Copy Number Variant Analysis and Expression Profiling of The
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Genetic Variation Across the Human Olfactory Receptor Repertoire Alters Odor Perception
bioRxiv preprint doi: https://doi.org/10.1101/212431; this version posted November 1, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 4.0 International license. Genetic variation across the human olfactory receptor repertoire alters odor perception Casey Trimmer1,*, Andreas Keller2, Nicolle R. Murphy1, Lindsey L. Snyder1, Jason R. Willer3, Maira Nagai4,5, Nicholas Katsanis3, Leslie B. Vosshall2,6,7, Hiroaki Matsunami4,8, and Joel D. Mainland1,9 1Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA 2Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York, USA 3Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, USA 4Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA 5Department of Biochemistry, University of Sao Paulo, Sao Paulo, Brazil 6Howard Hughes Medical Institute, New York, New York, USA 7Kavli Neural Systems Institute, New York, New York, USA 8Department of Neurobiology and Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina, USA 9Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA *[email protected] ABSTRACT The human olfactory receptor repertoire is characterized by an abundance of genetic variation that affects receptor response, but the perceptual effects of this variation are unclear. To address this issue, we sequenced the OR repertoire in 332 individuals and examined the relationship between genetic variation and 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. -
SNP Genotypes of Olfactory Receptor Genes Associated with Olfactory Ability in German Shepherd Dogs
SHORT COMMUNICATION doi: 10.1111/age.12389 SNP genotypes of olfactory receptor genes associated with olfactory ability in German Shepherd dogs † ‡ – M. Yang*, G.-J. Geng , W. Zhang , L. Cui§, H.-X. Zhang and J.-L. Zheng‡ † *Police-dog Technology Department, National Police University of China, Shenyang, Liaoning 110034, China. Technology Department, ‡ Shenyang Traffic Police Detachment, Shenyang, Liaoning 110001, China. Forensic Medicine Department, National Police University of China, Shenyang, Liaoning 110854, China. §Document Inspection Department, National Police University of China, Shenyang, Liaoning – 110854, China. Mark Inspection Department, National Police University of China, Shenyang, Liaoning 110854, China. Summary To find out the relationship between SNP genotypes of canine olfactory receptor genes and olfactory ability, 28 males and 20 females from German Shepherd dogs in police service were scored by odor detection tests and analyzed using the Beckman GenomeLab SNPstream. The representative 22 SNP loci from the exonic regions of 12 olfactory receptor genes were investigated, and three kinds of odor (human, ice drug and trinitrotoluene) were detected. The results showed that the SNP genotypes at the OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR2K2-like:c.518G>A, OR4C11-like: c.511T>G and OR4C11-like:c.692G>A loci had a statistically significant effect on the scenting abilities (P < 0.001). The kind of odor influenced the performances of the dogs (P < 0.001). In addition, there were interactions between genotype and the kind of odor at the following loci: OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR4C11-like:c.511T>G and OR4C11-like:c.692G>A(P< 0.001). -
Copy Number Variation in Fetal Alcohol Spectrum Disorder
Biochemistry and Cell Biology Copy number variation in fetal alcohol spectrum disorder Journal: Biochemistry and Cell Biology Manuscript ID bcb-2017-0241.R1 Manuscript Type: Article Date Submitted by the Author: 09-Nov-2017 Complete List of Authors: Zarrei, Mehdi; The Centre for Applied Genomics Hicks, Geoffrey G.; University of Manitoba College of Medicine, Regenerative Medicine Reynolds, James N.; Queen's University School of Medicine, Biomedical and Molecular SciencesDraft Thiruvahindrapuram, Bhooma; The Centre for Applied Genomics Engchuan, Worrawat; Hospital for Sick Children SickKids Learning Institute Pind, Molly; University of Manitoba College of Medicine, Regenerative Medicine Lamoureux, Sylvia; The Centre for Applied Genomics Wei, John; The Centre for Applied Genomics Wang, Zhouzhi; The Centre for Applied Genomics Marshall, Christian R.; The Centre for Applied Genomics Wintle, Richard; The Centre for Applied Genomics Chudley, Albert; University of Manitoba Scherer, Stephen W.; The Centre for Applied Genomics Is the invited manuscript for consideration in a Special Fetal Alcohol Spectrum Disorder Issue? : Keyword: Fetal alcohol spectrum disorder, FASD, copy number variations, CNV https://mc06.manuscriptcentral.com/bcb-pubs Page 1 of 354 Biochemistry and Cell Biology 1 Copy number variation in fetal alcohol spectrum disorder 2 Mehdi Zarrei,a Geoffrey G. Hicks,b James N. Reynolds,c,d Bhooma Thiruvahindrapuram,a 3 Worrawat Engchuan,a Molly Pind,b Sylvia Lamoureux,a John Wei,a Zhouzhi Wang,a Christian R. 4 Marshall,a Richard F. Wintle,a Albert E. Chudleye,f and Stephen W. Scherer,a,g 5 aThe Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital 6 for Sick Children, Toronto, Ontario, Canada 7 bRegenerative Medicine Program, University of Manitoba, Winnipeg, Canada 8 cCentre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada. -
A High-Resolution Integrated Map of Copy Number Polymorphisms Within
Nicholas et al. BMC Genomics 2011, 12:414 http://www.biomedcentral.com/1471-2164/12/414 RESEARCHARTICLE Open Access A high-resolution integrated map of copy number polymorphisms within and between breeds of the modern domesticated dog Thomas J Nicholas1, Carl Baker1, Evan E Eichler1,2 and Joshua M Akey1* Abstract Background: Structural variation contributes to the rich genetic and phenotypic diversity of the modern domestic dog, Canis lupus familiaris, although compared to other organisms, catalogs of canine copy number variants (CNVs) are poorly defined. To this end, we developed a customized high-density tiling array across the canine genome and used it to discover CNVs in nine genetically diverse dogs and a gray wolf. Results: In total, we identified 403 CNVs that overlap 401 genes, which are enriched for defense/immunity, oxidoreductase, protease, receptor, signaling molecule and transporter genes. Furthermore, we performed detailed comparisons between CNVs located within versus outside of segmental duplications (SDs) and find that CNVs in SDs are enriched for gene content and complexity. Finally, we compiled all known dog CNV regions and genotyped them with a custom aCGH chip in 61 dogs from 12 diverse breeds. These data allowed us to perform the first population genetics analysis of canine structural variation and identify CNVs that potentially contribute to breed specific traits. Conclusions: Our comprehensive analysis of canine CNVs will be an important resource in genetically dissecting canine phenotypic and behavioral variation. Background domestication, examine relatedness among breeds, and The domestication of the modern dog from their wolf identify signatures of artificial selection [4,7-9]. -
Single Cell Derived Clonal Analysis of Human Glioblastoma Links
SUPPLEMENTARY INFORMATION: Single cell derived clonal analysis of human glioblastoma links functional and genomic heterogeneity ! Mona Meyer*, Jüri Reimand*, Xiaoyang Lan, Renee Head, Xueming Zhu, Michelle Kushida, Jane Bayani, Jessica C. Pressey, Anath Lionel, Ian D. Clarke, Michael Cusimano, Jeremy Squire, Stephen Scherer, Mark Bernstein, Melanie A. Woodin, Gary D. Bader**, and Peter B. Dirks**! ! * These authors contributed equally to this work.! ** Correspondence: [email protected] or [email protected]! ! Supplementary information - Meyer, Reimand et al. Supplementary methods" 4" Patient samples and fluorescence activated cell sorting (FACS)! 4! Differentiation! 4! Immunocytochemistry and EdU Imaging! 4! Proliferation! 5! Western blotting ! 5! Temozolomide treatment! 5! NCI drug library screen! 6! Orthotopic injections! 6! Immunohistochemistry on tumor sections! 6! Promoter methylation of MGMT! 6! Fluorescence in situ Hybridization (FISH)! 7! SNP6 microarray analysis and genome segmentation! 7! Calling copy number alterations! 8! Mapping altered genome segments to genes! 8! Recurrently altered genes with clonal variability! 9! Global analyses of copy number alterations! 9! Phylogenetic analysis of copy number alterations! 10! Microarray analysis! 10! Gene expression differences of TMZ resistant and sensitive clones of GBM-482! 10! Reverse transcription-PCR analyses! 11! Tumor subtype analysis of TMZ-sensitive and resistant clones! 11! Pathway analysis of gene expression in the TMZ-sensitive clone of GBM-482! 11! Supplementary figures and tables" 13" "2 Supplementary information - Meyer, Reimand et al. Table S1: Individual clones from all patient tumors are tumorigenic. ! 14! Fig. S1: clonal tumorigenicity.! 15! Fig. S2: clonal heterogeneity of EGFR and PTEN expression.! 20! Fig. S3: clonal heterogeneity of proliferation.! 21! Fig. -
WO 2019/068007 Al Figure 2
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/068007 Al 04 April 2019 (04.04.2019) W 1P O PCT (51) International Patent Classification: (72) Inventors; and C12N 15/10 (2006.01) C07K 16/28 (2006.01) (71) Applicants: GROSS, Gideon [EVIL]; IE-1-5 Address C12N 5/10 (2006.0 1) C12Q 1/6809 (20 18.0 1) M.P. Korazim, 1292200 Moshav Almagor (IL). GIBSON, C07K 14/705 (2006.01) A61P 35/00 (2006.01) Will [US/US]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., C07K 14/725 (2006.01) P.O. Box 4044, 7403635 Ness Ziona (TL). DAHARY, Dvir [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (21) International Application Number: Box 4044, 7403635 Ness Ziona (IL). BEIMAN, Merav PCT/US2018/053583 [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (22) International Filing Date: Box 4044, 7403635 Ness Ziona (E.). 28 September 2018 (28.09.2018) (74) Agent: MACDOUGALL, Christina, A. et al; Morgan, (25) Filing Language: English Lewis & Bockius LLP, One Market, Spear Tower, SanFran- cisco, CA 94105 (US). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of national protection available): AE, AG, AL, AM, 62/564,454 28 September 2017 (28.09.2017) US AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/649,429 28 March 2018 (28.03.2018) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (71) Applicant: IMMP ACT-BIO LTD. -
Genome-Wide Screening Identifies Genes and Biological Processes
Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 10-12-2018 Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene-Induced Apoptosis Tengyu Ko Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Cancer Biology Commons, Cell Biology Commons, and the Genomics Commons Recommended Citation Ko, Tengyu, "Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene- Induced Apoptosis" (2018). LSU Doctoral Dissertations. 4715. https://digitalcommons.lsu.edu/gradschool_dissertations/4715 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. GENOME-WIDE SCREENING IDENTIFIES GENES AND BIOLOGICAL PROCESSES IMPLICATED IN CHEMORESISTANCE AND ONCOGENE- INDUCED APOPTOSIS A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical and Veterinary Medical Sciences through the Department of Comparative Biomedical Sciences by Tengyu Ko B.S., University of California, Santa Barbara 2010 December 2018 ACKNOWLEDGEMENTS I would like to express my sincerest gratitude to my major supervisor Dr. Shisheng Li for giving me the opportunity to join his team and the freedom to pursue projects. I appreciate all of his thoughts and efforts. Truly, none of these findings would be possible without his supervisions, supports, insightful discussions, and patience. -
Genome-Wide Profiling of Druggable Active Tumor Defense Mechanisms to Enhance Cancer Immunotherapy
bioRxiv preprint doi: https://doi.org/10.1101/843185; this version posted November 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. Genome-wide profiling of druggable active tumor defense mechanisms to enhance cancer immunotherapy Rigel J. Kishton1,2,*,#, Shashank J. Patel1,2,†,*, Suman K. Vodnala1,2, Amy E. Decker3, Yogin Patel1,2, Madhusudhanan Sukumar1,2, Tori N. Yamamoto1,2,4, Zhiya Yu1,2, Michelle Ji1,2, Amanda N. Henning1,2, Devikala Gurusamy1,2, Douglas C. Palmer1,2, Winifred Lo1, Anna Pasetto1, Parisa Malekzadeh1, Drew C. Deniger1, Kris C. Wood3, Neville E. Sanjana5,6, Nicholas P. Restifo1,2, #, § 1Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA 2Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA 3Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA 4Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA 5New York Genome Center, New York, NY 10013 USA 6Department of Biology, New York University, New York, NY 10003, USA *These authors contributed equally to this work. †Present address: NextCure Inc., Beltsville, MD 20705, USA §Present address: Lyell Immunopharma, South San Francisco, CA 94080, USA #Corresponding authors. NPR: [email protected]. RJK: [email protected]. bioRxiv preprint doi: https://doi.org/10.1101/843185; this version posted November 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. -
Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib
Supplementary Online Content Chen G, McQuade JL, Panka DJ, et al. Clinical, molecular and immune analysis of dabrafenib-trametinib combination treatment for metastatic melanoma that progressed during BRAF inhibitor monotherapy: a phase 2 clinical trial. JAMA Oncology. Published online April 28, 2016. doi:10.1001/jamaoncol.2016.0509. eMethods. eReferences. eTable 1. Clinical efficacy eTable 2. Adverse events eTable 3. Correlation of baseline patient characteristics with treatment outcomes eTable 4. Patient responses and baseline IHC results eFigure 1. Kaplan-Meier analysis of overall survival eFigure 2. Correlation between IHC and RNAseq results eFigure 3. pPRAS40 expression and PFS eFigure 4. Baseline and treatment-induced changes in immune infiltrates eFigure 5. PD-L1 expression eTable 5. Nonsynonymous mutations detected by WES in baseline tumors This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 eMethods Whole exome sequencing Whole exome capture libraries for both tumor and normal samples were constructed using 100ng genomic DNA input and following the protocol as described by Fisher et al.,3 with the following adapter modification: Illumina paired end adapters were replaced with palindromic forked adapters with unique 8 base index sequences embedded within the adapter. In-solution hybrid selection was performed using the Illumina Rapid Capture Exome enrichment kit with 38Mb target territory (29Mb baited). The targeted region includes 98.3% of the intervals in the Refseq exome database. Dual-indexed libraries were pooled into groups of up to 96 samples prior to hybridization. -
Gene and Protein Networks in Understanding Cellular Function
Gene and Protein Networks in Understanding Cellular Function Sonja Katriina Lehtinen A thesis sumbitted to University College London for the degree of Doctor of Philosophy March 2015 1 I, Sonja Lehtinen, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Sonja Lehtinen 2 March, 2015 2 Abstract Over the past decades, networks have emerged as a useful way of representing complex large-scale systems in a variety of fields. In cellular and molecular biology, gene and protein networks have attracted considerable interest as tools for making sense of increasingly large volumes of data. Despite this interest, there is still substantial debate over how to best exploit network models in cellular biology. This thesis explores the use of gene and protein networks in various biological contexts. The first part of the thesis (Chapter 2) examines protein function prediction using network-based `guilt-by-association' approaches. Given the falling costs of genome sequencing and the availability of large volumes of biological data, automated annotation of gene and protein function is becoming increasingly useful. Chapter 2 describes the development of a new network-based protein function prediction method and compares it to a leading algorithm on a number of benchmarks. Biases in benchmarking methods are also explicitly explored. The second part (Chapters 3 and 4) explores network approaches in under- standing loss of function variation in the human genome. For a number of genes, homozygous loss of function appears to have no detrimental effect. -
Positive Selection, Relaxation, and Acceleration in the Evolution of the Human and Chimp Genome
Positive Selection, Relaxation, and Acceleration in the Evolution of the Human and Chimp Genome Leonardo Arbiza1, Joaquı´n Dopazo2, Herna´n Dopazo1* 1 Pharmacogenomics and Comparative Genomics Unit, Centro de Investigacio´nPrı´ncipe Felipe (CIPF), Valencia, Spain, 2 Functional Genomics Unit, Bioinformatics Department, Centro de Investigacio´nPrı´ncipe Felipe (CIPF), Valencia, Spain For years evolutionary biologists have been interested in searching for the genetic bases underlying humanness. Recent efforts at a large or a complete genomic scale have been conducted to search for positively selected genes in human and in chimp. However, recently developed methods allowing for a more sensitive and controlled approach in the detection of positive selection can be employed. Here, using 13,198 genes, we have deduced the sets of genes involved in rate acceleration, positive selection, and relaxation of selective constraints in human, in chimp, and in their ancestral lineage since the divergence from murids. Significant deviations from the strict molecular clock were observed in 469 human and in 651 chimp genes. The more stringent branch-site test of positive selection detected 108 human and 577 chimp positively selected genes. An important proportion of the positively selected genes did not show a significant acceleration in rates, and similarly, many of the accelerated genes did not show significant signals of positive selection. Functional differentiation of genes under rate acceleration, positive selection, and relaxation was not statistically significant between human and chimp with the exception of terms related to G-protein coupled receptors and sensory perception. Both of these were over-represented under relaxation in human in relation to chimp. -
The Mouse Solitary Odorant Receptor Gene Promoters As Models for the Study of Odorant Receptor Gene Choice
RESEARCH ARTICLE The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice Andrea Degl'Innocenti1,2*, Marta Parrilla1☯, Bettina Harr3☯, Meike Teschke3☯ 1 Max-Planck-Institut für Biophysik, Frankfurt am Main, Germany, 2 Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy, 3 Abteilung Evolutionsgenetik, Max-Planck- Institut für Evolutionsbiologie, Plön, Germany ☯ These authors contributed equally to this work. * [email protected] Abstract OPEN ACCESS Citation: Degl'Innocenti A, Parrilla M, Harr B, Background Teschke M (2016) The Mouse Solitary Odorant In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice. PLoS ONE 11(1): Among these, the main olfactory epithelium detects most conventional odorants. Olfactory e0144698. doi:10.1371/journal.pone.0144698 sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an Editor: Johannes Reisert, Monell Chemical Senses extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Center, UNITED STATES Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a sin- Received: June 26, 2015 gle odorant receptor gene is transcribed in a given mature neuron, through a still uncharac- terized molecular mechanism known as odorant receptor gene choice. Accepted: November 23, 2015 Published: January 21, 2016 Copyright: © 2016 Degl'Innocenti et al. This is an Aim open access article distributed under the terms of the Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any (we call them solitary) from the others within a region broader than 1 Mb upstream and medium, provided the original author and source are downstream with respect to their transcript's coordinates.