Sacsin (SACS) (NM 014363) Human Tagged ORF Clone – RC219094 | Origene

Total Page:16

File Type:pdf, Size:1020Kb

Sacsin (SACS) (NM 014363) Human Tagged ORF Clone – RC219094 | Origene OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC219094 Sacsin (SACS) (NM_014363) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: Sacsin (SACS) (NM_014363) Human Tagged ORF Clone Tag: Myc-DDK Symbol: SACS Synonyms: ARSACS; DNAJC29; PPP1R138; SPAX6 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin ORF Nucleotide >RC219094 representing NM_014363 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGAGACCAAGGAGAACAGGTGGGTCCCGGTGACCGTGCTCCCCGGCTGCGTGGGCTGCAGGACCGTCG CGGCGCTGGCGTCCTGGACCGTGCGCGATGTGAAGGAACGTATCTTCGCGGAGACTGGCTTCCCGGTGTC GGAGCAGCGGCTGTGGCGCGGCGGCCGCGAGTTATCTGACTGGATCAAGATTGGAGATCTGACTTCCAAA AATTGTCATCTTTTTGTAAACCTTCAATCAAAAGGCTTAAAAGGGGGAGGTCGATTTGGTCAGACAACGC CACCACTTGTTGATTTTCTCAAGGACATTTTGAGAAGATATCCAGAAGGAGGACAGATTCTTAAGGAATT AATTCAGAATGCAGAAGATGCTGGGGCGACAGAAGTTAAATTTTTATATGATGAAACTCAATACGGAACA GAGACTCTTTGGTCAAAAGATATGGCGCCATATCAGGGGCCAGCTCTCTATGTGTACAACAACGCGGTTT TCACCCCAGAGGACTGGCACGGCATTCAAGAAATAGCAAGAAGCAGGAAAAAGGATGATCCTCTGAAGGT CGGAAGATTTGGAATTGGGTTTAATTCTGTCTATCATATAACAGATGTTCCTTGTATCTTTAGTGGTGAC CAAATCGGGATGCTAGATCCTCATCAAACACTTTTTGGCCCACATGAATCAGGCCAATGTTGGAAACTCA AAGATGACAGCAAAGAAATTAGTGAACTTTCAGACCAGTTTGCACCATTTGTTGGCATTTTTGGAAGCAC CAAGGAAACATTTATAAACGGCAATTTTCCAGGAACATTTTTCCGTTTCCCTCTTCGCCTACAACCTTCA CAACTTAGTAGTAACCTCTACAATAAGCAGAAGGTTCTTGAGTTGTTTGAGTCTTTTAGGGCAGATGCAG ACACAGTGCTGCTCTTTCTGAAAAGTGTGCAGGATGTTTCCTTATATGTCCGAGAGGCTGACGGAACAGA GAAACTGGTGTTTAGAGTGACTTCGAGTGAGAGTAAGGCACTGAAACATGAGCGGCCGAATTCTATAAAG ATTCTGGGAACTGCTATAAGTAACTATTGTAAAAAGACTCCAAGCAATAACATCACCTGTGTAACATATC ACGTAAATATTGTTTTAGAAGAGGAGAGTACTAAGGATGCACAGAAAACATCTTGGTTGGTGTGTAACAG TGTGGGTGGGCGAGGGATCAGTAGTAAGCTTGACTCTTTAGCTGATGAACTGAAATTTGTCCCAATCATT GGAATAGCCATGCCTTTATCAAGCAGAGATGATGAAGCAAAAGGAGCAACGTCTGATTTCTCAGGAAAAG CATTTTGTTTCCTTCCTTTACCACCTGGTGAGGAAAGCAGCACAGGCCTCCCAGTTCACATCAGTGGGTT CTTTGGCCTTACTGATAACCGCAGGAGCATAAAATGGAGAGAGCTGGACCAGTGGAGAGACCCGGCAGCC TTATGGAATGAGTTTCTTGTCATGAATGTTGTCCCCAAAGCTTATGCTACTCTGATCTTAGATTCAATAA This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 8 Sacsin (SACS) (NM_014363) Human Tagged ORF Clone – RC219094 AACGTCTGGAGATGGAAAAGAGCTCTGATTTCCCCTTGTCAGTTGATGTTATCTATAAGCTTTGGCCGGA GGCGAGCAAAGTCAAGGTGCACTGGCAACCGGTGTTAGAGCCTCTGTTCAGCGAGCTGTTGCAGAATGCA GTGATTTATTCAATTAGCTGTGACTGGGTCAGGTTGGAGCAGGTGTACTTCTCAGAACTTGATGAAAATT TAGAATACACAAAAACTGTGCTCAACTACCTCCAGAGCTCAGGGAAGCAGATTGCCAAGGTACCAGGGAA TGTGGATGCTGCTGTTCAGCTCACAGCTGCCTCTGGCACAACACCTGTGAGGAAGGTGACGCCCGCGTGG GTGCGGCAGGTGCTGCGGAAGTGTGCACACCTGGGCTGTGCTGAAGAAAAGCTTCACCTTCTAGAATTTG TGCTTTCTGACCAAGCCTACAGTGAGCTGCTTGGGCTGGAGCTGCTCCCTTTACAAAATGGCAATTTTGT CCCCTTCTCCTCATCTGTATCAGACCAAGATGTCATTTATATTACCTCAGCAGAATATCCAAGGTCCCTT TTCCCAAGTCTTGAAGGAAGATTTATTTTGGATAACTTGAAACCTCACCTTGTGGCTGCTTTAAAGGAAG CTGCCCAAACCCGAGGAAGACCATGTACTCAGCTGCAGCTTCTAAATCCAGAACGATTTGCACGTCTTAT CAAGGAAGTAATGAATACATTCTGGCCTGGCAGAGAATTGATTGTTCAATGGTATCCATTTGATGAAAAC AGAAATCACCCATCTGTTTCATGGCTTAAGATGGTTTGGAAAAATCTTTATATACATTTTTCAGAGGATT TGACTTTATTTGATGAGATGCCACTTATCCCCAGAACTATACTAGAGGAAGGTCAGACATGTGTGGAACT CATTAGACTCAGGATTCCATCGTTAGTCATTTTAGACGATGAATCTGAAGCACAGCTTCCAGAATTTTTA GCAGACATTGTACAAAAACTTGGAGGGTTTGTCCTTAAAAAATTAGATGCATCTATACAACATCCGCTTA TTAAAAAATATATTCATTCACCATTACCAAGTGCTGTTTTGCAGATAATGGAGAAGATGCCATTGCAGAA ATTGTGTAATCAAATAACTTCGCTACTTCCAACACACAAAGATGCCCTGAGGAAGTTCTTGGCTAGTTTA ACCGATAGCAGTGAGAAAGAGAAAAGAATTATTCAAGAATTGGCAATATTCAAGCGCATTAACCATTCTT CTGATCAGGGAATTTCCTCTTATACAAAATTGAAAGGTTGTAAAGTCTTACACCATACTGCCAAACTCCC AGCAGATCTGCGACTTTCTATTTCAGTAATAGACAGTAGTGATGAAGCTACTATTCGTCTGGCAAACATG TTGAAAATAGAACAGTTAAAGACCACTAGCTGCTTAAAGCTTGTTTTAAAAGATATTGAAAATGCATTTT ATTCACATGAAGAGGTAACACAGCTTATGTTATGGGTCCTTGAGAATCTATCTTCTCTTAAAAATGAGAA TCCAAATGTGCTTGAGTGGTTAACACCATTAAAATTCATCCAGATATCACAGGAACAGATGGTATCAGCT GGTGAACTCTTTGACCCTGATATAGAAGTACTAAAGGATCTCTTTTGTAATGAAGAAGGAACCTATTTCC CACCCTCAGTTTTTACCTCACCAGATATTCTTCACTCCTTAAGACAGATTGGTTTAAAAAACGAAGCCAG TCTCAAAGAAAAGGATGTTGTGCAAGTGGCAAAAAAAATTGAAGCCTTACAGGTCGGTGCTTGTCCTGAT CAAGATGTTCTTCTGAAGAAAGCCAAAACCCTCTTACTGGTTTTAAATAAGAATCACACACTGTTGCAAT CATCTGAAGGAAAGATGACATTGAAGAAAATAAAATGGGTTCCAGCCTGCAAGGAAAGGCCTCCAAATTA TCCAGGCTCTTTGGTCTGGAAAGGAGATCTCTGTAATCTCTGTGCACCACCAGATATGTGTGATGTAGGC CATGCAATTCTCATTGGCTCCTCACTTCCTCTTGTTGAAAGTATCCATGTAAACCTGGAAAAAGCATTAG GGATCTTCACAAAACCTAGCCTTAGTGCTGTCTTAAAACACTTTAAAATTGTTGTTGATTGGTATTCTTC AAAAACCTTTAGTGATGAAGACTACTATCAATTCCAGCATATTTTGCTTGAGATTTACGGATTCATGCAT GATCATCTAAATGAAGGGAAAGATTCTTTTAGAGCCTTAAAATTTCCATGGGTTTGGACTGGCAAAAAGT TTTGTCCACTTGCCCAGGCTGTGATTAAACCAATCCATGATCTTGACCTTCAGCCTTATTTGCATAATGT ACCTAAAACCATGGCAAAATTCCACCAACTATTTAAGGTCTGTGGTTCAATAGAGGAGTTGACATCAGAT CATATTTCCATGGTTATTCAGAAGATATATCTCAAAAGTGACCAAGATCTCAGTGAACAAGAAAGCAAAC AAAATCTTCATCTTATGTTGAATATTATCAGATGGCTGTATAGCAATCAGATTCCAGCAAGCCCCAACAC ACCAGTTCCTATACATCATAGCAAAAATCCTTCTAAACTTATCATGAAGCCAATTCACGAATGCTGTTAT TGTGACATTAAAGTTGATGACCTTAATGACTTACTTGAAGATTCTGTGGAACCAATCATTTTGGTGCATG AGGACATACCCATGAAAACTGCAGAATGGCTAAAAGTTCCATGCCTTAGTACAAGACTGATAAATCCTGA AAACATGGGATTTGAGCAGTCAGGACAAAGAGAGCCACTTACTGTAAGAATTAAAAATATTCTGGAAGAA TACCCTTCAGTGTCAGATATTTTTAAAGAACTACTTCAAAACGCTGATGATGCAAATGCAACAGAATGCA GTTTCTTGATTGATATGAGAAGAAATATGGACATAAGAGAGAATCTCCTAGACCCAGGGATGGCAGCTTG TCATGGACCTGCTTTGTGGTCATTCAACAATTCTCAATTCTCAGATTCAGATTTTGTGAACATAACTAGG TTAGGAGAATCTTTAAAAAGGGGAGAAGTTGACAAAGTTGGAAAATTTGGTCTTGGATTTAATTCTGTGT ACCATATCACTGACATTCCCATCATTATGAGTCGGGAATTCATGATAATGTTCGATCCAAACATAAATCA TATCAGTAAACACATTAAAGACAAATCCAATCCTGGGATCAAAATTAATTGGAGTAAACAACAGAAAAGA CTTAGAAAATTTCCTAATCAGTTCAAACCATTTATAGATGTATTTGGCTGTCAGTTACCTTTGACTGTAG AAGCACCTTACAGCTATAATGGAACCCTTTTCCGACTGTCCTTTAGAACTCAACAGGAAGCAAAAGTGAG TGAAGTTAGTAGTACGTGCTACAATACAGCAGATATTTATTCTCTTGTGGATGAATTTAGTCTCTGTGGA CACAGGCTTATCATTTTCACTCAGAGTGTAAAGTCAATGTATTTGAAGTACTTGAAAATTGAGGAAACCA ACCCCAGTTTAGCACAAGATACAGTAATAATTAAAAAAAAATCCTGCTCTTCCAAAGCATTGAACACACC This product is to be used for laboratory only. Not for diagnostic or therapeutic use. ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 2 / 8 Sacsin (SACS) (NM_014363) Human Tagged ORF Clone – RC219094 TGTCTTAAGTGTTTTAAAAGAGGCTGCTAAGCTCATGAAGACTTGCAGCAGCAGTAATAAAAAGCTTCCC AGTGATGAACCAAAGTCATCTTGCATTCTTCAGATCACAGTGGAAGAATTTCACCATGTGTTCAGAAGGA TTGCTGATTTACAGTCGCCACTTTTTAGAGGTCCAGATGATGACCCAGCTGCTCTCTTTGAAATGGCTAA GTCTGGCCAATCAAAAAAGCCATCAGATGAGTTGTCACAGAAAACAGTAGAGTGTACCACGTGGCTTCTG TGTACTTGCATGGACACAGGAGAGGCTCTGAAGTTTTCCCTGAGTGAGAGTGGAAGAAGACTAGGACTGG TTCCATGTGGGGCAGTAGGAGTTCAGCTGTCAGAAATCCAGGACCAGAAGTGGACAGTGAAACCACACAT TGGAGAGGTGTTTTGCTATTTACCTTTACGAATAAAAACAGGCTTGCCAGTTCATATCAATGGGTGCTTT GCTGTTACATCAAATAGGAAAGAAATCTGGAAAACAGATACAAAAGGACGATGGAATACCACGTTCATGA GACATGTTATTGTGAAAGCTTACTTACAGGTACTGAGTGTCTTACGGGACCTGGCCACTAGTGGGGAGCT AATGGATTATACTTACTATGCAGTATGGCCCGATCCTGATTTAGTTCATGATGATTTTTCTGTAATTTGC CAAGGATTTTATGAAGATATAGCTCATGGAAAAGGGAAAGAACTGACCAAAGTCTTCTCTGATGGATCTA CTTGGGTTTCCATGAAGAACGTAAGATTTCTAGATGACTCTATACTTAAAAGAAGAGATGTTGGTTCAGC AGCCTTCAAGATATTTTTGAAATACCTCAAGAAGACTGGGTCCAAAAACCTTTGTGCTGTTGAACTTCCT TCTTCGGTAAAATTAGGATTTGAAGAAGCTGGCTGCAAACAGATACTACTTGAAAACACATTTTCAGAGA AACAGTTTTTTTCTGAAGTGTTTTTTCCAAATATTCAAGAAATTGAAGCAGAACTTAGAGATCCTTTAAT GATCTTTGTTCTAAATGAAAAAGTTGATGAGTTCTCGGGAGTTCTTCGTGTTACTCCATGTATTCCTTGT TCCTTGGAGGGGCATCCTTTGGTTTTGCCATCAAGATTGATCCACCCCGAAGGACGAGTTGCAAAGTTAT TTGATATTAAAGATGGGAGATTCCCTTATGGTTCTACTCAGGATTATCTCAATCCTATTATTTTGATTAA ACTAGTTCAGTTAGGTATGGCAAAAGATGATATTTTATGGGATGATATGCTAGAACGTGCAGTGTCAGTA GCTGAAATTAATAAAAGTGATCATGTTGCTGCATGCCTAAGAAGTAGTATCTTATTGAGTCTTATCGATG AGAAACTAAAAATAAGGGATCCTAGAGCAAAGGATTTTGCTGCAAAATATCAAACAATCCGCTTCCTTCC ATTTCTGACAAAACCAGCAGGTTTTTCTTTGGACTGGAAAGGCAACAGTTTTAAGCCTGAAACCATGTTT GCAGCAACTGACCTTTATACAGCTGAACATCAAGATATAGTTTGTCTTTTGCAACCAATTCTAAATGAAA ATTCCCATTCTTTTAGAGGTTGTGGTTCAGTGTCATTGGCTGTTAAAGAGTTTTTGGGATTACTCAAGAA GCCAACAGTTGATCTGGTTATAAACCAATTGAAAGAAGTAGCAAAATCAGTTGATGATGGAATTACACTG TACCAGGAGAATATCACCAATGCTTGCTACAAATACCTTCATGAAGCCTTGATGCAAAATGAAATCACTA AGATGTCAATTATTGATAAGTTAAAACCCTTTAGCTTCATTCTAGTTGAGAATGCATATGTTGACTCAGA AAAGGTTTCTTTTCATTTAAATTTTGAGGCGGCACCATACCTTTATCAGTTGCCTAATAAGTATAAAAAT AATTTCCGCGAACTTTTTGAAACCGTGGGTGTGAGGCAGTCATGCACTGTTGAAGATTTTGCTCTTGTTT TGGAATCTATTGATCAAGAAAGAGGAACAAAGCAAATAACAGAAGAGAATTTTCAGCTTTGCCGACGAAT AATCAGTGAAGGAATATGGAGTCTCATTAGAGAAAAGAAACAAGAATTTTGTGAGAAAAATTATGGCAAG ATATTATTGCCAGATACTAATCTTATGCTTCTCCCTGCTAAATCGTTATGCTACAATGATTGCCCTTGGA TAAAAGTAAAGGATACCACTGTAAAATATTGTCATGCTGACATACCCAGGGAAGTAGCAGTAAAACTAGG AGCAGTCCCAAAGCGACACAAAGCCTTAGAAAGATATGCATCCAATGTCTGTTTTACAACACTTGGCACA GAATTTGGGCAGAAAGAAAAATTGACCAGCAGAATTAAGAGCATCCTTAATGCATATCCTTCTGAAAAGG AAATGTTGAAAGAGCTTCTTCAAAATGCTGATGATGCAAAGGCGACAGAAATCTGTTTTGTGTTTGATCC TAGACAGCATCCAGTTGATAGAATATTTGATGATAAGTGGGCCCCATTGCAAGGGCCAGCACTTTGTGTG TACAACAACCAGCCATTTACAGAAGATGATGTTAGAGGAATTCAGAATCTTGGAAAAGGCACGAAAGAGG GAAATCCTTATAAAACTGGACAGTATGGAATAGGATTCAATTCTGTGTATCATATCACAGACTGCCCATC TTTTATTTCTGGCAATGACATCCTGTGTATTTTTGATCCTCATGCCAGATATGCACCAGGGGCCACATCC ATTAGTCCCGGACGCATGTTTAGAGATTTGGATGCAGATTTTAGGACACAGTTCTCAGATGTTCTGGATC TTTATCTGGGAACCCATTTTAAACTGGATAATTGCACAATGTTCAGATTTCCTCTTCGTAATGCAGAAAT GGCAAAAGTTTCGGAAATTTCGTCTGTTCCAGCATCAGACAGAATGGTCCAGAATCTTTTGGACAAACTG CGCTCAGATGGGGCAGAACTTCTAATGTTTCTTAATCACATGGAAAAAATTTCTATTTGTGAAATAGATA
Recommended publications
  • Environmental Influences on Endothelial Gene Expression
    ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community.
    [Show full text]
  • A Reduction in Drp1-Mediated Fission Compromises
    HMG Advance Access published June 26, 2016 Human Molecular Genetics, 2016, Vol. 0, No. 0 1–13 doi: 10.1093/hmg/ddw173 Advance Access Publication Date: 10 June 2016 Original Article ORIGINAL ARTICLE A reduction in Drp1-mediated fission compromises mitochondrial health in autosomal recessive spastic Downloaded from ataxia of Charlevoix Saguenay Teisha Y. Bradshaw1, Lisa E.L. Romano1, Emma J. Duncan1, 1 3 2 3 Suran Nethisinghe , Rosella Abeti , Gregory J. Michael , Paola Giunti , http://hmg.oxfordjournals.org/ Sascha Vermeer4 and J. Paul Chapple1,* 1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, United Kingdom, 2Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom, 3Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, United Kingdom and 4Department of Clinical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands at University College London on December 9, 2016 *To whom correspondence should be addressed at: Tel: þ44 2078826242; Fax: þ44 207 882 6197; Email [email protected] Abstract The neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is caused by loss of function of sacsin, a modular protein that is required for normal mitochondrial network organization. To further understand cellular consequences of loss of sacsin, we performed microarray analyses in sacsin knockdown cells and ARSACS patient fibroblasts. This identified altered transcript levels for oxidative phosphorylation and oxidative stress genes. These changes in mitochondrial gene networks were validated by quantitative reverse transcription PCR.
    [Show full text]
  • Product Description P441-A2 SACS-V01
    MRC-Holland ® Product Description version A2-01; Issued 23 April 2020 MLPA Product Description SALSA® MLPA® Probemix P441-A2 SACS To be used with the MLPA General Protocol. Version A2. Compared to version A1, four reference probes have been replaced. For complete product history see page 5. Catalogue numbers: • P441-025R: SALSA MLPA Probemix P441 SACS, 25 reactions. • P441-050R: SALSA MLPA Probemix P441 SACS, 50 reactions. • P441-100R: SALSA MLPA Probemix P441 SACS, 100 reactions. To be used in combination with a SALSA MLPA reagent kit and Coffalyser.Net data analysis software. MLPA reagent kits are either provided with FAM or Cy5.0 dye-labelled PCR primer, suitable for Applied Biosystems and Beckman/SCIEX capillary sequencers, respectively (see www.mlpa.com). Certificate of Analysis: Information regarding storage conditions, quality tests, and a sample electropherogram from the current sales lot is available at www.mlpa.com. Precautions and warnings: For professional use only. Always consult the most recent product description AND the MLPA General Protocol before use: www.mlpa.com. It is the responsibility of the user to be aware of the latest scientific knowledge of the application before drawing any conclusions from findings generated with this product. General information: The SALSA MLPA Probemix P441 SACS is a research use only (RUO) assay for the detection of deletions or duplications in the SACS gene, which is associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). ARSACS is a neurodegenerative disorder, characterised by early-onset progressive cerebellar ataxia with spasticity and peripheral neuropathy. The classic form of ARSACS is often displayed in early childhood, leading to delayed walking in young toddlers, while individuals with disease onset in teenage or early-adult years are also being described more recently.
    [Show full text]
  • 1 Mutational Heterogeneity in Cancer Akash Kumar a Dissertation
    Mutational Heterogeneity in Cancer Akash Kumar A dissertation Submitted in partial fulfillment of requirements for the degree of Doctor of Philosophy University of Washington 2014 June 5 Reading Committee: Jay Shendure Pete Nelson Mary Claire King Program Authorized to Offer Degree: Genome Sciences 1 University of Washington ABSTRACT Mutational Heterogeneity in Cancer Akash Kumar Chair of the Supervisory Committee: Associate Professor Jay Shendure Department of Genome Sciences Somatic mutation plays a key role in the formation and progression of cancer. Differences in mutation patterns likely explain much of the heterogeneity seen in prognosis and treatment response among patients. Recent advances in massively parallel sequencing have greatly expanded our capability to investigate somatic mutation. Genomic profiling of tumor biopsies could guide the administration of targeted therapeutics on the basis of the tumor’s collection of mutations. Central to the success of this approach is the general applicability of targeted therapies to a patient’s entire tumor burden. This requires a better understanding of the genomic heterogeneity present both within individual tumors (intratumoral) and amongst tumors from the same patient (intrapatient). My dissertation is broadly organized around investigating mutational heterogeneity in cancer. Three projects are discussed in detail: analysis of (1) interpatient and (2) intrapatient heterogeneity in men with disseminated prostate cancer, and (3) investigation of regional intratumoral heterogeneity in
    [Show full text]
  • Population Genetics of the Coral Acropora Millepora: Towards a Genomic Predictor of Bleaching
    bioRxiv preprint doi: https://doi.org/10.1101/867754; this version posted December 6, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Population genetics of the coral Acropora millepora: Towards a genomic predictor of bleaching Zachary L. Fuller∗1, Veronique J.L. Mocellin2, Luke Morris2, Neal Cantin2, Jihanne Shepherd1, Luke Sarre1, Julie Peng3, Yi Liao4,5, Joseph Pickrell6, Peter Andolfatto1, Mikhail Matzy4, Line K. Bayy2, and Molly Przeworskiy1,2,3 1Department of Biological Sciences, Columbia University 2Australia Institute of Marine Science 3Lewis-Sigler Institute for Integrative Genomics, Princeton University 4Department of Integrative Biology, University of Texas at Austin 5Department of Ecology and Evolutionary Biology, University of California, Irvine 6Gencove, Inc. New York 7Department of Systems Biology, Columbia University 8Program for Mathematical Genomics, Columbia University 6 December 2019 Abstract Although reef-building corals are rapidly declining worldwide, responses to bleaching vary both within and among species. Because these inter-individual differences are partly her- itable, they should in principle be predictable from genomic data. Towards that goal, we generated a chromosome-scale genome assembly for the coral Acropora millepora. We then obtained whole genome sequences for 237 phenotyped samples collected at 12 reefs distributed along the Great Barrier Reef, among which we inferred very little population structure. Scanning the genome for evidence of local adaptation, we detected signatures of long-term balancing selection in the heat-shock co-chaperone sacsin. We further used 213 of the samples to conduct a genome-wide association study of visual bleaching score, in- corporating the polygenic score derived from it into a predictive model for bleaching in the wild.
    [Show full text]
  • Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
    Copyright by John Francis Anderson 2011 THE ROLE OF SACSIN AS A MOLECULAR CHAPERONE by John Francis Anderson, B.S. Dissertation Presented to the Faculty of the Graduate School of The University of Texas Medical Branch in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas Medical Branch May 2011 Dedication To my wife, Erika R. Anderson. Acknowledgements I am indebted to my mentor, Dr. José M. Barral for his investment in my education. Dr. Barral taught me that curiosity drives scientific investigation and rigorous experiments derive new knowledge. This combination of values is rare to find in a mentor and I am extremely grateful for my experience in his lab. I would like to acknowledge Jason J. Chandler and Paige Spencer for technical assistance. I am especially grateful to Dr. Efrain Siller for daily assistance and discussions on all aspects of this project. I would like to thank Dr. Christian Kaiser providing me a practical education on the design and performance biochemical experiments. I acknowledge Dr. Bernard Brais for generously sharing his time and resources; he provided the rare opportunity to visit an ARSACS patient in her home as well as supplied us with SACS knockout mouse brains. My committee members, Dr. Henry F. Epstein, Dr. Andres F. Oberhauser, Dr. George R Jackson, and Dr. Robert O. Fox and Dr. Darren F. Boehning provided invaluable guidance throughout this work for which I am very grateful. I would like to especially thank Dr. Darren F. Boehning and Dr. Henry F. Epstein for being involved in the details of my project from the beginning of my education at UTMB, through sharing reagents and expertise as well as serving on my committee.
    [Show full text]
  • Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
    Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo
    [Show full text]
  • Hereditary Spastic Paraplegias: Clinical Spectrum in Sudan, Further Deciphering of the Molecular Bases of Autosomal Recessive Forms and New Genes Emerging
    Hereditary spastic paraplegias : clinical spectrum in Sudan, further deciphering of the molecular bases of autosomal recessive forms and new genes emerging Liena Elbaghir Omer Elsayed To cite this version: Liena Elbaghir Omer Elsayed. Hereditary spastic paraplegias : clinical spectrum in Sudan, further deciphering of the molecular bases of autosomal recessive forms and new genes emerging. Neurons and Cognition [q-bio.NC]. Université Pierre et Marie Curie - Paris VI; University of Khartoum, 2016. English. NNT : 2016PA066056. tel-01438739 HAL Id: tel-01438739 https://tel.archives-ouvertes.fr/tel-01438739 Submitted on 18 Jan 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université Pierre et Marie Curie University of Khartoum Cerveau-Cognition-Comportement (ED3C) Institut du Cerveau et de la Moelle Epinière / Equipe Bases Moléculaires, Physiopathologie Et Traitement Des Maladies Neurodégénératives Hereditary spastic paraplegias: clinical spectrum in Sudan, further deciphering of the molecular bases of autosomal recessive forms and new genes emerging
    [Show full text]
  • Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
    REVIEWARTICLE Autosomal Recessive Michael H Parkinson Spastic Ataxia of is a Clinical Research Fellow in the Department of Molecular Neuroscience, UCL Institute of Neurology, University of London and an Honorary Specialist Registrar in Neurology at the National Hospital for Charlevoix-Saguenay Neurology and Neurosurgery, Queen Square, London, UK. He is currently working on a (ARSACS) PhD in clinical and molecular biological aspects of recessive ataxias with a particular interest in ARSACS and Friedreich’s ataxia. History and origins Québec was one of the first regions of North Summary America to be colonised by Europeans and • ARSACS is a rare autosomal recessive the majority of French Canadians living in disorder characterised clinically by Québec Province today are thought to cerebellar ataxia, spasticity, pyramidal descend from these original founders. As a signs, peripheral neuropathy and result, a number of rare neurogenetic disor- skeletal foot abnormalities ders show increased prevalence or local vari- • It is caused by mutations in the SACS ants in this region, including Friedreich’s gene which encodes the 520kDa ataxia (FRDA), and other hereditary ataxias, protein sacsin Fion Bremner spastic parapareses and neuropathies.1 • The availability of the genetic test is a Consultant Neuro-ophthalmologist at Québec City was founded in 1608 under the the National Hospital for Neurology & has extended the clinical spectrum to Neurosurgery, Queen Square, London, UK. include examples without spasticity rule of the French crown and between 1665 His research interests include evaluation of or ataxia and 1725, around forty families migrated from neurological diseases using pupillometry and • Retinal examination shows retinal there to the isolated mountainous region of ocular coherence tomography (OCT).
    [Show full text]
  • 393LN V 393P 344SQ V 393P Probe Set Entrez Gene
    393LN v 393P 344SQ v 393P Entrez fold fold probe set Gene Gene Symbol Gene cluster Gene Title p-value change p-value change chemokine (C-C motif) ligand 21b /// chemokine (C-C motif) ligand 21a /// chemokine (C-C motif) ligand 21c 1419426_s_at 18829 /// Ccl21b /// Ccl2 1 - up 393 LN only (leucine) 0.0047 9.199837 0.45212 6.847887 nuclear factor of activated T-cells, cytoplasmic, calcineurin- 1447085_s_at 18018 Nfatc1 1 - up 393 LN only dependent 1 0.009048 12.065 0.13718 4.81 RIKEN cDNA 1453647_at 78668 9530059J11Rik1 - up 393 LN only 9530059J11 gene 0.002208 5.482897 0.27642 3.45171 transient receptor potential cation channel, subfamily 1457164_at 277328 Trpa1 1 - up 393 LN only A, member 1 0.000111 9.180344 0.01771 3.048114 regulating synaptic membrane 1422809_at 116838 Rims2 1 - up 393 LN only exocytosis 2 0.001891 8.560424 0.13159 2.980501 glial cell line derived neurotrophic factor family receptor alpha 1433716_x_at 14586 Gfra2 1 - up 393 LN only 2 0.006868 30.88736 0.01066 2.811211 1446936_at --- --- 1 - up 393 LN only --- 0.007695 6.373955 0.11733 2.480287 zinc finger protein 1438742_at 320683 Zfp629 1 - up 393 LN only 629 0.002644 5.231855 0.38124 2.377016 phospholipase A2, 1426019_at 18786 Plaa 1 - up 393 LN only activating protein 0.008657 6.2364 0.12336 2.262117 1445314_at 14009 Etv1 1 - up 393 LN only ets variant gene 1 0.007224 3.643646 0.36434 2.01989 ciliary rootlet coiled- 1427338_at 230872 Crocc 1 - up 393 LN only coil, rootletin 0.002482 7.783242 0.49977 1.794171 expressed sequence 1436585_at 99463 BB182297 1 - up 393
    [Show full text]
  • A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: a Simple System for Complex, Heterogeneous Diseases
    International Journal of Molecular Sciences Review A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases Weronika Rzepnikowska 1, Joanna Kaminska 2 , Dagmara Kabzi ´nska 1 , Katarzyna Bini˛eda 1 and Andrzej Kocha ´nski 1,* 1 Neuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, 02-106 Warsaw, Poland; [email protected] (W.R.); [email protected] (D.K.); [email protected] (K.B.) 2 Institute of Biochemistry and Biophysics Polish Academy of Sciences, 02-106 Warsaw, Poland; [email protected] * Correspondence: [email protected] Received: 19 May 2020; Accepted: 15 June 2020; Published: 16 June 2020 Abstract: Charcot–Marie–Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Secondly, the molecular mechanisms underlying the observed symptoms are extremely diverse and are probably different for most of the disease subtypes. Finally, there is no possibility of finding one efficient cure for all, or even the majority of CMT diseases. Every subtype of CMT needs an individual approach backed up by its own research field. Thus, it is little surprise that our knowledge of CMT disease as a whole is selective and therapeutic approaches are limited. There is an urgent need to develop new CMT models to fill the gaps.
    [Show full text]
  • The Cellular Phenotype of the Neurodegenerative Disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
    The Cellular Phenotype of the Neurodegenerative Disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Teisha Y Bradshaw A thesis submitted to Queen Mary, University of London, for the degree of Doctor of Philosophy September 2014 Centre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London 1 Abstract _____________________________________________________________________________ Abstract Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is an early onset neurodegenerative disorder resulting from mutations in the SACS gene that encodes the protein sacsin. Sacsin is a 520kDa multi-domain protein localised at the cytosolic face of the outer mitochondrial membrane with suggested roles in proteostasis and most recently in the regulation of mitochondrial morphology. An excessively interconnected mitochondrial network was observed as a consequence of reduced levels of sacsin protein following SACS knockdown in neuroblastoma cells as well as in an ARSACS patient carrying the common Quebec homozygous SACS mutation 8844delT. Moreover, it was suggested that sacsin has a role in mitochondrial fission as it was found to interact with mitochondrial fission protein Dynamin related protein 1 (Drp1). The aim of this thesis was to explore sacsin’s role in the regulation of mitochondrial morphology and dynamics in non-Quebec ARSACS patients and sacsin knockdown fibroblasts. This study shows that loss of sacsin function promotes a more interconnected mitochondrial network in non-Quebec ARSACS patients and in sacsin knockdown fibroblasts. Moreover, recruitment of the essential mitochondrial fission protein Drp1 to the mitochondria was significantly reduced in ARSACS patient cells and in sacsin knockdown fibroblasts. This reduced recruitment of Drp1 to mitochondria also occurred when cells were treated to induce mitochondrial fission.
    [Show full text]