Background: Non syndromic oculocutaneous albinism type (OCA) is caused by mutations in tyrosinase (TYR), OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes. Screening for mutations is important in families with oculocutaneous albinism patients in order to accurately diagnose the albinism type, genetic counseling and future therapeutic purposes.
Objectives: The Aim of this study was to investigate the founder effect of most frequent mutations in OCA patients.
Methods: TYR gene was sequenced in 26 unrelated inbred OCA families as well as 56 unrelated healthy individuals. In addition, homozygosity mapping was performed using 13 STR markers for 6 OCA loci (TYR, OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes). Different mutations were found in these genes from which a single base duplication (c.286dupA) and two single base substitutions c.996G > A (p.M332I) and c.230G > A (p.R77Q) had the most frequencies among the OCA families. In order to investigate the founder effect of these mutations, the haplotypes of two STR markers (TYR-S1 and TYR-S2) inside the TYR gene were ascertained.
Results: It was revealed that families with similar mutation harbored similar haplotype for the TYR STR markers too. 
Conclusions: We conclude that these mutations are possible founder mutations in the Iranian population.

Background: Blepharophimosis-ptosis-epicanthus syndrome (BPES) is a rare genetic disorder with autosomal dominant inheritance. There are two distinct phenotypes: BPES type I, which is associated with eyelid abnormalities as well as female infertility or premature menopause due to ovarian resistance to gonadotropins, whereas in type II only eyelid abnormalities are present. Mutations in the forkhead transcription factor 2 (FOXL2) gene are responsible for both types of BPES.
Objectives: The purpose of this study was to identify mutations in FOXL2 in two Iranian families (from Tehran) with BPES who were referred to Tehran Medical Genetics laboratory.
Methods: The peripheral blood was collected from the affectedmembersof two BPES familiesandgenomicDNAwas extracted using salting out method. Then, direct sequencing of whole exon of FOXL2 genewas performed.
Results: Two frameshift mutations were identified in FOXL2 gene in two familial cases including NM_023067:c.102_103insA (p.G35Rfs*61)as a novel mutation and NM_023067:c.855_871dup (p.H291Rfs*71) (17-bp insertion). Both mutations cause the protein to be truncated and are responsible for a severe phenotype (BPES type I) which was in harmony with our finding.
Conclusions: Our results increased the spectrum of FOXL2 mutations and confirm the mutations associated with BPES type I.

Background: HepatitisCvirus (HCV) infection is a global health problem. Most cases of HCVinfection do not resolve spontaneously. Combination therapy with pegylated interferon- (PegIFN-alpha) and ribavirin (RBV) is the standard treatment for patients with HCV infection. The success of treatment is affected by several host, viral, and treatment factors. Available works have demonstrated significant role of interleukin 28B (IL28B) polymorphisms in predicting HCV infection treatment outcomes. This suggests the possibility of tailored therapy in HCV infected patients. HCV is one of the most common causes of liver disease worldwide. If untreated, this infection can develop chronic hepatitis in 50%-85% of patients. The aim of current study is to determine the association of interleukin-28B (IL-28B) rs-12979860 polymorphism in response to peginterferon-alpha (PegIFN-alpha) and ribavirin combination therapy in Iranian patients with chronic hepatitis C genotype 1 infection.
Methods: This cross-sectional study was carried out on 70 Iranian patients with chronic hepatitis C infection (genotype 1) receiving PegIFN-alpha and ribavirin. DNAwas extracted from blood samples. Specific primers were used to amplify targeted polymorphisms.
Results: In this study, 71.4% of patients reached sustained virological response (SVR). The prevalence of CC, CT and TT genotypes were 38.6%, 42.8% and 18.6% respectively. The rate of SVR was 96.3 for CC genotype, whereas this rate was 66.7 for CT and 30.8 for TT genotypes. We found an association between end of treatment response (ETR) and IL-28B genotypes as 100% of patients bearing CC genotype reached ETR, but ETR rate was 45.85% in CT group and 10.2% in TT group. Six months follow-up showed that there was a significant difference between response to treatment in patients IL-28B-CC and TT (P < 0.001). Data regression analysis showed that CC genotype was an independent predicting factor, significantly associated with higher SVR (P = 0.005 (OR=36.1; 95% CI = 3 - 434.2)). In contrast, absence of C allele (TT genotype) was significantly correlated with the failure of response (P = 0.005 (OR = 36.1; 95% CI = 3 - 434.2)).
Conclusions: The results showed that IL-28B rs12979860 was an important predictor of HCV treatment response.

The prevalence of diabetes – especially diabetes type II- is increasing steadily; according to WHO reports it will increase to 366 million people by the year 2030. Microvascular complications including Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are increased in patients with diabetes mellitus. Case-control association studies have demonstrated that rs1617640 SNP in the promoter of erythropoietin (EPO) gene is significantly associated with PDR and ESRD. In the mentioned SNP, TT genotype is considered as risk genotype which means that EPO concentration in human vitreous body in these people shall be higher. People with TT genotype are much more at risk of retinopathies. In this study we investigated the existence of rs1617640 EPO gene  polymorphism among 150 healthy subjects and 150 subjects with diabetes type II who referred to Yazd central laboratory. Then the association of rs1617640 SNP with complications among diabetic patients were examined by ARMS-PCR method. The results were analyzed using GraphPad software (version 5.00). Prevalence of genotype GG was 8% in patients and 1.3% in the control group. GT was 51.3% in patients, and 86.7% in the control group, and finally TT was observed in 40.7% in patients, and 12% of control group. The TT genotype was 37.6% in patients with retinopathy and 42.6% in non-retinopathy patients. Our study demonstrates that the prevalence of rs1617640 SNP has significant difference between diabetic patients and control group; whereas there was not any significant relationship between this polymorphism and the complications of diabetes in patients. Together our study reveals that rs1617640 SNP may be associated with susceptibility to diabetes type II; however it seems that this polymorphism is not significantly related to the diabetic complications in Yazd.

The capability of cancer cells including tumor initiation, maintenance, and extension is associated with cancer stem cells. The substantial features of CSCs are self - renewal and pluripotency. Therapeutic resistance of CSCs can result in cancer recurrence and failure of cancer treatment. Isolation and characterization of CSCs are required for targeted cancer therapies. CSCs can be distinguished and separated by surface markers. In this review, after definition of CSC hypothesis, different markers of CSC are introduced. The information about CSC markers provides promise for better isolation and more effective CSC-targeting therapeutic in future.

Nesfatin-1 (NUCB2) gene, was introduced as a novel satiety factor involves in the control of energy homeostasis in the hypothalamus. Since NUCB2/nesfatin-1 has an effect on diabetes and obesity, it is a candidate gene that can be responsible for causing coronary artery disease (CAD).Therefore, we aimed to identify the association between rs214101 (C/T) SNP of NUCB2 gene and the possible amplified effects of this genetic variation together on the development risk of CAD in this study.This study was carried out in 110 patients with CAD, and 69 CAD-free controls. The NUCB2/nesfatin-1 rs214101 genotypes were analysed by PCR-RFLP technique. The CC genotype frequency of the NUCB2 rs214101 was greater in control group than CAD group (34.8% vs.52.7%; P = 0,019).The CC-genotype was associated with low serum HDL-C level compared to T allele in female CAD subgroup (P = 0.031), but, not in males. Unlike the CAD group, it was observed that the male control subjects carrying CC genotype have higher serum HDL-cholesterol and diastolic blood pressure levels than those with T allele (P = 0.043 and P = 0.031, respectively) but, not in females. Logistic regression analysis confirmed that the NUCB2/Nesfatin-1 rs214101 CC-genotype is associated with low serum HDL-cholesterol in femaleCADpatients. Our results suggest that the CC genotype of NUCB2 rs214101 may contribute to susceptibility CAD risk in relation to low HDL-C and that the genetic effect could differ by gender.

Hemophilia is a coagulation disorder in which bleeding time is prolonged. There are a number of hemophilia subtypes and more than 4,000,000 individuals are suffered worldwide. The most common types of hemophilia are type A and B in which coagulation factor VIII and IX are defected respectively. Type A hemophilia is responsible for 80% to 85% of cases. The genes of 8 and 9 coagulation factors located on the long arm of X chromosome and mutation in these genes causes disturbance in coagulation. This disease is a very good target for gene therapy because if amount of protein production reaches 1% that of normal the disease phenotype is modified. Different methods of hemophilia gene therapy include increased production of coagulation factors via insertion of attributed genes into patient’s stem cells by vectors, or insertion of transgenes into differentiated cells with prolonged survival such as muscle or liver cells. One of the most recent advances in hemophilia gene therapy is using induced pluripotent stem cells (iPS) for gene transfer. Hepatocytes are very good candidates for hemophilia gene therapy due to their natural capacity for production of coagulation factors. Myocytes are also suitable for injection of transgene because they are available and have sufficient secretory power. Most important and useful viral vectors for hemophilia are retroviral, lentiviral, and Adeno- Associated viruses. Amongthese only the retroviral vectors target dividing cells.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Currently a single accurate method for diagnosis of MS is lacking. Exosomes are small membranous transport vesicles providing a means of cell-tocell communication by transporting their cargo. Considering accumulating evidence emphasizing potential role of exosomes in the regulation of the immune system, circulating exosomes represent promising candidate biomarkers multiple sclerosis.

Congenital enterokinase deficiency is a rare autosomal recessive disorder of gastrointestinal tract in newborns. Enterokinase initiates digestion of protein by conversion of trypsinogen into trypsin. We analyzed the parents of unaffected deceased newborn with congenital enterokinase deficiency by exome sequencing. The results of exome sequencing identified a novel heterozygous frameshift deletion, c.151-155del p.Ala51Trpfs*5, in TMPRSS15 gene. Direct sequencing confirmed that the couple had heterozygous status. TMPRSS15 gene mutations are completely rare. To date, one small deletion and three nonsense mutations are reported in this gene in Human Gene Mutation Database (HGMD®). The identified mutation leads to complete absence of enzymatic activity.

Background: The type II form of neurofibromatosis (NF2) is an autosomal dominant multiple neoplasia syndrome characterized by tumors of the eighth cranial nerve (usually bilateral), meningiomas of the brain, and schwannomas of the dorsal roots of the spinal cord. The incidence of neurofibromatosistype II is 1 in 25,000 live births.
Methods: To further understand the genetic spectrum of NF2, we analyzed an individual affected with multifocal schwanomatosis by whole exome sequencing. Potential candidate mutations were checked in additional familymembersto determine if the putative mutation segregated with disease status.
Results: No pathogenic variant was identified in NF1 and NF2 genes however, a novel nonsense homozygous mutation p.Q675X in PMS1 gene was identified. Direct sequencing confirmed that the patient is homozygous and her parents are heterozygous for the identified variant.
Conclusions: To the best of our knowledge it is the first report of involvement of PMS1 mutations in NF2. However, genetic testing of NF1 and NF2 genes in affected tissues to rule out somatic mutations as well as functional study for the identified variant are required to clarify under what circumstances mutations of this gene cause tumorigenesis.

In the last two decades, stem cell therapy has been developed rapidly. Stem cells have now emerged as a new treatment for many major disorders including neurodegenerative diseases such multiple sclerosis (MS). Recently, the attention of researchers working onMShave been attracted to cell therapy using therapeutic stem cells (TSCs). In this brief narrative reviewweexplore the application of TSCs in last 5 years registered clinical trials. At the end, we will discuss the challenges and hopes ahead of therapeutic stem cells in treating MS patients.

Background: PRODH is one of the genes that exists in 22q11.2 location and encodes the prolin oxidase enzyme (POX) in the mitochondrial inner membrane and is expressed in the liver, kidney and brain. The importance of the accompaniment of the PRODH gene’s polymorphisms and mutations in increasing the risk of getting afflicted with schizophrenia has been proven in previous Linkage and Association studies. Proline dehydrogenase enzyme (POX) accelerates the converting of prolin into glutamate. Decreased enzyme causes hyperprolinemia resulting in increased proline and decreased glutamate. The activity of NMDA and AMPA receptors decrease and low activation of these receptors cause negative symptoms of schizophrenia disorder. V427M mutation in PRODH has been proven to decrease pox enzyme activity and is associated with schizophrenia disorder.
Objectives: In this project the rs2238731 variant in the PRODH gene was genotyped in 95 schizophrenic patients whose diseases are psychiatrically confirmed and also in 120 healthy people without any history of schizophrenia and bipolarity in their pedigree. For this purpose, their peripheral blood was taken.
Methods: In this study, the PCR-RFLP approach has been adopted in order to identify this variant. The SPSS 24.0 software has been used in order to statistically analyze the association of mutant variants and normal variants among the two groups afflicted with the disease and non-afflicted with the disease. The goal of this study was to shed light over the accompaniment of the rs2238731 variant in the PRODH gene with the risk of getting afflicted with schizophrenia among the Iranian patients.
Results: According to our result, there is no association between V427M missense mutation and schizophrenia disorder in Iranian patients. So the V427M missense mutation could not be regarded as co-related with increasing risk of schizophrenia in Iranian patients.

Background: Chronic exposure to benzene or its derivative (benzoquinone and hydroquinone) in humans may result in bone marrow damage followed by development of leukemia. Induction of extra cellular signaling pathways in microenvironment of bone marrow of patients with acute myeloid leukemia (AML) may lead to progression of disease and treatment resistance. Mesenchymal stromal cells (MSCs) are a subpopulation of multipotent cells of non-haematopoietic origin. They are increasingly recognized as a central component of the bone marrow (BM) microenvironment that contributes to the structure and function of theBM niche. MSCs play significant roles in regulation of homing, self-renewal, differentiation, and proliferation of hematopoietic stem cells (HSC) through production of various crucial elements in hematopoietic niche. Niches are local tissue microenvironments that maintain and regulate stem cells. Previous studies have shown that benzene is one of the important risk factors for AML.
Objectives: This study aimed to evaluate the effect of low doses of benzoquinone on the expression levels of some hematopoietic function related genes including CXCL12 and Kit ligand (KITLG) in MSCs.
Methods: MSCs obtained from bone marrow mononuclear cells of healthy volunteer and cultured in the proper medium. After characterization with standard methods, MSCs were exposed to two doses of 5 and 10 micro molar (ɱM) of benzoquinone; then, the expression of KITLG and CXCL12 genes were evaluated by real time PCR method.
Results: The results indicated that the expression of KITLG and CXCL12 genes were increased after treatment with benzoquinone, specifically with 5 ɱMdose.
Conclusions: The results of our study along with well-established role of KITLG/SCF signaling pathways and the CXCL12-CXCL4 axis in maintenance of the niche and cancer development, benzene metabolite, benzoquinone, is among the major factors in causing acute myelogenous leukemia.

Background: PRODH is one of the genes that exists in 22q11.2 location and encodes the prolin oxidase enzyme (POX) in the mitochondrial inner membrane and is expressed in the liver, kidney and brain. The importance of the accompaniment of the PRODH gene’s polymorphisms and mutations in increasing the risk of getting afflicted with schizophrenia has been proven in previous Linkage and Association studies. Proline dehydrogenase enzyme (POX) accelerates the converting of prolin into glutamate. Decreased enzyme causes hyperprolinemia resulting in increased proline and decreased glutamate. The activity of NMDA and AMPA receptors decrease and low activation of these receptors cause negative symptoms of schizophrenia disorder. V427M mutation in PRODH has been proven to decrease pox enzyme activity and is associated with schizophrenia disorder.
Objectives: In this project the rs2238731 variant in the PRODH gene was genotyped in 95 schizophrenic patients whose diseases are psychiatrically confirmed and also in 120 healthy people without any history of schizophrenia and bipolarity in their pedigree. For this purpose, their peripheral blood was taken.
Methods: In this study, the PCR-RFLP approach has been adopted in order to identify this variant. The SPSS 24.0 software has been used in order to statistically analyze the association of mutant variants and normal variants among the two groups afflicted with the disease and non-afflicted with the disease. The goal of this study was to shed light over the accompaniment of the rs2238731 variant in the PRODH gene with the risk of getting afflicted with schizophrenia among the Iranian patients.
Results: According to our result, there is no association between V427M missense mutation and schizophrenia disorder in Iranian patients. So the V427M missense mutation could not be regarded as co-related with increasing risk of schizophrenia in Iranian patients.

Background: Short tandem repeat (STR) markers are extensively being used forhumanidentification as well as paternity and forensic analysis of biological evidence.
Objectives: The aim of this study was to investigate the allelic frequencies and several forensic and paternity parameters of 15 autosomal short tandem repeat (STR) loci D3S1358, D16S5391, D7S820, D8S1179, D21S11, D18S51, D5S818, D13S317, FGA, THO1, TPOX, CSF1PO, vWA , D2S1338, and D19S433 in the Iranian population.
Methods: Estimation of allelic frequencies and several forensic and paternity parameters of 15 STR loci were performed with the AmpFLSTR Identifilerr kit (Applied Biosystems) for 274 unrelated individuals living in Iran.
Results: No deviation from Hardy-Weinberg equilibrium was found in any loci studied in this population. Among the 15 STR loci analyzed in the Iranian sample, the most discriminating loci were D21S11, D2S1338, D19S433, D18S51 and FGA with the highest power of discrimination. The allelic distribution also was compared to 13 other populations including 3 Iranian population living in Syria, Dubai, the USA and in Fars province and 8 population from published studies of Azerbaijan, Bolu in Turkey, Morocco, Syria, Iraq, Saudi Arabia, Turkey, East Anatolia, and Pakistan.
Conclusions: It was concluded that the population of present study had the least similarity with Azerbyjani (11 loci) and most similarity with the Iranian population in USA (15 loci).

Background: Chronic myeloproliferative disorders (CMPD) occur due toclonal proliferation of the single hematopoietic stem cells and result in an increased number of mature and immature cells in the peripheral blood. The mutations in JAK2 gene are identified in large numbers of CMPD patients.
Objectives: The aim of this study was to investigate thep.V617F (c.1849G > T) mutation as well as exon 12 mutations in JAK2 gene in the CMPD patients.
Methods: Philadelphia chromosome negative CMPD patients were recruited for this study. In order to study p.V617F and JAK2 exon 12 mutations in JAK2 gene, FRET probe real-time PCR, allele specific PCR and PCR-direct sequencing were utilized.
Results: JAK2 p.V617F mutation was found in polycythemia vera, Essential thrombocytosis and idiopathic myelofibrosis (67%, 52% and 50% respectively) but not in idiopathic erythrocytosis patients. Also no mutation was found in JAK2 exon 12 of these patients.
Conclusions: Our data regarding p.V617F was in concordance with the previous studies. The absence of any mutation in exon 12 of our patients may be due to extracting DNA from whole blood cells instead of granulocytes, that may impact the detection rate of cycle sequencing method.

Advances in nucleic acid based molecular diagnosis techniques, provided the basis for efficient, accurate and rapid detection of biological/ pathological agents. However, these techniques suffer from major limitations including lack of the genomic sequence of high-risk pathogens to calibrate techniques as positive controls, false positive results and restrictions on access to existing commercial tests. However with the advent of synthetic biology, it is possible to construct appropriate positive controls. Artificial genetic constructs are the synthetic constructs that contain genetic materials from highly dangerous bacteria or viruses, which can be used as positive controls in molecular techniques such as PCR. In this review, we introduce positive controls and simulator positive controls firstly and discuss about artificial genetic constructs, procedure of design and synthesis secondly. Finally, we discussed about single and chimeric artificial genetic constructs as two main categories of these positive control.

Background: Burkholderia bacteria are species from protobacter and the pathogens of this species include Burkholderia mallei and pseudomallei causing glanders. The yellow fever virus is a blavovirus that has a single-stranded polyribonucleotide genome (positive strand). Yellow fever is a type of acute viral disease, also called black vomit. Even though considerable advances have been made in the development and use of molecular techniques for the detection of pathogens such as Burkholderia species and yellow fever, a major problem in these techniques is lack of proper positive control. Recently developed geneticallymodifiedvectors andsimulator construct have provided engineered tools that can be used as a positive control in molecular diagnosis.
Methods: In the current study, we first designed and produced chimeric simulator constructs, containing specific genes from Burkholderia mallei, pseudomallei, and yellow fever virus. Then, the operational efficiency of the designed structures was evaluated using a single and dual-mode quantitative (using SYBER Green) and qualitative (using the TaqMan probe) Real-time PCR.
Results: The minimum and maximum sensitivity of designed construct for Burkholderia and yellow fever detection was indicated
to be 0.1 pg and 10 ng, respectively.
Conclusions: Our findings suggest that this positive control constructs can be used for development of new diagnostic kits.

Background: Breast cancer is one of the most common types of cancers and the leading cause of death, especially in women throughout the world. Various genetics and environmental factors have been identified as a risk factor for development of breast cancer. Long non-coding RNAs (lncRNAs) have gained significant attention in recent years as new and crucial players in cancer development. Curcumin is a plant compound that has been shown to inhibit various aspects of cancer including apoptosis, inhibition of cell proliferation, invasion and angiogenesis.
Objectives: Elevated expression level of two lncRNAs, HULC and Linc-ROR, has been reported as contributing factor to the development of breast cancer. Therefore, we aimed to investigate the effect of nanocurcumin on expression levels of these genes. Besides, apoptotic effect of nanocurcumin on MCF7 cells was investigated.
Methods: MCF7 cells were exposed to various concentrations of nanocurcumin and their metabolic activity was measured by MTT assay. The level of HULC and Linc-ROR genes was evaluated by real-time PCR. Apoptosis was also determined by Annexin test.
Results: Twenty micromollar (m) concentrations of nanocurcumin significantly decreased the expression of HULC and Linc-ROR
genes (P < 0.05). These concentrations also led to significantly higher apoptosis rate in MCF7 cells (97%) compared to cell treated with curcumin.
Conclusions: Our findings suggested that nanocurcumin exhibits apoptotic effects on breast cancer MCF7 cells by reducing the expression level of two proto-oncogene lncRNAs, HULC and Linc-ROR, which are both involved in downregulation of p53.