Genes

28 pages, 777 KiB

Open AccessReview

The Present and Future of Whole Genome Sequencing (WGS) and Whole Metagenome Sequencing (WMS) for Surveillance of Antimicrobial Resistant Microorganisms and Antimicrobial Resistance Genes across the Food Chain

by Elena A. Oniciuc, Eleni Likotrafiti, Adrián Alvarez-Molina, Miguel Prieto, Jesús A. Santos and Avelino Alvarez-Ordóñez

Genes 2018, 9(5), 268; https://doi.org/10.3390/genes9050268 - 22 May 2018

Cited by 108 | Viewed by 20138 | Correction

Abstract

Antimicrobial resistance (AMR) surveillance is a critical step within risk assessment schemes, as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions, and detecting new trends and emerging threats linked to food. Surveillance of AMR is currently [...] Read more.

Antimicrobial resistance (AMR) surveillance is a critical step within risk assessment schemes, as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions, and detecting new trends and emerging threats linked to food. Surveillance of AMR is currently based on the isolation of indicator microorganisms and the phenotypic characterization of clinical, environmental and food strains isolated. However, this approach provides very limited information on the mechanisms driving AMR or on the presence or spread of AMR genes throughout the food chain. Whole-genome sequencing (WGS) of bacterial pathogens has shown potential for epidemiological surveillance, outbreak detection, and infection control. In addition, whole metagenome sequencing (WMS) allows for the culture-independent analysis of complex microbial communities, providing useful information on AMR genes occurrence. Both technologies can assist the tracking of AMR genes and mobile genetic elements, providing the necessary information for the implementation of quantitative risk assessments and allowing for the identification of hotspots and routes of transmission of AMR across the food chain. This review article summarizes the information currently available on the use of WGS and WMS for surveillance of AMR in foodborne pathogenic bacteria and food-related samples and discusses future needs that will have to be considered for the routine implementation of these next-generation sequencing methodologies with this aim. In particular, methodological constraints that impede the use at a global scale of these high-throughput sequencing (HTS) technologies are identified, and the standardization of methods and protocols is suggested as a measure to upgrade HTS-based AMR surveillance schemes. Full article

(This article belongs to the Special Issue Genetics and Genomics of Foodborne Pathogens)

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Graphical abstract

11 pages, 424 KiB

Open AccessArticle

Validation of Ion Torrent^TM Inherited Disease Panel with the PGM^TM Sequencing Platform for Rapid and Comprehensive Mutation Detection

by Abeer E. Mustafa, Tariq Faquih, Batoul Baz, Rana Kattan, Abdulelah Al-Issa, Asma I. Tahir, Faiqa Imtiaz, Khushnooda Ramzan, Moeenaldeen Al-Sayed, Mohammed Alowain, Zuhair Al-Hassnan, Hamad Al-Zaidan, Mohamed Abouelhoda, Bashayer R. Al-Mubarak and Nada A. Al Tassan

Genes 2018, 9(5), 267; https://doi.org/10.3390/genes9050267 - 22 May 2018

Cited by 9 | Viewed by 7344

Abstract

Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS) platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a [...] Read more.

Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS) platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP) consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%). The sensitivity for detecting single nucleotide variants (SNVs) and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM), delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation. Full article

(This article belongs to the Special Issue Emerging Applications for Next Generation Sequencing)

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15 pages, 4072 KiB

Open AccessArticle

Comparative Analysis of DNA Methylation Reveals Specific Regulations on Ethylene Pathway in Tomato Fruit

by Jinhua Zuo, Yunxiang Wang, Benzhong Zhu, Yunbo Luo, Qing Wang and Lipu Gao

Genes 2018, 9(5), 266; https://doi.org/10.3390/genes9050266 - 21 May 2018

Cited by 18 | Viewed by 4763

Abstract

DNA methylation is an essential feature of epigenetic regulation and plays a role in various physiological and biochemical processes at CG, CHG, and CHH sites in plants. LeERF1 is an ethylene response factor (ERF) found in tomatoes which plays an important role in [...] Read more.

DNA methylation is an essential feature of epigenetic regulation and plays a role in various physiological and biochemical processes at CG, CHG, and CHH sites in plants. LeERF1 is an ethylene response factor (ERF) found in tomatoes which plays an important role in ethylene signal transduction. To explore the characteristics of DNA methylation in the ethylene pathway, sense-/antisense-LeERF1 transgenic tomato fruit were chosen for deep sequencing and bioinformatics parsing. The methylation type with the greatest distribution was CG, (71.60–72.80%) and CHH was found least frequently (10.70–12.50%). The level of DNA methylation was different among different tomato genomic regions. The differentially methylated regions (DMRs) and the differentially expressed genes (DEGs) were conjointly analyzed and 3030 different expressed genes were found, of which several are involved in ethylene synthesis and signaling transduction (such as ACS, ACO, MADS-Box, ERFs, and F-box). Furthermore, the relationships between DNA methylation and microRNAs (miRNAs) were also deciphered, providing basic information for the further study of DNA methylation and small RNAs involved in the ethylene pathway. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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19 pages, 2457 KiB

Open AccessReview

Influence of Maternal Aging on Mitochondrial Heterogeneity, Inheritance, and Function in Oocytes and Preimplantation Embryos

by Dori C. Woods, Konstantin Khrapko and Jonathan L. Tilly

Genes 2018, 9(5), 265; https://doi.org/10.3390/genes9050265 - 21 May 2018

Cited by 37 | Viewed by 7251

Abstract

Contrasting the equal contribution of nuclear genetic material from maternal and paternal sources to offspring, passage of mitochondria, and thus mitochondrial DNA (mtDNA), is uniparental through the egg. Since mitochondria in eggs are ancestral to all somatic mitochondria of the next generation and [...] Read more.

Contrasting the equal contribution of nuclear genetic material from maternal and paternal sources to offspring, passage of mitochondria, and thus mitochondrial DNA (mtDNA), is uniparental through the egg. Since mitochondria in eggs are ancestral to all somatic mitochondria of the next generation and to all cells of future generations, oocytes must prepare for the high energetic demands of maturation, fertilization and embryogenesis while simultaneously ensuring that their mitochondrial genomes are inherited in an undamaged state. Although significant effort has been made to understand how the mtDNA bottleneck and purifying selection act coordinately to prevent silent and unchecked spreading of invisible mtDNA mutations through the female germ line across successive generations, it is unknown if and how somatic cells of the immediate next generation are spared from inheritance of detrimental mtDNA molecules. Here, we review unique aspects of mitochondrial activity and segregation in eggs and early embryos, and how these events play into embryonic developmental competency in the face of advancing maternal age. Full article

(This article belongs to the Special Issue Mitochondria and Aging)

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18 pages, 1612 KiB

Open AccessFeature PaperReview

The Guppy Sex Chromosome System and the Sexually Antagonistic Polymorphism Hypothesis for Y Chromosome Recombination Suppression

by Deborah Charlesworth

Genes 2018, 9(5), 264; https://doi.org/10.3390/genes9050264 - 19 May 2018

Cited by 30 | Viewed by 8119

Abstract

Sex chromosomes regularly evolve suppressed recombination, distinguishing them from other chromosomes, and the reason for this has been debated for many years. It is now clear that non-recombining sex-linked regions have arisen in different ways in different organisms. A major hypothesis is that [...] Read more.

Sex chromosomes regularly evolve suppressed recombination, distinguishing them from other chromosomes, and the reason for this has been debated for many years. It is now clear that non-recombining sex-linked regions have arisen in different ways in different organisms. A major hypothesis is that a sex-determining gene arises on a chromosome and that sexually antagonistic (SA) selection (sometimes called intra-locus sexual conflict) acting at a linked gene has led to the evolution of recombination suppression in the region, to reduce the frequency of low fitness recombinant genotypes produced. The sex chromosome system of the guppy (Poecilia reticulata) is often cited as supporting this hypothesis because SA selection has been demonstrated to act on male coloration in natural populations of this fish, and probably contributes to maintaining polymorphisms for the genetic factors involved. I review classical genetic and new molecular genetic results from the guppy, and other fish, including approaches for identifying the genome regions carrying sex-determining loci, and suggest that the guppy may exemplify a recently proposed route to sex chromosome evolution. Full article

(This article belongs to the Special Issue The Evolutionary Life Cycle of Sex Chromosomes)

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21 pages, 1012 KiB

Open AccessReview

Regulation Mediated by N-Acyl Homoserine Lactone Quorum Sensing Signals in the Rhizobium-Legume Symbiosis

by Nieves Calatrava-Morales, Matthew McIntosh and María J. Soto

Genes 2018, 9(5), 263; https://doi.org/10.3390/genes9050263 - 18 May 2018

Cited by 58 | Viewed by 7344

Abstract

Soil-dwelling bacteria collectively referred to as rhizobia synthesize and perceive N-acyl-homoserine lactone (AHL) signals to regulate gene expression in a population density-dependent manner. AHL-mediated signaling in these bacteria regulates several functions which are important for the establishment of nitrogen-fixing symbiosis with legume [...] Read more.

Soil-dwelling bacteria collectively referred to as rhizobia synthesize and perceive N-acyl-homoserine lactone (AHL) signals to regulate gene expression in a population density-dependent manner. AHL-mediated signaling in these bacteria regulates several functions which are important for the establishment of nitrogen-fixing symbiosis with legume plants. Moreover, rhizobial AHL act as interkingdom signals triggering plant responses that impact the plant-bacteria interaction. Both the regulatory mechanisms that control AHL synthesis in rhizobia and the set of bacterial genes and associated traits under quorum sensing (QS) control vary greatly among the rhizobial species. In this article, we focus on the well-known QS system of the alfalfa symbiont Sinorhizobium (Ensifer) meliloti. Bacterial genes, environmental factors and transcriptional and posttranscriptional regulatory mechanisms that control AHL production in this Rhizobium, as well as the effects of the signaling molecule on bacterial phenotypes and plant responses will be reviewed. Current knowledge of S. meliloti QS will be compared with that of other rhizobia. Finally, participation of the legume host in QS by interfering with rhizobial AHL perception through the production of molecular mimics will also be addressed. Full article

(This article belongs to the Special Issue Genetic Networks and Gene Regulation Mechanisms for Quorum Sensing and Quorum Quenching in Bacteria)

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26 pages, 1870 KiB

Open AccessArticle

Genomic Differentiation during Speciation-with-Gene-Flow: Comparing Geographic and Host-Related Variation in Divergent Life History Adaptation in Rhagoletis pomonella

by Meredith M. Doellman, Gregory J. Ragland, Glen R. Hood, Peter J. Meyers, Scott P. Egan, Thomas H. Q. Powell, Peter Lazorchak, Mary M. Glover, Cheyenne Tait, Hannes Schuler, Daniel A. Hahn, Stewart H. Berlocher, James J. Smith, Patrik Nosil and Jeffrey L. Feder

Genes 2018, 9(5), 262; https://doi.org/10.3390/genes9050262 - 18 May 2018

Cited by 35 | Viewed by 7186

Abstract

A major goal of evolutionary biology is to understand how variation within populations gets partitioned into differences between reproductively isolated species. Here, we examine the degree to which diapause life history timing, a critical adaptation promoting population divergence, explains geographic and host-related genetic [...] Read more.

A major goal of evolutionary biology is to understand how variation within populations gets partitioned into differences between reproductively isolated species. Here, we examine the degree to which diapause life history timing, a critical adaptation promoting population divergence, explains geographic and host-related genetic variation in ancestral hawthorn and recently derived apple-infesting races of Rhagoletis pomonella. Our strategy involved combining experiments on two different aspects of diapause (initial diapause intensity and adult eclosion time) with a geographic survey of genomic variation across four sites where apple and hawthorn flies co-occur from north to south in the Midwestern USA. The results demonstrated that the majority of the genome showing significant geographic and host-related variation can be accounted for by initial diapause intensity and eclosion time. Local genomic differences between sympatric apple and hawthorn flies were subsumed within broader geographic clines; allele frequency differences within the races across the Midwest were two to three-fold greater than those between the races in sympatry. As a result, sympatric apple and hawthorn populations displayed more limited genomic clustering compared to geographic populations within the races. The findings suggest that with reduced gene flow and increased selection on diapause equivalent to that seen between geographic sites, the host races may be recognized as different genotypic entities in sympatry, and perhaps species, a hypothesis requiring future genomic analysis of related sibling species to R. pomonella to test. Our findings concerning the way selection and geography interplay could be of broad significance for many cases of earlier stages of divergence-with-gene flow, including (1) where only modest increases in geographic isolation and the strength of selection may greatly impact genetic coupling and (2) the dynamics of how spatial and temporal standing variation is extracted by selection to generate differences between new and discrete units of biodiversity. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Reproductive Isolation)

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10 pages, 254 KiB

Open AccessArticle

Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study

by Julia E.C. Van Steenhoven, Anne Kuijer, Paul J. Van Diest, Joost M. Van Gorp, Marieke Straver, Sjoerd G. Elias, Jelle Wesseling, Emiel Rutgers, Johanna N.H. Timmer-Bonte, Peter Nieboer, Tineke J. Smilde, Alex Imholz, Charlotte F.J.M. Blanken, Sabine Siesling and Thijs Van Dalen

Genes 2018, 9(5), 261; https://doi.org/10.3390/genes9050261 - 17 May 2018

Cited by 5 | Viewed by 3770

Abstract

In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, “MammaPrint”) use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, “BluePrint”) versus surrogate pathological subtyping (PS). Between [...] Read more.

In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, “MammaPrint”) use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, “BluePrint”) versus surrogate pathological subtyping (PS). Between 1 January 2013 and 31 December 2015, 595 clinical intermediate risk ER+ early stage breast cancer patients were enrolled. Hormone receptor (HR) and HER2 receptor status were determined by conventional pathology using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Ki67 was assessed in a subset of patients. The overall concordance between PS and MS for luminal type cancers (A and B together) was 98%. The concordance between PS and MS for luminal A and luminal B type cancers based on the Bloom Richardson histological grade (BR) (n = 586) or Ki67 (n = 185) was low: 64% (Kappa 0.20 [95% CI 0.11–0.28]) and 65% (Kappa 0.22 [95% CI 0.062–0.37]), respectively. In this prospective study (NCT02209857) of a selection of ER+ and predominantly HER2− early-stage breast cancer patients, the additional ability of the 80-GS to distinguish between luminal, HER2-type and basal-like cancers was inherently very limited. The distinction of luminal-type tumors into A and B according to Ki67 status or BR grade versus the 70-GS revealed poor concordance. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

20 pages, 5911 KiB

Open AccessArticle

Identification and Characterization of the WOX Family Genes in Five Solanaceae Species Reveal Their Conserved Roles in Peptide Signaling

by Xiaoxu Li, Madiha Hamyat, Cheng Liu, Salman Ahmad, Xiaoming Gao, Cun Guo, Yuanying Wang and Yongfeng Guo

Genes 2018, 9(5), 260; https://doi.org/10.3390/genes9050260 - 17 May 2018

Cited by 38 | Viewed by 6520 | Correction

Abstract

Members of the plant-specific WOX (WUSCHEL-related homeobox) transcription factor family have been reported to play important roles in peptide signaling that regulates stem cell maintenance and cell fate specification in various developmental processes. Even though remarkable advances have been made in studying WOX [...] Read more.

Members of the plant-specific WOX (WUSCHEL-related homeobox) transcription factor family have been reported to play important roles in peptide signaling that regulates stem cell maintenance and cell fate specification in various developmental processes. Even though remarkable advances have been made in studying WOX genes in Arabidopsis, little is known about this family in Solanaceae species. A total of 45 WOX members from five Solanaceae species were identified, including eight members from Solanum tuberosum, eight from Nicotiana tomentosiformis, 10 from Solanum lycopersicum, 10 from Nicotiana sylvestris and nine from Nicotiana tabacum. The newly identified WOX members were classified into three clades and nine subgroups based on phylogenetic analysis using three different methods. The patterns of exon-intron structure and motif organization of the WOX proteins agreed with the phylogenetic results. Gene duplication events and ongoing evolution were revealed by additional branches on the phylogenetic tree and the presence of a partial WUS-box in some non-WUS clade members. Gene expression with or without CLE (clavata3 (clv3)/embryo surrounding region-related) peptide treatments revealed that tobacco WOX genes showed similar or distinct expression patterns compared with their Arabidopsis homologues, suggesting either functional conservation or divergence. Expression of Nicotiana tabacum WUSCHEL (NtabWUS) in the organizing center could rescue the wus-1 mutant phenotypes in Arabidopsis, implying conserved roles of the Solanaceae WOX proteins in peptide-mediated regulation of plant development. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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13 pages, 748 KiB

Open AccessArticle

Chronic and Occult Hepatitis B Virus Infection in Pregnant Women in Botswana

by Tshepiso Mbangiwa, Ishmael Kasvosve, Motswedi Anderson, Prisca K. Thami, Wonderful T. Choga, Austen Needleman, Bonolo B. Phinius, Sikhulile Moyo, Melvin Leteane, Jean Leidner, Jason T. Blackard, Gloria Mayondi, Betsy Kammerer, Rosemary M. Musonda, Max Essex, Shahin Lockman and Simani Gaseitsiwe

Genes 2018, 9(5), 259; https://doi.org/10.3390/genes9050259 - 17 May 2018

Cited by 27 | Viewed by 6175

Abstract

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women [...] Read more.

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women in Botswana. Samples from 752 pregnant women were tested for hepatitis B surface antigen (HBsAg), and HBsAg-positive samples were tested for hepatitis B e antigen (HBeAg) and HBV DNA load. Samples that were HBsAg negative were screened for occult HBV infection by determining the HBV DNA load. HBV genotypes were determined based on a 415-base-pair fragment of the surface gene. Among the 752 women tested during pregnancy or early postpartum, 16 (2.1%) (95% confidence interval (CI): 2.0–2.2) were HBsAg-positive. The prevalence of chronic HBV infection was higher (3.1%) among HIV-infected (95% CI: 3.0–3.2) compared with HIV-uninfected women (1.1%) (95% CI: 1.07–1.1, p = 0.057). Among the 622 HBsAg-negative women, the prevalence of occult HBV infection was 6.6% (95% CI: 6.5–6.7). Three of thirteen HBsAg-positive participants were HBeAg-positive, and all were HIV-negative. Of the 11 maternal samples successfully genotyped, five (45.5%) were genotype D3, five (45.5%) were genotype A1, and one was genotype E (9%). Low and similar proportions of HIV-infected and -uninfected pregnant women in Botswana had occult or chronic HBV infection. We identified a subset of HIV-negative pregnant women who had high HBV DNA levels and were HBeAg-positive, and thus likely to transmit HBV to their infants. Full article

(This article belongs to the Special Issue Hepatitis B Virus Infection: An Update on Epidemiology, Diagnosis, Treatment and Prevention)

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12 pages, 688 KiB

Open AccessArticle

The Cross-Entropy Based Multi-Filter Ensemble Method for Gene Selection

by Yingqiang Sun, Chengbo Lu and Xiaobo Li

Genes 2018, 9(5), 258; https://doi.org/10.3390/genes9050258 - 17 May 2018

Cited by 21 | Viewed by 4254

Abstract

The gene expression profile has the characteristics of a high dimension, low sample, and continuous type, and it is a great challenge to use gene expression profile data for the classification of tumor samples. This paper proposes a cross-entropy based multi-filter ensemble (CEMFE) [...] Read more.

The gene expression profile has the characteristics of a high dimension, low sample, and continuous type, and it is a great challenge to use gene expression profile data for the classification of tumor samples. This paper proposes a cross-entropy based multi-filter ensemble (CEMFE) method for microarray data classification. Firstly, multiple filters are used to select the microarray data in order to obtain a plurality of the pre-selected feature subsets with a different classification ability. The top N genes with the highest rank of each subset are integrated so as to form a new data set. Secondly, the cross-entropy algorithm is used to remove the redundant data in the data set. Finally, the wrapper method, which is based on forward feature selection, is used to select the best feature subset. The experimental results show that the proposed method is more efficient than other gene selection methods and that it can achieve a higher classification accuracy under fewer characteristic genes. Full article

(This article belongs to the Special Issue Selected Papers from the Bioinformatics and Intelligent Information Processing Conference (BIIP2018))

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11 pages, 1387 KiB

Open AccessCommunication

AtPAP2, a Unique Member of the PAP Family, Functions in the Plasma Membrane

by Qingqing Sun, Jinyu Li, Wenzhen Cheng, Huihong Guo, Xiaomin Liu and Hongbo Gao

Genes 2018, 9(5), 257; https://doi.org/10.3390/genes9050257 - 17 May 2018

Cited by 8 | Viewed by 4469

Abstract

Purple acid phosphatases (PAPs) play various physiological roles in plants. AtPAP2 was previously shown to localize to both chloroplasts and mitochondria and to modulate carbon metabolism in Arabidopsis. Over-expression of AtPAP2 resulted in faster growth and increased biomass in several plant species, [...] Read more.

Purple acid phosphatases (PAPs) play various physiological roles in plants. AtPAP2 was previously shown to localize to both chloroplasts and mitochondria and to modulate carbon metabolism in Arabidopsis. Over-expression of AtPAP2 resulted in faster growth and increased biomass in several plant species, indicating its great potential for crop improvement of phosphate use and yield. Here, we studied the localization of AtPAP2 by transient expression in tobacco leaves. The results showed AtPAP2 was localized to the plasma membrane through the secretory pathway, which is different from previous studies. We also found that AtPAP2 had a close relationship with fungal PAP2-like proteins based on phylogenetic analysis. In addition, the C-terminal transmembrane domain conserved in land plants is unique among other AtPAPs except AtPAP9, which is a close homolog of AtPAP2. Taken together, our results provide information for further study of AtPAP2 in understanding its special function in crop improvement. Full article

(This article belongs to the Special Issue Plant Genomics and Epigenomics for Trait Improvement)

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13 pages, 508 KiB

Open AccessArticle

Characterization of Antimicrobial Resistance Determinants and Class 1 and Class 2 Integrons in Salmonella enterica spp., Multidrug-Resistant Isolates from Pigs

by Héctor Argüello, Beatriz Guerra, Irene Rodríguez, Pedro Rubio and Ana Carvajal

Genes 2018, 9(5), 256; https://doi.org/10.3390/genes9050256 - 16 May 2018

Cited by 24 | Viewed by 4787

Abstract

Antimicrobial resistance (AMR) and Salmonella spp., are primary concerns in public health. The present study characterizes the AMR determinants of 62 multi-drug resistant (MDR) Salmonella enterica spp., isolates from swine, which were obtained between 2004–2006, a major source of human salmonellosis. The AMR [...] Read more.

Antimicrobial resistance (AMR) and Salmonella spp., are primary concerns in public health. The present study characterizes the AMR determinants of 62 multi-drug resistant (MDR) Salmonella enterica spp., isolates from swine, which were obtained between 2004–2006, a major source of human salmonellosis. The AMR determinants were investigated by PCR, checking the presence of class 1 and class 2 integrons and 29 resistance genes. Genes sul1, blaTEM1-like, aadA2, tet(A), and dfrA12 were more prevalent (p < 0.05) within the determinants that were checked for each of these antimicrobials. Co-existence of different genes conferring resistance to the same antimicrobial was common. No differences in AMR determinants prevalence were observed between Salmonella Typhimurium and other serovars from the study. Class 1 integrons were detected in 48 of 62 isolates, again with no differences being linked to any serovar. Nine different variable regions were observed, 1000 bp/aadA2-1200 bp/blaPSE-1 (13 isolates) and blaOXA-like/aadA1 (eight isolates) were the most common. Four isolates, including S. Typhimurium (2), Salmonella Bredeney (1), and Salmonella Kapemba (1) harboured a class 2 integron 2300 bp estX-sat2-aadA1. Results from the study highlight the importance of class 1 integrons and certain genes in MDR swine Salmonella isolates. The information is of relevance for monitoring in the forthcoming scope of reduction of antibiotic usage in swine production. Full article

(This article belongs to the Special Issue Genetics and Genomics of Foodborne Pathogens)

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24 pages, 7477 KiB

Open AccessFeature PaperReview

The Changing Landscape in the Genetic Etiology of Human Tooth Agenesis

by Meredith A. Williams and Ariadne Letra

Genes 2018, 9(5), 255; https://doi.org/10.3390/genes9050255 - 16 May 2018

Cited by 41 | Viewed by 6224

Abstract

Despite much progress in understanding the genetics of syndromic tooth agenesis (TA), the causes of the most common, isolated TA remain elusive. Recent studies have identified novel genes and variants contributing to the etiology of TA, and revealed new pathways in which tooth [...] Read more.

Despite much progress in understanding the genetics of syndromic tooth agenesis (TA), the causes of the most common, isolated TA remain elusive. Recent studies have identified novel genes and variants contributing to the etiology of TA, and revealed new pathways in which tooth development genes belong. Further, the use of new research approaches including next-generation sequencing has provided increased evidence supporting an oligogenic inheritance model for TA, and may explain the phenotypic variability of the condition. In this review, we present current knowledge about the genetic mechanisms underlying syndromic and isolated TA in humans, and highlight the value of incorporating next-generation sequencing approaches to identify causative and/or modifier genes that contribute to the etiology of TA. Full article

(This article belongs to the Special Issue DNA Variations in Evolution and Human Diseases)

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29 pages, 1077 KiB

Open AccessReview

The Role of Transposable Elements in Speciation

by Antonio Serrato-Capuchina and Daniel R. Matute

Genes 2018, 9(5), 254; https://doi.org/10.3390/genes9050254 - 15 May 2018

Cited by 117 | Viewed by 16274

Abstract

Understanding the phenotypic and molecular mechanisms that contribute to genetic diversity between and within species is fundamental in studying the evolution of species. In particular, identifying the interspecific differences that lead to the reduction or even cessation of gene flow between nascent species [...] Read more.

Understanding the phenotypic and molecular mechanisms that contribute to genetic diversity between and within species is fundamental in studying the evolution of species. In particular, identifying the interspecific differences that lead to the reduction or even cessation of gene flow between nascent species is one of the main goals of speciation genetic research. Transposable elements (TEs) are DNA sequences with the ability to move within genomes. TEs are ubiquitous throughout eukaryotic genomes and have been shown to alter regulatory networks, gene expression, and to rearrange genomes as a result of their transposition. However, no systematic effort has evaluated the role of TEs in speciation. We compiled the evidence for TEs as potential causes of reproductive isolation across a diversity of taxa. We find that TEs are often associated with hybrid defects that might preclude the fusion between species, but that the involvement of TEs in other barriers to gene flow different from postzygotic isolation is still relatively unknown. Finally, we list a series of guides and research avenues to disentangle the effects of TEs on the origin of new species. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Reproductive Isolation)

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17 pages, 11322 KiB

Open AccessArticle

Role of SdiA on Biofilm Formation by Atypical Enteropathogenic Escherichia coli

by Hebert F. Culler, Samuel C. F. Couto, Juliana S. Higa, Renato M. Ruiz, Min J. Yang, Vanessa Bueris, Marcia R. Franzolin and Marcelo P. Sircili

Genes 2018, 9(5), 253; https://doi.org/10.3390/genes9050253 - 15 May 2018

Cited by 35 | Viewed by 5841

Abstract

Atypical enteropathogenic Escherichia coli are capable to form biofilm on biotic and abiotic surfaces, regardless of the adherence pattern displayed. Several E. coli mechanisms are regulated by Quorum sensing (QS), including virulence factors and biofilm formation. Quorum sensing is a signaling system that [...] Read more.

Atypical enteropathogenic Escherichia coli are capable to form biofilm on biotic and abiotic surfaces, regardless of the adherence pattern displayed. Several E. coli mechanisms are regulated by Quorum sensing (QS), including virulence factors and biofilm formation. Quorum sensing is a signaling system that confers bacteria with the ability to respond to chemical molecules known as autoinducers. Suppressor of division inhibitor (SdiA) is a QS receptor present in atypical enteropathogenic E. coli (aEPEC) that detects acyl homoserine lactone (AHL) type autoinducers. However, these bacteria do not encode an AHL synthase, but they are capable of sensing AHL molecules produced by other species, establishing an inter-species bacterial communication. In this study, we performed experiments to evaluate pellicle, ring-like structure and biofilm formation on wild type, sdiA mutants and complemented strains. We also evaluated the transcription of genes involved in different stages of biofilm formation, such as bcsA, csgA, csgD, fliC and fimA. The sdiA mutants were capable of forming thicker biofilm structures and showed increased motility when compared to wild type and complemented strains. Moreover, they also showed denser pellicles and ring-like structures. Quantitative real-time PCR (qRT-PCR) analysis demonstrated increased csgA, csgD and fliC transcription on mutant strains. Biofilm formation, as well as csgD, csgA and fimA transcription decreased on wild type strains by the addition of AHL. These results indicate that SdiA participates on the regulation of these phenotypes in aEPEC and that AHL addition enhances the repressor effect of this receptor on the transcription of biofilm and motility related genes. Full article

(This article belongs to the Special Issue Genetic Networks and Gene Regulation Mechanisms for Quorum Sensing and Quorum Quenching in Bacteria)

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25 pages, 4477 KiB

Open AccessArticle

Investigating the Epigenetic Discrimination of Identical Twins Using Buccal Swabs, Saliva, and Cigarette Butts in the Forensic Setting

by Athina Vidaki, Vivian Kalamara, Elena Carnero-Montoro, Timothy D. Spector, Jordana T. Bell and Manfred Kayser

Genes 2018, 9(5), 252; https://doi.org/10.3390/genes9050252 - 14 May 2018

Cited by 21 | Viewed by 8162

Abstract

Monozygotic (MZ) twins are typically indistinguishable via forensic DNA profiling. Recently, we demonstrated that epigenetic differentiation of MZ twins is feasible; however, proportions of twin differentially methylated CpG sites (tDMSs) identified in reference-type blood DNA were not replicated in trace-type blood DNA. Here [...] Read more.

Monozygotic (MZ) twins are typically indistinguishable via forensic DNA profiling. Recently, we demonstrated that epigenetic differentiation of MZ twins is feasible; however, proportions of twin differentially methylated CpG sites (tDMSs) identified in reference-type blood DNA were not replicated in trace-type blood DNA. Here we investigated buccal swabs as typical forensic reference material, and saliva and cigarette butts as commonly encountered forensic trace materials. As an analog to a forensic case, we analyzed one MZ twin pair. Epigenome-wide microarray analysis in reference-type buccal DNA revealed 25 candidate tDMSs with >0.5 twin-to-twin differences. MethyLight quantitative PCR (qPCR) of 22 selected tDMSs in trace-type DNA revealed in saliva DNA that six tDMSs (27.3%) had >0.1 twin-to-twin differences, seven (31.8%) had smaller (<0.1) but robustly detected differences, whereas for nine (40.9%) the differences were in the opposite direction relative to the microarray data; for cigarette butt DNA, results were 50%, 22.7%, and 27.3%, respectively. The discrepancies between reference-type and trace-type DNA outcomes can be explained by cell composition differences, method-to-method variation, and other technical reasons including bisulfite conversion inefficiency. Our study highlights the importance of the DNA source and that careful characterization of biological and technical effects is needed before epigenetic MZ twin differentiation is applicable in forensic casework. Full article

(This article belongs to the Special Issue Forensic Genomics)

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1 pages, 135 KiB

Open AccessErratum

Erratum: Dan Li et al.; Transcription Factor and lncRNA Regulatory Networks Identify Key Elements in Lung Adenocarcinoma. Genes 2018, 9, 12

by Dan Li, William Yang, Jialing Zhang, Jack Y. Yang, Renchu Guan and Mary Qu Yang

Genes 2018, 9(5), 251; https://doi.org/10.3390/genes9050251 - 14 May 2018

Cited by 1 | Viewed by 2712

Abstract

The authors wish to make the following change to their paper [...] Full article

9 pages, 223 KiB

Open AccessReview

Brain Mitochondria, Aging, and Parkinson’s Disease

by Mario Rango and Nereo Bresolin

Genes 2018, 9(5), 250; https://doi.org/10.3390/genes9050250 - 11 May 2018

Cited by 57 | Viewed by 6522

Abstract

This paper reconsiders the role of mitochondria in aging and in Parkinson’s Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered [...] Read more.

This paper reconsiders the role of mitochondria in aging and in Parkinson’s Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered autophagy, and mitochondrial dysfunction. Beyond declined oxidative phosphorylation, mitochondrial dysfunction consists of a decline of beta-oxidation as well as of the Krebs cycle. Not inherited mitochondrial DNA (mtDNA) mutations are acquired over time and parallel the decrease in oxidative phosphorylation. Many of these mitochondrial alterations are also found in the PD brain specifically in the substantia nigra (SN). mtDNA deletions and development of respiratory chain deficiency in SN neurons of aged individuals as well as of individuals with PD converge towards a shared pathway, which leads to neuronal dysfunction and death. Finally, several nuclear genes that are mutated in hereditary PD are usually implicated in mitochondrial functioning to a various extent and their mutation may cause mitochondrial impairment. In conclusion, a tight link exists between mitochondria, aging, and PD. Full article

(This article belongs to the Special Issue Mitochondria and Aging)

17 pages, 2668 KiB

Open AccessReview

Selecting the Best: Evolutionary Engineering of Chemical Production in Microbes

by Denis Shepelin, Anne Sofie Lærke Hansen, Rebecca Lennen, Hao Luo and Markus J. Herrgård

Genes 2018, 9(5), 249; https://doi.org/10.3390/genes9050249 - 11 May 2018

Cited by 35 | Viewed by 7621

Abstract

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing [...] Read more.

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing down rational engineering of industrially relevant strains. An alternative concept to rational engineering is to use evolution as the driving force to select for desired changes, an approach often described as evolutionary engineering. In evolutionary engineering, in vivo selections for a desired phenotype are combined with either generation of spontaneous mutations or some form of targeted or random mutagenesis. Evolutionary engineering has been used to successfully engineer easily selectable phenotypes, such as utilization of a suboptimal nutrient source or tolerance to inhibitory substrates or products. In this review, we focus primarily on a more challenging problem—the use of evolutionary engineering for improving the production of chemicals in microbes directly. We describe recent developments in evolutionary engineering strategies, in general, and discuss, in detail, case studies where production of a chemical has been successfully achieved through evolutionary engineering by coupling production to cellular growth. Full article

(This article belongs to the Special Issue Microbial Metabolic Engineering)

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17 pages, 3703 KiB

Open AccessArticle

Mapping Grain Iron and Zinc Content Quantitative Trait Loci in an Iniadi-Derived Immortal Population of Pearl Millet

by Sushil Kumar, Charles Tom Hash, Thirunavukkarasu Nepolean, Mahesh D. Mahendrakar, Chellapilla Tara Satyavathi, Govind Singh, Abhishek Rathore, Rattan S. Yadav, Rajeev Gupta and Rakesh K. Srivastava

Genes 2018, 9(5), 248; https://doi.org/10.3390/genes9050248 - 11 May 2018

Cited by 73 | Viewed by 6270

Abstract

Pearl millet is a climate-resilient nutritious crop requiring low inputs and is capable of giving economic returns in marginal agro-ecologies. In this study, we report large-effect iron (Fe) and zinc (Zn) content quantitative trait loci (QTLs) using diversity array technology (DArT) and [...] Read more.

Pearl millet is a climate-resilient nutritious crop requiring low inputs and is capable of giving economic returns in marginal agro-ecologies. In this study, we report large-effect iron (Fe) and zinc (Zn) content quantitative trait loci (QTLs) using diversity array technology (DArT) and simple sequence repeats (SSRs) markers to generate a genetic linkage map using 317 recombinant inbred line (RIL) population derived from the (ICMS 8511-S1-17-2-1-1-B-P03 × AIMP 92901-S1-183-2-2-B-08) cross. The base map [seven linkage groups (LGs)] of 196 loci was 964.2 cM in length (Haldane). AIMP 92901-S1-183-2-2-B-08 is an Iniadi line with high grain Fe and Zn, tracing its origin to the Togolese Republic, West Africa. The content of grain Fe in the RIL population ranged between 20 and 131 ppm (parts per million), and that of Zn from 18 to 110 ppm. QTL analysis revealed a large number of QTLs for high grain iron (Fe) and zinc (Zn) content. A total of 19 QTLs for Fe and Zn were detected, of which 11 were for Fe and eight were for Zn. The portion of the observed phenotypic variance explained by different QTLs for grain Fe and Zn content varied from 9.0 to 31.9% (cumulative 74%) and from 9.4 to 30.4% (cumulative 65%), respectively. Three large-effect QTLs for both minerals were co-mapped in this population, one on LG1 and two on LG7. The favorable QTL alleles of both mineral micronutrients were contributed by the male parent (AIMP 92901-deriv-08). Three putative epistasis interactions were observed for Fe content, while a single digenic interaction was found for Zn content. The reported QTLs may be useful in marker-assisted selection (MAS) programs, in genomic selection (GS) breeding pipelines for seed and restorer parents, and in population improvement programs for pearl millet. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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36 pages, 3631 KiB

Open AccessReview

Journey into Bone Models: A Review

by Julia Scheinpflug, Moritz Pfeiffenberger, Alexandra Damerau, Franziska Schwarz, Martin Textor, Annemarie Lang and Frank Schulze

Genes 2018, 9(5), 247; https://doi.org/10.3390/genes9050247 - 10 May 2018

Cited by 91 | Viewed by 12059

Abstract

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells [...] Read more.

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed. Full article

(This article belongs to the Special Issue From the Lab-on-a-Chip to the Organ-on-a-Chip)

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15 pages, 1547 KiB

Open AccessReview

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA

by Siqi Li, Zhengping Xu and Jinghao Sheng

Genes 2018, 9(5), 246; https://doi.org/10.3390/genes9050246 - 10 May 2018

Cited by 220 | Viewed by 13330

Abstract

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived [...] Read more.

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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12 pages, 3795 KiB

Open AccessArticle

Transcription Factor Binding Site Enrichment Analysis in Co-Expression Modules in Celiac Disease

by Irati Romero-Garmendia, Koldo Garcia-Etxebarria, Hector Hernandez-Vargas, Izortze Santin, Amaia Jauregi-Miguel, Leticia Plaza-Izurieta, Marie-Pierre Cros, Maria Legarda, Iñaki Irastorza, Zdenko Herceg, Nora Fernandez-Jimenez and Jose Ramon Bilbao

Genes 2018, 9(5), 245; https://doi.org/10.3390/genes9050245 - 10 May 2018

Cited by 4 | Viewed by 4630

Abstract

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified [...] Read more.

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gliadin was observed. Using transcriptome-wide co-expression analyses we are able to propose novel genes involved in CD pathogenesis that respond upon gliadin stimulation, also in non-celiac models. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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14 pages, 4515 KiB

Open AccessArticle

Chitinase mRNA Levels Determined by QPCR in Crab-Eating Monkey (Macaca fascicularis) Tissues: Species-Specific Expression of Acidic Mammalian Chitinase and Chitotriosidase

by Maiko Uehara, Eri Tabata, Kazuhiro Ishii, Akira Sawa, Misa Ohno, Masayoshi Sakaguchi, Vaclav Matoska, Peter O. Bauer and Fumitaka Oyama

Genes 2018, 9(5), 244; https://doi.org/10.3390/genes9050244 - 9 May 2018

Cited by 6 | Viewed by 9104

Abstract

Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey (Macaca fascicularis) is one of the most frequently used nonhuman primate models [...] Read more.

Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey (Macaca fascicularis) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule. Levels of AMCase and CHIT1 messenger RNAs (mRNAs) were highest in the stomach and the lung, respectively, when compared to other tissues. Comparative gene expression analysis of mouse, monkey, and human using monkey–mouse–human hybrid standard DNA showed that the AMCase mRNA levels were exceptionally high in mouse and monkey stomachs while very low in the human stomach. As for the CHIT1 mRNA, we detected higher levels in the monkey lung when compared with those of mouse and human. The differences of mRNA expression between the species in the stomach tissues were basically reflecting the levels of the chitinolytic activities. These results indicate that gene expression of AMCase and CHIT1 differs between mammalian species and requiring special attention in handling data in chitinase-related studies in particular organisms. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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18 pages, 2253 KiB

Open AccessReview

The Oncojanus Paradigm of Respiratory Complex I

by Giulia Leone, Houda Abla, Giuseppe Gasparre, Anna Maria Porcelli and Luisa Iommarini

Genes 2018, 9(5), 243; https://doi.org/10.3390/genes9050243 - 7 May 2018

Cited by 20 | Viewed by 5645

Abstract

Mitochondrial respiratory function is now recognized as a pivotal player in all the aspects of cancer biology, from tumorigenesis to aggressiveness and chemotherapy resistance. Among the enzymes that compose the respiratory chain, by contributing to energy production, redox equilibrium and oxidative stress, complex [...] Read more.

Mitochondrial respiratory function is now recognized as a pivotal player in all the aspects of cancer biology, from tumorigenesis to aggressiveness and chemotherapy resistance. Among the enzymes that compose the respiratory chain, by contributing to energy production, redox equilibrium and oxidative stress, complex I assumes a central role. Complex I defects may arise from mutations in mitochondrial or nuclear DNA, in both structural genes or assembly factors, from alteration of the expression levels of its subunits, or from drug exposure. Since cancer cells have a high-energy demand and require macromolecules for proliferation, it is not surprising that severe complex I defects, caused either by mutations or treatment with specific inhibitors, prevent tumor progression, while contributing to resistance to certain chemotherapeutic agents. On the other hand, enhanced oxidative stress due to mild complex I dysfunction drives an opposite phenotype, as it stimulates cancer cell proliferation and invasiveness. We here review the current knowledge on the contribution of respiratory complex I to cancer biology, highlighting the double-edged role of this metabolic enzyme in tumor progression, metastasis formation, and response to chemotherapy. Full article

(This article belongs to the Special Issue The Double-Edged Role of Noncanonical Oncogenes and Tumor Suppressor Genes in Cancer Progression; An Oncojanus Function)

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13 pages, 400 KiB

Open AccessFeature PaperArticle

Regulation of the X Chromosome in the Germline and Soma of Drosophila melanogaster Males

by Eliza Argyridou and John Parsch

Genes 2018, 9(5), 242; https://doi.org/10.3390/genes9050242 - 4 May 2018

Cited by 11 | Viewed by 5202

Abstract

During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster. We observe nearly complete X [...] Read more.

During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster. We observe nearly complete X chromosome dosage compensation in male somatic tissues, but not in testis. The X chromosome contains disproportionately fewer genes with high expression in testis than the autosomes, even after accounting for the lack of dosage compensation, which suggests that another mechanism suppresses their expression in the male germline. This is consistent with studies of reporter genes and transposed genes, which find that the same gene has higher expression when autosomal than when X-linked. Using a new reporter gene that is expressed in both testis and somatic tissues, we find that the suppression of X-linked gene expression is limited to genes with high expression in testis and that the extent of the suppression is positively correlated with expression level. Full article

(This article belongs to the Special Issue The Evolutionary Life Cycle of Sex Chromosomes)

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58 pages, 1749 KiB

Open AccessReview

Telomere Maintenance Mechanisms in Cancer

by Tiago Bordeira Gaspar, Ana Sá, José Manuel Lopes, Manuel Sobrinho-Simões, Paula Soares and João Vinagre

Genes 2018, 9(5), 241; https://doi.org/10.3390/genes9050241 - 3 May 2018

Cited by 92 | Viewed by 11968

Abstract

Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative [...] Read more.

Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the TERT promoter (TERTp), amplification of the genes TERT and TERC, polymorphic variants of the TERT gene and of its promoter, rearrangements of the TERT gene, epigenetic changes, ALT, and non-defined TMM (NDTMM). We gathered information from over fifty thousand patients reported in 288 papers in the last years. This wide data collection enabled us to portray, by organ/system and histotypes, the prevalence of TERTp mutations, TERT and TERC amplifications, and ALT in human tumours. Based on this information, we discuss the putative future clinical impact of the aforementioned mechanisms on the malignant transformation process in different setups, and provide insights for screening, prognosis, and patient management stratification. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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19 pages, 4281 KiB

Open AccessArticle

Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study

by Antonio Salas, Jacobo Pardo-Seco, Ruth Barral-Arca, Miriam Cebey-López, Alberto Gómez-Carballa, Irene Rivero-Calle, Sara Pischedda, María-José Currás-Tuala, Jorge Amigo, José Gómez-Rial, Federico Martinón-Torres and On behalf of GENDRES Network

Genes 2018, 9(5), 240; https://doi.org/10.3390/genes9050240 - 3 May 2018

Cited by 10 | Viewed by 5672

Abstract

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with [...] Read more.

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1; chromosome 2; p-value_IBS = 3.71 × 10⁻¹³) and rs576099063 (gene TSPAN15; chromosome 10; p-value_IBS = 2.36 × 10⁻⁸) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9, MUC6, MUC3A and APOB, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes (MUC6 and MUC3A), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases. Full article

(This article belongs to the Special Issue Complex Genetic Loci)

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16 pages, 1195 KiB

Open AccessReview

Did Lizards Follow Unique Pathways in Sex Chromosome Evolution?

by Shayer Mahmood Ibney Alam, Stephen D. Sarre, Dianne Gleeson, Arthur Georges and Tariq Ezaz

Genes 2018, 9(5), 239; https://doi.org/10.3390/genes9050239 - 3 May 2018

Cited by 30 | Viewed by 8394

Abstract

Reptiles show remarkable diversity in modes of reproduction and sex determination, including high variation in the morphology of sex chromosomes, ranging from homomorphic to highly heteromorphic. Additionally, the co-existence of genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) within and among sister [...] Read more.

Reptiles show remarkable diversity in modes of reproduction and sex determination, including high variation in the morphology of sex chromosomes, ranging from homomorphic to highly heteromorphic. Additionally, the co-existence of genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) within and among sister clades makes this group an attractive model to study and understand the evolution of sex chromosomes. This is particularly so with Lizards (Order Squamata) which, among reptiles, show extraordinary morphological diversity. They also show no particular pattern of sex chromosome degeneration of the kind observed in mammals, birds and or even in snakes. We therefore speculate that sex determination sensu sex chromosome evolution is labile and rapid and largely follows independent trajectories within lizards. Here, we review the current knowledge on the evolution of sex chromosomes in lizards and discuss how sex chromosome evolution within that group differs from other amniote taxa, facilitating unique evolutionary pathways. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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