Genes

13 pages, 5191 KiB

Open AccessArticle

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

by Yana Li, Qiu Jiang, Zhiwen Ding, Guijian Liu, Peng Yu, Guoliang Jiang, Ziqing Yu, Chunjie Yang, Juying Qian, Hong Jiang and Yunzeng Zou

Genes 2018, 9(1), 56; https://doi.org/10.3390/genes9010056 - 22 Jan 2018

Cited by 15 | Viewed by 5617

Abstract

The molecular mechanisms underlying the development of ischemic cardiomyopathy (ICM) remain poorly understood. Gene expression profiling is helpful to discover the molecular changes taking place in ICM. The aim of this study was to identify the genes that are significantly changed during the [...] Read more.

The molecular mechanisms underlying the development of ischemic cardiomyopathy (ICM) remain poorly understood. Gene expression profiling is helpful to discover the molecular changes taking place in ICM. The aim of this study was to identify the genes that are significantly changed during the development of heart failure caused by ICM. The differentially expressed genes (DEGs) were identified from 162 control samples and 227 ICM patients. PANTHER was used to perform gene ontology (GO), and Reactome for pathway enrichment analysis. A protein–protein interaction network was established using STRING and Cytoscape. A further validation was performed by real-time polymerase chain reaction (RT-PCR). A total of 255 common DEGs was found. Gene ontology, pathway enrichment, and protein–protein interaction analysis showed that nucleic acid-binding proteins, enzymes, and transcription factors accounted for a great part of the DEGs, while immune system signaling and cytokine signaling displayed the most significant changes. Furthermore, seven hub genes and nine transcription factors were identified. Interestingly, the top five upregulated DEGs were located on chromosome Y, and four of the top five downregulated DEGs were involved in immune and inflammation signaling. Further, the top DEGs were validated by RT-PCR in human samples. Our study explored the possible molecular mechanisms of heart failure caused by ischemic heart disease. Full article

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

► Show Figures

Figure 1

13 pages, 2187 KiB

Open AccessArticle

Metagenomics of Bacterial Diversity in Villa Luz Caves with Sulfur Water Springs

by Giuseppe D’Auria, Alejandro Artacho, Rafael A. Rojas, José S. Bautista, Roberto Méndez, María T. Gamboa, Jesús R. Gamboa and Rodolfo Gómez-Cruz

Genes 2018, 9(1), 55; https://doi.org/10.3390/genes9010055 - 22 Jan 2018

Cited by 23 | Viewed by 5924

Abstract

New biotechnology applications require in-depth preliminary studies of biodiversity. The methods of massive sequencing using metagenomics and bioinformatics tools offer us sufficient and reliable knowledge to understand environmental diversity, to know new microorganisms, and to take advantage of their functional genes. Villa Luz [...] Read more.

New biotechnology applications require in-depth preliminary studies of biodiversity. The methods of massive sequencing using metagenomics and bioinformatics tools offer us sufficient and reliable knowledge to understand environmental diversity, to know new microorganisms, and to take advantage of their functional genes. Villa Luz caves, in the southern Mexican state of Tabasco, are fed by at least 26 groundwater inlets, containing 300–500 mg L⁻¹ H₂S and <0.1 mg L⁻¹ O₂. We extracted environmental DNA for metagenomic analysis of collected samples in five selected Villa Luz caves sites, with pH values from 2.5 to 7. Foreign organisms found in this underground ecosystem can oxidize H₂S to H₂SO₄. These include: biovermiculites, a bacterial association that can grow on the rock walls; snottites, that are whitish, viscous biofilms hanging from the rock walls, and sacks or bags of phlegm, which live within the aquatic environment of the springs. Through the emergency food assistance program (TEFAP) pyrosequencing, a total of 20,901 readings of amplification products from hypervariable regions V1 and V3 of 16S rRNA bacterial gene in whole and pure metagenomic DNA samples were generated. Seven bacterial phyla were identified. As a result, Proteobacteria was more frequent than Acidobacteria. Finally, acidophilic Proteobacteria was detected in UJAT5 sample. Full article

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

► Show Figures

Figure 1

20 pages, 5029 KiB

Open AccessArticle

Genome-Wide Identification and Characterization of the Potato bHLH Transcription Factor Family

by Ruoqiu Wang, Peng Zhao, Nana Kong, Ruize Lu, Yue Pei, Chenxi Huang, Haoli Ma and Qin Chen

Genes 2018, 9(1), 54; https://doi.org/10.3390/genes9010054 - 22 Jan 2018

Cited by 106 | Viewed by 9610

Abstract

Plant basic/helix–loop–helix (bHLH) transcription factors participate in a number of biological processes, such as growth, development and abiotic stress responses. The bHLH family has been identified in many plants, and several bHLH transcription factors have been functionally characterized in Arabidopsis. However, no [...] Read more.

Plant basic/helix–loop–helix (bHLH) transcription factors participate in a number of biological processes, such as growth, development and abiotic stress responses. The bHLH family has been identified in many plants, and several bHLH transcription factors have been functionally characterized in Arabidopsis. However, no systematic identification of bHLH family members has been reported in potato (Solanum tuberosum). Here, 124 StbHLH genes were identified and named according to their chromosomal locations. The intron numbers varied from zero to seven. Most StbHLH proteins had the highly conserved intron phase 0, which accounted for 86.2% of the introns. According to the Neighbor-joining phylogenetic tree, 259 bHLH proteins acquired from Arabidopsis and potato were divided into 15 groups. All of the StbHLH genes were randomly distributed on 12 chromosomes, and 20 tandem duplicated genes and four pairs of duplicated gene segments were detected in the StbHLH family. The gene ontology (GO) analysis revealed that StbHLH mainly function in protein and DNA binding. Through the RNA-seq and quantitative real time PCR (qRT-PCR) analyses, StbHLH were found to be expressed in various tissues and to respond to abiotic stresses, including salt, drought and heat. StbHLH1, 41 and 60 were highly expressed in flower tissues, and were predicted to be involved in flower development by GO annotation. StbHLH45 was highly expressed in salt, drought and heat stress, which suggested its important role in abiotic stress response. The results provide comprehensive information for further analyses of the molecular functions of the StbHLH gene family. Full article

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

► Show Figures

Figure 1

13 pages, 2790 KiB

Open AccessArticle

MHC-Dependent Mate Selection within 872 Spousal Pairs of European Ancestry from the Health and Retirement Study

by Zhen Qiao, Joseph E. Powell and David M. Evans

Genes 2018, 9(1), 53; https://doi.org/10.3390/genes9010053 - 22 Jan 2018

Cited by 13 | Viewed by 5155

Abstract

Disassortative mating refers to the phenomenon in which individuals with dissimilar genotypes and/or phenotypes mate with one another more frequently than would be expected by chance. Although the existence of disassortative mating is well established in plant and animal species, the only documented [...] Read more.

Disassortative mating refers to the phenomenon in which individuals with dissimilar genotypes and/or phenotypes mate with one another more frequently than would be expected by chance. Although the existence of disassortative mating is well established in plant and animal species, the only documented example of negative assortment in humans involves dissimilarity at the major histocompatibility complex (MHC) locus. Previous studies investigating mating patterns at the MHC have been hampered by limited sample size and contradictory findings. Inspired by the sparse and conflicting evidence, we investigated the role that the MHC region played in human mate selection using genome-wide association data from 872 European American spouses from the Health and Retirement Study (HRS). First, we treated the MHC region as a whole, and investigated genomic similarity between spouses using three levels of genomic variation: single-nucleotide polymorphisms (SNPs), classical human leukocyte antigen (HLA) alleles (both four-digit and two-digit classifications), and amino acid polymorphisms. The extent of MHC dissimilarity between spouses was assessed using a permutation approach. Second, we investigated fine scale mating patterns by testing for deviations from random mating at individual SNPs, HLA genes, and amino acids in HLA molecules. Third, we assessed how extreme the spousal relatedness at the MHC region was compared to the rest of the genome, to distinguish the MHC-specific effects from genome-wide effects. We show that neither the MHC region, nor any single SNPs, classic HLA alleles, or amino acid polymorphisms within the MHC region, were significantly dissimilar between spouses relative to non-spouse pairs. However, dissimilarity in the MHC region was extreme relative to the rest of genome for both spousal and non-spouse pairs. Despite the long-standing controversy, our analyses did not support a significant role of MHC dissimilarity in human mate choice. Full article

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

► Show Figures

Figure 1

18 pages, 1002 KiB

Open AccessArticle

Differential Gene Expression in Response to Salinity and Temperature in a Haloarcula Strain from Great Salt Lake, Utah

by Swati Almeida-Dalmet, Carol D. Litchfield, Patrick Gillevet and Bonnie K. Baxter

Genes 2018, 9(1), 52; https://doi.org/10.3390/genes9010052 - 22 Jan 2018

Cited by 12 | Viewed by 5283 | Correction

Abstract

Haloarchaea that inhabit Great Salt Lake (GSL), a thalassohaline terminal lake, must respond to the fluctuating climate conditions of the elevated desert of Utah. We investigated how shifting environmental factors, specifically salinity and temperature, affected gene expression in the GSL haloarchaea, NA6-27, which [...] Read more.

Haloarchaea that inhabit Great Salt Lake (GSL), a thalassohaline terminal lake, must respond to the fluctuating climate conditions of the elevated desert of Utah. We investigated how shifting environmental factors, specifically salinity and temperature, affected gene expression in the GSL haloarchaea, NA6-27, which we isolated from the hypersaline north arm of the lake. Combined data from cultivation, microscopy, lipid analysis, antibiotic sensitivity, and 16S rRNA gene alignment, suggest that NA6-27 is a member of the Haloarcula genus. Our prior study demonstrated that archaea in the Haloarcula genus were stable in the GSL microbial community over seasons and years. In this study, RNA arbitrarily primed PCR (RAP-PCR) was used to determine the transcriptional responses of NA6-27 grown under suboptimal salinity and temperature conditions. We observed alteration of the expression of genes related to general stress responses, such as transcription, translation, replication, signal transduction, and energy metabolism. Of the ten genes that were expressed differentially under stress, eight of these genes responded in both conditions, highlighting this general response. We also noted gene regulation specific to salinity and temperature conditions, such as osmoregulation and transport. Taken together, these data indicate that the GSL Haloarcula strain, NA6-27, demonstrates both general and specific responses to salinity and/or temperature stress, and suggest a mechanistic model for homeostasis that may explain the stable presence of this genus in the community as environmental conditions shift. Full article

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

► Show Figures

Figure 1

13 pages, 4456 KiB

Open AccessArticle

MiR-93-5p Promotes Cell Proliferation through Down-Regulating PPARGC1A in Hepatocellular Carcinoma Cells by Bioinformatics Analysis and Experimental Verification

by Xinrui Wang, Zhijun Liao, Zhimin Bai, Yan He, Juan Duan and Leyi Wei

Genes 2018, 9(1), 51; https://doi.org/10.3390/genes9010051 - 22 Jan 2018

Cited by 33 | Viewed by 4701

Abstract

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A, formerly known as PGC-1a) is a transcriptional coactivator and metabolic regulator. Previous studies are mainly focused on the association between PPARGC1A and hepatoma. However, the regulatory mechanism remains unknown. A microRNA associated with cancer (oncomiR), miR-93-5p, [...] Read more.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A, formerly known as PGC-1a) is a transcriptional coactivator and metabolic regulator. Previous studies are mainly focused on the association between PPARGC1A and hepatoma. However, the regulatory mechanism remains unknown. A microRNA associated with cancer (oncomiR), miR-93-5p, has recently been found to play an essential role in tumorigenesis and progression of various carcinomas, including liver cancer. Therefore, this paper aims to explore the regulatory mechanism underlying these two proteins in hepatoma cells. Firstly, an integrative analysis was performed with miRNA–mRNA modules on microarray and The Cancer Genome Atlas (TCGA) data and obtained the core regulatory network and miR-93-5p/PPARGC1A pair. Then, a series of experiments were conducted in hepatoma cells with the results including miR-93-5p upregulated and promoted cell proliferation. Thirdly, the inverse correlation between miR-93-5p and PPARGC1A expression was validated. Finally, we inferred that miR-93-5p plays an essential role in inhibiting PPARGC1A expression by directly targeting the 3′-untranslated region (UTR) of its mRNA. In conclusion, these results suggested that miR-93-5p overexpression contributes to hepatoma development by inhibiting PPARGC1A. It is anticipated to be a promising therapeutic strategy for patients with liver cancer in the future. Full article

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

► Show Figures

Figure 1

16 pages, 529 KiB

Open AccessReview

Single-Cell Genomic Analysis in Plants

by Yuxuan Yuan, HueyTyng Lee, Haifei Hu, Armin Scheben and David Edwards

Genes 2018, 9(1), 50; https://doi.org/10.3390/genes9010050 - 22 Jan 2018

Cited by 28 | Viewed by 8188

Abstract

Individual cells in an organism are variable, which strongly impacts cellular processes. Advances in sequencing technologies have enabled single-cell genomic analysis to become widespread, addressing shortcomings of analyses conducted on populations of bulk cells. While the field of single-cell plant genomics is in [...] Read more.

Individual cells in an organism are variable, which strongly impacts cellular processes. Advances in sequencing technologies have enabled single-cell genomic analysis to become widespread, addressing shortcomings of analyses conducted on populations of bulk cells. While the field of single-cell plant genomics is in its infancy, there is great potential to gain insights into cell lineage and functional cell types to help understand complex cellular interactions in plants. In this review, we discuss current approaches for single-cell plant genomic analysis, with a focus on single-cell isolation, DNA amplification, next-generation sequencing, and bioinformatics analysis. We outline the technical challenges of analysing material from a single plant cell, and then examine applications of single-cell genomics and the integration of this approach with genome editing. Finally, we indicate future directions we expect in the rapidly developing field of plant single-cell genomic analysis. Full article

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

► Show Figures

Figure 1

19 pages, 2982 KiB

Open AccessArticle

Applications of Probe Capture Enrichment Next Generation Sequencing for Whole Mitochondrial Genome and 426 Nuclear SNPs for Forensically Challenging Samples

by Shelly Y. Shih, Nikhil Bose, Anna Beatriz R. Gonçalves, Henry A. Erlich and Cassandra D. Calloway

Genes 2018, 9(1), 49; https://doi.org/10.3390/genes9010049 - 22 Jan 2018

Cited by 39 | Viewed by 13076 | Correction

Abstract

The application of next generation sequencing (NGS) for the analysis of mitochondrial (mt) DNA, short tandem repeats (STRs), and single nucleotide polymorphism (SNPs) has demonstrated great promise for challenging forensic specimens, such as degraded, limited, and mixed samples. Target enrichment using probe capture [...] Read more.

The application of next generation sequencing (NGS) for the analysis of mitochondrial (mt) DNA, short tandem repeats (STRs), and single nucleotide polymorphism (SNPs) has demonstrated great promise for challenging forensic specimens, such as degraded, limited, and mixed samples. Target enrichment using probe capture rather than PCR amplification offers advantages for analysis of degraded DNA since two intact PCR primer sites in the template DNA molecule are not required. Furthermore, NGS software programs can help remove PCR duplicates to determine initial template copy numbers of a shotgun library. Moreover, the same shotgun library prepared from a limited DNA source can be enriched for mtDNA as well as nuclear markers by hybrid capture with the relevant probe panels. Here, we demonstrate the use of this strategy in the analysis of limited and mock degraded samples using our custom probe capture panels for massively parallel sequencing of the whole mtgenome and 426 SNP markers. We also applied the mtgenome capture panel in a mixed sample and analyzed using both phylogenetic and variant frequency based bioinformatics tools to resolve the minor and major contributors. Finally, the results obtained on individual telogen hairs demonstrate the potential of probe capture NGS analysis for both mtDNA and nuclear SNPs for challenging forensic specimens. Full article

(This article belongs to the Special Issue Forensic Genomics)

► Show Figures

Figure 1

19 pages, 703 KiB

Open AccessReview

PGC1α: Friend or Foe in Cancer?

by Francesca Mastropasqua, Giulia Girolimetti and Maria Shoshan

Genes 2018, 9(1), 48; https://doi.org/10.3390/genes9010048 - 22 Jan 2018

Cited by 62 | Viewed by 7126

Abstract

The PGC1 family (Peroxisome proliferator-activated receptor γ (PPARγ) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1α isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. [...] Read more.

The PGC1 family (Peroxisome proliferator-activated receptor γ (PPARγ) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1α isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. Given the altered and highly adaptable metabolism of tumor cells, it is of interest to investigate PGC1α in cancer. Both high and low levels of PGC1α expression have been reported to be associated with cancer and worse prognosis, and PGC1α has been attributed with oncogenic as well as tumor suppressive features. Early in carcinogenesis PGC1α may be downregulated due to a protective anticancer role, and low levels likely reflect a glycolytic phenotype. We suggest mechanisms of PGC1α downregulation and how these might be connected to the increased cancer risk that obesity is now known to entail. Later in tumor progression PGC1α is often upregulated and is reported to contribute to increased lipid and fatty acid metabolism and/or a tumor cell phenotype with an overall metabolic plasticity that likely supports drug resistance as well as metastasis. We conclude that in cancer PGC1α is neither friend nor foe, but rather the obedient servant reacting to metabolic and environmental cues to benefit the tumor cell. 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)

► Show Figures

Graphical abstract

13 pages, 2155 KiB

Open AccessArticle

Analysis of the Genetic Diversity and Population Structure of Austrian and Belgian Wheat Germplasm within a Regional Context Based on DArT Markers

by Mohamed A. El-Esawi, Jacques Witczak, Abd El-Fatah Abomohra, Hayssam M. Ali, Mohamed S. Elshikh and Margaret Ahmad

Genes 2018, 9(1), 47; https://doi.org/10.3390/genes9010047 - 22 Jan 2018

Cited by 22 | Viewed by 6051

Abstract

Analysis of crop genetic diversity and structure provides valuable information needed to broaden the narrow genetic base as well as to enhance the breeding and conservation strategies of crops. In this study, 95 Austrian and Belgian wheat cultivars maintained at the Centre for [...] Read more.

Analysis of crop genetic diversity and structure provides valuable information needed to broaden the narrow genetic base as well as to enhance the breeding and conservation strategies of crops. In this study, 95 Austrian and Belgian wheat cultivars maintained at the Centre for Genetic Resources (CGN) in the Netherlands were characterised using 1052 diversity array technology (DArT) markers to evaluate their genetic diversity, relationships and population structure. The rarefacted allelic richness recorded in the Austrian and Belgian breeding pools (A₂₅ = 1.396 and 1.341, respectively) indicated that the Austrian germplasm contained a higher genetic diversity than the Belgian pool. The expected heterozygosity (H_E) values of the Austrian and Belgian pools were 0.411 and 0.375, respectively. Moreover, the values of the polymorphic information content (PIC) of the Austrian and Belgian pools were 0.337 and 0.298, respectively. Neighbour-joining tree divided each of the Austrian and Belgian germplasm pools into two genetically distinct groups. The structure analyses of the Austrian and Belgian pools were in a complete concordance with their neighbour-joining trees. Furthermore, the 95 cultivars were compared to 618 wheat genotypes from nine European countries based on a total of 141 common DArT markers in order to place the Austrian and Belgian wheat germplasm in a wider European context. The rarefacted allelic richness (A₁₀) varied from 1.224 (Denmark) to 1.397 (Austria). Cluster and principal coordinates (PCoA) analyses divided the wheat genotypes of the nine European countries into two main clusters. The first cluster comprised the Northern and Western European wheat genotypes, whereas the second included the Central European cultivars. The structure analysis of the 618 European wheat genotypes was in a complete concordance with the results of cluster and PCoA analyses. Interestingly, a highly significant difference was recorded between regions (26.53%). In conclusion, this is the first study to reveal the high diversity levels and structure of the uncharacterised Austrian and Belgian wheat germplasm maintained at the CGN as well as place them in a wider European context. The results should help plant breeders to utilise the most promising wheat genotypes of this study in future breeding programmes for enhancing wheat cultivars. Full article

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

► Show Figures

Figure 1

12 pages, 476 KiB

Open AccessArticle

The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina

by Agustín Rolandelli, Joaquín M. Pellegrini, Nicolás O. Amiano, María C. Santilli, María P. Morelli, Florencia A. Castello, Nancy L. Tateosian, Alberto Levi, Nicolás Casco, Domingo J. Palmero and Verónica E. García

Genes 2018, 9(1), 46; https://doi.org/10.3390/genes9010046 - 22 Jan 2018

Cited by 15 | Viewed by 5547

Abstract

Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 [...] Read more.

Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 polymorphism (G→A) was reported to alter the binding of transcription factors to this region, influencing IFNG production. Using a case-control study, we found an association between the AA and AG genotypes and tuberculosis resistance (AA vs. GG: odds ratio (OR) = 0.235, p-value = 0.012; AG vs. GG: OR = 0.303, p-value = 0.044; AA vs. AG: OR = 0.776, p-value = 0.427; AA + AG vs. GG: OR = 0.270, p-value = 0.022). Moreover, Mtb-antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants (p-value = 0.034) and presented the greatest percentage of CD4⁺IFNG⁺ lymphocytes (p-value = 0.035), in comparison with GG carriers. No association between the polymorphism and clinical parameters of tuberculosis severity was detected. However, our findings indicate that the rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker of tuberculosis resistance in the Argentinean population. Full article

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

► Show Figures

Figure 1

11 pages, 1478 KiB

Open AccessArticle

Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications

by A. Mesut Erzurumluoglu, Denis Baird, Tom G. Richardson, Nicholas J. Timpson and Santiago Rodriguez

Genes 2018, 9(1), 45; https://doi.org/10.3390/genes9010045 - 22 Jan 2018

Cited by 5 | Viewed by 7614

Abstract

Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation [...] Read more.

Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort (n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein (FTO) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach. Full article

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

► Show Figures

Figure 1

15 pages, 3548 KiB

Open AccessArticle

Molecular Network-Based Identification of Competing Endogenous RNAs in Thyroid Carcinoma

by Minjia Lu, Xingyu Xu, Baohang Xi, Qi Dai, Chenli Li, Li Su, Xiaonan Zhou, Min Tang, Yuhua Yao and Jialiang Yang

Genes 2018, 9(1), 44; https://doi.org/10.3390/genes9010044 - 19 Jan 2018

Cited by 25 | Viewed by 5765

Abstract

RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in determining gene expression regulations in many cancers. However, the roles of ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a novel pipeline called Molecular Network-based Identification of [...] Read more.

RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in determining gene expression regulations in many cancers. However, the roles of ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a novel pipeline called Molecular Network-based Identification of ceRNA (MNIceRNA) to identify ceRNAs in thyroid carcinoma. MNIceRNA first constructs micro RNA (miRNA)–messenger RNA (mRNA)long non-coding RNA (lncRNA) networks from miRcode database and weighted correlation network analysis (WGCNA), based on which to identify key drivers of differentially expressed RNAs between normal and tumor samples. It then infers ceRNAs of the identified key drivers using the long non-coding competing endogenous database (lnCeDB). We applied the pipeline into The Cancer Genome Atlas (TCGA) thyroid carcinoma data. As a result, 598 lncRNAs, 1025 mRNAs, and 90 microRNA (miRNAs) were inferred to be differentially expressed between normal and thyroid cancer samples. We then obtained eight key driver miRNAs, among which hsa-mir-221 and hsa-mir-222 were key driver RNAs identified by both miRNA–mRNA–lncRNA and WGCNA network. In addition, hsa-mir-375 was inferred to be significant for patients’ survival with 34 associated ceRNAs, among which RUNX2, DUSP6 and SEMA3D are known oncogenes regulating cellular proliferation and differentiation in thyroid cancer. These ceRNAs are critical in revealing the secrets behind thyroid cancer progression and may serve as future therapeutic biomarkers. Full article

(This article belongs to the Special Issue Computational Approaches for Disease Gene Identification)

► Show Figures

Figure 1

15 pages, 1092 KiB

Open AccessReview

Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of Plant Transcriptomes

by Dong An, Hieu X. Cao, Changsheng Li, Klaus Humbeck and Wenqin Wang

Genes 2018, 9(1), 43; https://doi.org/10.3390/genes9010043 - 18 Jan 2018

Cited by 46 | Viewed by 9809

Abstract

Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of [...] Read more.

Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications. Such applications of Iso-Seq facilitate the understanding of gene structure, post-transcriptional regulatory networks, and subsequently proteomic diversity. In this review, we summarize its applications in plant transcriptome study, specifically pointing out challenges associated with each step in the experimental design and highlight the development of bioinformatic pipelines. We aim to provide the community with an integrative overview and a comprehensive guidance to Iso-Seq, and thus to promote its applications in plant research. Full article

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

► Show Figures

Figure 1

18 pages, 2273 KiB

Open AccessArticle

Copy Number Variation in SOX6 Contributes to Chicken Muscle Development

by Shudai Lin, Xiran Lin, Zihao Zhang, Mingya Jiang, Yousheng Rao, Qinghua Nie and Xiquan Zhang

Genes 2018, 9(1), 42; https://doi.org/10.3390/genes9010042 - 17 Jan 2018

Cited by 22 | Viewed by 4832

Abstract

Copy number variations (CNVs), which cover many functional genes, are associated with complex diseases, phenotypic diversity and traits that are economically important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a key role in fast-twitch muscle fiber differentiation of [...] Read more.

Copy number variations (CNVs), which cover many functional genes, are associated with complex diseases, phenotypic diversity and traits that are economically important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a key role in fast-twitch muscle fiber differentiation of zebrafish and mice, but it is still unknown whether SOX6 plays a role in chicken skeletal muscle development. We identified two copy number polymorphisms (CNPs) which were significantly related to different traits on the genome level in chickens by AccuCopy^® and CNVplex^® analyses. Notably, five white recessive rock (CN = 1, CN = 3) variant individuals and two Xinghua (CN = 3) variant individuals contain a CNP13 (chromosome5: 10,500,294–10,675,531) which overlaps with SOX6. There is a disordered region in SOX6 proteins 265–579 aa coded by a partial CNV overlapping region. A quantitative real-time polymerase chain reaction showed that the expression level of SOX6 mRNA was positively associated with CNV and highly expressed during the skeletal muscle cell differentiation in chickens. After the knockdown of the SOX6, the expression levels of IGFIR1, MYF6, SOX9, SHOX and CCND1 were significantly down-regulated. All of them directly linked to muscle development. These results suggest that the number of CNVs in the CNP13 is positively associated with the expression level of SOX6, which promotes the proliferation and differentiation of skeletal muscle cells by up-regulating the expression levels of the muscle-growth-related genes in chickens as in other animal species. Full article

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

► Show Figures

Figure 1

17 pages, 2864 KiB

Open AccessArticle

Network-Based Methods for Identifying Key Active Proteins in the Extracellular Electron Transfer Process in Shewanella oneidensis MR-1

by Dewu Ding and Xiao Sun

Genes 2018, 9(1), 41; https://doi.org/10.3390/genes9010041 - 16 Jan 2018

Cited by 10 | Viewed by 4226

Abstract

Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as [...] Read more.

Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as energy production, wastewater treatment, and bioremediation. Genome-wide proteomics data was used to determine the active proteins involved in activating the EET process. We identified 1012 proteins with decreased expression and 811 proteins with increased expression when the EET process changed from inactivation to activation. We then networked these proteins to construct the active protein networks, and identified the top 20 key active proteins by network centralization analysis, including metabolism- and energy-related proteins, signal and transcriptional regulatory proteins, translation-related proteins, and the EET-related proteins. We also constructed the integrated protein interaction and transcriptional regulatory networks for the active proteins, then found three exclusive active network motifs involved in activating the EET process—Bi-feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein–Protein Interaction (PPI)—and identified the active proteins involved in these motifs. Both enrichment analysis and comparative analysis to the whole-genome data implicated the multiheme c-type cytochromes and multiple signal processing proteins involved in the process. Furthermore, the interactions of these motif-guided active proteins and the involved functional modules were discussed. Collectively, by using network-based methods, this work reported a proteome-wide search for the key active proteins that potentially activate the EET process. Full article

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

► Show Figures

Figure 1

20 pages, 2372 KiB

Open AccessReview

Transcriptional-Readthrough RNAs Reflect the Phenomenon of “A Gene Contains Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and Thus Are Not Chimeric RNAs

by Yan He, Chengfu Yuan, Lichan Chen, Mingjuan Lei, Lucas Zellmer, Hai Huang and Dezhong Joshua Liao

Genes 2018, 9(1), 40; https://doi.org/10.3390/genes9010040 - 16 Jan 2018

Cited by 25 | Viewed by 6231

Abstract

Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a [...] Read more.

Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a true readthrough event still awaits more evidence and trans-splicing that joins two transcripts together remains as a possible mechanism. We regard those genomic loci that are transcriptionally read through as unannotated genes, because their transcriptional and posttranscriptional regulations are the same as those of already-annotated genes, including fusion genes formed due to genetic alterations. Therefore, readthrough RNAs and fusion-gene-derived RNAs are not chimeras. Only those two-gene RNAs formed at the RNA level, likely via trans-splicing, without corresponding genes as genomic parents, should be regarded as authentic chimeric RNAs. However, since in human cells, procedural and mechanistic details of trans-splicing have never been disclosed, we doubt the existence of trans-splicing. Therefore, there are probably no authentic chimeras in humans, after readthrough and fusion-gene derived RNAs are all put back into the group of ordinary RNAs. Therefore, it should be further determined whether in human cells all two-neighboring-gene RNAs are derived from transcriptional readthrough and whether trans-splicing truly exists. Full article

(This article belongs to the Special Issue The Value of Being Different: Ultraconserved Genomic Elements, Micro Peptides and Chimeric RNAs)

► Show Figures

Figure 1

14 pages, 647 KiB

Open AccessReview

by Francesco Ravaioli, Maria G. Bacalini, Claudio Franceschi and Paolo Garagnani

Genes 2018, 9(1), 39; https://doi.org/10.3390/genes9010039 - 16 Jan 2018

Cited by 10 | Viewed by 4655

Abstract

Aging is a complex multi-layered phenomenon. The study of aging in humans is based on the use of biological material from hard-to-gather tissues and highly specific cohorts. The introduction of cell reprogramming techniques posed promising features for medical practice and basic research. Recently, [...] Read more.

Aging is a complex multi-layered phenomenon. The study of aging in humans is based on the use of biological material from hard-to-gather tissues and highly specific cohorts. The introduction of cell reprogramming techniques posed promising features for medical practice and basic research. Recently, a growing number of studies have been describing the generation of induced pluripotent stem cells (iPSCs) from old or centenarian biologic material. Nonetheless, Reprogramming techniques determine a profound remodelling on cell epigenetic architecture whose extent is still largely debated. Given that cell epigenetic profile changes with age, the study of cell-fate manipulation approaches on cells deriving from old donors or centenarians may provide new insights not only on regenerative features and physiology of these cells, but also on reprogramming-associated and age-related epigenetic derangement. Full article

(This article belongs to the Special Issue The Epigenetics of Aging and Longevity)

► Show Figures

Figure 1

14 pages, 2097 KiB

Open AccessArticle

Comparative Transcriptome Analysis Identifies Putative Genes Involved in Steroid Biosynthesis in Euphorbia tirucalli

by Weibo Qiao, Changfu Li, Isidore Mosongo, Qin Liang, Mengdi Liu and Xin Wang

Genes 2018, 9(1), 38; https://doi.org/10.3390/genes9010038 - 15 Jan 2018

Cited by 9 | Viewed by 5115

Abstract

Phytochemical analysis of different Euphorbia tirucalli tissues revealed a contrasting tissue-specificity for the biosynthesis of euphol and β-sitosterol, which represent the two pharmaceutically active steroids in E. tirucalli. To uncover the molecular mechanism underlying this tissue-specificity for phytochemicals, a comprehensive E. tirucalli [...] Read more.

Phytochemical analysis of different Euphorbia tirucalli tissues revealed a contrasting tissue-specificity for the biosynthesis of euphol and β-sitosterol, which represent the two pharmaceutically active steroids in E. tirucalli. To uncover the molecular mechanism underlying this tissue-specificity for phytochemicals, a comprehensive E. tirucalli transcriptome derived from its root, stem, leaf and latex was constructed, and a total of 91,619 unigenes were generated with 51.08% being successfully annotated against the non-redundant (Nr) protein database. A comparison of the transcriptome from different tissues discovered members of unigenes in the upstream steps of sterol backbone biosynthesis leading to this tissue-specific sterol biosynthesis. Among them, the putative oxidosqualene cyclase (OSC) encoding genes involved in euphol synthesis were notably identified, and their expressions were significantly up-regulated in the latex. In addition, genome-wide differentially expressed genes (DEGs) in the different E. tirucalli tissues were identified. The cluster analysis of those DEGs showed a unique expression pattern in the latex compared with other tissues. The DEGs identified in this study would enrich the insights of sterol biosynthesis and the regulation mechanism of this latex-specificity. Full article

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

► Show Figures

Graphical abstract

4 pages, 137 KiB

Open AccessEditorial

An Introduction to Integrative Genomics and Systems Medicine in Cancer

by Xiaolong Cheng and Victor X. Jin

Genes 2018, 9(1), 37; https://doi.org/10.3390/genes9010037 - 12 Jan 2018

Cited by 2 | Viewed by 3285

Abstract

In this Special Issue (SI), with a theme of “Integrative Genomics and Systems Medicine in Cancer”, we have collected a total of 12 research and review articles from researchers in the field of genomics and systems medicine[...] Full article

(This article belongs to the Special Issue Integrative Genomics and Systems Medicine in Cancer)

16 pages, 2028 KiB

Open AccessReview

Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex

by Mariana Diaz and Ales Pecinka

Genes 2018, 9(1), 36; https://doi.org/10.3390/genes9010036 - 12 Jan 2018

Cited by 33 | Viewed by 7023

Abstract

Chromosome organization, dynamics and stability are required for successful passage through cellular generations and transmission of genetic information to offspring. The key components involved are Structural maintenance of chromosomes (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin complex chromosome condensation and the [...] Read more.

Chromosome organization, dynamics and stability are required for successful passage through cellular generations and transmission of genetic information to offspring. The key components involved are Structural maintenance of chromosomes (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin complex chromosome condensation and the SMC5/6 complex is specialized in the maintenance of genome stability. Here we summarize recent knowledge on the composition and molecular functions of SMC5/6 complex. SMC5/6 complex was originally identified based on the sensitivity of its mutants to genotoxic stress but there is increasing number of studies demonstrating its roles in the control of DNA replication, sister chromatid resolution and genomic location-dependent promotion or suppression of homologous recombination. Some of these functions appear to be due to a very dynamic interaction with cohesin or other repair complexes. Studies in Arabidopsis indicate that, besides its canonical function in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating plant development, abiotic stress responses, suppression of autoimmune responses and sexual reproduction. Full article

(This article belongs to the Special Issue DNA Damage Responses in Plants)

► Show Figures

Figure 1

19 pages, 9084 KiB

Open AccessArticle

Dissection of Myogenic Differentiation Signatures in Chickens by RNA-Seq Analysis

by Tingting Li, Genxi Zhang, Pengfei Wu, Lian Duan, Guohui Li, Qiuhong Liu and Jinyu Wang

Genes 2018, 9(1), 34; https://doi.org/10.3390/genes9010034 - 11 Jan 2018

Cited by 15 | Viewed by 4476

Abstract

A series of elaborately regulated and orchestrated changes in gene expression profiles leads to muscle growth and development. In this study, RNA sequencing was used to profile embryonic chicken myoblasts and fused myotube transcriptomes, long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) at [...] Read more.

A series of elaborately regulated and orchestrated changes in gene expression profiles leads to muscle growth and development. In this study, RNA sequencing was used to profile embryonic chicken myoblasts and fused myotube transcriptomes, long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) at four stages of myoblast differentiation. Of a total of 2484 lncRNA transcripts, 2288 were long intergenic non-coding RNAs (lincRNAs) and 198 were antisense lncRNAs. Additionally, 1530 lncRNAs were neighboring 2041 protein-coding genes (<10 kb upstream and downstream) and functionally enriched in several pathways related to skeletal muscle development that have been extensively studied, indicating that these genes may be in cis-regulatory relationships. In addition, Pearson’s correlation coefficients demonstrated that 990 lncRNAs and 7436 mRNAs were possibly in trans-regulatory relationships. These co-expressed mRNAs were enriched in various developmentally-related biological processes, such as myocyte proliferation and differentiation, myoblast differentiation, and myoblast fusion. The number of transcripts (906 lncRNAs and 4422 mRNAs) differentially expressed across various stages declined with the progression of differentiation. Then, 4422 differentially expressed genes were assigned to four clusters according to K-means analysis. Genes in the K1 cluster likely play important roles in myoblast proliferation and those in the K4 cluster were likely associated with the initiation of myoblast differentiation, while genes in the K2 and K3 clusters were likely related to myoblast fusion. This study provides a catalog of chicken lncRNAs and mRNAs for further experimental investigations and facilitates a better understanding of skeletal muscle development. Full article

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

► Show Figures

Figure 1

13 pages, 733 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Genes in 2017

by Genes Editorial Office

Genes 2018, 9(1), 33; https://doi.org/10.3390/genes9010033 - 11 Jan 2018

Viewed by 2808

Abstract

Peer review is an essential part in the publication process, ensuring that Genes maintains high quality standards for its published papers.[...] Full article

19 pages, 8324 KiB

Open AccessArticle

Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing Data

by Yumin Wang, Tingting Qin, Wangqiang Hu, Binghua Chen, Meijie Dai and Gang Xu

Genes 2018, 9(1), 32; https://doi.org/10.3390/genes9010032 - 11 Jan 2018

Cited by 10 | Viewed by 4803

Abstract

This study aimed to investigate the mechanisms underlying the development of the androgen-independent phenotype in prostate cancer. Methylation patterns were detected in androgen-independent and androgen-dependent lymph node carcinoma of the prostate (LNCaP) prostate carcinoma cells based on methylated DNA immunoprecipitation-bisulfite sequencing data and [...] Read more.

This study aimed to investigate the mechanisms underlying the development of the androgen-independent phenotype in prostate cancer. Methylation patterns were detected in androgen-independent and androgen-dependent lymph node carcinoma of the prostate (LNCaP) prostate carcinoma cells based on methylated DNA immunoprecipitation-bisulfite sequencing data and differentially methylated regions (DMRs) were identified. Differentially expressed genes (DEGs) and micro RNAs (miRNAs) with DMRs (named MDEGs and MDEmiRNAs) were identified by combining transcriptome and methylation data, and transcription factor (TF)-DEGs with DMRs in promoter (PMDEGs) and MDEmiRNA-MDEGs networks were constructed. Furthermore, a time-course analysis of gene transcription during androgen deprivation was performed based on microarray data and DMRs, MDEGs, and DEmiRNAs were validated. In total, 18,447 DMRs, 3369 MDEGs, 850 PMDEGs, and 1 MDEmiRNA (miR-429) were identified. A TF-target network (94 PMDEGs and 5 TFs) and a miRNA–target network (172 MDEGs and miR-429) were constructed. Based on the time-course analysis of genes in the networks, NEDD4L and PBX3 were targeted by SOX5, while GNAQ, ANLN, and KIF11 were targeted by miR-429. The expression levels of these genes and miR-429 were confirmed by quantitative real-time polymerase chain reaction. Additionally, 109 DMRs were confirmed using additional public datasets. The regulatory pathways SOX5-NEDD4L/PBX3, miR429-GNAQ/ANLN—RHOA, and miR429-ANLN—KIF11 may participate in the progression of the androgen-independent phenotype in prostate cancer. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

► Show Figures

Figure 1

19 pages, 4591 KiB

Open AccessBrief Report

Physiological and Comparative Genomic Analysis of Arthrobacter sp. SRS-W-1-2016 Provides Insights on Niche Adaptation for Survival in Uraniferous Soils

by Ashvini Chauhan, Ashish Pathak, Rajneesh Jaswal, Bobby Edwards III, Demario Chappell, Christopher Ball, Reyna Garcia-Sillas, Paul Stothard and John Seaman

Genes 2018, 9(1), 31; https://doi.org/10.3390/genes9010031 - 11 Jan 2018

Cited by 22 | Viewed by 5172

Abstract

Arthrobacter sp. strain SRS-W-1-2016 was isolated on high concentrations of uranium (U) from the Savannah River Site (SRS) that remains co-contaminated by radionuclides, heavy metals, and organics. SRS is located on the northeast bank of the Savannah River (South Carolina, USA), which is [...] Read more.

Arthrobacter sp. strain SRS-W-1-2016 was isolated on high concentrations of uranium (U) from the Savannah River Site (SRS) that remains co-contaminated by radionuclides, heavy metals, and organics. SRS is located on the northeast bank of the Savannah River (South Carolina, USA), which is a U.S. Department of Energy (DOE) managed ecosystem left historically contaminated from decades of nuclear weapons production activities. Predominant contaminants within the impacted SRS environment include U and Nickel (Ni), both of which can be transformed microbially into less toxic forms via metal complexation mechanisms. Strain SRS-W-1-2016 was isolated from the uraniferous SRS soils on high concentrations of U (4200 μM) and Ni (8500 μM), but rapid growth was observed at much lower concentrations of 500 μM U and 1000 μM Ni, respectively. Microcosm studies established with strain SRS-W-1-2016 revealed a rapid decline in the concentration of spiked U such that it was almost undetectable in the supernatant by 72 h of incubation. Conversely, Ni concentrations remained unchanged, suggesting that the strain removed U but not Ni under the tested conditions. To obtain a deeper understanding of the metabolic potential, a draft genome sequence of strain SRS-W-1-2016 was obtained at a coverage of 90×, assembling into 93 contigs with an N50 contig length of 92,788 bases. The genomic size of strain SRS-W-1-2016 was found to be 4,564,701 bases with a total number of 4327 putative genes. An in-depth, genome-wide comparison between strain SRS-W-1-2016 and its four closest taxonomic relatives revealed 1159 distinct genes, representing 26.7% of its total genome; many associating with metal resistance proteins (e.g., for cadmium, cobalt, and zinc), transporter proteins, stress proteins, cytochromes, and drug resistance functions. Additionally, several gene homologues coding for resistance to metals were identified in the strain, such as outer membrane efflux pump proteins, peptide/nickel transport substrate and ATP-binding proteins, a high-affinity nickel-transport protein, and the spoT gene, which was recently implicated in bacterial resistance towards U. Detailed genome mining analysis of strain SRS-W-1-2016 also revealed the presence of a plethora of secondary metabolite biosynthetic gene clusters likely facilitating resistance to antibiotics, biocides, and metals. Additionally, several gene homologous for the well-known oxygenase enzyme system were also identified, potentially functioning to generate energy via the breakdown of organic compounds and thus enabling the successful colonization and natural attenuation of contaminants by Arthrobacter sp. SRS-W-1-2016 at the SRS site. Full article

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

► Show Figures

Figure 1

21 pages, 3691 KiB

Open AccessArticle

Characterization of Translationally Controlled Tumour Protein from the Sea Anemone Anemonia viridis and Transcriptome Wide Identification of Cnidarian Homologues

by Aldo Nicosia, Carmelo Bennici, Girolama Biondo, Salvatore Costa, Marilena Di Natale, Tiziana Masullo, Calogera Monastero, Maria Antonietta Ragusa, Marcello Tagliavia and Angela Cuttitta

Genes 2018, 9(1), 30; https://doi.org/10.3390/genes9010030 - 11 Jan 2018

Cited by 6 | Viewed by 4844

Abstract

Gene family encoding translationally controlled tumour protein (TCTP) is defined as highly conserved among organisms; however, there is limited knowledge of non-bilateria. In this study, the first TCTP homologue from anthozoan was characterised in the Mediterranean Sea anemone, Anemonia viridis. The release [...] Read more.

Gene family encoding translationally controlled tumour protein (TCTP) is defined as highly conserved among organisms; however, there is limited knowledge of non-bilateria. In this study, the first TCTP homologue from anthozoan was characterised in the Mediterranean Sea anemone, Anemonia viridis. The release of the genome sequence of Acropora digitifera, Exaiptasia pallida, Nematostella vectensis and Hydra vulgaris enabled a comprehensive study of the molecular evolution of TCTP family among cnidarians. A comparison among TCTP members from Cnidaria and Bilateria showed conserved intron exon organization, evolutionary conserved TCTP signatures and 3D protein structure. The pattern of mRNA expression profile was also defined in A. viridis. These analyses revealed a constitutive mRNA expression especially in tissues with active proliferation. Additionally, the transcriptional profile of A. viridis TCTP (AvTCTP) after challenges with different abiotic/biotic stresses showed induction by extreme temperatures, heavy metals exposure and immune stimulation. These results suggest the involvement of AvTCTP in the sea anemone defensome taking part in environmental stress and immune responses. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

► Show Figures

Figure 1

15 pages, 9501 KiB

Open AccessArticle

The Landscape of Small Non-Coding RNAs in Triple-Negative Breast Cancer

by Yan Guo, Hui Yu, Jing Wang, Quanhu Sheng, Shilin Zhao, Ying-Yong Zhao and Brian D. Lehmann

Genes 2018, 9(1), 29; https://doi.org/10.3390/genes9010029 - 10 Jan 2018

Cited by 23 | Viewed by 6122

Abstract

Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, [...] Read more.

Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, and distinct mRNA transcriptional subtypes exhibiting unique biology. High-throughput sequencing has extended cancer research far beyond protein coding regions that include non-coding small RNAs, such as miRNA, isomiR, tRNA, snoRNAs, snRNA, yRNA, 7SL, and 7SK. In this study, we performed small RNA profiling of 26 TNBC cell lines, and compared the abundance of non-coding RNAs among the transcriptional subtypes of triple negative breast cancer. We also examined their co-expression pattern with corresponding mRNAs. This study provides a detailed description of small RNA expression in triple-negative breast cancer cell lines that can aid in the development of future biomarker and novel targeted therapies. Full article

(This article belongs to the Special Issue Non-coding RNAs)

► Show Figures

Figure 1

11 pages, 4503 KiB

Open AccessArticle

Structural and Evolutionary Relationships in the Giant Sex Chromosomes of Three Microtus Species

by Luz Lamelas, María Arroyo, Francisco Javier Fernández, Juan Alberto Marchal and Antonio Sánchez

Genes 2018, 9(1), 27; https://doi.org/10.3390/genes9010027 - 10 Jan 2018

Cited by 6 | Viewed by 3758

Abstract

The genus Microtus has high karyotypic diversity. The existence of notable differences in the length of its sex chromosomes contributes to this variation. Variations in size are attributed to the enlargement of their heterochromatin content, which is of such magnitude in some species [...] Read more.

The genus Microtus has high karyotypic diversity. The existence of notable differences in the length of its sex chromosomes contributes to this variation. Variations in size are attributed to the enlargement of their heterochromatin content, which is of such magnitude in some species that they are referred to as “giant sex chromosomes”. Here, we perform an intra- and interspecific analysis of the molecular composition of the heterochromatic blocks in three species with giant sex chromosomes (Microtus chrotorrhinus, M. cabrerae and M. agrestis). Our results show that the heterochromatic content is very similar in both the X and Y chromosomes of M. chrotorrhinus, and that their molecular composition is more closely related to the heterochromatic blocks of M. agrestis than to the sex heterochromatin of M. cabrerae; however, species-specific differences do clearly exist. Interestingly, the euchromatic regions of the X chromosome of all three of these species share a homologous region composed of heterochromatic-related sequences. Our results therefore reinforce the idea that certain similarities in the original organization of these X chromosomes could have facilitated their later enlargement. Full article

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

► Show Figures

Figure 1

16 pages, 3059 KiB

Open AccessArticle

Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes

by Galuh D. N. Astuti, L. Ingeborgh Van den Born, M. Imran Khan, Christian P. Hamel, Béatrice Bocquet, Gaël Manes, Mathieu Quinodoz, Manir Ali, Carmel Toomes, Martin McKibbin, Mohammed E. El-Asrag, Lonneke Haer-Wigman, Chris F. Inglehearn, Graeme C. M. Black, Carel B. Hoyng, Frans P. M. Cremers and Susanne Roosing

Genes 2018, 9(1), 21; https://doi.org/10.3390/genes9010021 - 10 Jan 2018

Cited by 19 | Viewed by 6342

Abstract

Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is [...] Read more.

Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 (SNRNP200) and Zinc Finger Protein 513 (ZNF513), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 (DHX32) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed. Full article

(This article belongs to the Special Issue Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations and Inheritance Models)

► Show Figures

Figure 1

23 pages, 621 KiB

Open AccessReview

MiRNA Influences in Neuroblast Modulation: An Introspective Analysis

by Vanessa Zammit, Byron Baron and Duncan Ayers

Genes 2018, 9(1), 26; https://doi.org/10.3390/genes9010026 - 09 Jan 2018

Cited by 9 | Viewed by 4115

Abstract

Neuroblastoma (NB) is the most common occurring solid paediatric cancer in children under the age of five years. Whether of familial or sporadic origin, chromosome abnormalities contribute to the development of NB and cause dysregulation of microRNAs (miRNAs). MiRNAs are small non-coding, single [...] Read more.

Neuroblastoma (NB) is the most common occurring solid paediatric cancer in children under the age of five years. Whether of familial or sporadic origin, chromosome abnormalities contribute to the development of NB and cause dysregulation of microRNAs (miRNAs). MiRNAs are small non-coding, single stranded RNAs that target messenger RNAs at the post-transcriptional levels by repressing translation within all facets of human physiology. Such gene ‘silencing’ activities by miRNAs allows the development of regulatory feedback loops affecting multiple functions within the cell, including the possible differentiation of neural stem cell (NSC) lineage selection. Neurogenesis includes stages of self-renewal and fate specification of NSCs, migration and maturation of young neurones, and functional integration of new neurones into the neural circuitry, all of which are regulated by miRNAs. The role of miRNAs and their interaction in cellular processes are recognised aspects of cancer genetics, and miRNAs are currently employed as biomarkers for prognosis and tumour characterisation in multiple cancer models. Consequently, thorough understanding of the mechanisms of how these miRNAs interplay at the transcriptomic level will definitely lead to the development of novel, bespoke and efficient therapeutic measures, with this review focusing on the influences of miRNAs on neuroblast modulations leading to neuroblastoma. Full article

(This article belongs to the Special Issue Non-coding RNAs)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 9, Issue 1 (January 2018) – 54 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI