Genes

14 pages, 1831 KiB

Open AccessReview

Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools

by Nancy Martínez-Montiel^1,†, Maricruz Anaya-Ruiz², Martín Pérez-Santos³ and Rebeca D. Martínez-Contreras^1,4,*

¹ Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla CP 72570, Mexico

² Centro de Investigación Biomédica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social (IMSS), Metepec, Puebla CP 74360, Mexico

³ Centro Universitario de Vinculación, Dirección de Innovación y Transferencia de Conocimiento, Benemérita Universidad Autónoma de Puebla, Puebla CP 72570, Mexico

⁴ Edificio IC11, Ciudad Universitaria, Col. San Manuel, Puebla CP 72570, Mexico

^† Current address: Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada.

Genes 2017, 8(10), 217; https://doi.org/10.3390/genes8100217 - 5 Oct 2017

Cited by 29 | Viewed by 7745

Abstract

Alternative splicing is a key molecular mechanism now considered as a hallmark of cancer that has been associated with the expression of distinct isoforms during the onset and progression of the disease. The leading cause of cancer-related deaths in women worldwide is breast [...] Read more.

Alternative splicing is a key molecular mechanism now considered as a hallmark of cancer that has been associated with the expression of distinct isoforms during the onset and progression of the disease. The leading cause of cancer-related deaths in women worldwide is breast cancer, and even when the role of alternative splicing in this type of cancer has been established, the function of this mechanism in breast cancer biology is not completely decoded. In order to gain a comprehensive view of the role of alternative splicing in breast cancer biology and development, we summarize here recent findings regarding alternative splicing events that have been well documented for breast cancer evolution, considering its prognostic and therapeutic value. Moreover, we analyze how the response to endocrine and chemical therapies could be affected due to alternative splicing and differential expression of variant isoforms. With all this knowledge, it becomes clear that targeting alternative splicing represents an innovative approach for breast cancer therapeutics and the information derived from current studies could guide clinical decisions with a direct impact in the clinical advances for breast cancer patients nowadays. Full article

(This article belongs to the Special Issue Aberrant Pre-mRNA Splicing in Disease)

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17 pages, 613 KiB

Open AccessArticle

Optimized mtDNA Control Region Primer Extension Capture Analysis for Forensically Relevant Samples and Highly Compromised mtDNA of Different Age and Origin

by Mayra Eduardoff^1,*, Catarina Xavier¹, Christina Strobl¹, Andrea Casas-Vargas² and Walther Parson^1,3,*

¹ Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria

² Grupo de Genética de Poblaciones e Identificación, Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia

³ Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA

Genes 2017, 8(10), 237; https://doi.org/10.3390/genes8100237 - 21 Sep 2017

Cited by 52 | Viewed by 7831

Abstract

The analysis of mitochondrial DNA (mtDNA) has proven useful in forensic genetics and ancient DNA (aDNA) studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR) is commonly sequenced using established [...] Read more.

The analysis of mitochondrial DNA (mtDNA) has proven useful in forensic genetics and ancient DNA (aDNA) studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR) is commonly sequenced using established Sanger-type Sequencing (STS) protocols involving fragment sizes down to approximately 150 base pairs (bp). Recent developments include Massively Parallel Sequencing (MPS) of (multiplex) PCR-generated libraries using the same amplicon sizes. Molecular genetic studies on archaeological remains that harbor more degraded aDNA have pioneered alternative approaches to target mtDNA, such as capture hybridization and primer extension capture (PEC) methods followed by MPS. These assays target smaller mtDNA fragment sizes (down to 50 bp or less), and have proven to be substantially more successful in obtaining useful mtDNA sequences from these samples compared to electrophoretic methods. Here, we present the modification and optimization of a PEC method, earlier developed for sequencing the Neanderthal mitochondrial genome, with forensic applications in mind. Our approach was designed for a more sensitive enrichment of the mtDNA CR in a single tube assay and short laboratory turnaround times, thus complying with forensic practices. We characterized the method using sheared, high quantity mtDNA (six samples), and tested challenging forensic samples (n = 2) as well as compromised solid tissue samples (n = 15) up to 8 kyrs of age. The PEC MPS method produced reliable and plausible mtDNA haplotypes that were useful in the forensic context. It yielded plausible data in samples that did not provide results with STS and other MPS techniques. We addressed the issue of contamination by including four generations of negative controls, and discuss the results in the forensic context. We finally offer perspectives for future research to enable the validation and accreditation of the PEC MPS method for final implementation in forensic genetic laboratories. Full article

(This article belongs to the Special Issue Novel and Neglected Areas of Ancient DNA Research)

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10 pages, 226 KiB

Open AccessCommunication

Development of Genome-Wide SSR Markers from Angelica gigas Nakai Using Next Generation Sequencing

by Jinsu Gil^1,†, Yurry Um^2,†, Serim Kim¹, Ok Tae Kim³, Sung Cheol Koo³, Chinreddy Subramanyam Reddy³

, Seong-Cheol Kim⁴

, Chang Pyo Hong⁵

, Sin-Gi Park⁵, Ho Bang Kim⁶, Dong Hoon Lee⁷, Byung-Hoon Jeong⁸, Jong-Wook Chung¹ and Yi Lee^1,*

¹ Department of Industrial Plant Science & Technology, Chungbuk National University, Chungju 28644, Korea

² Forest Medicinal Resources Research Center, National Institute of Forest Science, Yeongju 36040, Korea

³ Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Korea

⁴ Research Institute of Climate Change and Agriculture, National Institute of Horticultural and Herbal Science, Rural Development Administration, Jeju 63240, Korea

⁵ TheragenEtex Bio Institute, Suwon 16229, Korea

⁶ Life Sciences Research Institute, Biomedic Co., Ltd., Bucheon 14548, Korea

⁷ Department of Biosystems Engineering, Chungbuk National University, Chungju 28644, Korea

⁸ Korea Zoonosis Research Institute, Chonbuk National University, Iksan 54531, Korea

^† These authors contributed equally to this work.

Genes 2017, 8(10), 238; https://doi.org/10.3390/genes8100238 - 21 Sep 2017

Cited by 20 | Viewed by 4693

Abstract

Angelica gigas Nakai is an important medicinal herb, widely utilized in Asian countries especially in Korea, Japan, and China. Although it is a vital medicinal herb, the lack of sequencing data and efficient molecular markers has limited the application of a genetic approach [...] Read more.

Angelica gigas Nakai is an important medicinal herb, widely utilized in Asian countries especially in Korea, Japan, and China. Although it is a vital medicinal herb, the lack of sequencing data and efficient molecular markers has limited the application of a genetic approach for horticultural improvements. Simple sequence repeats (SSRs) are universally accepted molecular markers for population structure study. In this study, we found over 130,000 SSRs, ranging from di- to deca-nucleotide motifs, using the genome sequence of Manchu variety (MV) of A. gigas, derived from next generation sequencing (NGS). From the putative SSR regions identified, a total of 16,496 primer sets were successfully designed. Among them, we selected 848 SSR markers that showed polymorphism from in silico analysis and contained tri- to hexa-nucleotide motifs. We tested 36 SSR primer sets for polymorphism in 16 A. gigas accessions. The average polymorphism information content (PIC) was 0.69; the average observed heterozygosity (H_O) values, and the expected heterozygosity (H_E) values were 0.53 and 0.73, respectively. These newly developed SSR markers would be useful tools for molecular genetics, genotype identification, genetic mapping, molecular breeding, and studying species relationships of the Angelica genus. Full article

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

19 pages, 3463 KiB

Open AccessArticle

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats

by Jing-Hua Wang¹

, Shambhunath Bose², Soo-Kyoung Lim¹, AbuZar Ansari¹, Young-Won Chin³, Han Seok Choi⁴ and Hojun Kim^1,*

¹ Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 814 Siksa, Goyang 10326, Gyeonggi-do, Korea

² NosQuest, USPACE 1A-1103, Daewang Pangyoro 660, Bundang-gu, Seongnam-si 13494, Gyeonggi-do, Korea

³ College of Pharmacy, Dongguk University-Seoul, Dongguk-lo 32, Goyang 10326, Gyeonggi-do, Korea

⁴ Department of endocrinology, Dongguk University, Dongguk-lo 32, Goyang 10326, Gyeonggi-do, Korea

Genes 2017, 8(10), 239; https://doi.org/10.3390/genes8100239 - 22 Sep 2017

Cited by 33 | Viewed by 6677

Abstract

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing [...] Read more.

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. Full article

(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)

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23 pages, 315 KiB

Open AccessReview

Extracellular Vesicle‐Associated RNA as a Carrier of Epigenetic Information

by Carlo Maria Di Liegro¹

, Gabriella Schiera¹

and Italia Di Liegro^2,*

¹ Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo (UNIPA), I‐90128 Palermo, Italy

² Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo,I‐90127 Palermo,Italy

Genes 2017, 8(10), 240; https://doi.org/10.3390/genes8100240 - 22 Sep 2017

Cited by 46 | Viewed by 6238

Abstract

Post‐transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis‐acting signals (zip codes), usually present in their 5′‐ and 3′‐untranslated regions (UTRs). By binding [...] Read more.

Post‐transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis‐acting signals (zip codes), usually present in their 5′‐ and 3′‐untranslated regions (UTRs). By binding to these signals, trans‐acting factors, such as RNA‐binding proteins (RBPs), and/or non‐coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non‐coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally transfer molecules, and hence properties, to neighboring cells. By interacting with proteins that are specifically sorted to EVs, mRNAs as well as ncRNAs can be transferred from cell to cell. In this review, we discuss the mechanisms underlying the sorting to EVs of different classes of molecules, as well as the role of extracellular RNAs and the associated proteins in altering gene expression in the recipient cells. Importantly, if, on the one hand, RBPs play a critical role in transferring RNAs through EVs, RNA itself could, on the other hand, function as a carrier to transfer proteins (i.e., chromatin modifiers, and transcription factors) that, once transferred, can alter the cell’s epigenome. Full article

(This article belongs to the Special Issue RNA Modification)

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14 pages, 6040 KiB

Open AccessArticle

Host-Induced Gene Silencing of Rice Blast Fungus Magnaporthe oryzae Pathogenicity Genes Mediated by the Brome Mosaic Virus

by Lin Zhu^1,2, Jian Zhu², Zhixue Liu², Zhengyi Wang⁴, Cheng Zhou^1,* and Hong Wang^2,3,*

¹ Key Laboratory of Bio-organic Fertilizer Creation, Ministry of Agriculture, Anhui Science and Technology University, Bengbu 233100, China

² School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

³ KWS SAAT SE, Einbeck 37574, Germany

⁴ College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China

Genes 2017, 8(10), 241; https://doi.org/10.3390/genes8100241 - 26 Sep 2017

Cited by 39 | Viewed by 6372

Abstract

Magnaporthe oryzae is a devastating plant pathogen, which has a detrimental impact on rice production worldwide. Despite its agronomical importance, some newly-emerging pathotypes often overcome race-specific disease resistance rapidly. It is thus desirable to develop a novel strategy for the long-lasting resistance of [...] Read more.

Magnaporthe oryzae is a devastating plant pathogen, which has a detrimental impact on rice production worldwide. Despite its agronomical importance, some newly-emerging pathotypes often overcome race-specific disease resistance rapidly. It is thus desirable to develop a novel strategy for the long-lasting resistance of rice plants to ever-changing fungal pathogens. Brome mosaic virus (BMV)-induced RNA interference (RNAi) has emerged as a useful tool to study host-resistance genes for rice blast protection. Planta-generated silencing of targeted genes inside biotrophic pathogens can be achieved by expression of M. oryzae-derived gene fragments in the BMV-mediated gene silencing system, a technique termed host-induced gene silencing (HIGS). In this study, the effectiveness of BMV-mediated HIGS in M. oryzae was examined by targeting three predicted pathogenicity genes, MoABC1, MoMAC1 and MoPMK1. Systemic generation of fungal gene-specific small interfering RNA (siRNA) molecules induced by inoculation of BMV viral vectors inhibited disease development and reduced the transcription of targeted fungal genes after subsequent M. oryzae inoculation. Combined introduction of fungal gene sequences in sense and antisense orientation mediated by the BMV silencing vectors significantly enhanced the efficiency of this host-generated trans-specific RNAi, implying that these fungal genes played crucial roles in pathogenicity. Collectively, our results indicated that BMV-HIGS system was a great strategy for protecting host plants against the invasion of pathogenic fungi. Full article

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

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10 pages, 1597 KiB

Open AccessArticle

Textile Hemp vs. Salinity: Insights from a Targeted Gene Expression Analysis

by Gea Guerriero^*

, Marc Behr

, Jean-Francois Hausman

and Sylvain Legay

Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), L-4362 Esch/Alzette, Luxembourg

Genes 2017, 8(10), 242; https://doi.org/10.3390/genes8100242 - 26 Sep 2017

Cited by 28 | Viewed by 5002

Abstract

Soil salinity is a serious threat to agriculture, because it compromises biomass production and plant productivity, by negatively affecting the vegetative growth and development of plants. Fiber crops like textile hemp (Cannabis sativa L.) are important natural resources that provide, sustainably, both cellulosic [...] Read more.

Soil salinity is a serious threat to agriculture, because it compromises biomass production and plant productivity, by negatively affecting the vegetative growth and development of plants. Fiber crops like textile hemp (Cannabis sativa L.) are important natural resources that provide, sustainably, both cellulosic and woody fibers for industry. In this work, the response to salinity (200 mM NaCl) of a fiber variety of hemp (Santhica 27) was studied using quantitative real-time PCR. The responses of plantlets aged 15 days were analyzed by microscopy and by measuring the changes in expression of cell wall-related genes, as well as in the general response to exogenous constraints. The results presented here show that a different response is present in the hemp hypocotyls and leaves. In the leaves, genes coding for heat shock proteins were significantly upregulated, together with a phytohormone-related transcript (ethylene-responsive factor 1 ERF1) and genes involved in secondary cell wall biosynthesis (cellulose synthase CesA4, fasciclin-like arabinogalactan proteins FLA10 and FLA8). Moreover, a tendency towards upregulation was also observed in the leaves for genes involved in lignification (4CL, CAD, PAL); a finding that suggests growth arrest. In the hypocotyl, the genes involved in lignification did not show changes in expression, while a gene related to expansion (expansin EXPA8), as well as transcripts coding for calcium-dependent lipid-binding family proteins (CALB), were upregulated. Microscopic analyses on the hypocotyl cross sections revealed changes in the vascular tissues of salt-exposed plantlets, where the lumen of xylem vessels was reduced. The gene expression results show that a different response is present in the hemp hypocotyls and leaves. The data presented contribute to our understanding of the regulatory gene network in response to salinity in different tissues of an important fiber crop. Full article

(This article belongs to the Special Issue Genetic Regulation of Abiotic Stress Responses)

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9 pages, 807 KiB

Open AccessArticle

Genetic Association between Amyotrophic Lateral Sclerosis and Cancer

by Y-h. Taguchi¹

and Hsiuying Wang^2,*

¹ Department of Physics, Chuo University, 1-13-27 Kasuga, Bunky-ku, Tokyo 112-8551, Japan

² Institute of Statistics, National Chiao Tung University, Hsinchu 30010, Taiwan

Genes 2017, 8(10), 243; https://doi.org/10.3390/genes8100243 - 27 Sep 2017

Cited by 23 | Viewed by 7289

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. An ALS drug, Riluzole, has been shown to induce two different anticancer effects on hepatocellular carcinoma (HCC). In light of this finding, we explore the relationship between ALS and cancer, especially for HCC, from [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. An ALS drug, Riluzole, has been shown to induce two different anticancer effects on hepatocellular carcinoma (HCC). In light of this finding, we explore the relationship between ALS and cancer, especially for HCC, from the molecular biological viewpoint. We establish biomarkers that can discriminate between ALS patients and healthy controls. A principal component analysis (PCA) based unsupervised feature extraction (FE) is used to find gene biomarkers of ALS based on microarray gene expression data. Based on this method, 101 probes were selected as biomarkers for ALS with 95% high accuracy to discriminate between ALS patients and controls. Most of the genes corresponding to these probes are shown to be related to various cancers. These findings might provide a new insight for developing new therapeutic options or drugs for both ALS and cancer. Full article

(This article belongs to the Special Issue Statistical Resources for the Interpretation and Integration of Human Genetic Association Studies)

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26 pages, 2026 KiB

Open AccessReview

Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips

by Frank Schulze^1,*

, Xinghua Gao², Darius Virzonis³, Samar Damiati^4,5

, Marlon R. Schneider¹ and Rimantas Kodzius^1,2,6,*

¹ German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), 10589 Berlin, Germany

² iSmart, Materials Genome Institute, Shanghai University (SHU), Shanghai 201800, China

³ Department of Electrical Engineering, Kaunas University of Technology, 35212 Panevezys, Lithuania

⁴ Department of Biochemistry, King Abdulaziz University, Jeddah 80203, Saudi Arabia

⁵ Institute for Synthetic Bioarchitecture, Department of Nanobiotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria

⁶ Mathematics and Natural Sciences Department, The American University of Iraq, Sulaimani, Sulaymaniyah 46001, Iraq

Genes 2017, 8(10), 244; https://doi.org/10.3390/genes8100244 - 27 Sep 2017

Cited by 92 | Viewed by 12065

Abstract

Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting [...] Read more.

Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5) values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC) technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs. 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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20 pages, 1767 KiB

Open AccessArticle

BARHL1 Is Downregulated in Alzheimer’s Disease and May Regulate Cognitive Functions through ESR1 and Multiple Pathways

by Debmalya Barh^1,2,*, María E. García-Solano^3,4, Sandeep Tiwari^1,2, Antaripa Bhattacharya¹, Neha Jain¹, Daniel Torres-Moreno^3,4, Belén Ferri⁵, Artur Silva⁶, Vasco Azevedo²

, Preetam Ghosh^1,7

, Kenneth Blum⁸, Pablo Conesa-Zamora^3,4 and George Perry^9,10

¹ Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India

² Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil

³ Department of Pathology, Santa Lucía General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain

⁴ Catholic University of Murcia (UCAM), 30107 Murcia, Spain

⁵ Department of Pathology, Virgen Arrixaca University Hospital (HUVA), Ctra. Madrid Cartagena sn, 30120 El Palmar, Spain

⁶ Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, 01-Guamá, Belém, PA 66075-110, Brazil

⁷ Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA

⁸ Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA

⁹ UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA

¹⁰ Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA

Genes 2017, 8(10), 245; https://doi.org/10.3390/genes8100245 - 28 Sep 2017

Cited by 15 | Viewed by 6701

Abstract

The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue [...] Read more.

The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer’s disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates β-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce β-amyloid processing and might also be involved in hearing and cognitive decline associated with AD. We have also hypothesized why estrogen replacement therapy improves AD condition. In addition, we have provided a feasible new mechanism to explain the abnormal function of mossy fibers and cerebellar granule cells related to memory and cognitive decline in AD apart from the Tau and amyloid pathogenesis through our BARHL1-ESR1 axis. Full article

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

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12 pages, 1013 KiB

Open AccessArticle

Pathway Enrichment Analysis with Networks

by Lu Liu^1,*, Jinmao Wei² and Jianhua Ruan^3,*

¹ College of Information Technology and Engineering, Marshall University, 1 John Marshall Dr, Huntington, WV 25755, USA

² College of Computer and Control Engineering, Nankai University, 94 Weijin Road, Tianjin 300071, China

³ Department of Computer Science, The University of Texas at San Antonio, 1 Utsa Cir, San Antonio, TX 78249, USA

Genes 2017, 8(10), 246; https://doi.org/10.3390/genes8100246 - 28 Sep 2017

Cited by 17 | Viewed by 8689

Abstract

Detecting associations between an input gene set and annotated gene sets (e.g., pathways) is an important problem in modern molecular biology. In this paper, we propose two algorithms, termed NetPEA and NetPEA’, for conducting network-based pathway enrichment analysis. Our algorithms consider not only [...] Read more.

Detecting associations between an input gene set and annotated gene sets (e.g., pathways) is an important problem in modern molecular biology. In this paper, we propose two algorithms, termed NetPEA and NetPEA’, for conducting network-based pathway enrichment analysis. Our algorithms consider not only shared genes but also gene–gene interactions. Both algorithms utilize a protein–protein interaction network and a random walk with a restart procedure to identify hidden relationships between an input gene set and pathways, but both use different randomization strategies to evaluate statistical significance and as a result emphasize different pathway properties. Compared to an over representation-based method, our algorithms can identify more statistically significant pathways. Compared to an existing network-based algorithm, EnrichNet, our algorithms have a higher sensitivity in revealing the true causal pathways while at the same time achieving a higher specificity. A literature review of selected results indicates that some of the novel pathways reported by our algorithms are biologically relevant and important. While the evaluations are performed only with KEGG pathways, we believe the algorithms can be valuable for general functional discovery from high-throughput experiments. Full article

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

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16 pages, 2620 KiB

Open AccessReview

Et tu, Brute? Not Even Intracellular Mutualistic Symbionts Escape Horizontal Gene Transfer

by Sergio López-Madrigal¹

and Rosario Gil^2,3,*

¹ Biologie Fonctionnelle Insectes et Interactions, UMR203 BF2I, INRA, INSA-Lyon, Université de Lyon, 69100 Villeurbanne, France

² Institute for Integrative Systems Biology (I2SysBio), Universitat de València/CSIC, 46980 Paterna (València), Spain

³ Departament de Genètica, Universitat de València, Dr. Moliner, 50, 46100 Burjassot (València), Spain

Genes 2017, 8(10), 247; https://doi.org/10.3390/genes8100247 - 29 Sep 2017

Cited by 18 | Viewed by 9006

Abstract

Many insect species maintain mutualistic relationships with endosymbiotic bacteria. In contrast to their free-living relatives, horizontal gene transfer (HGT) has traditionally been considered rare in long-term endosymbionts. Nevertheless, meta-omics exploration of certain symbiotic models has unveiled an increasing number of bacteria-bacteria and bacteria-host [...] Read more.

Many insect species maintain mutualistic relationships with endosymbiotic bacteria. In contrast to their free-living relatives, horizontal gene transfer (HGT) has traditionally been considered rare in long-term endosymbionts. Nevertheless, meta-omics exploration of certain symbiotic models has unveiled an increasing number of bacteria-bacteria and bacteria-host genetic transfers. The abundance and function of transferred loci suggest that HGT might play a major role in the evolution of the corresponding consortia, enhancing their adaptive value or buffering detrimental effects derived from the reductive evolution of endosymbionts’ genomes. Here, we comprehensively review the HGT cases recorded to date in insect-bacteria mutualistic consortia, and discuss their impact on the evolutionary success of these associations. Full article

(This article belongs to the Special Issue Horizontal Gene Transfer)

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18 pages, 3388 KiB

Open AccessTechnical Note

Alienness: Rapid Detection of Candidate Horizontal Gene Transfers across the Tree of Life

by Corinne Rancurel¹, Ludovic Legrand² and Etienne G. J. Danchin^1,*

¹ INRA, CNRS, ISA, Université Côte d’Azur, 06903 Sophia Antipolis Cedex, France

² LIPM, INRA, CNRS, Université de Toulouse, 31326 Castanet-Tolosan Cedex, France

Genes 2017, 8(10), 248; https://doi.org/10.3390/genes8100248 - 29 Sep 2017

Cited by 40 | Viewed by 11330

Abstract

Horizontal gene transfer (HGT) is the transmission of genes between organisms by other means than parental to offspring inheritance. While it is prevalent in prokaryotes, HGT is less frequent in eukaryotes and particularly in Metazoa. Here, we propose Alienness, a taxonomy-aware web application [...] Read more.

Horizontal gene transfer (HGT) is the transmission of genes between organisms by other means than parental to offspring inheritance. While it is prevalent in prokaryotes, HGT is less frequent in eukaryotes and particularly in Metazoa. Here, we propose Alienness, a taxonomy-aware web application available at http://alienness.sophia.inra.fr. Alienness parses BLAST results against public libraries to rapidly identify candidate HGT in any genome of interest. Alienness takes as input the result of a BLAST of a whole proteome of interest against any National Center for Biotechnology Information (NCBI) protein library. The user defines recipient (e.g., Metazoa) and donor (e.g., bacteria, fungi) branches of interest in the NCBI taxonomy. Based on the best BLAST E-values of candidate donor and recipient taxa, Alienness calculates an Alien Index (AI) for each query protein. An AI > 0 indicates a better hit to candidate donor than recipient taxa and a possible HGT. Higher AI represent higher gap of E-values between candidate donor and recipient and a more likely HGT. We confirmed the accuracy of Alienness on phylogenetically confirmed HGT of non-metazoan origin in plant-parasitic nematodes. Alienness scans whole proteomes to rapidly identify possible HGT in any species of interest and thus fosters exploration of HGT more easily and largely across the tree of life. Full article

(This article belongs to the Special Issue Horizontal Gene Transfer)

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17 pages, 3602 KiB

Open AccessArticle

Comparative Genomics of Non-TNL Disease Resistance Genes from Six Plant Species

by Madhav P. Nepal^1,*

, Ethan J. Andersen¹, Surendra Neupane¹

and Benjamin V. Benson²

¹ Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA

² Sanford PROMISE, Sanford Research, Sioux Falls, SD 57104, USA

Genes 2017, 8(10), 249; https://doi.org/10.3390/genes8100249 - 30 Sep 2017

Cited by 23 | Viewed by 8616

Abstract

Disease resistance genes (R genes), as part of the plant defense system, have coevolved with corresponding pathogen molecules. The main objectives of this project were to identify non-Toll interleukin receptor, nucleotide-binding site, leucine-rich repeat (nTNL) genes and elucidate their evolutionary divergence across six [...] Read more.

Disease resistance genes (R genes), as part of the plant defense system, have coevolved with corresponding pathogen molecules. The main objectives of this project were to identify non-Toll interleukin receptor, nucleotide-binding site, leucine-rich repeat (nTNL) genes and elucidate their evolutionary divergence across six plant genomes. Using reference sequences from Arabidopsis, we investigated nTNL orthologs in the genomes of common bean, Medicago, soybean, poplar, and rice. We used Hidden Markov Models for sequence identification, performed model-based phylogenetic analyses, visualized chromosomal positioning, inferred gene clustering, and assessed gene expression profiles. We analyzed 908 nTNL R genes in the genomes of the six plant species, and classified them into 12 subgroups based on the presence of coiled-coil (CC), nucleotide binding site (NBS), leucine rich repeat (LRR), resistance to Powdery mildew 8 (RPW8), and BED type zinc finger domains. Traditionally classified CC-NBS-LRR (CNL) genes were nested into four clades (CNL A-D) often with abundant, well-supported homogeneous subclades of Type-II R genes. CNL-D members were absent in rice, indicating a unique R gene retention pattern in the rice genome. Genomes from Arabidopsis, common bean, poplar and soybean had one chromosome without any CNL R genes. Medicago and Arabidopsis had the highest and lowest number of gene clusters, respectively. Gene expression analyses suggested unique patterns of expression for each of the CNL clades. Differential gene expression patterns of the nTNL genes were often found to correlate with number of introns and GC content, suggesting structural and functional divergence. Full article

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

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12 pages, 226 KiB

Open AccessReview

Effects of Antidiabetic Drugs on Gut Microbiota Composition

by Sophie A. Montandon and François R. Jornayvaz^*

Service of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland

Genes 2017, 8(10), 250; https://doi.org/10.3390/genes8100250 - 30 Sep 2017

Cited by 111 | Viewed by 9000

Abstract

Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA); amino acids; bile acids or vitamins. It [...] Read more.

Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA); amino acids; bile acids or vitamins. It is becoming clear that gut microbiota is playing a prevalent role in pathologies such as metabolic syndrome; type 2 diabetes (T2D); inflammatory and bowel diseases. Obesity and related diseases; notably type 2 diabetes, induce gut dysbiosis. In this review; we aim to cover the current knowledge about the effects of antidiabetic drugs on gut microbiota diversity and composition as well as the potential beneficial effects mediated by specific taxa. Metformin is the first-line treatment against T2D. In addition to its glucose-lowering and insulin sensitizing effects, metformin promotes SCFA-producing and mucin-degrading bacteria. Other antidiabetic drugs discussed in this review show positive effects on dysbiosis; but without any consensus specifically regarding the Firmicutes to Bacteroidetes ratio. Thus, beneficial effects might be mediated by specific taxa. Full article

(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)

11 pages, 3234 KiB

Open AccessReview

Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

by Masafumi Matsuo^1,*, Hiroyuki Awano²

, Masaaki Matsumoto², Masashi Nagai², Tatsuya Kawaguchi³, Zhujun Zhang¹ and Hisahide Nishio⁴

¹ Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, Kobe 651-2180, Japan

² Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

³ Biomedical Analysis and Pathology Research Group, Discovery Science and Technology Department, Daiichi Sankyo RD Novare Co., Tokyo 134-8630, Japan

⁴ Department of Community Medicine and Social Healthcare Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

Genes 2017, 8(10), 251; https://doi.org/10.3390/genes8100251 - 1 Oct 2017

Cited by 16 | Viewed by 5778

Abstract

The Duchenne muscular dystrophy (DMD) gene is one of the largest genes in the human genome. The gene exhibits a complex arrangement of seven alternative promoters, which drive the expression of three full length and four shorter isoforms. Dp116, the second [...] Read more.

The Duchenne muscular dystrophy (DMD) gene is one of the largest genes in the human genome. The gene exhibits a complex arrangement of seven alternative promoters, which drive the expression of three full length and four shorter isoforms. Dp116, the second smallest product of the DMD gene, is a Schwann cell-specific isoform encoded by a transcript corresponding to DMD exons 56–79, starting from a promoter/exon S1 within intron 55. The physiological roles of Dp116 are poorly understood, because of its extensive homology with other isoforms and its expression in specific tissues. This review summarizes studies on Dp116, focusing on clinical findings and alternative activation of the upstream translation initiation codon that is predicted to produce Dp118. Full article

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

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23 pages, 2866 KiB

Open AccessArticle

Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

by Lei Chen^1,2,†

, Hongying Pan^3,4,†, Yu-Hang Zhang^5,†, Kaiyan Feng⁶, XiangYin Kong^5,*, Tao Huang^5,*

and Yu-Dong Cai^1,*

¹ School of Life Sciences, Shanghai University, Shanghai 200444, China

² College of Information Engineering, Shanghai Maritime University, Shanghai 201306, China

³ Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, USA

⁴ Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard University, Boston, MA 02115, USA

⁵ Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

⁶ Department of Computer Science, Guangdong AIB Polytechnic, Guangzhou 510507, Guangdong, China

Genes 2017, 8(10), 252; https://doi.org/10.3390/genes8100252 - 2 Oct 2017

Cited by 8 | Viewed by 5318

Abstract

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the [...] Read more.

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein–protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method. Full article

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

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9 pages, 2198 KiB

Open AccessCase Report

Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

by Ana Gonçalves^1,2,†, Jorge Oliveira^1,2,*,†

, Teresa Coelho³, Ricardo Taipa⁴

, Manuel Melo-Pires⁴, Mário Sousa^2,5,6 and Rosário Santos^1,2,7,*

¹ Unidade de Genética Molecular, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar do Porto, 4050-106 Porto, Portugal

² Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal

³ Serviço de Neurofisiologia, Departamento de Neurociências, Centro Hospitalar do Porto, 4099-001 Porto, Portugal

⁴ Unidade de Neuropatologia, Centro Hospitalar do Porto, 4099-001 Porto, Portugal

⁵ Departamento de Microscopia, Laboratório de Biologia Celular, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal

⁶ Centro de Genética da Reprodução Prof. Alberto Barros, 4050-313 Porto, Portugal

⁷ UCIBIO/REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal

^† These authors contributed equally to this work.

Genes 2017, 8(10), 253; https://doi.org/10.3390/genes8100253 - 3 Oct 2017

Cited by 26 | Viewed by 7675

Abstract

A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease [...] Read more.

A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD. Full article

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

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15 pages, 6191 KiB

Open AccessArticle

Alterations of miRNAs and Their Potential Roles in Arsenite-Induced Transformation of Human Bronchial Epithelial Cells

by Shiyan Gu, Donglei Sun, Xinyang Li

and Zunzhen Zhang^*

Department of Environmental and Occupational Health, West China School of Public Health, Sichuan University, Chengdu 610041, China

Genes 2017, 8(10), 254; https://doi.org/10.3390/genes8100254 - 3 Oct 2017

Cited by 9 | Viewed by 3916

Abstract

The alterations of micro RNAs (miRNAs) and their potential roles in arsenite-induced tumorigenesis are still poorly understood. In this study, miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by 2.5 μM [...] Read more.

The alterations of micro RNAs (miRNAs) and their potential roles in arsenite-induced tumorigenesis are still poorly understood. In this study, miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by 2.5 μM arsenite for 13 weeks. These cells exhibited a neoplastic phenotype manifested by increased levels of cellular proliferation and migration and clone formation. Subsequently, 191 dysregulated miRNAs were identified to be associated with arsenite-induced transformation by miRNA Array. Among them, six miRNAs were validated by their expression levels with quantitative real-time polymerase chain reaction (qPCR), and 17 miRNAs were further explored via their target genes as well as regulatory network. Three databases, TargetMiner, miRDB, and TarBase, were used to predict the target genes of the 17 miRNAs, and a total of 954 common genes were sorted. Results of Gene Ontology (GO) analyses showed that the 954 genes were involved in diverse terms of GO categories, such as positive regulation of macroautophagy, epithelial cell maturation, and synaptic vesicle clustering. Moreover, results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that most of these target genes were enriched in various cancer-related pathways, including non-small cell lung cancer, Wnt signaling pathway, cell cycle, and p53 signaling pathway. The miRNA-gene regulatory network, which was constructed by cytoscape software with miRNAs and their target genes, showed that miR-15b-5p, miR-106b-5p, and miR-320d were the core hubs. Collectively, our results provide new insights into miRNA-mediated mechanisms underlying arsenite-induced transformation, although more experimental verification is still needed to prove these predictions. Full article

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

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23 pages, 3657 KiB

Open AccessArticle

De Novo Assembly and Analysis of Tartary Buckwheat (Fagopyrum tataricum Garetn.) Transcriptome Discloses Key Regulators Involved in Salt-Stress Response

by Qi Wu^1,2,3,*,†, Xue Bai^1,2,3,†, Wei Zhao³, Dabing Xiang^1,2,3, Yan Wan^1,2,3, Jun Yan^1,2,3, Liang Zou^1,2,3 and Gang Zhao^1,2,3,*

¹ Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture, Chengdu 610106, China

² National Research and Development Center for Coarse Cereal Processing, Chengdu 610106, China

³ College of Pharmacy and Biological Engineering, Chengdu University, Chengdu 610106, China

^† These authors have contributed equally to this work.

Genes 2017, 8(10), 255; https://doi.org/10.3390/genes8100255 - 3 Oct 2017

Cited by 49 | Viewed by 6380

Abstract

Soil salinization has been a tremendous obstacle for agriculture production. The regulatory networks underlying salinity adaption in model plants have been extensively explored. However, limited understanding of the salt response mechanisms has hindered the planting and production in Fagopyrum tataricum, an economic [...] Read more.

Soil salinization has been a tremendous obstacle for agriculture production. The regulatory networks underlying salinity adaption in model plants have been extensively explored. However, limited understanding of the salt response mechanisms has hindered the planting and production in Fagopyrum tataricum, an economic and health-beneficial plant mainly distributing in southwest China. In this study, we performed physiological analysis and found that salt stress of 200 mM NaCl solution significantly affected the relative water content (RWC), electrolyte leakage (EL), malondialdehyde (MDA) content, peroxidase (POD) and superoxide dismutase (SOD) activities in tartary buckwheat seedlings. Further, we conducted transcriptome comparison between control and salt treatment to identify potential regulatory components involved in F. tataricum salt responses. A total of 53.15 million clean reads from control and salt-treated libraries were produced via an Illumina sequencing approach. Then we de novo assembled these reads into a transcriptome dataset containing 57,921 unigenes with N50 length of 1400 bp and total length of 44.5 Mb. A total of 36,688 unigenes could find matches in public databases. GO, KEGG and KOG classification suggested the enrichment of these unigenes in 56 sub-categories, 25 KOG, and 273 pathways, respectively. Comparison of the transcriptome expression patterns between control and salt treatment unveiled 455 differentially expressed genes (DEGs). Further, we found the genes encoding for protein kinases, phosphatases, heat shock proteins (HSPs), ATP-binding cassette (ABC) transporters, glutathione S-transferases (GSTs), abiotic-related transcription factors and circadian clock might be relevant to the salinity adaption of this species. Thus, this study offers an insight into salt tolerance mechanisms, and will serve as useful genetic information for tolerant elite breeding programs in future. Full article

(This article belongs to the Special Issue Genetic Regulation of Abiotic Stress Responses)

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14 pages, 5119 KiB

Open AccessArticle

The Genetic Basis of Pericentral Retinitis Pigmentosa—A Form of Mild Retinitis Pigmentosa

by Jason Comander^*, Carol Weigel-DiFranco, Matthew Maher, Emily Place, Aliete Wan, Shyana Harper, Michael A. Sandberg, Daniel Navarro-Gomez and Eric A. Pierce

Ocular Genomics Institute, Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA

Genes 2017, 8(10), 256; https://doi.org/10.3390/genes8100256 - 5 Oct 2017

Cited by 38 | Viewed by 8747

Abstract

Pericentral retinitis pigmentosa (RP) is an atypical form of RP that affects the near-peripheral retina first and tends to spare the far periphery. This study was performed to further define the genetic basis of this phenotype. We identified a cohort of 43 probands [...] Read more.

Pericentral retinitis pigmentosa (RP) is an atypical form of RP that affects the near-peripheral retina first and tends to spare the far periphery. This study was performed to further define the genetic basis of this phenotype. We identified a cohort of 43 probands with pericentral RP based on a comprehensive analysis of their retinal phenotype. Genetic analyses of DNA samples from these patients were performed using panel-based next-generation sequencing, copy number variations, and whole exome sequencing (WES). Mutations provisionally responsible for disease were found in 19 of the 43 families (44%) analyzed. These include mutations in RHO (five patients), USH2A (four patients), and PDE6B (two patients). Of 28 putatively pathogenic alleles, 15 (54%) have been previously identified in patients with more common forms of typical RP, while the remaining 13 mutations (46%) were novel. Burden testing of WES data successfully identified HGSNAT as a cause of pericentral RP in at least two patients, suggesting it is also a relatively common cause of pericentral RP. While additional sequencing might uncover new genes specifically associated with pericentral RP, the current results suggest that genetically pericentral RP is not a separate clinical entity, but rather is part of the spectrum of mild RP phenotypes. Full article

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

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13 pages, 3469 KiB

Open AccessArticle

Hybrid Sequencing of Full-Length cDNA Transcripts of Stems and Leaves in Dendrobium officinale

by Liu He¹, Shuhua Fu², Zhichao Xu¹, Jun Yan³, Jiang Xu⁴, Hong Zhou¹, Jianguo Zhou¹, Xinlian Chen¹, Ying Li¹, Kin Fai Au^2,5,* and Hui Yao^1,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA

³ Department of Plant Genetic Breeding, College of Agriculture and Biotechnology, China Agricultural University, Beijing 100193, China

⁴ Institute of Chinese Materia Medica, Academy of Chinese Medical Sciences, Beijing 100700, China

⁵ Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA

Genes 2017, 8(10), 257; https://doi.org/10.3390/genes8100257 - 5 Oct 2017

Cited by 22 | Viewed by 5396

Abstract

Dendrobium officinale is an extremely valuable orchid used in traditional Chinese medicine, so sought after that it has a higher market value than gold. Although the expression profiles of some genes involved in the polysaccharide synthesis have previously been investigated, little research has [...] Read more.

Dendrobium officinale is an extremely valuable orchid used in traditional Chinese medicine, so sought after that it has a higher market value than gold. Although the expression profiles of some genes involved in the polysaccharide synthesis have previously been investigated, little research has been carried out on their alternatively spliced isoforms in D. officinale. In addition, information regarding the translocation of sugars from leaves to stems in D. officinale also remains limited. We analyzed the polysaccharide content of D. officinale leaves and stems, and completed in-depth transcriptome sequencing of these two diverse tissue types using second-generation sequencing (SGS) and single-molecule real-time (SMRT) sequencing technology. The results of this study yielded a digital inventory of gene and mRNA isoform expressions. A comparative analysis of both transcriptomes uncovered a total of 1414 differentially expressed genes, including 844 that were up-regulated and 570 that were down-regulated in stems. Of these genes, one sugars will eventually be exported transporter (SWEET) and one sucrose transporter (SUT) are expressed to a greater extent in D. officinale stems than in leaves. Two glycosyltransferase (GT) and four cellulose synthase (Ces) genes undergo a distinct degree of alternative splicing. In the stems, the content of polysaccharides is twice as much as that in the leaves. The differentially expressed GT and transcription factor (TF) genes will be the focus of further study. The genes DoSWEET4 and DoSUT1 are significantly expressed in the stem, and are likely to be involved in sugar loading in the phloem. Full article

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

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14 pages, 3434 KiB

Open AccessReview

Chromosomal Evolution in Lower Vertebrates: Sex Chromosomes in Neotropical Fishes

by Marcelo de Bello Cioffi^1,*,†, Cassia Fernanda Yano^1,†, Alexandr Sember² and Luiz Antônio Carlos Bertollo¹

¹ Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, SP CEP 13565-905, Brazil

² Laboratory of Fish Genetics, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, Liběchov 277 21, Czech Republic

^† These authors have contributed equally to this work.

Genes 2017, 8(10), 258; https://doi.org/10.3390/genes8100258 - 5 Oct 2017

Cited by 34 | Viewed by 7166

Abstract

Abstract: Fishes exhibit the greatest diversity of species among vertebrates, offering a number of relevant models for genetic and evolutionary studies. The investigation of sex chromosome differentiation is a very active and striking research area of fish cytogenetics, as fishes represent one [...] Read more.

Abstract: Fishes exhibit the greatest diversity of species among vertebrates, offering a number of relevant models for genetic and evolutionary studies. The investigation of sex chromosome differentiation is a very active and striking research area of fish cytogenetics, as fishes represent one of the most vital model groups. Neotropical fish species show an amazing variety of sex chromosome systems, where different stages of differentiation can be found, ranging from homomorphic to highly differentiated sex chromosomes. Here, we draw attention on the impact of recent developments in molecular cytogenetic analyses that helped to elucidate many unknown questions about fish sex chromosome evolution, using excellent characiform models occurring in the Neotropical region, namely the Erythrinidae family and the Triportheus genus. While in Erythrinidae distinct XY and/or multiple XY-derived sex chromosome systems have independently evolved at least four different times, representatives of Triportheus show an opposite scenario, i.e., highly conserved ZZ/ZW system with a monophyletic origin. In both cases, recent molecular approaches, such as mapping of repetitive DNA classes, comparative genomic hybridization (CGH), and whole chromosome painting (WCP), allowed us to unmask several new features linked to the molecular composition and differentiation processes of sex chromosomes in fishes. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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15 pages, 7236 KiB

Open AccessArticle

Novel EDA or EDAR Mutations Identified in Patients with X-Linked Hypohidrotic Ectodermal Dysplasia or Non-Syndromic Tooth Agenesis

by Binghui Zeng^1,†

, Qi Zhao^2,†, Sijie Li¹, Hui Lu¹, Jiaxuan Lu¹, Lan Ma¹, Wei Zhao^1,* and Dongsheng Yu^1,*

¹ Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China

² Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 259; https://doi.org/10.3390/genes8100259 - 5 Oct 2017

Cited by 32 | Viewed by 6250

Abstract

Abstract: Both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic tooth agenesis (NSTA) result in symptoms of congenital tooth loss. This study investigated genetic causes in two families with XLHED and four families with NSTA. We screened for mutations of WNT10A, EDA, [...] Read more.

Abstract: Both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic tooth agenesis (NSTA) result in symptoms of congenital tooth loss. This study investigated genetic causes in two families with XLHED and four families with NSTA. We screened for mutations of WNT10A, EDA, EDAR, EDARADD, PAX9, MSX1, AXIN2, LRP6, and WNT10B through Sanger sequencing. Whole exome sequencing was performed for the proband of NSTA Family 4. Novel mutation c.1051G>T (p.Val351Phe) and the known mutation c.467G>A (p.Arg156His) of Ectodysplasin A (EDA) were identified in families with XLHED. Novel EDA receptor (EDAR) mutation c.73C>T (p.Arg25*), known EDA mutation c.491A>C (p.Glu164Ala), and known Wnt family member 10A (WNT10A) mutations c.511C>T (p.Arg171Cys) and c.742C>T (p.Arg248*) were identified in families with NSTA. The novel EDA and EDAR mutations were predicted as being pathogenic through bioinformatics analyses and structural modeling. Two variants of WNT10A, c.374G>A (p.Arg125Lys) and c.125A>G (p.Asn42Ser), were found in patients with NSTA. The two WNT10A variants were predicted to affect the splicing of message RNA, but minigene experiments showed normal splicing of mutated minigenes. This study uncovered the genetic foundations with respect to six families with XLHED or NSTA. We identified six mutations, of which two were novel mutations of EDA and EDAR. This is the first report of a nonsense EDAR mutation leading to NSTA. Full article

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

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16 pages, 814 KiB

Open AccessReview

Intercompartmental Piecewise Gene Transfer

by Przemyslaw Szafranski

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

Genes 2017, 8(10), 260; https://doi.org/10.3390/genes8100260 - 6 Oct 2017

Cited by 6 | Viewed by 4840

Abstract

Gene relocation from the residual genomes of organelles to the nuclear genome still continues, although as a scaled down evolutionary phenomenon, limited in occurrence mostly to protists (sensu lato) and land plants. During this process, the structural integrity of transferred genes [...] Read more.

Gene relocation from the residual genomes of organelles to the nuclear genome still continues, although as a scaled down evolutionary phenomenon, limited in occurrence mostly to protists (sensu lato) and land plants. During this process, the structural integrity of transferred genes is usually preserved. However, the relocation of mitochondrial genes that code for respiratory chain and ribosomal proteins is sometimes associated with their fragmentation into two complementary genes. Herein, this review compiles cases of piecewise gene transfer from the mitochondria to the nucleus, and discusses hypothesized mechanistic links between the fission and relocation of those genes. Full article

(This article belongs to the Special Issue Horizontal Gene Transfer)

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19 pages, 3990 KiB

Open AccessArticle

Expression Profiling of Mitogen-Activated Protein Kinase Genes Reveals Their Evolutionary and Functional Diversity in Different Rubber Tree (Hevea brasiliensis) Cultivars

by Xiang Jin^1,2,†, Liping Zhu^1,2,†, Qi Yao¹, Xueru Meng¹, Guohua Ding¹, Dan Wang¹, Quanliang Xie², Zheng Tong¹, Chengcheng Tao², Li Yu², Hongbin Li^2,*

and Xuchu Wang^1,2,*

¹ Institute of Tropical Biosciences and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China

² College of Life Sciences, Key Laboratory of Agrobiotechnology, Shihezi University, Shihezi 832003, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 261; https://doi.org/10.3390/genes8100261 - 6 Oct 2017

Cited by 14 | Viewed by 5374

Abstract

Rubber tree (Hevea brasiliensis) is the only commercially cultivated plant for producing natural rubber, one of the most essential industrial raw materials. Knowledge of the evolutionary and functional characteristics of kinases in H. brasiliensis is limited because of the long growth [...] Read more.

Rubber tree (Hevea brasiliensis) is the only commercially cultivated plant for producing natural rubber, one of the most essential industrial raw materials. Knowledge of the evolutionary and functional characteristics of kinases in H. brasiliensis is limited because of the long growth period and lack of well annotated genome information. Here, we reported mitogen-activated protein kinases in H. brasiliensis (HbMPKs) by manually checking and correcting the rubber tree genome. Of the 20 identified HbMPKs, four members were validated by proteomic data. Protein motif and phylogenetic analyses classified these members into four known groups comprising Thr-Glu-Tyr (TEY) and Thr-Asp-Tyr (TDY) domains, respectively. Evolutionary and syntenic analyses suggested four duplication events: HbMPK3/HbMPK6, HbMPK8/HbMPK9/HbMPK15, HbMPK10/HbMPK12 and HbMPK11/HbMPK16/HbMPK19. Expression profiling of the identified HbMPKs in roots, stems, leaves and latex obtained from three cultivars with different latex yield ability revealed tissue- and variety-expression specificity of HbMPK paralogues. Gene expression patterns under osmotic, oxidative, salt and cold stresses, combined with cis-element distribution analyses, indicated different regulation patterns of HbMPK paralogues. Further, Ka/Ks and Tajima analyses suggested an accelerated evolutionary rate in paralogues HbMPK10/12. These results revealed HbMPKs have diverse functions in natural rubber biosynthesis, and highlighted the potential possibility of using MPKs to improve stress tolerance in future rubber tree breeding. Full article

(This article belongs to the Special Issue Genetic Regulation of Abiotic Stress Responses)

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9 pages, 914 KiB

Open AccessArticle

Complete Mitochondrial Genome Sequencing of a Burial from a Romano–Christian Cemetery in the Dakhleh Oasis, Egypt: Preliminary Indications

by J. Eldon Molto^1,*, Odile Loreille^2,†

, Elizabeth K. Mallott³, Ripan S. Malhi⁴, Spence Fast², Jennifer Daniels-Higginbotham², Charla Marshall²

and Ryan Parr⁵

¹ Department of Anthropology, Western University, London, ON N6A 3K7, Canada

² Armed Forces Medical Examiner System—Armed Forces DNA Identification Laboratory (AFMES/AFDIL), Dover, DE 19902, USA

³ Department of Anthropology, Northwestern University, Evanston, IL 60208, USA

⁴ Department of Anthropology, University of Illinois at Urbana-Champaign, 109 Davenport Hall, 607 S. Mathews Ave, Urbana, IL 61801, USA & Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

⁵ Department of Anthropology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada

^† Current address: FBI Laboratory, 2501 Investigation Parkway, Quantico, VA 22135, USA.

Genes 2017, 8(10), 262; https://doi.org/10.3390/genes8100262 - 6 Oct 2017

Cited by 13 | Viewed by 12898

Abstract

The curse of ancient Egyptian DNA was lifted by a recent study which sequenced the mitochondrial genomes (mtGenome) of 90 ancient Egyptians from the archaeological site of Abusir el-Meleq. Surprisingly, these ancient inhabitants were more closely related to those from the Near East [...] Read more.

The curse of ancient Egyptian DNA was lifted by a recent study which sequenced the mitochondrial genomes (mtGenome) of 90 ancient Egyptians from the archaeological site of Abusir el-Meleq. Surprisingly, these ancient inhabitants were more closely related to those from the Near East than to contemporary Egyptians. It has been accepted that the timeless highway of the Nile River seeded Egypt with African genetic influence, well before pre-Dynastic times. Here we report on the successful recovery and analysis of the complete mtGenome from a burial recovered from a remote Romano–Christian cemetery, Kellis 2 (K2). K2 serviced the ancient municipality of Kellis, a village located in the Dakhleh Oasis in the southwest desert in Egypt. The data were obtained by high throughput sequencing (HTS) performed independently at two ancient DNA facilities (Armed Forces DNA Identification Laboratory, Dover, DE, USA and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA). These efforts produced concordant haplotypes representing a U1a1a haplogroup lineage. This result indicates that Near Eastern maternal influence previously identified at Abusir el-Meleq was also present further south, in ancient Kellis during the Romano–Christian period. Full article

(This article belongs to the Special Issue Novel and Neglected Areas of Ancient DNA Research)

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6 pages, 1244 KiB

Open AccessCommunication

Analysis of the Impact of Known SPINK1 Missense Variants on Pre-mRNA Splicing and/or mRNA Stability in a Full-Length Gene Assay

by Hao Wu^1,2,3,4,†, Arnaud Boulling^2,3,†, David N. Cooper⁵

, Zhao-Shen Li^1,4, Zhuan Liao^1,4,*, Claude Férec^2,3,6,7 and Jian-Min Chen^2,3,6,*

¹ Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China

² Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest 29238, France

³ Etablissement Français du Sang (EFS)—Bretagne, Brest 29200, France

⁴ Shanghai Institute of Pancreatic Diseases, Shanghai 200433, China

⁵ Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK

⁶ Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest 29238, France

⁷ Laboratoire de Génétique Moléculaire et d’Histocompatibilité, Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Brest 29200, France

^† These authors contributed equally to this work.

Genes 2017, 8(10), 263; https://doi.org/10.3390/genes8100263 - 10 Oct 2017

Cited by 11 | Viewed by 3729

Abstract

It is increasingly appreciated that missense variants may not only alter protein structure and function but may also influence pre-mRNA splicing and/or mRNA stability. Here we explore this issue in the context of currently known SPINK1 missense variants using a full-length gene assay. [...] Read more.

It is increasingly appreciated that missense variants may not only alter protein structure and function but may also influence pre-mRNA splicing and/or mRNA stability. Here we explore this issue in the context of currently known SPINK1 missense variants using a full-length gene assay. We demonstrated that 4 (17%) out of 24 variants tested significantly reduced pre-mRNA splicing and/or stability as compared with the wild-type. However, since the strongest effect observed was a 23% reduction from normal, the contribution of SPINK1 missense variants to the clinical phenotype through an impact on mRNA processing alone may be relatively minor compared with their effects in relation to protein structure/function. Full article

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10 pages, 492 KiB

Open AccessArticle

Targeted Next-Generation Sequencing Identification of Mutations in Disease Resistance Gene Analogs (RGAs) in Wild and Cultivated Beets

by Piergiorgio Stevanato¹

, Chiara Broccanello¹, Luca Pajola¹, Filippo Biscarini^2,3

, Chris Richards⁴, Lee Panella⁵, Mahdi Hassani^6,7, Elide Formentin^8,*, Claudia Chiodi¹, Giuseppe Concheri¹ and Bahram Heidari⁶

¹ Department of Agronomy, Animals, Natural Resources and Environment-DAFNAE, University of Padova, 35020 Legnaro (Padova), Italy

² Cardiff University, School of Medicine, Heath Park, CF14 4XN Cardiff, UK

³ Consiglio Nazionale delle Ricerche (CNR), 20133 Milan, Italy

⁴ USDA-ARS, National Laboratory for Genetic Resources Preservation, Fort Collins, 80521 CO, USA

⁵ Colorado State University, Department of Soil and Crop Sciences, Fort Collins, 80521 CO, USA

⁶ Department of Crop Production and Plant Breeding, School of Agriculture, Shiraz University, 7144165186 Shiraz, Iran

⁷ Sugar Beet Seed Institute (SBSI), 315854114 Karaj, Iran

⁸ Department of Biology, University of Padova, 35131 Padova, Italy

Genes 2017, 8(10), 264; https://doi.org/10.3390/genes8100264 - 11 Oct 2017

Cited by 10 | Viewed by 5904

Abstract

Resistance gene analogs (RGAs) were searched bioinformatically in the sugar beet (Beta vulgaris L.) genome as potential candidates for improving resistance against different diseases. In the present study, Ion Torrent sequencing technology was used to identify mutations in 21 RGAs. The DNA [...] Read more.

Resistance gene analogs (RGAs) were searched bioinformatically in the sugar beet (Beta vulgaris L.) genome as potential candidates for improving resistance against different diseases. In the present study, Ion Torrent sequencing technology was used to identify mutations in 21 RGAs. The DNA samples of ninety-six individuals from six sea beets (Beta vulgaris L. subsp. maritima) and six sugar beet pollinators (eight individuals each) were used for the discovery of single-nucleotide polymorphisms (SNPs). Target amplicons of about 200 bp in length were designed with the Ion AmpliSeq Designer system in order to cover the DNA sequences of the RGAs. The number of SNPs ranged from 0 in four individuals to 278 in the pollinator R740 (which is resistant to rhizomania infection). Among different groups of beets, cytoplasmic male sterile lines had the highest number of SNPs (132) whereas the lowest number of SNPs belonged to O-types (95). The principal coordinates analysis (PCoA) showed that the polymorphisms inside the gene Bv8_184910_pkon (including the CCCTCC sequence) can effectively differentiate wild from cultivated beets, pointing at a possible mutation associated to rhizomania resistance that originated directly from cultivated beets. This is unlike other resistance sources that are introgressed from wild beets. This gene belongs to the receptor-like kinase (RLK) class of RGAs, and is associated to a hypothetical protein. In conclusion, this first report of using Ion Torrent sequencing technology in beet germplasm suggests that the identified sequence CCCTCC can be used in marker-assisted programs to differentiate wild from domestic beets and to identify other unknown disease resistance genes in beet. Full article

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

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15 pages, 3472 KiB

Open AccessArticle

Molecular Cloning, Recombinant Expression and Antifungal Activity of BnCPI, a Cystatin in Ramie (Boehmeria nivea L.)

by Yongting Yu^1,*,†

, Gang Zhang^2,†, Zhimin Li¹, Yi Cheng¹, Chunsheng Gao¹, Liangbin Zeng¹, Jia Chen¹, Li Yan¹, Xiangping Sun¹, Litao Guo¹ and Zhun Yan^1,*

¹ Institute of Bast Fiber Crops and Center for Southern Economic Crops, Chinese Academy of Agricultural Science, Changsha 410205, China

² College of Pharmacy and Shaanxi Provincial Key Laboratory for Chinese Medicine Basis & New Drugs Research, Shaanxi University of Chinese Medicine, Xi’an 712406, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 265; https://doi.org/10.3390/genes8100265 - 11 Oct 2017

Cited by 12 | Viewed by 5383

Abstract

Phytocystatins play multiple roles in plant growth, development and resistance to pests and other environmental stresses. A ramie (Boehmeria nivea L.) phytocystatin gene, designated as BnCPI, was isolated from a ramie cDNA library and its full-length cDNA was obtained by rapid [...] Read more.

Phytocystatins play multiple roles in plant growth, development and resistance to pests and other environmental stresses. A ramie (Boehmeria nivea L.) phytocystatin gene, designated as BnCPI, was isolated from a ramie cDNA library and its full-length cDNA was obtained by rapid amplification of cDNA ends (RACE). The full-length cDNA sequence (691 bp) consisted of a 303 bp open reading frame (ORF) encoding a protein of 100 amino acids with deduced molecular mass of 11.06 kDa and a theoretical isoelectric point (pI) of 6.0. The alignment of genome DNA (accession no. MF153097) and cDNA sequences of BnCPI showed that an intron (~104 bp) exists in the coding region. The BnCPI protein contains most of the highly conserved blocks including Gly⁵-Gly⁶ at the N-terminal, the reactive site motif QxVxG (Q⁴⁹V⁵⁰V⁵¹S⁵²G⁵³), the L⁷⁹-W⁸⁰ block and the [LVI]-[AGT]-[RKE]-[FY]-[AS]-[VI]-x-[EDQV]-[HYFQ]-N (L²²G²³R²⁴ F²⁵A²⁶V²⁷ D²⁸D²⁹H³⁰ N³¹) block that is common among plant cystatins. BLAST analysis indicated that BnCPI is similar to cystatins from Glycine max (77%), Glycine soja (76%), Hevea brasiliensis (75%) and Ricinus communis (75%). The BnCPI was subcloned into expression vector pSmart-I and then overexpressed in Escherichia coli BL21 (DE3) as a His-tagged recombinant protein. The purified reBnCPI has a molecular mass of 11.4 kDa determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE). Purified reBnCPI can efficiently inhibit the protease activity of papain and ficin toward BANA (Nα-benzoyl-L-arginine-2-naphthyamide), as well as the mycelium growth of some important plant pathogenic fungi. The data further contribute to our understanding of the molecular functions of BnCPI. Full article

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

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3 pages, 148 KiB

Open AccessEditorial

Organ-on-Chip Technology: Current State and Future Developments

by Rimantas Kodzius^1,2,3,*

, Frank Schulze¹

, Xinghua Gao² and Marlon R. Schneider¹

¹ German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Berlin 10589, Germany

² iSmart, Materials Genome Institute, Shanghai University (SHU), Shanghai 201800, China

³ Mathematics and Natural Sciences Department, The American University of Iraq, Sulaimani, Sulaymaniyah 46001, Iraq

Genes 2017, 8(10), 266; https://doi.org/10.3390/genes8100266 - 11 Oct 2017

Cited by 28 | Viewed by 6224

Abstract

In the early days of pharmacy, the development of new drugs was frequently achieved by restless chemists who worked solitarily, day by day for years [...]
Full article

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

16 pages, 3390 KiB

Open AccessArticle

DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility

by Katharina Gegenschatz-Schmid¹, Gilvydas Verkauskas², Philippe Demougin³, Vytautas Bilius², Darius Dasevicius⁴, Michael B. Stadler^5,6 and Faruk Hadziselimovic^1,*

¹ Cryptorchidism Research Institute, Kindermedizinisches Zentrum Liestal, 4410 Liestal, Switzerland

² Children’s Surgery Centre, Faculty of Medicine, Vilnius of University, Vilnius 01513, Lithuania

³ Biozentrum, Life Sciences Training Facility, University of Basel, 4001 Basel, Switzerland

⁴ Institute for Pathology, National Centre of Pathology, Affiliate of Vilnius University Hospital Santariskiu Klinikos, 08406 Vilnius, Lithuania

⁵ Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland

⁶ Swiss Institute of Bioinformatics, Basel, Switzerland

Genes 2017, 8(10), 267; https://doi.org/10.3390/genes8100267 - 11 Oct 2017

Cited by 19 | Viewed by 5041

Abstract

Defective mini-puberty results in insufficient testosterone secretion that impairs the differentiation of gonocytes into dark-type (Ad) spermatogonia. The differentiation of gonocytes into Ad spermatogonia can be induced by administration of the gonadotropin-releasing hormone agonist, GnRHa (Buserelin, INN)). Nothing is known about the mechanism [...] Read more.

Defective mini-puberty results in insufficient testosterone secretion that impairs the differentiation of gonocytes into dark-type (Ad) spermatogonia. The differentiation of gonocytes into Ad spermatogonia can be induced by administration of the gonadotropin-releasing hormone agonist, GnRHa (Buserelin, INN)). Nothing is known about the mechanism that underlies successful GnRHa treatment in the germ cells. Using RNA-sequencing of testicular biopsies, we recently examined RNA profiles of testes with and without GnRHa treatment. Here, we focused on the expression patterns of known gene markers for gonocytes and spermatogonia, and found that DMRTC2, PAX7, BRACHYURY/T, and TERT were associated with defective mini-puberty and were responsive to GnRHa. These results indicate novel testosterone-dependent genes and provide valuable insight into the transcriptional response to both defective mini-puberty and curative GnRHa treatment, which prevents infertility in man with one or both undescended (cryptorchid) testes. Full article

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

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16 pages, 11249 KiB

Open AccessArticle

Low-Grade Dysplastic Nodules Revealed as the Tipping Point during Multistep Hepatocarcinogenesis by Dynamic Network Biomarkers

by Lina Lu^1,†, Zhonglin Jiang^1,†, Yulin Dai² and Luonan Chen^1,3,*

¹ Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China

² Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St., Suite 820, Houston, TX 77030, USA

³ School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 268; https://doi.org/10.3390/genes8100268 - 13 Oct 2017

Cited by 10 | Viewed by 5327

Abstract

Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem [...] Read more.

Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem is to identify when and how the critical transition happens during the HCC initiation period at a molecular level. In this work, for the first time, we revealed that LGDNs is the tipping point (i.e., pre-HCC state rather than HCC state) of hepatocarcinogenesis based on a series of gene expression profiles by a new mathematical model termed dynamic network biomarkers (DNB)—a group of dominant genes or molecules for the transition. Different from the conventional biomarkers based on the differential expressions of the observed genes (or molecules) for diagnosing a disease state, the DNB model exploits collective fluctuations and correlations of the observed genes, thereby predicting the imminent disease state or diagnosing the critical state. Our results show that DNB composed of 59 genes signals the tipping point of HCC (i.e., LGDNs). On the other hand, there are a large number of differentially expressed genes between cirrhosis and HGDNs, which highlighted the stark differences or drastic changes before and after the tipping point or LGDNs, implying the 59 DNB members serving as the early-warning signals of the upcoming drastic deterioration for HCC. We further identified the biological pathways responsible for this transition, such as the type I interferon signaling pathway, Janus kinase–signal transducers and activators of transcription (JAK–STAT) signaling pathway, transforming growth factor (TGF)-β signaling pathway, retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathway, cell adhesion molecules, and cell cycle. In particular, pathways related to immune system reactions and cell adhesion were downregulated, and pathways related to cell growth and death were upregulated. Furthermore, DNB was validated as an effective predictor of prognosis for HCV-induced HCC patients by survival analysis on independent data, suggesting a potential clinical application of DNB. This work provides biological insights into the dynamic regulations of the critical transitions during multistep hepatocarcinogenesis. Full article

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

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35 pages, 7510 KiB

Open AccessArticle

The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome

by Ludivine Renaud^1,2, Willian A. da Silveira³, E. Starr Hazard^3,4, Jonathan Simpson³, Silvia Falcinelli⁵, Dongjun Chung⁷, Oliana Carnevali⁵

and Gary Hardiman^1,2,3,6,7,*

¹ Division of Nephrology, Department of Medicine, Medical University of South Carolina (MUSC),Charleston, SC 29425, USA

² Laboratory for Marine Systems Biology, Hollings Marine Laboratory, Charleston, SC 29412, USA

³ Center for Genomic Medicine, Bioinformatics, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA

⁴ Library Science and Informatics, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA

⁵ Dipartimento Scienze della Vita e dell’Ambiente, Universita Politecnica delle Marche, 60131 Ancona, Italy

⁶ Department of Medicine, University of California, La Jolla, CA 92093, USA

⁷ Department of Public Health Sciences, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA

Genes 2017, 8(10), 269; https://doi.org/10.3390/genes8100269 - 13 Oct 2017

Cited by 29 | Viewed by 7330

Abstract

Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly [...] Read more.

Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome and transcriptome in adult zebrafish with the potential to cause adverse health outcomes including cancer. Full article

(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)

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17 pages, 5400 KiB

Open AccessArticle

The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

by Damir Hudetz^1,2,3,*

, Igor Borić^1,4,5, Eduard Rod¹, Željko Jeleč¹, Andrej Radić¹, Trpimir Vrdoljak^1,2, Andrea Skelin^1,6, Gordan Lauc^6,7

, Irena Trbojević-Akmačić⁶

, Mihovil Plečko⁸

, Ozren Polašek^4,7

and Dragan Primorac^{1,3,4,9,10,11,12,*}

¹ St. Catherine Specialty Hospital, 49210 Zabok/ 10000 Zagreb, Croatia

² Clinical Hospital “Sveti Duh”, 10000 Zagreb, Croatia

³ School of medicine, JJ Strossmayer University of Osijek, 31000 Osijek, Croatia

⁴ School of Medicine, University of Split, 21000 Split, Croatia

⁵ University of Rijeka, Medical School, 51000 Rijeka, Croatia

⁶ Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia

⁷ Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

⁸ School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

⁹ Gen-info, 10000 Zagreb, Croatia

¹⁰ Children’s Hospital Srebrnjak, 10000 Zagreb, Croatia

¹¹ Eberly College of Science, The Pennsylvania State University, University Park, State College, 16802 PA, USA

¹² The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, 06516 CT, USA

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Genes 2017, 8(10), 270; https://doi.org/10.3390/genes8100270 - 13 Oct 2017

Cited by 90 | Viewed by 8882

Abstract

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to [...] Read more.

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s) was performed in all patients. Patients were assessed for visual analogue scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12 months after the treatment. Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively charged contrast gadopentetate dimeglumine (Gd-DTPA²⁻) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG) content in hyaline cartilage, which is in line with observed VAS and clinical results. Full article

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

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14 pages, 2060 KiB

Open AccessArticle

Effects of Conjugated Linoleic Acid Supplementation on the Expression Profile of miRNAs in Porcine Adipose Tissue

by Qi Wang^1,†, Renli Qi^1,2,†

, Hong Liu¹, Jing Wang¹, Wenming Huang^3,*, Feiyun Yang^1,2,* and Jinxiu Huang^1,2,*

¹ Chongqing Academy of Animal Sciences, Chongqing 402460, China

² Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Chongqing Key Laboratory of Pig Industry Sciences, Chongqing 402460, China

³ The Department of Animal Husbandry, Rongchang Campus, Southwest University, Rongchang, Chongqing 402460, China

^† These two authors contributed equally to this work.

Genes 2017, 8(10), 271; https://doi.org/10.3390/genes8100271 - 13 Oct 2017

Cited by 6 | Viewed by 4512

Abstract

Conjugated linoleic acids (CLAs) play a major role in adipocyte differentiation and lipid metabolism in animals. MicroRNAs (miRNAs) appear to be involved in many biological processes in adipose tissue. However, the specific influence on miRNAs by CLA supplementation in porcine adipose tissue remains [...] Read more.

Conjugated linoleic acids (CLAs) play a major role in adipocyte differentiation and lipid metabolism in animals. MicroRNAs (miRNAs) appear to be involved in many biological processes in adipose tissue. However, the specific influence on miRNAs by CLA supplementation in porcine adipose tissue remains unclear. Thus, we continuously added 1.5% CLA to the pig diet from the embryo stage to the finishing period and conducted a high-throughput sequencing approach to analyse the changes in adipose tissue miRNAs. We identified 283 known porcine miRNAs, and 14 miRNAs were differentially expressed in response to CLA treatment. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the targets of the 14 differentially expressed miRNAs were involved in the Wnt signalling pathway. The CLA treatment downregulated the gene expression of PPARγ, C/EBPα, FAS, and FATP1 in both subcutaneous and abdominal fat tissues; the analysis showed that ssc-miR-21 expression was significantly correlated with PPARγ expression (p<0.05), and speculated that ssc-miR-21 might influence adipogenesis through PPARγ. In conclusion, our study analysed the miRNA profiles in porcine adipose tissues by CLA treatment, and demonstrated that miRNAs are important regulators of fat lipogenesis. This study provides valuable information for the molecular regulatory mechanism of CLA on adipose tissue. Full article

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

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25 pages, 1114 KiB

Open AccessReview

Chromosomal Evolution in Chiroptera

by Cibele G. Sotero-Caio¹, Robert J. Baker² and Marianne Volleth^3,*

¹ Department of Genetics, Universidade Federal de Pernambuco, Recife 50740-600, Brazil

² Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA

³ Department of Human Genetics, Otto-von-Guericke University, Magdeburg 39120, Germany

Genes 2017, 8(10), 272; https://doi.org/10.3390/genes8100272 - 13 Oct 2017

Cited by 32 | Viewed by 9236

Abstract

Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n [...] Read more.

Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62). As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae), focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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28 pages, 5173 KiB

Open AccessArticle

The History of Tree and Shrub Taxa on Bol'shoy Lyakhovsky Island (New Siberian Archipelago) since the Last Interglacial Uncovered by Sedimentary Ancient DNA and Pollen Data

by Heike H. Zimmermann^1,2,*

, Elena Raschke¹, Laura S. Epp¹, Kathleen R. Stoof-Leichsenring¹, Lutz Schirrmeister¹

, Georg Schwamborn¹ and Ulrike Herzschuh^1,2,3,*

¹ Alfred-Wegener-Institute Helmholtz Centre for Polar and Marine Research, Periglacial Research Unit, Telegrafenberg A43, 14473 Potsdam, Germany

² Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam-Golm, Germany

³ Institute of Earth and Environmental Sciences, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam-Golm, Germany

Genes 2017, 8(10), 273; https://doi.org/10.3390/genes8100273 - 13 Oct 2017

Cited by 42 | Viewed by 7572

Abstract

Ecosystem boundaries, such as the Arctic-Boreal treeline, are strongly coupled with climate and were spatially highly dynamic during past glacial-interglacial cycles. Only a few studies cover vegetation changes since the last interglacial, as most of the former landscapes are inundated and difficult to [...] Read more.

Ecosystem boundaries, such as the Arctic-Boreal treeline, are strongly coupled with climate and were spatially highly dynamic during past glacial-interglacial cycles. Only a few studies cover vegetation changes since the last interglacial, as most of the former landscapes are inundated and difficult to access. Using pollen analysis and sedimentary ancient DNA (sedaDNA) metabarcoding, we reveal vegetation changes on Bol’shoy Lyakhovsky Island since the last interglacial from permafrost sediments. Last interglacial samples depict high levels of floral diversity with the presence of trees (Larix, Picea, Populus) and shrubs (Alnus, Betula, Ribes, Cornus, Saliceae) on the currently treeless island. After the Last Glacial Maximum, Larix re-colonised the island but disappeared along with most shrub taxa. This was probably caused by Holocene sea-level rise, which led to increased oceanic conditions on the island. Additionally, we applied two newly developed larch-specific chloroplast markers to evaluate their potential for tracking past population dynamics from environmental samples. The novel markers were successfully re-sequenced and exhibited two variants of each marker in last interglacial samples. SedaDNA can track vegetation changes as well as genetic changes across geographic space through time and can improve our understanding of past processes that shape modern patterns. Full article

(This article belongs to the Special Issue Novel and Neglected Areas of Ancient DNA Research)

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14 pages, 6750 KiB

Open AccessArticle

Transcriptomic Analysis of Long Non-Coding RNAs and Coding Genes Uncovers a Complex Regulatory Network That Is Involved in Maize Seed Development

by Ming Zhu^1,2

, Min Zhang², Lijuan Xing², Wenzong Li², Haiyang Jiang¹, Lei Wang^2,* and Miaoyun Xu^2,*

¹ School of Life Sciences, Anhui Agricultural University, Hefei 230000, China

² Biotechnology Research Institute/The National Key Facility for Crop Gene Resources and Genetic Improvement, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Genes 2017, 8(10), 274; https://doi.org/10.3390/genes8100274 - 17 Oct 2017

Cited by 43 | Viewed by 5803

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of maize plant. However, few focused on seed development of maize. Here, we identified 753 lncRNA candidates in maize genome from six seed samples. Similar to the mRNAs, lncRNAs showed [...] Read more.

Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of maize plant. However, few focused on seed development of maize. Here, we identified 753 lncRNA candidates in maize genome from six seed samples. Similar to the mRNAs, lncRNAs showed tissue developmental stage specific and differential expression, indicating their putative role in seed development. Increasing evidence shows that crosstalk among RNAs mediated by shared microRNAs (miRNAs) represents a novel layer of gene regulation, which plays important roles in plant development. Functional roles and regulatory mechanisms of lncRNAs as competing endogenous RNAs (ceRNA) in plants, particularly in maize seed development, are unclear. We combined analyses of consistently altered 17 lncRNAs, 840 mRNAs and known miRNA to genome-wide investigate potential lncRNA-mediated ceRNA based on “ceRNA hypothesis”. The results uncovered seven novel lncRNAs as potential functional ceRNAs. Functional analyses based on their competitive coding-gene partners by Gene Ontology (GO) and KEGG biological pathway demonstrated that combined effects of multiple ceRNAs can have major impacts on general developmental and metabolic processes in maize seed. These findings provided a useful platform for uncovering novel mechanisms of maize seed development and may provide opportunities for the functional characterization of individual lncRNA in future studies. Full article

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

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14 pages, 2301 KiB

Open AccessArticle

Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa

by Mercedes Ruiz-Estévez, Mohammed Bakkali

, Rubén Martín-Blázquez and Manuel A. Garrido-Ramos^*

Departamento de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain

Genes 2017, 8(10), 275; https://doi.org/10.3390/genes8100275 - 17 Oct 2017

Cited by 13 | Viewed by 4924

Abstract

We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox ( [...] Read more.

We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa. Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4, and VsBELL6) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive identification and characterization of TALE homeobox genes in V. speciosa, and gives novel insights about the role of these genes in fern development. Full article

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

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18 pages, 3741 KiB

Open AccessReview

Functional Characterization of Rare RAB12 Variants and Their Role in Musician’s and Other Dystonias

by Eva Hebert^1,†, Friederike Borngräber^1,2,3,†, Alexander Schmidt^1,2,3, Aleksandar Rakovic¹, Ingrid Brænne⁴, Anne Weissbach¹, Jennie Hampf¹, Eva-Juliane Vollstedt¹, Leopold Größer⁵, Susen Schaake¹, Michaela Müller⁴, Humera Manzoor^1,6, Hans-Christian Jabusch⁷, Daniel Alvarez-Fischer¹, Meike Kasten^1,8, Vladimir S. Kostic⁹, Thomas Gasser¹⁰, Kirsten E. Zeuner¹¹, Han-Joon Kim¹², Beomseok Jeon¹², Peter Bauer¹³, Eckart Altenmüller¹⁴, Christine Klein¹ and Katja Lohmann^1,* Show full author list Hide full author list

¹ Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany

² Kurt Singer Institute for Music Physiology and Musicians’ Health, Hanns Eisler School of Music Berlin, 10595 Berlin, Germany

³ Berlin Center for Musicians’ Medicine, Charité—University Medicine Berlin, 10117 Berlin, Germany

⁴ Institute for Integrative and Experimental Genomics, University of Luebeck, 23538 Luebeck, Germany

⁵ Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany

⁶ School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan

⁷ Institute of Musician’s Medicine, University of Music, 01069 Dresden, Germany

⁸ Department of Psychiatry and Psychotherapy, University of Lübeck, 23538 Lubeck, Germany

⁹ Department of Neurodegenerative Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia

¹⁰ Department of Neurology, University of Tübingen, 72076 Tubingen, Germany

¹¹ Department of Neurology, University of Kiel, 24105 Kiel, Germany

¹² Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Seoul 03080, Korea

¹³ Centogene AG, 18057 Rostock, Germany

¹⁴ Institute of Music Physiology and Musician’s Medicine, Hanover University of Music, Drama and Media, 30175 Hanover, Germany

^† These two authors contributed equally to this study.

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Genes 2017, 8(10), 276; https://doi.org/10.3390/genes8100276 - 18 Oct 2017

Cited by 7 | Viewed by 5863

Abstract

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD) and writer’s dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. [...] Read more.

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD) and writer’s dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson’s disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val (n = 6); p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias. Full article

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

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19 pages, 7677 KiB

Open AccessArticle

Further Insights into the Ciliary Gene and Protein KIZ and Its Murine Ortholog PLK1S1 Mutated in Rod-Cone Dystrophy

by Said El Shamieh^1,2

, Cécile Méjécase¹, Matteo Bertelli³, Angélique Terray¹, Christelle Michiels¹, Christel Condroyer¹, Stéphane Fouquet¹, Maxime Sadoun¹, Emmanuelle Clérin¹, Binqian Liu¹, Thierry Léveillard¹, Olivier Goureau¹, José-Alain Sahel^1,4,5,6,7,8, Isabelle Audo^1,4,8,*,† and Christina Zeitz^1,*,†

¹ Sorbonne Universités, UPMC University Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 75012 Paris, France

² Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, 115020 Beirut, Lebanon

³ Magi Euregio, 39100 Bolzano (BZ), Italy

⁴ Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC 1423, 75012 Paris, France

⁵ Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France

⁶ Académie des Sciences-Institut de France, 75006 Paris, France

⁷ Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburg, PA 15213, USA

⁸ Institute of Ophthalmology, University College of London, London, EC1V 9EL, UK

^† Equal contributions.

Genes 2017, 8(10), 277; https://doi.org/10.3390/genes8100277 - 18 Oct 2017

Cited by 8 | Viewed by 5427

Abstract

We identified herein additional patients with rod-cone dystrophy (RCD) displaying mutations in KIZ, encoding the ciliary centrosomal protein kizuna and performed functional characterization of the respective protein in human fibroblasts and of its mouse ortholog PLK1S1 in the retina. Mutation screening was [...] Read more.

We identified herein additional patients with rod-cone dystrophy (RCD) displaying mutations in KIZ, encoding the ciliary centrosomal protein kizuna and performed functional characterization of the respective protein in human fibroblasts and of its mouse ortholog PLK1S1 in the retina. Mutation screening was done by targeted next generation sequencing and subsequent Sanger sequencing validation. KIZ mRNA levels were assessed on blood and serum-deprived human fibroblasts from a control individual and a patient, compound heterozygous for the c.52G>T (p.Glu18*) and c.119_122del (p.Lys40Ilefs*14) mutations in KIZ. KIZ localization, documentation of cilium length and immunoblotting were performed in these two fibroblast cell lines. In addition, PLK1S1 immunolocalization was conducted in mouse retinal cryosections and isolated rod photoreceptors. Analyses of additional RCD patients enabled the identification of two homozygous mutations in KIZ, the known c.226C>T (p.Arg76*) mutation and a novel variant, the c.3G>A (p.Met1?) mutation. Albeit the expression levels of KIZ were three-times lower in the patient than controls in whole blood cells, further analyses in control- and mutant KIZ patient-derived fibroblasts unexpectedly revealed no significant difference between the two genotypes. Furthermore, the averaged monocilia length in the two fibroblast cell lines was similar, consistent with the preserved immunolocalization of KIZ at the basal body of the primary cilia. Analyses in mouse retina and isolated rod photoreceptors showed PLK1S1 localization at the base of the photoreceptor connecting cilium. In conclusion, two additional patients with mutations in KIZ were identified, further supporting that defects in KIZ/PLK1S1, detected at the basal body of the primary cilia in fibroblasts, and the photoreceptor connecting cilium in mouse, respectively, are involved in RCD. However, albeit the mutations were predicted to lead to nonsense mediated mRNA decay, we could not detect changes upon expression levels, protein localization or cilia length in KIZ-mutated fibroblast cells. Together, our findings unveil the limitations of fibroblasts as a cellular model for RCD and call for other models such as induced pluripotent stem cells to shed light on retinal pathogenic mechanisms of KIZ mutations. Full article

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

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15 pages, 2252 KiB

Open AccessArticle

A DNA Structural Alphabet Distinguishes Structural Features of DNA Bound to Regulatory Proteins and in the Nucleosome Core Particle

by Bohdan Schneider^1,*

, Paulína Božíková¹

, Petr Čech²

, Daniel Svozil²

and Jiří Černý¹

¹ Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Průmyslová 595, CZ-252 50 Vestec, Prague West, Czech Republic

² Laboratory of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, CZ-166 28 Prague, Czech Republic

Genes 2017, 8(10), 278; https://doi.org/10.3390/genes8100278 - 18 Oct 2017

Cited by 10 | Viewed by 5951

Abstract

We analyzed the structural behavior of DNA complexed with regulatory proteins and the nucleosome core particle (NCP). The three-dimensional structures of almost 25 thousand dinucleotide steps from more than 500 sequentially non-redundant crystal structures were classified by using DNA structural alphabet CANA (Conformational [...] Read more.

We analyzed the structural behavior of DNA complexed with regulatory proteins and the nucleosome core particle (NCP). The three-dimensional structures of almost 25 thousand dinucleotide steps from more than 500 sequentially non-redundant crystal structures were classified by using DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and associations between ten CANA letters and sixteen dinucleotide sequences were investigated. The associations showed features discriminating between specific and non-specific binding of DNA to proteins. Important is the specific role of two DNA structural forms, A-DNA, and BII-DNA, represented by the CANA letters AAA and BB2: AAA structures are avoided in non-specific NCP complexes, where the wrapping of the DNA duplex is explained by the periodic occurrence of BB2 every 10.3 steps. In both regulatory and NCP complexes, the extent of bending of the DNA local helical axis does not influence proportional representation of the CANA alphabet letters, namely the relative incidences of AAA and BB2 remain constant in bent and straight duplexes. Full article

(This article belongs to the Special Issue Protein-DNA Interactions)

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8 pages, 721 KiB

Open AccessOpinion

Potential Role of Phase Separation of Repetitive DNA in Chromosomal Organization

by Shao-Jun Tang

Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA

Genes 2017, 8(10), 279; https://doi.org/10.3390/genes8100279 - 18 Oct 2017

Cited by 17 | Viewed by 5912

Abstract

The basic principles of chromosomal organization in eukaryotic cells remain elusive. Current mainstream research efforts largely concentrate on searching for critical packaging proteins involved in organizing chromosomes. I have taken a different perspective, by considering the role of genomic information in chromatins. In [...] Read more.

The basic principles of chromosomal organization in eukaryotic cells remain elusive. Current mainstream research efforts largely concentrate on searching for critical packaging proteins involved in organizing chromosomes. I have taken a different perspective, by considering the role of genomic information in chromatins. In particular, I put forward the concept that repetitive DNA elements are key chromosomal packaging modules, and their intrinsic property of homology-based interaction can drive chromatin folding. Many repetitive DNA families have high copy numbers and clustered distribution patterns in the linear genomes. These features may facilitate the interactions among members in the same repeat families. In this paper, the potential liquid–liquid phase transition of repetitive DNAs that is induced by their extensive interaction in chromosomes will be considered. I propose that the interaction among repetitive DNAs may lead to phase separation of interacting repetitive DNAs from bulk chromatins. Phase separation of repetitive DNA may provide a physical mechanism that drives rapid massive changes of chromosomal conformation. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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17 pages, 3265 KiB

Open AccessArticle

Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe Inherited Retinal Dystrophies

by Valentina Di Iorio^1,†, Marianthi Karali^2,3,†, Raffaella Brunetti-Pierri¹, Mariaelena Filippelli¹, Giuseppina Di Fruscio², Mariateresa Pizzo³, Margherita Mutarelli³, Vincenzo Nigro^2,3, Francesco Testa¹, Sandro Banfi^2,3,* and Francesca Simonelli^1,*

¹ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Università degli Studi della Campania Luigi Vanvitelli, via Pansini 5, Naples 80131, Italy

² Medical Genetics, Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania Luigi Vanvitelli, via Luigi De Crecchio 7, Naples 80138, Italy

³ Telethon Institute of Genetics and Medicine, via Campi Flegrei 34, Pozzuoli 80078, Italy

^† These authors contributed equally to this work.

Genes 2017, 8(10), 280; https://doi.org/10.3390/genes8100280 - 20 Oct 2017

Cited by 24 | Viewed by 5905

Abstract

We performed a clinical and genetic characterization of a pediatric cohort of patients with inherited retinal dystrophy (IRD) to identify the most suitable cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18 years, with severe isolated IRD at [...] Read more.

We performed a clinical and genetic characterization of a pediatric cohort of patients with inherited retinal dystrophy (IRD) to identify the most suitable cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18 years, with severe isolated IRD at the time of presentation. The ophthalmological characterization also included assessment of the photoreceptor layer integrity in the macular region (ellipsoid zone (EZ) band). In parallel, we carried out a targeted, next-generation sequencing (NGS)-based analysis using a panel that covers over 150 genes with either an established or a candidate role in IRD pathogenesis. Based on the ophthalmological assessment, the cohort was composed of 24 Leber congenital amaurosis, 14 early onset retinitis pigmentosa, and 5 achromatopsia patients. We identified causative mutations in 58.1% of the cases. We also found novel genotype-phenotype correlations in patients harboring mutations in the CEP290 and CNGB3 genes. The EZ band was detectable in 40% of the analyzed cases, also in patients with genotypes usually associated with severe clinical manifestations. This study provides the first detailed clinical-genetic assessment of severe IRDs with infantile onset and lays the foundation of a standardized protocol for the selection of patients that are more likely to benefit from gene replacement therapeutic approaches. Full article

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

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15 pages, 2386 KiB

Open AccessArticle

Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line

by Amin Boroumand Moghaddam^1,2, Mona Moniri^1,2, Susan Azizi^1,*

, Raha Abdul Rahim³, Arbakariya Bin Ariff^1,4, Mohammad Navaderi⁵ and Rosfarizan Mohamad^1,6,*

¹ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

² Young Research and Elite Club, Sabzevar Branch, Islamic Azad University, Sabzevar, Iran

³ Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁴ Bioprocessing and Biomanufacturing Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁵ Young Research and Elite Club, Parand Branch, Islamic Azad University, Parand, Iran

⁶ Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Genes 2017, 8(10), 281; https://doi.org/10.3390/genes8100281 - 20 Oct 2017

Cited by 145 | Viewed by 9406

Abstract

Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of [...] Read more.

Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC₅₀) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G₁ phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC₂₅, 98.91% at IC₅₀, and 99.44% at IC₇₅. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways. Full article

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

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15 pages, 8968 KiB

Open AccessArticle

Chromosome Synapsis and Recombination in Male Hybrids between Two Chromosome Races of the Common Shrew (Sorex araneus L., Soricidae, Eulipotyphla)

by Nadezhda M. Belonogova^1,†, Andrei V. Polyakov^1,†, Tatyana V. Karamysheva¹, Anna A. Torgasheva^1,2, Jeremy B. Searle³ and Pavel M. Borodin^1,2,*

¹ Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Department, Novosibirsk 630090, Russia

² Novosibirsk State University, Department of Cytology and Genetics, Novosibirsk 630090, Russia

³ Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853, USA

^† These authors contributed equally to this work.

Genes 2017, 8(10), 282; https://doi.org/10.3390/genes8100282 - 20 Oct 2017

Cited by 5 | Viewed by 5274

Abstract

Hybrid zones between chromosome races of the common shrew (Sorex araneus) provide exceptional models to study the potential role of chromosome rearrangements in the initial steps of speciation. The Novosibirsk and Tomsk races differ by a series of Robertsonian fusions with [...] Read more.

Hybrid zones between chromosome races of the common shrew (Sorex araneus) provide exceptional models to study the potential role of chromosome rearrangements in the initial steps of speciation. The Novosibirsk and Tomsk races differ by a series of Robertsonian fusions with monobrachial homology. They form a narrow hybrid zone and generate hybrids with both simple (chain of three chromosomes) and complex (chain of eight or nine) synaptic configurations. Using immunolocalisation of the meiotic proteins, we examined chromosome pairing and recombination in males from the hybrid zone. Homozygotes and simple heterozygotes for Robertsonian fusions showed a low frequency of synaptic aberrations (<10%). The carriers of complex synaptic configurations showed multiple pairing abnormalities, which might lead to reduced fertility. The recombination frequency in the proximal regions of most chromosomes of all karyotypes was much lower than in the other regions. The strong suppression of recombination in the pericentromeric regions and co-segregation of race specific chromosomes involved in the long chains would be expected to lead to linkage disequilibrium between genes located there. Genic differentiation, together with the high frequency of pairing aberrations in male carriers of the long chains, might contribute to maintenance of the narrow hybrid zone. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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12 pages, 2100 KiB

Open AccessCommunication

Allelic Expression Imbalance in the Human Retinal Transcriptome and Potential Impact on Inherited Retinal Diseases

by Pablo Llavona^1,*, Michele Pinelli²

, Margherita Mutarelli², Veer Singh Marwah^2,3, Simone Schimpf-Linzenbold¹, Sebastian Thaler⁴, Efdal Yoeruek^4,5, Jan Vetter⁶, Susanne Kohl¹

and Bernd Wissinger¹

¹ Institute for Ophthalmic Research, Centre for Ophthalmology, 72076 Tuebingen, Germany

² Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy

³ Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland

⁴ Center for Ophthalmology, 72076 Tuebingen, Germany

⁵ Augenklinik Mülheim, 45468 Mülheim an der Ruhr, Germany

⁶ Universitäts-Augenklinik, 55131 Mainz, Germany

Genes 2017, 8(10), 283; https://doi.org/10.3390/genes8100283 - 20 Oct 2017

Cited by 16 | Viewed by 5863

Abstract

Inherited retinal diseases (IRDs) are often associated with variable clinical expressivity (VE) and incomplete penetrance (IP). Underlying mechanisms may include environmental, epigenetic, and genetic factors. Cis-acting expression quantitative trait loci (cis-eQTLs) can be implicated in the regulation of genes by [...] Read more.

Inherited retinal diseases (IRDs) are often associated with variable clinical expressivity (VE) and incomplete penetrance (IP). Underlying mechanisms may include environmental, epigenetic, and genetic factors. Cis-acting expression quantitative trait loci (cis-eQTLs) can be implicated in the regulation of genes by favoring or hampering the expression of one allele over the other. Thus, the presence of such loci elicits allelic expression imbalance (AEI) that can be traced by massive parallel sequencing techniques. In this study, we performed an AEI analysis on RNA-sequencing (RNA-seq) data, from 52 healthy retina donors, that identified 194 imbalanced single nucleotide polymorphisms(SNPs) in 67 IRD genes. Focusing on SNPs displaying AEI at a frequency higher than 10%, we found evidence of AEI in several IRD genes regularly associated with IP and VE (BEST1, RP1, PROM1, and PRPH2). Based on these SNPs commonly undergoing AEI, we performed pyrosequencing in an independent sample set of 17 healthy retina donors in order to confirm our findings. Indeed, we were able to validate CDHR1, BEST1, and PROM1 to be subjected to cis-acting regulation. With this work, we aim to shed light on differentially expressed alleles in the human retina transcriptome that, in the context of autosomal dominant IRD cases, could help to explain IP or VE. Full article

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

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11 pages, 2109 KiB

Open AccessBrief Report

Genome-Wide Identification and Analysis of MAPK and MAPKK Gene Families in Bread Wheat (Triticum aestivum L.)

by Haoshuang Zhan^1,†, Hong Yue^1,†, Xian Zhao¹, Meng Wang¹, Weining Song^1,2 and Xiaojun Nie^1,*

¹ State Key Laboratory of Crop Stress Biology in Arid Areas, College of Agronomy and Yangling Branch of China Wheat Improvement Center, Northwest A&F University, Yangling 712100, China

² Australia-China Joint Research Centre for Abiotic and Biotic Stress Management in Agriculture, Horticulture and Forestry, Yangling 712100, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 284; https://doi.org/10.3390/genes8100284 - 20 Oct 2017

Cited by 45 | Viewed by 6433

Abstract

The mitogen-activated protein kinase (MAPK) cascade is a universal signal transduction module that plays a vital role in regulating growth and development, as well as environmental stress responses in plants. Wheat is one of the most important crops worldwide. Although the MAPK kinase [...] Read more.

The mitogen-activated protein kinase (MAPK) cascade is a universal signal transduction module that plays a vital role in regulating growth and development, as well as environmental stress responses in plants. Wheat is one of the most important crops worldwide. Although the MAPK kinase kinase (MAP3K) family in wheat has been investigated, the MAPK and MAPK kinase (MAP2K) gene families remain unknown at present. Here, 54 MAPK and 18 MAPKK genes were identified in wheat using recent genomic information. Phylogenetic analysis of Triticum aestivum L. MAPKs and MAPKKs (TaMAPKs and TaMAPKKs) together with homologous genes from other species classified them into four groups, and the clustering was consistent with the genomic exon/intron structures. Conserved motif analysis found that MAPK proteins contained a typical TXY phosphorylation site and MAPKK proteins contained an S/T-X5-S/T motif. RNA-seq data mapping analysis showed that MAPK and MAPKK genes in group IV had tissue-specific expression profiles, whereas each group I member showed relatively high expression in all organs. Expression patterns of TaMAPK and TaMAPKK genes under stress conditions were also investigated and stress-responsive candidates were identified. Co-expression network analysis identified 11 TaMAPK genes and 6 TaMAPKK genes involved in the interaction network pathway. Overall, this study provided useful information for evolutionary and functional surveys of MAPK and MAPKK gene families in wheat and beyond. Full article

(This article belongs to the Special Issue Evolution and Biodiversity of the Plant Genome Architecture)

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8 pages, 1322 KiB

Open AccessCommunication

Novel Tetra-Primer ARMS-PCR Assays for Thiopurine Intolerance Susceptibility Mutations NUDT15 c.415C>T and TPMT c.719A>G (TPMT*3C) in East Asians

by Chi-Chun Ho^†, Wai-Ying Fong^†, Yuen-Hon Lee and Wing-Tat Poon^*

¹ Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 285; https://doi.org/10.3390/genes8100285 - 23 Oct 2017

Cited by 9 | Viewed by 5981

Abstract

Thiopurines are clinically useful in the management of diverse immunological and malignant conditions. Nevertheless, these purine analogues can cause lethal myelosuppression, which may be prevented by prospective testing for variants in the thiopurine S-methyltransferase (TPMT) and, in East Asians, Nudix hydrolase [...] Read more.

Thiopurines are clinically useful in the management of diverse immunological and malignant conditions. Nevertheless, these purine analogues can cause lethal myelosuppression, which may be prevented by prospective testing for variants in the thiopurine S-methyltransferase (TPMT) and, in East Asians, Nudix hydrolase 15 (NUDT15) genes. Two single-tube, tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) assays were developed to genotype the common loss-of-function variants NUDT15 c.415C>T (rs116855232) and TPMT*3C c.719A>G (rs1142345). In a group of 60 unselected patients, one and seven were found to be homozygous and heterozygous, respectively, for NUDT15 c.415C>T; one was found to be heterozygous for TPMT*3C c.719A>G. There was no non-specific amplification, and the genotypes were 100% concordant with Sanger sequencing. Limit-of-detection for both assays was below 1 ng of heterozygous template per reaction. Time- and cost-effective ARMS-PCR assays, suitable for genotyping East-Asian patients for thiopurine intolerance, were successfully developed and validated. Full article

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

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2 pages, 333 KiB

Open AccessCorrection

Correction: Gustafson et al., Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree. Genes 2017, 8, 210

by Kevin Gustafson¹, Jacque L. Duncan^1,*

, Pooja Biswas^2,3, Angel Soto-Hermida³, Hiroko Matsui⁴, David Jakubosky⁴, John Suk³, Amalio Telenti⁵, Kelly A. Frazer^4,6

and Radha Ayyagari³

¹ Ophthalmology, University of California, San Francisco, San Francisco, CA 94143-0730, USA

² REVA University, Bengaluru, Karnataka 560034, India

³ Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093-0946, USA

⁴ Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA

⁵ Human Longevity, Inc., San Diego, CA 92121, USA

⁶ Department of Pediatrics, Rady Children’s Hospital, Division of Genome Information Sciences, San Diego, CA 92093, USA

Genes 2017, 8(10), 286; https://doi.org/10.3390/genes8100286 - 23 Oct 2017

Cited by 3 | Viewed by 4050

Abstract

Following publication of our article [1], we identified discrepancies between the pedigree shown in Figure 1 and the rest of the text.[...] Full article

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

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17 pages, 1076 KiB

Open AccessArticle

The Transcriptomes of Xiphinema index and Longidorus elongatus Suggest Independent Acquisition of Some Plant Parasitism Genes by Horizontal Gene Transfer in Early-Branching Nematodes

by Etienne G.J. Danchin¹, Laetitia Perfus-Barbeoch^1,†, Corinne Rancurel^1,†, Peter Thorpe^2,†, Martine Da Rocha¹, Simon Bajew², Roy Neilson³, Elena Sokolova (Guzeeva)^2,4, Corinne Da Silva⁵, Julie Guy⁵, Karine Labadie⁵, Daniel Esmenjaud¹, Johannes Helder⁶, John T. Jones^2,7 and Sebastian Eves-van Den Akker^8,9,*

¹ INRA, Université Côte d’Azur, CNRS, ISA, 06903, Sophia Antipolis Cedex, France

² Cell and Molecular Sciences Group, Dundee Effector Consortium, James Hutton Institute, Invergowrie, Dundee DD2 5DA, UK

³ Ecological Sciences Group, IPM@Hutton, James Hutton Institute, Invergowrie, Dundee DD2 5DA, UK

⁴ Centre of Parasitology of the A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Leninskii Prospect 33, Moscow 119071, Russia

⁵ Commissariat à l’Energie Atomique (CEA), Institut de Génomique (IG), Genoscope, 92057, Evry, France

⁶ Laboratory of Nematology, Department of Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands

⁷ School of Biology, University of St Andrews, North Haugh, St Andrews KY16 9TZ, UK

⁸ Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK

⁹ School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK

^† These authors contributed equally to this work.

Genes 2017, 8(10), 287; https://doi.org/10.3390/genes8100287 - 23 Oct 2017

Cited by 16 | Viewed by 8376

Abstract

Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall [...] Read more.

Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall degrading enzymes from bacteria and fungi has been implicated in the evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq) to generate reference transcriptomes for two economically important nematode species, Xiphinema index and Longidorus elongatus, representative of two genera within the early-branching Clade 2 of the phylum Nematoda. We used a transcriptome-wide analysis to identify putative horizontal gene transfer events. This represents the first in-depth transcriptome analysis from any plant-parasitic nematode of this clade. For each species, we assembled ~30 million Illumina reads into a reference transcriptome. We identified 62 and 104 transcripts, from X. index and L. elongatus, respectively, that were putatively acquired via horizontal gene transfer. By cross-referencing horizontal gene transfer prediction with a phylum-wide analysis of Pfam domains, we identified Clade 2-specific events. Of these, a GH12 cellulase from X. index was analysed phylogenetically and biochemically, revealing a likely bacterial origin and canonical enzymatic function. Horizontal gene transfer was previously shown to be a phenomenon that has contributed to the evolution of plant parasitism among nematodes. Our findings underline the importance and the extensiveness of this phenomenon in the evolution of plant-parasitic life styles in this speciose and widespread animal phylum. Full article

(This article belongs to the Special Issue Horizontal Gene Transfer)

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24 pages, 23136 KiB

Open AccessArticle

Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor Genes in Brassica napus

by Yan Zhou^1,2,†, Daixiang Xu^1,2,†, Ledong Jia^1,2, Xiaohu Huang^1,2, Guoqiang Ma^1,2, Shuxian Wang^1,2, Meichen Zhu^1,2, Aoxiang Zhang^1,2, Mingwei Guan^1,2, Kun Lu^1,2

, Xinfu Xu^1,2, Rui Wang^1,2, Jiana Li^1,2,* and Cunmin Qu^1,2,*

¹ Chongqing Rapeseed Engineering Research Center, College of Agronomy and Biotechnology, Southwest University, Chongqing 400716, China

² Academy of Agricultural Sciences, Southwest University, Chongqing 400716, China

^† These authors contributed equally to this work.

Genes 2017, 8(10), 288; https://doi.org/10.3390/genes8100288 - 24 Oct 2017

Cited by 76 | Viewed by 6926

Abstract

The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed (Brassica napus). In this study, we identified 247 [...] Read more.

The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed (Brassica napus). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B. napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B. napus and its parental lines and for molecular breeding studies of bZIP genes in B. napus. Full article

(This article belongs to the Special Issue Estimating Phylogenies from Large Genomic Datasets)

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10 pages, 1715 KiB

Open AccessArticle

Identification of Gene Expression Changes in the Aorta of ApoE Null Mice Fed a High-Fat Diet

by Dan Xi¹, Jinzhen Zhao¹, Miao Zhao², Weijun Fu¹, Zhigang Guo³ and Hui Chen^1,*

¹ Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, No. 1023, South Shatai Road, Baiyun District, Guangzhou 510515, China

² College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

³ Department of Cardiology, Huqiao Medical Center, Nanfang Hospital, Southern Medical University, No. 1023, South Shatai Road, Baiyun District, Guangzhou 510515, China

Genes 2017, 8(10), 289; https://doi.org/10.3390/genes8100289 - 24 Oct 2017

Cited by 5 | Viewed by 5042

Abstract

Atherosclerosis is a chronic multifactorial inflammatory disease with high worldwide prevalence, and has become the leading cause of death. In the present study, we analyzed global gene expression changes in the aorta of Apolipoprotein E (ApoE) null mice fed a high-fat diet by [...] Read more.

Atherosclerosis is a chronic multifactorial inflammatory disease with high worldwide prevalence, and has become the leading cause of death. In the present study, we analyzed global gene expression changes in the aorta of Apolipoprotein E (ApoE) null mice fed a high-fat diet by using RNA-seq. We identified a total of 280 differentially expressed genes, of which 163 genes were upregulated and 117 genes were downregulated by high-fat diet compared with normal diet. Functional clustering and gene network analysis revealed that fatty acid metabolic process is crucial for atherosclerosis. By examining of the promoter regions of differentially expressed genes, we identified four causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have anti-atherosclerotic effects due to their ability to reverse gene expression during atherosclerosis. Our study provides a valuable resource for in-depth understanding of the mechanism underlying atherosclerosis. Full article

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