Comparative Biochemistry and Physiology, Part D, Vol. 5, Pp. 45-54 (2010)
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Invited Review: Genetic and Genomic Mouse Models for Livestock Research
Archives Animal Breeding – serving the animal science community for 60 years Arch. Anim. Breed., 61, 87–98, 2018 https://doi.org/10.5194/aab-61-87-2018 Open Access © Author(s) 2018. This work is distributed under the Creative Commons Attribution 4.0 License. Archives Animal Breeding Invited review: Genetic and genomic mouse models for livestock research Danny Arends, Deike Hesse, and Gudrun A. Brockmann Albrecht Daniel Thaer-Institut für Agrar- und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, 10115 Berlin, Germany Correspondence: Danny Arends ([email protected]) and Gudrun A. Brockmann ([email protected]) Received: 7 December 2017 – Revised: 3 January 2018 – Accepted: 8 January 2018 – Published: 13 February 2018 Abstract. Knowledge about the function and functioning of single or multiple interacting genes is of the utmost significance for understanding the organism as a whole and for accurate livestock improvement through genomic selection. This includes, but is not limited to, understanding the ontogenetic and environmentally driven regula- tion of gene action contributing to simple and complex traits. Genetically modified mice, in which the functions of single genes are annotated; mice with reduced genetic complexity; and simplified structured populations are tools to gain fundamental knowledge of inheritance patterns and whole system genetics and genomics. In this re- view, we briefly describe existing mouse resources and discuss their value for fundamental and applied research in livestock. 1 Introduction the generation of targeted mutations found their way from model animals to livestock species. Through this progress, During the last 10 years, tools for genome analyses model organisms attain a new position in fundamental sci- have developed tremendously. -
Identification of Key Candidate Genes and Molecular Pathways in White Fat
Pan et al. Human Genomics (2019) 13:55 https://doi.org/10.1186/s40246-019-0239-x PRIMARY RESEARCH Open Access Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology Yuyan Pan, Jiaqi Liu* and Fazhi Qi* Abstract Background: Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. Results: In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (β3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs. -
A Clinicopathological and Molecular Genetic Analysis of Low-Grade Glioma in Adults
A CLINICOPATHOLOGICAL AND MOLECULAR GENETIC ANALYSIS OF LOW-GRADE GLIOMA IN ADULTS Presented by ANUSHREE SINGH MSc A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy Brain Tumour Research Centre Research Institute in Healthcare Sciences Faculty of Science and Engineering University of Wolverhampton November 2014 i DECLARATION This work or any part thereof has not previously been presented in any form to the University or to any other body whether for the purposes of assessment, publication or for any other purpose (unless otherwise indicated). Save for any express acknowledgments, references and/or bibliographies cited in the work, I confirm that the intellectual content of the work is the result of my own efforts and of no other person. The right of Anushree Singh to be identified as author of this work is asserted in accordance with ss.77 and 78 of the Copyright, Designs and Patents Act 1988. At this date copyright is owned by the author. Signature: Anushree Date: 30th November 2014 ii ABSTRACT The aim of the study was to identify molecular markers that can determine progression of low grade glioma. This was done using various approaches such as IDH1 and IDH2 mutation analysis, MGMT methylation analysis, copy number analysis using array comparative genomic hybridisation and identification of differentially expressed miRNAs using miRNA microarray analysis. IDH1 mutation was present at a frequency of 71% in low grade glioma and was identified as an independent marker for improved OS in a multivariate analysis, which confirms the previous findings in low grade glioma studies. -
Fusion Transcripts and Transcribed Retrotransposed Loci Discovered Through Comprehensive Transcriptome Analysis Using Paired-End Ditags (Pets)
Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs) Yijun Ruan,1,6 Hong Sain Ooi,2 Siew Woh Choo,2 Kuo Ping Chiu,2 Xiao Dong Zhao,1 K.G. Srinivasan,1 Fei Yao,1 Chiou Yu Choo,1 Jun Liu,1 Pramila Ariyaratne,2 Wilson G.W. Bin,2 Vladimir A. Kuznetsov,2 Atif Shahab,3 Wing-Kin Sung,2,4 Guillaume Bourque,2 Nallasivam Palanisamy,5 and Chia-Lin Wei1,6 1Genome Technology and Biology Group, Genome Institute of Singapore, Singapore 138672, Singapore; 2Information and Mathematical Science Group, Genome Institute of Singapore, Singapore 138672, Singapore; 3Bioinformatics Institute, Singapore 138671, Singapore; 4School of Computing, National University of Singapore, Singapore 117543, Singapore; 5Cancer Biology Group, Genome Institute of Singapore, Singapore 138672, Singapore Identification of unconventional functional features such as fusion transcripts is a challenging task in the effort to annotate all functional DNA elements in the human genome. Paired-End diTag (PET) analysis possesses a unique capability to accurately and efficiently characterize the two ends of DNA fragments, which may have either normal or unusual compositions. This unique nature of PET analysis makes it an ideal tool for uncovering unconventional features residing in the human genome. Using the PET approach for comprehensive transcriptome analysis, we were able to identify fusion transcripts derived from genome rearrangements and actively expressed retrotransposed pseudogenes, which would be difficult to capture by other means. Here, we demonstrate this unique capability through the analysis of 865,000 individual transcripts in two types of cancer cells. -
3313.Full.Pdf
[CANCER RESEARCH Vol. 6, 3313–3319, June 15, 2000] New Evidence for an Extra-Hepatic Role of N-acetylglucosaminyltransferase III in the Progression of Diethylnitrosamine-induced Liver Tumors in Mice1 Xiaoping Yang, Mantu Bhaumik, Riddhi Bhattacharyya, Shih Gong, Charles E. Rogler, and Pamela Stanley2 Departments of Cell Biology [X. Y., M. B., R. B., P. S.] and Medicine and Microbiology/Immunology [S. G., C. E. R.], Albert Einstein College of Medicine, New York, New York 10461 ABSTRACT exhibit reduced experimental metastasis (10). Overexpression of Gl- cNAc-TIII in PC12 cells perturbs their ability to respond to nerve N-acetylglucosaminyltransferase III (GlcNAc-TIII) is encoded by the growth factor (11), and overexpression in a glioma cell line inhibits Mgat3 gene and catalyzes the addition of the bisecting GlcNAc to the core of N-glycans. Mice lacking GlcNAc-TIII due to the insertion mutation epidermal growth factor receptor function (12). K562 cells expressing Mgat3tm1Pst (termed Mgat3neo), exhibit retarded progression of liver tu- a transfected Mgat3 gene are comparatively resistant to natural killer mors induced by diethylnitrosamine (DEN; M. Bhaumik et al., Cancer cell cytotoxicity and colonize spleen more effectively (13). In mice Res., 58: 2881–2887, 1998). This phenotype seemed to be due to a reduc- overexpressing a Mgat3 transgene in hepatocytes, a reduction in tion, in activity or amount, of a circulating glycoprotein(s) that enhances secretion of apolipoprotein and lipids from liver was reported (14). DEN-induced liver tumor progression. Here, we provide new evidence to Transgenic mice overexpressing a Mgat3 transgene in hematopoietic support this hypothesis. First, we show that mice with a deletion mutation ⌬ cells were found to have a defect in stroma-dependent hemopoiesis of the Mgat3 gene coding exon (Mgat3tmlJxm, termed Mgat3 ) also exhibit retarded progression of DEN-induced liver tumors. -
Network Inference from Glycoproteomics Data Reveals New Reactions in the Igg Glycosylation Pathway
ARTICLE DOI: 10.1038/s41467-017-01525-0 OPEN Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway Elisa Benedetti1, Maja Pučić-Baković2, Toma Keser 3, Annika Wahl4,5, Antti Hassinen6, Jeong-Yeh Yang7, Lin Liu7, Irena Trbojević-Akmačić2, Genadij Razdorov 2, Jerko Štambuk2, Lucija Klarić2,8,9, Ivo Ugrina 3,10,11, Maurice H.J. Selman12, Manfred Wuhrer 12, Igor Rudan 8, Ozren Polasek13,14, Caroline Hayward 9, Harald Grallert4,5,15, Konstantin Strauch16,17, Annette Peters5, Thomas Meitinger18, Christian Gieger4,5, Marija Vilaj2, Geert-Jan Boons7,19, Kelley W. Moremen7, Tatiana Ovchinnikova20, Nicolai Bovin20, Sakari Kellokumpu6, Fabian J. Theis 1,21, Gordan Lauc2,3 & Jan Krumsiek 1,14 Immunoglobulin G (IgG) is a major effector molecule of the human immune response, and aberrations in IgG glycosylation are linked to various diseases. However, the molecular mechanisms underlying protein glycosylation are still poorly understood. We present a data- driven approach to infer reactions in the IgG glycosylation pathway using large-scale mass- spectrometry measurements. Gaussian graphical models are used to construct association networks from four cohorts. We find that glycan pairs with high partial correlations represent enzymatic reactions in the known glycosylation pathway, and then predict new biochemical reactions using a rule-based approach. Validation is performed using data from a GWAS and results from three in vitro experiments. We show that one predicted reaction is enzymatically feasible and that one rejected reaction does not occur in vitro. Moreover, in contrast to previous knowledge, enzymes involved in our predictions colocalize in the Golgi of two cell lines, further confirming the in silico predictions. -
Proteomics of Lipid Accumulation and DGAT Inhibition in Hepg2 Liver Carcinoma Cells
Proteomics of lipid accumulation and DGAT inhibition in HepG2 liver carcinoma cells. By Bhumika Bhatt-Wessel A thesis submitted to Victoria University of Wellington in fulfilment of the requirement for the degree of Doctor of Philosophy In Cell and Molecular Biology. Victoria University of Wellington 2017. i ABSTRACT Non-alcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome in the liver. It is marked by hepatocyte accumulation of triacylglycerol (TAG) rich lipid droplets. In some patients, the disease progresses to non-alcoholic steatohepatitis (NASH), characterized by cellular damage, inflammation and fibrosis. In some cases, cirrhosis and liver failure may occur. However, the pathogenesis of NAFLD is still unclear. The present project is based on the hypothesis that hepatocytes are equipped with mechanisms that allow them to manage lipid accumulation to a certain extent. Continued or increased lipid accumulation beyond this triggers molecular mechanisms such as oxidative stress, lipid peroxidation and cell death that aggravate the condition and cause disease progression. The aim of this project is to study the effects of lipid accumulation on the cells using proteomics approach to identify proteins involved in the disease progression. A cell culture model was used in the study. HepG2 cells, a human liver carcinoma cell line, were treated with a mixture of fatty acids (FA) to induce lipid accumulation. The lipid accumulation in HepG2 cells was measured with Oil red O assay and the effect of lipid accumulation on the proliferation of the cells was measured using an MTT cell proliferation assay. HepG2 cells treated with 1 mM FA mixture for 6 hours induced lipid accumulation 1.4 times of control with 90% of cell proliferation capacity of the control cells. -
Supplementary Material Table of Contents
Supplementary M aterial Table of Contents 1 - Online S u pplementary Methods ………………………………………………...… . …2 1.1 Study population……………………………………………………………..2 1.2 Quality control and principal component analysis …………………………..2 1.3 Statistical analyses………………………………………… ………………...3 1.3.1 Disease - specific association testing ……………………………… ..3 1.3.2 Cross - phenotype meta - analysis …………………………………… .3 1.3.3 Model search ……………………………………………………… .4 1.3.4 Novelty of the variants …………………………………………… ..4 1.3.5 Functional Enrichment Analy sis ………………………………… ...4 1.3.6 Drug Target Enrichment Analysis ………………………………… 5 2 - Supplementary Figures………………………………………...………………… . …. 7 3 - Members of the Myositis Genetics Consortium (MYOGEN) ……………………. ..16 4 - Members of the Scleroderma Genetics Consortium ………………… ……………...17 5 - Supplementary References………………………………………………………… . .18 6 - Supplementary Tables………………………………………………………… . ……22 1 Online supplementary m ethods Study population This study was conducted using 12,132 affected subjects and 23 ,260 controls of European des cent population and all of them have been included in previously published GWAS as summarized in Table S1. [1 - 6] Briefly, a total of 3,255 SLE cases and 9,562 ancestry matched controls were included from six countrie s across Europe and North America (Spain, Germany, Netherlands, Italy, UK, and USA). All of the included patients were diagnosed based on the standard American College of Rheumatology (ACR) classification criteria. [7] Previously described GWAS data from 2,363 SSc cases and 5,181 ancestry -
A Systems Genetics Approach to Revealing the Pdgfb Molecular Network of the Retina
Molecular Vision 2020; 26:459-471 <http://www.molvis.org/molvis/v26/459> © 2020 Molecular Vision Received 19 November 2019 | Accepted 17 June 2020 | Published 19 June 2020 A systems genetics approach to revealing the Pdgfb molecular network of the retina Shasha Li,1,2 Fuyi Xu,2 Lin Liu,1 Rong Ju,3 Jonas Bergquist,1,4 Qing Yin Zheng,5,6 Jia Mi,1 Lu Lu,2 Xuri Li,3 Geng Tian1 (The first two authors contributed equally to this work.) 1Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China; 2Department of Genetics, Genomics and informatics, University of Tennessee Health Science Center, Memphis, TN; 3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China; 4Analytical Chemistry and Neurochemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden; 5Transformative Otology and Neuroscience Center, Case Western Reserve University School of Medicine, Cleveland, OH; 6Departments of Otolaryngology, Case Western Reserve University School of Medicine, Cleveland, OH. Purpose: Platelet-derived growth factor (PDGF) signaling is well known to be involved in vascular retinopathies. Among the PDGF family, the subunit B (PDGFB) protein is considered a promising therapeutic target. This study aimed to identify the genes and potential pathways through which PDGFB affects retinal phenotypes by using a systems genetics approach. Methods: Gene expression data had been previously generated in a laboratory for the retinas of 75 C57BL/6J(B6) X DBA/2J (BXD) recombinant inbred (RI) strains. Using this data, the genetic correlation method was used to identify genes correlated to Pdgfb. A correlation between intraocular pressure (IOP) and Pdgfb was calculated based on the Pearson correlation coefficient. -
Supplementary Information – Postema Et Al., the Genetics of Situs Inversus Totalis Without Primary Ciliary Dyskinesia
1 Supplementary information – Postema et al., The genetics of situs inversus totalis without primary ciliary dyskinesia Table of Contents: Supplementary Methods 2 Supplementary Results 5 Supplementary References 6 Supplementary Tables and Figures Table S1. Subject characteristics 9 Table S2. Inbreeding coefficients per subject 10 Figure S1. Multidimensional scaling to capture overall genomic diversity 11 among the 30 study samples Table S3. Significantly enriched gene-sets under a recessive mutation model 12 Table S4. Broader list of candidate genes, and the sources that led to their 13 inclusion Table S5. Potential recessive and X-linked mutations in the unsolved cases 15 Table S6. Potential mutations in the unsolved cases, dominant model 22 2 1.0 Supplementary Methods 1.1 Participants Fifteen people with radiologically documented SIT, including nine without PCD and six with Kartagener syndrome, and 15 healthy controls matched for age, sex, education and handedness, were recruited from Ghent University Hospital and Middelheim Hospital Antwerp. Details about the recruitment and selection procedure have been described elsewhere (1). Briefly, among the 15 people with radiologically documented SIT, those who had symptoms reminiscent of PCD, or who were formally diagnosed with PCD according to their medical record, were categorized as having Kartagener syndrome. Those who had no reported symptoms or formal diagnosis of PCD were assigned to the non-PCD SIT group. Handedness was assessed using the Edinburgh Handedness Inventory (EHI) (2). Tables 1 and S1 give overviews of the participants and their characteristics. Note that one non-PCD SIT subject reported being forced to switch from left- to right-handedness in childhood, in which case five out of nine of the non-PCD SIT cases are naturally left-handed (Table 1, Table S1). -
Glycosyltransferase B4GALNT2 As a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases
International Journal of Molecular Sciences Article Glycosyltransferase B4GALNT2 as a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases Michela Pucci, Nadia Malagolini and Fabio Dall’Olio * Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy; [email protected] (M.P.); [email protected] (N.M.) * Correspondence: [email protected]; Tel.: +39-051-2094704 Abstract: Background: glycosyltransferase B4GALNT2 and its cognate carbohydrate antigen Sda are highly expressed in normal colon but strongly downregulated in colorectal carcinoma (CRC). We previously showed that CRC patients expressing higher B4GALNT2 mRNA levels displayed longer survival. Forced B4GALNT2 expression reduced the malignancy and stemness of colon cancer cells. Methods: Kaplan–Meier survival curves were determined in “The Cancer Genome Atlas” (TCGA) COAD cohort for several glycosyltransferases, oncogenes, and tumor suppressor genes. Whole expression data of coding genes as well as miRNA and methylation data for B4GALNT2 were downloaded from TCGA. Results: the prognostic potential of B4GALNT2 was the best among the glycosyltransferases tested and better than that of many oncogenes and tumor suppressor genes; high B4GALNT2 expression was associated with a lower malignancy gene expression profile; differential methylation of an intronic B4GALNT2 gene position and miR-204-5p expression play major roles in B4GALNT2 regulation. Conclusions: high B4GALNT2 expression is a strong predictor of good prognosis in CRC as a part of a wider molecular signature that includes ZG16, ITLN1, BEST2, and Citation: Pucci, M.; Malagolini, N.; GUCA2B. Differential DNA methylation and miRNA expression contribute to regulating B4GALNT2 Dall’Olio, F. -
Pathway Analysis Report
Pathway Analysis Report This report contains the pathway analysis results for the submitted sample ''. Analysis was per- formed against Reactome version 73 on 02/08/2020. The web link to these results is: https://reactome.org/PathwayBrowser/#/ANALYSIS=MjAyMDA4MDIxNDU3NTRfNzM4NDA%3D Please keep in mind that analysis results are temporarily stored on our server. The storage period depends on usage of the service but is at least 7 days. As a result, please note that this URL is only valid for a limited time period and it might have expired. Table of Contents 1. Introduction 2. Properties 3. Genome-wide overview 4. Most significant pathways 5. Pathways details 6. Identifiers found 7. Identifiers not found 1. Introduction Reactome is a curated database of pathways and reactions in human biology. Reactions can be con- sidered as pathway 'steps'. Reactome defines a 'reaction' as any event in biology that changes the state of a biological molecule. Binding, activation, translocation, degradation and classical bio- chemical events involving a catalyst are all reactions. Information in the database is authored by expert biologists, entered and maintained by Reactome’s team of curators and editorial staff. Re- actome content frequently cross-references other resources e.g. NCBI, Ensembl, UniProt, KEGG (Gene and Compound), ChEBI, PubMed and GO. Orthologous reactions inferred from annotation for Homo sapiens are available for 17 non-human species including mouse, rat, chicken, puffer fish, worm, fly, yeast, rice, and Arabidopsis. Pathways are represented by simple diagrams follow- ing an SBGN-like format. Reactome's annotated data describe reactions possible if all annotated proteins and small mo- lecules were present and active simultaneously in a cell.