DOCSLIB.ORG

The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene Within the Ovary

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene Within the Ovary The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary. Laurence Drouilhet, Camille Mansanet, Julien Sarry, Kamila Canale-Tabet, Philippe Bardou, Florent Woloszyn, Jérôme Lluch, Grégoire Harichaux, Catherine Viguié, Danielle Monniaux, et al. To cite this version: Laurence Drouilhet, Camille Mansanet, Julien Sarry, Kamila Canale-Tabet, Philippe Bardou, et al.. The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary.. PLoS Genetics, Public Library of Science, 2013, 9 (9), pp.e1003809. 10.1371/journal.pgen.1003809. hal-01129778 HAL Id: hal-01129778 https://hal.archives-ouvertes.fr/hal-01129778 Submitted on 29 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary Laurence Drouilhet1., Camille Mansanet2., Julien Sarry1, Kamila Tabet1, Philippe Bardou3, Florent Woloszyn1,Je´rome Lluch4, Gre´goire Harichaux2,5, Catherine Viguie´ 6, Danielle Monniaux2, Loys Bodin7, Philippe Mulsant1, Ste´phane Fabre1,2* 1 INRA-ENVT, UMR 444, Laboratoire de Ge´ne´tique Cellulaire, Castanet-Tolosan, France, 2 INRA UMR 85, CNRS UMR 7247, Universite´ de Tours, IFCE, Physiologie de la Reproduction et des Comportements, Nouzilly, France, 3 INRA, SIGENAE, Laboratoire de Ge´ne´tique Cellulaire, Castanet-Tolosan, France, 4 INRA, GeT-PlaGe Genotoul, Castanet-Tolosan, France, 5 INRA, Plate-forme d’Analyse Inte´grative des Biomole´cules, Laboratoire de Spectrome´trie de Masse, Nouzilly, France, 6 UMR 1331 INRA-ENVT- EIP-INPT-UPS, Toxicologie Alimentaire, Toulouse, France, 7 INRA, UR 631, Station d’Ame´lioration Ge´ne´tique des Animaux, Castanet-Tolosan, France Abstract Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecLL. Our previous work localized FecL on sheep chromosome 11 within a locus of 1.1 Mb encompassing 20 genes. With the aim to identify the FecL gene, we developed a high throughput sequencing strategy of long-range PCR fragments spanning the locus of FecLL carrier and non-carrier ewes. Resulting informative markers defined a new 194.6 kb minimal interval. The reduced FecL locus contained only two genes, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and beta-1,4-N-acetyl-galactosaminyl transferase 2 (B4GALNT2), and we identified two SNP in complete linkage disequilibrium with FecLL. B4GALNT2 appeared as the best positional and expressional candidate for FecL, since it showed an ectopic expression in the ovarian follicles of FecLL/FecLL ewes at mRNA and protein levels. In FecLL carrier ewes only, B4GALNT2 transferase activity was localized in granulosa cells and specifically glycosylated proteins were detected in granulosa cell extracts and follicular fluids. The identification of these glycoproteins by mass spectrometry revealed at least 10 proteins, including inhibin alpha and betaA subunits, as potential targets of B4GALNT2 activity. Specific ovarian protein glycosylation by B4GALNT2 is proposed as a new mechanism of ovulation rate regulation in sheep, and could contribute to open new fields of investigation to understand female infertility pathogenesis. Citation: Drouilhet L, Mansanet C, Sarry J, Tabet K, Bardou P, et al. (2013) The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary. PLoS Genet 9(9): e1003809. doi:10.1371/journal.pgen.1003809 Editor: Tosso Leeb, University of Bern, Switzerland Received April 5, 2013; Accepted August 6, 2013; Published September 26, 2013 Copyright: ß 2013 Drouilhet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the French ‘‘Conseil Re´gional Midi-Pyre´ne´es’’, ‘‘Agence Nationale de la Recherche’’ GENOVUL project (ANR-05- GANI-001-01) and European Union contract SABRE (FOOD-CT-2006-01625). LD and CM were supported in part by a grant from the ‘‘Fonds d’Aide a` la Recherche Organon, FARO’’ and ‘‘Re´gion Centre’’, respectively. The high-resolution mass spectrometer was financed (SMHART project) by the European Regional Development Fund (ERDF), the Conseil Re´gional du Centre, the French National Institute for Agricultural Research (INRA) and the French National Institute of Health and Medical Research (INSERM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] . These authors contributed equally to this work. Introduction prolific sheep are now considered as valuable models for identifying genes and mutations involved in mechanisms control- Women, cattle, goats and ewes have generally one or two ling the ovarian function, for agronomical purposes such as genetic offspring, whereas other mammals, such as sows, rodents and dogs selection of prolificacy, and for clinical purposes in the case of are prolific and produce more than three offspring. It relies on the female infertility or subfertility. number of ovulations at each estrus cycle i.e. the ovulation rate In the meat strain of the Lacaune sheep breed, large variation in (OR), for which the underlying genetic mechanism was puzzling litter size has been observed and genetic studies explained this until the identification of fecundity genes in sheep, bone variation by the segregation of at least two major genes influencing morphogenetic protein-15 (BMP15), growth and differentiation OR and prolificacy, one being X-linked and named FecX, the factor-9 (GDF9) and BMP receptor-1B (BMPR1B) [1]. Following second being autosomal and named FecL [3,4]. FecX is known as the discovery of sheep fecundity genes, several research groups BMP15 and in the Lacaune breed, the mutant allele (FecXL) have focused on BMP15 and GDF9 and they have found numerous associated with high prolificacy was identified as a pCys321Tyr mutations associated with human ovarian pathologies such as substitution altering the BMP15 protein function [3]. Heterozy- premature ovarian failure or polycystic ovary syndrome [2]. Thus, gous FecXL mutation is associated with a twofold increase in OR, PLOS Genetics | www.plosgenetics.org 1 September 2013 | Volume 9 | Issue 9 | e1003809 B4GALNT2 as Fecundity Gene Author Summary encompassing 488 kb on the ovine chromosome 11 (OAR11, ovine genome version 3.1 released October 2012) and corre- Prolific sheep have proven to be a valuable model to sponded to a block of synteny of 479 kb on bovine chromosome 19 identify genes and mutations implicated in ovarian (BTA19, bovine genome version 4.6.1 released October 2011). function and female fertility. Indeed, fecundity genes of This entire region was sequenced with the Roche 454 sequencing the Bone Morphogenetic Protein (BMP) family discovered technology, using long-range PCR, in one heterozygous L/+ in sheep was evidenced as genetic candidates to explain animal and two homozygous +/+ and L/L animals. Sixty-two female infertility pathologies. Studying French Lacaune polymorphisms were evidenced and an appropriate subset was sheep breed, we discovered another fecundity gene genotyped on the recombinant animals allowing the reduction of named B4GALNT2, encoding a glycosylation enzyme that the locus. This new interval of localization, comprised between is not related to the BMP family. The high prolificacy of two SNP markers on OAR11 g.36910171T.C (recombinant ewe Lacaune sheep was explained by overexpression of nu990855) and g.37107627G.C (recombinant ewe nu60718), was B4GALNT2 in the ovary leading to atypical glycosylation estimated at 197 kb based on ovine genome OARv3.1 (Figure 1). of inhibin, an important hormone regulating ovarian This region encompasses 3 predicted protein-coding genes on the function. Our findings open promising fields of investiga- tion to better understand female fertility disorders. ovine genome, named B4GALNT2 (beta-1,4-N-acetyl-galactosami- nyl transferase 2), EZR (ezrin) and IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1). but homozygous FecXL/FecXL ewes are sterile, thus mimicking the phenotype observed for the other 5 mutations described in the Screening of the polymorphisms fully associated with the ovine BMP15 gene [5–7]. FecLL mutation The influence of the autosomal FecLL mutation on OR is In order to identify all the polymorphisms contained within this additive with one copy increasing OR by about 1.5 and two copies 197 kb interval, we analyzed separately
Load more

Recommended publications
  • Hippo and Sonic Hedgehog Signalling Pathway Modulation of Human Urothelial Tissue Homeostasis
    Hippo and Sonic Hedgehog signalling pathway modulation of human urothelial tissue homeostasis Thomas Crighton PhD University of York Department of Biology November 2020 Abstract The urinary tract is lined by a barrier-forming, mitotically-quiescent urothelium, which retains the ability to regenerate following injury. Regulation of tissue homeostasis by Hippo and Sonic Hedgehog signalling has previously been implicated in various mammalian epithelia, but limited evidence exists as to their role in adult human urothelial physiology. Focussing on the Hippo pathway, the aims of this thesis were to characterise expression of said pathways in urothelium, determine what role the pathways have in regulating urothelial phenotype, and investigate whether the pathways are implicated in muscle-invasive bladder cancer (MIBC). These aims were assessed using a cell culture paradigm of Normal Human Urothelial (NHU) cells that can be manipulated in vitro to represent different differentiated phenotypes, alongside MIBC cell lines and The Cancer Genome Atlas resource. Transcriptomic analysis of NHU cells identified a significant induction of VGLL1, a poorly understood regulator of Hippo signalling, in differentiated cells. Activation of upstream transcription factors PPARγ and GATA3 and/or blockade of active EGFR/RAS/RAF/MEK/ERK signalling were identified as mechanisms which induce VGLL1 expression in NHU cells. Ectopic overexpression of VGLL1 in undifferentiated NHU cells and MIBC cell line T24 resulted in significantly reduced proliferation. Conversely, knockdown of VGLL1 in differentiated NHU cells significantly reduced barrier tightness in an unwounded state, while inhibiting regeneration and increasing cell cycle activation in scratch-wounded cultures. A signalling pathway previously observed to be inhibited by VGLL1 function, YAP/TAZ, was unaffected by VGLL1 manipulation.
    [Show full text]
  • The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene Within the Ovary
    The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary Laurence Drouilhet1., Camille Mansanet2., Julien Sarry1, Kamila Tabet1, Philippe Bardou3, Florent Woloszyn1,Je´rome Lluch4, Gre´goire Harichaux2,5, Catherine Viguie´ 6, Danielle Monniaux2, Loys Bodin7, Philippe Mulsant1, Ste´phane Fabre1,2* 1 INRA-ENVT, UMR 444, Laboratoire de Ge´ne´tique Cellulaire, Castanet-Tolosan, France, 2 INRA UMR 85, CNRS UMR 7247, Universite´ de Tours, IFCE, Physiologie de la Reproduction et des Comportements, Nouzilly, France, 3 INRA, SIGENAE, Laboratoire de Ge´ne´tique Cellulaire, Castanet-Tolosan, France, 4 INRA, GeT-PlaGe Genotoul, Castanet-Tolosan, France, 5 INRA, Plate-forme d’Analyse Inte´grative des Biomole´cules, Laboratoire de Spectrome´trie de Masse, Nouzilly, France, 6 UMR 1331 INRA-ENVT- EIP-INPT-UPS, Toxicologie Alimentaire, Toulouse, France, 7 INRA, UR 631, Station d’Ame´lioration Ge´ne´tique des Animaux, Castanet-Tolosan, France Abstract Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecLL. Our previous work localized FecL on sheep chromosome 11 within a locus of 1.1 Mb encompassing 20 genes. With the aim to identify the FecL gene, we developed a high throughput sequencing strategy of long-range PCR fragments spanning the locus of FecLL carrier and non-carrier ewes. Resulting informative markers defined a new 194.6 kb minimal interval.
    [Show full text]
  • A Chromosome-Centric Human Proteome Project (C-HPP) To
    computational proteomics Laboratory for Computational Proteomics www.FenyoLab.org E-mail: [email protected] Facebook: NYUMC Computational Proteomics Laboratory Twitter: @CompProteomics Perspective pubs.acs.org/jpr A Chromosome-centric Human Proteome Project (C-HPP) to Characterize the Sets of Proteins Encoded in Chromosome 17 † ‡ § ∥ ‡ ⊥ Suli Liu, Hogune Im, Amos Bairoch, Massimo Cristofanilli, Rui Chen, Eric W. Deutsch, # ¶ △ ● § † Stephen Dalton, David Fenyo, Susan Fanayan,$ Chris Gates, , Pascale Gaudet, Marina Hincapie, ○ ■ △ ⬡ ‡ ⊥ ⬢ Samir Hanash, Hoguen Kim, Seul-Ki Jeong, Emma Lundberg, George Mias, Rajasree Menon, , ∥ □ △ # ⬡ ▲ † Zhaomei Mu, Edouard Nice, Young-Ki Paik, , Mathias Uhlen, Lance Wells, Shiaw-Lin Wu, † † † ‡ ⊥ ⬢ ⬡ Fangfei Yan, Fan Zhang, Yue Zhang, Michael Snyder, Gilbert S. Omenn, , Ronald C. Beavis, † # and William S. Hancock*, ,$, † Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States ‡ Stanford University, Palo Alto, California, United States § Swiss Institute of Bioinformatics (SIB) and University of Geneva, Geneva, Switzerland ∥ Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States ⊥ Institute for System Biology, Seattle, Washington, United States ¶ School of Medicine, New York University, New York, United States $Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia ○ MD Anderson Cancer Center, Houston, Texas, United States ■ Yonsei University College of Medicine, Yonsei University,
    [Show full text]
  • The Relevance of Bioinformatic Tools in the Study of Polymorphisms of the B4GALNT2 Gene and Its Association with Cancer
    Current Research in Bioinformatics Original Research Paper The Relevance of Bioinformatic Tools in the Study of Polymorphisms of the B4GALNT2 Gene and its Association with Cancer 1,2Eddaikra Atika, 1Haddouche Hayet and 2Touil-Boukoffa Chafia 1Department of Cell Biology and Physiology, Faculty of Nature and Life, SAAD DAHLEB University Blida1, Algeria, Algiers 2Laboratory of Cellular and Molecular Research, Cytokines and NO Synthase, Faculty of Biological Sciences (FSB), USTHB, Algiers Article history Abstract: The human gene B4GALNT2 encodes an enzyme (β1,4-N- Received: 25-12-2019 acetylgalactosaminyltransferase II) that controls the expression of the Revised: 11-02-2020 blood group Sda carbohydrate’s antigen. This gene is located in position Accepted: 25-02-2020 17q21,32 and consists of 11 exons. The characterization and understanding of genetic variation is a real challenge in human genetics, Corresponding Author: Atika Eddaikra both for healthy individuals and diseased ones. The in silico study of the Department of Cell Biology and B4GALNT2 gene’s polymorphism using a bioinformatic methodology by Physiology, Faculty of Nature means of analyzing various databases and open source web browsers has and Life, SAAD DAHLEB shown that this gene is characterized by a polymorphic profile that has a University Blida1, Algeria, very large number of Cosmic SNPs associated with different types of Algiers; B.P:270 Route de cancer. The prediction of the 3D structure in silico is an important step to Soumâa – Blida, Algeria better understand the overall architecture of the B4GALNT2 protein. The Email: [email protected] chosen model this study is one of chondroitin synthase with a recovery percentage of 20.10% relative to the target sequence.
    [Show full text]
  • PB #ISAG2017 1 @Isagofficial #ISAG2017 #ISAG2017
    Bioinformatics · Comparative Genomics · Computational Biology Epigenetics · Functional Genomics · Genome Diversity · Geno Genome Sequencing · Immunogenetics · Integrative Geno · Microbiomics · Population Genomics · Systems Biolog Genetic Markers and Selection · Genetics and Dis Gene Editing · Bioinformatics · Comparative Computational Biology · Epigenetics · Fun Genome Diversity · Genome Sequeng Integrative Genomics · Microbiom Population Genomics · Syste Genetic Markers and Sel Genetics and Disease Gene Editing · Bi O’Brien Centre for Science Bioinformati and O’Reilly Hall, University College Dublin, Dublin, Ireland ABSTRACTMINI PROGRAMME BOOK www.isag.us/2017 PB #ISAG2017 1 @isagofficial #ISAG2017 #ISAG2017 Contents ORAL PRESENTATIONS 1 Animal Forensic Genetics Workshop 1 Applied Genetics and Genomics in Other Species of Economic Importance 3 Domestic Animal Sequencing and Annotation 5 Genome Edited Animals 8 Horse Genetics and Genomics 9 Avian Genetics and Genomics 12 Comparative MHC Genetics: Populations and Polymorphism 16 Equine Genetics and Thoroughbred Parentage Testing Workshop 19 Genetics of Immune Response and Disease Resistance 20 ISAG-FAO Genetic Diversity 24 Ruminant Genetics and Genomics 28 Animal Epigenetics 31 Cattle Molecular Markers and Parentage Testing 33 Companion Animal Genetics and Genomics 34 Microbiomes 37 Pig Genetics and Genomics 40 Novel, Groundbreaking Research/Methodology Presentation 44 Applied Genetics of Companion Animals 44 Applied Sheep and Goat Genetics 45 Comparative and Functional Genomics 47 Genetics
    [Show full text]
  • Copy Number Variation and Genome Evolution in Humans and Chimpanzees
    Downloaded from genome.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press Copy number variation and evolution in humans and chimpanzees George H. Perry1,2,6, Fengtang Yang3, Tomas Marques-Bonet4, Carly Murphy2, Tomas Fitzgerald3, Arthur S. Lee2, Courtney Hyland2, Anne C. Stone1, Matthew E. Hurles3, Chris Tyler- Smith3, Evan E. Eichler4, Nigel P. Carter3, Charles Lee2,5, Richard Redon3,6,7 1 School of Human Evolution & Social Change, Arizona State University, Tempe, AZ 85287; 2 Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115; 3 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; 4 Department of Genome Sciences, University of Washington School of Medicine and the Howard Hughes Medical Institute, Seattle, WA 98195; 5 Harvard Medical School, Boston, MA 02115. 6 These authors contributed equally to this work. 7 Corresponding author: E-mail: [email protected] Keywords: genome evolution, structural variation, gene duplication Running title: Human and chimpanzee copy number variation 1 Downloaded from genome.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Copy number variants (CNVs) underlie many aspects of human phenotypic diversity and provide the raw material for gene duplication and gene family expansion. However, our understanding of their evolutionary significance remains limited. We performed comparative genomic hybridization on a single human microarray platform to identify CNVs among the genomes of 30 humans and 30 chimpanzees, as well as fixed copy number differences between species. We found that human and chimpanzee CNVs occur in orthologous genomic regions far more often than expected by chance and are strongly associated with the presence of highly homologous intra-chromosomal segmental duplications.
    [Show full text]
  • High Expression of the Sd Synthase B4GALNT2 Associates with Good
    cells Article High Expression of the Sda Synthase B4GALNT2 Associates with Good Prognosis and Attenuates Stemness in Colon Cancer Michela Pucci y, Inês Gomes Ferreira y, Martina Orlandani, Nadia Malagolini, Manuela Ferracin and Fabio Dall’Olio * Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, Via San Giacomo 14, 40126 Bologna, Italy; [email protected] (M.P.); [email protected] (I.G.F.); [email protected] (M.O.); [email protected] (N.M.); [email protected] (M.F.) * Correspondence: [email protected]; Tel.: +39-051-2094704 These authors have equal contribution. y Received: 25 February 2020; Accepted: 7 April 2020; Published: 11 April 2020 Abstract: Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by B4GALNT2 were studied in LS174T cells transfected with B4GALNT2 cDNA. Results: TCGA data indicate that patients with high B4GALNT2 expression in cancer tissues display longer survival than non-expressers. In LS174T cells, expression of B4GALNT2 did not affect the ability to heal a scratch wound or to form colonies in standard growth conditions but markedly reduced the growth in soft agar, the tridimensional (3D) growth as spheroids, and the number of cancer stem cells, indicating a specific effect of B4GALNT2 on the growth in poor adherence and stemness.
    [Show full text]
  • Identification of Human Glycosyltransferase Genes
    www.nature.com/scientificreports OPEN Identifcation of human glycosyltransferase genes expressed in erythroid cells predicts potential Received: 23 November 2017 Accepted: 8 March 2018 carbohydrate blood group loci Published: xx xx xxxx Magnus Jöud 1,2, Mattias Möller 1 & Martin L. Olsson 1,2 Glycans are biologically important structures synthesised by glycosyltransferase (GT) enzymes. Disruptive genetic null variants in GT genes can lead to serious illness but benign phenotypes are also seen, including antigenic diferences on the red blood cell (RBC) surface, giving rise to blood groups. To characterise known and potential carbohydrate blood group antigens without a known underlying gene, we searched public databases for human GT loci and investigated their variation in the 1000 Genomes Project (1000 G). We found 244 GT genes, distributed over 44 families. All but four GT genes had missense variants or other variants predicted to alter the amino acid sequence, and 149 GT genes (61%) had variants expected to cause null alleles, often associated with antigen-negative blood group phenotypes. In RNA-Seq data generated from erythroid cells, 155 GT genes were expressed at a transcript level comparable to, or higher than, known carbohydrate blood group loci. Filtering for GT genes predicted to cause a benign phenotype, a set of 30 genes remained, 16 of which had variants in 1000 G expected to result in null alleles. Our results identify potential blood group loci and could serve as a basis for characterisation of the genetic background underlying carbohydrate RBC antigens. Glycosyltransferases (GTs) are the enzymes (enzyme commission [EC] 2.4) that catalyse glycosylation, resulting in a wealth of glycan variants present on glycoproteins, glycosphingolipids and proteoglycans1.
    [Show full text]
  • Functional Relationship of CRC-Associated Glycans with Malignant Phenotype and Transcriptome Changes
    Alma Mater Studiorum – Università di Bologna DOTTORATO DI RICERCA IN Oncologia, Ematologia e Patologia Ciclo XXXI Settore Concorsuale: 06/A2 Settore Scientifico Disciplinare: MED04 Functional relationship of colorectal cancer- associated glycans with malignant phenotype and transcriptome changes Presentata da: Inês Isabel Gomes Ferreira Coordinatore Dottorato: Prof. Pier-Luigi Lollini Supervisore: Prof. Fabio Dall’Olio Esame finale anno 2019 Acknowledgements To the Marie Sklodowska Curie European committee for awarded me as one of the PhD students of the project H2020 GlyCoCan; To the Department of Experimental, Diagnostic and Specialty Medicine from Università di Bologna, for hosting me in this PhD project; To Professor Fabio Dall’Olio for accepting me as his PhD student in the Department of Experimental, Diagnostic and Specialty Medicine from Università di Bologna; for all the guidance and all knowledge passed to me during my period in his laboratory; To Professor Paula Videira from New University of Lisbon (Lisbon-Portugal) and Doctor Daniel Spencer from Ludger (Oxford-United Kingdom) for accepting me during my period aboard in their research laboratories; To Doctor Mariella Chiricolo and Doctor Nadia Malagolini for all the friendship, technical support and guidance during this PhD; To Doctor Francesco Vasuri from S.Orsola-Malpighi Hospital (Bologna-Italy) for all the work collaboration regarding the clinical samples; To Professor Manuela Ferracin from Università di Bologna for all the work collaboration regarding microarray analysis/TCGA database and for all the wise advices; To Professor Yoann Rombouts and Doctor Alexandre Stella from Institut de Pharmacologie et de Biologie Structurale (Toulouse-France) for the glycoproteomic analysis; To Doctor Rad Kozak from Ludger (Oxford-United Kingdom) for the help in glycomic data analysis; To LTTA microarray facility from University of Ferrara for all the technical support in the transcriptomic analysis; To my laboratory colleagues (Mariangela Catera, Giulia Venturi and Michella Pucci).
    [Show full text]
  • Interspecific Introgressive Origin of Genomic Diversity in the House Mouse
    Interspecific introgressive origin of genomic diversity in the house mouse Kevin J. Liua,1,2, Ethan Steinberga, Alexander Yozzoa, Ying Songb,3, Michael H. Kohnb,1, and Luay Nakhleha,b,1 aDepartment of Computer Science and bBioSciences, Rice University, Houston, TX 77005 Edited by John C. Avise, University of California, Irvine, CA, and approved November 12, 2014 (received for review April 4, 2014) We report on a genome-wide scan for introgression between the introgression from M. spretus into some M. m. domesticus pop- house mouse (Mus musculus domesticus) and the Algerian mouse ulations in the wild, involving the vitamin K epoxide reductase (Mus spretus), using samples from the ranges of sympatry and subcomponent 1 (Vkorc1) gene, which was later shown to be allopatry in Africa and Europe. Our analysis reveals wide variabil- more widespread in Europe, albeit geographically restricted to ity in introgression signatures along the genomes, as well as parts of southwestern and central Europe (11). across the samples. We find that fewer than half of the autosomes Major, unanswered questions arise from these studies. First, is in each genome harbor all detectable introgression, whereas the the vicinity around the Vkorc1 gene an isolated case of adaptive X chromosome has none. Further, European mice carry more introgression in the house mouse genome, or do many other such M. spretus alleles than the sympatric African ones. Using the regions exist? Second, is introgression between M. spretus and length distribution and sharing patterns of introgressed genomic M. m. domesticus common outside the range of sympatry? Third, tracts across the samples, we infer, first, that at least three distinct have there been other hybridization events, and, in particular, hybridization events involving M.
    [Show full text]
  • Interspecific Introgressive Origin of Genomic Diversity in the House Mouse
    Interspecific introgressive origin of genomic diversity in the house mouse Kevin J. Liua,1,2, Ethan Steinberga, Alexander Yozzoa, Ying Songb,3, Michael H. Kohnb,1, and Luay Nakhleha,b,1 aDepartment of Computer Science and bBioSciences, Rice University, Houston, TX 77005 Edited by John C. Avise, University of California, Irvine, CA, and approved November 12, 2014 (received for review April 4, 2014) We report on a genome-wide scan for introgression between the introgression from M. spretus into some M. m. domesticus pop- house mouse (Mus musculus domesticus) and the Algerian mouse ulations in the wild, involving the vitamin K epoxide reductase (Mus spretus), using samples from the ranges of sympatry and subcomponent 1 (Vkorc1) gene, which was later shown to be allopatry in Africa and Europe. Our analysis reveals wide variabil- more widespread in Europe, albeit geographically restricted to ity in introgression signatures along the genomes, as well as parts of southwestern and central Europe (11). across the samples. We find that fewer than half of the autosomes Major, unanswered questions arise from these studies. First, is in each genome harbor all detectable introgression, whereas the the vicinity around the Vkorc1 gene an isolated case of adaptive X chromosome has none. Further, European mice carry more introgression in the house mouse genome, or do many other such M. spretus alleles than the sympatric African ones. Using the regions exist? Second, is introgression between M. spretus and length distribution and sharing patterns of introgressed genomic M. m. domesticus common outside the range of sympatry? Third, tracts across the samples, we infer, first, that at least three distinct have there been other hybridization events, and, in particular, hybridization events involving M.
    [Show full text]
  • Biomedical Informatics
    BIOMEDICAL INFORMATICS Abstract GENE LIST AUTOMATICALLY DERIVED FOR YOU (GLAD4U): DERIVING AND PRIORITIZING GENE LISTS FROM PUBMED LITERATURE JEROME JOURQUIN Thesis under the direction of Professor Bing Zhang Answering questions such as ―Which genes are related to breast cancer?‖ usually requires retrieving relevant publications through the PubMed search engine, reading these publications, and manually creating gene lists. This process is both time-consuming and prone to errors. We report GLAD4U (Gene List Automatically Derived For You), a novel, free web-based gene retrieval and prioritization tool. The quality of gene lists created by GLAD4U for three Gene Ontology terms and three disease terms was assessed using ―gold standard‖ lists curated in public databases. We also compared the performance of GLAD4U with that of another gene prioritization software, EBIMed. GLAD4U has a high overall recall. Although precision is generally low, its prioritization methods successfully rank truly relevant genes at the top of generated lists to facilitate efficient browsing. GLAD4U is simple to use, and its interface can be found at: http://bioinfo.vanderbilt.edu/glad4u. Approved ___________________________________________ Date _____________ GENE LIST AUTOMATICALLY DERIVED FOR YOU (GLAD4U): DERIVING AND PRIORITIZING GENE LISTS FROM PUBMED LITERATURE By Jérôme Jourquin Thesis Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Biomedical Informatics May, 2010 Nashville, Tennessee Approved: Professor Bing Zhang Professor Hua Xu Professor Daniel R. Masys ACKNOWLEDGEMENTS I would like to express profound gratitude to my advisor, Dr. Bing Zhang, for his invaluable support, supervision and suggestions throughout this research work.
    [Show full text]