DOCSLIB.ORG

Uq00522f8 OA.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Uq00522f8 OA.Pdf 1 2 DR THAISE MELO (Orcid ID : 0000-0003-0983-4602) 3 DR MARINA R. S. FORTES (Orcid ID : 0000-0002-7254-1960) 4 5 6 Article type : Original Article 7 8 9 Short Running Title: Across-breed QTL validation for sexual precocity in tropical cattle 10 Title: ACROSS-BREED VALIDATION STUDY CONFIRMS AND IDENTIFIES 11 NEW LOCI ASSOCIATED WITH SEXUAL PRECOCITY IN BRAHMAN AND 12 NELLORE CATTLE1 13 Thaise Pinto de Melo*, Marina Rufino Salinas Fortes†‡, Ben Hayes‡, Lucia Galvão de 14 Albuquerque*§, Roberto Carvalheiro*§ 15 16 *Department of Animal Science, School of Agricultural and Veterinarian Sciences, 17 FCAV/ UNESP - Sao Paulo State University, Jaboticabal, Sao Paulo, 14884-900, 18 Brazil. 19 †The University of Queensland, School of Chemistry and Molecular Biosciences, St 20 Lucia, Queensland 4072, Australia. 21 ‡The University of Queensland, Queensland Alliance for Agriculture and Food 22 Innovation, St Lucia, Queensland 4072, Australia. 23 §National Council for Scientific and Technological Development (CNPq), Brasília, 24 Distrito Federal, Brazil. 25 Corresponding author: Roberto Carvalheiro, School of Agricultural and Veterinarian 26 Sciences, FCAV/ UNESP - Sao Paulo State University, Jaboticabal, Brazil. Email: 27 [email protected] Manuscript 28 This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/JBG.12429 This article is protected by copyright. All rights reserved 29 ABSTRACT: The aim of this study was to identify candidate regions associated with 30 sexual precocity in Bos indicus. Nellore and Brahman were set as validation and 31 discovery populations, respectively. SNP selected in Brahman to validate in Nellore 32 were from: gene regions affecting reproductive traits (G1), and significant SNP (P ≤ 10- 33 3) from a meta-analysis (G2). In the validation population early pregnancy (EP) and 34 scrotal circumference (SC) were evaluated. To perform GWAS in validation population 35 we used regression and Bayes C. SNP with P ≤ 10-3 in regression and Bayes Factor ≥ 3 36 in Bayes C were deemed significant. Significant SNP (for EP or SC) or SNP in their ± 37 250 Kb vicinity region, which were in at least one discovery set (G1 or G2) were 38 considered validated. SNP identified in both G1 and G2 were considered candidate. For 39 EP 145 SNP were validated in G1 and 41 in G2, for SC these numbers were 14 and 2. 40 For EP 21 candidate SNP were detected (G1 and G2). For SC no candidate SNP were 41 identified. Validated SNP and their vicinity region were located close to QTL or genes 42 related to reproductive traits and were enriched in gene ontology terms related with 43 reproductive success. These are therefore, strong candidate regions for sexual precocity 44 in Nellore and Brahman. 45 Keywords: Bos indicus, discovery population, reproductive traits, SNP validation, 46 tropical beef cattle 47 INTRODUCTION 48 49 Across-breed validation studies are commonly used to validate quantitative trait 50 loci (QTL) for several traits. In Genome-wide association studies (GWAS) those 51 significant markers under an empirical P-value for the same or correlated traits in 52 different breeds are likely tagging QTL that segregate across-breeds. These QTLs may 53 harbor some important genes affecting both populations. Karlsson et al. (2007) used this 54 approach to validate single nucleotide polymorphisms (SNP) markers in different dog 55 breeds. They notice that this strategy was highly efficient to fine-mapping across 56 breeds. 57 The probability of finding common QTL for correlated traits in breeds that share 58 common ancestry is expected to be higher than in breeds with very distinct genetic Author Manuscript 59 origin. This is because breeds that do not share a recent common ancestor are more 60 genetically distinct from each other. Genetic differences increase with distance to 61 common ancestors. Distinct genetic origin affects the linkage disequilibrium pattern 62 between SNPs at long-ranges, and by consequence it affects QTL mapping (Goddard & This article is protected by copyright. All rights reserved 63 Hayes, 2009). As Nellore and Brahman are both Bos indicus breeds, and Brahman was 64 originally developed by three base breeds, Gir, Guzerat and Nellore (Briggs & Briggs, 65 1980), the likelihood of both breeds sharing QTL controlling correlated traits is higher 66 than in unrelated breeds. 67 Several strategies have been used to conduct across-breed validation studies. 68 Pryce et al. (2010) used two dairy breeds to validate QTL for milk production and 69 fertility traits. They distributed Holstein bulls in a discovery population and younger 70 Holstein bulls and Jersey bulls in a validation population. SNP that were detected as 71 significant at an empirical threshold P-value in discovery and validation populations 72 were considered validated. Also validating fertility traits in dairy cattle, Höglund et al. 73 (2014) used three breeds to validate genomic associations. They used one breed as 74 discovery population and the other two breeds as validation populations. They argued 75 that using two populations simultaneously to validate significant associations is a 76 powerful strategy to decrease the risk of false positive association. 77 Genic regions are strong candidate regions to present QTL segregating across 78 related breeds because it is expected that the metabolic pathways in which these genes 79 are involved are conserved across breeds. Also, regions with pleiotropic effect across 80 related traits could result in higher number of true positive validated associations across 81 breeds, because genes that are controlling multiple traits in a breed might preserve 82 similar pattern of pleiotropic effect in another related breed (Saatchi et al., 2014). 83 The aim of this study was to validate in a Nellore population genomic regions 84 associated with sexual precocity that were reported for Brahman. We used as discovery 85 data two SNP sets pre-selected in a Brahman population, 1) from gene regions 86 previously reported as significant for reproductive traits, and 2) from significant 87 associations detected in a meta-analysis study of sexual precocity traits. 88 89 MATERIAL AND METHODS 90 Ethics Statement 91 All managements and procedures involving production, maintenance and use of 92 Nellore animals were certified and approved by the National Council of Animal Author Manuscript 93 Experimentation Control (CONCEA, 2008) and Use Committee at University of Sao 94 Paulo, Jaboticabal Campus (18.340/16). Regarding Brahman animals, Animal care and 95 Use committee approval was not required because the data is from existing databases 96 described in the following section. This article is protected by copyright. All rights reserved 97 98 Discovery population 99 The discovery population was composed by Brahman animals. Phenotypes were 100 provided by Cooperative Research Centre for Beef Genetic Technologies (Beef CRC). 101 Brahman phenotypes included the female traits age when the first corpus luteum (CL) 102 was observed (AGECL), first postpartum anoestrus interval (PPAI), ability to ovulate 103 prior to weaning the calf (PW), and the male traits scrotal circumference (SC) measured 104 at 12, 18 and 24 months of age (SC12, SC18, SC24). 105 The AGECL was defined as the number of days from the heifer birth to the first 106 CL detected. PPAI, measured in days, was calculated as the difference between the 107 calving date and the date of the first observed ovulation postpartum. PW, a binary trait 108 was defined as 0 for females that had success to ovulate before weaning her calf or 1 for 109 those females that failed. For all female traits ovarian ultrasounds were carried out to 110 verify the presence of CL that is an indicator of the ovulation, at every 4 to 6 weeks 111 after heifers achieved 200 Kg of weight. 112 Scrotal circumference was measured in cm, with a standard metal tape. For 113 females and males, contemporary groups (CG) were defined by the concatenation year 114 of birth and management group information (defined as cohorts). The age of young 115 bulls at recording was considered a covariate for SC. Details about animals, cohorts and 116 phenotypes are described in Johnston et al. (2009), Johnston et al. (2010), Burns et al. 117 (2013), Corbet et al. (2013) and Fortes et al. (2018). 118 Animals were genotyped with the Illumina BovineSNP50 V1 and V2. Genotypes 119 were imputed for high-density panel using Beagle software v.3.2 (Browning & 120 Browning, 2009) and a reference population of representative animals of the Beef CRC 121 population genotyped using the high-density Illumina Bovine HD Assay (Illumina, San 122 Diego, CA, USA), as described by Fortes et al. (2013a). Quality control excluded 123 samples with call rate < 98%, SNP in non-autosomal regions, with call rate < 85% and 124 minor allele frequency (MAF) < 0.02. The number of SNP after quality control was 125 625,041 for females and 612,992 for males. Details about genotypes and imputation are 126 described in Fortes et al. (2013a). Author Manuscript 127 128 Validation population 129 Data from Nellore animals were used as validation population. Phenotypic 130 information was obtained from Alliance Nellore dataset. The animals considered in this This article is protected by copyright. All rights reserved 131 study were born in eight farms distributed over Midwest, Southeast and Northeast of 132 Brazil. In general, two breeding seasons are applied during the year, where the females 133 are either artificially inseminated or naturally mated. The heifers are exposed in the 134 early breeding season at around 16 months of age. After 60 days of the early breeding 135 season, pregnancy is confirmed and those females that failed in conceiving in the first 136 breeding season had a second opportunity at around 2 years old.
Load more

Recommended publications
  • Analysis of Gene Expression Data for Gene Ontology
    ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • A Molecular and Genetic Analysis of Otosclerosis
    A molecular and genetic analysis of otosclerosis Joanna Lauren Ziff Submitted for the degree of PhD University College London January 2014 1 Declaration I, Joanna Ziff, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Where work has been conducted by other members of our laboratory, this has been indicated by an appropriate reference. 2 Abstract Otosclerosis is a common form of conductive hearing loss. It is characterised by abnormal bone remodelling within the otic capsule, leading to formation of sclerotic lesions of the temporal bone. Encroachment of these lesions on to the footplate of the stapes in the middle ear leads to stapes fixation and subsequent conductive hearing loss. The hereditary nature of otosclerosis has long been recognised due to its recurrence within families, but its genetic aetiology is yet to be characterised. Although many familial linkage studies and candidate gene association studies to investigate the genetic nature of otosclerosis have been performed in recent years, progress in identifying disease causing genes has been slow. This is largely due to the highly heterogeneous nature of this condition. The research presented in this thesis examines the molecular and genetic basis of otosclerosis using two next generation sequencing technologies; RNA-sequencing and Whole Exome Sequencing. RNA–sequencing has provided human stapes transcriptomes for healthy and diseased stapes, and in combination with pathway analysis has helped identify genes and molecular processes dysregulated in otosclerotic tissue. Whole Exome Sequencing has been employed to investigate rare variants that segregate with otosclerosis in affected families, and has been followed by a variant filtering strategy, which has prioritised genes found to be dysregulated during RNA-sequencing.
    [Show full text]
  • Regulation of Neuronal Gene Expression and Survival by Basal NMDA Receptor Activity: a Role for Histone Deacetylase 4
    The Journal of Neuroscience, November 12, 2014 • 34(46):15327–15339 • 15327 Cellular/Molecular Regulation of Neuronal Gene Expression and Survival by Basal NMDA Receptor Activity: A Role for Histone Deacetylase 4 Yelin Chen,1 Yuanyuan Wang,1 Zora Modrusan,3 Morgan Sheng,1 and Joshua S. Kaminker1,2 Departments of 1Neuroscience, 2Bioinformatics and Computational Biology, and 3Molecular Biology, Genentech Inc., South San Francisco, California 94080 Neuronal gene expression is modulated by activity via calcium-permeable receptors such as NMDA receptors (NMDARs). While gene expression changes downstream of evoked NMDAR activity have been well studied, much less is known about gene expression changes that occur under conditions of basal neuronal activity. In mouse dissociated hippocampal neuronal cultures, we found that a broad NMDAR antagonist, AP5, induced robust gene expression changes under basal activity, but subtype-specific antagonists did not. While some of the gene expression changes are also known to be downstream of stimulated NMDAR activity, others appear specific to basal NMDARactivity.ThegenesalteredbyAP5treatmentofbasalcultureswereenrichedforpathwaysrelatedtoclassIIahistonedeacetylases (HDACs), apoptosis, and synapse-related signaling. Specifically, AP5 altered the expression of all three class IIa HDACs that are highly expressed in the brain, HDAC4, HDAC5, and HDAC9, and also induced nuclear accumulation of HDAC4. HDAC4 knockdown abolished a subset of the gene expression changes induced by AP5, and led to neuronal death under
    [Show full text]
  • What Is the Extent of the Role Played by Genetic Factors in Periodontitis?
    Perio Insight 4 Summer 2017 www.efp.org/perioinsight DEBATE EXPERT VIEW FOCUS RESEARCH Editor: Joanna Kamma What is the extent of the role played by genetic factors in periodontitis? Discover latest JCP research hile genetic factors are known to play a role in In a comprehensive overview of current knowledge, The Journal of Clinical Periodontology Wperiodontitis, a lot of research still needs to be they outline what is known today and discuss the (JCP) is the official scientific publication done to understand the mechanisms that are involved. most promising lines for future inquiry. of the European Federation of Indeed, the limited extent to which the genetic They note that the phenotypes of aggressive Periodontology (EFP). It publishes factors associated with periodontitis have been periodontitis (AgP) and chronic periodontitis (CP) may research relating to periodontal and peri- identified is “somewhat disappointing”, say Bruno not be as distinct as previously assumed because they implant diseases and their treatment. G. Loos and Deon P.M. Chin, from the Academic share genetic and other risk factors. The six JCP articles summarised in this Centre for Dentistry in Amsterdam. More on pages 2-5 edition of Perio Insight cover: (1) how periodontitis changes renal structures by oxidative stress and lipid peroxidation; (2) gingivitis and lifestyle influences on high-sensitivity C-reactive protein and interleukin 6 in adolescents; (3) the long-term efficacy of periodontal Researchers call regenerative therapies; (4) tooth loss in generalised aggressive periodontitis; (5) the association between diabetes for global action mellitus/hyperglycaemia and peri- implant diseases; (6) the efficacy of on periodontal collagen matrix seal and collagen sponge on ridge preservation in disease combination with bone allograft.
    [Show full text]
  • Reporterseq Reveals Genome-Wide Dynamic Modulators of the Heat
    RESEARCH ARTICLE ReporterSeq reveals genome-wide dynamic modulators of the heat shock response across diverse stressors Brian D Alford1†, Eduardo Tassoni-Tsuchida1,2†, Danish Khan1, Jeremy J Work1, Gregory Valiant3, Onn Brandman1* 1Department of Biochemistry, Stanford University, Stanford, United States; 2Department of Biology, Stanford University, Stanford, United States; 3Department of Computer Science, Stanford University, Stanford, United States Abstract Understanding cellular stress response pathways is challenging because of the complexity of regulatory mechanisms and response dynamics, which can vary with both time and the type of stress. We developed a reverse genetic method called ReporterSeq to comprehensively identify genes regulating a stress-induced transcription factor under multiple conditions in a time- resolved manner. ReporterSeq links RNA-encoded barcode levels to pathway-specific output under genetic perturbations, allowing pooled pathway activity measurements via DNA sequencing alone and without cell enrichment or single-cell isolation. We used ReporterSeq to identify regulators of the heat shock response (HSR), a conserved, poorly understood transcriptional program that protects cells from proteotoxicity and is misregulated in disease. Genome-wide HSR regulation in budding yeast was assessed across 15 stress conditions, uncovering novel stress-specific, time- specific, and constitutive regulators. ReporterSeq can assess the genetic regulators of any transcriptional pathway with the scale of pooled genetic screens and the precision of pathway- specific readouts. *For correspondence: [email protected] †These authors contributed equally to this work Introduction Competing interests: The The heat shock response (HSR) is a conserved stress response that shields cells from cytoplasmic authors declare that no proteotoxicity by increasing the expression of protective proteins (Lindquist, 1986; Mori- competing interests exist.
    [Show full text]
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • A Genome-Wide Rnai Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila
    A Genome-Wide RNAi Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila Doctoral Thesis In partial fulfilment of the requirements for the degree “Doctor rerum naturalium (Dr. rer. nat.)” in the Molecular Medicine Study Programme at the Georg-August University Göttingen submitted by Hannes Voßfeldt born in Zerbst/Anhalt, Germany Göttingen, January 2012 FÜR MEINE FAMILIE - IM GEDENKEN AN NADINE DU FEHLST. … IT MATTERS NOT HOW STRAIT THE GATE, HOW CHARGED WITH PUNISHMENTS THE SCROLL, I AM THE MASTER OF MY FATE: I AM THE CAPTAIN OF MY SOUL. … Invictus – William Ernest Henley Members of the Thesis Committee: Supervisor Prof. Dr. med. Jörg B. Schulz Head of Department of Neurology University Medical Centre RWTH Aachen University Pauwelsstrasse 30 52074 Aachen Second member of the Thesis Committee Prof. Dr. rer. nat. Ernst A. Wimmer Head of Department of Developmental Biology Johann Friedrich Blumenbach Institute of Zoology and Anthropology Georg-August University Göttingen Justus-von-Liebig-Weg 11 37077 Göttingen Third member of the Thesis Committee Dr. rer. nat. Till Marquardt Research Group Developmental Neurobiology European Neuroscience Institute Göttingen Grisebachstrasse 5 37077 Göttingen Date of Disputation: 2 April 2012 Affidavit I hereby declare that my doctoral thesis entitled “A Genome-Wide RNAi Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila” has been written independently with no other sources and aids than quoted. Göttingen, January 2012 Hannes Voßfeldt LIST OF PUBLICATIONS IV List of Publications Parts of this work have already been published with authorisation of Prof. Jörg B. Schulz, Head of the Department of Neurology, University Medical Centre of the RWTH Aachen University, on behalf of the thesis committee.
    [Show full text]
  • Nuclear Export of Ubiquitinated Proteins Via the UBIN-POST System
    Nuclear export of ubiquitinated proteins via the PNAS PLUS UBIN-POST system Shoshiro Hirayamaa,1,2, Munechika Sugiharab,1, Daisuke Moritoc,d, Shun-ichiro Iemurae, Tohru Natsumee, Shigeo Murataa, and Kazuhiro Nagatab,c,d,2 aLaboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan; bFaculty of Life Sciences, Kyoto Sangyo University, Kyoto, 603-8555, Japan; cInstitute for Protein Dynamics, Kyoto Sangyo University, Kyoto, 603-8555, Japan; dCore Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, 332-0012, Japan; and eBiomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, 135-0064, Japan Edited by Brenda A. Schulman, Max Planck Institute of Biochemistry, Martinsried, Germany, and approved March 19, 2018 (received for review June 19, 2017) Although mechanisms for protein homeostasis in the cytosol have folding enzymes with a broad range of activities, two strong and been studied extensively, those in the nucleus remain largely flexible proteolytic machineries (namely, the UPS and autophagy), unknown. Here, we identified that a protein complex mediates and regulated protein deposition systems, such as the aggresome, export of polyubiquitinated proteins from the nucleus to the aggresome-like induced structure (ALIS), insoluble protein de- cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing pro- posit (IPOD), and juxta nuclear quality control compartment tein, shuttled between the nucleus and the cytosol in a CRM1- (JUNQ), which sequester damaged proteins (9–11). Thus, the dependent manner, despite the lack of intrinsic nuclear export signal cytosol constitutes a robust system for maintaining protein ho- (NES). Instead, the UBIN binding protein polyubiquitinated substrate meostasis that extends to distinct organelles within the cytosol.
    [Show full text]
  • Molecular and Epigenetic Features of Melanomas and Tumor Immune
    Seremet et al. J Transl Med (2016) 14:232 DOI 10.1186/s12967-016-0990-x Journal of Translational Medicine RESEARCH Open Access Molecular and epigenetic features of melanomas and tumor immune microenvironment linked to durable remission to ipilimumab‑based immunotherapy in metastatic patients Teofila Seremet1,3*† , Alexander Koch2†, Yanina Jansen1, Max Schreuer1, Sofie Wilgenhof1, Véronique Del Marmol3, Danielle Liènard3, Kris Thielemans4, Kelly Schats5, Mark Kockx5, Wim Van Criekinge2, Pierre G. Coulie6, Tim De Meyer2, Nicolas van Baren6,7 and Bart Neyns1 Abstract Background: Ipilimumab (Ipi) improves the survival of advanced melanoma patients with an incremental long-term benefit in 10–15 % of patients. A tumor signature that correlates with this survival benefit could help optimizing indi- vidualized treatment strategies. Methods: Freshly frozen melanoma metastases were collected from patients treated with either Ipi alone (n: 7) or Ipi combined with a dendritic cell vaccine (TriMixDC-MEL) (n: 11). Samples were profiled by immunohistochemistry (IHC), whole transcriptome (RNA-seq) and methyl-DNA sequencing (MBD-seq). Results: Patients were divided in two groups according to clinical evolution: durable benefit (DB; 5 patients) and no clinical benefit (NB; 13 patients). 20 metastases were profiled by IHC and 12 were profiled by RNA- and MBD-seq. 325 genes were identified as differentially expressed between DB and NB. Many of these genes reflected a humoral and cellular immune response. MBD-seq revealed differences between DB and NB patients in the methylation of genes linked to nervous system development and neuron differentiation. DB tumors were more infiltrated by CD8+ and PD-L1+ cells than NB tumors.
    [Show full text]
  • NFKBIL1 Antibody (Center) Blocking Peptide Synthetic Peptide Catalog # Bp10682c
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 NFKBIL1 Antibody (Center) Blocking peptide Synthetic peptide Catalog # BP10682c Specification NFKBIL1 Antibody (Center) Blocking NFKBIL1 Antibody (Center) Blocking peptide - peptide - Background Product Information This gene encodes a divergent member of the Primary Accession Q9UBC1 I-kappa-Bfamily of proteins. Its function has not been determined. The genelies within the major histocompatibility complex (MHC) class NFKBIL1 Antibody (Center) Blocking peptide - Additional Information Iregion on chromosome 6. Multiple transcript variants encodingdifferent isoforms have been found for this gene. [provided byRefSeq]. Gene ID 4795 NFKBIL1 Antibody (Center) Blocking Other Names peptide - References NF-kappa-B inhibitor-like protein 1, Inhibitor of kappa B-like protein, I-kappa-B-like Clancy, R.M., et al. Arthritis Rheum. protein, IkappaBL, Nuclear factor of kappa 62(11):3415-3424(2010)Bailey, S.D., et al. light polypeptide gene enhancer in B-cells Diabetes Care inhibitor-like 1, NFKBIL1, IKBL 33(10):2250-2253(2010)Ucisik-Akkaya, E., et Format al. Mol. Hum. Reprod. Peptides are lyophilized in a solid powder 16(10):770-777(2010)Rose, J.E., et al. Mol. format. Peptides can be reconstituted in Med. 16 (7-8), 247-253 (2010) :Owecki, M.K., solution using the appropriate buffer as et al. Pol. Merkur. Lekarski needed. 28(167):366-370(2010) Storage Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C. Precautions This product is for research use only. Not for use in diagnostic or therapeutic procedures.
    [Show full text]