DOCSLIB.ORG

A Prospective Screening of Gene Copy Number Variation in Brazilian

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Prospective Screening of Gene Copy Number Variation in Brazilian Pró-Reitoria Acadêmica Curso de Biomedicina Trabalho de Conclusão de Curso VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAIS EM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA Autora: Priscilla Orosco Taveira Orientador: Dr. Tulio Cesar de Lima Lins Brasília - DF 2015 1 PRISCILLA OROSCO TAVEIRA VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAIS EM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA Artigo apresentado ao curso de graduação em Biomedicina da Universidade Católica de Brasília como requisito parcial para obtenção do título de Bacharel em Biomedicina. Orientador: Dr. Tulio Cesar de Lima Lins Brasília 2015 2 Artigo de TCC II, de autoria Priscilla Orosco Taveira, intitulado “VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAISEM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA”, apresentado como requisito parcial para a obtenção do grau de Bacharel em Biomedicina da Universidade Católica de Brasília, em 24 de Setembro de 2015, defendida e aprovada pela banca examinadora abaixo assinada: ____________________________________________________ Orientador Dr. Tulio Cesar de Lima Lins Pós - doutorando em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília _____________________________________________________ Prof. Dra. Rosangela Vieira de Andrade Curso de Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília _____________________________________________________ Prof. Dra. Marcela Aparecida Chiabai Pós- doutoranda em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília BRASÍLIA 2015 3 Resumo As variantes do número de cópias (CNVs) representam um recurso importante de variação no genoma humano. Alguns genes envolvidos por CNVs são distribuídos de forma diferente entre os grupos de população humana entretanto é importante compreender a distribuição de CNV dentro e entre as populações especialmente naquelas com ascendência miscigenada, tais como as populações brasileiras. O objetivo do estudo foi investigar a variabilidade de um conjunto de CNVs incorporados a genes numa amostra da população brasileira. Os mesmos foram escolhidos com base em dados que mostram que eles possuem uma distribuição diferenciada na variação de cópia entre Africanos e Europeus. Quatro genes (POLRJ4, PCDHB13, NPEPPS e AMY1) foram investigados por qPCR em uma amostra de 96 brasileiros, previamente classificados por ascendência genética. O gene AMY1apresentou um número de cópias variáveis na gama de 1 a 8 cópias, em quanto que o NPEPPS variou de 1 a 5 cópias. A baixa variabilidade foi identificada pelos genes POLRJ4 e PCDHB13, mostrando duas cópias em frequência de 0,875 e 0,917, respectivamente. A ascendência genética não se correlacionou com o número de cópias dos genes AMY1 e NPEPPS. Os resultados proporcionaram uma visão ampla da frequência correspondente a variação do número de cópias do gene em uma amostra da população brasileira, atuando como referência para posteriores estudos genéticos da população o qual pode correlacionar esses polimorfismos com outras características fenotípicas. 4 Anexo 1. Artigo científico: A Prospective Screening of Gene Coy Number Variation in Brazilian Admixed Population Sample Autores: Dianny Elizabeth Jimenez, Tulio Cesar de Lima Lins, Priscilla Orosco Taveira e Rinaldo Wellerson Pereira Revista: Hereditary Genetics. Volume 3, Issue 1, p. 125. 31 Jan, 2014. ISSN:2161-1041. doi:10.4172/2161-1041.1000125 Jimenez et al., Hereditary Genet 2014, 3:1 Hereditary Genetics http://dx.doi.org/10.4172/2161-1041.1000125 Research Article Open Access A Prospective Screening of Gene Copy Number Variation in Brazilian Admixed Population Sample Dianny Elizabeth Jimenez¹, Tulio Cesar de Lima Lins², Priscilla Orosco Taveira¹, Rinaldo Wellerson Pereira¹,²* 1Programa de Pos-Graduaçao em Ciencias Genomicas e Biotecnologia, Universidade Catolica de Brasilia, Brasilia, DF, Brazil 2Programa de Pos-Graduacao em Patologia Molecular, Universidade de Brasilia, Brasilia, DF, Brazil Abstract Copy number variants (CNVs) represent an important source of variation in the human genome. Some CNVS embedded genes are differently distributed among the human population groups. Therefore, it is important to understand the distribution of CNV within and between populations, especially in those with admixed ancestry, such as the Brazilians. The aim of the study was to investigate the variability of a set of CNV-embedded genes in a sample of the Brazilian population. The CNV-embedded genes were chosen based on data showing that they have differential copy variation distribution between African and Europeans. Four genes (POLR2J4, PCDHB13, NPEPPS and AMY1) were investigated by qPCR in a sample of 96 Brazilians, previously classified by genetic ancestry. The gene AMY1 showed a variable copy numbers in the range of 1 to 8 copies whereas NPEPPS ranged from 1 to 5 copies. A low variability was identified for the POLR2J4 and PCDHB13 genes, showing 2 copies in frequency of 0.875 and 0.917, respectively. Genetic ancestry was not correlated to the number of copies of the AMY1and NPEPPS genes. The results provided an overview of the corresponding frequency of gene copy number variation in a sample of the Brazilian population, serving as reference for further genetic population studies, which may correlate these polymorphisms with other phenotypic features. Keywords: qPCR; CNV; POLR2J4; PCDHB13; NPEPPS; AMY1 Material and Methods Introduction Samples Copy number variations (CNVs) are deletions or duplications of The study analyzed DNA samples from 96 (51 men and 45 DNA segments of at least 1000 bases (1 kb) up to several Mb in size women) unrelated Brazilians. The European, African and Native present in a variable range of copy numbers when compared to a American genetic ancestry proportions were previously estimated reference genome [1-4]. Their occurrence is variable among human in the sample with 28 ancestry informative markers [28]. DNA from populations, making them a wide source of population differentiation peripheral blood was extracted by a saline precipitation method, and [5-7]. Copy number polymorphisms (CNPs) are CNVs with population the concentration and quality were determined with NanoDrop® ND-1000 Spectrophotometer (Thermo Scientific, USA). A unique frequencies of at least 1% [8-12]. sample with a high quantity DNA was selected as a calibrator sample CNVs play an important role over several genetic diseases for quality control in all qPCR reactions. All samples were taken with susceptibility, such as obesity, diabetes, cancer and neuropsychiatric the knowledge and consent of the donors, and the Ethic Committee of diseases [7,11-14]. In addition, the genetic heritability of non- Universidade Catolica de Brasilia approved the research protocol. pathological human traits can also be explained by CNVs [15-18]. For Copy number polymorphism estimation instance, adaptive evolution on chemosensation and immune response [19]. Patterns of copy number in salivary amylase gene have also a The four selected genes (AMY1, NPEPPS, PCDH-BETA13 and correlation with human populations with different dietary history, POLR2J4) are within CNV regions that were recognized as polymorphic, revealing an evolutionary selection for copy numbers in cultures with and their copy numbers were differently distributed in representative higher starch diets [20]. Thus, CNV may have exerted an important role populations of European, African and Asian ancestry in a previous in the evolution of physiological adaptations modeling the stratification study [7] and structural variants were accessed in the Database of of continental populations [2]. The literature describes CNVs loci Genomic Variants (DGV, http://dgv.tcag.ca/). showing significant copy number differences between different ethnic Custom TaqMan® copy numbers assays were acquired from Applied groups [14,21-24], including some that are population-specific [25,26]. Biosystems®/Life Technologies® (Table 1). As an endogenous control, a region with a known number of two copies in a human diploid genome, The use of Ancestry-Informative markers (SNPs and Indels polymorphism) has long been used to evaluate population stratification and admixture. It has been used to depict the Brazilian population as one of high heterogeneity, characterized by varying admixture from *Corresponding author: Rinaldo Wellerson Pereira, SGAN 916 Modulo B, “Bloco parental populations, such as European, African and Native Americans C” 2º Andar, Sala C-207 – Brasilia–DF, Brazil, CEP 70790-160, Tel: +55-61-3448- [27-29]. However, studies conducted in the Brazilian population 7222; Fax: +55-61-3347-4797; E-mail: rinaldo.pereira@catolica.edu.br evaluated CNV only as a source of pathological variation and, up to Received December 26, 2013; Accepted January 29, 2014; Published January the moment, no investigation considered general population samples 31, 2014 as a source of phenotypic variation, especially relating CNVs and Citation: Jimenez DE, de Lima Lins TC, Taveira PO, Pereira RW (2014) A genetic ancestry. In order to determine the polymorphism degree in Prospective Screening of Gene Copy Number Variation in Brazilian Admixed individuals from the Brazilian population, this study aimed to assess Population Sample. Hereditary Genet 3: 125. doi:10.4172/2161-1041.1000125 the copy number of the CNVs embedded genes AMY1, NPEPPS, Copyright: © 2014 Jimenez DE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits PCDHB13
Load more

Recommended publications
  • Homeobox Genes Gain Trimethylation of Histone H3 Lysine 4 in Glioblastoma Tissue
    Biosci. Rep. (2016) / 36 / art:e00347 / doi 10.1042/BSR20160028 Homeobox genes gain trimethylation of histone H3 lysine 4 in glioblastoma tissue Kun Luo*1, Donghui Luo† and Hao Wen‡1 *Department of Neurosurgery, Xinjiang Evidence-Based Medicine Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China †Department of Neurology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ‡State Key Laboratory Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China Synopsis Glioblastoma multiforme (GBM) exhibits considerable heterogeneity and associates with genome-wide alterations of the repressed chromatin marks DNA methylation and H3 lysine 27 trimethylation (H3K27me3). Tri-methylation on lysine 4 of histone H3 (H3K4me3) is an activating epigenetic mark that is enriched at promoter and promotes expression. It will be helpful in GBM diagnosis and treatment to identify the alteration of H3K4me3 between human GBM and GBM-surrounding tissues. Here, we performed an analysis using next-generation sequencing techniques to identify H3K4me3 modification in a case of GBM and the GBM-surrounding tissues. The results revealed a global decrease in H3K4me3 in GBM, especially at promoters and CpG islands. In GBM, homeobox genes gain H3K4me3, whereas the cell–cell adhesion-related cadherin genes lose H3K4me3. The products of the homeobox genes are highly connected with Ras-signalling and PI3K-Akt signalling pathways. Using The Cancer Genome Atlas (TCGA) data, we inferred the homeobox-regulated genes’ expression is higher in 548 GBM cases than in 27 lower grade glioma cases giving that OLIG2 expression can be a reference.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Assessing the Non-Genetic and Genetic Factors Affecting Refraction in the Aging Adult Population
    ASSESSING THE NON-GENETIC AND GENETIC FACTORS AFFECTING REFRACTION IN THE AGING ADULT POPULATION by Samantha Bomotti A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, MD January, 2018 ©2018 Samantha Bomotti All Rights Reserved Abstract Refractive errors are the most common form of visual impairment in the world, and are becoming an increasing public health burden as the world’s population ages. Refractive errors arise from changes in the shape of the eye, such as axial length and corneal curvature, or from aging of the lens. Refraction is a quantitative trait underlying refractive errors. The goal of this project was to investigate the non-genetic and genetic factors affecting refraction, a complex multifactorial trait, in the aging adult population. We used phenotypic data available from the population-based Beaver Dam Eye Study (BDES) consisting of 4,972 individuals aged 43-86 years at baseline to identify and characterize the association of nuclear sclerosis, among other factors, with refraction and changes in refraction. We then imputed exome array data in a subset of BDES participants to enhance our coverage of protein-coding regions and identify variants associated with refraction or either of its biological determinants, axial length and corneal curvature. Finally, we conducted a heritability analysis to determine whether the heritability of refraction varied by nuclear sclerosis severity, and to quantify the genetic or environmental influences shared between refraction and nuclear sclerosis. We determined nuclear cataract is the primary contributor to the myopic shift observed in older persons, as only those with nuclear cataract experienced a myopic shift while those without nuclear cataract did not.
    [Show full text]
  • A Co-Culture Genome-Wide Rnai Screen with Mammary Epithelial
    Burleigh et al. Breast Cancer Research (2015) 17:4 DOI 10.1186/s13058-014-0510-y RESEARCH ARTICLE Open Access A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation Angela Burleigh1, Steven McKinney1, Jazmine Brimhall1, Damian Yap1, Peter Eirew1, Steven Poon1, Viola Ng1, Adrian Wan1, Leah Prentice1,2, Lois Annab3, J Carl Barrett4, Carlos Caldas5, Connie Eaves6 and Samuel Aparicio1* Abstract Introduction: The extracellular signals regulating mammary epithelial cell growth are of relevance to understanding the pathophysiology of mammary epithelia, yet they remain poorly characterized. In this study, we applied an unbiased approach to understanding the functional role of signalling molecules in several models of normal physiological growth and translated these results to the biological understanding of breast cancer subtypes. Methods: We developed and utilized a cytogenetically normal clonal line of hTERT immortalized human mammary epithelial cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide small interfering RNA (siRNA) screen for evaluation of the functional effect of silencing each gene. Our selected endpoint was inhibition of growth. In rigorous postscreen validation processes, including quantitative RT-PCR, to ensure on-target silencing, deconvolution of pooled siRNAs and independent confirmation of effects with lentiviral short-hairpin RNA constructs, we identified a subset of genes required for mammary epithelialcellgrowth.Usingthree-dimensionalMatrigelgrowthand differentiation assays and primary human mammary epithelial cell colony assays, we confirmed that these growth effects were not limited to the 184-hTERT cell line. We utilized the METABRIC dataset of 1,998 breast cancer patients to evaluate both the differential expression of these genes across breast cancer subtypes and their prognostic significance.
    [Show full text]
  • Functional Test of PCDHB11, the Most Human-Specific Neuronal Surface Protein Guilherme Braga De Freitas, Rafaella Araújo Gonçalves and Matthias Gralle*
    de Freitas et al. BMC Evolutionary Biology (2016) 16:75 DOI 10.1186/s12862-016-0652-x RESEARCHARTICLE Open Access Functional test of PCDHB11, the most human-specific neuronal surface protein Guilherme Braga de Freitas, Rafaella Araújo Gonçalves and Matthias Gralle* Abstract Background: Brain-expressed proteins that have undergone functional change during human evolution may contribute to human cognitive capacities, and may also leave us vulnerable to specifically human diseases, such as schizophrenia, autism or Alzheimer’s disease. In order to search systematically for those proteins that have changed the most during human evolution and that might contribute to brain function and pathology, all proteins with orthologs in chimpanzee, orangutan and rhesus macaque and annotated as being expressed on the surface of cells in the human central nervous system were ordered by the number of human-specific amino acid differences that are fixed in modern populations. Results: PCDHB11, a beta-protocadherin homologous to murine cell adhesion proteins, stood out with 12 substitutions and maintained its lead after normalizing for protein size and applying weights for amino acid exchange probabilities. Human PCDHB11 was found to cause homophilic cell adhesion, but at lower levels than shown for other clustered protocadherins. Homophilic adhesion caused by a PCDHB11 with reversion of human- specific changes was as low as for modern human PCDHB11; while neither human nor reverted PCDHB11 adhered to controls, they did adhere to each other. A loss of function in PCDHB11 is unlikely because intra-human variability did not increase relative to the other human beta-protocadherins. Conclusions: The brain-expressed protein with the highest number of human-specific substitutions is PCDHB11.
    [Show full text]
  • Predict AID Targeting in Non-Ig Genes Multiple Transcription Factor
    Downloaded from http://www.jimmunol.org/ by guest on September 26, 2021 is online at: average * The Journal of Immunology published online 20 March 2013 from submission to initial decision 4 weeks from acceptance to publication Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes Jamie L. Duke, Man Liu, Gur Yaari, Ashraf M. Khalil, Mary M. Tomayko, Mark J. Shlomchik, David G. Schatz and Steven H. Kleinstein J Immunol http://www.jimmunol.org/content/early/2013/03/20/jimmun ol.1202547 Submit online. Every submission reviewed by practicing scientists ? is published twice each month by http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://www.jimmunol.org/content/suppl/2013/03/20/jimmunol.120254 7.DC1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 26, 2021. Published March 20, 2013, doi:10.4049/jimmunol.1202547 The Journal of Immunology Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes Jamie L. Duke,* Man Liu,†,1 Gur Yaari,‡ Ashraf M. Khalil,x Mary M. Tomayko,{ Mark J. Shlomchik,†,x David G.
    [Show full text]
  • Thousands of Cpgs Show DNA Methylation Differences in ACPA-Positive Individuals
    G C A T T A C G G C A T genes Article Thousands of CpGs Show DNA Methylation Differences in ACPA-Positive Individuals Yixiao Zeng 1,2, Kaiqiong Zhao 2,3, Kathleen Oros Klein 2, Xiaojian Shao 4, Marvin J. Fritzler 5, Marie Hudson 2,6,7, Inés Colmegna 6,8, Tomi Pastinen 9,10, Sasha Bernatsky 6,8 and Celia M. T. Greenwood 1,2,3,9,11,* 1 PhD Program in Quantitative Life Sciences, Interfaculty Studies, McGill University, Montréal, QC H3A 1E3, Canada; yixiao.zeng@mail.mcgill.ca 2 Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada; kaiqiong.zhao@mail.mcgill.ca (K.Z.); kathleen.klein@mail.mcgill.ca (K.O.K.); marie.hudson@mcgill.ca (M.H.) 3 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC H3A 1A2, Canada 4 Digital Technologies Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, Canada; xiaojian.shao@nrc-cnrc.gc.ca 5 Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada; fritzler@ucalgary.ca 6 Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada; ines.colmegna@mcgill.ca (I.C.); sasha.bernatsky@mcgill.ca (S.B.) 7 Division of Rheumatology, Jewish General Hospital, Montréal, QC H3T 1E2, Canada 8 Division of Rheumatology, McGill University, Montréal, QC H3G 1A4, Canada 9 Department of Human Genetics, McGill University, Montréal, QC H3A 0C7, Canada; tomi.pastinen@mcgill.ca 10 Center for Pediatric Genomic Medicine, Children’s Mercy, Kansas City, MO 64108, USA 11 Gerald Bronfman Department of Oncology, McGill University, Montréal, QC H4A 3T2, Canada * Correspondence: celia.greenwood@mcgill.ca Citation: Zeng, Y.; Zhao, K.; Oros Abstract: High levels of anti-citrullinated protein antibodies (ACPA) are often observed prior to Klein, K.; Shao, X.; Fritzler, M.J.; Hudson, M.; Colmegna, I.; Pastinen, a diagnosis of rheumatoid arthritis (RA).
    [Show full text]
  • Family-Based Whole Exome Sequencing of Atopic Dermatitis Complicated with Cataracts
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 35), pp: 59446-59454 Research Paper Family-based whole exome sequencing of atopic dermatitis complicated with cataracts Wenxin Luo1,*, Wangdong Xu2,*, Lin Xia3, Dan Xie3, Lin Wang4, Zaipei Guo5, Yue Cheng1, Yi Liu2 and Weimin Li1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China 2Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China 3State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China 4Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China 5Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China *Wenxin Luo and Wangdong Xu contributed equally to this work, and should be considered as the co-first author Correspondence to: Weimin Li, email: weimin003@163.com Keywords: atopic dermatitis, cataracts, mutation Received: November 07, 2016 Accepted: June 02, 2017 Published: July 31, 2017 Copyright: Luo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Atopic dermatitis (AD) is a common skin disorder with elevated prevalence. Cataract induced by AD rarely occurs in adolescent and young adult patients, which is also called atopic cataract. Using whole exome sequencing, we aimed to explore genetic alterations among AD and atopic cataract. Result: We recruited a 19 year-old Chinese male with AD accompanied with cataracts, his father with AD and his mother without AD or cataract.
    [Show full text]
  • Gene Expression Profile and Genomic Alterations in Colonic Tumours
    Femia et al. BMC Cancer 2010, 10:194 http://www.biomedcentral.com/1471-2407/10/194 RESEARCH ARTICLE Open Access Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats Angelo Pietro Femia1, Cristina Luceri1, Simona Toti1, Augusto Giannini2, Piero Dolara1, Giovanna Caderni1* Abstract Background: Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. Methods: For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Results: Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFa/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated.
    [Show full text]
  • Whole-Transcriptome Analysis of Fully Viable Energy Efficient Glycolytic
    CANCER GENOMICS & PROTEOMICS 17 : 469-497 (2020) doi:10.21873/cgp.20205 Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase ELIZABETH MAZZIO 1, RAMESH BADISA 1, NZINGA MACK 1, SHAMIR CASSIM 2, MASA ZDRALEVIC 3# , JACQUES POUYSSEGUR 2,3 and KARAM F.A. SOLIMAN 1 1College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, U.S.A.; 2Department of Medical Biology, Centre Scientifique de Monaco, Monaco, Monaco; 3University Côte d'Azur, IRCAN, CNRS, Centre A. Lacassagne, Nice, France Abstract. Background/Aim: Nearly all mammalian tumors viability. These findings show a high biochemical energy of diverse tissues are believed to be dependent on efficiency as measured by ATP in glycolysis-null cells. Next, fermentative glycolysis, marked by elevated production of transcriptomic analysis conducted on 48,226 mRNA lactic acid and expression of glycolytic enzymes, most notably transcripts reflect 273 differentially expressed genes (DEGS) lactic acid dehydrogenase (LDH). Therefore, there has been in the GPI KO clone set, 193 DEGS in the LDHA/B DKO significant interest in developing chemotherapy drugs that clone set with 47 DEGs common to both KO clones. selectively target various isoforms of the LDH enzyme. Glycolytic-null cells reflect up-regulation in gene transcripts However, considerable questions remain as to the typically associated with nutrient deprivation / fasting and consequences of biological ablation of LDH or upstream possible use of fats for energy: thioredoxin interacting protein targeting of the glycolytic pathway. Materials and Methods: (TXNIP), mitochondrial 3-hydroxy-3-methylglutaryl-CoA In this study, we explore the biochemical and whole synthase 2 (HMGCS2), PPAR γ coactivator 1 α ( PGC-1 α), transcriptomic effects of CRISPR-Cas9 gene knockout (KO) and acetyl-CoA acyltransferase 2 (ACAA2).
    [Show full text]
  • Author Affiliations
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.16.452676; this version posted July 16, 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. Tirtakusuma et al. Lineage switching in MLL-AF4 leukaemias 1 Epigenetic regulator genes direct lineage switching in MLL-AF4 leukaemia 2 Ricky Tirtakusuma1, Katarzyna Szoltysek1,2,3, Paul Milne4, Vasily V Grinev5, Anetta Ptasinska6, 3 Claus Meyer7, Sirintra Nakjang1, Jayne Y Hehir-Kwa2, Daniel Williamson1, Pierre Cauchy6, 4 Salam A Assi6, Maria R Imperato6, Fotini Vogiatzi9, Shan Lin10, Mark Wunderlich10, Janine 5 Stutterheim2, Alexander Komkov8, Elena Zerkalenkova8, Paul Evans11, Hesta McNeill1, Alex 6 Elder1, Natalia Martinez-Soria1, Sarah E Fordham1, Yuzhe Shi1, Lisa J Russell1, Deepali Pal1, 7 Alex Smith12, Zoya Kingsbury13, Jennifer Becq13, Cornelia Eckert14, Oskar A Haas15, Peter 8 Carey16, Simon Bailey1,16, Roderick Skinner1,16, Natalia Miakova8, Matthew Collin4, Venetia 9 Bigley4, Muzlifa Haniffa17,18,19, Rolf Marschalek7, Christine J Harrison1, Catherine A Cargo11, 10 Denis Schewe9, Yulia Olshanskaya8, Michael J Thirman20, Peter N Cockerill6, James C 11 Mulloy10, Helen J Blair1, Josef Vormoor1,2, James M Allan1, Constanze Bonifer6*, Olaf 12 Heidenreich1,2*†, Simon Bomken1,16*† 13 Author Affiliations 14 1Wolfson Childhood Cancer Research Centre, Centre for Cancer, Translational and Clinical 15 Research Institute, Newcastle University, Newcastle upon Tyne, UK 16 2Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands 17 3Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland 18 4Translational and Clinical Research Institute, Newcastle University, Framlington Place, 19 Newcastle upon Tyne, UK 20 5Department of Genetics, the Faculty of Biology, Belarusian State University, 220030 Minsk, 21 Republic of Belarus.
    [Show full text]