Mouse Trim27 Knockout Project (CRISPR/Cas9)

Total Page:16

File Type:pdf, Size:1020Kb

Mouse Trim27 Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Trim27 Knockout Project (CRISPR/Cas9) Objective: To create a Trim27 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Trim27 gene (NCBI Reference Sequence: NM_009054 ; Ensembl: ENSMUSG00000021326 ) is located on Mouse chromosome 13. 8 exons are identified, with the ATG start codon in exon 1 and the TGA stop codon in exon 8 (Transcript: ENSMUST00000021761). Exon 2~7 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a gene trap allele exhibit exhibit increased potassium/calcium channel activity and TCR- stimulated calcium influx in Th1 and Th2 CD4 T cells. Mice homozygous for another gene trap allele exhibit decreased incidence of chemically-induced tumors. Exon 2 starts from about 27.36% of the coding region. Exon 2~7 covers 34.18% of the coding region. The size of effective KO region: ~9263 bp. The KO region does not have any other known gene. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 4 5 6 7 8 Legends Exon of mouse Trim27 Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 1069 bp section upstream of Exon 2 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 Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 783 bp section downstream of Exon 7 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. Page 3 of 9 https://www.alphaknockout.com Overview of the GC Content Distribution (up) Window size: 300 bp Sequence 12 Summary: Full Length(1069bp) | A(24.79% 265) | C(24.04% 257) | T(26.01% 278) | G(25.16% 269) Note: The 1069 bp section upstream of Exon 2 is analyzed to determine the GC content. Significant high GC-content regions are found. The gRNA site is selected outside of these high GC-content regions. Overview of the GC Content Distribution (down) Window size: 300 bp Sequence 12 Summary: Full Length(783bp) | A(31.67% 248) | C(18.9% 148) | T(28.48% 223) | G(20.95% 164) Note: The 783 bp section downstream of Exon 7 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 4 of 9 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 1069 1 1069 1069 100.0% chr13 + 21180916 21181984 1069 browser details YourSeq 33 635 788 1069 97.2% chr1 - 161288550 161288706 157 browser details YourSeq 29 721 791 1069 96.8% chr10 + 115551441 115551559 119 browser details YourSeq 26 767 797 1069 96.5% chr11 + 8645031 8645065 35 browser details YourSeq 25 414 442 1069 80.8% chr3 - 111630976 111631001 26 browser details YourSeq 23 161 184 1069 100.0% chr11 + 66257481 66257505 25 browser details YourSeq 23 767 792 1069 96.2% chr10 + 61288936 61288964 29 browser details YourSeq 22 767 788 1069 100.0% chr12 - 62184215 62184236 22 browser details YourSeq 22 767 788 1069 100.0% chr10 - 111186010 111186031 22 browser details YourSeq 22 767 788 1069 100.0% chr10 + 16892361 16892382 22 browser details YourSeq 22 767 788 1069 100.0% chr1 + 72637136 72637157 22 browser details YourSeq 21 773 793 1069 100.0% chr8 - 53242451 53242471 21 browser details YourSeq 21 767 787 1069 100.0% chr1 - 128376371 128376391 21 browser details YourSeq 21 638 658 1069 100.0% chr10 + 32289872 32289892 21 browser details YourSeq 21 767 787 1069 100.0% chr1 + 79356881 79356901 21 browser details YourSeq 20 767 786 1069 100.0% chr12 - 3417177 3417196 20 browser details YourSeq 20 767 786 1069 100.0% chr10 - 117331242 117331261 20 Note: The 1069 bp section upstream of Exon 2 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 783 1 783 783 100.0% chr13 + 21191248 21192030 783 browser details YourSeq 48 494 615 783 87.5% chr10 + 39386715 39386834 120 browser details YourSeq 36 514 608 783 95.0% chr3 + 41640447 41640542 96 browser details YourSeq 31 496 536 783 87.9% chr10 + 30412763 30412803 41 browser details YourSeq 30 152 184 783 97.0% chr1 + 179300612 179300679 68 browser details YourSeq 28 549 591 783 86.7% chr19 - 26918944 26918984 41 browser details YourSeq 27 212 242 783 96.6% chr7 - 53283754 53283785 32 browser details YourSeq 26 496 529 783 78.6% chr6 - 23130310 23130338 29 browser details YourSeq 26 551 591 783 89.3% chr8 + 70829008 70829047 40 browser details YourSeq 25 215 242 783 84.7% chr3 + 75252591 75252616 26 browser details YourSeq 25 160 186 783 88.5% chr2 + 31525401 31525426 26 browser details YourSeq 24 496 529 783 70.4% chr1 - 69572195 69572221 27 browser details YourSeq 24 513 536 783 100.0% chr13 + 61683509 61683532 24 browser details YourSeq 23 155 179 783 96.0% chr10 + 22654928 22654952 25 browser details YourSeq 22 154 175 783 100.0% chr7 - 44718591 44718612 22 browser details YourSeq 22 508 529 783 100.0% chr2 - 61666516 61666537 22 browser details YourSeq 22 508 529 783 100.0% chr19 - 34888695 34888716 22 browser details YourSeq 22 508 529 783 100.0% chr19 - 30254630 30254651 22 browser details YourSeq 22 508 529 783 100.0% chr17 - 26725941 26725962 22 browser details YourSeq 22 508 531 783 95.9% chr1 - 93494890 93494913 24 Note: The 783 bp section downstream of Exon 7 is BLAT searched against the genome. No significant similarity is found. Page 5 of 9 https://www.alphaknockout.com Gene and protein information: Trim27 tripartite motif-containing 27 [ Mus musculus (house mouse) ] Gene ID: 19720, updated on 12-Aug-2019 Gene summary Official Symbol Trim27 provided by MGI Official Full Name tripartite motif-containing 27 provided by MGI Primary source MGI:MGI:97904 See related Ensembl:ENSMUSG00000021326 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 Rfp; Gm19403; AW538890 Expression Ubiquitous expression in ovary adult (RPKM 33.3), adrenal adult (RPKM 32.0) and 28 other tissues See more Orthologs human all Genomic context Location: 13 A2; 13 7.67 cM See Trim27 in Genome Data Viewer Exon count: 10 Annotation release Status Assembly Chr Location 108 current GRCm38.p6 (GCF_000001635.26) 13 NC_000079.6 (21179450..21194723) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 13 NC_000079.5 (21271828..21284726) Chromosome 13 - NC_000079.6 Page 6 of 9 https://www.alphaknockout.com Transcript information: This gene has 7 transcripts Gene: Trim27 ENSMUSG00000021326 Description tripartite motif-containing 27 [Source:MGI Symbol;Acc:MGI:97904] Gene Synonyms Rfp Location Chromosome 13: 21,179,445-21,194,724 forward strand. GRCm38:CM001006.2 About this gene This gene has 7 transcripts (splice variants), 152 orthologues, 73 paralogues, is a member of 1 Ensembl protein family and is associated with 12 phenotypes. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Trim27- ENSMUST00000222544.1 4312 513aa ENSMUSP00000152730.1 Protein coding CCDS36607 Q62158 TSL:5 206 GENCODE basic APPRIS P1 Trim27- ENSMUST00000021761.12 4204 513aa ENSMUSP00000021761.5 Protein coding CCDS36607 Q62158 TSL:1 201 GENCODE basic APPRIS P1 Trim27- ENSMUST00000223065.1 2046 314aa ENSMUSP00000152179.1 Protein coding - A0A1Y7VKW0 TSL:1 207 GENCODE basic Trim27- ENSMUST00000221464.1 1400 337aa ENSMUSP00000152230.1 Protein coding - A0A1Y7VJ13 TSL:5 205 GENCODE basic Trim27- ENSMUST00000139287.3 683 61aa ENSMUSP00000115397.3 Nonsense mediated - F6U3T5 CDS 5' 204 decay incomplete TSL:5 Trim27- ENSMUST00000124052.2 1750 No - Retained intron - - TSL:NA 202 protein Trim27- ENSMUST00000124794.1 439 No - Retained intron - - TSL:3 203 protein Page 7 of 9 https://www.alphaknockout.com 35.28 kb Forward strand 21.17Mb 21.18Mb 21.19Mb 21.20Mb Genes (Comprehensive set... Trim27-206 >protein coding Trim27-201 >protein coding Trim27-202 >retained intron Trim27-204 >nonsense mediated decay Trim27-207 >protein coding Trim27-205 >protein coding Trim27-203 >retained intron Contigs < AC138330.4 Genes < Gm47806-201lncRNA (Comprehensive set... Regulatory Build 21.17Mb 21.18Mb 21.19Mb 21.20Mb Reverse strand 35.28 kb Regulation Legend CTCF Enhancer Open Chromatin Promoter Promoter Flank Gene Legend Protein Coding Ensembl protein coding Non-Protein Coding processed transcript RNA gene Page 8 of 9 https://www.alphaknockout.com Transcript: ENSMUST00000021761 14.79 kb Forward strand Trim27-201 >protein coding ENSMUSP00000021... Low complexity (Seg) Coiled-coils (Ncoils) Superfamily SSF57850 SSF57845 Concanavalin A-like lectin/glucanase domain superfamily SMART Zinc finger, RING-type SPRY-associated B-box-type zinc finger SPRY domain Prints Zinc finger, B-box, chordata Butyrophylin-like, SPRY domain Pfam PF15227 B-box-type zinc finger SPRY domain SPRY-associated PROSITE profiles Zinc finger, RING-type B30.2/SPRY domain B-box-type zinc finger PROSITE patterns Zinc finger, RING-type, conserved site PANTHER PTHR24103:SF362 PTHR24103 Gene3D Zinc finger, RING/FYVE/PHD-type 2.60.120.920 3.30.40.200 CDD cd16594 B-box-type zinc finger TRIM27, PRY/SPRY domain All sequence SNPs/i..
Recommended publications
  • Analysis of Trans Esnps Infers Regulatory Network Architecture
    Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation.
    [Show full text]
  • Knock-In Mice Limits Responses to Muramyl Dipeptide in Alters
    Blau Syndrome−Associated Nod2 Mutation Alters Expression of Full-Length NOD2 and Limits Responses to Muramyl Dipeptide in Knock-in Mice This information is current as of September 28, 2021. Jae Dugan, Eric Griffiths, Paige Snow, Holly Rosenzweig, Ellen Lee, Brieanna Brown, Daniel W. Carr, Carlos Rose, James Rosenbaum and Michael P. Davey J Immunol published online 26 November 2014 http://www.jimmunol.org/content/early/2014/11/26/jimmun Downloaded from ol.1402330 Supplementary http://www.jimmunol.org/content/suppl/2014/11/26/jimmunol.140233 http://www.jimmunol.org/ Material 0.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 26, 2014, doi:10.4049/jimmunol.1402330 The Journal of Immunology Blau Syndrome–Associated Nod2 Mutation Alters Expression of Full-Length NOD2 and Limits Responses to Muramyl Dipeptide in Knock-in Mice Jae Dugan,*,† Eric Griffiths,* Paige Snow,* Holly Rosenzweig,*,‡,x Ellen Lee,‡ Brieanna Brown,‡ Daniel W.
    [Show full text]
  • Genome-Wide Analysis of Transcriptional Bursting-Induced Noise in Mammalian Cells
    bioRxiv preprint doi: https://doi.org/10.1101/736207; this version posted August 15, 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. Title: Genome-wide analysis of transcriptional bursting-induced noise in mammalian cells Authors: Hiroshi Ochiai1*, Tetsutaro Hayashi2, Mana Umeda2, Mika Yoshimura2, Akihito Harada3, Yukiko Shimizu4, Kenta Nakano4, Noriko Saitoh5, Hiroshi Kimura6, Zhe Liu7, Takashi Yamamoto1, Tadashi Okamura4,8, Yasuyuki Ohkawa3, Itoshi Nikaido2,9* Affiliations: 1Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-0046, Japan 2Laboratory for Bioinformatics Research, RIKEN BDR, Wako, Saitama, 351-0198, Japan 3Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, 812-0054, Japan 4Department of Animal Medicine, National Center for Global Health and Medicine (NCGM), Tokyo, 812-0054, Japan 5Division of Cancer Biology, The Cancer Institute of JFCR, Tokyo, 135-8550, Japan 6Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Kanagawa, 226-8503, Japan 7Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147, USA 8Section of Animal Models, Department of Infectious Diseases, National Center for Global Health and Medicine (NCGM), Tokyo, 812-0054, Japan 9Bioinformatics Course, Master’s/Doctoral Program in Life Science Innovation (T-LSI), School of Integrative and Global Majors (SIGMA), University of Tsukuba, Wako, 351-0198, Japan *Corresponding authors Corresponding authors e-mail addresses Hiroshi Ochiai, [email protected] Itoshi Nikaido, [email protected] bioRxiv preprint doi: https://doi.org/10.1101/736207; this version posted August 15, 2019.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • University of Alberta
    University of Alberta Tripartite-motif family members in the White Pekin duck (Anas platyrhynchos) modulate antiviral gene expression by Alysson Heather Blaine A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Physiology, Cell and Developmental Biology Biological Sciences ©Alysson Heather Blaine Fall 2013 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. Abstract Wild waterfowl, including mallard ducks, are the natural reservoir of avian influenza A virus and are resistant to highly pathogenic strains. This is primarily due to the robust innate immune response of ducks. Shortly after exposure to both highly pathogenic (A/Viet Nam/1203/04 (H5N1)) and low pathogenic (A/mallard/BC/500/05 (H5N2)) avian influenza, many immune genes are upregulated including members of the diverse tripartite-motif (TRIM) family. TRIM proteins have species-specific antiviral roles in a variety of viral infections. I have identified a contig of TRIM genes located adjacent to the MHC locus in the White Pekin duck (Anas platyrhynchos) genome.
    [Show full text]
  • Delineation of Key Regulatory Elements Identifies Points Of
    DELINEATION OF KEY REGULATORY ELEMENTS IDENTIFIES POINTS OF VULNERABILITY IN THE MITOGEN-ACTIVATED SIGNALING NETWORK SUPPLEMENTARY MATERIALS List of contents Supplementary Figures with legends 1. Figure S1: Distribution of primary siRNA screen data, and standardization of assay procedure. 2. Figure S2: Scatter plot of screen data. 3. Figure S3: Functional relevance of the identified targets and Calculation of residence time from PDT and cell cycle distribution. 4. Figure S4: FACS profiles for ABL1 and AKT1. Table for data in Figure 5B. 5. Figure S5: Venn diagram showing the results of the comparative analysis of other screen results 6. Figure S6: Dose response profiles for the AKT1 + ABL1 inhibitor combination for CH1, list of the 14 cell lines and their description, effect of ABL1+AKT1 inhibitor combination on increase in apoptotic cells and G1 arrest in 14 cell lines, effects of CHEK1 inhibitor on combination C1,C2 on 4 cell lines. Supplementary Tables 1. Table S1: siRNA screen results for targeted kinases and phosphatases. 2. Table S2: Gene expression status of the validated hits. 3. Table S3: Role played by identified RNAi hits in regulation of cell cycle, the effect on PDTs along with phase-specific RTs. 4. Table S4: List of molecules classified as cell cycle targets. 5. Table S5: High confidence network used for graph theory analysis. 6. Table S6: Occurrences of nodes in shortest path networks. 7. Table S7: Network file used as SNAVI background. 8. Table S8: Classification of nodes present in modules according to specificity. Legends for tables Supplementary Experimental Procedures References Figure S1 A 450 400 G1 S 350 G2 300 250 200 150 100 50 Distribution of molecules Distribution 0 -6-4-20246 Z-score 350 200 400 G1 S 300 G2 150 300 250 200 100 200 150 100 50 100 Distribution of molecules 50 0 0 0 -4 -2 0 2 4 -4-20246 -4-20246 Z-score B PLK1 GAPDH PLCg BTK PLCg CDC2A PLCg CHEK1 PLCg MET Distribution profiles of complete primary screen and western blots showing knockdown efficiency.
    [Show full text]
  • The MER41 Family of Hervs Is Uniquely Involved in the Immune-Mediated Regulation of Cognition/Behavior-Related Genes
    bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 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. The MER41 family of HERVs is uniquely involved in the immune-mediated regulation of cognition/behavior-related genes: pathophysiological implications for autism spectrum disorders Serge Nataf*1, 2, 3, Juan Uriagereka4 and Antonio Benitez-Burraco 5 1CarMeN Laboratory, INSERM U1060, INRA U1397, INSA de Lyon, Lyon-Sud Faculty of Medicine, University of Lyon, Pierre-Bénite, France. 2 University of Lyon 1, Lyon, France. 3Banque de Tissus et de Cellules des Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France. 4Department of Linguistics and School of Languages, Literatures & Cultures, University of Maryland, College Park, USA. 5Department of Spanish, Linguistics, and Theory of Literature (Linguistics). Faculty of Philology. University of Seville, Seville, Spain * Corresponding author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 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. ABSTRACT Interferon-gamma (IFNa prototypical T lymphocyte-derived pro-inflammatory cytokine, was recently shown to shape social behavior and neuronal connectivity in rodents. STAT1 (Signal Transducer And Activator Of Transcription 1) is a transcription factor (TF) crucially involved in the IFN pathway.
    [Show full text]
  • Sex Differences in Genetic Associations with Longevity
    Supplementary Online Content Zeng Y, Nie C, Min J, et al. Sex Differences in Genetic Associations With Longevity. JAMA Netw Open. 2018;1(4):e181670. doi:10.1001/jamanetworkopen.2018.1670 eAppendix. Supplementary Material eReferences eTable 1. Sample Size and Ages of the Sex-Specific CLHLS GWAS Datasets eTable 2. The 11 Male-Specific Pathways Significantly Enriched and Associated With Longevity (P<0.005 and FDR<0.05) and the Significant Genes in These Pathways eTable 3. The 34 Female-Specific Pathways Significantly Enriched and Associated With Longevity (P<0.005 and FDR<0.05) and the Significant Genes in These Pathways eTable 4. The 35 Male-Specific Loci Associated With Longevity and Replicated in North and South Datasets, With a 10-5≤P<10-4 in Males but Not Significant in Females eTable 5. The 25 Female-Specific Loci Associated With Longevity and Replicated in North and South Datasets, With a 10-5≤P<10-4 in Females but Not Significant in Males eTable 6. Power Estimates for Male- and Female-Specific GWAS eTable 7. Parameters Used and Outcome of Power Estimates for the Sex-Specific PRS Analyses on Longevity Based on CLHLS GWAS Data, Using the AVENGEME Software eFigure 1. Manhattan Plots Showing Association of Longevity: Male eFigure 2. Manhattan Plots Showing Association of Longevity: Female eFigure 3. Quantile-Quantile Plots: Male eFigure 4. Quantile-Quantile Plots: Female This supplementary material has been provided by the authors to give readers additional information about their work. © 2018 Zeng Y et al. JAMA Network Open. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eAppendix.
    [Show full text]
  • Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Renuka Nayak University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Computational Biology Commons, and the Genomics Commons Recommended Citation Nayak, Renuka, "Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress" (2010). Publicly Accessible Penn Dissertations. 1559. https://repository.upenn.edu/edissertations/1559 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1559 For more information, please contact [email protected]. Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Abstract Genes interact in networks to orchestrate cellular processes. Here, we used coexpression networks based on natural variation in gene expression to study the functions and interactions of human genes. We asked how these networks change in response to stress. First, we studied human coexpression networks at baseline. We constructed networks by identifying correlations in expression levels of 8.9 million gene pairs in immortalized B cells from 295 individuals comprising three independent samples. The resulting networks allowed us to infer interactions between biological processes. We used the network to predict the functions of poorly-characterized human genes, and provided some experimental support. Examining genes implicated in disease, we found that IFIH1, a diabetes susceptibility gene, interacts with YES1, which affects glucose transport. Genes predisposing to the same diseases are clustered non-randomly in the network, suggesting that the network may be used to identify candidate genes that influence disease susceptibility.
    [Show full text]
  • Supplemental Data
    Supplementary Table 1. Gene sets from Figure 6. Lists of genes from each individual gene set defined in Figure 6, including the fold-change in expression of each gene in treatment group pair-wise comparisons. ENSEMBL: Ensembl gene identifier; Symbol: official gene symbol; logFC: log fold change; p value: significance of fold-change in a pair-wise comparison, P<0.05 cut-off; FDR: false discovery rate, expected proportion of false positives among the differentially expressed genes in a pair-wise comparison (FDR<0.25 cut-off). Sup. Table 1 SET I CP versus Sal CP versus CP+DCA DCA versus Sal ENSEMBL Symbol logFC PValue FDR logFC PValue FDR logFC PValue FDR Desc ENSMUSG00000020326 Ccng1 2.64 0.00 0.00 -0.06 0.13 0.96 0.40 0.00 0.23 cyclin G1 [Source:MGI Symbol;Acc:MGI:102890] ENSMUSG00000031886 Ces2e 3.97 0.00 0.00 -0.24 0.02 0.28 0.01 1.00 1.00 carboxylesterase 2E [Source:MGI Symbol;Acc:MGI:2443170] ENSMUSG00000041959 S100a10 2.31 0.00 0.00 -0.21 0.02 0.23 -0.11 0.53 1.00 S100 calcium binding protein A10 (calpactin) [Source:MGI Symbol;Acc:MGI:1339468] ENSMUSG00000092341 Malat1 1.09 0.00 0.00 -0.11 0.20 1.00 0.66 0.00 0.00 metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA) [Source:MGI Symbol;Acc:MGI:1919539] ENSMUSG00000072949 Acot1 1.73 0.00 0.00 -0.22 0.01 0.12 -0.44 0.01 1.00 acyl-CoA thioesterase 1 [Source:MGI Symbol;Acc:MGI:1349396] ENSMUSG00000064339 mt-Rnr2 1.09 0.00 0.00 -0.08 0.17 1.00 0.67 0.00 0.07 mitochondrially encoded 16S rRNA [Source:MGI Symbol;Acc:MGI:102492] ENSMUSG00000025934 Gsta3 1.86 0.00 0.00 -0.28
    [Show full text]
  • Drosophila Models of Pathogenic Copy-Number Variant Genes Show Global and Non-Neuronal Defects During Development
    bioRxiv preprint doi: https://doi.org/10.1101/855338; this version posted November 26, 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 4.0 International license. 1 Drosophila models of pathogenic copy-number variant genes show global and 2 non-neuronal defects during development 3 4 Tanzeen Yusuff1,4, Matthew Jensen1,4, Sneha Yennawar1,4, Lucilla Pizzo1, Siddharth 5 Karthikeyan1, Dagny J. Gould1, Avik Sarker1, Yurika Matsui1,2, Janani Iyer1, Zhi-Chun Lai1,2, 6 and Santhosh Girirajan1,3* 7 8 1. Department of Biochemistry and Molecular Biology, Pennsylvania State University, 9 University Park, PA 16802 10 2. Department of Biology, Pennsylvania State University, University Park, PA 16802 11 3. Department of Anthropology, Pennsylvania State University, University Park, PA 16802 12 13 4 contributed equally to work 14 15 16 *Correspondence: 17 Santhosh Girirajan, MBBS, PhD 18 205A Life Sciences Building 19 Pennsylvania State University 20 University Park, PA 16802 21 E-mail: [email protected] 22 Phone: 814-865-0674 23 1 bioRxiv preprint doi: https://doi.org/10.1101/855338; this version posted November 26, 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 4.0 International license. 24 ABSTRACT 25 While rare pathogenic CNVs are associated with both neuronal and non-neuronal phenotypes, 26 functional studies evaluating these regions have focused on the molecular basis of neuronal 27 defects.
    [Show full text]
  • Tripartite-Motif Family Genes Associated with Cancer Stem Cells
    Int. J. Med. Sci. 2020, Vol. 17 2905 Ivyspring International Publisher International Journal of Medical Sciences 2020; 17(18): 2905-2916. doi: 10.7150/ijms.51260 Research Paper Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma Guangzhen Wu1,#, Yingkun Xu2,#, Lin Li3, Jianyi Li2, Ningke Ruan4, Jian Dong5, Zhuyuan Si6, Qinghua Xia2,7,, Qifei Wang1, 1. Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, China 2. Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China 3. Department of Orthopedics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China 4. The Nursing College of Zhengzhou University, Zhengzhou, Henan, 450001, China 5. Department of Sports Medicine and Adult Reconstructive Surgery, The Affiliated Drum Tower Hospital of Nanjing University School of Medicine, Nanjing, Jiangsu, 210008, China 6. Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China 7. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China #First authors: Guangzhen Wu and Yingkun Xu contributed equally to this study. Corresponding authors: Qifei Wang, Department of Urology, The First Affiliated Hospital of Dalian Medical University, No.222 Zhongshan Road, Dalian, Liaoning, 116011, China; Tel: +86-18098876008; E-mail: [email protected]; Qinghua Xia, Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 9677 Jingshidong Road, Jinan, Shandong, 250021, China; Tel: +86-15168889221; E-mail: [email protected].
    [Show full text]