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From genome to gene: A review of genes and genetic variations associated with type 2 diabetes
Mahdi Safarpour , Ahmad Ebrahimi , Maryam Sadat Daneshpour ,
Volume 73, Issue 9 (12-2015)
Abstract

Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146 however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10-2) to strong association in European descent populations (P= 2.0×10-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.


Study of genetics, phenotypic and behavioral properties of eubacteria and archaebacteria
Hamid Kazemian , Zahra Pakbaz , Seyed Mostafa Hosseini , Mohammad Reza Pourmand ,
Volume 74, Issue 3 (6-2016)
Abstract

Background: The genome of the bacteria has considerable diversity in terms of sequence of nucleotide bases and change over the time. With the advancement of bioinformatics science possibility of the vast comparison to living organisms has risen. During the last two decades many information about genome sequencing of pathogenic and non-pathogenic bacteria have been published. Using this information and to find connections between them and many phenotypic characteristics and behavior of bacteria could be used in many studies. In this study we compared some of the genetic, phenotypic and behavioral properties of archaebacteria and eubacteria.

Methods: In this analytical study, genomic Information of 286 species of archaebacteria and 122 species of eubacteria were collected from the NCBI (National Center for Biotechnology Information) site which was conducted in April to June 2015. Mean of gene size, gene number, protein number and C+G content compared in the two groups of archaebacteria and eubacteria. Association of genomic characterization of bacteria with several other characteristics were analyzed using SPSS statistical software version 19 (Chicago, IL, USA). For this purpose, the Pearson correlation coefficient (Pearson), Student’s t-test and ANOVA test (One-way analysis of variance) was used. The P values less than 0.05 was considered as significant level.

Results: There was significant association between means discrepancy in two group (P= 0.01). The genome size of eubacteria and archaebacteria have significant association with some of the characteristics of bacteria, such as the C+G content, the number of proteins, genes and habitats of the bacteria (P= 0.01). As well as there was significant association between genome size and features such as number of pseudogene, mobility and type of breathing in eubacteria (P= 0.01) but not in archaebacterial (P˃ 0.05).

Conclusion: Many characteristics of eubacteria and archaebacteria are significantly associated with genomic properties. Comparison genomics of bacteria will help in identification of evolutionary origins as well as differences between different categories of bacterial.


Associations of common polymorphisms in GCKR with metabolic syndrome
Asiyeh Sadat Zahedi , Bahareh Sedaghati-Khayat , Sara Behnami , Fereidoun Azizi , Maryam Sadat Daneshpour ,
Volume 76, Issue 7 (10-2018)
Abstract
Background: Metabolic syndrome (MetS) is characterized by a combination of cardio-metabolic risk factors. Given that genetic factors have been shown to contribute to individual susceptibility to MetS, the identification of genetic markers for disease risk is essential. Recent studies revealed that rs780094 and rs1260326 of glucokinase regulatory gene (GCKR) are associated with serum triglycerides, plasma glucose levels and metabolic syndrome. The aim of this study was to investigate associations of GCKR gene variants with metabolic syndrome and its components.
Methods: This case-control study was conducted from April to August 2017. In this study, 8710 adults (3522 males and 5188 females), over 19 years, were randomly selected from the Tehran Lipid and Glucose Study (TLGS) population. Based on joint interim statement (JIS) criteria, the subjects were divided into two groups: case and control. Genotyping was performed by HumanOmniExpress-24 v1.0 BeadChips (Illumina, San Diego, CA, USA).
Results: Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Comparisons of allele frequencies by the Chi-square test revealed that frequencies of TT genotype of both polymorphisms were significantly higher among patient group than healthy group. Logistic regression analysis with adjustment for age, gender and CRP revealed that the GCKR polymorphisms (rs1260326: odds ratio 2.7, 95% CI 1.6-4.6, rs780094: odds ratio 2.5, 95% CI 1.5-4.2) were significantly associated with MetS. Frequency of TT genotype was more in persons who had C-reactive protein (CRP) levels above 3 mg/l. The minor T allele of both polymorphisms was significantly associated with increases in the blood serum concentration triglyceride and to a decrease in fasting plasma glucose levels.
Conclusion: The results of our study indicated that, rs780094 and rs1260326 common polymorphisms of the GCKR gene were associated with serum triglycerides levels, fasting plasma glucose levels, and metabolic syndrome in a sample of the Tehranian population (TLGS), as it was already confirmed the inverse effect of this polymorphisms on triglycerides and glucose levels in previous studies.

Impact of viral oncoproteins on human genome methylation: a review article
Farzane Hayati, Esma’il Akade, Negar Dinarvand, Gholam Abbas Kaydani , Shahram Jalilian,
Volume 82, Issue 6 (9-2024)
Abstract
Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), hepatitis B virus (HBV), human papilloma virus (HPV), Merkel cell polyomavirus (MCPyV), human lymphotropic virus type 1 (HTLV-1) and Hepatitis C virus (HCV) are among the most important viruses that cause cancer in humans. These viruses are collectively known as oncoviruses due to their potential to induce malignant transformations in host cells. Oncoviruses exert their cancer-causing effects by utilizing various viral oncoproteins and non-coding RNAs, which can drive host cells toward malignancy through multiple pathways. One critical strategy these viruses employ involves altering the host cell's regulatory mechanisms, particularly by influencing DNA methylation processes.
DNA methylation is a crucial modification that occurs on the promoter regions of genes, effectively reducing their expression levels. Under normal cellular conditions, a delicate balance of methylation and demethylation is maintained by a specific set of enzymes. Key players in this process include DNA methyltransferases (DNMTs) and TET methylcytosine dioxygenases (TETs), which are pivotal in regulating gene expression through methylation. These enzymes are prime targets for oncoviruses because, by altering their activity, viruses can hijack the host cell's regulatory machinery. Viral oncoproteins, though diverse in structure and function, often converge on disrupting the expression of these enzymes. By doing so, they induce widespread changes in DNA methylation patterns, effectively reprogramming the gene expression landscape of the host cell. This reprogramming is not random; rather, it is a calculated mechanism through which oncoviruses can manipulate the cell cycle, promoting uncontrolled cellular proliferation and progression towards cancer. By suppressing or activating specific genes, these viruses can push cells past normal checkpoints, eventually leading to tumor formation. Despite the critical role of DNA methylation in cancer development, the precise mechanisms by which oncoviruses modulate these methylation processes are not fully understood. Researchers have made significant progress in exploring the connection between viral infections and cancer, but many of the detailed pathways through which oncoviruses control methylation remain to be elucidated. As a result, this area remains a fertile ground for further research, offering potential avenues for therapeutic intervention in virus-induced cancers.

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