DOCSLIB.ORG

Inbreeding and Inbreeding Depression in Linebred Beef Cattle (PDF)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

INBREEDING AND INBREEDING DEPRESSION IN LINEBRED BEEF CATTLE by Jordan Kelley Hieber A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Animal Science MONTANA STATE UNIVERSITY Bozeman, Montana April 2020 ©COPYRIGHT by Jordan Kelley Hieber 2020 All Rights Reserved ii DEDICATION To my family and close friends for their continuous support and countless words of encouragement. To my great papa, great grandma, and grandpa who I know are watching over me and cheering me on from above. ii ACKNOWLEDGEMENTS First and foremost, I must thank Drs. Jennifer Thomson, Jane Ann Boles, and Rachel Endecott for their constant support and friendship since I moved to Montana, and Dr. Elhamidi Hay for his expertise and being a member of my committee. This project also would not have been possible without the funding provided by the Montana State University Montana Agricultural Experiment Station, the United States Department of Agriculture – Agriculture Research Service, and the Montana State University Graduate School. I would like to thank those at the Northern Agricultural Research Center who helped collect data and work cows for my project, especially Dr. Darrin Boss, Julia Dafoe, and Cory Parsons. To my academic “siblings” and fellow graduate students, thank you for all the laughs, support, and shoulders to lean on. I also cannot forget all the amazing faculty and staff within ABB that have provided guidance and given countless words of encouragement. I owe the largest thank you to my support system over the last four years, my family and friends. Thank you for providing an endless amount of support and reassurance throughout this adventure, I love you all! To my boyfriend, thank you for all of your support! You may be a recent addition to my life, but you have provided limitless encouragement. Staying up with me during the late nights means more to me than you’ll know. I love you more! iii TABLE OF CONTENTS 1. INTRODUCTION AND LITERATURE REVIEW ...................................................... 1 Introduction ..................................................................................................................... 1 Inbreeding and Inbreeding Depression in Linebred Beef Cattle ............................ 1 Genetic Improvement with the Carcass Merit Program ......................................... 2 Linebreeding and Heterosis ............................................................................................ 3 Inbreeding and Inbreeding Depression ........................................................................... 5 Effects of Inbreeding on Production Traits ..................................................................... 9 Line 1 and Line 4 Hereford Histories ........................................................................... 10 Line 1 .................................................................................................................... 10 Line 4 .................................................................................................................... 12 Methodology ................................................................................................................. 12 Runs of Homozygosity ......................................................................................... 12 Genome-Wide Association Studies ...................................................................... 14 Carcass Characteristics and Maternal Performance ...................................................... 17 2. INBREEDING LEVELS OF THE LINE 4 HEREFORD CATTLE POPULATION ............................................................................................................. 21 Introduction ................................................................................................................... 21 Materials and Methods .................................................................................................. 22 Results and Discussion ................................................................................................. 26 Conclusions ................................................................................................................... 31 3. INBREEDING LEVELS OF THE LINE 1 HEREFORD CATTLE POPULATION ............................................................................................................. 45 Introduction ................................................................................................................... 45 Materials and Methods .................................................................................................. 46 Results and Discussion ................................................................................................. 50 Conclusions ................................................................................................................... 55 4. IDENTIFICATION OF GENETIC MARKERS AND QTL FOR CARCASS QUALITY TRAITS WITHIN THE AMERICAN SIMMENTAL ASSOCIATION CARCASS MERIT PROGRAM ...................................................... 71 Introduction ................................................................................................................... 71 Materials and Methods .................................................................................................. 72 Results and Discussion ................................................................................................. 75 Single-locus Model ............................................................................................... 75 Multi-locus Model ................................................................................................ 77 Genetic Correlations ............................................................................................. 78 iv TABLE OF CONTENTS CONTINUED Conclusions ................................................................................................................... 79 5. CONCLUDING REMARKS ........................................................................................ 83 REFERENCES CITED ..................................................................................................... 87 APPENDICES ................................................................................................................ 105 APPENDIX A: Line 4 Supplementary Tables and Figures ................................ 106 APPENDIX B: Line 1 Supplementary Tables and Figures ................................ 211 APPENDIX C: American Simmental Association Carcass Merit Program Single-Locus Model Supplementary Tables and Figures ................................................................................ 276 APPENDIX D: American Simmental Association Carcass Merit Program Multi-Locus Model Supplementary Tables and Figures ................................................................................ 319 v LIST OF TABLES Table Page 1. Runs of homozygosity (ROH) locations and number of significant single nucleotide polymorphism (SNP) for each trait in each location ............ 33 2. Strongly significant single nucleotide polymorphism (SNP; located above -log10(p-value) of 5 x 10-4) on a Manhattan plot ................................... 35 3. Runs of homozygosity (ROH) locations and number of significant single nucleotide polymorphism (SNP) for each trait in each location ............ 57 4. Strongly significant single nucleotide polymorphism (SNP; located above -log10(p-value) of 5 x 10-4) on a Manhattan plot ................................... 59 5. Genome-wide association significant markers (located above -log10(p-value) of 5 x 10-8) on a Manhattan plot ............................................. 80 6. Genetic correlations between carcass and maternal traits ................................. 81 vi LIST OF FIGURES Figure Page 1. A heatmap showing relatedness of individuals within the Line 4 population. The dark blue line diagonal line is individuals plotted against themselves and the darkest blue boxes above or below the diagonal represent individuals that are more related ........................................ 36 2. A principle component analysis (PCA) plot containing a scatter plot for individual animals on the first and second principle components .............. 37 3. Number of animals by year of birth between 1964 and 2018, and trend of average pedigree inbreeding (blue line) .............................................. 38 4. Manhattan plot for birth weight (BW). Genome-wide significance threshold was -log10(p-value) of 5 x 10-4 and vertical clusters of markers indicate suggestive QTL ..................................................................... 39 5. Regions of the genome with runs of homozygosity (ROH) on an individual chromosome basis (left side of chromosomes, blue lines) and significant single nucleotide polymorphism (SNP; p < 0.005) for birth weight (BW) identified by regression analysis (right side of chromosomes, red arrows). Height of arrow corresponds to number of consecutive significant SNP ......................................................................... 40 6. Regions of the genome with runs of homozygosity (ROH) on an individual chromosome basis (left side of chromosomes, blue lines) and significant single nucleotide polymorphism (SNP; p < 0.005) for weaning weight (WW) identified by regression analysis (right side of chromosomes, red arrows). Height of arrow corresponds to number of consecutive significant SNP ........................................................................
Recommended publications
  • Analyses of Allele-Specific Gene Expression in Highly Divergent

    Analyses of Allele-Specific Gene Expression in Highly Divergent

    ARTICLES Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance James J Crowley1,10, Vasyl Zhabotynsky1,10, Wei Sun1,2,10, Shunping Huang3, Isa Kemal Pakatci3, Yunjung Kim1, Jeremy R Wang3, Andrew P Morgan1,4,5, John D Calaway1,4,5, David L Aylor1,9, Zaining Yun1, Timothy A Bell1,4,5, Ryan J Buus1,4,5, Mark E Calaway1,4,5, John P Didion1,4,5, Terry J Gooch1,4,5, Stephanie D Hansen1,4,5, Nashiya N Robinson1,4,5, Ginger D Shaw1,4,5, Jason S Spence1, Corey R Quackenbush1, Cordelia J Barrick1, Randal J Nonneman1, Kyungsu Kim2, James Xenakis2, Yuying Xie1, William Valdar1,4, Alan B Lenarcic1, Wei Wang3,9, Catherine E Welsh3, Chen-Ping Fu3, Zhaojun Zhang3, James Holt3, Zhishan Guo3, David W Threadgill6, Lisa M Tarantino7, Darla R Miller1,4,5, Fei Zou2,11, Leonard McMillan3,11, Patrick F Sullivan1,5,7,8,11 & Fernando Pardo-Manuel de Villena1,4,5,11 Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Because regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in further characterizing these mechanisms. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. Effects from these variants influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect.
  • Comprehensive Molecular Characterization of Gastric Adenocarcinoma

    Comprehensive Molecular Characterization of Gastric Adenocarcinoma

    Comprehensive molecular characterization of gastric adenocarcinoma The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Bass, A. J., V. Thorsson, I. Shmulevich, S. M. Reynolds, M. Miller, B. Bernard, T. Hinoue, et al. 2014. “Comprehensive molecular characterization of gastric adenocarcinoma.” Nature 513 (7517): 202-209. doi:10.1038/nature13480. http://dx.doi.org/10.1038/ nature13480. Published Version doi:10.1038/nature13480 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987344 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2014 September 22. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nature. 2014 September 11; 513(7517): 202–209. doi:10.1038/nature13480. Comprehensive molecular characterization of gastric adenocarcinoma A full list of authors and affiliations appears at the end of the article. Abstract Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer
  • Mechanical Forces Induce an Asthma Gene Signature in Healthy Airway Epithelial Cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T

    Mechanical Forces Induce an Asthma Gene Signature in Healthy Airway Epithelial Cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T

    www.nature.com/scientificreports OPEN Mechanical forces induce an asthma gene signature in healthy airway epithelial cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T. Kho4, Kelan Tantisira1, Marc Santolini 1,5, Feixiong Cheng6,7,8, Jennifer A. Mitchel3, Maureen McGill3, Michael J. O’Sullivan3, Margherita De Marzio1,3, Amitabh Sharma1, Scott H. Randell9, Jefrey M. Drazen3, Jefrey J. Fredberg3 & Scott T. Weiss1,3* Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufcient to induce infammatory, late repair, and fbrotic pathways. Remarkably, this molecular profle of non-asthmatic cells after compression recapitulated the profle of asthmatic cells before compression. Together, these results show that even in the absence of any infammatory stimulus, mechanical compression alone is sufcient to induce an asthma-like molecular signature. Bronchial epithelial cells (BECs) form a physical barrier that protects pulmonary airways from inhaled irritants and invading pathogens1,2. Moreover, environmental stimuli such as allergens, pollutants and viruses can induce constriction of the airways3 and thereby expose the bronchial epithelium to compressive mechanical stress. In BECs, this compressive stress induces structural, biophysical, as well as molecular changes4,5, that interact with nearby mesenchyme6 to cause epithelial layer unjamming1, shedding of soluble factors, production of matrix proteins, and activation matrix modifying enzymes, which then act to coordinate infammatory and remodeling processes4,7–10.
  • Seq2pathway Vignette

    Seq2pathway Vignette

    seq2pathway Vignette Bin Wang, Xinan Holly Yang, Arjun Kinstlick May 19, 2021 Contents 1 Abstract 1 2 Package Installation 2 3 runseq2pathway 2 4 Two main functions 3 4.1 seq2gene . .3 4.1.1 seq2gene flowchart . .3 4.1.2 runseq2gene inputs/parameters . .5 4.1.3 runseq2gene outputs . .8 4.2 gene2pathway . 10 4.2.1 gene2pathway flowchart . 11 4.2.2 gene2pathway test inputs/parameters . 11 4.2.3 gene2pathway test outputs . 12 5 Examples 13 5.1 ChIP-seq data analysis . 13 5.1.1 Map ChIP-seq enriched peaks to genes using runseq2gene .................... 13 5.1.2 Discover enriched GO terms using gene2pathway_test with gene scores . 15 5.1.3 Discover enriched GO terms using Fisher's Exact test without gene scores . 17 5.1.4 Add description for genes . 20 5.2 RNA-seq data analysis . 20 6 R environment session 23 1 Abstract Seq2pathway is a novel computational tool to analyze functional gene-sets (including signaling pathways) using variable next-generation sequencing data[1]. Integral to this tool are the \seq2gene" and \gene2pathway" components in series that infer a quantitative pathway-level profile for each sample. The seq2gene function assigns phenotype-associated significance of genomic regions to gene-level scores, where the significance could be p-values of SNPs or point mutations, protein-binding affinity, or transcriptional expression level. The seq2gene function has the feasibility to assign non-exon regions to a range of neighboring genes besides the nearest one, thus facilitating the study of functional non-coding elements[2]. Then the gene2pathway summarizes gene-level measurements to pathway-level scores, comparing the quantity of significance for gene members within a pathway with those outside a pathway.
  • List of Genes Associated with Sudden Cardiac Death (Scdgseta) Gene

    List of Genes Associated with Sudden Cardiac Death (Scdgseta) Gene

    List of genes associated with sudden cardiac death (SCDgseta) mRNA expression in normal human heart Entrez_I Gene symbol Gene name Uniprot ID Uniprot name fromb D GTEx BioGPS SAGE c d e ATP-binding cassette subfamily B ABCB1 P08183 MDR1_HUMAN 5243 √ √ member 1 ATP-binding cassette subfamily C ABCC9 O60706 ABCC9_HUMAN 10060 √ √ member 9 ACE Angiotensin I–converting enzyme P12821 ACE_HUMAN 1636 √ √ ACE2 Angiotensin I–converting enzyme 2 Q9BYF1 ACE2_HUMAN 59272 √ √ Acetylcholinesterase (Cartwright ACHE P22303 ACES_HUMAN 43 √ √ blood group) ACTC1 Actin, alpha, cardiac muscle 1 P68032 ACTC_HUMAN 70 √ √ ACTN2 Actinin alpha 2 P35609 ACTN2_HUMAN 88 √ √ √ ACTN4 Actinin alpha 4 O43707 ACTN4_HUMAN 81 √ √ √ ADRA2B Adrenoceptor alpha 2B P18089 ADA2B_HUMAN 151 √ √ AGT Angiotensinogen P01019 ANGT_HUMAN 183 √ √ √ AGTR1 Angiotensin II receptor type 1 P30556 AGTR1_HUMAN 185 √ √ AGTR2 Angiotensin II receptor type 2 P50052 AGTR2_HUMAN 186 √ √ AKAP9 A-kinase anchoring protein 9 Q99996 AKAP9_HUMAN 10142 √ √ √ ANK2/ANKB/ANKYRI Ankyrin 2 Q01484 ANK2_HUMAN 287 √ √ √ N B ANKRD1 Ankyrin repeat domain 1 Q15327 ANKR1_HUMAN 27063 √ √ √ ANKRD9 Ankyrin repeat domain 9 Q96BM1 ANKR9_HUMAN 122416 √ √ ARHGAP24 Rho GTPase–activating protein 24 Q8N264 RHG24_HUMAN 83478 √ √ ATPase Na+/K+–transporting ATP1B1 P05026 AT1B1_HUMAN 481 √ √ √ subunit beta 1 ATPase sarcoplasmic/endoplasmic ATP2A2 P16615 AT2A2_HUMAN 488 √ √ √ reticulum Ca2+ transporting 2 AZIN1 Antizyme inhibitor 1 O14977 AZIN1_HUMAN 51582 √ √ √ UDP-GlcNAc: betaGal B3GNT7 beta-1,3-N-acetylglucosaminyltransfe Q8NFL0
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    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.
  • Redefining the Specificity of Phosphoinositide-Binding by Human

    Redefining the Specificity of Phosphoinositide-Binding by Human

    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.163253; this version posted June 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins Nilmani Singh1†, Adriana Reyes-Ordoñez1†, Michael A. Compagnone1, Jesus F. Moreno Castillo1, Benjamin J. Leslie2, Taekjip Ha2,3,4,5, Jie Chen1* 1Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; 2Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205; 3Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218; 4Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205; 5Howard Hughes Medical Institute, Baltimore, MD 21205, USA †These authors contributed equally to this work. *Correspondence: [email protected]. bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.163253; this version posted June 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. ABSTRACT Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employed a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates.
  • Genome-Wide Copy Number Variant Analysis For

    Genome-Wide Copy Number Variant Analysis For

    An et al. BMC Medical Genomics (2016) 9:2 DOI 10.1186/s12920-015-0163-4 RESEARCH ARTICLE Open Access Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population Yu An1,2,4, Wenyuan Duan3, Guoying Huang4, Xiaoli Chen5,LiLi5, Chenxia Nie6, Jia Hou4, Yonghao Gui4, Yiming Wu1, Feng Zhang2, Yiping Shen7, Bailin Wu1,4,7* and Hongyan Wang8* Abstract Background: Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. Methods: We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Results: Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD.
  • Datasheet Blank Template

    Datasheet Blank Template

    SAN TA C RUZ BI OTEC HNOL OG Y, INC . Fe65L (Y-14): sc-104237 BACKGROUND PRODUCT Fe65L (Fe65-like protein), also known as APBB2 (amyloid β (A4) precursor Each vial contains 200 µg IgG in 1.0 ml of PBS with < 0.1% sodium azide protein-binding, family B, member 2), is a 758 amino acid protein that contains and 0.1% gelatin. one WW domain and 2 PID domains. Binding to the intracellular domain of Blocking peptide available for competition studies, sc-104237 P, (100 µg the -amyloid precursor protein, Fe65L is thought to modulate the internal - β peptide in 0.5 ml PBS containing < 0.1% sodium azide and 0.2% BSA). ization and, therefore, the accessibility and function of β-amyloid. Via its ability to control the intracellular accumulation of -amyloid, Fe65L is thought β APPLICATIONS to play a role in the pathogenesis of Alzheimer’s disease. Multiple isoforms of Fe65L exist due to alternative splicing events. The gene encoding Fe65L Fe65L (Y-14) is recommended for detection of Fe65L of mouse, rat and maps to human chromosome 4, which encodes nearly 6% of the human human origin by Western Blotting (starting dilution 1:200, dilution range genome and has the largest gene deserts (regions of the genome with no 1:100-1:1000), immunoprecipitation [1-2 µg per 100-500 µg of total protein protein encoding genes) of all of the human chromosomes. Defects in some (1 ml of cell lysate)], immunofluorescence (starting dilution 1:50, dilution of the genes located on chromosome 4 are associated with Huntington’s range 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution dis ease, Ellis-van Creveld syndrome, methylmalonic acidemia and polycystic range 1:30-1:3000).
  • The UBE2L3 Ubiquitin Conjugating Enzyme: Interplay with Inflammasome Signalling and Bacterial Ubiquitin Ligases

    The UBE2L3 Ubiquitin Conjugating Enzyme: Interplay with Inflammasome Signalling and Bacterial Ubiquitin Ligases

    The UBE2L3 ubiquitin conjugating enzyme: interplay with inflammasome signalling and bacterial ubiquitin ligases Matthew James George Eldridge 2018 Imperial College London Department of Medicine Submitted to Imperial College London for the degree of Doctor of Philosophy 1 Abstract Inflammasome-controlled immune responses such as IL-1β release and pyroptosis play key roles in antimicrobial immunity and are heavily implicated in multiple hereditary autoimmune diseases. Despite extensive knowledge of the mechanisms regulating inflammasome activation, many downstream responses remain poorly understood or uncharacterised. The cysteine protease caspase-1 is the executor of inflammasome responses, therefore identifying and characterising its substrates is vital for better understanding of inflammasome-mediated effector mechanisms. Using unbiased proteomics, the Shenoy grouped identified the ubiquitin conjugating enzyme UBE2L3 as a target of caspase-1. In this work, I have confirmed UBE2L3 as an indirect target of caspase-1 and characterised its role in inflammasomes-mediated immune responses. I show that UBE2L3 functions in the negative regulation of cellular pro-IL-1 via the ubiquitin- proteasome system. Following inflammatory stimuli, UBE2L3 assists in the ubiquitylation and degradation of newly produced pro-IL-1. However, in response to caspase-1 activation, UBE2L3 is itself targeted for degradation by the proteasome in a caspase-1-dependent manner, thereby liberating an additional pool of IL-1 which may be processed and released. UBE2L3 therefore acts a molecular rheostat, conferring caspase-1 an additional level of control over this potent cytokine, ensuring that it is efficiently secreted only in appropriate circumstances. These findings on UBE2L3 have implications for IL-1- driven pathology in hereditary fever syndromes, and autoinflammatory conditions associated with UBE2L3 polymorphisms.
  • AZIN1 Purified Maxpab Rabbit Polyclonal Antibody (D01P)

    AZIN1 Purified Maxpab Rabbit Polyclonal Antibody (D01P)

    AZIN1 purified MaxPab rabbit polyclonal antibody (D01P) Catalog # : H00051582-D01P 規格 : [ 100 ug ] List All Specification Application Image Product Rabbit polyclonal antibody raised against a full-length human AZIN1 Western Blot (Tissue lysate) Description: protein. Immunogen: AZIN1 (NP_056962.2, 1 a.a. ~ 448 a.a) full-length human protein. Sequence: MKGFIDDANYSVGLLDEGTNLGNVIDNYVYEHTLTGKNAFFVGDLGKIVK KHSQWQNVVAQIKPFYTVKCNSAPAVLEILAALGTGFACSSKNEMALVQE enlarge LGVPPENIIYISPCKQVSQIKYAAKVGVNILTCDNEIELKKIARNHPNAKVLLHI ATEDNIGGEEGNMKFGTTLKNCRHLLECAKELDVQIIGVKFHVSSACKES Western Blot (Transfected QVYVHALSDARCVFDMAGEIGFTMNMLDIGGGFTGTEFQLEEVNHVISP lysate) LLDIYFPEGSGVKIISEPGSYYVSSAFTLAVNIIAKKVVENDKFPSGVEKTG SDEPAFMYYMNDGVYGSFASKLSEDLNTIPEVHKKYKEDEPLFTSSLWG PSCDELDQIVESCLLPELNVGDWLIFDNMGADSFHEPSAFNDFQRPAIYY MMSFSDWYEMQDAGITSDSMMKNFFFVPSCIQLSQEDSFSAEA Host: Rabbit enlarge Reactivity: Human Quality Control Antibody reactive against mammalian transfected lysate. Testing: Storage Buffer: In 1x PBS, pH 7.4 Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Applications Western Blot (Tissue lysate) AZIN1 MaxPab rabbit polyclonal antibody. Western Blot analysis of AZIN1 expression in human placenta. Protocol Download Western Blot (Transfected lysate) Page 1 of 2 2016/5/23 Western Blot analysis of AZIN1 expression in transfected 293T cell line (H00051582-T02) by AZIN1 MaxPab polyclonal antibody. Lane 1: AZIN1 transfected lysate(49.50 KDa). Lane 2: Non-transfected lysate. Protocol
  • Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses

    Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses

    medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened.