Genotype Frequency Distributions of 28 SNP Markers in Two Commercial
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Human Leucine-Rich Repeat Proteins: a Genome-Wide Bioinformatic Categorization and Functional Analysis in Innate Immunity
Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity Aylwin C. Y. Nga,b,1, Jason M. Eisenberga,b,1, Robert J. W. Heatha, Alan Huetta, Cory M. Robinsonc, Gerard J. Nauc, and Ramnik J. Xaviera,b,2 aCenter for Computational and Integrative Biology, and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; bThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; and cMicrobiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved June 11, 2010 (received for review February 17, 2010) In innate immune sensing, the detection of pathogen-associated proteins have been implicated in human diseases to date, notably molecular patterns by recognition receptors typically involve polymorphisms in NOD2 in Crohn disease (8, 9), CIITA in leucine-rich repeats (LRRs). We provide a categorization of 375 rheumatoid arthritis and multiple sclerosis (10), and TLR5 in human LRR-containing proteins, almost half of which lack other Legionnaire disease (11). identifiable functional domains. We clustered human LRR proteins Most LRR domains consist of a chain of between 2 and 45 by first assigning LRRs to LRR classes and then grouping the proteins LRRs (12). Each repeat in turn is typically 20 to 30 residues long based on these class assignments, revealing several of the resulting and can be divided into a highly conserved segment (HCS) fol- protein groups containing a large number of proteins with certain lowed by a variable segment (VS). -
Transdifferentiation of Human Mesenchymal Stem Cells
Transdifferentiation of Human Mesenchymal Stem Cells Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Julius-Maximilians-Universität Würzburg vorgelegt von Tatjana Schilling aus San Miguel de Tucuman, Argentinien Würzburg, 2007 Eingereicht am: Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Martin J. Müller Gutachter: PD Dr. Norbert Schütze Gutachter: Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am: Hiermit erkläre ich ehrenwörtlich, dass ich die vorliegende Dissertation selbstständig angefertigt und keine anderen als die von mir angegebenen Hilfsmittel und Quellen verwendet habe. Des Weiteren erkläre ich, dass diese Arbeit weder in gleicher noch in ähnlicher Form in einem Prüfungsverfahren vorgelegen hat und ich noch keinen Promotionsversuch unternommen habe. Gerbrunn, 4. Mai 2007 Tatjana Schilling Table of contents i Table of contents 1 Summary ........................................................................................................................ 1 1.1 Summary.................................................................................................................... 1 1.2 Zusammenfassung..................................................................................................... 2 2 Introduction.................................................................................................................... 4 2.1 Osteoporosis and the fatty degeneration of the bone marrow..................................... 4 2.2 Adipose and bone -
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DISSERTATION submitted to the Combined Faculties for the Natural Sciences and for Mathematics of the Ruperto-Carola University of Heidelberg, Germany for the degree of Doctor of Natural Sciences presented by M.Sc. Daniela Casarrubea born in Palermo (Italy) Oral examination: 1st February 2013 A NEW MOUSE MODEL WITH GAIN OF IRON REGULATORY PROTEIN 1 FUNCTION Referees: 1. Dr. Darren Gilmour 2. Prof. Dr. Klaus Unsicker SUMMARY SUMMARY Disorders of iron metabolism account for some of the most common human diseases, such as anemias and hemochromatosis. To maintain physiological iron balance, homeostatic mechanisms are normally in place both at the systemic and the cellular level. Cellular iron homeostasis is secured by Iron Regulatory Proteins (IRP) −1 and −2 through their binding to cis- regulatory iron-responsive elements (IRE) in target mRNAs encoding proteins with key functions in iron metabolism. In turn, the IRE−binding activity of the two IRPs is feedback regulated by the cellular labile iron pool. Mouse models with IRP deficiency have contributed valuable insights into the in vivo roles of the IRP/IRE system as well as mammalian iron biology. However, the physiological consequences of gain of IRP function have so far remained unexplored. To investigate the importance of adequate IRP expression in vivo, we have generated a mouse model allowing conditional gain of IRP function using Cre/Lox technology. This new line expresses a flag-tagged IRP1 mutant (IRP1*), which escapes iron-mediated regulation, being constitutively active in its IRE binding form. Systemic expression of the IRP1* transgene from the Rosa26 locus yields viable animals with gain of IRE-binding activity in all organs that were analyzed. -
Mouse Fbxl5 Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Fbxl5 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Fbxl5 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Fbxl5 gene (NCBI Reference Sequence: NM_001159963 ; Ensembl: ENSMUSG00000039753 ) is located on Mouse chromosome 5. 11 exons are identified, with the ATG start codon in exon 1 and the TGA stop codon in exon 11 (Transcript: ENSMUST00000047857). Exon 4 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Fbxl5 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-430B21 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a null mutation display embryonic lethality before turning of the embryo with iron overload, growth retardation, and hemorrhage. Mice heterozygous for a knock-out allele exhibit abnormal iron homeostasis when fed a low iron diet. Exon 4 starts from about 19.18% of the coding region. The knockout of Exon 4 will result in frameshift of the gene. The size of intron 3 for 5'-loxP site insertion: 2486 bp, and the size of intron 4 for 3'-loxP site insertion: 2572 bp. The size of effective cKO region: ~687 bp. The cKO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 4 11 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Fbxl5 Homology arm cKO region loxP site Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. -
An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice
bioRxiv preprint doi: https://doi.org/10.1101/378711; this version posted August 19, 2018. 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-ND 4.0 International license. 1 Title: 2 An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice 3 Short Title: 4 Genomic response to selection for longer limbs 5 One-sentence summary: 6 Genome sequencing of mice selected for longer limbs reveals that rapid selection response is 7 due to both discrete loci and polygenic adaptation 8 Authors: 9 João P. L. Castro 1,*, Michelle N. Yancoskie 1,*, Marta Marchini 2, Stefanie Belohlavy 3, Marek 10 Kučka 1, William H. Beluch 1, Ronald Naumann 4, Isabella Skuplik 2, John Cobb 2, Nick H. 11 Barton 3, Campbell Rolian2,†, Yingguang Frank Chan 1,† 12 Affiliations: 13 1. Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany 14 2. University of Calgary, Calgary AB, Canada 15 3. IST Austria, Klosterneuburg, Austria 16 4. Max Planck Institute for Cell Biology and Genetics, Dresden, Germany 17 Corresponding author: 18 Campbell Rolian 19 Yingguang Frank Chan 20 * indicates equal contribution 21 † indicates equal contribution 22 Abstract: 23 Evolutionary studies are often limited by missing data that are critical to understanding the 24 history of selection. Selection experiments, which reproduce rapid evolution under controlled 25 conditions, are excellent tools to study how genomes evolve under strong selection. Here we 1 bioRxiv preprint doi: https://doi.org/10.1101/378711; this version posted August 19, 2018. -
Retrotransposition of Gene Transcripts Leads to Structural Variation in Mammalian Genomes Adam D
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2013 Retrotransposition of gene transcripts leads to structural variation in mammalian genomes Adam D. Ewing University of California - Santa Cruz Tracy J. Ballinger University of California - Santa Cruz Dent Earl University of California - Santa Cruz Broad Institute Genome Sequencing and Analysis Program and Platform Christopher C. Harris Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Ewing, Adam D.; Ballinger, Tracy J.; Earl, Dent; Broad Institute Genome Sequencing and Analysis Program and Platform; Harris, Christopher C.; Ding, Li; Wilson, Richard K.; and Haussler, David, ,"Retrotransposition of gene transcripts leads to structural variation in mammalian genomes." Genome Biology.,. R22. (2013). https://digitalcommons.wustl.edu/open_access_pubs/1396 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Adam D. Ewing, Tracy J. Ballinger, Dent Earl, Broad Institute Genome Sequencing and Analysis Program and Platform, Christopher C. Harris, Li Ding, Richard K. Wilson, and David Haussler This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/1396 -
ALKBH5 Is a Mammalian RNA Demethylase That Impacts RNA Metabolism and Mouse Fertility
Molecular Cell Article ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility Guanqun Zheng,1,11 John Arne Dahl,3,11 Yamei Niu,2,11 Peter Fedorcsak,4 Chun-Min Huang,2 Charles J. Li,1 Cathrine B. Va˚ gbø,6 Yue Shi,2,7 Wen-Ling Wang,2,7 Shu-Hui Song,5 Zhike Lu,1 Ralph P.G. Bosmans,1 Qing Dai,1 Ya-Juan Hao,2,7 Xin Yang,2,7 Wen-Ming Zhao,5 Wei-Min Tong,8 Xiu-Jie Wang,9 Florian Bogdan,3 Kari Furu,3 Ye Fu,1 Guifang Jia,1 Xu Zhao,2,7 Jun Liu,10 Hans E. Krokan,6 Arne Klungland,3,* Yun-Gui Yang,2,7,* and Chuan He1,* 1Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA 2Genome Structure & Stability Group, BIG CAS-OSLO Genome Research Cooperation, Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, No.7 Beitucheng West Road, Chaoyang District, Beijing 100029, P.R. China 3Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, BIG CAS-OSLO Genome Research Cooperation, Oslo University Hospital, Oslo 0027, Norway 4Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo 0027, Norway 5Core Genomic Facility, Beijing Institute of Genomics, Chinese Academy of Sciences, No.7 Beitucheng West Road, Chaoyang District, Beijing 100029, P.R. China 6Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway 7University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, P.R. -
Human Leucine-Rich Repeat Proteins: a Genome-Wide Bioinformatic Categorization and Functional Analysis in Innate Immunity
Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity Aylwin C. Y. Nga,b,1, Jason M. Eisenberga,b,1, Robert J. W. Heatha, Alan Huetta, Cory M. Robinsonc, Gerard J. Nauc, and Ramnik J. Xaviera,b,2 aCenter for Computational and Integrative Biology, and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; bThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; and cMicrobiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved June 11, 2010 (received for review February 17, 2010) In innate immune sensing, the detection of pathogen-associated proteins have been implicated in human diseases to date, notably molecular patterns by recognition receptors typically involve polymorphisms in NOD2 in Crohn disease (8, 9), CIITA in leucine-rich repeats (LRRs). We provide a categorization of 375 rheumatoid arthritis and multiple sclerosis (10), and TLR5 in human LRR-containing proteins, almost half of which lack other Legionnaire disease (11). identifiable functional domains. We clustered human LRR proteins Most LRR domains consist of a chain of between 2 and 45 by first assigning LRRs to LRR classes and then grouping the proteins LRRs (12). Each repeat in turn is typically 20 to 30 residues long based on these class assignments, revealing several of the resulting and can be divided into a highly conserved segment (HCS) fol- protein groups containing a large number of proteins with certain lowed by a variable segment (VS). -
Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer
cancers Review Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer 1, 1, 1 2 Andrea Rodríguez-Alonso y, Alba Casas-Pais y, Daniel Roca-Lema , Begoña Graña , Gabriela Romay 1 and Angélica Figueroa 1,* 1 Epithelial Plasticity and Metastasis Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), 15006 A Coruña, Spain; [email protected] (A.R.-A.); [email protected] (A.C.-P.); [email protected] (D.R.-L.); [email protected] (G.R.) 2 Clinical Oncology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), 15006 A Coruña, Spain; [email protected] * Correspondence: angelica.fi[email protected] Andrea Rodríguez-Alonso and Alba Casas-Pais contributed equally and should be considered as y co-first authors. Received: 17 September 2020; Accepted: 22 October 2020; Published: 23 October 2020 Simple Summary: Cancer progression eventually may lead to metastasis, which is responsible for at least 90% cancer-related deaths. The epithelial-to-mesenchymal transition plays a critical role in promoting metastasis and is considered a new target in anticancer drug discovery. The E3 ubiquitin-ligases responsible for targeted protein degradation emerge as molecularly defined targets involved in epithelial-to-mesenchymal transition. This review highlights the novel E3 ubiquitin-ligases responsible for targeted protein degradation involved in epithelial-to-mesenchymal transition, a field that promises to be one of the greatest innovation in small-molecule drug discovery. -
The Iron Regulatory Protein/Iron Responsive Element (IRP/IRE) System: Functional Studies of New Target Mrnas and Pathological Implicatio Ns for Novel IRE Mutations
The Iron Regulatory Protein/Iron Responsive Element (IRP/IRE) system: functional studies of new target mRNAs and pathological implicatio ns for novel IRE mutations Sara Luscieti ADVERTIMENT . La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX ( www.tdx.cat ) i a través del Dipòsit Digital de la UB ( diposit.ub.edu ) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposici ó des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB . No s’autori tza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA . La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR ( www.tdx.cat ) y a través del Repositorio Di gital de la UB ( diposit.ub.edu ) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB . -
Theranostics F-Box Proteins and Cancer: an Update from Functional and Regulatory Mechanism to Therapeutic Clinical Prospects
Theranostics 2020, Vol. 10, Issue 9 4150 Ivyspring International Publisher Theranostics 2020; 10(9): 4150-4167. doi: 10.7150/thno.42735 Review F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects Dinesh Singh Tekcham2*, Di Chen2*, Yu Liu1,2, Ting Ling2, Yi Zhang1,2, Huan Chen2, Wen Wang2, Wuxiyar Otkur2, Huan Qi2, Tian Xia2, Xiaolong Liu2, Hai-long Piao2, Hongxu Liu1 1. Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China. 2. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. * Equal contribution Corresponding authors: Hai-long Piao, [email protected]; Hongxu Liu, [email protected] © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.12.04; Accepted: 2020.02.04; Published: 2020.03.04 Abstract E3 ubiquitin ligases play a critical role in cellular mechanisms and cancer progression. F-box protein is the core component of the SKP1–cullin 1–F-box (SCF)-type E3 ubiquitin ligase and directly binds to substrates by various specific domains. According to the specific domains, F-box proteins are further classified into three sub-families: 1) F-box with leucine rich amino acid repeats (FBXL); 2) F-box with WD 40 amino acid repeats (FBXW); 3) F-box only with uncharacterized domains (FBXO). Here, we summarize the substrates of F-box proteins, discuss the important molecular mechanism and emerging role of F-box proteins especially from the perspective of cancer development and progression. -
Identification and Interaction Analysis of Key Genes and Micrornas In
Mou et al. World Journal of Surgical Oncology (2017) 15:63 DOI 10.1186/s12957-017-1127-2 RESEARCH Open Access Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis Tong Mou†, Di Zhu†, Xufu Wei, Tingting Li, Daofeng Zheng, Junliang Pu, Zhen Guo and Zhongjun Wu* Abstract Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. However, present studies of its multiple gene interaction and cellular pathways still could not explain the initiation and development of HCC perfectly. To find the key genes and miRNAs as well as their potential molecular mechanisms in HCC, microarray data GSE22058, GSE25097, and GSE57958 were analyzed. Methods: The microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed using the DAVID database, and the protein–protein interaction (PPI) network was constructed using the Cytoscape software. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs). Results: A total of 115 differentially expressed genes (DEGs) were found in HCC, including 52 up-regulated genes and 63 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses from DAVID showed that up-regulated genes were significantly enriched in chromosome segregation and cell division, while the down-regulated genes were mainly involved in complement activation, protein activation cascades, carboxylic acid metabolic processes, oxoacid metabolic processes, and the immune response. From the PPI network, the 18 nodes with the highest degree were screened as hub genes.