DOCSLIB.ORG

Identification of Uncommon Recurrent Potocki-Lupski Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Identification of Uncommon Recurrent Potocki-Lupski Syndrome Please cite this article in press as: Zhang et al., Identification of Uncommon Recurrent Potocki-Lupski Syndrome-Associated Duplications and the Distribution of Rearrangement Types and Mechanisms in..., The American Journal of Human Genetics (2010), doi:10.1016/j.ajhg.2010.02.001 REPORT Identification of Uncommon Recurrent Potocki-Lupski Syndrome-Associated Duplications and the Distribution of Rearrangement Types and Mechanisms in PTLS Feng Zhang,1,8 Lorraine Potocki,1,3 Jacinda B. Sampson,4 Pengfei Liu,1 Amarilis Sanchez-Valle,1 Patricia Robbins-Furman,1 Alicia Delicado Navarro,5 Patricia G. Wheeler,6 J. Edward Spence,7 Campbell K. Brasington,7 Marjorie A. Withers,1 and James R. Lupski1,2,3,* Nonallelic homologous recombination (NAHR) can mediate recurrent rearrangements in the human genome and cause genomic disor- ders. Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders associated with a 3.7 Mb deletion and its reciprocal duplication in 17p11.2, respectively. In addition to these common recurrent rearrangements, an uncommon recurrent 5 Mb SMS-associated deletion has been identified. However, its reciprocal duplication predicted by the NAHR mechanism had not been identified. Here we report the molecular assays on 74 subjects with PTLS-associated duplications, 35 of whom are newly investi- gated. By both oligonucleotide-based comparative genomic hybridization and recombination hot spot analyses, we identified two cases of the predicted 5 Mb uncommon recurrent PTLS-associated duplication. Interestingly, the crossovers occur in proximity to a recently delineated allelic homologous recombination (AHR) hot spot-associated sequence motif, further documenting the common hot spot features shared between NAHR and AHR. An additional eight subjects with nonrecurrent PTLS duplications were identified. The smallest region of overlap (SRO) for all of the 74 PTLS duplications examined is narrowed to a 125 kb interval containing only RAI1, a gene recently further implicated in autism. Sequence complexities consistent with DNA replication-based mechanisms were identified in four of eight (50%) newly identified nonrecurrent PTLS duplications. Our findings of the uncommon recurrent PTLS-associated dupli- cation at a relative prevalence reflecting the de novo mutation rate and the distribution of 17p11.2 duplication types in PTLS reveal insights into both the contributions of new mutations and the different underlying mechanisms that generate genomic rearrangements causing genomic disorders. Potocki-Lupski syndrome (PTLS [MIM 610883]) is a of the human chromosome 17 (17p), rendering 17p recently recognized, 17p11.2 duplication-associated con- susceptible to genomic instability and genomic rearrange- dition with clinical features including infantile hypotonia, ments.10 In addition to the common deletion and duplica- failure to thrive, mental retardation, autism, behavioral tion rearrangements associated with SMS and PTLS, respec- abnormalities, sleep apnea, and structural cardiovascular tively, another recurrent 17p deletion that occurs less anomalies.1,2 The 3.7 Mb common type of PTLS-associated frequently than the common SMS deletion, i.e., an duplication is reciprocal to a common 17p11.2 deletion uncommon recurrent SMS deletion, has been observed to observed in association with Smith-Magenis syndrome result from NAHR utilizing alternative LCR substrates (SMS [MIM 182290]).3 Our previous molecular studies LCR17pA and LCR17pD (Figure 1).11,12 The NAHR mecha- demonstrated that these common duplication and deletion nism predicts a reciprocal duplication to this uncommon rearrangements are caused by the nonallelic homologous recurrent SMS deletion. Interestingly, evidence from recombination (NAHR) between the paralogous sequence sperm-based assays has revealed that this uncommon repeats, distal and proximal SMS-REPs (Figure 1).4–6 These recurrent 17p duplication occurs de novo at a frequency long (>200 kb) repeat sequences with high similarity of 8.74 3 10À7 in male gametes,13 suggesting its potential (>97%), i.e., low-copy repeats (LCRs) or segmental duplica- existence in live-born individuals. However, this specific tions (SDs), are vulnerable to NAHR.7–9 NAHR between duplication type, which is uncommon but predicted to direct LCRs or SDs can lead to reciprocal deletion and dupli- be recurrent, has never been detected in the PTLS subjects cation, whereas inversion of a genomic segment can occur of our previous investigations or in those of other groups. when flanking inverted LCRs act as substrates.7,8 NAHR- In this study we report two subjects with the uncommon associated events can result in recurrent rearrangements recurrent PTLS duplication, demonstrate the anticipated with a common size and clustered breakpoints.8 NAHR mechanism, show the proximity of the specific Serial segmental duplications during primate evolution strand exchanges to a recently described homologous led to the complex genomic architecture of the short arm recombination (HR) ‘‘hot spot’’ motif, determine the size 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; 2Department of Pediatrics, Baylor College of Medi- cine, Houston, TX 77030, USA; 3Texas Children’s Hospital, Houston, TX 77030, USA; 4Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA; 5Seccio´n de Gene´tica Me´dica, Hospital Universitario La Paz, 28046 Madrid, Spain; 6Division of Genetics and Metabolism, Nemours Children’s Clinic, Orlando, FL 32806, USA; 7Clinical Genetics, Levine Children’s Hospital at Carolinas Medical Center, Charlotte, NC 28232, USA; 8State Key Labo- ratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China *Correspondence: [email protected] DOI 10.1016/j.ajhg.2010.02.001. ª2010 by The American Society of Human Genetics. All rights reserved. The American Journal of Human Genetics 86, 1–9, March 12, 2010 1 AJHG 582 Please cite this article in press as: Zhang et al., Identification of Uncommon Recurrent Potocki-Lupski Syndrome-Associated Duplications and the Distribution of Rearrangement Types and Mechanisms in..., The American Journal of Human Genetics (2010), doi:10.1016/j.ajhg.2010.02.001 Figure 1. Identification of Two 5 Mb Uncommon +2 Recurrent PTLS-Associated Duplications uncommon +1 High-resolution oligonucleotide aCGH analyses re- SMS del 0 vealed the recurrent SMS- and PTLS-associated rear- ~5 Mb -1 rangements mediated by NAHR between the LCRs -2 on 17p. The following abbreviations are used: dele- tion, del; duplication, dup. The green (loss), black +2 (no change), and red (gain) dots show the relative common +1 intensities in log2ratio (deviation from horizontal SMS del 0 line of zero) and genomic locations of the oligonu- ~3.7 Mb -1 cleotide probes employed in our aCGH assay. -2 The regions that lack unique probes correspond to 15.0 Mb 16.0 Mb 17.1 Mb 18.2 Mb 19.2 Mb 20.3 Mb 21.4 Mb the LCRs. The 3.7 Mb common rearrangements are didistal t l SMSSMS-REP REP middleiddl SMSSMS-REP REP proximal i l SMSSMS-REP REP 17p mediated by the distal and proximal SMS-REPs de- LCR17pA RAI1 LCR17pD picted on the horizontal black lines representing proximal chromosome 17p, whereas the recombina- +2 +1 tions between LCR17pA and LCR17pD lead to the common PTLS dup 0 5 Mb uncommon recurrent rearrangements. The regions with copy number gains are indicated with ~3.737Mb Mb -1 red horizontal bars, and the losses are shown in -2 green. The known copy number polymorphisms uncommon +2 are indicated by arrows. PTLS dup ~5 Mb +1 BAB 2808 0 -1 -2 identified two subjects (2808 and 2959) with +2 copy number gain of the 5 Mb region located +1 BAB 2959 0 between LCR17pA and LCR17pD. These find- -1 ings are consistent with the predicted -2 uncommon recurrent 17p duplication (Fig- ure 1). This duplicated region includes the RAI1 (retinoic acid inducible 1 [MIM 607642]) distribution and type of PTLS-associated duplications, and gene that is responsible for SMS, as evidenced by deletion furthermore glean insights into the contribution of de mapping,15 and loss-of-function point mutations in non- novo mutations and different rearrangement mechanisms deletion patients.16 RAI1 is also considered to be the prime to genomic disorders. candidate dosage-sensitive gene causing PTLS, based upon mouse experiments that rescue the majority of the duplica- Identification of 5 Mb Uncommon Recurrent tion-associated phenotype by restoring this gene to PTLS-Associated Duplication disomic (n ¼ 2) copy number in the segmental trisomy To investigate the hypothesis that the reciprocal duplica- model.17 This interval also encompasses the entire tion to the uncommon recurrent SMS deletion can also 3.7 Mb region of the common PTLS duplication (Figure 1). lead to PTLS and to study the size distribution of the PTLS-associated duplications in 17p, we designed a high- NAHR Hot Spot Analyses of Uncommon Recurrent density oligonucleotide-based microarray for comparative PTLS-Associated Duplication genomic hybridization (CGH) assay to finely examine Recurrent deletion and duplication rearrangements result the location, size, genomic content, and breakpoint from NAHR between LCR substrate pairs.7,8 Notably, NAHR interval of the PTLS-associated 17p rearrangements. This strand exchanges are not randomly distributed across the array is based on the Agilent 4 3 44K format. Approxi- homologous LCR regions but occur predominantly within
Load more

Recommended publications
  • Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17P11.2 and the Syntenic Region of the Mouse
    Downloaded from genome.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Article Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17p11.2 and the Syntenic Region of the Mouse Weimin Bi,1,6 Jiong Yan,1,6 Paweł Stankiewicz,1 Sung-Sup Park,1,7 Katherina Walz,1 Cornelius F. Boerkoel,1 Lorraine Potocki,1,3 Lisa G. Shaffer,1 Koen Devriendt,4 Małgorzata J.M. Nowaczyk,5 Ken Inoue,1 and James R. Lupski1,2,3,8 Departments of 1Molecular & Human Genetics, 2Pediatrics, Baylor College of Medicine, 3Texas Children’s Hospital, Houston, Texas 77030, USA; 4Centre for Human Genetics, University Hospital Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium; 5Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4J9, Canada Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same ∼4 Mb interstitial genomic deletion within chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we constructed BAC/PAC contigs covering the SMS common deletion interval and its syntenic region on mouse chromosome 11. Comparative genome analysis reveals the absence of all three ∼200-kb SMS-REP low-copy repeats in the mouse and indicates that the evolution of SMS-REPs was accompanied by transposition of adjacent genes. Physical and genetic map comparisons in humans reveal reduced recombination in both sexes. Moreover, by examining the deleted regions in SMS patients with unusual-sized deletions, we refined the minimal Smith-Magenis critical region (SMCR) to an ∼1.1-Mb genomic interval that is syntenic to an ∼1.0-Mb region in the mouse.
    [Show full text]
  • Genetic Diagnosis and Respiratory Management Of
    UITNODIGING GENETIC DIAGNOSIS Voor het bijwonen van de openbare verdediging van AND RESPIRATORY het proefschrift Genetic diagnosis and respiratory management of primary ciliary dyskinesia dyskinesia ciliary of primary management respiratory and diagnosis Genetic GENETIC DIAGNOSIS MANAGEMENT OF AND RESPIRATORY MANAGEMENT OF PRIMARY CILIARY PRIMARY CILIARY DYSKINESIA DYSKINESIA Door Tamara Paff Tamara Paff dinsdag 7 november 2017 11:45 uur in de aula van de Vrije Universiteit de Boelelaan, 1105 TE Amsterdam Receptie aansluitend in Grand cafe The Basket op de VU campus Tamara Paff Johann Keplerstraat 8-1 hoog 1098 HL, Amsterdam +31645364292/ [email protected] Tamara Paff Tamara | Paranimfen Marian van der Meij [email protected] 06-15500488 Marc van der Schee [email protected] 06-40883602 14759 - Paff_R11,5_OMS_DEF.indd 1 25-09-17 10:25 UITNODIGING GENETIC DIAGNOSIS Voor het bijwonen van de openbare verdediging van AND RESPIRATORY het proefschrift Genetic diagnosis and respiratory management of primary ciliary dyskinesia dyskinesia ciliary of primary management respiratory and diagnosis Genetic GENETIC DIAGNOSIS MANAGEMENT OF AND RESPIRATORY MANAGEMENT OF PRIMARY CILIARY PRIMARY CILIARY DYSKINESIA DYSKINESIA Door Tamara Paff Tamara Paff Dag datum tijdstip in de aula van de Vrije Universiteit de Boelelaan, 1105 TE Amsterdam Receptie aansluitend in Grand cafe The Basket op de VU campus Tamara Paff Johann Keplerstraat 8-1 hoog 1098 HL, Amsterdam +31645364292/ [email protected] Tamara Paff Tamara Paranimfen Marian van der Meij | [email protected] 06-15500488 Marc van der Schee [email protected] 06-40883602 14759_TPaff_BW.indd 1 19-09-17 13:08 ProefschriftTamaraPaff_Cover+Bladwijzer.indd All Pages 15-08-17 12:47 The studies performed in this thesis were financially supported by the PCD support group (PCD belangengroep), Fonds NutsOhra, the “Dutch mudder” team and Chiesi.
    [Show full text]
  • TCTE1 Is a Conserved Component of the Dynein Regulatory Complex and Is Required for Motility and Metabolism in Mouse Spermatozoa
    TCTE1 is a conserved component of the dynein PNAS PLUS regulatory complex and is required for motility and metabolism in mouse spermatozoa Julio M. Castanedaa,b,1, Rong Huac,d,1, Haruhiko Miyatab, Asami Ojib,e, Yueshuai Guoc,d, Yiwei Chengc,d, Tao Zhouc,d, Xuejiang Guoc,d, Yiqiang Cuic,d, Bin Shenc, Zibin Wangc, Zhibin Huc,f, Zuomin Zhouc,d, Jiahao Shac,d, Renata Prunskaite-Hyyrylainena,g,h, Zhifeng Yua,i, Ramiro Ramirez-Solisj, Masahito Ikawab,e,k,2, Martin M. Matzuka,g,i,l,m,n,2, and Mingxi Liuc,d,2 aDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; bResearch Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan; cState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People’s Republic of China; dDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210029, People’s Republic of China; eGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan; fAnimal Core Facility of Nanjing Medical University, Nanjing 210029, People’s Republic of China; gCenter for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030; hFaculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland; iCenter for Drug Discovery, Baylor College of Medicine, Houston, TX 77030; jWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; kThe Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan; lDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; mDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and nDepartment of Pharmacology, Baylor College of Medicine, Houston, TX 77030 Contributed by Martin M.
    [Show full text]
  • Genomic Organization of the Approximately 1.5 Mb Smith
    European Journal of Human Genetics (2001) 9, 892 ± 902 ã 2001 Nature Publishing Group All rights reserved 1018-4813/01 $15.00 www.nature.com/ejhg ARTICLE Genomic organisation of the ~1.5 Mb Smith-Magenis syndrome critical interval: Transcription map, genomic contig, and candidate gene analysis Rebecca E Lucas1, Christopher N Vlangos1, Parimal Das4, Pragna I Patel4 and Sarah H Elsea*,1,2,3 1Genetics Graduate Program, Michigan State University, East Lansing, Michigan, MI 48824, USA; 2Department of Zoology, Michigan State University, East Lansing, Michigan, MI 48824, USA; 3Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, MI 48824, USA; 4Department of Neurology, Baylor College of Medicine, Houston, Texas, TX 77030, USA Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with an interstitial deletion of chromosome 17 involving band p11.2. SMS is hypothesised to be a contiguous gene syndrome in which the phenotype arises from the haploinsufficiency of multiple, functionally-unrelated genes in close physical proximity, although the true molecular basis of SMS is not yet known. In this study, we have generated the first overlapping and contiguous transcription map of the SMS critical interval, linking the proximal 17p11.2 region near the SMS-REPM and the distal region near D17S740 in a minimum tiling path of 16 BACs and two PACs. Additional clones provide greater coverage throughout the critical region. Not including the repetitive sequences that flank the critical interval, the map is comprised of 13 known genes, 14 ESTs, and six genomic markers, and is a synthesis of Southern hybridisation and polymerase chain reaction data from gene and marker localisation to BACs and PACs and database sequence analysis from the human genome project high-throughput draft sequence.
    [Show full text]
  • Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways
    biomolecules Article Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways Aayushi Srivastava 1,2,3,4 , Abhishek Kumar 1,5,6 , Sara Giangiobbe 1, Elena Bonora 7, Kari Hemminki 1, Asta Försti 1,2,3 and Obul Reddy Bandapalli 1,2,3,* 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; [email protected] (A.S.); [email protected] (A.K.); [email protected] (S.G.); [email protected] (K.H.); [email protected] (A.F.) 2 Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany 3 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany 4 Medical Faculty, Heidelberg University, D-69120 Heidelberg, Germany 5 Institute of Bioinformatics, International Technology Park, Bangalore 560066, India 6 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India 7 S.Orsola-Malphigi Hospital, Unit of Medical Genetics, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6221-42-1709 Received: 29 August 2019; Accepted: 10 October 2019; Published: 13 October 2019 Abstract: Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family.
    [Show full text]
  • PCM1 Is Necessary for Focal Ciliary Integrity and Is a Candidate for Severe Schizophrenia
    ARTICLE https://doi.org/10.1038/s41467-020-19637-5 OPEN PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia Tanner O. Monroe 1,2, Melanie E. Garrett3, Maria Kousi4, Ramona M. Rodriguiz5,6, Sungjin Moon7, Yushi Bai8, Steven C. Brodar8, Karen L. Soldano3, Jeremiah Savage9, Thomas F. Hansen10,11, Donna M. Muzny12,13, Richard A. Gibbs12,13, Lawrence Barak8, Patrick F. Sullivan14,15,16, Allison E. Ashley-Koch 3, ✉ Akira Sawa 17,18,19,20, William C. Wetsel 5,6,8,21, Thomas Werge 10,11,22,23 & Nicholas Katsanis 1,2 1234567890():,; The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, psychomotor, and cognitive abnormalities. RNAseq reveals changes in amine- and G-protein coupled receptor pathways. The physiological relevance of this phenotype is supported by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to rescue adult behavioral defects. Immunoprecipitations show an association with Pcm1 and D2Rs. Finally, we sequence PCM1 in two human cohorts with severe schizophrenia. Systematic modeling of all discovered rare alleles by zebrafish in vivo complementation reveals an enrichment for pathogenic alleles. Our data emphasize a role for the pericentriolar material in the postnatal brain, with progressive degenerative ciliary and behavioral phenotypes; and they support a contributory role for PCM1 in some individuals diagnosed with schizophrenia. 1 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
    [Show full text]
  • Attractor Molecular Signatures and Their Applications for Prognostic Biomarkers Wei-Yi Cheng
    Attractor Molecular Signatures and Their Applications for Prognostic Biomarkers Wei-Yi Cheng Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy of the Graduate School of Arts and Science COLUMBIA UNIVERSITY 2014 c 2013 Wei-Yi Cheng All rights reserved ABSTRACT Attractor Molecular Signatures and Their Applications for Prognostic Biomarkers Wei-Yi Cheng This dissertation presents a novel data mining algorithm identifying molecular sig- natures, called attractor metagenes, from large biological data sets. It also presents a computational model for combining such signatures to create prognostic biomarkers. Us- ing the algorithm on multiple cancer data sets, we identified three such gene co-expression signatures that are present in nearly identical form in different tumor types represent- ing biomolecular events in cancer, namely mitotic chromosomal instability, mesenchymal transition, and lymphocyte infiltration. A comprehensive experimental investigation us- ing mouse xenograft models on the mesenchymal transition attractor metagene showed that the signature was expressed in the human cancer cells, but not in the mouse stroma. The attractor metagenes were used to build the winning model of a breast cancer prog- nosis challenge. When applied on larger data sets from 12 different cancer types from The Cancer Genome Atlas \Pan-Cancer" project, the algorithm identified additional pan-cancer molecular signatures, some of which involve methylation sites, microRNA expression, and protein activity. Contents List of Figures iv List of Tables vi 1 Introduction 1 1.1 Background . 1 1.2 Previous Work on Identifying Cancer-Related Gene Signatures . 3 1.3 Contributions of the Thesis . 9 2 Attractor Metagenes 11 2.1 Derivation of an Attractor Metagene .
    [Show full text]
  • The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights Into Cell Differentiation and Function
    International Journal of Molecular Sciences Article The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function Yashwanth Subbannayya 1 , Markus Haug 1, Sneha M. Pinto 1, Varshasnata Mohanty 2, Hany Zakaria Meås 1, Trude Helen Flo 1, T.S. Keshava Prasad 2 and Richard K. Kandasamy 1,* 1 Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway; [email protected] (Y.S.); [email protected] (M.H.); [email protected] (S.M.P.); [email protected] (H.Z.M.); trude.fl[email protected] (T.H.F.) 2 Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore 575018, India; [email protected] (V.M.); [email protected] (T.S.K.P.) * Correspondence: [email protected] Abstract: CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells.
    [Show full text]
  • Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
    Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo
    [Show full text]
  • Downloaded from Ftp://Ftp.Uniprot.Org/ on July 3, 2019) Using Maxquant (V1.6.10.43) Search Algorithm
    bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.385096; this version posted November 17, 2020. 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-ND 4.0 International license. The proteomic landscape of resting and activated CD4+ T cells reveal insights into cell differentiation and function Yashwanth Subbannayya1, Markus Haug1, Sneha M. Pinto1, Varshasnata Mohanty2, Hany Zakaria Meås1, Trude Helen Flo1, T.S. Keshava Prasad2 and Richard K. Kandasamy1,* 1Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway 2Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India *Correspondence to: Professor Richard Kumaran Kandasamy Norwegian University of Science and Technology (NTNU) Centre of Molecular Inflammation Research (CEMIR) PO Box 8905 MTFS Trondheim 7491 Norway E-mail: [email protected] (Kandasamy R K) Tel.: +47-7282-4511 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.385096; this version posted November 17, 2020. 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-ND 4.0 International license. Abstract CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells.
    [Show full text]
  • Evolution and Diversity of Copy Number Variation in the Great Ape Lineage
    Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Evolution and diversity of copy number variation in the great ape lineage Peter H. Sudmant1, John Huddleston1,7, Claudia R. Catacchio2, Maika Malig1, LaDeana W. Hillier3, Carl Baker1, Kiana Mohajeri1, Ivanela Kondova4, Ronald E. Bontrop4, Stephan Persengiev4, Francesca Antonacci2, Mario Ventura2, Javier Prado-Martinez5, Tomas 5,6 1,7 Marques-Bonet , and Evan E. Eichler 1. Department of Genome Sciences, University of Washington, Seattle, WA, USA 2. University of Bari, Bari, Italy 3. The Genome Institute, Washington University School of Medicine, St. Louis, MO, USA 4. Department of Comparative Genetics, Biomedical Primate Research Centre, Rijswijk, The Netherlands 5. Institut de Biologia Evolutiva, (UPF-CSIC) Barcelona, Spain 6. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain 7. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA Correspondence to: Evan Eichler Department of Genome Sciences University of Washington School of Medicine Foege S-413A, Box 355065 3720 15th Ave NE Seattle, WA 98195 E-mail: [email protected] 1 Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Copy number variation (CNV) contributes to the genetic basis of disease and has significantly restructured the genomes of humans and great apes. The diversity and rate of this process, however, has not been extensively explored among the great ape lineages. We analyzed 97 deeply sequenced great ape and human genomes and estimate that 16% (469 Mbp) of the hominid genome has been affected by recent copy number changes.
    [Show full text]
  • Notch-Mediated Expansion of Cord Blood Progenitors
    Letters to the Editor 1948 patient number places some limitation on interpretation, there is a REFERENCES suggestion that this treatment could still be considered for patients 1 Auner HW, Szydlo R, Rone A, Chaidos A, Giles C, Kanfer E et al. Salvage autologous who may have not previously been referred for auto-HCT but who stem cell transplantation for multiple myeloma relapsing or progressing after up- now have relapsed disease. front autologous transplantation. Leuk Lymphoma 2013; 54: 2200–2204. Our adaptive study design ultimately determined that the 2 Shah N, Ahmed F, Bashir Q, Qureshi S, Dinh Y, Rondon G et al. Durable remission highest doses of lenalidomide (75 and 100 mg) were equivalent to with salvage second autotransplants in patients with multiple myeloma. Cancer 118 – achieve a balance between tolerability and efficacy. Owing to 2012; : 3549 3555. relatively small patient numbers, a longer follow-up time may 3 Lemieux E, Hulin C, Caillot D, Tardy S, Dorvaux V, Michel J et al. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma. Biol Blood further differentiate the true clinical effect of the dose escalation Marrow Transplant 2013; 19:445–449. and the impact of post-auto-HCT maintenance therapy, which 4 Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA et al. High- 63% of patients received. Unfortunately (although not surpris- dose chemotherapy plus autologous stem-cell transplantation as consolidation ingly), poor-risk cytogenetics independently predicted for poorer therapy in patients with relapsed multiple myeloma after previous autologous OS, reminding us of the continued need for innovative treatment stem-cell transplantation (NCRI myeloma × relapse (Intensive trial)): a randomised, options for these patients.
    [Show full text]