Rahim,Bijan Kaeikhaei,Taghi Akbari
Indian Journal of Human Genetics , 2007,
Abstract: Background : The hemoglobinopathies refer to a diverse group of inherited disorders characterized by a reduced synthesis of one or more globin chains (thalassemias) or the synthesis of structurally abnormal hemoglobin (Hb). The thalassemias often coexist with a variety of structural Hb variants giving rise to complex genotypes and an extremely wide spectrum of clinical and hematological phenotypes. Hematological and biochemical investigations and family studies provide essential clues to the different interactions and are fundamental to DNA diagnostics of the Hb disorders. Although DNA diagnostics have made a major impact on our understanding and detection of the hemoglobinopathies, DNA mutation testing should never be considered a shortcut or the test of first choice in the workup of a hemoglobinopathy. Materials and Methods: A careful three-tier approach involving: (1) Full blood count (2) Special hematological tests, followed by (3) DNA mutation analysis, provides the most effective way in which to detect primary gene mutations as well as gene-gene interactions that can influence the overall phenotype. With the exception of a few rare deletions and rearrangements, the molecular lesions causing hemoglobinopathies are all identifiable by PCR-based techniques. Furthermore, each at-risk ethnic group has its own combination of common Hb variants and thalassemia mutations. In Iran, there are many different forms of a and β thalassemia. Increasingly, different Hb variants are being detected and their effects per se or in combination with the thalassemias, provide additional diagnostic challenges. Results:We did step-by-step diagnosis workup in 800 patients with hemoglobinopathies who referred to Research center of Thalassemia and Hemoglobinopathies in Shafa Hospital of Ahwaz Joundishapour University of medical sciences, respectively. We detected 173 patients as iron deficiency anemia (IDA) and 627 individuals as thalassemic patients by use of different indices. We have successfully detected 75% (472/627) of the β -thalassemia mutations by using amplification refractory mutation system (ARMS) technique and 19% (130/627) of the β -thalassemia mutations by using Gap-PCR technique and 6% (25/627) as Hb variants by Hb electrophoresis technique. We did prenatal diagnosis (PND) for 176 couples which had background of thalassemia in first pregnancy. Result of PND diagnosis in the first trimester was 35% (62/176) affected fetus with β -thalassemia major and sickle cell disease that led to termination of the pregnancy. Conclusion:Almost all hemoglobinopathies can be
Molecular Analysis of HS-111 and 3`HS1 Variations in β-Thalassemia Intermedia Patients with High Levels of HbF
Mohammad Hamid,Morteza Karimipoor,Sirous Zeinali,Mohammad taghi Akbari
Cell Journal , 2010,
Abstract: Objective: To study the possible association between high levels of fetal haemoglobin(HbF) in β-thalassemia intermedia patients and HS-111 and 3`HS1 sequence variations.Materials and Methods: In this study, the 3' HS-1 and HS-111 regions of 30 -thalassaemiaintermedia patients ( °/ °) with high levels of HbF, 21 -thalassemia major patientsand 40 normal Iranian individuals were analyzed by single-strand conformation polymorphism(SSCP) and polymerase chain reaction (PCR) sequencing.Results: Two nucleotide variations in 3' HS111 (-21A>G) and 3`HS1 (179C>T) wereidentified. The most frequent sequence variation was 3' HS111 (-21A) in the intermediapatients and 3`HS111 (-21G) in the major thalassemia patients. In contrast to the 3`HS1marker, both 3'HS111 A and G variants showed a correlation with each studied group.Conclusion: The HS111 marker in conjunction with other parameters could be used asappropriate genetic markers to discriminate β-thalassemia intermedia patients (β°/β°) withhigh levels of HbF from β-thalassemia major patients.
The Frequency of DYT1 (GAG Deletion) Mutation in Primary Dystonia Patients from Iran
Mohammad Hamid,Mohammad Taghi Akbari,Gholam Ali Shahidi,Zahra Zand
Cell Journal , 2011,
Abstract: Objective: To determine the frequency of DYT1 mutation in Iranian patients affected withprimary dystonia.Materials and Methods: In this study, we investigated 60 patients with primary dystoniawho referred to the Tehran Medical Genetics Laboratory (TMGL) to determine thedeletional mutation of 904-906 del GAG in the DYT1 gene. DNA extracted from patients’peripheral blood was subjected to PCR-sequencing for exon 5 of the DYT1 gene. The collectionof samples was based on random sampling.Results: The deletional mutation of 904-906 del GAG in the DYT1 gene (15099 to 15101based on reference sequence: NG_008049.1) was identified in 11 patients (18.33%). Theaverage age of affected patients with this mutation was 13.64 ± 7.4 years.Conclusion: It can be concluded that the DYT1 deletional mutation of 904-906 del GAGhas a high frequency in Iranian patients in comparison with other non-Jewish populations.Therefore, this particular mutation may be the main representative of pathogenic DYT1gene for a large proportion of Iranian patients with primary dystonia.
Molecular Diagnosis of Duchenne/Becker Muscular Dystrophy: Analysis of Exons Deletion and Carrier Detection
Mohammad Taghi Akbari,Shohreh Zare Karizi,Shahryar Nafisi,Gholamreza Zamani
Cell Journal , 2010,
Abstract: Objective: Duchenne and Becker Muscular Dystrophy (DMD and BMD) are X-linked conditionsresulting from a defect in the dystrophin gene located at Xp21.2. DMD is the mostfrequent neuromuscular disease in humans (1/3500 male newborns). In approximately65% of DMD and BMD patients, deletions in the dystrophin gene have been identified asthe molecular determinant. The frequency and distribution of dystrophin gene deletions inDMD/BMD patients from different populations are different.The aim of this study was to delineate various types of deleted exons and their frequencyin affected male patients and identification of carrier females by linkage analysis.Materials and Methods: In this study 100 unrelated patients with DMD/BMD were studiedfor intragenic deletions in 28 exons and the promoter region of the dystrophin geneusing multiplex PCR. We also performed linkage analysis within the dystrophin gene utilizing8 short tandem repeat markers.Results: Fifty-two (52%) patients showed intragenic deletions. A total of 81% of the deletionswere located at the distal hot spot region (44-55 exons) and 19% of the deletionswere located at the proximal region (exon 2-19). The most frequent deleted exons were47(16%), 48 and 46 (11%).Most of the STR markers showed heterozygosity in the families studied. The linkageanalysis was useful for detecting carrier status.Conclusion: The present study suggests that intragenic dystrophin gene deletions occurwith the same frequency in Iranian patients compared with other ethnic groups.
Molecular Diagnosis of Congenital Adrenal Hyperplasia in Iran: Focusing on CYP21A2 Gene
Bahareh Rabbani,Nejat Mahdieh,Mohammad-Taghi Haghi Ashtiani,Mohammad-Taghi Akbari
Iranian Journal of Pediatrics , 2011,
Abstract: Congenital adrenal hyperplasia (CAH) is characterized by impaired biosynthesis of cortisol. 21-hydroxylase deficiency is the most common cause of CAH affecting 1 in 10000-15000 live births over the world. The frequency of the disorder is very high in Iran due to frequent consanguineous marriages. Although biochemical tests are used to confirm the clinical diagnosis, molecular methods could help to define accurate diagnosis of the genetic defect. Recent molecular approaches such as polymerase chain reaction based methods could be used to detect carriers and identify different genotypes of the affected individuals in Iran which may cause variable degrees of clinical expression of the condition. Molecular tests are also applied for prenatal diagnosis, and genetic counseling of the affected families. Here, we are willing to delineate mechanisms underlying the disease, genetic causes of CAH, genetic approaches being used in the country and recommendations for health care improvement on the basis of the molecular and clinical genetics to control and diminish such a high prevalent disorder in Iran. Also, the previous studies on CAH in Iran are gathered and a diagnostic algorithm for the genetic causes is proposed.
Analytical modeling of trilayer graphene nanoribbon Schottky-barrier FET for high-speed switching applications
Meisam Rahmani, Mohammad Taghi Ahmadi, Hediyeh Karimi Abadi, Mehdi Saeidmanesh, Elnaz Akbari and Razali Ismail
Nanoscale Research Letters , 2013, DOI: 10.1186/1556-276X-8-55
Abstract: Recent development of trilayer graphene nanoribbon Schottky-barrier field-effect transistors (FETs) will be governed by transistor electrostatics and quantum effects that impose scaling limits like those of Si metal-oxide-semiconductor field-effect transistors. The current--voltage characteristic of a Schottky-barrier FET has been studied as a function of physical parameters such as effective mass, graphene nanoribbon length, gate insulator thickness, and electrical parameters such as Schottky barrier height and applied bias voltage. In this paper, the scaling behaviors of a Schottky-barrier FET using trilayer graphene nanoribbon are studied and analytically modeled. A novel analytical method is also presented for describing a switch in a Schottky-contact double-gate trilayer graphene nanoribbon FET. In the proposed model, different stacking arrangements of trilayer graphene nanoribbon are assumed as metal and semiconductor contacts to form a Schottky transistor. Based on this assumption, an analytical model and numerical solution of the junction current--voltage are presented in which the applied bias voltage and channel length dependence characteristics are highlighted. The model is then compared with other types of transistors. The developed model can assist in comprehending experiments involving graphene nanoribbon Schottky-barrier FETs. It is demonstrated that the proposed structure exhibits negligible short-channel effects, an improved on-current, realistic threshold voltage, and opposite subthreshold slope and meets the International Technology Roadmap for Semiconductors near-term guidelines. Finally, the results showed that there is a fast transient between on-off states. In other words, the suggested model can be used as a high-speed switch where the value of subthreshold slope is small and thus leads to less power consumption.
Mutations of RAS Gene Family in Specimens of Bladder Cancer
Navaz Karimianpour,Parisa Mousavi-Shafaei,Abed-Ali Ziaee,Mohammad Taghi Akbari
Urology Journal , 2008,
Abstract: Introduction: Studies have shown different types of RAS mutations in human bladder tumors with a wide range of mutation frequencies in different patient populations. This study aimed to assess the frequency of specific-point mutations in the RAS gene family of a group of Iranian patients with bladder cancer. Materials and Methods: We examined the tumor specimens of 35 consecutive patients with transitional cell carcinoma. The DNA samples were evaluated for the occurrence of HRAS, KRAS, and NRAS activation using a polymerase chain reaction-restriction fragment length polymorphism technique. Results: None of the patients had mutations in the RAS gene family “hot spots” including codons 12, 13, and 61. Conclusion: We failed to find RAS mutations in our bladder tumor samples. These observations may reflect the involvement of different etiological factors in the induction of bladder tumor of which RAS mutation might not be present in all populations.
Detection of Rare Beta Globin Gene Mutation [+22 5UTR(G>A)] in an Infant, Despite Prenatal Screening
Mohammad Reza Mahdavi,Hosein Karami,Mohammad Taghi Akbari,Hosein Jalali,Payam Roshan
Case Reports in Hematology , 2013, DOI: 10.1155/2013/906292
Abstract: Background. Beta thalassemia is one of the most common hereditary disorders worldwide. In Iran, it is frequently reported from northern and southern provinces. In order to prevent child birth to be affected by this complication, prenatal screening and diagnosis are carried out nationwide. However, in some instances, this program is unable to identify rare mutations leading to thalassemia. Case Presentation. A married couple, who took part in prenatal screening and diagnosis, gave birth to a child who is affected by thalassemia major. After several molecular examinations, a rare mutation [+22 5UTR (G>A)] in compound heterozygote state along with a common mutation [codon 8 (-AA)] was found. Conclusion. This case study suggests that more advanced molecular evaluations must be integrated in prenatal screening programs to identify rare mutations and antenatal diagnosis of thalassemia cases. 1. Introduction Beta thalassemia is one of the most prevalent autosomal received disorders in the world that has affected more than 150–200 million people from more than 60 countries around the world. About 18000 beta thalassemia major patients live in Iran, and it is estimated that the number of beta thalassemia carriers reaches to two million people, while most of them are in northern and southern provinces. Genetic counseling, identification of mutations responsible for the disease and carrier persons, and prenatal diagnosis are the best methods for the management of the disease and prevention of emergence of new cases in the community. All of these services are routinely available in Iran [1–4]. So far more than 200 different mutations on beta globin gene that lead to beta thalassemia disease have been identified. Molecular investigations on beta thalassemia patients in Iran resulted in finding 43 different beta globin gene mutations, responsible for the disease. These mutations have different frequencies in different provinces of Iran, with various ethnicities. In each province, some mutations are classified as common mutations, while others are known as rare mutations. In all provinces of Iran 13 mutations cover more than 70–90% of identified mutations among beta thalassemia patients that are classified as common mutations. In Mazandaran province (a northern province of Iran), IVS-II-1(G>A) mutation alone, with the prevalence of 61% among affected persons, is the most common mutation among beta thalassemia patients, and codon 30 (7.5%), codon 22 (6.2%), and codon 8 (-AA) (5.4%) mutations are other common mutations following IVS-II-1 (G>A) mutation [3, 5, 6]. +22
The Effect of Bilayer Graphene Nanoribbon Geometry on Schottky-Barrier Diode Performance
Meisam Rahmani,Razali Ismail,Mohammad Taghi Ahmadi,Mohammad Javad Kiani,Mehdi Saeidmanesh,F. A. Hediyeh Karimi,Elnaz Akbari,Komeil Rahmani
Journal of Nanomaterials , 2013, DOI: 10.1155/2013/636239
Abstract: Bilayer graphene nanoribbon is a promising material with outstanding physical and electrical properties that offers a wide range of opportunities for advanced applications in future nanoelectronics. In this study, the application of bilayer graphene nanoribbon in schottky-barrier diode is explored due to its different stacking arrangements. In other words, bilayer graphene nanoribbon schottky-barrier diode is proposed as a result of contact between a semiconductor (AB stacking) and metal (AA stacking) layers. To this end, an analytical model joint with numerical solution of carrier concentration for bilayer graphene nanoribbon in the degenerate and nondegenerate regimes is presented. Moreover, to determine the proposed diode performance, the carrier concentration model is adopted to derive the current-voltage characteristic of the device. The simulated results indicate a strong bilayer graphene nanoribbon geometry and temperature dependence of current-voltage characteristic showing that the forward current of the diode rises by increasing of width. In addition, the lower value of turn-on voltage appears as the more temperature increases. Finally, comparative study indicates that the proposed diode has a better performance compared to the silicon schottky diode, graphene nanoribbon homo-junction contact, and graphene-silicon schottky diode in terms of electrical parameters such as turn-on voltage and forward current. 1. Introduction Graphene nanoribbon (GNR) has attracted much attention of researchers for nanoelectronic applications because of its uniqueness electronic characteristics such as linear energy dispersion and width-tunable energy band gap [1–5]. Due to quantum confinement effect, GNR with width and thickness less than De-Broglie wave length can be assumed as a one-dimensional (1D) material [6]. GNR as an unwrapped carbon nanotube (CNT) is illustrated in Figure 1. It is notable that the properties of GNR are similar to CNT, but the planar structure of GNR guarantees better rectification current-voltage characteristic due to more accessible contact compared to other carbon-based materials [6]. Bilayer graphene nanoribbon (BGN) with unique physical and electrical properties has been incorporated in different nanoscale devices such as field effect transistors (FETs), tunnel transistors, and schottky diodes [7–11]. The BGN schottky-barrier diode has turned out to be of great interest holding the fact that it presents better performance compared to conventional semiconductor junction contacts [12]. In this paper, analytical modeling of BGN
On Eigenvalues and Boundary Curvature of the Numerical Rang of Composition Operators on Hardy Space  [PDF]
Mohammad Taghi Heydari
Advances in Pure Mathematics (APM) , 2015, DOI: 10.4236/apm.2015.56032

For a bounded linear operator A on a Hilbert space H, let M(A) be the smallest possible constant in the inequality \"\". Here, p is a point on the smooth portion of the boundary \"\" of the numerical range of A. \"\" is the radius of curvature of \"\" at this point and \"\"?is the distance from p to the spectrum of A. In this paper,

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