DOCSLIB.ORG

SFU Thesis Template Files

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
SFU Thesis Template Files Enabling systems-level analyses of the host response to infectious diseases in bovine and other mammalian species by Amir Bahram Khosravizadeh Foroushani M.Sc. (Computer Science), University of Texas at Dallas, 2009 Diplom Informatik, University of Tuebingen, 2003 Thesis Submitted In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Department of Molecular Biology and Biochemistry Faculty of Science Amir Bahram Khosravizadeh Foroushani 2014 SIMON FRASER UNIVERSITY Summer 2014 Approval Name: Amir Bahram Khosravizadeh Foroushani Degree: Doctor of Philosophy Title of Thesis: Enabling systems-level analyses of the host response to infectious diseases in bovine and other mammalian species Examining Committee: Chair: Dr. Mark A. Brockman Associate Professor, Faculty of Health Sciences // Dept of Molecular Biology and Biochemistry Dr. Fiona S.L. Brinkman Senior Supervisor Professor, Department of Molecular Biology and Biochemistry Dr. David J. Lynn Supervisor Group leader, Computational Biology, AGRIC,Teagasc, Ireland By video conference (Adelaide, Australia) Dr. Jack Chen Supervisor Professor, Department of Molecular Biology and Biochemistry Dr. Willie Davidson Supervisor Professor, Department of Molecular Biology and Biochemistry Dr. Lisa Craig Internal Examiner Associate Professor, Department of Molecular Biology and Biochemistry Dr. Paul Pavlidis External Examiner Associate Professor, Psychiatry University of British Columbia Date Defended/Approved: September 29, 2014 ii Partial Copyright Licence iii Abstract The innate immune response is a critical branch of immunity, providing a first line of defense against pathogens and shaping subsequent adaptive immune responses. The complexity of this system necessitates the application of systems-level approaches. InnateDB is an integrated web-accessible database and systems biology platform being developed to facilitate the systems level analysis of innate immunity pathways and networks. One of the aims of this thesis was to enhance InnateDB with bovine data, thereby providing a resource for investigation of this agriculturally important model organism. Using an orthology based approach, over 70% of InnateDB’s human protein- protein interactions (PPIs), and a similar fraction of human pathways were reconstructed in cow and integrated into InnateDB. Pathway analysis, the statistical association of observations at the molecular level with processes at a more systems level, plays a crucial role in the interpretation of high- throughput experimental datasets. A widely neglected challenge in pathway analysis relates to the handling of multifunctional genes. I therefore developed SIGORA, a novel pathway analysis method that identifies genes and gene-pairs that are unique signatures of a pathway and examines their over-representation in a given list of genes of interest (e.g. the list of differentially expressed genes in an infectious condition). With several biological datasets, SIGORA outperformed traditional methods, delivering biologically more plausible and relevant results. This was also reflected in significantly lower false positive rates for simulated datasets. An additional challenge in high-throughput dataset interpretation concerns the lack of functional annotation for many genes. The guilt by association (GBA) principle was applied in a conservative manner to a large tissue expression dataset (105 Tissues, 13000 genes) to infer gene functions from co-expression data. Overall, 180 previously un-annotated bovine genes were assigned a putative function by this approach. In 20% of the cases, the inferred function was additionally supported by literature in other species. iv microRNAs are emerging as important innate immune response regulators and as biomarkers of disease. Determining microRNA functions requires the identification of their targets, yet computational prediction of such targets is challenging. As part of a group investigating microRNA roles in bovine mastitis, I used a combination of prediction tools to compile a list of likely targets. Here, the overall emerging picture (including pathway enrichment) is consistent with our current understanding of this condition. Collectively this work provides new tools and insights that may more broadly be used to improve systems-based analysis of bovine and other mammalian responses. Keywords: Computational Biology; Bioinformatics; innate immunity; bovine infectious diseases; pathway analysis; miRNAs. v Dedication To Ebrahim, Fatemeh and Zaneta vi Acknowledgements I am very thankful for the invaluable guidance and contribution of my supervisory committee; Dr. Fiona Brinkman, Dr. David Lynn, Dr. Willie Davidson and Dr. Jack Chen. I would like to acknowledge all project collaborators at Teagasc, SFU, UBC and TCD, in particular Nathan Lawless, Peter Vegh, Karin Breuer, Matthew Laird, Geoffrey Winsor, Matthew Whiteside, Raymond Lo, Anastasia Sribnaia, Carol Chen as well as Dr. Bob Hancock, Dr. Cliona O'Farrelly and Dr. Mathew McCabe. I would also like to acknowledge Lakshmi Matukumalli and other members of the Bovine Gene Atlas project for providing the bovine tissue expression data. This work has been generously supported by a four year Walsh Fellowship Scheme from Teagasc and a Special Graduate Entrance Scholarship (SGES) from SFU. vii Table of Contents Approval .......................................................................................................................... ii Partial Copyright Licence ............................................................................................... iii Abstract .......................................................................................................................... iv Dedication ...................................................................................................................... vi Acknowledgements ....................................................................................................... vii Table of Contents .......................................................................................................... viii List of Tables ................................................................................................................. xiii List of Figures................................................................................................................xiv List of Acronyms ............................................................................................................xvi Glossary ...................................................................................................................... xviii Preface or Executive Summary or Introductory Image ...................................................xxi Chapter 1. Introduction ............................................................................................... 1 1.1. Burden of infectious disease ................................................................................... 1 1.2. The importance of infectious disease in cattle ........................................................ 2 1.2.1. Zoonotic diseases and emerging diseases .................................................. 2 1.2.2. Animal infectious diseases in a changing world ........................................... 4 1.3. The immune system ............................................................................................... 5 1.3.1. The innate immune system ......................................................................... 6 1.3.2. A glance at the complexity of the innate immune response ......................... 8 1.4. Systems level approaches and immunology ......................................................... 12 1.4.1. Types of systems studies .......................................................................... 13 Experimental systems immunology ........................................................... 14 Modeling & simulation based systems immunology .................................. 15 Quantitative models........................................................................................... 15 Box1: Modeling and simulation ................................................................. 15 Qualitative and rule based models .................................................................... 16 Box2: Networks and network analysis ....................................................... 18 A) Descriptive power of network representation ............................................. 18 B) Network analysis ......................................................................................... 18 1.4.2. Integrative systems biology ....................................................................... 19 1.5. Pathways, pathway databases and pathway analysis ........................................... 21 1.6. miRNAs as novel regulators of innate immunity .................................................... 23 1.6.1. Biogenesis ................................................................................................ 23 1.6.2. Function and relevance to innate immunity ............................................... 24 1.6.3. Computational prediction of miRNA targets ............................................... 27 Phylogenetic conservation: ....................................................................... 27 Genomic context: ...................................................................................... 28 Thermodynamic stability: .........................................................................
Load more

Recommended publications
  • History of Cln7 Biology of Cln7 Symptoms Diagnosis Management Strategies
    Understanding CLN7 HISTORY OF CLN7 BIOLOGY OF CLN7 SYMPTOMS DIAGNOSIS MANAGEMENT STRATEGIES Understanding CLN7 Batten disease is a group of rare neurodegenerative diseases, also known as neuronal ceroid lipofuscinoses (NCLs). Each NCL disease is classified by the gene that causes it. The name of each gene begins with CLN – ceroid lipofuscinosis, neuronal – followed by a unique number that indicates the subtype. Changes in the normal function of these genes, due to pathogenic variants, lead to disruption of normal protein function. This disruption results in lysosomal dysfunction, and the accumulation of molecules in the cells throughout the body. The symptoms, severity, onset, and progression across the subtypes vary. Both males and females are affected. The CLN7 subtype of Batten disease is caused by a variant in the CLN7 gene, also called the MFSD8 gene, which leads to disruption of normal CLN7 protein function. The exact function of this protein is unknown. Individuals with CLN7 typically develop neurological signs and symptoms in early childhood, such as seizures, progressive deterioration in intellectual and motor capabilities, and loss of vision. The disease ultimately leads to a shortened lifespan. Source: Batten Disease Fact Sheet. (2019, June 24). Retrieved August 8, 2019, from link. History of CLN7 History of Batten Disease Batten disease, a common name for a rare class of diseases called neuronal ceroid lipofuscinoses (NCLs), was first described in 1903 by British neurologist and pediatrician Frederick Batten. Today, there are 13 known subtypes of Batten disease. Symptoms and disease management for each subtype of Batten disease vary, although several subtypes share similar features and symptoms.
    [Show full text]
  • CLN7 Disease
    CLN7 disease Description CLN7 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 7. The initial features are usually vision loss and problems with movement that might seem like clumsiness. Additional signs and symptoms of CLN7 disease include muscle twitches ( myoclonus), difficulty coordinating movements (ataxia), recurrent seizures (epilepsy), and speech impairment. Mental functioning and motor skills (such as sitting and walking) decline with age. Individuals with CLN7 disease typically do not survive past their teens. CLN7 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses ( NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. Frequency The incidence of CLN7 disease is unknown; more than 70 cases have been described in the scientific literature. CLN7 disease was first diagnosed in the Turkish population and was thought to be limited to individuals in that group. However, CLN7 disease has now been identified in people around the world. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. Causes Mutations in the MFSD8 gene cause CLN7 disease. The MFSD8 gene provides instructions for making a protein whose function is unknown. The MFSD8 protein is embedded in the membrane of cell compartments called lysosomes, which digest and recycle different types of molecules.
    [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]
  • The Novel Membrane-Bound Proteins MFSD1 and MFSD3 Are Putative SLC Transporters Affected by Altered Nutrient Intake
    J Mol Neurosci DOI 10.1007/s12031-016-0867-8 The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake Emelie Perland1,2 & Sofie V. Hellsten2 & Emilia Lekholm2 & Mikaela M. Eriksson2 & Vasiliki Arapi2 & Robert Fredriksson2 Received: 29 August 2016 /Accepted: 21 November 2016 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Membrane-bound solute carriers (SLCs) are essen- Introduction tial as they maintain several physiological functions, such as nutrient uptake, ion transport and waste removal. The SLC Membrane-bound transporters are physiologically important family comprise about 400 transporters, and we have identi- as they keep the homeostasis of soluble molecules within cel- fied two new putative family members, major facilitator su- lular compartments, and it is crucial to study their basic his- perfamily domain containing 1 (MFSD1) and 3 (MFSD3). tology and function to understand the human body. The solute They cluster phylogenetically with SLCs of MFS type, and carrier (SLC) superfamily is the largest group of membrane- both proteins are conserved in chordates, while MFSD1 is also bound transporters in human and it includes 395 members, found in fruit fly. Based on homology modelling, we predict divided in 52 families (Hediger et al. 2004). SLCs utilize 12 transmembrane regions, a common feature for MFS trans- ATP-independent mechanisms to move nutrients, ions, drugs porters. The genes are expressed in abundance in mice, with and waste over lipid membranes, and SLC deficiencies are specific protein staining along the plasma membrane in neu- associated with several human diseases (Hediger et al.
    [Show full text]
  • 4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
    [Show full text]
  • Transcriptional Control of Tissue-Resident Memory T Cell Generation
    Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2019 © 2019 Filip Cvetkovski All rights reserved ABSTRACT Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells.
    [Show full text]
  • A Bayesian Approach to Mediation Analysis Predicts 206 Causal Target Genes in Alzheimer’S Disease
    bioRxiv preprint first posted online Nov. 14, 2017; doi: http://dx.doi.org/10.1101/219428. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Title A Bayesian approach to mediation analysis predicts 206 causal target genes in Alzheimer’s disease Authors Yongjin Park+;1;2, Abhishek K Sarkar+;3, Liang He+;1;2, Jose Davila-Velderrain1;2, Philip L De Jager2;4, Manolis Kellis1;2 +: equal contribution. 1: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA 2: Broad Institute of MIT and Harvard, Cambridge, MA, USA 3: Department of Human Genetics, University of Chicago, Chicago, IL, USA 4: Department of Neurology, Columbia University Medical Center, New York, NY, USA MK: [email protected] Abstract Characterizing the intermediate phenotypes, such as gene expression, that mediate genetic effects on complex dis- eases is a fundamental problem in human genetics. Existing methods utilize genotypic data and summary statistics to identify putative disease genes, but cannot distinguish pleiotropy from causal mediation and are limited by overly strong assumptions about the data. To overcome these limitations, we develop Causal Multivariate Mediation within Extended Linkage disequilibrium (CaMMEL), a novel Bayesian inference framework to jointly model multiple medi- ated and unmediated effects relying only on summary statistics. We show in simulation that CaMMEL accurately distinguishes between mediating and pleiotropic genes unlike existing methods. We applied CaMMEL to Alzheimer’s disease (AD) and found 206 causal genes in sub-threshold loci (p < 10−4).
    [Show full text]
  • CLN7 Disease, Variant Late-Infantile
    There are grants and funds available to ensure that the work groups and individuals to help with the challenges that will involved is affordable. An occupational therapist will consult be faced is important. This support extends to wider family on all aspects of any adaptations and assist the family in members. There are several options to consider should undertaking this process. families wish to explore ways of maximising the limited time available to share with their children. Contacting a charitable CLN7 Disease, Variant Late-Infantile wish-granting organisation may lead to them being able to Will there be an impact on the child’s education? create some valuable and significant memories. Are there any alternative names? How are NCLs inherited? Education will continue to be important for the child and family Where can I get additional information and support? and there will be many aspects that require consideration and significant assistance from those around them. CLN7 disease, variant late-infantile may also be referred to Most forms of NCL are inherited as “autosomal recessive” The BDFA offers support to any family member, friend, as variant late-infantile CLN7 disease, alongside Variant Late disorders. This is one of several ways that a trait, disorder, The Children and Families Act 2014 came into force in professional or organisation involved in caring for a child with Infantile Neuronal Ceroid Lipofuscinosis; though was more or disease can be passed down through families. An September 2014. The introduction of the 0-25 Education, CLN7 disease or any other form of NCL throughout the UK. commonly known as Variant Late-Infantile Batten Disease.
    [Show full text]
  • Tibbo, Amy J. (2020) Compartmentalized Camp Signaling Via the PDE4- Popeye Protein Complex
    Tibbo, Amy J. (2020) Compartmentalized cAMP Signaling via the PDE4- Popeye Protein Complex. PhD thesis. http://theses.gla.ac.uk/81454/ Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] 1 Compartmentalized cAMP Signaling via the PDE4-Popeye Protein Complex Amy Jane Tibbo (BSc Hons) Thesis submitted in fulfilment of the requirements for Degree of Doctor of Philosophy Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow April 2020 2 Abstract The Popeye domain containing (POPDC) protein family are a unique family of transmembrane proteins with several proposed functions that are not fully understood. POPDC proteins are abundantly expressed in cardiac and skeletal muscle. Within the heart, POPDC1 has been shown to be highly expressed in the pace making centres and at moderate to low levels in the atria and ventricles. Given this localisation, a role for POPDC1 was hypothesised to be in the maintenance of normal heartbeat rhythm. Studies involving POPDC1 mutant mice and zebrafish provided evidence for this proposed function as the genetically modified model animals displayed cardiac arrhythmias as the predominant phenotype.
    [Show full text]
  • Chloride Channels Regulate Differentiation and Barrier Functions
    RESEARCH ARTICLE Chloride channels regulate differentiation and barrier functions of the mammalian airway Mu He1†*, Bing Wu2†, Wenlei Ye1, Daniel D Le2, Adriane W Sinclair3,4, Valeria Padovano5, Yuzhang Chen6, Ke-Xin Li1, Rene Sit2, Michelle Tan2, Michael J Caplan5, Norma Neff2, Yuh Nung Jan1,7,8, Spyros Darmanis2*, Lily Yeh Jan1,7,8* 1Department of Physiology, University of California, San Francisco, San Francisco, United States; 2Chan Zuckerberg Biohub, San Francisco, United States; 3Department of Urology, University of California, San Francisco, San Francisco, United States; 4Division of Pediatric Urology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco, United States; 5Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Heaven, United States; 6Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States; 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; 8Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States *For correspondence: Abstract The conducting airway forms a protective mucosal barrier and is the primary target of [email protected] (MH); [email protected] airway disorders. The molecular events required for the formation and function of the airway (SD); mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway [email protected] (LYJ) diseases,
    [Show full text]
  • Chicken Linkage Disequilibrium Is Much More Complex Over Much Longer Distance Than Previously Appreciated
    Look Over the Horizon - Chicken Linkage Disequilibrium is Much More Complex Over Much Longer Distance than Previously Appreciated Ehud Lipkin ( [email protected] ) Hebrew University of Jerusalem Janet E. Fulton Hy-Line (United States) Jacqueline Smith University of Edinburgh David W. Burt University of Edinburgh Morris Soller Hebrew University of Jerusalem Research Article Keywords: Chicken, long-range linkage disequilibrium, QTL, F6, LD blocks Posted Date: June 17th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-598396/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/23 Abstract Background Appreciable Linkage Disequilibrium (LD) is commonly found between pairs of loci close to one another, decreasing rapidly with distance between the loci. This provides the basis studies to map Quantitative Trait Loci Regions (QTLRs), where it is custom to assume that the closest sites to a signicant markers are the prime candidate to be the causative mutation. Nevertheless, Long-Range LD (LRLD) can also be found among well-separated sites. LD blocks are runs of genomic sites all having appreciable LD with one another. High LD and LRLD are often separated by genomic sites with which they have practically no LD. Thus, not only can LD be found among distant loci, but also its pattern may be complex, comprised of fragmented blocks. Here, chicken LRLD and LD blocks, and their relationship with previously described Marek’s Disease (MD) QTLRs, were studied in an F6 population from a full-sib advanced intercross line, and in eight commercial pure layer lines.
    [Show full text]
  • (Popdc2). Generation and Functional Characterization of a Null Mutant in Mice and Promoter Analysis
    The Popeye domain containing gene 2 (Popdc2). Generation and functional characterization of a null mutant in mice and promoter analysis. Dissertation For completion of the Doctorate degree in Natural Sciences at the Bayerische Julius-Maximilians-Universität Würzburg Alexander Froese from Dushanbe Würzburg 2007 Declaration: I hereby declare that the submitted dissertation was completed by myself and no other. I have not used any sources or materials other than those enclosed. Moreover I declare that the following dissertation has not been submitted further in this form or any other form, and has not been used to obtain any other equivalent qualifications at any other organisation/institution. Additionally, I have not applied for, nor will I attempt to apply for any other degree or qualification in relation to this work. Würzburg, den 21.12.2007 Alexander Froese The hereby submitted thesis was completed from January 2001 until April 2005 at the Cell and Molecular Biology Department, Technical University Braunschweig, Braunschweig and from May 2005 until December 2007 at the Department of Cell and Developmental Biology, University of Würzburg, under the supervision of Professor Dr. T. Brand. Members of the thesis committee: Chairman: Professor Dr. M. Müller Examiner: Professor Dr. T. Brand Examiner: PD Dr. S. Maier Submitted on: 21.12.2007 Date of oral exam: 20.02.2008 Wahrlich, wahrlich, ich sage euch: Wenn das Weizenkorn nicht in die Erde fällt und stirbt, bleibt es allein; wenn es aber stirbt, bringt es viel Frucht. Johannes 12;23-25 Истинно, истинно говорю вам: если пшеничное зерно, падши в землю, не умрёт, то останется одно; а если умрёт, то принесёт много плода.
    [Show full text]