DOCSLIB.ORG

Mouse Fnta Conditional Knockout Project (CRISPR/Cas9)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mouse Fnta Conditional Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Fnta Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Fnta conditional knockout Mouse model (C57BL/6N) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Fnta gene (NCBI Reference Sequence: NM_008033 ; Ensembl: ENSMUSG00000015994 ) is located on Mouse chromosome 8. 9 exons are identified, with the ATG start codon in exon 1 and the TAG stop codon in exon 9 (Transcript: ENSMUST00000016138). Exon 3 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Fnta gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-12C10 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: Exon 3 starts from about 25.38% of the coding region. The knockout of Exon 3 will result in frameshift of the gene. The size of intron 2 for 5'-loxP site insertion: 2265 bp, and the size of intron 3 for 3'-loxP site insertion: 1320 bp. The size of effective cKO region: ~615 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 3 4 9 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Fnta Homology arm cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the GC Content Distribution Window size: 300 bp Summary: Full Length(7115bp) | A(29.16% 2075) | C(20.04% 1426) | T(30.08% 2140) | G(20.72% 1474) Note: The sequence of homologous arms and cKO region is analyzed to determine the GC content. No significant high GC-content region is found. So this region is suitable for PCR screening or sequencing analysis. Page 3 of 7 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr8 - 26011455 26014454 3000 browser details YourSeq 121 553 716 3000 88.2% chr4 + 136250771 136251030 260 browser details YourSeq 108 554 703 3000 89.4% chr10 - 80460031 80460178 148 browser details YourSeq 107 555 826 3000 78.9% chr1 - 127686057 127686232 176 browser details YourSeq 105 566 725 3000 87.5% chr14 - 84269842 84270046 205 browser details YourSeq 103 554 712 3000 90.0% chr1 - 43952477 43952641 165 browser details YourSeq 97 557 828 3000 77.5% chr3 + 108161973 108162121 149 browser details YourSeq 96 553 724 3000 85.8% chr12 + 17531458 17531613 156 browser details YourSeq 95 553 687 3000 89.9% chr4 + 147819802 147819940 139 browser details YourSeq 95 573 833 3000 90.0% chr4 + 135852561 135852917 357 browser details YourSeq 91 523 664 3000 90.1% chrX - 73987709 73987855 147 browser details YourSeq 91 553 690 3000 88.8% chr1 - 133649700 133649837 138 browser details YourSeq 91 555 758 3000 78.9% chr7 + 29143459 29143644 186 browser details YourSeq 90 553 715 3000 91.8% chr17 - 83345580 83345843 264 browser details YourSeq 88 552 690 3000 89.3% chr17 + 80197146 80197296 151 browser details YourSeq 87 385 687 3000 75.3% chr10 - 75846978 75847141 164 browser details YourSeq 87 553 714 3000 84.5% chr3 + 58568185 58568334 150 browser details YourSeq 86 316 695 3000 89.9% chr16 - 37001172 37001683 512 browser details YourSeq 86 557 835 3000 75.3% chr6 + 39321282 39321432 151 browser details YourSeq 86 553 714 3000 83.1% chr12 + 52563389 52563537 149 Note: The 3000 bp section upstream of Exon 3 is BLAT searched against the genome. No significant similarity is found. BLAT Search Results (down) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr8 - 26007840 26010839 3000 browser details YourSeq 124 1433 1811 3000 89.3% chr7 + 88927734 88928157 424 browser details YourSeq 124 1435 1591 3000 93.2% chr1 + 170851689 170851855 167 browser details YourSeq 121 1433 1558 3000 98.5% chr4 - 107723732 107723858 127 browser details YourSeq 120 1410 1558 3000 94.7% chr16 - 4008262 4008733 472 browser details YourSeq 119 1433 1558 3000 97.7% chr2 + 137819104 137819230 127 browser details YourSeq 116 1437 1569 3000 96.1% chrX - 6841525 6841666 142 browser details YourSeq 116 1433 1568 3000 94.7% chr5 - 126073432 126073578 147 browser details YourSeq 114 1433 1570 3000 92.6% chr15 - 19477457 19477603 147 browser details YourSeq 114 1295 1558 3000 91.9% chr5 + 40371088 40371667 580 browser details YourSeq 113 1433 1558 3000 96.0% chr9 - 96903760 96903888 129 browser details YourSeq 113 1433 1587 3000 84.1% chr19 - 46427174 46427321 148 browser details YourSeq 113 1433 1558 3000 92.8% chr2 + 131110553 131110676 124 browser details YourSeq 113 1433 1909 3000 95.2% chr16 + 58581223 58581789 567 browser details YourSeq 112 1433 1575 3000 90.2% chrX - 135989518 135989672 155 browser details YourSeq 112 1433 1558 3000 98.3% chr8 - 113530373 113530504 132 browser details YourSeq 112 1435 1558 3000 96.0% chr8 - 46227846 46227975 130 browser details YourSeq 112 1434 1568 3000 91.8% chr6 - 9612249 9612383 135 browser details YourSeq 112 1433 1555 3000 96.7% chr12 - 32297131 32297253 123 browser details YourSeq 111 1433 1558 3000 95.9% chr5 - 151081458 151081584 127 Note: The 3000 bp section downstream of Exon 3 is BLAT searched against the genome. No significant similarity is found. Page 4 of 7 https://www.alphaknockout.com Gene and protein information: Fnta farnesyltransferase, CAAX box, alpha [ Mus musculus (house mouse) ] Gene ID: 14272, updated on 12-Aug-2019 Gene summary Official Symbol Fnta provided by MGI Official Full Name farnesyltransferase, CAAX box, alpha provided by MGI Primary source MGI:MGI:104683 See related Ensembl:ENSMUSG00000015994 Gene type protein coding RefSeq status VALIDATED Organism Mus musculus Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus Also known as FTA Expression Ubiquitous expression in placenta adult (RPKM 19.6), bladder adult (RPKM 17.6) and 28 other tissues See more Orthologs human all Genomic context Location: 8 A2; 8 14.27 cM See Fnta in Genome Data Viewer Exon count: 9 Annotation release Status Assembly Chr Location 108 current GRCm38.p6 (GCF_000001635.26) 8 NC_000074.6 (25998688..26015610, complement) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 8 NC_000074.5 (27109194..27126073, complement) Chromosome 8 - NC_000074.6 Page 5 of 7 https://www.alphaknockout.com Transcript information: This gene has 5 transcripts Gene: Fnta ENSMUSG00000015994 Description farnesyltransferase, CAAX box, alpha [Source:MGI Symbol;Acc:MGI:104683] Gene Synonyms FTA Location Chromosome 8: 25,998,722-26,015,650 reverse strand. GRCm38:CM001001.2 About this gene This gene has 5 transcripts (splice variants), 217 orthologues, 2 paralogues, is a member of 1 Ensembl protein family and is associated with 7 phenotypes. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Fnta-201 ENSMUST00000016138.10 1930 377aa ENSMUSP00000016138.9 Protein coding CCDS22205 Q541Z2 Q61239 TSL:1 GENCODE basic APPRIS P1 Fnta-203 ENSMUST00000209664.1 966 No protein - Retained intron - - TSL:3 Fnta-205 ENSMUST00000211718.1 950 No protein - Retained intron - - TSL:2 Fnta-204 ENSMUST00000209860.1 806 No protein - Retained intron - - TSL:2 Fnta-202 ENSMUST00000209247.1 635 No protein - Retained intron - - TSL:2 36.93 kb Forward strand 25.99Mb 26.00Mb 26.01Mb 26.02Mb Genes Gm45411-201 >lncRNA (Comprehensive set... Contigs < AC093366.9 Genes (Comprehensive set... < Pomk-201protein coding < Fnta-201protein coding < Hook3-201protein coding < Fnta-204retained intron < Fnta-205retained intron < Fnta-203retained intron < Fnta-202retained intron Regulatory Build 25.99Mb 26.00Mb 26.01Mb 26.02Mb Reverse strand 36.93 kb Regulation Legend CTCF Open Chromatin Promoter Promoter Flank Gene Legend Protein Coding merged Ensembl/Havana Non-Protein Coding processed transcript RNA gene Page 6 of 7 https://www.alphaknockout.com Transcript: ENSMUST00000016138 < Fnta-201protein coding Reverse strand 16.93 kb ENSMUSP00000016... MobiDB lite Low complexity (Seg) Coiled-coils (Ncoils) Superfamily SSF48439 Pfam Protein prenyltransferase, alpha subunit PROSITE profiles Protein prenyltransferase, alpha subunit PANTHER PTHR11129:SF5 PTHR11129 Gene3D 1.25.40.120 All sequence SNPs/i... Sequence variants (dbSNP and all other sources) Variant Legend missense variant splice region variant synonymous variant Scale bar 0 40 80 120 160 200 240 280 320 377 We wish to acknowledge the following valuable scientific information resources: Ensembl, MGI, NCBI, UCSC. Page 7 of 7.
Load more

Recommended publications
  • Alterations of Genetic Variants and Transcriptomic Features of Response to Tamoxifen in the Breast Cancer Cell Line
    Alterations of Genetic Variants and Transcriptomic Features of Response to Tamoxifen in the Breast Cancer Cell Line Mahnaz Nezamivand-Chegini Shiraz University Hamed Kharrati-Koopaee Shiraz University https://orcid.org/0000-0003-2345-6919 seyed taghi Heydari ( [email protected] ) Shiraz University of Medical Sciences https://orcid.org/0000-0001-7711-1137 Hasan Giahi Shiraz University Ali Dehshahri Shiraz University of Medical Sciences Mehdi Dianatpour Shiraz University of Medical Sciences Kamran Bagheri Lankarani Shiraz University of Medical Sciences Research Keywords: Tamoxifen, breast cancer, genetic variants, RNA-seq. Posted Date: August 17th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-783422/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/33 Abstract Background Breast cancer is one of the most important causes of mortality in the world, and Tamoxifen therapy is known as a medication strategy for estrogen receptor-positive breast cancer. In current study, two hypotheses of Tamoxifen consumption in breast cancer cell line (MCF7) were investigated. First, the effect of Tamoxifen on genes expression prole at transcriptome level was evaluated between the control and treated samples. Second, due to the fact that Tamoxifen is known as a mutagenic factor, there may be an association between the alterations of genetic variants and Tamoxifen treatment, which can impact on the drug response. Methods In current study, the whole-transcriptome (RNA-seq) dataset of four investigations (19 samples) were derived from European Bioinformatics Institute (EBI). At transcriptome level, the effect of Tamoxifen was investigated on gene expression prole between control and treatment samples.
    [Show full text]
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
    [Show full text]
  • Variation in Protein Coding Genes Identifies Information Flow
    bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. 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. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 2019. 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. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.
    [Show full text]
  • Correction for Zhou Et Al., Scaffold Association Factor B (SAFB) Is Required for Expression of Prenyltransferases and RAS Membra
    Correction CELL BIOLOGY Correction for “Scaffold association factor B (SAFB) is required for The authors note that Fig. 5 appeared incorrectly. Spe- expression of prenyltransferases and RAS membrane association,” cifically, in the middle panel of Fig. 5A, one of the bands by Mo Zhou, Leena Kuruvilla, Xiarong Shi, Stephen Viviano, was erroneously cropped out. The corrected figure and its Ian M. Ahearn, Caroline R. Amendola, Wenjuan Su, Sana Badri, legend appear below. The authors confirm that the correct James Mahaffey, Nicole Fehrenbacher, Jane Skok, Joseph image was derived from the same experiments as the other Schlessinger, Benjamin E. Turk, David A. Calderwood, and Mark images in the figure, and that the error does not affect R. Philips, which was first published November 30, 2020; 10.1073/ the interpretation of the data. The online version has been pnas.2005712117 (Proc. Natl. Acad. Sci. U.S.A. 117,31914–31922). corrected. A shNT shSAFB * B 60% - + - + FTI S P S P S P S P Total Ras 40% 100% ** RhoGDI 20% 50% CORRECTION CIMPR in cytosolic fraction FTI treated vs untreated vs untreated FTI treated percentage of total Ras percentage 0% 0% shNT shSAFB GTP-loaded Ras in A549 stables, shNT shSAFB C KRAS4B-dependent lung tumor KRAS4B-independent lung A549 H1437 %cell viability %cell viability FTI (log10, µM) dose response FTI (log10, µM) dose response H358 H1975 %cell viability %cell viability FTI (log10, µM) dose response FTI (log10, µM) dose response Fig. 5. Loss of SAFB diminishes membrane association and GTP loading of KRAS4B and sensitizes KRAS4B-dependent lung tumor cells to FTI treatment.
    [Show full text]
  • Comparative Map Alignment of BTA27 and HSA4 and 8 to Identify Conserved Segments of Genome Containing Fat Deposition QTL Tad S
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UNL | Libraries University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Roman L. Hruska U.S. Meat Animal Research U.S. Department of Agriculture: Agricultural Center Research Service, Lincoln, Nebraska 2000 Comparative map alignment of BTA27 and HSA4 and 8 to identify conserved segments of genome containing fat deposition QTL Tad S. Sonstegard USDA-ARS Gene Evaluation and Mapping Laboratory, Beltsville Agricultural Research Center Wes M. Garrett USDA-ARS, [email protected] Melissa S. Ashwell USDA-ARS Gene Evaluation and Mapping Laboratory, Beltsville Agricultural Research Center Gary L. Bennett USDA-ARS, [email protected] Steven M. Kappes USDA-ARS See next page for additional authors Follow this and additional works at: http://digitalcommons.unl.edu/hruskareports Sonstegard, Tad S.; Garrett, Wes M.; Ashwell, Melissa S.; Bennett, Gary L.; Kappes, Steven M.; and Van Tassell, Curtis P., "Comparative map alignment of BTA27 and HSA4 and 8 to identify conserved segments of genome containing fat deposition QTL" (2000). Roman L. Hruska U.S. Meat Animal Research Center. 427. http://digitalcommons.unl.edu/hruskareports/427 This Article is brought to you for free and open access by the U.S. Department of Agriculture: Agricultural Research Service, Lincoln, Nebraska at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Roman L. Hruska U.S. Meat Animal Research Center by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Tad S. Sonstegard, Wes M. Garrett, Melissa S. Ashwell, Gary L.
    [Show full text]
  • Correction for Zhou Et Al., Scaffold Association Factor B (SAFB) Is Required for Expression of Prenyltransferases and RAS Membra
    Correction CELL BIOLOGY Correction for “Scaffold association factor B (SAFB) is required for The authors note that Fig. 5 appeared incorrectly. Spe- expression of prenyltransferases and RAS membrane association,” cifically, in the middle panel of Fig. 5A, one of the bands by Mo Zhou, Leena Kuruvilla, Xiarong Shi, Stephen Viviano, was erroneously cropped out. The corrected figure and its Ian M. Ahearn, Caroline R. Amendola, Wenjuan Su, Sana Badri, legend appear below. The authors confirm that the correct James Mahaffey, Nicole Fehrenbacher, Jane Skok, Joseph image was derived from the same experiments as the other Schlessinger, Benjamin E. Turk, David A. Calderwood, and Mark images in the figure, and that the error does not affect R. Philips, which was first published November 30, 2020; 10.1073/ the interpretation of the data. The online version has been pnas.2005712117 (Proc. Natl. Acad. Sci. U.S.A. 117,31914–31922). corrected. A shNT shSAFB * B 60% - + - + FTI S P S P S P S P Total Ras 40% 100% ** RhoGDI 20% 50% CORRECTION CIMPR in cytosolic fraction FTI treated vs untreated vs untreated FTI treated percentage of total Ras percentage 0% 0% shNT shSAFB GTP-loaded Ras in A549 stables, shNT shSAFB C KRAS4B-dependent lung tumor KRAS4B-independent lung A549 H1437 %cell viability %cell viability FTI (log10, µM) dose response FTI (log10, µM) dose response H358 H1975 %cell viability %cell viability FTI (log10, µM) dose response FTI (log10, µM) dose response Fig. 5. Loss of SAFB diminishes membrane association and GTP loading of KRAS4B and sensitizes KRAS4B-dependent lung tumor cells to FTI treatment.
    [Show full text]
  • Biomedical Informatics
    BIOMEDICAL INFORMATICS Abstract GENE LIST AUTOMATICALLY DERIVED FOR YOU (GLAD4U): DERIVING AND PRIORITIZING GENE LISTS FROM PUBMED LITERATURE JEROME JOURQUIN Thesis under the direction of Professor Bing Zhang Answering questions such as ―Which genes are related to breast cancer?‖ usually requires retrieving relevant publications through the PubMed search engine, reading these publications, and manually creating gene lists. This process is both time-consuming and prone to errors. We report GLAD4U (Gene List Automatically Derived For You), a novel, free web-based gene retrieval and prioritization tool. The quality of gene lists created by GLAD4U for three Gene Ontology terms and three disease terms was assessed using ―gold standard‖ lists curated in public databases. We also compared the performance of GLAD4U with that of another gene prioritization software, EBIMed. GLAD4U has a high overall recall. Although precision is generally low, its prioritization methods successfully rank truly relevant genes at the top of generated lists to facilitate efficient browsing. GLAD4U is simple to use, and its interface can be found at: http://bioinfo.vanderbilt.edu/glad4u. Approved ___________________________________________ Date _____________ GENE LIST AUTOMATICALLY DERIVED FOR YOU (GLAD4U): DERIVING AND PRIORITIZING GENE LISTS FROM PUBMED LITERATURE By Jérôme Jourquin Thesis Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Biomedical Informatics May, 2010 Nashville, Tennessee Approved: Professor Bing Zhang Professor Hua Xu Professor Daniel R. Masys ACKNOWLEDGEMENTS I would like to express profound gratitude to my advisor, Dr. Bing Zhang, for his invaluable support, supervision and suggestions throughout this research work.
    [Show full text]
  • Evaluation of Variability in High Resolution Protein Structures by Global Distance Scoring
    bioRxiv preprint doi: https://doi.org/10.1101/202028; this version posted December 16, 2017. 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. Evaluation of variability in high resolution protein structures by global distance scoring Risa Anzai, Yoshiki Asami, Waka Inoue, Hina Ueno, Koya Yamada, Tetsuji Okada Department of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan. Corresponding author: Tetsuji Okada, Department of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan. +81-3-3986-0221, [email protected] Abstract Systematic analysis of statistical and dynamical properties of proteins is critical to understanding cellular events. Extraction of biologically relevant information from a set of high-resolution structures is important because it can provide mechanistic details behind the functional properties of protein families, enabling rational comparison between families. Most of the current structure comparisons are pairwise-based, which hampers the global analysis of increasing contents in the Protein Data Bank. Additionally, pairing of protein structures introduces uncertainty with respect to reproducibility because it frequently accompanies other settings for superimposition. This study introduces intramolecular distance scoring, for the analysis of human proteins, for each of which at least several high-resolution are available. We show that the results are comprehensively used to overview advances at the atomic level exploration of each protein and protein family.
    [Show full text]
  • Genomic Landscape of Metastatic Colorectal Cancer
    ARTICLE Received 22 Feb 2014 | Accepted 2 Oct 2014 | Published 14 Nov 2014 DOI: 10.1038/ncomms6457 OPEN Genomic landscape of metastatic colorectal cancer Josien C. Haan1, Mariette Labots2, Christian Rausch1, Miriam Koopman3, Jolien Tol4, Leonie J.M. Mekenkamp5, Mark A. van de Wiel6, Danielle Israeli1, Hendrik F. van Essen1, Nicole C.T. van Grieken1, Quirinus J.M. Voorham1, Linda J.W. Bosch1, Xueping Qu7, Omar Kabbarah7, Henk M.W. Verheul2, Iris D. Nagtegaal5, Cornelis J.A. Punt8, Bauke Ylstra1,* & Gerrit A. Meijer1,* Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values o0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1–q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy. 1 Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. 2 Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
    [Show full text]
  • A Gene for Universal Congenital Alopecia Maps to Chromosome 8P21-22 Markus M
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Am. J. Hum. Genet. 62:386–390, 1998 A Gene for Universal Congenital Alopecia Maps to Chromosome 8p21-22 Markus M. No¨then,1 Sven Cichon,1 Ina R. Vogt,1 Susanne Hemmer,1 Roland Kruse,1 Michael Knapp,2 Tobias Ho¨ller,2 Muhammad Faiyaz ul Haque,4,5 Sayedul Haque,4 Peter Propping,1 Mahmud Ahmad,4 and Marcella Rietschel1,3 1Institute of Human Genetics, 2Institute for Medical Statistics, and 3Department of Psychiatry, University of Bonn, Bonn; 4Department of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; and 5Medical Genetics, Ahmanson Department of Pediatrics, Cedars-Sinai Research Institute, Los Angeles Summary alopecia may occur either in isolation or with associated defects. On the basis of such associations, several dif- Complete or partial congenital absence of hair (congen- ferent syndromes featuring congenital alopecia can be ital alopecia) may occur either in isolation or with as- distinguished (Birnbaum and Baden 1987; Feinstein et sociated defects. The majority of families with isolated al. 1987; Vogt et al. 1988). The isolated form of con- congenital alopecia has been reported to follow an au- genital alopecia has been reported in sporadic and fa- tosomal-recessive mode of inheritance (MIM 203655). milial cases. In familial cases, inheritance is usu- As yet, no gene has been linked to isolated congenital ally autosomal recessive (MIM 203655 [http:// alopecia, nor has linkage been established to a specific www3.ncbi.nlm.nih.gov:80/htbin-post/Omim/dispmim? region of the genome.
    [Show full text]
  • Identification of Target Genes in Laryngeal Squamous Cell Carcinoma
    Oncogene (2006) 25, 6997–7008 & 2006 Nature Publishing Group All rights reserved 0950-9232/06 $30.00 www.nature.com/onc ONCOGENOMICS Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses A-K Ja¨ rvinen1,2, R Autio3, S Haapa-Paananen4, M Wolf4, M Saarela3, R Gre´ nman5,6, I Leivo7, O Kallioniemi4,AAMa¨ kitie2 and O Monni1 1Biomedicum Biochip Center and Institute of Biomedicine, University of Helsinki, Helsinki, Finland; 2Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland; 3Institute of Signal Processing, Tampere University of Technology, Tampere, Finland; 4Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku, Finland; 5Department of Otorhinolaryngology – Head and Neck Surgery, Turku University Central Hospital, Turku, Finland; 6Department of Medical Biochemistry, Turku University, Turku, Finland and 7Department of Pathology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland Molecular mechanisms contributing to initiation and Introduction progression of head and necksquamous cell carcinoma are still poorly known. Numerous genetic alterations Squamous cell carcinoma of the upper aerodigestive have been described, but molecular consequences of tract is the most common type of malignant head and such alterations in most cases remain unclear. Here, neck tumors. The major etiological factors for head we performed an integrated high-resolution microarray and neck squamous cell carcinoma (HNSCC) are analysis of gene copy number and expression in 20 tobacco and alcohol consumption, and its incidence is laryngeal cancer cell lines and primary tumors. Our aim substantially higher in men than in women.
    [Show full text]
  • An Investigation of the Antigastric Cancer Effect in Tumor Microenvironment of Radix Rhei Et Rhizome: a Network Pharmacology Study
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 9913952, 9 pages https://doi.org/10.1155/2021/9913952 Research Article An Investigation of the Antigastric Cancer Effect in Tumor Microenvironment of Radix Rhei Et Rhizome: A Network Pharmacology Study Xinmiao Wang ,1 Guanghui Zhu ,1,2 Haoyu Yang ,1,2 Ruike Gao ,1 Zhe Wu ,1 Ying Zhang,1 Xiaoyu Zhu,1 Xiaoxiao Zhang,1 and Jie Li 1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China 2Beijing University of Traditional Chinese Medicine, Beijing 100029, China Correspondence should be addressed to Jie Li; [email protected] Received 27 March 2021; Revised 20 May 2021; Accepted 11 June 2021; Published 24 June 2021 Academic Editor: Yibin Feng Copyright © 2021 Xinmiao Wang et al. +is 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. Background. Tumor microenvironment (TME) takes a vital effect on the occurrence and development of cancer. Radix Rhei Et Rhizome (RRER, Da-Huang in pinyin), a classical Chinese herb, has been widely used in gastric cancer (GC) for many years in China. However, inadequate systematic studies have focused on the anti-GC effect of RRER in TME. +is study intended to uncover the mechanism of it by network pharmacology. Methods. We collected compounds and targets of RRER from traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. GC targets were obtained from GeneCards. Protein- protein interaction (PPI) network and RRER-GC-target network were built by STRING and Cytoscape 3.2.1.
    [Show full text]