Whole exome sequencing and homozygosity mapping reveals genetic defects in consanguineous Iranian families with inherited retinal dystrophies

Acknowledgements This research was funded by the Swiss National Science Foundation (Grant #176097 to CR). We would like to express gratitude to the patients and all their family members that participated in this study for their valuable cooperation and participation.Peer reviewedPublisher PD

The frequency of human leukocyte antigen-DRB1 alleles, using sequence-based genotyping in 68 parents-child trios study in Iranian subjects

Background: The human leukocyte antigen-DRB1 (HLA-DRB1) locus is one of the most polymorphic human loci and has a crucial role in the immune system. Assessing the allelic frequencies of HLA-DRB1 locus would be a fundamental factor in defining the origin of populations, relationships with other populations, disease association studies and the constitution of unrelated bone marrow donor registries. In the current study HLA-DRB1 alleles and their frequencies are determined in a family-based study by DNA sequencing-based typing high-resolution (2 field) level of typing. Materials and Methods: Genomic DNA from 3 members of 68 unrelated families (a total of 204 individuals) was extracted. Exon 2 of DRB1 gene was amplified and performed useing AssignTM SBT v4.7 sequence analysis software.Results: We had DRB1*11:04 with frequency of 0.0931, DRB1*03:01 with 0.0882, DRB1*11:01 with 0.0735, DRB1*13:01 with 0.071 and also alleles DRB1*08:03, DRB1*13:42, DRB1*14:04 and DRB1*14:07 with frequency of 0.0024.Conclusion: A total of 34 different alleles were found in the study subjects with DRB1*11:04, DRB1*03:01, DRB1*11:01 being the most frequent alleles respectively.  

MicroRNAs as Biomarkers for Early Diagnosis, Prognosis, and Therapeutic Targeting of Ovarian Cancer

Ovarian cancer is the major cause of gynecologic cancer-related mortality. Regardless of outstanding advances, which have been made for improving the prognosis, diagnosis, and treatment of ovarian cancer, the majority of the patients will die of the disease. Late-stage diagnosis and the occurrence of recurrent cancer after treatment are the most important causes of the high mortality rate observed in ovarian cancer patients. Unraveling the molecular mechanisms involved in the pathogenesis of ovarian cancer may help find new biomarkers and therapeutic targets for ovarian cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression, mostly at the posttranscriptional stage, through binding to mRNA targets and inducing translational repression or degradation of target via the RNA-induced silencing complex. Over the last two decades, the role of miRNAs in the pathogenesis of various human cancers, including ovarian cancer, has been documented in multiple studies. Consequently, these small RNAs could be considered as reliable markers for prognosis and early diagnosis. Furthermore, given the function of miRNAs in various cellular pathways, including cell survival and differentiation, targeting miRNAs could be an interesting approach for the treatment of human cancers. Here, we review our current understanding of the most updated role of the important dysregulation of miRNAs and their roles in the progression and metastasis of ovarian cancer. Furthermore, we meticulously discuss the significance of miRNAs as prognostic and diagnostic markers. Lastly, we mention the opportunities and the efforts made for targeting ovarian cancer through inhibition and/or stimulation of the miRNAs

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Funding Information: We would like to thank all of the participating families. We are also grateful to the Swiss Confederation for the award of a PhD fellowship to AUR, to Mashhad University of Medical Sciences for supporting part of the work, in the framework of the PhD thesis of AS, to the Swiss National Science Foundation for grant # 176097 to CR, and to the Fondation Guillaume Gentil for support to ASF.Peer reviewedPublisher PD

The association between PD-1 gene polymorphisms and susceptibility to multiple sclerosis

AbstractProgrammed cell death 1 (PD-1) is an immune checkpoint and has been reported to be associated with several autoimmune diseases. We aimed to investigate the association between human PD-1 gene (PDCD1) polymorphisms and multiple sclerosis (MS). This case-control study was conducted on 229 MS patients and 246 healthy controls. Genotyping of rs36084323 (PD-1.1 G/A), rs11568821 (PD-1.3 G/A) and rs2227981 (PD-1.5 C/T) polymorphisms was performed by PCR-RFLP technique. The frequency difference of PD-1.1 genotypes and alleles (−536 G/A) between patients and healthy controls was not significant. Regarding PD-1.3, the AA + AG genotype was found to be relatively higher in the control group. Concerning PD-1.5 (+7785 C/T), the frequency of T allele carriers (TT + CT) was relatively higher in MS patients, which was marginally insignificant (p = .07). PD-1 gene polymorphisms may be associated with MS; however, accurate conclusions require further studies with a larger number of samples

An introduction to expression and regulation of cancer/testis antigens (CTAs): review article

Cancer/testis antigens (CTAs) are a kind of antigens that their expression mostly is restricted in testis and female’s genital organs. Tumor cells often express antigens whose expression is normally limited to germ cells. CTAs are composed of a vast gene family of closely related members and are commonly classified into two groups: the CT-X antigens that are encoded by the X chromosome and the non-X CTAs that are encoded by the autosomes. CTA are extensively and variably dispersed between tumors of diverse histotypes. CTA are broadly expressed in tumors, but not in normal tissue except for testis that is not available to the immune system, actually, the blood-testis barrier and the lack of HLA class I expression on the surface of germ cells avoid the immune system from the interaction with CTA proteins to be identified as non-self-structures. Consequently, CTA can be regarded as fundamentally tumor-specific targets. With extensive investigations on the function of this important biological molecules, their functions are somewhat revealed. Because of their high immunogenicity, tumor-limited, and biased expression, detection of these molecules provides unprecedented chances for further research and clinical development in the field of immunotherapy and cancer diagnosis. Also, growing evidence discloses that a number of CTAs stimulate epithelial mesenchymal transition (EMT) and generation of cancer stem-like cells, increasing metastasis, invasion and tumorigenesis. According to recent clinical attention, more features of CTA regulation are explored. CTA expression has been confirmed in a variety of human cancer tissues and some of them have been discovered to cause humoral and/or cellular immune responses in cancer patients, likewise, they displayed intertumor and intratumor heterogeneity in expression levels. CTAs are excellent targets for targeted tumor therapy, anticancer drug discovery, and diagnostic biomarkers, similarly, appreciated genes in the study of promoting tumorigenesis, immunotherapy, and malignant progression. This review summaries and classifies our current understanding of the complex and biased process of CTAs mRNA and protein expression in cancer, and provide the most current information on their function and regulation. &nbsp

PDCD1 Single Nucleotide Polymorphisms in Iranian Patients With Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous cluster of complex diseases, in which both the genetic and environmental factors seem to play a role in the development of the disease. The current study aims to assess the association of programmed cell death 1 (PDCD1, also called PD-1) gene variants with JIA vulnerability in Iranian population. In this case-control association study, we investigated a group of 50 Iranian patients with JIA in comparison with 202 healthy controls and evaluated the frequency of alleles, genotypes, and haplotypes of PDCD1 single-nucleotide polymorphisms (SNPs), comprising PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T, using PCR-RFLP method. Both the allelic and genotype frequencies of PD-1.1, PD-1.3 and PD-1.9 were similar in two groups of patients and controls. Moreover, no significant difference was observed between the two groups of patients and controls for GGC (PD-1.1 G, PD-1.3 G, PD-1.9 C), GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C), and AGT (PD-1.1 A, PD-1.3 G, PD-1.9 T) haplotypes. Our results did not show any association between PDCD1 SNPs and the development of JIA in Iranian population

Genetics and immunodysfunction underlying Behçet’s disease and immunomodulant treatment approaches

Behçet’s disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes

Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC