DOCSLIB.ORG

Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization ORIGINAL ARTICLE Print ISSN 1738-5520 / On-line ISSN 1738-5555 DOI 10.4070/kcj.2011.41.7.385 Copyright © 2011 The Korean Society of Cardiology Open Access Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization Suk Min Seo, MD1, Yoon Seok Koh, MD1, Hae Ok Jung, MD1, Jin Soo Choi, MD2, Pum Joon Kim, MD1, Sang Hong Baek, MD1, Ho-Joong Youn, MD1, Kweon-Haeng Lee, MD3, and Ki-Bae Seung, MD1 1Cardiovascular Center and Cardiology Division, 2Catholic Neuroscience Center, 3Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea ABSTRACT Background and Objectives: Vasospastic angina (VA) is a specific type of coronary artery disease and develops as a result of coronary artery spasm. Recently, a few studies have revealed that VA caused by coronary artery spasm is related to genetic traits. The objective of this study was to use the recently developed technique of array comparative genomic hybridization (CGH) to screen the genetic aberrations of VA. Subjects and Methods: To identify candidate genes that might be causally involved in the pathogenesis of VA, genomic deoxyribonucleic acids were extracted from whole blood of 28 patients with VA who presented at Department of Cardiology at Seoul St. Mary’s Hospital, Seoul, Korea. The copy number profiles of these patients was then analyzed using array CGH and reverse transcriptase (RT) quantitative polymerase chain reaction (PCR). Results: Array CGH revealed gains in 31 different regions, with losses in the 4q35.2, 7q22.1, 10q26.3, 15q11.2, 16p13.11, 17p11.2 and 19q13.3 regions (more than 32% aberration in these regions). Several loci were found to be frequently including gains of 5p and 11q (50% of samples). The most common losses were found in 7q (54% of samples). Copy number aberrations in chromosomal regions were detected and corresponding genes were confirmed by RT quantitative PCR. The fold change levels were highest in the CTDP1 (18q23), HDAC10 (22q13.33), KCNQ1 (11p15.5-p15.4), NINJ2 (12p13.33), NOTCH2 (1p12-p11.2), PCSK6 (15q26.3), SDHA (5p15.33), and MUC17 (7q22.1) genes. Conclusion: Many candidate chromosomal regions that might be related to the pathogenesis of VA were detected by array CGH and should be systematically investi- gated to establish the causative and specific genes for VA.( Korean Circ J 2011;41:385-393) KEY WORDS: Array comparative genomic hybridization; Vasospastic angina. Introduction fibrillation or electro mechanical dissociation, and even sud- den cardiac death.1) The incidence of VA is higher in Asians Vasospastic angina (VA), also called Prinzmetal’s angina or than Caucasians or Blacks,2)3) which strongly suggests that ge- variant angina, is a specific type of coronary artery disease and netic traits might be involved in the pathogenesis of VA.4-11) is developed due to not atherosclerosis but coronary artery Studies have shown that the loss of Kir6.1 {pore-forming spasm. This disease can cause acute coronary syndrome, in- inwardly rectifying K+ (Kir) channel subunit} or SUR2 (sulfo- cluding acute myocardial infarction, ventricular tachycardia, nylurea receptor regulatory subunit of KATP channel) by re- Received: September 10, 2010 lated gene deletions in mice induced VA.4)5) So far, only these Revision Received: November 5, 2010 two genes have been shown to be associated with gene copy Accepted: December 16, 2010 Correspondence: Hae Ok Jung, MD, Cardiovascular Center and Car- number alterations. Other investigations showed gene poly- diology Division, College of Medicine, The Catholic University of Korea, morphisms6-8) and functional expression9-11) in VA. Related 505 Banpo-dong, Seocho-gu, Seoul 137-040, Korea Tel: 82-2-2258-1302, Fax: 82-2-591-1506 gene polymorphisms in VA included an endothelial nitric 6) 7) E-mail: [email protected] oxide synthase gene, adrenergic receptor gene, and the pa- 8) 9) • The authors have no financial conflicts of interest. raoxonase 1 gene. The Rho-associated kinase gene and se- 10)11) cc This is an Open Access article distributed under the terms of the Cre- rotonin receptor (5-HT1Dβ) gene were also shown to be re- ative Commons Attribution Non-Commercial License (http://creativecom- lated to VA by their functional expression. To date, there have mons.org/licenses/by-nc/3.0) which permits unrestricted non-commer- cial use, distribution, and reproduction in any medium, provided the origi- been no studies on deoxyribonucleic acid (DNA) copy num- nal work is properly cited. ber alterations in the whole human genome among patients 385 386 DNA Copy Number Aberrations in Vasospastic Angina with VA. The recent development of array-comparative ge- Table 1. The clinical characteristics of patients with vasospastic angina nomic hybridization (CGH) provides a means to quantita- tively measure DNA copy number aberrations and to map Characteristic Value them directly to genomic sequences.12-14) Also, tiling resolu- Number of samples 28 tion DNA microarrays comprised of large-insert genomic Age, mean±standard deviation (years) 56.4±11.4 clones such as bacterial artificial chromosomes (BACs) are a Male (%) 20 (71.4) very useful and accurate method for detecting genomic ab- Current smoker (%) 11 (39.3) 15)16) errations in many genetic diseases. Furthermore, array- Current alcohol drinking (%) 14 (50) CGH with BAC clones, has been proven to be a very useful and accurate tool for detecting genomic aberrations in whole fer (BioPrime® DNA Labeling System, Invitrogen, Carlsbad, blood samples for schizophrenia, epilepsy and mental retar- CA, USA) at 98-100°C for 5 minutes, and then cooled on ice dation,17-19) as well as in tissue from some cancers.20-24) Both for 5 minutes. The denatured DNA was differentially labeled fluorescencein situ hybridization (FISH) and real-time poly- with 3 μL of 1 mM Cy3- and Cy5-conjugated dCTP by ran- merase chain reaction (RT-PCR) have also been applied em- dom primed labeling (Perkin Elmer, Waltham, MA, USA). pirically to confirm array-CGH results.17)18)21-24) The mixture was incubated with a Klenow fragment at 37°C In the study presented here, we analyzed genomic DNA copy overnight. After labeling, unincorporated nucleotides were number aberrations in whole blood from 28 patients with removed using MicroSpinTM G-50 columns (Amersham Bio- VA using array CGH. Genetic aberrations, for a subset of gain- sciences, Buckinghamshire, UK). Cy3- and Cy5-labeled test ed or lost gene, were confirmed by RT-PCR. DNA and reference DNA were mixed with 50 μL of human Cot-1 DNA for blocking of repeat sequences. After purifica- Subjects and Methods tion, this mixture was resolved in hybridization buffer (Mac- rogen) containing yeast tRNA for blocking of non-specific nu- Clinical description cleotides binding. Peripheral blood samples were collected from 28 patients After the MACArrayTM-Karyo 4K BAC-chip was prehy- with VA at the Department of Cardiology at Seoul St. Mary’s bridized in hybridization buffer with salmon sperm DNA Hospital, Seoul, Korea. In this study, the diagnosis of VA was for 1 hour, chips were hybridized with the purification mix- made when patients met all of the following criteria: 1) re- ture. It was then incubated for 72 hours in the 37°C hybridiz- petitive burning or squeezing retrosternal chest pain, 2) def- ation chamber (BioMicro systems, Salt Lake City, UT, USA). inite positive response by coronary angiography with intra After hybridization was complete, array chips were washed in coronary acetylcholine provocation test, 3) no significant athe- 50% formamide-2x SSC at 46°C for 15 minutes, and 0.1% rosclerotic stenosis in coronary artery (<50% narrowing of SDS-2x SSC at 46°C for 30 minutes. Next, the chips were wa- the coronary luminal diameter) according to quantitative co- shed in 50% sodium phosphate-0.1% NP40 for 15 minutes ronary angiography. Blood samples were collected from 8 followed by washing with 2x SSC for 15 minutes at room women and 20 men, aged 34-71 years (mean age±standard temperature. After spin drying, hybridized arrays were scann- deviation, 56.44±11.4 in years). The clinical characteristics ed with a GenepixTM (Axon Instruments, Sunnyvale, CA, USA). of the patients are shown in Table 1. Genomic DNA was extr- acted using a Puregene DNA isolation kit (Qiagen, Hilden, Data analysis Germany). Reference DNA was pooled from 10 gender-mat- Raw signal intensities from the arrays were measured us- ched (male), normal, healthy control subjects. All patients gave ing the MAC Viewer v1.6.3 software (Macrogen). Log2 (Cy3 written informed consent to participate in this study. The pro- intensity/Cy5 intensity ratios) were normalized by using the tocol of this study was approved by the institutional review median of fluorescence ratios computed from the houseke- board of Seoul St. Mary’s Hospital, The Catholic University eping DNA control fragments linearly distributed across the of Korea. genome. Measurements flagged as unreliable by MAC Vie- wer v1.6.3 were removed from subsequent analysis. The th- Array comparative genomic hybridization reshold corresponds to 2 standard deviation (SD) values from Array CGH analyses were conducted on 28 individual sam- the mean. The information on each individual clone was ob- ples using commercial MACArrayTM Karyo 4K BAC-chips tained from the UCSC Genome Bioinformatics database (Macrogen, Seoul, Korea) with 4,030 BAC clones, in dupli- (May 2004 freeze, http://genome.ucsc.edu). cate, on the whole human genome with a resolution of about 1 Mbp. Array CGH was performed as described previous- Reverse transcriptase quantitative polymerase ly.25) Briefly, 500-700 ng target and reference DNAs were de- chain reaction natured in the presence of random primer and reaction buf- To confirm the level of genomic imbalances identified by Suk Min Seo, et al.
Load more

Recommended publications
  • Congenital Cataracts–Facial Dysmorphism–Neuropathy
    Orphanet Journal of Rare Diseases BioMed Central Review Open Access Congenital Cataracts – Facial Dysmorphism – Neuropathy Luba Kalaydjieva* Address: Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Hospital Avenue, WA 6009 Nedlands, Australia Email: Luba Kalaydjieva* - [email protected] * Corresponding author Published: 29 August 2006 Received: 11 July 2006 Accepted: 29 August 2006 Orphanet Journal of Rare Diseases 2006, 1:32 doi:10.1186/1750-1172-1-32 This article is available from: http://www.OJRD.com/content/1/1/32 © 2006 Kalaydjieva; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed. Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. During general anaesthesia, patients with CCFDN require careful monitoring as they have an elevated risk of complications. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Diagnosis is clinical and is supported by electrophysiological and brain imaging studies.
    [Show full text]
  • Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers
    Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers. by Kelly Kennaley A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Molecular and Cellular Pathology) in the University of Michigan 2019 Doctoral Committee: Associate Professor Zaneta Nikolovska-Coleska, Co-Chair Adjunct Associate Professor Scott A. Tomlins, Co-Chair Associate Professor Eric R. Fearon Associate Professor Alexey I. Nesvizhskii Kelly R. Kennaley [email protected] ORCID iD: 0000-0003-2439-9020 © Kelly R. Kennaley 2019 Acknowledgements I have immeasurable gratitude for the unwavering support and guidance I received throughout my dissertation. First and foremost, I would like to thank my thesis advisor and mentor Dr. Scott Tomlins for entrusting me with a challenging, interesting, and impactful project. He taught me how to drive a project forward through set-backs, ask the important questions, and always consider the impact of my work. I’m truly appreciative for his commitment to ensuring that I would get the most from my graduate education. I am also grateful to the many members of the Tomlins lab that made it the supportive, collaborative, and educational environment that it was. I would like to give special thanks to those I’ve worked closely with on this project, particularly Dr. Moloy Goswami for his mentorship, Lei Lucy Wang, Dr. Sumin Han, and undergraduate students Bhavneet Singh, Travis Weiss, and Myles Barlow. I am also grateful for the support of my thesis committee, Dr. Eric Fearon, Dr. Alexey Nesvizhskii, and my co-mentor Dr. Zaneta Nikolovska-Coleska, who have offered guidance and critical evaluation since project inception.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Triplet Repeat Length Bias and Variation in the Human Transcriptome
    Triplet repeat length bias and variation in the human transcriptome Michael Mollaa,1,2, Arthur Delcherb,1, Shamil Sunyaevc, Charles Cantora,d,2, and Simon Kasifa,e aDepartment of Biomedical Engineering and dCenter for Advanced Biotechnology, Boston University, Boston, MA 02215; bCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742; cDepartment of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and eCenter for Advanced Genomic Technology, Boston University, Boston, MA 02215 Contributed by Charles Cantor, July 6, 2009 (sent for review May 4, 2009) Length variation in short tandem repeats (STRs) is an important family including Huntington’s disease (10) and hereditary ataxias (11, 12). of DNA polymorphisms with numerous applications in genetics, All Huntington’s patients exhibit an expanded number of copies in medicine, forensics, and evolutionary analysis. Several major diseases the CAG tandem repeat subsequence in the N terminus of the have been associated with length variation of trinucleotide (triplet) huntingtin gene. Moreover, an increase in the repeat length is repeats including Huntington’s disease, hereditary ataxias and spi- anti-correlated to the onset age of the disease (13). Multiple other nobulbar muscular atrophy. Using the reference human genome, we diseases have also been associated with copy number variation of have catalogued all triplet repeats in genic regions. This data revealed tandem repeats (8, 14). Researchers have hypothesized that inap- a bias in noncoding DNA repeat lengths. It also enabled a survey of propriate repeat variation in coding regions could result in toxicity, repeat-length polymorphisms (RLPs) in human genomes and a com- incorrect folding, or aggregation of a protein.
    [Show full text]
  • Common Variants in SOX-2 and Congenital Cataract Genes Contribute to Age-Related Nuclear Cataract
    ARTICLE https://doi.org/10.1038/s42003-020-01421-2 OPEN Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract Ekaterina Yonova-Doing et al.# 1234567890():,; Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this dis- ease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cat- aract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye. #A list of authors and their affiliations appears at the end of the paper. COMMUNICATIONS BIOLOGY | (2020) 3:755 | https://doi.org/10.1038/s42003-020-01421-2 | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-020-01421-2 ge-related cataract is the leading cause of blindness, structure (meta-analysis genomic inflation factor λ = 1.009, accounting for more than one-third of blindness Supplementary Table 4 and Supplementary Fig.
    [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]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
    Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A.
    [Show full text]
  • Integrated Analysis of Human Influenza a (H1N1) Virus Infection
    BIOCELL Tech Science Press 2021 45(4): 885-899 Integrated analysis of human influenza A (H1N1) virus infection- related genes to construct a suitable diagnostic model WENBIAO CHEN; KEFAN BI; JINGJING JIANG; XUJUN ZHANG; HONGYAN DIAO* State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China Key words: Human influenza A, H1N1 virus, Gene, Diagnosis model Abstract: The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus, which aids in the understanding of its underlying pathogenic mechanism. In this study, analyses of the characteristic of the H1N1 virus infection-related genes, their biological functions, and infection-related reversal drugs were performed. Additionally, we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection. There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection. They were used during the protein– protein interaction (PPI) analysis, and we obtained a total of 1725 interacting genes. Then, we performed a weighted gene co-expression network analysis (WGCNA) on these genes, and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection. These modules contained 60 genes, and they were used to construct this diagnostic model, which showed an effective prediction value. Besides, these 60 genes were involved in the biological functions of this infectious virus, like the cellular response to type I interferon and in the negative regulation of the viral life cycle.
    [Show full text]
  • Investigating Trait Variability of Gene Co-Expression Network Architecture in Brain by Manipulating Genomic Signatures of Schizophrenia Risk
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.04.442668; this version posted May 7, 2021. 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. Investigating trait variability of gene co-expression network architecture in brain by manipulating genomic signatures of schizophrenia risk Eugenia Radulescua,1, Qiang Chena, Giulio Pergolaa,b, Nicholas J Eaglesa, Joshua M Stolza, Joo Heon Shina, Thomas M Hydea,c,d, Joel E Kleinmana,c, Daniel R Weinbergera,c,d,e,f,1 Affiliations: a. Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA b. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy c. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA d. Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA e. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA f. McKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA 1Address correspondence to: Daniel R. Weinberger Lieber Institute for Brain Development 855 North Wolfe Street Baltimore, Maryland 21205 410-955-1000 ([email protected]) Eugenia Radulescu Lieber Institute for Brain Development 855 North Wolfe Street Baltimore, Maryland 21205 410-955-1000 ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.04.442668; this version posted May 7, 2021.
    [Show full text]
  • Datasheet: VPA00440 Product Details
    Datasheet: VPA00440 Description: RABBIT ANTI FCP1 Specificity: FCP1 Format: Purified Product Type: PrecisionAb™ Polyclonal Isotype: Polyclonal IgG Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Rabbit polyclonal antibody purified by affinity chromatography Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN ) Stabilisers 3 Immunogen KLH conjugated synthetic peptide corresponding to amino acid 247-276 of human FCP1 External Database Links UniProt: Q9Y5B0 Related reagents Entrez Gene: 9150 CTDP1 Related reagents Synonyms FCP1 Page 1 of 2 Specificity Rabbit anti Human FCP1 antibody recognizes FCP1, also known as RNA polymerase II subunit A C-terminal domain phosphatase, serine phosphatase FCP1a or transcription factor IIF-associating CTD phosphatase 1. The CTDP1 gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression.
    [Show full text]
  • Chromosome 18 Gene Dosage Map 2.0
    Human Genetics (2018) 137:961–970 https://doi.org/10.1007/s00439-018-1960-6 ORIGINAL INVESTIGATION Chromosome 18 gene dosage map 2.0 Jannine D. Cody1,2 · Patricia Heard1 · David Rupert1 · Minire Hasi‑Zogaj1 · Annice Hill1 · Courtney Sebold1 · Daniel E. Hale1,3 Received: 9 August 2018 / Accepted: 14 November 2018 / Published online: 17 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chro- mosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.
    [Show full text]