Genetics Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. An Introspective Update on the Influence of miRNAs in Breast Carcinoma and Neuroblastoma Chemoresistance Thu, 04 Dec 2014 00:10:00 +0000 Chemoresistance to conventional cytotoxic drugs may occur in any type of cancer and this can either be inherent or develop through time. Studies have linked this acquired resistance to the abnormal expression of microRNAs (miRNAs) that normally silence genes. At abnormal levels, miRNAs can either gain ability to silence tumour suppressor genes or else lose ability to silence oncogenes. miRNAs can also affect pathways that are involved in drug metabolism, such as drug efflux pumps, resulting in a resistant phenotype. The scope of this review is to provide an introspective analysis on the specific niches of breast carcinoma and neuroblastoma research. Alessia Carta, Rachel Chetcuti, and Duncan Ayers Copyright © 2014 Alessia Carta et al. All rights reserved. MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders Thu, 06 Nov 2014 07:03:26 +0000 Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism. Elif Funda Sener, Didem Behice Oztop, and Yusuf Ozkul Copyright © 2014 Elif Funda Sener et al. All rights reserved. Clinical Presentation and Microarray Analysis of Peruvian Children with Atypical Development and/or Aberrant Behavior Mon, 20 Oct 2014 12:28:09 +0000 We report our experience with high resolution microarray analysis in infants and young children with developmental disability and/or aberrant behavior enrolled at the Centro Ann Sullivan del Peru in Lima, Peru, a low income country. Buccal cells were collected with cotton swabs from 233 participants for later DNA isolation and identification of copy number variation (deletions/duplications) and regions of homozygosity (ROH) for estimating consanguinity status in 15 infants and young children (12 males, 3 females; mean age ± SD = 28.1 m  m; age range 14 m–41 m) randomly selected for microarray analysis. An adequate DNA yield was found in about one-half of the enrolled participants. Ten participants showed deletions or duplications containing candidate genes reported to impact behavior or cognitive development. Five children had ROHs which could have harbored recessive gene alleles contributing to their clinical presentation. The coefficient of inbreeding was calculated and three participants showed first-second cousin relationships, indicating consanguinity. Our preliminary study showed that DNA isolated from buccal cells using cotton swabs was suboptimal, but yet in a subset of participants the yield was adequate for high resolution microarray analysis and several genes were found that impact development and behavior and ROHs identified to determine consanguinity status. Merlin G. Butler, Kelly Usrey, Jennifer L. Roberts, Stephen R. Schroeder, and Ann M. Manzardo Copyright © 2014 Merlin G. Butler et al. All rights reserved. Power Estimation for Gene-Longevity Association Analysis Using Concordant Twins Tue, 16 Sep 2014 00:00:00 +0000 Statistical power is one of the major concerns in genetic association studies. Related individuals such as twins are valuable samples for genetic studies because of their genetic relatedness. Phenotype similarity in twin pairs provides evidence of genetic control over the phenotype variation in a population. The genetic association study on human longevity, a complex trait that is under control of both genetic and environmental factors, has been confronted by the small sample sizes of longevity subjects which limit statistical power. Twin pairs concordant for longevity have increased probability for carrying beneficial genes and thus are useful samples for gene-longevity association analysis. We conducted a computer simulation to estimate the power of association study using longevity concordant twin pairs. We observed remarkable power increases in using singletons from longevity concordant twin pairs as cases in comparison with cases of sporadic proband. A similar power would require doubled sample sizes for fraternal twins than for identical twins who are concordant for longevity suggesting that longevity concordant identical twins are more efficient samples than fraternal twins. We also observed an approximate of 2- to 3-fold increase in sample sizes needed for longevity cutoff at age 90 as compared with that at age 95. Overall, our results showed high value of twins in genetic association studies on human longevity. Qihua Tan, Jing Hua Zhao, Torben Kruse, and Kaare Christensen Copyright © 2014 Qihua Tan et al. All rights reserved. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes Mon, 01 Sep 2014 00:00:00 +0000 Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population. Dorra Hmida-Ben Brahim, Marwa Chourabi, Sana Ben Amor, Imed Harrabi, Saoussen Trabelsi, Marwa Haddaji-Mastouri, Moez Gribaa, Sihem Sassi, Fatma Ezzahra Gahbiche, Turkia Lamouchi, Soumaya Mougou-Zereli, Sofiane Ben Ammou, and Ali Saad Copyright © 2014 Dorra Hmida-Ben Brahim et al. All rights reserved. Generalized Portrait of Cancer Metabolic Pathways Inferred from a List of Genes Overexpressed in Cancer Wed, 27 Aug 2014 12:59:51 +0000 More than half a century from postulated Warburg theory of cancer cells origin, a question of changed metabolism in cancer is again taking the central place. Generalized picture of cancer metabolism was replaced by analysis of signaling and oncogenes in each type of cancer for several decades. However, now empowered with wealth of knowledge about tumor suppressors, oncogenes, and signaling pathways, reprogramming of cellular metabolism (e.g., increased glycolysis to respiration ratio in cancer cells) reemerged as an important element of cancer progression. To analyze level of expression of various proteins including metabolic enzymes across various cancers we used dbEST and Unigene data. We delineated a list of genes that are overexpressed in different types of cancer. We also grouped overexpressed enzymes into KEGG pathways and analyzed adjacent pathways to describe enzymatic reactions that take place in cancer cells and to identify major players that are abundant in cancer protein machinery. Glycolysis/gluconeogenesis and oxidative phosphorylation are the most abundant pathways although several other pathways are enriched in genes from our list. Ubiquitously overexpressed genes could be marked as nonspecific cancer-associated genes when analyzing genes that are overexpressed in certain types of cancer. Thus the list of overexpressed genes may be a useful tool for cancer research. Eugenia Poliakov, David Managadze, and Igor B. Rogozin Copyright © 2014 Eugenia Poliakov et al. All rights reserved. Complexity of Gene Expression Evolution after Duplication: Protein Dosage Rebalancing Sun, 17 Aug 2014 15:49:04 +0000 Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the “ortholog conjecture” (OC). Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes. Igor B. Rogozin Copyright © 2014 Igor B. Rogozin. All rights reserved. Immune Reactions in Behçet’s Disease Mon, 02 Jun 2014 11:43:43 +0000 Fumio Kaneko, Dongsik Bang, Rafi Haner Direskeneli, Shigeaki Ohno, and Yoshiaki Ishigatsubo Copyright © 2014 Fumio Kaneko et al. All rights reserved. Molecular Characterization of Sudanese and Southern Sudanese Chicken Breeds Using mtDNA D-Loop Thu, 24 Apr 2014 13:43:49 +0000 The objective of this study was to assess the genetic relationships and diversity and to estimate the amount of gene flow among the five chicken populations from Sudan and South Sudan and commercial strain of egg line White Leghorn chickens. The chicken populations were genotyped using mtDNA D-loop as a molecular marker. PCR product of the mtDNA D-loop segment was 600 bp and 14 haplotypes were identified. The neighbor-joining phylogenetic tree indicated that the indigenous Sudanese chickens can be grouped into two clades, IV and IIIa only. Median joining networks analysis showed that haplotype LBB49 has the highest frequency. The hierarchal analysis of molecular variance (AMOVA) showed that genetic variation within the population was 88.6% and the differentiation among the population was 11.4%. When the populations was redefined into two geographical zones, rich and poor Savanna, the results were fractioned into three genetic variations: between individuals within population 95.5%, between populations within the group 0.75%, and genetic variation between groups 3.75%. The pair wise showed high genetic difference between Betwil populations and the rest with ranging from 0.1492 to 0.2447. We found that there is large number of gene exchanges within the Sudanese indigenous chicken (). Charles E. Wani, Ibrahim A. Yousif, Muntasir E. Ibrahim, and Hassan H. Musa Copyright © 2014 Charles E. Wani et al. All rights reserved. Application of Microsatellite Markers in Conservation Genetics and Fisheries Management: Recent Advances in Population Structure Analysis and Conservation Strategies Mon, 07 Apr 2014 11:50:03 +0000 Microsatellites are the most popular and versatile genetic marker with myriads of applications in population genetics, conservation biology, and evolutionary biology. These are the arrays of DNA sequences, consisting of tandemly repeating mono-, di-, tri-, and tetranucleotide units, which are distributed throughout the genomes of most eukaryotic species. Microsatellites are codominant in nature, highly polymorphic, easily typed, and Mendelian inherited, all properties which make them very suitable for the study of population structure and pedigree analysis and capable of detecting differences among closely related species. PCR for microsatellites can be automated for identifying simple sequence repeat polymorphism. Small amount of blood samples or alcohol preserved tissue is adequate for analyzing them. Most of the microsatellites are noncoding, and therefore variations are independent of natural selection. These properties make microsatellites ideal genetic markers for conservation genetics and fisheries management. This review addresses the applications of microsatellite markers in conservation genetics and recent advances in population structure analysis in the context of fisheries management. P. M. Abdul-Muneer Copyright © 2014 P. M. Abdul-Muneer. All rights reserved. One-Year Period Prevalence of Oral Aphthous Ulcers and Oral Health-Related Quality of Life in Patients with Behçet’s Disease Sun, 09 Mar 2014 12:38:34 +0000 The aim of this study was to investigate the 1-year period prevalence of oral aphthous ulcers (OAUs) and their association with oral health-related quality of life (OHQOL) in patients with Behçet’s disease (BD) and in the general population. In this cross-sectional study, 675 patients with Behçet’s disease (BD group) and 1,097 males and females in the Japanese general population (control group) completed both questionnaires on their OAU status during the prior year and the General Oral Health Assessment Index (GOHAI). In the BD group, 84% of patients reported experiencing an OAU during the previous year, and the mean number of OAUs/year was 13. In the control group, 31% of individuals experienced an OAU during the previous year, and the mean number of OAUs/year was one. Multivariate analysis indicated that both BD patients (OR, 6.2; 95% CI, 4.8–8.0) and controls (OR, 2.6; 95% CI, 2.0–3.5) who had OAUs at least twice per year were more likely to have GOHAI scores below the norm than were controls who had fewer than two OAUs per year. The association between HLA-B*51 and OAUs remains unknown. The presence of OAUs has a negative effect on the OHQOL of patients with BD. Mariko Naito, Yoshimi Suzukamo, Kenji Wakai, Miki Azechi, Fumio Kaneko, Takeo Nakayama, Nobuyuki Hamajima, and Shunichi Fukuhara Copyright © 2014 Mariko Naito et al. All rights reserved. A New Diagnostic Way for Behcet's Disease: Skin Prick with Self-Saliva Thu, 23 Jan 2014 13:19:35 +0000 Behcet's disease (BD) is a mysterious multisystemic disorder characterized by recurrent involvement of mucocutaneous (including recurrent aphthous stomatitis; RAS), ocular, intestinal, vascular, and/or nervous system organs. Previously, the positivity of “pathergy test”, which is one of the diagnostic examinations, was reported to be related to the possession of HLA-B51 gene in BD patients, even though the positivity is low and different from the countries. Here, instead of the ordinal pathergy test, we would like to propose the prick with self-saliva as a new diagnostic way for patients with RAS of BD based on the genetic intrinsic factors including HLA-B51 and extrinsic triggering factors. BD patients are considered to acquire the hypersensitivity against oral streptococci through the innate immune mechanism in the oral cavity. Bes-1 gene and 65 kD of heat shock protein (HSP-65) derived from oral S. sanguinis are supposed to play important roles as extrinsic factors in BD pathogenesis. Although the prick positivity was not related to the possession of HLA-B51 gene, the method is suggested to be a significant way for BD diagnosis. The results also suggest that BD symptoms are due to the vascular immune responses by monocytes expressed oral streptococcal agents of the patients. Fumio Kaneko, Ari Togashi, Erika Nomura, and Koichiro Nakamura Copyright © 2014 Fumio Kaneko et al. All rights reserved. Expression of Potential Regulatory Genes in Abdominal Adipose Tissue of Broiler Chickens during Early Development Thu, 16 Jan 2014 09:12:26 +0000 The identities of genes that underlie population variation in adipose tissue development in farm animals are poorly understood. Previous studies in our laboratory have suggested that increased fat tissue involves the expression modulation of an array of genes in broiler chickens. Of special interest are eight genes, FGFR3, EPHB2, IGFBP2, GREM1, TNC, COL3A1, ACBD7, and SCD. To understand their expression regulation and response to dietary manipulation, we investigated their mRNA levels after dietary manipulation during early development. Chickens were fed either a recommended standard or a high caloric diet from hatch to eight weeks of age (WOA). The high caloric diet markedly affected bodyweight of the broiler birds. mRNA levels of the eight genes in the abdominal adipose tissue were assayed at 2, 4, 6, and 8 WOA using RT-qPCR. Results indicate that (1) FGFR3 mRNA level was affected significantly by diet, age, and diet:age interaction; (2) COL3A mRNA level was repressed by high caloric diet; (3) mRNA levels of EPHB2, ACBD7, and SCD were affected by age; (4) mRNA level of TNC was modulated by age:diet interaction; (5) changes in GREM1 and IGFBP2 mRNA levels were not statistically different. Ann Bohannon-Stewart, Gary Kelley, Boniface Kimathi, Sri Harsha K. V. Subramanya, Joseph Donkor, Carl Darris, James Tyus, Ashley Payne, Shannon Byers, Dafeng Hui, Samuel Nahashon, Fur-Chi Chen, Michael Ivy, and Xiaofei Wang Copyright © 2014 Ann Bohannon-Stewart et al. All rights reserved. Innate and Adaptive Responses to Heat Shock Proteins in Behcet’s Disease Tue, 31 Dec 2013 09:51:39 +0000 Behcet’s disease (BD) is a systemic, chronic inflammatory disorder with both innate and adaptive immune responses. Heat shock proteins (HSP) are highly conserved molecules in different species with scavenger activity and involved in correct folding of newly synthesized proteins. T and B cell responses against HSPs are observed in BD patients in both and T-cell populations. 60-kD HSP (HSP60) is also shown to be recognized by pattern recognition receptors such as toll-like receptors (TLR) and is suggested to be an endogenous “danger” signal to the immune system with rapid inflammatory cytokine releases and enhancement of adaptive Th1-type responses. Elucidating the exact role of HSPs in BD pathogenesis might pave the way to less toxic therapeutic approaches to BD, such as antibacterial therapies and immunomodulation. H. Direskeneli Copyright © 2013 H. Direskeneli. All rights reserved. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease Mon, 30 Dec 2013 11:51:11 +0000 Behcet’s disease (BD) is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th) cell subset, were increased in patients with BD, and both Th type 1 (Th1) and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes. Jun Shimizu, Fumio Kaneko, and Noboru Suzuki Copyright © 2013 Jun Shimizu et al. All rights reserved. Feasibility of Whole RNA Sequencing from Single-Cell mRNA Amplification Mon, 23 Dec 2013 11:39:05 +0000 Single-cell sampling with RNA-seq analysis plays an important role in reference laboratory; cytogenomic diagnosis for specimens on glass-slides or rare cells in circulating blood for tumor and genetic diseases; measurement of sensitivity and specificity in tumor-tissue genomic analysis with mixed-cells; mechanism analysis of differentiation and proliferation of cancer stem cell for academic purpose. Our single- cell RNA-seq technique shows that fragments were 250–450 bp after fragmentation, amplification, and adapter addition. There were 11.6 million reads mapped in raw sequencing reads (19.6 million). The numbers of mapped genes, mapped transcripts, and mapped exons were 31,332, 41,210, and 85,786, respectively. All QC results demonstrated that RNA-seq techniques could be used for single-cell genomic performance. Analysis of the mapped genes showed that the number of genes mapped by RNA-seq (6767 genes) was much higher than that of differential display (288 libraries) among similar specimens which we have developed and published. The single-cell RNA-seq can detect gene splicing using different subtype TGF-beta analysis. The results from using Q-rtPCR tests demonstrated that sensitivity is 76% and specificity is 55% from single-cell RNA-seq technique with some gene expression missing (2/8 genes). However, it will be feasible to use RNA-seq techniques to contribute to genomic medicine at single-cell level. Yunbo Xu, Hongliang Hu, Jie Zheng, and Biaoru Li Copyright © 2013 Yunbo Xu et al. All rights reserved. DNA Methylation Pattern as Important Epigenetic Criterion in Cancer Mon, 23 Dec 2013 09:09:48 +0000 Epigenetic modifications can affect the long-term gene expression without any change in nucleotide sequence of the DNA. Epigenetic processes intervene in the cell differentiation, chromatin structure, and activity of genes since the embryonic period. However, disorders in genes’ epigenetic pattern can affect the mechanisms such as cell division, apoptosis, and response to the environmental stimuli which may lead to the incidence of different diseases and cancers. Since epigenetic changes may return to their natural state, they could be used as important targets in the treatment of cancer and similar malignancies. The aim of this review is to assess the epigenetic changes in normal and cancerous cells, the causative factors, and epigenetic therapies and treatments. Mehrdad Ghavifekr Fakhr, Majid Farshdousti Hagh, Dariush Shanehbandi, and Behzad Baradaran Copyright © 2013 Mehrdad Ghavifekr Fakhr et al. All rights reserved. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Type 1: A Light on Molecular Mechanisms Thu, 12 Dec 2013 08:36:38 +0000 Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy associated with cardiac arrhythmias originating in the right ventricle, heart failure, and sudden cardiac death. Development of ARVD/C type 1 has been attributed to differential expression of transforming growth factor beta 3 (TGFβ3). Several mechanisms underlying the molecular basis of ARVD/C type 1 have been proposed. Evaluating previously described mechanisms might elucidate how TGFβ3 contributes to disease progression in ARVD/C type 1. Here we review how TGFβ3 can induce fibrogenesis through Smad and/or β-catenin signaling. Moreover, the role of apoptosis is addressed. Finally the extent to which the immune system has been demonstrated to be a modulating and amplifying agent in the onset and progression of ARVD/C in general is discussed. Koen L. A. Vanderschuren, Tom Sieverink, and Ronald Wilders Copyright © 2013 Koen L. A. Vanderschuren et al. All rights reserved. Lack of TEK Gene Mutation in Patients with Cutaneomucosal Venous Malformations from the North-Western Region of Algeria Mon, 09 Dec 2013 15:53:38 +0000 Background. Venous malformations (VM) result from an error in vascular morphogenesis. The first gene suspected in their development is the TEK gene (tyrosine kinase, endothelial). Mutations of this gene have been identified in several Belgian families with a dominant form of the disease. Therefore, we investigated whether mutations in this TEK gene could explain the MV development in patients of families from Tlemcen region (north-western Algeria). Methods. Genomic DNA was extracted from leucocytes of ten patients. The search for mutations in all the 23 exons and in the 5′ and 3′ intronic sequences flanking the TEK gene was performed using PCR amplification and direct sequencing of amplified genomic DNA. Additionally, a search for somatic mutations of the gene TEK was performed on a biopsy of the venous malformation from one of the ten eligible patients. Results. The sequencing of the 23 exons of the TEK gene revealed neither germinal mutation in our ten patients nor somatic mutation in the tissue of the biopsy. Conclusion. The absence of mutation in the TEK gene in the population studied suggests that the TEK gene is not necessarily involved in the onset of VM; its association with these malformations may differ from one population to another. Nabila Brahami, Mourad Aribi, Badr-Eddine Sari, Philippe Khau Van Kien, Isabelle Touitou, Gérard Lefranc, and Mouna Barat-Houari Copyright © 2013 Nabila Brahami et al. All rights reserved. PCR-SSCP Variation of IGF1 and PIT1 Genes and Their Association with Estimated Breeding Values of Growth Traits in Makooei Sheep Mon, 09 Dec 2013 08:03:19 +0000 Molecular biology techniques genetic improvement by facilitating identification, mapping and analysis of polymorphism of genes by encoding proteins that act on metabolic pathways involved in economically interesting traits. This use of genetic markers can aid identification of those animals with the highest breeding values in sheep. On the basis of sheep genome mapping, information was examined on the ovine IGF1 and PIT1 genes as a possible genetic marker for growth traits in sheep. The current study was designed to estimate the frequencies of putative IGF-1 and PIT-1 genes SNPs and investigate associations with calculated EBVs of growth traits in Makooei sheep. PCR-SSCP analysis of the exon1 of IGF-I gene and include a part of intron2, exon3 and a part of intron3 and PIT-1 gene revealed the following banding patterns; three (AA, AG, GG) and four AA (p1), AB (p2), CC (p3), CD (p4), banding patterns respectively. Results from this study demonstrated higher performance of AA animals in BW and GBW, and AG animal in WW and W6 that may be related to the role of IGF-1 at the pre-puberty and puberty stages. Also higher performance of p3 animals in W9, YW and GSN, and p1 animal in GNY may be related to the PIT-1 role in post-puberty. Masoud Negahdary, Abbas Hajihosseinlo, and Marziyeh Ajdary Copyright © 2013 Masoud Negahdary et al. All rights reserved. Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis Mon, 02 Dec 2013 09:19:42 +0000 Background. Idiopathic erythrocytosis is the term reserved for cases with unexplained origins of abnormally increased hemoglobin after initial investigation. Extensive molecular investigation of genes associated with oxygen sensing and erythropoietin signaling pathways, in those cases, usually involves sequencing all of their exons and it may be time consuming. Aim. To perform a strategy for molecular investigation of patients with idiopathic erythrocytosis regarding oxygen sensing and erythropoietin signaling pathways. Methods. Samples of patients with idiopathic erythrocytosis were evaluated for the EPOR, VHL, PHD2, and HIF-2α genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2α mutation. Sequencing did not identify any pathogenic mutation in 4 of 5 cases studied in any of the studied genes. Three known nonpathogenic polymorphisms were found (VHL p.P25L, rs35460768; HIF-2α p.N636N, rs35606117; HIF-2α p.P579P, rs184760160). Conclusion. Extensive molecular investigation of cases considered as idiopathic erythrocytosis does not frequently change the treatment of the patient. However, we propose a complementary molecular investigation of those cases comprising genes associated with erythrocytosis phenotype to meet both academic and genetic counseling purposes. Carla Luana Dinardo, Paulo Caleb Junior Lima Santos, Isolmar Tadeu Schettert, Renata Alonso Gadi Soares, Jose Eduardo Krieger, and Alexandre Costa Pereira Copyright © 2013 Carla Luana Dinardo et al. All rights reserved. Immunopathogenic Role of Herpes Simplex Virus in Behçet’s Disease Sun, 24 Nov 2013 13:39:45 +0000 The role of viral infections, such as herpes simplex virus (HSV) infection, in the pathogenesis of Behçet’s disease (BD) has been investigated for many years. HSV has been detected in peripheral blood leukocytes, saliva, and genital ulcers of patients with BD. Various cell adhesion molecules on cultured endothelial cells have been induced by HSV in a TNF-α dependent manner. In addition, a BD-like animal model was developed by inoculating ICR mouse earlobes with HSV, and antiviral treatment was effective in improving BD-like symptoms in this model. Still, there are several incompletely characterized proteins that possess antiviral properties and are being investigated as mediators of viral infection-related chronic inflammatory reactions. Although the role of HSV in the pathogenesis of BD remains to be fully established, recent research findings regarding HSV in BD have expanded our understanding of the disease and will hopefully lead to the development of more effective therapeutic agents in the near future. Do Young Kim, Suhyun Cho, Min Ju Choi, Seonghyang Sohn, Eun-So Lee, and Dongsik Bang Copyright © 2013 Do Young Kim et al. All rights reserved. Diagnostic Genetics at a Distance: Von Hippel-Lindau Disease and a Novel Mutation Mon, 26 Aug 2013 08:30:04 +0000 Genetic testing at a distance is commonplace where members of a family with a segregating germline mutation are geographically separated. For the most part, this challenge is addressed through the intervention of health professionals in taking and/or processing blood samples for subsequent couriering of DNA to a referral laboratory. In some circumstances, however, the collecting of pivotal clinical material may involve direct patient involvement. We describe such a situation where noninvasive saliva samples were provided by members of a family manifesting Von Hippel-Lindau (VHL) disease. The analysis identified a novel mutation in the VHL gene that was used to exclude other family members as being at risk of VHL disease. Clare Brookes, Debra O. Prosser, Jennifer M. Love, R. J. McKinlay Gardner, and Donald R. Love Copyright © 2013 Clare Brookes et al. All rights reserved. Regression Modeling and Meta-Analysis of Diagnostic Accuracy of SNP-Based Pathogenicity Detection Tools for UGT1A1 Gene Mutation Tue, 13 Aug 2013 08:08:20 +0000 Aims. This review summarized all available evidence on the accuracy of SNP-based pathogenicity detection tools and introduced regression model based on functional scores, mutation score, and genomic variation degree. Materials and Methods. A comprehensive search was performed to find all mutations related to Crigler-Najjar syndrome. The pathogenicity prediction was done using SNP-based pathogenicity detection tools including SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59 different SNPs related to missense mutations in the UGT1A1 gene, were reviewed. Results. Comparing the diagnostic OR, our model showed high detection potential (diagnostic OR: 16.71, 95% CI: 3.38–82.69). The highest MCC and ACC belonged to our suggested model (46.8% and 73.3%), followed by SIFT (34.19% and 62.71%). The AUC analysis showed a significance overall performance of our suggested model compared to the selected SNP-based pathogenicity detection tool (). Conclusion. Our suggested model is comparable to the well-established SNP-based pathogenicity detection tools that can appropriately reflect the role of a disease-associated SNP in both local and global structures. Although the accuracy of our suggested model is not relatively high, the functional impact of the pathogenic mutations is highlighted at the protein level, which improves the understanding of the molecular basis of mutation pathogenesis. Fakher Rahim, Hamid Galehdari, Javad Mohammadi-asl, and Najmaldin Saki Copyright © 2013 Fakher Rahim et al. All rights reserved. Hidden Y Chromosome Mosaicism in 48 Egyptian Patients with Turner’s Syndrome Sun, 28 Jul 2013 08:57:52 +0000 Background. The presence of Y chromosome material in Turner’s syndrome (TS) patients is a risk factor for the development of gonadoblastoma. Although conventional cytogenetic analysis is the definitive diagnosis of TS, low level Y chromosome mosaicism may be missed. Molecular analysis has demonstrated a higher proportion of mosaicism, but there is controversy regarding the prevalence of Y chromosome-derived material in those patients. Aim and Methods. This study was conducted to investigate the prevalence of hidden Y chromosome mosaicism in 48 TS Egyptian patients using polymerase chain reaction (PCR) for molecular DNA analysis of SRY gene and compare our results with those in the literature. Results. None of TS patients had a cytogenetically obvious Y chromosome; Y chromosome material was detected only at molecular analysis. SRY gene was found in 9 TS patients (18.75%) with the classical 45,X karyotype, whereas all other patients were SRY negative. Conclusion. Cytogenetically undetected Y chromosome mosaicism is common in TS patients; these data reinforce the need for adequate diagnosis of Y chromosome material in those patients. Molecular screening for Y chromosome-derived DNA should be routinely carried out in all TS patients. Mervat M. El-Eshmawy, Sohier Yahia, Faeza A. El-Dahtory, Sahar Hamed, El Hadidy M. El Hadidy, and Mohamed Ragab Copyright © 2013 Mervat M. El-Eshmawy et al. All rights reserved. Molecular Genetic Diversity and Quantitation of Methanogen in Ruminal Fluid of Buffalo (Bubalus bubalis) Fed Ration (Wheat Straw and Concentrate Mixture Diet) Wed, 05 Jun 2013 16:23:56 +0000 High roughage diet causes more methane emissions; however, the total methanogen abundance is not influenced by roughage proportion. Technologies to reduce methane emissions are lacking, and development of inhibitors and vaccines that mitigate rumen-derived methane by targeting methanogens relies on present knowledge of the methanogens. In this work, we have investigated molecular diversity of rumen methanogens of Surti buffalo. DNA from rumen fluid was extracted, and 16S rRNA encoding genes were amplified using methanogen specific primer to generate 16S rDNA clone libraries. Seventy-six clones were randomly selected and analysed by RFLP resulting in 21 operational taxonomic units (OTUs). BLAST analysis with available sequences in database revealed sequences of 13 OTUs (55 clones) showing similarity with Methanomicrobium sp, 3 OTUs (15 clones) with Methanobrevibacter sp. The remaining 5 OTUs (6 clones) belonged to uncultured archaea. The phylogenetic analysis indicated that methanogenic communities found in the library were clustered in the order of Methanomicrobiales (18 OTUs) and Methanobacteriales (3 OTUs). The population of Methanomicrobiales, Methanobacteriales, and Methanococcales were also observed, accounting for 1.94%, 0.72%, and 0.47% of total archaea, respectively. K. M. Singh, A. K. Tripathi, P. R. Pandya, S. Parnerkar, R. K. Kothari, and C. G. Joshi Copyright © 2013 K. M. Singh et al. All rights reserved. Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy Tue, 19 Feb 2013 11:22:46 +0000 Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by homozygous expansion of a GAA·TTC trinucleotide repeat within the first intron of the FXN gene, leading to reduced FXN transcription and decreased levels of frataxin protein. Recent advances in FRDA research have revealed the presence of several epigenetic modifications that are either directly or indirectly involved in this FXN gene silencing. Although epigenetic marks may be inherited from one generation to the next, modifications of DNA and histones can be reversed, indicating that they are suitable targets for epigenetic-based therapy. Unlike other trinucleotide repeat disorders, such as Huntington disease, the large expansions of GAA·TTC repeats in FRDA do not produce a change in the frataxin amino acid sequence, but they produce reduced levels of normal frataxin. Therefore, transcriptional reactivation of the FXN gene provides a good therapeutic option. The present paper will initially focus on the epigenetic changes seen in FRDA patients and their role in the silencing of FXN gene and will be concluded by considering the potential epigenetic therapies. Chiranjeevi Sandi, Sahar Al-Mahdawi, and Mark A. Pook Copyright © 2013 Chiranjeevi Sandi et al. All rights reserved. Community Genetic Services in Iran Wed, 05 Dec 2012 13:34:31 +0000 The aim of the study was to report a description of the primary, secondary, and tertiary level services available for genetic disorders in Iran. For the purpose of this study, essential data were collected from every facility providing community genetic services in Tabriz city of Iran using a prestructured checklist. Technical information was filled in the predesigned forms using diagnostic records of each client/patient. Information was also gathered from community genetic services clients through a face-to-face interview at these facilities to assess the quality of services provided. Primary prevention measures were available in 80 percent of centres in the study population. Diagnostic techniques were fully available in the study area both in public and private sectors. Screening of congenital hypothyroidism and thalassemia has been successfully performed across the country by the Ministry of Health. Other screening programs have also been initiated by the country health authorities for neural tube defects, Down syndrome, and phenylketonuria. The high cost of genetic services at secondary and tertiary levels does not allow many people to get access to these services despite their needs. Governments will therefore need to allocate necessary resources to make the essential genetic services available for everyone needing these in the community. Shirin Atri Barzanjeh, Mozhgan Behshid, Mohammad Bagher Hosseini, Maryam Ezari, Mahdieh Taghizadeh, and Saeed Dastgiri Copyright © 2012 Shirin Atri Barzanjeh et al. All rights reserved. Filling the Silent Void: Genetic Therapies for Hearing Impairment Tue, 04 Dec 2012 14:32:58 +0000 The inner ear cytoarchitecture forms one of the most intricate and delicate organs in the human body and is vulnerable to the effects of genetic disorders, aging, and environmental damage. Owing to the inability of the mammalian cochlea to regenerate sensory hair cells, the loss of hair cells is a leading cause of deafness in humans. Millions of individuals worldwide are affected by the emotionally and financially devastating effects of hearing impairment (HI). This paper provides a brief introduction into the key role of genes regulating inner ear development and function. Potential future therapies that leverage on an improved understanding of these molecular pathways are also described in detail. Joel Sng and Thomas Lufkin Copyright © 2012 Joel Sng and Thomas Lufkin. All rights reserved. The Epigenetics of Emerging and Nonmodel Organisms Wed, 28 Nov 2012 15:43:36 +0000 Vett K. Lloyd, Jennifer A. Brisson, Kathleen A. Fitzpatrick, Lori A. McEachern, and Eveline C. Verhulst Copyright © 2012 Vett K. Lloyd et al. All rights reserved.