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Frontiers in Genetics

Zhenhua Zhu, Zheng Jin, Yuyou Deng, Lai Wei, Xiaowei Yuan, Mei Zhang, Dahui Sun
Background: Soft tissue sarcomas (STS) are heterogeneous tumors derived from mesenchymal cells that differentiate into soft tissues. The prognosis of patients who present with an STS is influenced by the regulation of a complex gene network. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with STS (Samples = 156). Results: Among the 11 modules identified, the black and blue modules were highly correlated with STS. However, using preservation analysis, the black module demonstrated low preservation, therefore the blue module was chosen as the module of interest...
2019: Frontiers in Genetics
Dirk H Ostareck, Antje Ostareck-Lederer
Innate immune response is triggered by pathogen components, like lipopolysaccharides (LPS) of gram-negative bacteria. LPS initiates Toll-like receptor 4 (TLR4) signaling, which involves mitogen activated protein kinases (MAPK) and nuclear factor kappa B (NFκB) in different pathway branches and ultimately induces inflammatory cytokine and chemokine expression, macrophage migration and phagocytosis. Timely gene transcription and post-transcriptional control of gene expression confer the adequate synthesis of signaling molecules...
2019: Frontiers in Genetics
Akio Onogi
Genome-wide association mapping (GWA) has been widely applied to a variety of species to identify genomic regions responsible for quantitative traits. The use of multivariate information could enhance the detection power of GWA. Although mixed-effect models are frequently used for GWA, the utility of F -tests for multivariate mixed-effect models is not well-recognized. Thus, we compared the F -tests for univariate and multivariate mixed-effect models with simulations. The superiority of the multivariate F -test over the univariate test varied depending on three parameters: phenotypic correlation between variates ( r ), relative size of quantitative trait locus effects between variates ( a d ), and missing proportion of phenotypic records ( m prop )...
2019: Frontiers in Genetics
Zuobin Zhu, Xiaoxiao Han, Yuechen Wang, Wei Liu, Yue Lu, Chang Xu, Xitao Wang, Lin Hao, Yuanjian Song, Shi Huang, Joshua D Rizak, Ying Li, Conghui Han
Previous studies have found that fecundity is a multigenic trait regulated, in part, by mitochondrial-nuclear (mit-n) genetic interactions. However, the identification of specific nuclear genetic loci or genes interacting with the mitochondrial genome and contributing to the quantitative trait fecundity is an unsolved issue. Here, a panel of recombinant inbred advanced intercrossed lines (RIAILs), established from a cross between the N2 and CB4856 strains of C. elegans , were used to characterize the underlying genetic basis of mit-n genetic interactions related to fecundity...
2019: Frontiers in Genetics
Jane E Symonds, Shannon M Clarke, Nick King, Seumas P Walker, Brian Blanchard, David Sutherland, Rodney Roberts, Mark A Preece, Mike Tate, Peter Buxton, Ken G Dodds
Over the past 40 years New Zealand (NZ) aquaculture has grown into a significant primary industry. Tonnage is small on a global scale, but the industry has built an international reputation for the supply of high quality seafood to many overseas markets. Since the early 1990s the industry has recognized the potential gains from selective breeding and the challenge has been to develop programs that can overcome biological obstacles (such as larval rearing and mortality) and operate cost-effectively on a relatively small scale while still providing significant gains in multiple traits of economic value...
2019: Frontiers in Genetics
Petra Zur Lage, Fay G Newton, Andrew P Jarman
The motile cilium/flagellum is an ancient eukaryotic organelle. The molecular machinery of ciliary motility comprises a variety of cilium-specific dynein motor complexes along with other complexes that regulate their activity. Assembling the motors requires the function of dedicated "assembly factors" and transport processes. In humans, mutation of any one of at least 40 different genes encoding components of the motility apparatus causes Primary Ciliary Dyskinesia (PCD), a disease of defective ciliary motility...
2019: Frontiers in Genetics
Elaina M Maldonado, Fatma Taha, Joyeeta Rahman, Shamima Rahman
Primary mitochondrial diseases form one of the most common and severe groups of genetic disease, with a birth prevalence of at least 1 in 5000. These disorders are multi-genic and multi-phenotypic (even within the same gene defect) and span the entire age range from prenatal to late adult onset. Mitochondrial disease typically affects one or multiple high-energy demanding organs, and is frequently fatal in early life. Unfortunately, to date there are no known curative therapies, mostly owing to the rarity and heterogeneity of individual mitochondrial diseases, leading to diagnostic odysseys and difficulties in clinical trial design...
2019: Frontiers in Genetics
Qiguo Dai, Maozu Guo, Xiaodong Duan, Zhixia Teng, Yueyue Fu
Non-coding RNA (ncRNA) plays important roles in many critical regulation processes. Many ncRNAs perform their regulatory functions by the form of RNA-protein complexes. Therefore, identifying the interaction between ncRNA and protein is fundamental to understand functions of ncRNA. Under pressures from expensive cost of experimental techniques, developing an accuracy computational predictive model has become an indispensable way to identify ncRNA-protein interaction. A powerful predicting model of ncRNA-protein interaction needs a good feature set of characterizing the interaction...
2019: Frontiers in Genetics
Qiongqiong Wu, Peiyao Li, Minghua Wu, Qiang Liu
CircRNAs (circular RNAs) are a class of RNAs generated from circularization with multiple novel functions. Recent studies have revealed the aberrant expression and aberrant functions of circRNAs in various tumors; thus, circRNAs have been recognized as promising cancer biomarkers. However, the underlying mechanisms behind their aberrant expression and functions remain unclear. In this review, we discuss at length the cancer-specific deregulation of circRNAs and the potential underlying aberrant events in circRNA biogenesis, localization and removal in cancer cells...
2019: Frontiers in Genetics
Paolo Ronza, Diego Robledo, Roberto Bermúdez, Ana Paula Losada, Belén G Pardo, Paulino Martínez, María Isabel Quiroga
Enteromyxosis, caused by Enteromyxum scophthalmi , is one of the most devastating diseases stemming from myxozoan parasites in turbot ( Scophthalmus maximus L.), being a limiting factor for its production. The disease develops as a cachectic syndrome, associated to catarrhal enteritis and leukocytic depletion, with morbidity and mortality rates usually reaching 100%. To date, no effective treatment exists and there are different unknown issues concerning its pathogenesis. The gross and microscopic lesions associated to enteromyxosis have been thoroughly described, and several morphopathological studies have been carried out to elucidate the mechanisms of this host-parasite interaction...
2019: Frontiers in Genetics
Kathrin Klein, Roman Tremmel, Stefan Winter, Sarah Fehr, Florian Battke, Tim Scheurenbrand, Elke Schaeffeler, Saskia Biskup, Matthias Schwab, Ulrich M Zanger
We developed a panel-based NGS pipeline for comprehensive analysis of 340 genes involved in absorption, distribution, metabolism and excretion (ADME) of drugs, other xenobiotics, and endogenous substances. The 340 genes comprised phase I and II enzymes, drug transporters and regulator/modifier genes within their entire coding regions, adjacent intron regions and 5' and 3'UTR regions, resulting in a total panel size of 1,382 kbp. We applied the ADME NGS panel to sequence genomic DNA from 150 Caucasian liver donors with available comprehensive gene expression data...
2019: Frontiers in Genetics
Elise Schaefer, Clarisse Delvallée, Laura Mary, Corinne Stoetzel, Véronique Geoffroy, Caroline Marks-Delesalle, Muriel Holder-Espinasse, Jamal Ghoumid, Hélène Dollfus, Jean Muller
Bardet-Biedl syndrome (BBS; MIM 209900) is a rare ciliopathy characterized by retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. Mutations in 22 BBS genes have been identified to cause the disease. We report a family with typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, cognitive impairment, and atrioventricular septal defect) mutated in IFT27/BBS19 . IFT27 is part of the Intraflagellar transport (IFT), a bidirectional mechanism allowing the protein motility within the cilia...
2019: Frontiers in Genetics
Greco Hernández, Jorge L Ramírez, Abraham Pedroza-Torres, Luis A Herrera, Miguel A Jiménez-Ríos
Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. Despite the advances understanding the molecular processes driving the onset and progression of this disease, as well as the continued implementation of screening programs, PCa still remains a significant cause of morbidity and mortality, in particular in low-income countries. It is only recently that defects of the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template, have begun to gain attention as an important cause of cancer development in different human tissues, including prostate...
2019: Frontiers in Genetics
Ping Luo, Yulian Ding, Xiujuan Lei, Fang-Xiang Wu
With the advances in high-throughput technologies, millions of somatic mutations have been reported in the past decade. Identifying driver genes with oncogenic mutations from these data is a critical and challenging problem. Many computational methods have been proposed to predict driver genes. Among them, machine learning-based methods usually train a classifier with representations that concatenate various types of features extracted from different kinds of data. Although successful, simply concatenating different types of features may not be the best way to fuse these data...
2019: Frontiers in Genetics
Cong Wang, Ziying Liu, Yuepeng Ke, Fen Wang
Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions...
2019: Frontiers in Genetics
Aanchal Mongia, Debarka Sengupta, Angshul Majumdar
Motivation: Single-cell RNA sequencing has been proved to be revolutionary for its potential of zooming into complex biological systems. Genome-wide expression analysis at single-cell resolution provides a window into dynamics of cellular phenotypes. This facilitates the characterization of transcriptional heterogeneity in normal and diseased tissues under various conditions. It also sheds light on the development or emergence of specific cell populations and phenotypes. However, owing to the paucity of input RNA, a typical single cell RNA sequencing data features a high number of dropout events where transcripts fail to get amplified...
2019: Frontiers in Genetics
Lei Deng, Jiacheng Wang, Jingpu Zhang
MicroRNAs (miRNAs) have been demonstrated to play significant biological roles in many human biological processes. Inferring the functions of miRNAs is an important strategy for understanding disease pathogenesis at the molecular level. In this paper, we propose an integrated model, PmiRGO, to infer the gene ontology (GO) functions of miRNAs by integrating multiple data sources, including the expression profiles of miRNAs, miRNA-target interactions, and protein-protein interactions (PPI). PmiRGO starts by building a global network consisting of three networks...
2019: Frontiers in Genetics
Huilin Xie, Nanchao Hong, Erge Zhang, Fen Li, Kun Sun, Yu Yu
Copy number variants (CNVs) are major variations contributing to the gene heterogeneity of congenital heart diseases (CHD). pulmonary atresia with ventricular septal defect (PA-VSD) is a rare form of cyanotic CHD characterized by complex manifestations and the genetic determinants underlying PA-VSD are still largely unknown. We investigated rare CNVs in a recruited cohort of 100 unrelated patients with PA-VSD, PA-IVS, or TOF and a population-matched control cohort of 100 healthy children using whole-exome sequencing...
2019: Frontiers in Genetics
Vinay K Mayya, Thomas F Duchaine
The sequences and structures of 3'-untranslated regions (3'UTRs) of messenger RNAs govern their stability, localization, and expression. 3'UTR regulatory elements are recognized by a wide variety of trans -acting factors that include microRNAs (miRNAs), their associated machinery, and RNA-binding proteins (RBPs). In turn, these factors instigate common mechanistic strategies to execute the regulatory programs encoded by 3'UTRs. Here, we review classes of factors that recognize 3'UTR regulatory elements and the effector machineries they guide toward mRNAs to dictate their expression and fate...
2019: Frontiers in Genetics
Haiming Liu, Nan Wu, Zhe Zhang, XiaoDan Zhong, Hao Zhang, Hao Guo, Yongzhan Nie, Yuanning Liu
Gastric cancer (GC) is a considerable global health burden. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and play important roles in GC. However, only a few lncRNAs have been functionally characterized. In this study, we identified that long intergenic non-protein coding RNA 941 ( LINC00941 ) is a potential biomarker for diagnosis and prognosis from the cancer genome atlas (TCGA), and we found that the expression of LINC00941 is associated with tumor depth and distant metastasis in GC...
2019: Frontiers in Genetics
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