Genes

18 pages, 1885 KiB

Open AccessArticle

Mixing Genetically and Morphologically Distinct Populations in Translocations: Asymmetrical Introgression in A Newly Established Population of the Boodie (Bettongia lesueur)

by Rujiporn Thavornkanlapachai, Harriet R. Mills, Kym Ottewell, Judy Dunlop, Colleen Sims, Keith Morris, Felicity Donaldson and W. Jason Kennington

Genes 2019, 10(9), 729; https://doi.org/10.3390/genes10090729 - 19 Sep 2019

Cited by 21 | Viewed by 3211

Abstract

The use of multiple source populations provides a way to maximise genetic variation and reduce the impacts of inbreeding depression in newly established translocated populations. However, there is a risk that individuals from different source populations will not interbreed, leading to population structure [...] Read more.

The use of multiple source populations provides a way to maximise genetic variation and reduce the impacts of inbreeding depression in newly established translocated populations. However, there is a risk that individuals from different source populations will not interbreed, leading to population structure and smaller effective population sizes than expected. Here, we investigate the genetic consequences of mixing two isolated, morphologically distinct island populations of boodies (Bettongia lesueur) in a translocation to mainland Australia over three generations. Using 18 microsatellite loci and the mitochondrial D-loop region, we monitored the released animals and their offspring between 2010 and 2013. Despite high levels of divergence between the two source populations (F_ST = 0.42 and ϕ_ST = 0.72), there was clear evidence of interbreeding between animals from different populations. However, interbreeding was non-random, with a significant bias towards crosses between the genetically smaller-sized Barrow Island males and the larger-sized Dorre Island females. This pattern of introgression was opposite to the expectation that male–male competition or female mate choice would favour larger males. This study shows how mixing diverged populations can bolster genetic variation in newly established mammal populations, but the ultimate outcome can be difficult to predict, highlighting the need for continued genetic monitoring to assess the long-term impacts of admixture. Full article

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

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16 pages, 3798 KiB

Open AccessArticle

Hepatic Transcriptomics Reveals that Lipogenesis Is a Key Signaling Pathway in Isocitrate Dehydrogenase 2 Deficient Mice

by Jeong Hoon Pan, Jingsi Tang, Mersady C. Redding, Kaleigh E. Beane, Cara L. Conner, Yun Jeong Cho, Jiangchao Zhao, Jun Ho Kim, Byungwhi C. Kong, Jin Hyup Lee and Jae Kyeom Kim

Genes 2019, 10(9), 728; https://doi.org/10.3390/genes10090728 - 19 Sep 2019

Cited by 1 | Viewed by 3098

Abstract

Mitochondrial nicotinamide adenine dinucleotide phosphate (NADP⁺)-dependent isocitrate dehydrogenase (IDH2) plays a key role in the intermediary metabolism and energy production via catalysing oxidative decarboxylation of isocitrate to α-ketoglutarate in the tricarboxylic acid (TCA) cycle. Despite studies reporting potential interlinks between IDH2 [...] Read more.

Mitochondrial nicotinamide adenine dinucleotide phosphate (NADP⁺)-dependent isocitrate dehydrogenase (IDH2) plays a key role in the intermediary metabolism and energy production via catalysing oxidative decarboxylation of isocitrate to α-ketoglutarate in the tricarboxylic acid (TCA) cycle. Despite studies reporting potential interlinks between IDH2 and various diseases, there is lack of effort to comprehensively characterize signature(s) of IDH2 knockout (IDH2 KO) mice. A total of 6583 transcripts were identified from both wild-type (WT) and IDH2 KO mice liver tissues. Afterwards, 167 differentially expressed genes in the IDH2 KO group were short-listed compared to the WT group based on our criteria. The online bioinformatic analyses indicated that lipid metabolism is the most significantly influenced metabolic process in IDH2 KO mice. Moreover, the TR/RXR activation pathway was predicted as the top canonical pathway significantly affected by IDH2 KO. The key transcripts found in the bioinformatic analyses were validated by qPCR analysis, corresponding to the transcriptomics results. Further, an additional qPCR analysis confirmed that IDH2 KO caused a decrease in hepatic de novo lipogenesis via the activation of the fatty acid β-oxidation process. Our unbiased transcriptomics approach and validation experiments suggested that IDH2 might play a key role in homeostasis of lipid metabolism. Full article

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13 pages, 1854 KiB

Open AccessArticle

Forming Big Datasets through Latent Class Concatenation of Imperfectly Matched Databases Features

by Christopher W. Bartlett, Brett G. Klamer, Steven Buyske, Stephen A. Petrill and William C. Ray

Genes 2019, 10(9), 727; https://doi.org/10.3390/genes10090727 - 19 Sep 2019

Cited by 2 | Viewed by 2545

Abstract

Informatics researchers often need to combine data from many different sources to increase statistical power and study subtle or complicated effects. Perfect overlap of measurements across academic studies is rare since virtually every dataset is collected for a unique purpose and without coordination [...] Read more.

Informatics researchers often need to combine data from many different sources to increase statistical power and study subtle or complicated effects. Perfect overlap of measurements across academic studies is rare since virtually every dataset is collected for a unique purpose and without coordination across parties not-at-hand (i.e., informatics researchers in the future). Thus, incomplete concordance of measurements across datasets poses a major challenge for researchers seeking to combine public databases. In any given field, some measurements are fairly standard, but every organization collecting data makes unique decisions on instruments, protocols, and methods of processing the data. This typically denies literal concatenation of the raw data since constituent cohorts do not have the same measurements (i.e., columns of data). When measurements across datasets are similar prima facie, there is a desire to combine the data to increase power, but mixing non-identical measurements could greatly reduce the sensitivity of the downstream analysis. Here, we discuss a statistical method that is applicable when certain patterns of missing data are found; namely, it is possible to combine datasets that measure the same underlying constructs (or latent traits) when there is only partial overlap of measurements across the constituent datasets. Our method, ROSETTA empirically derives a set of common latent trait metrics for each related measurement domain using a novel variation of factor analysis to ensure equivalence across the constituent datasets. The advantage of combining datasets this way is the simplicity, statistical power, and modeling flexibility of a single joint analysis of all the data. Three simulation studies show the performance of ROSETTA on datasets with only partially overlapping measurements (i.e., systematically missing information), benchmarked to a condition of perfectly overlapped data (i.e., full information). The first study examined a range of correlations, while the second study was modeled after the observed correlations in a well-characterized clinical, behavioral cohort. Both studies consistently show significant correlations >0.94, often >0.96, indicating the robustness of the method and validating the general approach. The third study varied within and between domain correlations and compared ROSETTA to multiple imputation and meta-analysis as two commonly used methods that ostensibly solve the same data integration problem. We provide one alternative to meta-analysis and multiple imputation by developing a method that statistically equates similar but distinct manifest metrics into a set of empirically derived metrics that can be used for analysis across all datasets. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Intelligent Biology and Medicine (ICIBM 2019))

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16 pages, 3744 KiB

Open AccessArticle

Heterologous Expression of GbTCP4, a Class II TCP Transcription Factor, Regulates Trichome Formation and Root Hair Development in Arabidopsis

by Yi Wang, Yuehua Yu, Quanjia Chen, Guanghong Bai, Wenwei Gao, Yanying Qu and Zhiyong Ni

Genes 2019, 10(9), 726; https://doi.org/10.3390/genes10090726 - 19 Sep 2019

Cited by 11 | Viewed by 3355

Abstract

Two class I family teosinte branched1/cycloidea/proliferating cell factor1 (TCP) proteins from allotetraploid cotton are involved in cotton fiber cell differentiation and elongation and root hair development. However, the biological function of most class II TCP proteins is unclear. This study sought to reveal [...] Read more.

Two class I family teosinte branched1/cycloidea/proliferating cell factor1 (TCP) proteins from allotetraploid cotton are involved in cotton fiber cell differentiation and elongation and root hair development. However, the biological function of most class II TCP proteins is unclear. This study sought to reveal the characteristics and functions of the sea-island cotton class II TCP gene GbTCP4 by biochemical, genetic, and molecular biology methods. GbTCP4 protein localizes to nuclei, binding two types of TCP-binding cis-acting elements, including the one in its promoter. Expression pattern analysis revealed that GbTCP4 is widely expressed in tissues, with the highest level in flowers. GbTCP4 is expressed at different fiber development stages and has high transcription in fibers beginning at 5 days post anthesis (DPA). GbTCP4 overexpression increases primary root hair length and density and leaf and stem trichomes in transgenic Arabidopsis relative to wild-type plants (WT). GbTCP4 binds directly to the CAPRICE (CPC) promoter, increasing CPC transcript levels in roots and reducing them in leaves. Compared with WT plants, lignin content in the stems of transgenic Arabidopsis overexpressing GbTCP4 increased, and AtCAD5 gene transcript levels increased. These results suggest that GbTCP4 regulates trichome formation and root hair development in Arabidopsis and may be a candidate gene for regulating cotton fiber elongation. Full article

(This article belongs to the Special Issue Novel Insights into the Genetics of Root Development (2019))

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15 pages, 3771 KiB

Open AccessArticle

A Transcriptome Analysis Identifies Biological Pathways and Candidate Genes for Feed Efficiency in DLY Pigs

by Xingwang Wang, Shaoyun Li, Jie Wu, Rongrong Ding, Jianping Quan, Enqin Zheng, Jie Yang and Zhenfang Wu

Genes 2019, 10(9), 725; https://doi.org/10.3390/genes10090725 - 18 Sep 2019

Cited by 7 | Viewed by 3912

Abstract

Feed cost accounts for approximately 65–75% of overall commercial pork production costs. Therefore, improving the feed efficiency of pig production is important. In this study, 12 individuals with either extremely high (HE) or low (LE) feed efficiency were selected from 225 Duroc × [...] Read more.

Feed cost accounts for approximately 65–75% of overall commercial pork production costs. Therefore, improving the feed efficiency of pig production is important. In this study, 12 individuals with either extremely high (HE) or low (LE) feed efficiency were selected from 225 Duroc × (Landrace × Yorkshire) (DLY) pigs. After the pigs were slaughtered, we collected small intestine mucosal tissue. Next, RNA sequencing (RNA-seq) analysis was used to reveal the presence and quantity of genes expressed between these extremely HE- and LE-groups. We found 433 significantly differentially expressed genes (DEGs) between the HE- and LE-groups. Of these, 389 and 44 DEGs were upregulated and downregulated in the HE-group, respectively. An enrichment analysis showed that the DEGs were mainly enriched in functions related to apical plasma membrane composition, transporter activity, transport process and hormone regulation of digestion and absorption. Protein network interaction and gene function analyses revealed that SLC2A2 was an important candidate gene for FE in pigs, which may give us a deeper understanding of the mechanism of feed efficiency. Furthermore, some significant DEGs identified in the current study could be incorporated into artificial selection programs for increased feeding efficiency in pigs. Full article

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14 pages, 2845 KiB

Open AccessArticle

Characterization of the Complete Mitochondrial Genome of Harpalus sinicus and Its Implications for Phylogenetic Analyses

by Xiaolei Yu, Wei Tan, Huanyu Zhang, Weiling Jiang, Han Gao, Wenxiu Wang, Yuxia Liu, Yu Wang and Xiaoxuan Tian

Genes 2019, 10(9), 724; https://doi.org/10.3390/genes10090724 - 18 Sep 2019

Cited by 14 | Viewed by 3986

Abstract

In this study, we report the complete mitochondrial genome of Harpalus sinicus (occasionally named as the Chinese ground beetle) which is the first mitochondrial genome for Harpalus. The mitogenome is 16,521 bp in length, comprising 37 genes, and a control region. The [...] Read more.

In this study, we report the complete mitochondrial genome of Harpalus sinicus (occasionally named as the Chinese ground beetle) which is the first mitochondrial genome for Harpalus. The mitogenome is 16,521 bp in length, comprising 37 genes, and a control region. The A + T content of the mitogenome is as high as 80.6%. A mitochondrial origins of light-strand replication (OL)-like region is found firstly in the insect mitogenome, which can form a stem-loop hairpin structure. Thirteen protein-coding genes (PCGs) share high homology, and all of them are under purifying selection. All tRNA genes (tRNAs) can be folded into the classic cloverleaf secondary structures except tRNA-Ser (GCU), which lacks a dihydrouridine (DHU) stem. The secondary structure of two ribosomal RNA genes (rRNAs) is predicted based on previous insect models. Twelve types of tandem repeats and two stem-loop structures are detected in the control region, and two stem-loop structures may be involved in the initiation of replication and transcription. Additionally, phylogenetic analyses based on mitogenomes suggest that Harpalus is an independent lineage in Carabidae, and is closely related to four genera (Abax, Amara, Stomis, and Pterostichus). In general, this study provides meaningful genetic information for Harpalus sinicus and new insights into the phylogenetic relationships within the Carabidae. Full article

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

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20 pages, 356 KiB

Open AccessReview

Thyroid Cancer in the Pediatric Population

by Vera A. Paulson, Erin R. Rudzinski and Douglas S. Hawkins

Genes 2019, 10(9), 723; https://doi.org/10.3390/genes10090723 - 18 Sep 2019

Cited by 137 | Viewed by 9610

Abstract

Thyroid cancer is rare in the pediatric population, but thyroid carcinomas occurring in children carry a unique set of clinical, pathologic, and molecular characteristics. In comparison to adults, children more often present with aggressive, advanced stage disease. This is at least in part [...] Read more.

Thyroid cancer is rare in the pediatric population, but thyroid carcinomas occurring in children carry a unique set of clinical, pathologic, and molecular characteristics. In comparison to adults, children more often present with aggressive, advanced stage disease. This is at least in part due to the underlying biologic and molecular differences between pediatric and adult thyroid cancer. Specifically, papillary thyroid carcinoma (which accounts for approximately 90% of pediatric thyroid cancer) has a high rate of gene fusions which influence the histologic subtypes encountered in pediatric thyroid tumors, are associated with more extensive extrathyroidal disease, and offer unique options for targeted medical therapies. Differences are also seen in pediatric follicular thyroid cancer, although there are few studies of non-papillary pediatric thyroid tumors published in the literature due to their rarity, and in medullary carcinoma, which is most frequently diagnosed in the pediatric population in the setting of prophylactic thyroidectomies for known multiple endocrine neoplasia syndromes. The overall shift in the spectrum of histotypes and underlying molecular alterations common in pediatric thyroid cancer is important to recognize as it may directly influence diagnostic test selection and therapeutic recommendations. Full article

(This article belongs to the Special Issue Thyroid Cancer: Genetics and Targeted Therapies)

14 pages, 2794 KiB

Open AccessArticle

The Expanded SWEET Gene Family Following Whole Genome Triplication in Brassica rapa

by Yanping Wei, Dong Xiao, Changwei Zhang and Xilin Hou

Genes 2019, 10(9), 722; https://doi.org/10.3390/genes10090722 - 18 Sep 2019

Cited by 16 | Viewed by 4010

Abstract

The SWEET family, which includes transcripts of a cohort of plant hexose and sucrose transporters, is considered key to improving crop stress tolerance and yield through its role in manipulating the carbohydrate partitioning process. The functions and regulatory roles of this gene family [...] Read more.

The SWEET family, which includes transcripts of a cohort of plant hexose and sucrose transporters, is considered key to improving crop stress tolerance and yield through its role in manipulating the carbohydrate partitioning process. The functions and regulatory roles of this gene family are variable among different species; thus, to determine these roles, more species-specific information is needed. Brassica rapa displays complicated regulation after a whole-genome triplication (WGT) event, which provides enormous advantages for use in genetic studies, thus it is an ideal model for exploring the functional and regulatory roles of SWEETs from a genetic perspective. In this study, the results of a homology search and phylogenetic relationship analysis revealed the evolutionary footprint of SWEETs among different plant taxa, which showed that plant SWEETs may have originated from Clade II and then expanded from vascular plants. The amino acid sequence characteristics and an analysis of the exon-intron structure of BrSWEETs duplicates clarified that SWEETs retention occurred after a WGT event in B. rapa. An analysis of the transcriptional levels of BrSWEETs in different tissues identified the expression differences among duplicated co-orthologs. In addition, qRT-PCR indicated that the BrSWEETs’ co-orthologs were varied in their stress responses. This study greatly enriches our knowledge of SWEETs in the B. rapa species, which will contribute to future studies on the Brassica-specific regulatory pathways and to creating genetic innovations. Full article

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

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13 pages, 579 KiB

Open AccessArticle

Detection of Differentially Methylated Regions Using Bayes Factor for Ordinal Group Responses

by Fengjiao Dunbar, Hongyan Xu, Duchwan Ryu, Santu Ghosh, Huidong Shi and Varghese George

Genes 2019, 10(9), 721; https://doi.org/10.3390/genes10090721 - 17 Sep 2019

Cited by 2 | Viewed by 2519

Abstract

Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation, because they play an important role in regulating gene expression without changes in the DNA sequence. There have been significant advances in developing statistical methods to detect differentially methylated regions [...] Read more.

Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation, because they play an important role in regulating gene expression without changes in the DNA sequence. There have been significant advances in developing statistical methods to detect differentially methylated regions (DMRs) associated with binary disease status. Most of these methods are being developed for detecting differential methylation rates between cases and controls. We consider multiple severity levels of disease, and develop a Bayesian statistical method to detect the region with increasing (or decreasing) methylation rates as the disease severity increases. Patients are classified into more than two groups, based on the disease severity (e.g., stages of cancer), and DMRs are detected by using moving windows along the genome. Within each window, the Bayes factor is calculated to test the hypothesis of monotonic increase in methylation rates corresponding to severity of the disease versus no difference. A mixed-effect model is used to incorporate the correlation of methylation rates of nearby CpG sites in the region. Results from extensive simulation indicate that our proposed method is statistically valid and reasonably powerful. We demonstrate our approach on a bisulfite sequencing dataset from a chronic lymphocytic leukemia (CLL) study. Full article

(This article belongs to the Special Issue Statistical Methods for the Analysis of Genomic Data)

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40 pages, 1003 KiB

Open AccessReview

Physical Activity and Brain Health

by Carlo Maria Di Liegro, Gabriella Schiera, Patrizia Proia and Italia Di Liegro

Genes 2019, 10(9), 720; https://doi.org/10.3390/genes10090720 - 17 Sep 2019

Cited by 157 | Viewed by 40679

Abstract

Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It [...] Read more.

Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It has been also acknowledged that lifestyle and diet can induce epigenetic modifications which modify chromatin structure and gene expression, thus causing even heritable metabolic outcomes. Many studies have shown that PA can reverse at least some of the unwanted effects of sedentary lifestyle, and can also contribute in delaying brain aging and degenerative pathologies such as Alzheimer’s Disease, diabetes, and multiple sclerosis. Most importantly, PA improves cognitive processes and memory, has analgesic and antidepressant effects, and even induces a sense of wellbeing, giving strength to the ancient principle of “mens sana in corpore sano” (i.e., a sound mind in a sound body). In this review we will discuss the potential mechanisms underlying the effects of PA on brain health, focusing on hormones, neurotrophins, and neurotransmitters, the release of which is modulated by PA, as well as on the intra- and extra-cellular pathways that regulate the expression of some of the genes involved. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise)

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16 pages, 3614 KiB

Open AccessCommunication

WGCNA Analysis of Salt-Responsive Core Transcriptome Identifies Novel Hub Genes in Rice

by Mingdong Zhu, Hongjun Xie, Xiangjin Wei, Komivi Dossa, Yaying Yu, Suozhen Hui, Guohua Tang, Xiaoshan Zeng, Yinghong Yu, Peisong Hu and Jianlong Wang

Genes 2019, 10(9), 719; https://doi.org/10.3390/genes10090719 - 17 Sep 2019

Cited by 56 | Viewed by 8927

Abstract

Rice, being a major staple food crop and sensitive to salinity conditions, bears heavy yield losses due to saline soil. Although some salt responsive genes have been identified in rice, their applications in developing salt tolerant cultivars have resulted in limited achievements. Herein, [...] Read more.

Rice, being a major staple food crop and sensitive to salinity conditions, bears heavy yield losses due to saline soil. Although some salt responsive genes have been identified in rice, their applications in developing salt tolerant cultivars have resulted in limited achievements. Herein, we used bioinformatic approaches to perform a meta-analysis of three transcriptome datasets from salinity and control conditions in order to reveal novel genes and the molecular pathways underlying rice response to salt. From a total of 28,432 expressed genes, we identify 457 core differentially expressed genes (DEGs) constitutively responding to salt, regardless of the stress duration, genotype, or the tissue. Gene co-expression analysis divided the core DEGs into three different modules, each of them contributing to salt response in a unique metabolic pathway. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted key biological processes and metabolic pathways involved in the salt response. We identified important novel hub genes encoding proteins of different families including CAM, DUF630/632, DUF581, CHL27, PP2-13, LEA4-5, and transcription factors, which could be functionally characterized using reverse genetic experiments. This novel repertoire of candidate genes related to salt response in rice will be useful for engineering salt tolerant varieties. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Current Challenges and Perspectives)

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17 pages, 2811 KiB

Open AccessArticle

Allele-Specific Expression of CD4⁺ T Cells in Response to Marek’s Disease Virus Infection

by Hao Bai, Yanghua He, Yi Ding, José A. Carrillo, Ramesh K. Selvaraj, Huanmin Zhang, Jilan Chen and Jiuzhou Song

Genes 2019, 10(9), 718; https://doi.org/10.3390/genes10090718 - 17 Sep 2019

Cited by 4 | Viewed by 3874

Abstract

Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens. MD is a chronic infectious disease that threatens the poultry industry. However, the mechanisms of genetic resistance for MD are [...] Read more.

Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens. MD is a chronic infectious disease that threatens the poultry industry. However, the mechanisms of genetic resistance for MD are complex and not completely understood. In this study, to identify high-confidence candidate genes of MD genetic resistance, high throughput sequencing (RNA-seq) was used to obtain transcriptomic data of CD4⁺ T cells isolated from MDV-infected and non-infected groups of two reciprocal crosses of individuals mating by two highly inbred chicken lines (6₃ MD-resistant and 7₂ MD-susceptible). After RNA-seq analysis with two biological replicates in each group, we identified 61 and 123 single nucleotide polymorphisms (SNPs) (false discovery rate (FDR) < 0.05) annotated in 39 and 132 genes in intercrosses 6₃ × 7₂ and 7₂ × 6₃, respectively, which exhibited allele-specific expression (ASE) in response to MDV infection. Similarly, we identified 62 and 79 SNPs annotated in 66 and 96 genes in infected and non-infected groups, respectively. We identified 534 and 1543 differentially expressed genes (DEGs) (FDR < 0.05) related to MDV infection in intercrosses 6₃ × 7₂ and 7₂ × 6₃, respectively. We also identified 328 and 20 DEGs in infected and non-infected groups, respectively. The qRT-PCR using seven DEGs further verified our results of RNA-seq analysis. The qRT-PCR of 11 important ASE genes was performed for gene functional validation in CD4⁺ T cells and tumors. Combining the analyses, six genes (MCL1, SLC43A2, PDE3B, ADAM33, BLB1, and DMB2), especially MCL1, were highlighted as the candidate genes with the potential to be involved in MDV infection. Gene-set enrichment analysis revealed that many ASE genes are linked to T cell activation, T cell receptor (TCR), B cell receptor (BCR), ERK/MAPK, and PI3K/AKT-mTOR signaling pathways, which play potentially important roles in MDV infection. Our approach underlines the importance of comprehensive functional studies for gaining valuable biological insight into the genetic factors behind MD and other complex traits, and our findings provide additional insights into the mechanisms of MD and disease resistance breeding in poultry. Full article

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

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24 pages, 5022 KiB

Open AccessReview

Advances of Molecular Markers and Their Application for Body Variables and Carcass Traits in Qinchuan Cattle

by Sayed Haidar Abbas Raza, Rajwali Khan, Sameh A. Abdelnour, Mohamed E. Abd El-Hack, Asmaa F. Khafaga, Ayman Taha, Husein Ohran, Chugang Mei, Nicola M. Schreurs and Linsen Zan

Genes 2019, 10(9), 717; https://doi.org/10.3390/genes10090717 - 17 Sep 2019

Cited by 33 | Viewed by 6055

Abstract

This review considers the unique characteristics of Chinese cattle and intramuscular fat content (IMF) as factors influencing meat quality, including tenderness, flavor, and juiciness of meat. Due to its nutritional qualities, meat contributes to a healthy and balanced diet. The intramuscular fat content [...] Read more.

This review considers the unique characteristics of Chinese cattle and intramuscular fat content (IMF) as factors influencing meat quality, including tenderness, flavor, and juiciness of meat. Due to its nutritional qualities, meat contributes to a healthy and balanced diet. The intramuscular fat content and eating quality of beef are influenced by many factors, which can generally be divided into on-farm and pre-slaughter factors (breed, sex of cattle, age at slaughter, housing system, diet, and pre-slaughter handling) and postmortem factors (post-slaughter processing, chilling temperature, and packaging). Meat quality traits can also be influenced by the individual genetic background of the animal. Worldwide, the function of genes and genetic polymorphisms that have potential effects on fattening of cattle and beef quality have been investigated. The use of DNA markers is recognized as a powerful and efficient approach to achieve genetic gain for desirable phenotypic characteristics, which is helpful for economic growth. The polymorphisms of the SIRT4, SIRT6, SIRT7, CRTC3, ABHD5, KLF6, H-FABP, and ELOVL6 genes for body and growth characteristics of cattle, and also for beef quality, are considered with the aim of highlighting the significance of beef intramuscular fat content, and that growth, body, and meat quality characteristics are polygenically regulated. Full article

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

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17 pages, 1860 KiB

Open AccessArticle

Expression of ZNF695 Transcript Variants in Childhood B-Cell Acute Lymphoblastic Leukemia

by Ricardo De la Rosa, Vanessa Villegas-Ruíz, Marcela Concepción Caballero-Palacios, Eleazar Israel Pérez-López, Chiharu Murata, Martha Zapata-Tarres, Rocio Cárdenas-Cardos, Rogelio Paredes-Aguilera, Roberto Rivera-Luna and Sergio Juárez-Méndez

Genes 2019, 10(9), 716; https://doi.org/10.3390/genes10090716 - 16 Sep 2019

Cited by 12 | Viewed by 2935

Abstract

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been [...] Read more.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for ~2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates. Full article

(This article belongs to the Special Issue Associations Between Non-Coding RNA and Diseases)

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17 pages, 1061 KiB

Open AccessArticle

Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss

by Kenjiro Sugiyama, Hideaki Moteki, Shin-ichiro Kitajiri, Tomohiro Kitano, Shin-ya Nishio, Tomomi Yamaguchi, Keiko Wakui, Satoko Abe, Akiko Ozaki, Remi Motegi, Hirooki Matsui, Masato Teraoka, Yumiko Kobayashi, Tomoki Kosho and Shin-ichi Usami

Genes 2019, 10(9), 715; https://doi.org/10.3390/genes10090715 - 16 Sep 2019

Cited by 15 | Viewed by 4518

Abstract

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese [...] Read more.

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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18 pages, 3614 KiB

Open AccessArticle

NCBI’s Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements

by Ryan Connor, Rodney Brister, Jan P. Buchmann, Ward Deboutte, Rob Edwards, Joan Martí-Carreras, Mike Tisza, Vadim Zalunin, Juan Andrade-Martínez, Adrian Cantu, Michael D’Amour, Alexandre Efremov, Lydia Fleischmann, Laura Forero-Junco, Sanzhima Garmaeva, Melissa Giluso, Cody Glickman, Margaret Henderson, Benjamin Kellman, David Kristensen, Carl Leubsdorf, Kyle Levi, Shane Levi, Suman Pakala, Vikas Peddu, Alise Ponsero, Eldred Ribeiro, Farrah Roy, Lindsay Rutter, Surya Saha, Migun Shakya, Ryan Shean, Matthew Miller, Benjamin Tully, Christopher Turkington, Ken Youens-Clark, Bert Vanmechelen and Ben Busby Show full author list Hide full author list

Genes 2019, 10(9), 714; https://doi.org/10.3390/genes10090714 - 16 Sep 2019

Cited by 9 | Viewed by 7590

Abstract

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon [...] Read more.

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon. Full article

(This article belongs to the Special Issue Viral Diagnostics Using Next-Generation Sequencing)

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14 pages, 1453 KiB

Open AccessArticle

The Global Prader–Willi Syndrome Registry: Development, Launch, and Early Demographics

by Jessica Bohonowych, Jennifer Miller, Shawn E. McCandless and Theresa V. Strong

Genes 2019, 10(9), 713; https://doi.org/10.3390/genes10090713 - 14 Sep 2019

Cited by 36 | Viewed by 10009

Abstract

Advances in technologies offer new opportunities to collect and integrate data from a broad range of sources to advance the understanding of rare diseases and support the development of new treatments. Prader–Willi syndrome (PWS) is a rare, complex neurodevelopmental disorder, which has a [...] Read more.

Advances in technologies offer new opportunities to collect and integrate data from a broad range of sources to advance the understanding of rare diseases and support the development of new treatments. Prader–Willi syndrome (PWS) is a rare, complex neurodevelopmental disorder, which has a variable and incompletely understood natural history. PWS is characterized by early failure to thrive, followed by the onset of excessive appetite (hyperphagia). Additional characteristics include multiple endocrine abnormalities, hypotonia, hypogonadism, sleep disturbances, a challenging neurobehavioral phenotype, and cognitive disability. The Foundation for Prader–Willi Research’s Global PWS Registry is one of more than twenty-five registries developed to date through the National Organization of Rare Disorders (NORD) IAMRARE Registry Program. The Registry consists of surveys covering general medical history, system-specific clinical complications, diet, medication and supplement use, as well as behavior, mental health, and social information. Information is primarily parent/caregiver entered. The platform is flexible and allows addition of new surveys, including updatable and longitudinal surveys. Launched in 2015, the PWS Registry has enrolled 1696 participants from 37 countries, with 23,550 surveys completed. This resource can improve the understanding of PWS natural history and support medical product development for PWS. Full article

(This article belongs to the Special Issue Genetics of Prader-Willi syndrome)

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14 pages, 11404 KiB

Open AccessArticle

The Pituitary Transcriptional Response Related to Feed Conversion in Pigs

by Katarzyna Piórkowska, Kacper Żukowski, Mirosław Tyra, Magdalena Szyndler-Nędza, Karolina Szulc, Ewa Skrzypczak and Katarzyna Ropka-Molik

Genes 2019, 10(9), 712; https://doi.org/10.3390/genes10090712 - 14 Sep 2019

Cited by 6 | Viewed by 2786

Abstract

Over the decades, pig breeding objectives have focused on improving the meat content in the carcass without taking into consideration the more effective fattening indicators that affect feed conversion. At present, pig growth traits associated particularly with animal feeding have become crucial due [...] Read more.

Over the decades, pig breeding objectives have focused on improving the meat content in the carcass without taking into consideration the more effective fattening indicators that affect feed conversion. At present, pig growth traits associated particularly with animal feeding have become crucial due to their economic significance. This is especially evident in countries where pigs are maintained on large farms. The present study indicates that pituitary differentially expressed genes (DEGs) are activated in response to variable feed conversion (FC) in pigs. The experiment included two native Polish breeds: Puławska and Złotnicka White (ZW). The whole pituitary transcriptome was sequenced using next-generation sequencing (NGS) technology. The RNA-seq method identified over 500 and 300 DEGs in the pituitaries of the ZW and the Puławska pig populations, respectively, that were associated with hormonal regulation, notch signaling, and Wnt pathways. Lower FC in the ZW pigs favoured increased fat content in the body and significantly higher prolactin expression. The obtained results indicate that low FC values in pigs are related to slower growth or increased fat content, which suggests various pituitary responses. Therefore, the identified candidate genes were not directly associated with feed conversion values but with other factors. However, the present study delivers new insights into pituitary regulation in pigs. Full article

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

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12 pages, 5078 KiB

Open AccessArticle

Metallothioneins in Failure of Dental Implants and Periodontitis Down Syndrome Patients

by Maria Baus-Domínguez, Raquel Gómez-Díaz, Jose-Ramón Corcuera-Flores, Daniel Torres-Lagares, José-Cruz Ruiz-Villandiego, Guillermo Machuca-Portillo, José-Luis Gutiérrez-Pérez and María-Angeles Serrera-Figallo

Genes 2019, 10(9), 711; https://doi.org/10.3390/genes10090711 - 14 Sep 2019

Cited by 9 | Viewed by 4148

Abstract

Background: Sometimes dental implants seem to be the only therapeutic alternative for the oral rehabilitation of patients with Down syndrome, given that they usually lose all their teeth early due to suffering aggressive periodontitis and they do not usually have the skills required [...] Read more.

Background: Sometimes dental implants seem to be the only therapeutic alternative for the oral rehabilitation of patients with Down syndrome, given that they usually lose all their teeth early due to suffering aggressive periodontitis and they do not usually have the skills required to wear removable prostheses. However, the evolution of dental implants in these patients shows very adverse results. It is possible that basal genetic alterations, or at least some characteristics of these, may underlie these clinical results. The metabolic pathway of metallothioneins, molecules with an important influence on bone metabolism, could be one of the said alterations. Aims: To determine whether the expression of metallothioneins (MTs) and their metabolic pathway may be identified and related to the periodontitis and lack of osseointegration of dental implants in Down syndrome patients. Materials and Methods: Retrospective study of cases and controls by comparing patients with Down syndrome, periodontal disease, and implant failure (four patients, test group) with patients with Down syndrome, without periodontal disease, and without implant failure after two years of following (seven patients, control group), by extracting peripheral blood at the time of the dental examination to extract RNA and its subsequent processing in relation to gene expression of the metabolic pathway of metallothioneins. Results: The results identified low expression in the group of patients with periodontal disease and implant failure of genes MT1E, MT1H, MT1X, MT1A, MT1B, MT1C, MT1L, MT2A, MT1M, and MT1G. Conclusions: The low MT1 and MT2 gene expression seems to be related to the onset of periodontal disease and implant rejection in Down syndrome patients, although more data are required to confirm whether this relationship is due to one of the two conditions, to both independently, or to the two jointly—this last option being indicated by our current study. Full article

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

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22 pages, 1228 KiB

Open AccessArticle

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

by Minting Zhang, Shuhuang Lin, Xiaoling Yuan, Ziqi Lin and Zunnan Huang

Genes 2019, 10(9), 710; https://doi.org/10.3390/genes10090710 - 13 Sep 2019

Cited by 9 | Viewed by 3181

Abstract

Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case–control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This [...] Read more.

Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case–control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, p_c < 0.005) and DQB1*06 (OR = 0.604, p_c = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, p_c = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, p_c < 0.013), DRB1*04 (OR = 1.954, p_c < 0.013), and DRB1*09 (OR = 1.346, p_c < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, p_c < 0.013) and DRB1*13 (OR = 0.583, p_c < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA. Full article

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

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33 pages, 5156 KiB

Open AccessReview

Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

by Elena Tirrò, Federica Martorana, Chiara Romano, Silvia Rita Vitale, Gianmarco Motta, Sandra Di Gregorio, Michele Massimino, Maria Stella Pennisi, Stefania Stella, Adriana Puma, Fiorenza Gianì, Marco Russo, Livia Manzella and Paolo Vigneri

Genes 2019, 10(9), 709; https://doi.org/10.3390/genes10090709 - 13 Sep 2019

Cited by 65 | Viewed by 6585

Abstract

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, [...] Read more.

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer. Full article

(This article belongs to the Special Issue Thyroid Cancer: Genetics and Targeted Therapies)

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14 pages, 2824 KiB

Open AccessArticle

The First Highly Contiguous Genome Assembly of Pikeperch (Sander lucioperca), an Emerging Aquaculture Species in Europe

by Julien Alban Nguinkal, Ronald Marco Brunner, Marieke Verleih, Alexander Rebl, Lidia de los Ríos-Pérez, Nadine Schäfer, Frieder Hadlich, Marcus Stüeken, Dörte Wittenburg and Tom Goldammer

Genes 2019, 10(9), 708; https://doi.org/10.3390/genes10090708 - 13 Sep 2019

Cited by 25 | Viewed by 5769

Abstract

The pikeperch (Sander lucioperca) is a fresh and brackish water Percid fish natively inhabiting the northern hemisphere. This species is emerging as a promising candidate for intensive aquaculture production in Europe. Specific traits like cannibalism, growth rate and meat quality require [...] Read more.

The pikeperch (Sander lucioperca) is a fresh and brackish water Percid fish natively inhabiting the northern hemisphere. This species is emerging as a promising candidate for intensive aquaculture production in Europe. Specific traits like cannibalism, growth rate and meat quality require genomics based understanding, for an optimal husbandry and domestication process. Still, the aquaculture community is lacking an annotated genome sequence to facilitate genome-wide studies on pikeperch. Here, we report the first highly contiguous draft genome assembly of Sander lucioperca. In total, 413 and 66 giga base pairs of DNA sequencing raw data were generated with the Illumina platform and PacBio Sequel System, respectively. The PacBio data were assembled into a final assembly size of ~900 Mb covering 89% of the 1,014 Mb estimated genome size. The draft genome consisted of 1966 contigs ordered into 1,313 scaffolds. The contig and scaffold N50 lengths are 3.0 Mb and 4.9 Mb, respectively. The identified repetitive structures accounted for 39% of the genome. We utilized homologies to other ray-finned fishes, and ab initio gene prediction methods to predict 21,249 protein-coding genes in the Sander lucioperca genome, of which 88% were functionally annotated by either sequence homology or protein domains and signatures search. The assembled genome spans 97.6% and 96.3% of Vertebrate and Actinopterygii single-copy orthologs, respectively. The outstanding mapping rate (99.9%) of genomic PE-reads on the assembly suggests an accurate and nearly complete genome reconstruction. This draft genome sequence is the first genomic resource for this promising aquaculture species. It will provide an impetus for genomic-based breeding studies targeting phenotypic and performance traits of captive pikeperch. Full article

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

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21 pages, 3004 KiB

Open AccessArticle

Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae

by Min Jung Kwun, Marco R. Oggioni, Stephen D. Bentley, Christophe Fraser and Nicholas J. Croucher

Genes 2019, 10(9), 707; https://doi.org/10.3390/genes10090707 - 13 Sep 2019

Cited by 3 | Viewed by 3165

Abstract

A diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae cells, but many isolates remain uninfected. The best-characterised defences against horizontal transmission of MGEs are restriction-modification systems (RMSs), of which there are two phase-variable examples in S. pneumoniae. Additionally, the [...] Read more.

A diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae cells, but many isolates remain uninfected. The best-characterised defences against horizontal transmission of MGEs are restriction-modification systems (RMSs), of which there are two phase-variable examples in S. pneumoniae. Additionally, the transformation machinery has been proposed to limit vertical transmission of chromosomally integrated MGEs. This work describes how these mechanisms can act in concert. Experimental data demonstrate RMS phase variation occurs at a sub-maximal rate. Simulations suggest this may be optimal if MGEs are sometimes vertically inherited, as it reduces the probability that an infected cell will switch between RMS variants while the MGE is invading the population, and thereby undermine the restriction barrier. Such vertically inherited MGEs can be deleted by transformation. The lack of between-strain transformation hotspots at known prophage att sites suggests transformation cannot remove an MGE from a strain in which it is fixed. However, simulations confirmed that transformation was nevertheless effective at preventing the spread of MGEs into a previously uninfected cell population, if a recombination barrier existed between co-colonising strains. Further simulations combining these effects of phase variable RMSs and transformation found they synergistically inhibited MGEs spreading, through limiting both vertical and horizontal transmission. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Streptococcus pneumoniae)

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14 pages, 1721 KiB

Open AccessArticle

Transcriptional Analysis of FOXO1, C/EBP-α and PPAR-γ2 Genes and Their Association with Obesity-Related Insulin Resistance

by Hatim Boughanem, Amanda Cabrera-Mulero, Mercedes Millán-Gómez, Lourdes Garrido-Sánchez, Fernando Cardona, Francisco José Tinahones, Inmaculada Moreno-Santos and Manuel Macías-González

Genes 2019, 10(9), 706; https://doi.org/10.3390/genes10090706 - 12 Sep 2019

Cited by 25 | Viewed by 5923

Abstract

Background: Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic [...] Read more.

Background: Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic genes, such as proliferator-activated receptor γ type 2 (PPAR-γ2), CCAAT/enhancer-binding protein type α (C/EBP-α), and forkhead box protein class O type 1 (FOXO1) in VAT should shed light on their association with obesity-related insulin resistance. Methods: To test this idea, we studied the expression profile of C/EBP-α, FOXO1 and PPAR-γ2 in VAT from non-obese individuals, and low insulin (LIR-MO) and high insulin morbidly obese (HIR-MO) subjects, through a combination of RT-qPCR, co-immunoprecipitation, ELISA, Western blot analysis and EMSA assays. Results: Our results show that C/EBP-α and PPAR-γ2 were down-expressed in HIR-MO individuals, while FOXO1 was overexpressed. In addition, the PPAR-γ2–RXR-α heterodimer showed weak activity and bound weakly to the putative IGFBP-2–PPRE promoter sequence in VAT from HIR-MO subjects when compared with LIR-MO individuals. Conclusions: These results show that PPAR-γ2, C/EBP-α, FOXO1 and IGFBP-2 have a close relationship with insulin resistance in VAT of morbidly obese individuals. Full article

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11 pages, 2346 KiB

Open AccessArticle

BACE1 Inhibition Using 2’-OMePS Steric Blocking Antisense Oligonucleotides

by Madhuri Chakravarthy and Rakesh N Veedu

Genes 2019, 10(9), 705; https://doi.org/10.3390/genes10090705 - 12 Sep 2019

Cited by 6 | Viewed by 3468

Abstract

Amyloid beta-peptide is produced by the cleavage of amyloid precursor protein by two secretases, a β-secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a γ-secretase. It has been hypothesised that partial inhibition of BACE1 in individuals with a high risk of [...] Read more.

Amyloid beta-peptide is produced by the cleavage of amyloid precursor protein by two secretases, a β-secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a γ-secretase. It has been hypothesised that partial inhibition of BACE1 in individuals with a high risk of developing Alzheimer’s disease may be beneficial in preventing cognitive decline. In this study, we report the development of a novel antisense oligonucleotide (AO) that could efficiently downregulate the BACE1 transcript and partially inhibit BACE1 protein. We designed and synthesised a range of 2’-OMethyl-modified antisense oligonucleotides with a phosphorothioate backbone across various exons of the BACE1 transcript, of which AO2, targeting exon 2, efficiently downregulated BACE1 RNA expression by 90%. The sequence of AO2 was later synthesised with a phosphorodiamidate morpholino chemistry, which was found to be not as efficient at downregulating BACE1 expression as the 2’-OMethyl antisense oligonucleotides with a phosphorothioate backbone variant. AO2 also reduced BACE1 protein levels by 45%. In line with our results, we firmly believe that AO2 could be used as a potential preventative therapeutic strategy for Alzheimer’s disease. Full article

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

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19 pages, 3482 KiB

Open AccessArticle

Genetic Characteristic and RNA-Seq Analysis in Transparent Mutant of Carp–Goldfish Nucleocytoplasmic Hybrid

by Lingling Zhou, Hongwei Liang, Xiaoyun Zhou, Jingyi Jia, Cheng Ye, Qiongyao Hu, Shaohua Xu, Yongning Yu, Guiwei Zou and Guangfu Hu

Genes 2019, 10(9), 704; https://doi.org/10.3390/genes10090704 - 12 Sep 2019

Cited by 5 | Viewed by 5486

Abstract

In teleost, pigment in the skin and scales played important roles in various biological processes. Iridophores, one of the main pigment cells in teleost, could produce silver pigments to reflect light. However, the specific mechanism of the formation of silver pigments is still [...] Read more.

In teleost, pigment in the skin and scales played important roles in various biological processes. Iridophores, one of the main pigment cells in teleost, could produce silver pigments to reflect light. However, the specific mechanism of the formation of silver pigments is still unclear. In our previous study, some transparent mutant individuals were found in the carp–goldfish nucleocytoplasmic hybrid (CyCa hybrid) population. In the present study, using transparent mutants (TM) and wild type (WT) of the CyCa hybrid as a model, firstly, microscopic observations showed that the silver pigments and melanin were both lost in the scales of transparent mutants compared to that in wild types. Secondly, genetic study demonstrated that the transparent trait in the CyCa hybrid was recessively inherent, and controlled by an allele in line with Mendelism. Thirdly, RNA-Seq analysis showed that differential expression genes (DEGs) between wild type and transparent mutants were mainly enriched in the metabolism of guanine, such as hydrolase, guanyl nucleotide binding, guanyl ribonucleotide binding, and GTPase activity. Among the DEGs, purine nucleoside phosphorylase 4a (pnp4a) and endothelin receptor B (ednrb) were more highly expressed in the wild type compared to the transparent mutant (p < 0.05). Finally, miRNA-Seq analysis showed that miRNA-146a and miR-153b were both more highly expressed in the transparent mutant compared to that in wild type (p < 0.05). Interaction analysis between miRNAs and mRNAs indicated that miRNA-146a was associated with six DEGs (MGAT5B, MFAP4, GP2, htt, Sema6b, Obscn) that might be involved in silver pigmentation. Full article

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

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15 pages, 2598 KiB

Open AccessArticle

A Comparative Transcriptome Analysis Reveals Physiological Maturation Properties of Mycelia in Pleurotus tuoliensis

by Fang Du, Nu Er zi ya Ya Li mai mai ti, Qingxiu Hu, Yajie Zou, Dou Ye and Haijun Zhang

Genes 2019, 10(9), 703; https://doi.org/10.3390/genes10090703 - 11 Sep 2019

Cited by 8 | Viewed by 2789

Abstract

Pleurotus tuoliensis is a precious edible fungus with extremely high nutritive and medicinal value. The cultivation period of P. tuoliensis is longer than those of other Pleurotus species, which is mainly due to a longer mycelium physiological maturation period (30–60 days). Currently, the [...] Read more.

Pleurotus tuoliensis is a precious edible fungus with extremely high nutritive and medicinal value. The cultivation period of P. tuoliensis is longer than those of other Pleurotus species, which is mainly due to a longer mycelium physiological maturation period (30–60 days). Currently, the molecular processes underlying physiological maturation of the mycelium remain unclear. We performed a comparative transcriptomic analysis of immature and mature mycelia using RNA-seq. De novo transcriptome assembly resulted in identification of 17,030 unigenes. 451 differentially expressed genes—including those encoding nucleoside diphosphate kinase (NDPK), glycoside hydrolase family proteins, exopolygalacturonase, and versatile peroxidases—were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that nucleotide synthesis and energy metabolism are highly active during the physiological maturation of mycelia, and genes related to these pathways were significantly upregulated in mature mycelia. NDPK is predicted to be essential for mycelia maturation. Our findings contribute to a comprehensive understanding of mycelia maturation in a commercially important fungal species. Future efforts will focus on the function of NDPK and the mechanism by which it regulates mycelia maturation. Full article

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

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17 pages, 1894 KiB

Open AccessArticle

Identifying Interaction Clusters for MiRNA and MRNA Pairs in TCGA Network

by Xinqing Dai, Lizhong Ding, Hannah Liu, Zesheng Xu, Hui Jiang, Samuel K Handelman and Yongsheng Bai

Genes 2019, 10(9), 702; https://doi.org/10.3390/genes10090702 - 11 Sep 2019

Cited by 12 | Viewed by 3667

Abstract

Existing methods often fail to recognize the conversions for the biological roles of the pairs of genes and microRNAs (miRNAs) between the tumor and normal samples. We have developed a novel cluster scoring method to identify messenger RNA (mRNA) and miRNA interaction pairs [...] Read more.

Existing methods often fail to recognize the conversions for the biological roles of the pairs of genes and microRNAs (miRNAs) between the tumor and normal samples. We have developed a novel cluster scoring method to identify messenger RNA (mRNA) and miRNA interaction pairs and clusters while considering tumor and normal samples jointly. Our method has identified 54 significant clusters for 15 cancer types selected from The Cancer Genome Atlas project. We also determined the shared clusters across tumor types and/or subtypes. In addition, we compared gene and miRNA overlap between lists identified in our liver hepatocellular carcinoma (LIHC) study and regulatory relationships reported from human and rat nonalcoholic fatty liver disease studies (NAFLD). Finally, we analyzed biological functions for the single significant cluster in LIHC and uncovered a significantly enriched pathway (phospholipase D signaling pathway) with six genes represented in the cluster, symbols: DGKQ, LPAR2, PDGFRB, PIK3R3, PTGFR and RAPGEF3. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Intelligent Biology and Medicine (ICIBM 2019))

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19 pages, 7022 KiB

Open AccessArticle

The Soybean Laccase Gene Family: Evolution and Possible Roles in Plant Defense and Stem Strength Selection

by Quan Wang, Guang Li, Kaijie Zheng, Xiaobin Zhu, Jingjing Ma, Dongmei Wang, Kuanqiang Tang, Xingxing Feng, Jiantian Leng, Hui Yu, Suxin Yang and Xianzhong Feng

Genes 2019, 10(9), 701; https://doi.org/10.3390/genes10090701 - 11 Sep 2019

Cited by 28 | Viewed by 4218

Abstract

Laccase is a widely used industrial oxidase for food processing, dye synthesis, paper making, and pollution remediation. At present, laccases used by industries come mainly from fungi. Plants contain numerous genes encoding laccase enzymes that show properties which are distinct from that of [...] Read more.

Laccase is a widely used industrial oxidase for food processing, dye synthesis, paper making, and pollution remediation. At present, laccases used by industries come mainly from fungi. Plants contain numerous genes encoding laccase enzymes that show properties which are distinct from that of the fungal laccases. These plant-specific laccases may have better potential for industrial purposes. The aim of this work was to conduct a genome-wide search for the soybean laccase genes and analyze their characteristics and specific functions. A total of 93 putative laccase genes (GmLac) were identified from the soybean genome. All 93 GmLac enzymes contain three typical Cu-oxidase domains, and they were classified into five groups based on phylogenetic analysis. Although adjacent members on the tree showed highly similar exon/intron organization and motif composition, there were differences among the members within a class for both conserved and differentiated functions. Based on the expression patterns, some members of laccase were expressed in specific tissues/organs, while some exhibited a constitutive expression pattern. Analysis of the transcriptome revealed that some laccase genes might be involved in providing resistance to oomycetes. Analysis of the selective pressures acting on the laccase gene family in the process of soybean domestication revealed that 10 genes could have been under artificial selection during the domestication process. Four of these genes may have contributed to the transition of the soft and thin stem of wild soybean species into strong, thick, and erect stems of the cultivated soybean species. Our study provides a foundation for future functional studies of the soybean laccase gene family. Full article

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

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20 pages, 895 KiB

Open AccessReview

Overcoming Fish Defences: The Virulence Factors of Yersinia ruckeri

by Agnieszka Wrobel, Jack C. Leo and Dirk Linke

Genes 2019, 10(9), 700; https://doi.org/10.3390/genes10090700 - 11 Sep 2019

Cited by 36 | Viewed by 6768

Abstract

Yersinia ruckeri is the causative agent of enteric redmouth disease, a bacterial infection of marine and freshwater fish. The disease mainly affects salmonids, and outbreaks have significant economic impact on fish farms all over the world. Vaccination routines are in place against the [...] Read more.

Yersinia ruckeri is the causative agent of enteric redmouth disease, a bacterial infection of marine and freshwater fish. The disease mainly affects salmonids, and outbreaks have significant economic impact on fish farms all over the world. Vaccination routines are in place against the major serotypes of Y. ruckeri but are not effective in all cases. Despite the economic importance of enteric redmouth disease, a detailed molecular understanding of the disease is lacking. A considerable number of mostly omics-based studies have been performed in recent years to identify genes related to Y. ruckeri virulence. This review summarizes the knowledge on Y. ruckeri virulence factors. Understanding the molecular pathogenicity of Y. ruckeri will aid in developing more efficient vaccines and antimicrobial compounds directed against enteric redmouth disease. Full article

(This article belongs to the Special Issue Host-Bacterial Associations in Marine Organisms)

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Genes, Volume 10, Issue 9 (September 2019) – 99 articles

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