Introduction: The use of Sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is not common in most of malarious areas because of sensivity of this parasite to chloroquine. But, Plasmodium vivax isolates are exposed to SP because of mixed infection with P.falciparum and this subject has lead to emergence of mutations in P.vdhfr gene. As Plasmodium vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug would be necessary.Methods: In this study, 50 blood samples of symptomatic patients were collected from four separated geographical regions of south-east of Iran. Point mutations at residues 57, 58 were detected by PCR-RFLP method.Results: Polymorphism at positions 58R, of Pvdhfr gene has been found in 12% of isolates and mutation at residue F57 was not detected. Alleles with two points mutations in Pvdhfr gene were not found.Conclusion: This study showed that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP determines that this subject can lead to emergence of influence mutations in increase of drug resistance. So, this fact must be considered in development of malaria control program.

Background: In prostate cancer, mutated p53 alleles typically contain missense single-base substitution in codon 72 that resides within exons 5-8. Stable p53 proteins in tumor cell nuclei have been associated with malignancy. A role of p53 is the regulation of drug transporters like ABCC1 (MRP1) by an effect on promoter region.Objectives: The objective of this study was to identify association of mutations of p53 at codon 72 and 282 and promoter region of ABCC1 with increased risks of prostate cancer.Materials and Methods: Formalin fixed, paraffin-embedded malignant tissues of 45 patients and 45 control samples were evaluated. PCR-RFLP using BstUI for codon 72 and HpaII restriction enzyme for codon 282 p53 gene, and G-1666A promoter region of ABCC1 gene was performed. To assess the frequency of these mutations and to detect new mutations in cancerous samples, PCR-SSCP analysis was performed.Results: The frequencies of CC, GC and GG genotypes of codon 72 of p53 were 33.33%, 46.67% and 20.00% in patients with cancer and 15.56%, 48.89% and 35.55% in controls, respectively. The relative allele frequencies of ABCC1 promoter polymorphism were 60.00% A and 40.00% G in patients as opposed to 37.78% for A and 62.22% for G in controls.Genotypic frequencies of p53 codon 72 and G1666A of ABCC1 in patients vs. Controls were statistically significant (p<0.05). The study of these samples with PCR-SSCP displayed some new banding patterns.Conclusions: The present findings suggest that CC homozygosity in codon 72 of p53 gene and AA genotype in G-1666A of ABCC1 gene may play a role in combination in prostate cancer and increased susceptibility for this malignancy in the Iranian Kurdish population.

The aim of this study was to use site directed mutagenesis technique to construct a vector in which serine363 and serine375 residues of the COOH-terminal portion of the m-opioid receptor (MOR) were substituted by alanine. These constructs are essential in studying G-protein coupled receptor kinase-mediated MOR desensitization. The nested PCR carried out for conversion of serine363 and serine375 to alanine resulted in the production of a band comparable to the expected size of 1400 bp. Restriction analysis of these bands confirmed the integrity of the PCR products. Ligation of the mutated PCR product into pcDNA3 and its digestion with appropriate restriction enzymes further confirmed the integrity of the PCR product and its orientation into the vector.

The bioluminescence process is a widespread phenomenon in nature. The luciferase enzymes are identified in some domains of life, but the luciferases from the Lampyridae family are considered for biological applications. The molecular cloning of a new type of Iranian firefly luciferase from Lampyroidea maculata was reported, previously. In this study, the rare Codons of the Iranian insect luciferase gene were analyzed using the computational databases as ATGme, RACC, LaTcOm, and Sherlocc. Also, the structural modeling process of this enzyme was performed. Next, the status of these rare Codons in this structural model was evaluatedusing SPDBV 4. 10 and PyMOL 2. 3. 2 software. In the following, the substrate binding site in the enzyme's active site was studied using the AutoDock Vina 1. 5. 4. By molecular modeling, some rare Codons were identified that may have a critical role in the structure and function of this luciferase. AutoDock Vina was used in the molecular docking that recognizes Asp531 that yield closely related to luciferin and AMP binding site. These bioinformatics analyzes play an important role in the design of new drugs.

Background: Progressive familial intrahepatic cholestases (PFIC) are a spectrum of autosomal progressive liver diseases developing to end-stage liver disease. ATP8B1 deficiency caused by mutations in ATP8B1 gene encoding a P-type ATPase leads to PFIC1. The gene for PFIC1 has been mapped on a 19-cM region of 18q21-q22, and a gene defect in ATP8B1 can cause deregulations in bile salt transporters through decreased expression and/or activity of FXR. Point mutations are the most common, with the majority being missense or nonsense mutations. In addition, approximately 15% of disease-causing ATP8B1 mutations are annotated as splicing disrupting alteration given that they are located at exon-intron borders. Objective: Here, we describe the hidden layer of computational biology information of rare Codons in ATP8B1, which can help us for drug design. Methods: Some rare Codons in different locations of ATP8b1 gene were identified using several web servers and by in-silico modelling of ATP8b1 in Phyre2 and I-TASSER server, some rare Codons were evaluated. Results: Some of these rare Codons were located at special positions which seem to have a critical role in proper folding of ATP8b1 protein. Structural analysis showed that some of rare Codons are related to mutations in ATP8B1 that are responsible for PFIC1 disease, which may have a critical role in ensuring the correct folding. Conclusion: Investigation of such hidden information can enhance our understanding of ATP8b1 folding. Moreover, studies of these rare Codons help us to clarify their role in rational design of new and effective drugs.

Luciferase enzymes are involved in the bioluminescence reaction (light emission by living organisms), The bioluminescence process is a widespread phenomenon in the Nature, These enzymes are identified in some domains of life, but the luciferases from lampyrid genus are considered of for biological applications, The molecular cloning of a new type of firefly luciferase from Luciola lateralis was reported, previously, Here, we study its substrate binding site and rare codon with molecular docking and bioinformatics studies, By molecular modelling, some rare Codons were identified that may have a critical role in structure and function of this luciferase, AutoDock Vina was used in the molecular docking that recognizes some residues that yield closely related with luciferin and AMP binding site, These types of studies help in the discovery of the light production reaction, Evaluation of these hidden information’ s can improve the knowledge of luciferases folding and protein expression challenges and help in design of new drugs,

Objectives: Congenital prothrombin (factor II) deficiency is an inherited rare bleeding disorder with an autosomal recessive manner. The prevalence of this disorder is about one in 2 000 000 people in general population, but it is more common in areas with a high rate of consanguinity. To date, there is no report on the absence of prothrombin, which is a life-threating disorder. Considering the importance of factor II in body homeostasis, this study aimed to find any possible mutation of coagulation factor II Codons in patients with inherited factor II deficiency in southeastern Iran. Materials and Methods: This study was conducted on 12 patients with inherited deficiency of prothrombin. Early diagnosis was based on clinical symptoms, laboratory evaluation, and family history. Then, the function level of prothrombin was measured, the initial diagnosis of disease was confirmed, and polymerase chain reaction (PCR) analysis was performed. Finally, gene sequencing and genotyping of factor II was done. Results: Molecular analysis indicated a point mutation in exon 7 in three patients and a frameshift mutation in exon 14 due to addition of a thymine base at position 1760-1761 in one patient, both of which have been reported for the first time. Conclusions: Molecular methods performed on patients from Southeastern Iranian population in terms of coagulation factor II deficiency revealed a substitution mutation in exon 7 in three patients and a frameshift mutation in exon 14 in one patient, both of which were reported for the first time. Considering the significant difference between the clinical symptoms of the present study and previous studies, probably the type of mutations reported in this study (for the first time) caused these clinical symptoms, but statistical studies did not show any relationship between the type of mutation and the occurrence of clinical symptoms. And it needs more investigations on more patients, with a larger population.

Introduction: Endometriosis is a prevalent gynecological disorder among women which is diagnosed by the growth of endometrial tissue outside of uterus and is mainly accompanied by severe pelvic pain and infertility. P53 also known as cellular tumor antigen P53 inside Codons 11, 72 and 248 are contained with single nucleotide changes in which tends to be nearly rampant. This will probably be increasing the chances of endometriosis infection to some great extent. Our aim was to evaluate the connection between endometriosis and polymorphism inside the Codons 11, 72 and 248 of P53 gene.Methods: In this study, single nucleotide changes in Codons 11, 72 and 284 of TP53 gene among 44 persons infected with endometriosis and the same studying population for noninfected group have been examined. After primer design and amplification of polymorphic sequences by PCR, the polymorphisms of related Codons have been evaluated by the digestion method (RFLP).Results: In this study on the codon 72, there were seen differences in the distribution of genotype frequencies of normal polymorphic subjects and control subjects with endometriosis. At Codons 11 and 248, there were observed no significant correlations between polymorphic and normal genotypes of endometriosis and non-endometriosis groups.Conclusion: According to the results, we can say that probably polymorphism.

Colorectal cancer (CRC) is the most gastrointestinal cancer in United States and Europe. It is the third most common cancer in Iranian men, and fourth in Iranian women. Codons 12 and 13 are the hot spots for mutations in colorectal cancer patients, which encodes the activated RAS protein. According to recent researches, somatic mutations in Codons 12, 13 (exon1) of K-ras gene are discovered in 20% - 50% human CRCs. The aim of this study was to estimate the contribution of K-ras gene mutations in Codons 12, 13 in the incidence, and its association with clinicopathologic information like age, sex, familial history, site of primary and histology in Iranian colorectal cancer patients. In this study, we have analyzed 59 tissue specimens of colorectal cancer patients using PCR/sequencing method for Codons 12, 13 of K-ras gene.20.3% of patients (10 in codon 12 and 2 in codon 13) have shown a point mutation. About 60% of mutations occur in rectum and 41.7% in colon. More than 80% of mutations were in adenocarcinomas and less mutations in mucinous. Most mutations were found over the age of 60. Only two patients (16.6%) had a familial history for cancer. According to low rates of k-ras mutations in Codons 12, 13, we can say they are not common in Iranian patients. The mutation pattern for Iranian patients differs from other nationalities. Perhaps we can find point mutations in other exons, and we suggest whole genome sequencing for our patients.

Background and Objectives: Acute myeloid leukemia (AML) comprises a heterogenic group of malignant disorders involving cell maturation arrest at an undifferentiated stage in bone marrow. Activation of NRAS proto-oncogene due to point mutations plays a major role in AML malignancy. Since there was no report on the frequency of N-RAS gene mutations in Iranian AML patients, therefore, we decided to determine its frequency and compare the results with age, sex and FAB subtypes.Materials and Methods: In this descriptive study, 60 de novo AML patients from Tehran Shariati hospital, hematologyoncology and bone marrow transplantation center were screened for the mutations of N-RAS gene at Codons 12, 13 and 61. DNA was extracted from peripheral blood samples before the start of chemotherapy. The above mentioned Codons were amplified by PCR and analyzed by restriction endnuclease enzymes.Results: We were able to detect mutations in 12 out of 60 (20%) patients. Most of the mutations were detected in men with an age over 40 years old. The frequency of mutations for Codons 12, 13 and 61 were 15%, 11.6% and 5% respectively. Most of the mutations (33.3%) were found to happen in AML-M4 FAB subtype. We could not detect any mutation in AML-MO, M6 and M7. Conclusions: We detected mutations in 20% of our AML patients. In general, the frequency of the mutations we found was in agreement with the results of other studies. However, a study with more patients and a wider range of age using a combination of PCR-RFLP and direct gene sequencing is highly recommended.