Santa Cruz Biotechnology, Inc. 1.800.457.3801 831.457.3800 Fax 831.457.3801 Europe +00800 4573 8000 49 6221 4503 0

Total Page:16

File Type:pdf, Size:1020Kb

Santa Cruz Biotechnology, Inc. 1.800.457.3801 831.457.3800 Fax 831.457.3801 Europe +00800 4573 8000 49 6221 4503 0 Produktinformation Diagnostik & molekulare Diagnostik Laborgeräte & Service Zellkultur & Verbrauchsmaterial Forschungsprodukte & Biochemikalien Weitere Information auf den folgenden Seiten! See the following pages for more information! Lieferung & Zahlungsart Lieferung: frei Haus Bestellung auf Rechnung SZABO-SCANDIC Lieferung: € 10,- HandelsgmbH & Co KG Erstbestellung Vorauskassa Quellenstraße 110, A-1100 Wien T. +43(0)1 489 3961-0 Zuschläge F. +43(0)1 489 3961-7 [email protected] • Mindermengenzuschlag www.szabo-scandic.com • Trockeneiszuschlag • Gefahrgutzuschlag linkedin.com/company/szaboscandic • Expressversand facebook.com/szaboscandic SAN TA C RUZ BI OTEC HNOL OG Y, INC . ETFA shRNA (h) Lentiviral Particles: sc-62259-V BACKGROUND APPLICATIONS ETFA (electron-transfer-flavoprotein, α polypeptide), also known as EMA, GA2 ETFA shRNA (h) Lentiviral Particles is recommended for the inhibition of or MADD, is a 333 amino acid protein that localizes to the mitochondrial ma- ETFA expression in human cells. trix and belongs to the ETF α-subunit/fixB family. Existing as a heterodimer with ETFB, ETFA uses FAD as a cofactor and serves as a specific electron ac- SUPPORT REAGENTS ceptor for several dehydrogenases, effectively transferring electrons to the Control shRNA Lentiviral Particles: sc-108080. Available as 200 µl frozen mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase. Defects viral stock containing 1.0 x 10 6 infectious units of virus (IFU); contains an in the gene encoding ETFA are the cause of glutaric aciduria type IIA (GAIIA), shRNA construct encoding a scrambled sequence that will not lead to the a condition that is characterized by the excretion of lactic, ethylmalonic, bu- specific degradation of any known cellular mRNA. tyric, isobutyric, 2-methyl-butyric, glutaric and isovaleric acids. The gene en- coding ETFA maps to human chromosome 15, which houses over 700 genes GENE EXPRESSION MONITORING and comprises nearly 3% of the human genome. ETFA (H-8): sc-365982 is recommended as a control antibody for monitoring REFERENCES of ETFA gene expression knockdown by Western Blotting (starting dilution 1:200, dilution range 1:100-1:1000) or immunofluorescence (starting dilution 1. Frerman, F.E. 1988. Acyl-CoA dehydrogenases, electron transfer flavopro tein 1:50, dilution range 1:50-1:500). and electron transfer flavoprotein dehydrogenase. Biochem. Soc. Trans. 16: 416-418. To ensure optimal results, the following support (secondary) reagents are recommended: 1) Western Blotting: use goat anti-mouse IgM-HRP: sc-2064 2. Indo, Y., et al. 1991. Molecular characterization of variant α-subunit of elec - (dilution range: 1:500-1:5,000), TBS Blotto A Blocking Reagent: sc-2333 and tron transfer flavoprotein in three patients with glutaric acidemia type II— Western Blotting Luminol Reagent: sc-2048. 2) Immunofluorescence: use goat and identification of glycine substitution for valine-157 in the sequence of anti-mouse IgM-FITC: sc-2082 (dilution range: 1:100-1:400) or goat anti- mouse the precursor, producing an unstable mature protein in a patient. Am. J. IgM-TR: sc-2983 (dilution range: 1:100-1:400) with UltraCruz™ Mounting Hum. Genet. 49: 575-580. Medium: sc-24941. 3. Freneaux, E., et al. 1992. Glutaric acidemia type II. Heterogeneity in β-oxi - dation flux, polypeptide synthesis, and complementary DNA mutations in RT-PCR REAGENTS the α subunit of electron transfer flavoprotein in eight patients. J. Clin. Semi-quantitative RT-PCR may be performed to monitor ETFA gene expres sion Invest. 90: 1679-1686. knockdown using RT-PCR Primer: ETFA (h)-PR: sc-62259-PR (20 µl). Annealing temperature for the primers should be 55-60° C and the extension tempera - CHROMOSOMAL LOCATION ture should be 68-72° C. Genetic locus: ETFA (human) mapping to 15q24.2. BIOSAFETY PRODUCT Lentiviral particles can be employed in standard Biosafety Level 2 tissue ETFA shRNA (h) Lentiviral Particles is a pool of concentrated, transduction- culture facilities (and should be treated with the same level of caution as ready viral particles containing 3 target-specific constructs that encode with any other potentially infectious reagent). Lentiviral particles are repli- 19-25 nt (plus hairpin) shRNA designed to knock down gene expression. cation-incompetent and are designed to self-inactivate after transduction Each vial contains 200 µl frozen stock containing 1.0 x 10 6 infectious units and integration of shRNA constructs into genomic DNA of target cells. of virus (IFU) in Dulbecco’s Modified Eagle’s Medium with 25 mM HEPES pH 7.3. Suitable for 10-20 transductions. Also see ETFA siRNA (h): sc-62259 RESEARCH USE and ETFA shRNA Plasmid (h): sc-62259-SH as alternate gene silencing The purchase of this product conveys to the buyer the nontransferable right prod ucts. to use the purchased amount of the product and all replicates and derivatives for research purposes conducted by the buyer in his laboratory only (whether STORAGE the buyer is an academic or for-profit entity). The buyer cannot sell or other - Store lentiviral particles at -80º C. Stable for at least one year from the wise transfer (a) this product (b) its components or (c) materials made using date of shipment. Once thawed, particles can be stored at 4º C for up to this product or its components to a third party, or otherwise use this product one week. Avoid repeated freeze thaw cycles. or its components or materials made using this product or its components for Commercial Purposes. PROTOCOLS See our web site at www.scbt.com or our catalog for detailed protocols and support products. Santa Cruz Biotechnology, Inc. 1.800.457.3801 831.457.3800 fax 831.457.3801 Europe +00800 4573 8000 49 6221 4503 0 www.scbt.com.
Recommended publications
  • UNIVERSITY of CALIFORNIA, SAN DIEGO Functional Analysis of Sall4
    UNIVERSITY OF CALIFORNIA, SAN DIEGO Functional analysis of Sall4 in modulating embryonic stem cell fate A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Molecular Pathology by Pei Jen A. Lee Committee in charge: Professor Steven Briggs, Chair Professor Geoff Rosenfeld, Co-Chair Professor Alexander Hoffmann Professor Randall Johnson Professor Mark Mercola 2009 Copyright Pei Jen A. Lee, 2009 All rights reserved. The dissertation of Pei Jen A. Lee is approved, and it is acceptable in quality and form for publication on microfilm and electronically: ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ Co-Chair ______________________________________________________________ Chair University of California, San Diego 2009 iii Dedicated to my parents, my brother ,and my husband for their love and support iv Table of Contents Signature Page……………………………………………………………………….…iii Dedication…...…………………………………………………………………………..iv Table of Contents……………………………………………………………………….v List of Figures…………………………………………………………………………...vi List of Tables………………………………………………….………………………...ix Curriculum vitae…………………………………………………………………………x Acknowledgement………………………………………………….……….……..…...xi Abstract………………………………………………………………..…………….....xiii Chapter 1 Introduction ..…………………………………………………………………………….1 Chapter 2 Materials and Methods……………………………………………………………..…12
    [Show full text]
  • Identification of Differentially Expressed Genes in Human Bladder Cancer Through Genome-Wide Gene Expression Profiling
    521-531 24/7/06 18:28 Page 521 ONCOLOGY REPORTS 16: 521-531, 2006 521 Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling KAZUMORI KAWAKAMI1,3, HIDEKI ENOKIDA1, TOKUSHI TACHIWADA1, TAKENARI GOTANDA1, KENGO TSUNEYOSHI1, HIROYUKI KUBO1, KENRYU NISHIYAMA1, MASAKI TAKIGUCHI2, MASAYUKI NAKAGAWA1 and NAOHIKO SEKI3 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Departments of 2Biochemistry and Genetics, and 3Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan Received February 15, 2006; Accepted April 27, 2006 Abstract. Large-scale gene expression profiling is an effective CKS2 gene not only as a potential biomarker for diagnosing, strategy for understanding the progression of bladder cancer but also for staging human BC. This is the first report (BC). The aim of this study was to identify genes that are demonstrating that CKS2 expression is strongly correlated expressed differently in the course of BC progression and to with the progression of human BC. establish new biomarkers for BC. Specimens from 21 patients with pathologically confirmed superficial (n=10) or Introduction invasive (n=11) BC and 4 normal bladder samples were studied; samples from 14 of the 21 BC samples were subjected Bladder cancer (BC) is among the 5 most common to microarray analysis. The validity of the microarray results malignancies worldwide, and the 2nd most common tumor of was verified by real-time RT-PCR. Of the 136 up-regulated the genitourinary tract and the 2nd most common cause of genes we detected, 21 were present in all 14 BCs examined death in patients with cancer of the urinary tract (1-7).
    [Show full text]
  • Using Structural Knowledge in the Protein Data Bank to Inform The
    Mahajan and Mande BMC Bioinformatics (2017) 18:201 DOI 10.1186/s12859-017-1550-y RESEARCH ARTICLE Open Access Using structural knowledge in the protein data bank to inform the search for potential host-microbe protein interactions in sequence space: application to Mycobacterium tuberculosis Gaurang Mahajan1,2* and Shekhar C. Mande1 Abstract Background: A comprehensive map of the human-M. tuberculosis (MTB) protein interactome would help fill the gaps in our understanding of the disease, and computational prediction can aid and complement experimental studies towards this end. Several sequence-based in silico approaches tap the existing data on experimentally validated protein-protein interactions (PPIs); these PPIs serve as templates from which novel interactions between pathogen and host are inferred. Such comparative approaches typically make use of local sequence alignment, which, in the absence of structural details about the interfaces mediating the template interactions, could lead to incorrect inferences, particularly whenmulti-domainproteinsareinvolved. Results: We propose leveraging the domain-domain interaction (DDI) information in PDB complexes to score and prioritize candidate PPIs between host and pathogen proteomes based on targeted sequence-level comparisons. Our method picks out a small set of human-MTB protein pairs as candidates for physical interactions, and the use of functional meta-data suggests that some of them could contribute to the in vivo molecular cross-talk between pathogen and host that regulates the course of the infection. Further, we present numerical data for Pfam domain families that highlights interaction specificity on the domain level. Not every instance of a pair of domains, for which interaction evidence has been found in a few instances (i.e.
    [Show full text]
  • Downloaded from the App Store and Nucleobase, Nucleotide and Nucleic Acid Metabolism 7 Google Play
    Hoytema van Konijnenburg et al. Orphanet J Rare Dis (2021) 16:170 https://doi.org/10.1186/s13023-021-01727-2 REVIEW Open Access Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app Eva M. M. Hoytema van Konijnenburg1†, Saskia B. Wortmann2,3,4†, Marina J. Koelewijn2, Laura A. Tseng1,4, Roderick Houben6, Sylvia Stöckler‑Ipsiroglu5, Carlos R. Ferreira7 and Clara D. M. van Karnebeek1,2,4,8* Abstract Background: The Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disabil‑ ity (collectively ‘treatable IDs’). Our aim is to update the 2012 review on treatable IDs and App to capture the advances made in the identifcation of new IMDs along with increased pathophysiological insights catalyzing therapeutic development and implementation. Methods: Two independent reviewers queried PubMed, OMIM and Orphanet databases to reassess all previously included disorders and therapies and to identify all reports on Treatable IDs published between 2012 and 2021. These were included if listed in the International Classifcation of IMDs (ICIMD) and presenting with ID as a major feature, and if published evidence for a therapeutic intervention improving ID primary and/or secondary outcomes is avail‑ able. Data on clinical symptoms, diagnostic testing, treatment strategies, efects on outcomes, and evidence levels were extracted and evaluated by the reviewers and external experts. The generated knowledge was translated into a diagnostic algorithm and updated version of the App with novel features. Results: Our review identifed 116 treatable IDs (139 genes), of which 44 newly identifed, belonging to 17 ICIMD categories.
    [Show full text]
  • Genome-Wide Association Study Identifies Multiple Susceptibility Loci
    ARTICLE Received 8 May 2015 | Accepted 4 Sep 2015 | Published 1 Oct 2015 DOI: 10.1038/ncomms9559 OPEN Genome-wide association study identifies multiple susceptibility loci for glioma Ben Kinnersley1, Marianne Labussie`re2, Amy Holroyd1, Anna-Luisa Di Stefano2,3,4, Peter Broderick1, Jayaram Vijayakrishnan1, Karima Mokhtari2,3,5, Jean-Yves Delattre2,3,4, Konstantinos Gousias6, Johannes Schramm6, Minouk J. Schoemaker1, Sarah J. Fleming7, Stefan Herms8,9, Stefanie Heilmann8, Stefan Schreiber10,11, Heinz-Erich Wichmann12,13, Markus M. No¨then8, Anthony Swerdlow1,14, Mark Lathrop5,15,16, Matthias Simon6, Melissa Bondy17, Marc Sanson2,3,4 & Richard S. Houlston1 Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P ¼ 3.02 Â 10 À 9) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P ¼ 4.32 Â 10 À 8), 11q23.2 (rs648044, near ZBTB16, P ¼ 6.26 Â 10 À 11), 12q21.2 (rs12230172, P ¼ 7.53 Â 10 À 11) and 15q24.2 (rs1801591, near ETFA, P ¼ 5.71 Â 10 À 9). Our findings provide further insights into the genetic basis of the different glioma subtypes. 1 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK.
    [Show full text]
  • 1 Supplementary Information ADCK2 Haploinsufficiency Reduces
    Supplementary information ADCK2 haploinsufficiency reduces mitochondrial lipid oxidation and causes myopathy associated with CoQ deficiency.. Luis Vázquez-Fonseca1,8,§, Jochen Schäfer2,§, Ignacio Navas-Enamorado1,7, Carlos Santos-Ocaña1,10, Juan D. Hernández-Camacho1,10, Ignacio Guerra1, María V. Cascajo1,10, Ana Sánchez-Cuesta1,10, Zoltan Horvath2#, Emilio Siendones1, Cristina Jou3,10, Mercedes Casado3,10, Purificación Gutiérrez1, Gloria Brea-Calvo1,10, Guillermo López-Lluch1,10, Daniel M. Fernández-Ayala1,10, Ana B. Cortés- Rodríguez1,10, Juan C. Rodríguez-Aguilera1,10, Cristiane Matté4, Antonia Ribes5,10, Sandra Y. Prieto- Soler6, Eduardo Dominguez-del-Toro6, Andrea di Francesco8, Miguel A. Aon8, Michel Bernier8, Leonardo Salviati9, Rafael Artuch3,10, Rafael de Cabo8, Sandra Jackson2 and Plácido Navas1,10 1 Supplementary Results Case report The male index patient (subject II-3, Fig. S1A) presented to our clinic at 45 years of age with a 15-year history of slowly progressive muscle weakness and myalgia, which occurred at rest but worsened with exercise. Past medical history was unremarkable except for renal disease of unknown cause in childhood, which spontaneously improved. Family history was negative for neurological disease. On examination, moderate proximal symmetrical myopathy, more pronounced in the arms, was noted and the patient was unable to lift his arms above the horizontal position. The patient had a hyperlordotic, waddling gait and was only able to walk 100 meters without the aid of crutches. Bilateral scapular winging was present, and bilateral atrophy of the biceps, triceps, and quadriceps was noted, whilst the deltoid muscles were well preserved. Calf hypertrophy was present. The Trendelenburg sign was positive, and the patient was unable to rise from squatting.
    [Show full text]
  • Pure Duplication of the Distal Long Arm of Chromosome 15 with Ebstein Anomaly and Clavicular Anomaly
    Hindawi Publishing Corporation Case Reports in Genetics Volume 2011, Article ID 898706, 5 pages doi:10.1155/2011/898706 Case Report Pure Duplication of the Distal Long Arm of Chromosome 15 with Ebstein Anomaly and Clavicular Anomaly Rachel O’Connor,1 Amel Al-Murrani,1 Salim Aftimos,2 Philip Asquith,1 Roberto Mazzaschi,1 Dominique Eyrolle-Guignot,3 Alice M. George,1 and Donald R. Love1, 4 1 Diagnostic Genetics, LabPlus, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand 2 Northern Regional Genetic Service, Auckland City Hospital, Private Bag 92024, Auckland 1142, New Zealand 3 Maternit´e Andrea De Balmain, Centre Hospitalier du Taaone, BP 1640, 98 713 Papeete, Polyn´esie Franc¸aise, France 4 School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand Correspondence should be addressed to Donald R. Love, [email protected] Received 24 June 2011; Accepted 21 July 2011 Academic Editors: D. J. Bunyan, P. D. Cotter, and G. Velagaleti Copyright © 2011 Rachel O’Connor et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This report is of a patient with pure trisomy of 15q24-qter who presents with the rare Ebstein anomaly and a previously unreported skeletal anomaly. Chromosome microarray analysis allowed high-resolution identification of the extent of the trisomy and provided a means of achieving higher-resolution breakpoint data. The phenotypic expression of unbalanced chromosomal regions is a complex phenomenon, and fine mapping of the involved region, as described here, is only a first step on the path to its full understanding.
    [Show full text]
  • Gnomad Lof Supplement
    1 gnomAD supplement gnomAD supplement 1 Data processing 4 Alignment and read processing 4 Variant Calling 4 Coverage information 5 Data processing 5 Sample QC 7 Hard filters 7 Supplementary Table 1 | Sample counts before and after hard and release filters 8 Supplementary Table 2 | Counts by data type and hard filter 9 Platform imputation for exomes 9 Supplementary Table 3 | Exome platform assignments 10 Supplementary Table 4 | Confusion matrix for exome samples with Known platform labels 11 Relatedness filters 11 Supplementary Table 5 | Pair counts by degree of relatedness 12 Supplementary Table 6 | Sample counts by relatedness status 13 Population and subpopulation inference 13 Supplementary Figure 1 | Continental ancestry principal components. 14 Supplementary Table 7 | Population and subpopulation counts 16 Population- and platform-specific filters 16 Supplementary Table 8 | Summary of outliers per population and platform grouping 17 Finalizing samples in the gnomAD v2.1 release 18 Supplementary Table 9 | Sample counts by filtering stage 18 Supplementary Table 10 | Sample counts for genomes and exomes in gnomAD subsets 19 Variant QC 20 Hard filters 20 Random Forest model 20 Features 21 Supplementary Table 11 | Features used in final random forest model 21 Training 22 Supplementary Table 12 | Random forest training examples 22 Evaluation and threshold selection 22 Final variant counts 24 Supplementary Table 13 | Variant counts by filtering status 25 Comparison of whole-exome and whole-genome coverage in coding regions 25 Variant annotation 30 Frequency and context annotation 30 2 Functional annotation 31 Supplementary Table 14 | Variants observed by category in 125,748 exomes 32 Supplementary Figure 5 | Percent observed by methylation.
    [Show full text]
  • V12a58-Dash Pgmkr
    Molecular Vision 2006; 12:499-505 <http://www.molvis.org/molvis/v12/a58/> ©2006 Molecular Vision Received 30 September 2005 | Accepted 26 April 2006 | Published 12 May 2006 Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis Durga Prasad Dash,1 Giuliana Silvestri,2 Anne E. Hughes1 Departments of 1Medical Genetics and 2Ophthalmology, Queen’s University of Belfast, Belfast, United Kingdom Purpose: To report the fine mapping of the keratoconus with cataract locus on chromosome 15q and the mutational analysis of positional candidate genes. Methods: Genotyping of two novel microsatellite markers and a single nucleotide polymorphism (SNP) in the critical region of linkage for keratoconus with cataract on 15q was performed. Positional candidate genes (MORF4L1, KIAA1055, ETFA, AWP1, REC14, KIAA1199, RCN2, FA H , IDH3A, MTHFS, ADAMTS7, MAN2C1, PTPN9, KIAA1024, ARNT2, BCL2A1, ISL2, C15ORF22 (P24B), DNAJA4, FLJ14594, CIB2 (KIP2), C15ORF5, and PSMA4) prioritized on the basis of ocular expression and probable function were screened by PCR-based DNA sequencing methods. Results: We report the refinement of the linkage region for keratoconus with cataract to an interval of approximately 5.5 Mb flanked by the MAN2C1 gene and the D15S211 marker on chromosome 15q. Mutational analysis of positional candi- date genes detected many sequence variations and single nucleotide polymorphisms. None of the sequence variants were considered pathogenic as they were also found in unaffected family members and normal control DNA samples. Conclusions: Fine mapping of the keratoconus with cataract locus on 15q has reduced the linked region to 5.5 Mb, thereby excluding 28 candidate genes.
    [Show full text]
  • Pathogenic Nssnps That Increase the Risks of Cancers Among the Orang
    www.nature.com/scientificreports OPEN Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays Nurul Ain Khoruddin1,2, Mohd NurFakhruzzaman Noorizhab1,3, Lay Kek Teh1,3, Farida Zuraina Mohd Yusof1,2 & Mohd Zaki Salleh1,3* Single-nucleotide polymorphisms (SNPs) are the most common genetic variations for various complex human diseases, including cancers. Genome-wide association studies (GWAS) have identifed numerous SNPs that increase cancer risks, such as breast cancer, colorectal cancer, and leukemia. These SNPs were cataloged for scientifc use. However, GWAS are often conducted on certain populations in which the Orang Asli and Malays were not included. Therefore, we have developed a bioinformatic pipeline to mine the whole-genome sequence databases of the Orang Asli and Malays to determine the presence of pathogenic SNPs that might increase the risks of cancers among them. Five diferent in silico tools, SIFT, PROVEAN, Poly-Phen-2, Condel, and PANTHER, were used to predict and assess the functional impacts of the SNPs. Out of the 80 cancer-related nsSNPs from the GWAS dataset, 52 nsSNPs were found among the Orang Asli and Malays. They were further analyzed using the bioinformatic pipeline to identify the pathogenic variants. Three nsSNPs; rs1126809 (TYR), rs10936600 (LRRC34), and rs757978 (FARP2), were found as the most damaging cancer pathogenic variants. These mutations alter the protein interface and change the allosteric sites of the respective proteins. As TYR , LRRC34, and FARP2 genes play important roles in numerous cellular processes such as cell proliferation, diferentiation, growth, and cell survival; therefore, any impairment on the protein function could be involved in the development of cancer.
    [Show full text]
  • From Novel Disease Genes to New Mouse Models - a Complementary Approach
    TECHNISCHE UNIVERSITÄT MÜNCHEN FAKULTÄT WISSENSCHAFTSZENTRUM WEIHENSTEPHAN FÜR ERNÄHRUNG, LANDNUTZUNG UND UMWELT LEHRSTUHL FÜR ENTWICKLUNGSGENETIK From Novel Disease Genes to New Mouse Models - A Complementary Approach Caroline Alexandra Biagosch Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Prof. Dr. Martin Hrab ĕ de Angelis Prüfer der Dissertation: 1. Priv.-Doz. Dr. Thomas Floss 2. Prof. Angelika Schniecke, Ph.D. Die Dissertation wurde am 10.10.2016 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 08.03.2017 angenommen. To my family. TABLE OF CONTENTS ABSTRACT ......................................................................................................................... 9 English .............................................................................................................................................. 9 German ........................................................................................................................................... 11 I. IDENTIFICATION OF A NEW DISEASE-ASSOCIATED GENE – FBXL4 .... 13 I.1. INTRODUCTION .............................................................................................................. 13 I.1.1. Genetic disease and mitochondriopathies
    [Show full text]
  • Evolutionary Turnover of Mammalian Transcription Start Sites
    Downloaded from genome.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Evolutionary turnover of mammalian transcription start sites Martin C. Frith,1,3 Jasmina Ponjavic,1,5 David Fredman,4 Chikatoshi Kai,1 Jun Kawai,1 Piero Carninci,1,2 Yoshihide Hayshizaki,1,2 and Albin Sandelin1,6 1Genome Exploration Research Group, RIKEN Genomic Sciences Centre (GSC), RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan; 2Genome Science Laboratory, Discovery and Research Institute, RIKEN Wako Institute, Wako, Saitama, 351-0198, Japan; 3Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia; 4Computational Biology Unit, Bergen Center for Computational Science, University of Bergen, HIB, N-5008 Bergen, Norway Alignments of homologous genomic sequences are widely used to identify functional genetic elements and study their evolution. Most studies tacitly equate homology of functional elements with sequence homology. This assumption is violated by the phenomenon of turnover, in which functionally equivalent elements reside at locations that are nonorthologous at the sequence level. Turnover has been demonstrated previously for transcription- factor-binding sites. Here, we show that transcription start sites of equivalent genes do not always reside at equivalent locations in the human and mouse genomes. We also identify two types of partial turnover, illustrating evolutionary pathways that could lead to complete turnover. These findings suggest that the signals
    [Show full text]