Chromosomal Breakpoints in Primary Colon Cancer Cluster at Sites of Structural Variants in the Genome
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Manual Annotation and Analysis of the Defensin Gene Cluster in the C57BL
BMC Genomics BioMed Central Research article Open Access Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome Clara Amid*†1, Linda M Rehaume*†2, Kelly L Brown2,3, James GR Gilbert1, Gordon Dougan1, Robert EW Hancock2 and Jennifer L Harrow1 Address: 1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK, 2University of British Columbia, Centre for Microbial Disease & Immunity Research, 2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada and 3Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden Email: Clara Amid* - [email protected]; Linda M Rehaume* - [email protected]; Kelly L Brown - [email protected]; James GR Gilbert - [email protected]; Gordon Dougan - [email protected]; Robert EW Hancock - [email protected]; Jennifer L Harrow - [email protected] * Corresponding authors †Equal contributors Published: 15 December 2009 Received: 15 May 2009 Accepted: 15 December 2009 BMC Genomics 2009, 10:606 doi:10.1186/1471-2164-10-606 This article is available from: http://www.biomedcentral.com/1471-2164/10/606 © 2009 Amid et al; 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 Background: Host defense peptides are a critical component of the innate immune system. Human alpha- and beta-defensin genes are subject to copy number variation (CNV) and historically the organization of mouse alpha-defensin genes has been poorly defined. -
Mapping DNA Structural Variation in Dogs
Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Resource Mapping DNA structural variation in dogs Wei-Kang Chen,1,4 Joshua D. Swartz,1,4,5 Laura J. Rush,2 and Carlos E. Alvarez1,3,6 1Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio 43205, USA; 2Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA; 3Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH to create the first map of DNA copy number variation (CNV) or SV in dogs. The extent of this variation, and some of the gene classes affected, are similar to those of mice and humans. Most canine CNVs affect genes, including disease and candidate disease genes, and are thus likely to be functional. We identified many CNVs that may be breed or breed class specific. Cluster analysis of CNV regions showed that dog breeds tend to group according to breed classes. Our combined findings suggest many CNVs are (1) in linkage disequilibrium with flanking sequence, and (2) associated with breed-specific traits. -
Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications
Stem Cell Rev and Rep DOI 10.1007/s12015-016-9662-8 Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications Behnam Ahmadian Baghbaderani 1 & Adhikarla Syama2 & Renuka Sivapatham3 & Ying Pei4 & Odity Mukherjee2 & Thomas Fellner1 & Xianmin Zeng3,4 & Mahendra S. Rao5,6 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract We have recently described manufacturing of hu- help determine which set of tests will be most useful in mon- man induced pluripotent stem cells (iPSC) master cell banks itoring the cells and establishing criteria for discarding a line. (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Keywords Induced pluripotent stem cells . Embryonic stem Reports, 5(4), 647–659, 2015). In this manuscript, we de- cells . Manufacturing . cGMP . Consent . Markers scribe the detailed characterization of the two iPSC clones generated using this process, including whole genome se- quencing (WGS), microarray, and comparative genomic hy- Introduction bridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibra- Induced pluripotent stem cells (iPSCs) are akin to embryonic tion material and with a reporter subclone and lines made by a stem cells (ESC) [2] in their developmental potential, but dif- similar process from different donors. We believe that iPSCs fer from ESC in the starting cell used and the requirement of a are likely to be used to make multiple clinical products. We set of proteins to induce pluripotency [3]. Although function- further believe that the lines used as input material will be used ally identical, iPSCs may differ from ESC in subtle ways, at different sites and, given their immortal status, will be used including in their epigenetic profile, exposure to the environ- for many years or even decades. -
ABSTRACT DATA DRIVEN APPROACHES to IDENTIFY DETERMINANTS of HEART DISEASES and CANCER RESISTANCE Avinash Das Sahu, Doctor Of
ABSTRACT Title of dissertation: DATA DRIVEN APPROACHES TO IDENTIFY DETERMINANTS OF HEART DISEASES AND CANCER RESISTANCE Avinash Das Sahu, Doctor of Philosophy, 2016 Dissertation directed by: Professor Sridhar Hannenhalli Department of Computer Science Cancer and cardio-vascular diseases are the leading causes of death world-wide. Caused by systemic genetic and molecular disruptions in cells, these disorders are the manifestation of profound disturbance of normal cellular homeostasis. People suffering or at high risk for these disorders need early diagnosis and personalized therapeutic intervention. Successful implementation of such clinical measures can significantly improve global health. However, development of effective therapies is hindered by the challenges in identifying genetic and molecular determinants of the onset of diseases; and in cases where therapies already exist, the main challenge is to identify molecular determinants that drive resistance to the therapies. Due to the progress in sequencing technologies, the access to a large genome-wide biolog- ical data is now extended far beyond few experimental labs to the global research community. The unprecedented availability of the data has revolutionized the ca- pabilities of computational researchers, enabling them to collaboratively address the long standing problems from many different perspectives. Likewise, this thesis tackles the two main public health related challenges using data driven approaches. Numerous association studies have been proposed to identify genomic variants that determine disease. However, their clinical utility remains limited due to their inability to distinguish causal variants from associated variants. In the presented thesis, we first propose a simple scheme that improves association studies in su- pervised fashion and has shown its applicability in identifying genomic regulatory variants associated with hypertension. -
High-Resolution Analysis of Chromosomal Alterations in Adult Acute Lymphoblastic Leukemia
Elmer Press Original Article J Hematol. 2014;3(3):65-71 High-Resolution Analysis of Chromosomal Alterations in Adult Acute Lymphoblastic Leukemia Lam Kah Yuena, c, Zakaria Zubaidaha, Ivyna Bong Pau Nia, Megat Baharuddin Puteri Jamilatul Noora, Esa Ezaliaa, Chin Yuet Menga, Ong Tee Chuanb, Vegappan Subramanianb, Chang Kiang Mengb Abstract Introduction Background: Chromosomal alterations occur frequently in acute Acute lymphoblastic leukemia (ALL) is a heterogeneous lymphoblastic leukemia (ALL), affecting either the chromosome disease, resulting from the accumulation of chromosomal al- number or structural changes. These alterations can lead to inacti- terations either in the form of numerical or structural chang- vation of tumor suppressor genes and/or activation of oncogenes. es such as amplification, deletion, inversion or translocation. The objective of this study was to identify recurrent and/or novel The frequency of chromosomal alterations in adult ALL is chromosomal alterations in adult ALL using single nucleotide poly- 64-85% [1], compared to 60-69% in childhood ALL. Trans- morphism (SNP) array analysis. location t(9.22), one of the most common recurring chromo- Methods: We studied 41 cases of adult ALL compared with healthy somal alterations, is found in 20-40% adult ALL patients [2], normal controls using SNP array. and its incidence increases with age. Some of the chromo- somal alterations are significantly associated with remission Results: Our analysis revealed 43 copy number variant regions, duration, complete remission rate and disease-free survival of which 44% were amplifications and 56% were deletions. The [1]. Increasing age is also associated with lower remission most common amplifications were on chromosome regions 8p23.1 rates, shorter remissions and poor outcomes in adult ALL (71%), 1q44 (66%), 1q23.3 (54%), 11q23.3 (54%), 12p13.33 [1]. -
Genomic Alterations on 8P21-P23 Are the Most Frequent Genetic Events in Stage I Squamous Cell Carcinoma of the Lung
EXPERIMENTAL AND THERAPEUTIC MEDICINE 9: 345-350, 2015 Genomic alterations on 8p21-p23 are the most frequent genetic events in stage I squamous cell carcinoma of the lung JIUN KANG Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan 330-718, Republic of Korea Received April 23, 2014; Accepted October 31, 2014 DOI: 10.3892/etm.2014.2123 Abstract. Genetic alterations in the early stages of cancer genetic changes, and chromosomal aberrations are a hallmark have a close correlation with tumor initiation and poten- of cancer cells, occurring at a high prevalence in SCC. Although tially activate downstream pathways implicated in tumor a number of studies have been performed to evaluate genetic progression; however, the method of initiation in sporadic events associated with the development and progression of neoplasias is largely unknown. In this study, whole-genome SCC (2,3), the molecular mechanism remains to be uncovered, microarray-comparative genomic hybridization was and the identification of predictive markers is crucial. performed to identify the early genetic alterations that define Genetic alterations in the early stages of cancer have a the prognosis of patients with stage I squamous cell carcinoma close correlation with tumor initiation, and potentially activate (SCC) of the lung. The most striking finding was the high downstream pathways that are implicated in tumor progres- frequency of copy number losses and hemizygous deletions on sion. With the recent advances of computed tomographic chromosome 8p, which occurred in 94.7% (18/19) and 63.2% technology, the number of patients diagnosed with stage I (12/19) of the cases, respectively, with a delineated minimal lung SCC has been increasing (3). -
Robles JTO Supplemental Digital Content 1
Supplementary Materials An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma based on mRNA, microRNA and DNA Methylation Biomarkers Ana I. Robles1, Eri Arai2, Ewy A. Mathé1, Hirokazu Okayama1, Aaron Schetter1, Derek Brown1, David Petersen3, Elise D. Bowman1, Rintaro Noro1, Judith A. Welsh1, Daniel C. Edelman3, Holly S. Stevenson3, Yonghong Wang3, Naoto Tsuchiya4, Takashi Kohno4, Vidar Skaug5, Steen Mollerup5, Aage Haugen5, Paul S. Meltzer3, Jun Yokota6, Yae Kanai2 and Curtis C. Harris1 Affiliations: 1Laboratory of Human Carcinogenesis, NCI-CCR, National Institutes of Health, Bethesda, MD 20892, USA. 2Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan. 3Genetics Branch, NCI-CCR, National Institutes of Health, Bethesda, MD 20892, USA. 4Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan. 5Department of Chemical and Biological Working Environment, National Institute of Occupational Health, NO-0033 Oslo, Norway. 6Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), 08916 Badalona (Barcelona), Spain. List of Supplementary Materials Supplementary Materials and Methods Fig. S1. Hierarchical clustering of based on CpG sites differentially-methylated in Stage I ADC compared to non-tumor adjacent tissues. Fig. S2. Confirmatory pyrosequencing analysis of DNA methylation at the HOXA9 locus in Stage I ADC from a subset of the NCI microarray cohort. 1 Fig. S3. Methylation Beta-values for HOXA9 probe cg26521404 in Stage I ADC samples from Japan. Fig. S4. Kaplan-Meier analysis of HOXA9 promoter methylation in a published cohort of Stage I lung ADC (J Clin Oncol 2013;31(32):4140-7). Fig. S5. Kaplan-Meier analysis of a combined prognostic biomarker in Stage I lung ADC. -
Caractérisation De Nouveaux Gènes Et Polymorphismes Potentiellement Impliqués Dans Les Interactions Hôtes-Pathogènes
Aix-Marseille Université, Faculté de Médecine de Marseille Ecole Doctorale des Sciences de la Vie et de la Santé THÈSE DE DOCTORAT Présentée par Charbel ABOU-KHATER Date et lieu de naissance: 08-Juilllet-1990, Zahlé, LIBAN En vue de l’obtention du grade de Docteur de l’Université d’Aix-Marseille Mention: Biologie, Spécialité: Microbiologie Caractérisation de nouveaux gènes et polymorphismes potentiellement impliqués dans les interactions hôtes-pathogènes Publiquement soutenue le 5 Juillet 2017 devant le jury composé de : Pr. Daniel OLIVE Directeur de Thèse Pr. Brigitte CROUAU-ROY Rapporteur Dr. Benoît FAVIER Rapporteur Dr. Pierre PONTAROTTI Examinateur Thèse codirigée par Pr. Daniel OLIVE et Dr Laurent ABI-RACHED Laboratoires d’accueil URMITE Research Unit on Emerging Infectious and Tropical Diseases, UMR 6236, Faculty of Medicine, 27, Boulevard Jean Moulin, 13385 Marseille, France CRCM, Centre de Recherche en Cancérologie de Marseille,Inserm 1068, 27 Boulevard Leï Roure, BP 30059, 13273 Marseille Cedex 09, France 2 Acknowledgements First and foremost, praises and thanks to God, Holy Mighty, Holy Immortal, All-Holy Trinity, for His showers of blessings throughout my whole life and to whom I owe my very existence. Glory to the Father, and to the Son, and to the Holy Spirit: now and ever and unto ages of ages. I would like to express my sincere gratitude to my advisors Prof. Daniel Olive and Dr. Laurent Abi-Rached, for the continuous support, for their patience, motivation, and immense knowledge. Someday, I hope to be just like you. A special thanks to my “Godfather” who perfectly fulfilled his role, Dr. -
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[Inserm-00719917, V1] Integrated Analysis of Somatic Mutations and Focal Copy-Number Changes Identifies Key Genes and Pathways I
a Final target bases 46.2 Mb Target bases covered 43.3 Mb Percent target bases covered 93.81% Average depth 73.3 Median depth 70 Coverage at 25x 75.9% Coverage at 10x 87.0% Coverage at 4x 92.3% Coverage at 1x 96.0% b 100 75 50 25 Reads depth (X) depth Reads 0 1 2 3 4 5 6 7 8 9 5 6 2 10 11 12 13 14 1 1 17 18 19 20 21 2 X # Chromosome c 1.0 Author manuscript, published in "Nature Genetics 2012;44(6):694-8" 0.8 0.6 0.4 Coverage in target regions target in 0.2 Coveragex1 Coveragex4 Coveragex10 Coveragex25 0.0 1 2 3 4 5 6 7 8 9 5 8 1 4 7 8 1 4 10 11 12 13 14 1 16 17 1 19 20 2 22 23 2 25 26 2 28 29 30 31 32 33 34 35 36 37 3 39 40 4 42 43 4 45 46 47 48 # Exomes DOI : Supplementary Figure 1. Statistics of mapping of sequencing reads 10.1038/ng.2256 inserm-00719917, version 1 - 22 Jul 2012 a, summary statistics for whole-exome sequence reads of 24 HCC with their non tumor liver tissues. b, mean depth (with 95% IC) of reads on each chromosome, c, cumulative fraction of coding bases covered in captured regions. A 1-fold, 4-fold, 10-fold and 25- fold coverage were considered (mean with 95% IC) per exome (numbered #1-48). $ Bioinforma5cs$workflow$ Variant$calling$Tumor$ ! Variant$calling$Normal$ 1,775,892$variants$ $ Database$extrac5on$ ! dbSNP$ 1,577,724$$ 198,168$ $ background$known$polymorphisms$ $ Coding$SNPs/Indels$ (targeted$sequencing$of$exons)$ ! Intronic,$ 16,498$ UTR$ synonymous$$ 65,947$ variants$ non$coding$variants$ 44,172$nonsynonymous$ $coding$SNPs/Indels$ $ $ Quality$check$of$reads$ (Mean$size$±3SD,$Paired$end,$Phred$>=10,$$N>=$6)$ -
Effects of Sphingosine-1-Phosphate on Cell Viability, Differentiation, And
International Journal of Molecular Sciences Article Effects of Sphingosine-1-Phosphate on Cell Viability, Differentiation, and Gene Expression of Adipocytes Xiyuan Wu 1, Meena Kishore Sakharkar 1, Martin Wabitsch 2 and Jian Yang 1,* 1 Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada; [email protected] (X.W.); [email protected] (M.K.S.) 2 Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstr. 24, 89075 Ulm, Germany; [email protected] * Correspondence: [email protected] Received: 29 October 2020; Accepted: 4 December 2020; Published: 5 December 2020 Abstract: Sphingosine-1-phosphate (S1P) is a highly potent sphingolipid metabolite, which controls numerous physiological and pathological process via its extracellular and intracellular functions. The breast is mainly composed of epithelial cells (mammary gland) and adipocytes (stroma). Adipocytes play an important role in regulating the normal functions of the breast. Compared to the vast amount studies on breast epithelial cells, the functions of S1P in breast adipocytes are much less known. Thus, in the current study, we used human preadipocyte cell lines SGBS and mouse preadipocyte cell line 3T3-L1 as in vitro models to evaluate the effects of S1P on cell viability, differentiation, and gene expression in adipocytes. Our results showed that S1P increased cell viability in SGBS and 3T3-L1 preadipocytes but moderately reduced cell viability in differentiated SGBS and 3T3-L1 adipocytes. S1P was also shown to inhibit adipogenic differentiation of SGBS and 3T3-L1 at concentration higher than 1000 nM. -
This Thesis Has Been Submitted in Fulfilment of the Requirements for a Postgraduate Degree (E.G
This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. The use of multiple platform “omics” datasets to define new biomarkers in oral cancer and to determine biological processes underpinning heterogeneity of the disease Anas A M Saeed Thesis submitted for the degree of Doctor of Philosophy Edinburgh Dental Institute College of Medicine and Veterinary Medicine University of Edinburgh April 2013 Contents Table of Contents Declaration ................................................................................................................. xi Acknowledgements ................................................................................................... xii List of Abbreviations ............................................................................................. -
Francine Blumental De Abreu
VARIAÇÃO NO NÚMERO DE CÓPIAS GENÔMICAS NA AVALIAÇÃO DE GENES PRINCIPAIS DE PREDISPOSIÇÃO EM PACIENTES COM SÍNDROME DE MAMA-CÓLON TRIADOS PARA MUTAÇÕES NOS GENES BRCA1, BRCA2, TP53, CHEK2, MLH1 E MSH2 FRANCINE BLUMENTAL DE ABREU Tese apresentada à Fundação Antônio Prudente para obtenção do Título de Doutor em Ciências Área de concentração: Oncologia Orientadora: Profª Dra. Silvia Regina Rogatto São Paulo 2012 FICHA CATALOGRÁFICA Preparada pela Biblioteca da Fundação Antônio Prudente Abreu, Francine Blumental de Variação no número de cópias genômicas na avaliação de genes principais de predisposição em pacientes com síndrome de mama- cólon triados para mutações nos genes BRCA1, BRCA2, TP53, CHEK2, MLH1 E MSH2 / Francine Blumental de Abreu – São Paulo, 2012. 245p. Tese (Doutorado)-Fundação Antônio Prudente. Curso de Pós-Graduação em Ciências - Área de concentração: Oncologia. Orientadora: Silvia Regina Rogatto Descritores: 1. SÍNDROME DE LYNCH. 2. NEOPLASIAS DA MAMA. 3. VARIAÇÃO DO NÚMERO DE CÓPIA DO DNA. 4. HIBRIDIZAÇÃO GENÔMICA COMPARATIVA. DEDICATÓRIA A minha família!!!! AGRADECIMENTOS À minha família... Edilucia (II:5) e Antonio (II:6) por serem mais do que pais, por serem mais do que amigos, por serem os meus super heróis! Obrigada pelos abraços, pelas palavras de apoio e de ensinamento, pelo carinho, pelo amor incondicional! Obrigada por estarem sempre disponíveis, por estenderem as mãos depois de uma “rasteira” da vida, por enxugarem as minhas lágrimas! Obrigada principalmente por me fazerem acreditar que momentos difíceis existem,