Genetics Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Genetics in Genomic Era Wed, 25 Mar 2015 12:29:12 +0000 Eugenia Poliakov, David N. Cooper, Elena I. Stepchenkova, and Igor B. Rogozin Copyright © 2015 Eugenia Poliakov et al. All rights reserved. Importance of Genetic Diversity Assessment in Crop Plants and Its Recent Advances: An Overview of Its Analytical Perspectives Thu, 19 Mar 2015 12:40:44 +0000 The importance of plant genetic diversity (PGD) is now being recognized as a specific area since exploding population with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world. Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources (PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to food and nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especially on agriculturally important crops (mostly field crops); (ii) risk associated with narrowing the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in pregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussion benefits the plant scientist community in order to use the new methods and technology for better and rapid assessment, for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnological techniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglecting environmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks look into several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, and access to database, for prebreeding activities. Since plant breeding research and cultivar development are integral components of improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global food production network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available for measuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus, it improves the understanding of tools and its practical applicability to the researchers. M. Govindaraj, M. Vetriventhan, and M. Srinivasan Copyright © 2015 M. Govindaraj et al. All rights reserved. Unlimited Thirst for Genome Sequencing, Data Interpretation, and Database Usage in Genomic Era: The Road towards Fast-Track Crop Plant Improvement Thu, 19 Mar 2015 11:29:29 +0000 The number of sequenced crop genomes and associated genomic resources is growing rapidly with the advent of inexpensive next generation sequencing methods. Databases have become an integral part of all aspects of science research, including basic and applied plant and animal sciences. The importance of databases keeps increasing as the volume of datasets from direct and indirect genomics, as well as other omics approaches, keeps expanding in recent years. The databases and associated web portals provide at a minimum a uniform set of tools and automated analysis across a wide range of crop plant genomes. This paper reviews some basic terms and considerations in dealing with crop plant databases utilization in advancing genomic era. The utilization of databases for variation analysis with other comparative genomics tools, and data interpretation platforms are well described. The major focus of this review is to provide knowledge on platforms and databases for genome-based investigations of agriculturally important crop plants. The utilization of these databases in applied crop improvement program is still being achieved widely; otherwise, the end for sequencing is not far away. Arun Prabhu Dhanapal and Mahalingam Govindaraj Copyright © 2015 Arun Prabhu Dhanapal and Mahalingam Govindaraj. All rights reserved. Caspase Activation and Aberrant Cell Growth in a p53+/+ Cell Line from a Li-Fraumeni Syndrome Family Wed, 18 Mar 2015 14:01:51 +0000 Wild-type p53 is well known to induce cell cycle arrest and apoptosis to block aberrant cell growth. However, p53’s unique role in apoptosis and cell proliferation in Li-Fraumeni Syndrome (LFS) has not been well elucidated. The aim of this study is to characterize the activity of wild-type p53 protein in LFS family dominated by a germline negative mutant p53. As expected, etoposide-treated wild-type p53-containing cell lines, LFS 2852 and control Jurkat, showed a greater rate of caspase- and annexin V-induced apoptotic cell death compared to the p53-mutant LFS 2673 cell line although mitochondrial and nuclear assays could not detect apoptosis in these organelles. The most intriguing part of the observation was the abnormal proliferation rate of the wild-type p53-containing cell line, which grew twice as fast as 2673 and Jurkat cells. This is important because apoptosis inducers acting through the mitochondrial death pathway are emerging as promising drugs against tumors where the role of p53 is not only to target gene regulation but also to block cell proliferation. This study casts a long shadow on the possible dysregulation of p53 mediators that enable cell proliferation. The deregulation of proliferation pathways represents an important anticancer therapeutic strategy for patients with the LFS phenotype. Zaki A. Sherif Copyright © 2015 Zaki A. Sherif. All rights reserved. Inheritance Pattern of Temephos Resistance, an Organophosphate Insecticide, in Aedes aegypti (L.) Mon, 16 Mar 2015 11:31:15 +0000 The present paper reports the mode of inheritance of resistance in laboratory induced temephos resistant and susceptible strains of Ae. aegypti. Homozygous resistant and susceptible strains of Ae. aegypti were generated by selective inbreeding at a diagnostic dose of 0.02 mg/L of temephos. Genetic crosses were carried out between these strains to determine the inheritance pattern of temephos resistance. The log-dosage probit mortality relationships and degree of dominance (D) were calculated. The dosage-mortality (d-m) line of the F1 generation was nearer to the resistant parent than the susceptible one. The “D” value was calculated as 0.15 indicating that the temephos resistant gene is incompletely dominant. The d-m lines of the F2 generation and progeny from the backcross exhibited clear plateaus of mortality across a range of doses indicating that temephos resistance is controlled by a single gene. Comparison of the mortality data with the theoretical expectations using the test revealed no significant difference, confirming a monogenic pattern of inheritance. In conclusion, the study provides evidence that the temephos resistance in Ae. aegypti follows an incompletely dominant and monogenic mode of inheritance. Vinaya Shetty, Deepak Sanil, and N. J. Shetty Copyright © 2015 Vinaya Shetty et al. All rights reserved. Genetic Variant in the CYP19A1 Gene Associated with Coronary Artery Disease Mon, 16 Mar 2015 10:39:23 +0000 The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the biosynthesis of estrogens. The rs10046 polymorphism of CYP19A1 gene has been investigated in two studies on the occurrence of hypertension, but there are no studies on its correlation with coronary artery disease (CAD). We investigated 189 subjects who were hospitalized at “KAT” General Hospital of Athens and underwent coronary angiography. Of these, 123 were found with CAD with an average age of 60 years and constituted the patients group and 66 subjects with an average age of 58 years without damage in the coronary vessels and constituted the control group (healthy). The frequencies of genotypes CC, CT, and TT of rs10046 polymorphism are significantly different between the group of CAD patients and the control group (0.34, 0.48, and 0.18 versus 0.20, 0.48, and 0.32, resp., ) as the frequency of C allele (0.58 versus 0.44, resp., OR = 1.771 and ). We found similar results for men, but not for women (small sample). The results of this study show that the rs10046 (C/T) polymorphism of CYP19A1 gene exhibits correlation with CAD and that patients with C allele have an increased probability of manifesting the disease. Konstantina Bampali, Charalampos Grassos, Angeliki Mouzarou, Charalampos Liakos, Georgios Mertzanos, Klea Lamnissou, and Dimitrios Babalis Copyright © 2015 Konstantina Bampali et al. 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.