DOCSLIB.ORG

Bioactive Peptides Hidden in Human Salivary Proteins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Journal of Oral Biosciences 59 (2017) 71–79 Contents lists available at ScienceDirect Journal of Oral Biosciences journal homepage: www.elsevier.com/locate/job Review Bioactive peptides hidden in human salivary proteins Eiichi Saitoh a,n, Masayuki Taniguchi b, Akihito Ochiai b, Tetsuo Kato c, Akane Imai d, Satoko Isemura d a Graduate School of Technology, Niigata Institute of Technology, 1719 Fujihashi, Kashiwazaki, Niigata 945-1195, Japan b Department of Materials Science and Technology, Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan c Laboratory of Chemistry, Tokyo Dental College, Tokyo 101-0062, Japan d Department of Dental Hygiene, The Nippon Dental University College at Niigata, Niigata 951-8580, Japan article info abstract Article history: Background: Extensive peptidomic studies of human saliva have resulted in considerable advances in the field Received 28 September 2016 of proteomics. As the next generation in salivary research, a comprehensive understanding of the biological Received in revised form functions of in vivo peptides generated by proteolysis in the oral cavity has been long awaited. A cyclopedic 4 November 2016 functional analysis of salivary peptides may bring promising therapeutic agents and novel clinical applications. Accepted 17 November 2016 Highlight: (1) This review article refers to bioactive peptides hidden in salivary parent proteins. (2) Functions of Available online 5 December 2016 the peptides as anti-microbial, anti-viral, wound-closing, and anti-pain are described. (3) Biological sig- Keywords: nificances of the repeated structures in salivary proline-rich proteins are emphasized. Human salivary proteome Conclusion: Human salivary proteins have the ability to generate bioactive peptides upon proteolytic cleavage. Bioactive peptides in salivary proteins & 2016 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved. Antimicrobial activity Wound-closing factor Anti-cancer activity Contents 1. Introduction.........................................................................................................71 2. A gift from the human genome project to salivary research. 72 2.1. Multiple proteins are produced by one gene . 72 2.2. Two gene clusters encoding major salivary proteins . 73 2.2.1. The gene cluster on chromosome 4q13.3 . 73 2.2.2. The gene cluster on chromosome 12p13.2 . 74 3. Bioactive peptides hidden in salivary proteins. 75 3.1. Bioactive peptides in statherin, histatin 1, and histatin 3 . 75 3.2. Bioactive peptides in P-B, P-B1, and PBLP . 76 3.3. Bioactive peptides in salivary mucins. 77 3.4. Bioactive peptides in aPRPs, bPRPs, and gPRPs . 77 4. Concluding remarks. 77 Ethicalapproval..........................................................................................................77 Conflictofinterest........................................................................................................77 Acknowledgments. 78 References..............................................................................................................78 Abbreviations: N-, amino-; C-, carboxyl-; PRP, proline rich protein; a, acidic; b, basic; g, glycosylated n Corresponding author. E-mail address: [email protected] (E. Saitoh). http://dx.doi.org/10.1016/j.job.2016.11.005 1349-0079/& 2016 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved. 72 E. Saitoh et al. / Journal of Oral Biosciences 59 (2017) 71–79 Fig. 1. Chromosomal localization of the genes encoding salivary (or lacrimal) proteins. Open squares indicate noncoding exon regions. Closed squares denote coding exon regions. Gray squares indicate exons encoding the PRPs-specific repeating unit G(P)nG(K/R)PQ and its related sequences. 1. Introduction dilution and cleaning, digestion, lubrication, and protection of tooth enamel are granted by parent proteins and occasionally their pro- To develop diagnostic systems based on human salivary protein cessed forms [7]. These biological functions are related not only to components, extensive proteomic and peptidomic studies have been oral health, but also to systemic health. The environment of the oral performed involving whole saliva (WS), parotid saliva (PS), sub- cavity, the “port of entry” of the gastrointestinal tract, is likened to a mandibular/sublingual saliva (SM/SL-S), and exosomes in WS over high-performance and elaborate incubator because the pH and tem- the past decade. Previous studies of the human salivary proteome perature in the cavity and gastrointestinal tract are precisely con- identified 914 proteins in the PS proteome [1],917intheSM/SL-S trolled. The oral cavity contains culture media rich in nutrients sup- proteome [1], 491 in the parotid exosome [2], 187 in two types of plied by dietary foods, in which notable proteolytic events take place exosomes in WS [3], and 56 in minor salivary gland secretions [4]. on salivary and dietary proteins. The predominate peptide fragments WS proteins in the oral cavity predominantly originate from three present in WS have been reported to be derived from aRRPs, bPRPs, major salivary glands: the parotid, submandibular, and sublingual gPRP,P-B,statherin,andhistatins[8]. Oppenheim et al. [8] have dis- glands. Many proteins have been identified in WS, including acidic covered unique proteases in WS that cleave preferentially after a (a) proline-rich proteins (PRPs), basic (b) PRPs, glycosylated (g) PRPs, glutamine residue for the tripeptide sequence -KPQ- in aPRPs, bPRPs, P-B, cystatins, histatins, statherin, mucous glycoproteins, mucin 5 and gPRP. The PRP-specificrepeatingunit,G(P)nG(K/R)PQ, and its (MG1), mucin 7 (MG2), immunoglobulins, amylase, and agglutinin related sequences are excised by proteases. These excised peptides [5]. Multiple variations based on genetic polymorphisms have been display completely different functions than the parent proteins [9,10] observed for each protein [6]. and were of unknown relevance until now. It has been gradually re- According to the NCBI gene database (http://www.ncbi.nlm.nih.gov/ cognized that the peptide fragments created by proteases from oral gene/), salivary proteins, including statherin, histatin 3, histatin 1, P-B1, epithelial cells, bacteria, and a serum-like gingival crevicular transu- P-B, BPLP, and mucin 7, are encoded by a set of clustered genes loca- date, play important roles in both the oral cavity and further down- lized on chromosome 4 [Cytogenetic location: 4q13.3, Genomic stream in the alimentary canal. Despite the identification of more coordinates: 4: 69,995,930-70,482,997; - STATH (encoding statherin) - than 4000 different salivary peptides and protein species [11],phy- HTN3 (alias HIS2; encoding histatin 3) - HTN1 (HIS1;histatin1)-PBI siological functions of salivary peptides are beginning to be under- (SMR3A or PROL5; P-B1 or SMR3A) - PBII (SMR3B or PROL3; P-B or stood and only recently have applications of these peptides been SMR3B) - OPRPN (PROL1; basic proline-rich lacrimal protein BPLP) - examined. MUC7 (mucin 7) -]. Moreover, lacrimal proline-rich protein (LPRP), two In this review article, we summarize the bioactive peptides aPRPs, one bPRP, and three gPRPs are encoded by another gene cluster identified so far that are hidden in major human salivary proteins. [Cytogenetic location: 12p13.2, Genomic coordinates: 12: 10,845,849- 11,501,041; - PRR4 (alias PROL4; encoding LPRP) - PRH1 (encoding aPRP) - PRH2 (aPRP) - PRB3 (gPRP) - PRB4 (gPRP) - PRB1 (bPRP) - PRB2 2. A gift from the human genome project to salivary research (gPRP) -]. The PRH2 geneislocatedintheforwardstrandofchromo- some 4 but the other six genes are in the reverse strand. 2.1. Multiple proteins are produced by one gene Most of the established biological functions of saliva such as an- timicrobial properties, wound repairing, pain control, buffering, Brief maps of two gene clusters encoding major salivary proteins E. Saitoh et al. / Journal of Oral Biosciences 59 (2017) 71–79 73 Fig. 2. Summary of biological information for statherin, histatin 3, histatin 4, P-B1, and P-B. Nomenclature of each gene, UniProt/Swiss-Prot number, and amino acid sequence of each protein are present in the NCBI gene and UniProt/Swiss-Prot database. The signal sequence for each protein is shown in italics. The N-terminal and C-terminal amino acid residues for each protein are numbered. Antimicrobial peptide sequence in statherin (P02808) is indicated by a dotted underline. The histatin 5 sequence in histatin 3 (P15516) is indicated by a triple underline. The minimal domain required for wound healing activity in histatin 1 (P15515) is indicated by a solid underline. The opiorphin homolog (QRGPR) in P-B1 (Q99954), P-B (P02814), and P-B variant (Q508X8Q504 Â 8) is indicated by a double underline. The possible N-glyco- sylation site (N-C-S) in the amino acid sequence of P-B variant is underlined. Sugar chain is indicated by duplex-closed circles. on chromosome 4q13.3 and chromosome 12p13.2 are illustrated in amino acid sequences encoded by the genes (STATH, HTN3, HTN1, Fig. 1 and are based on data resulting from the human genome pro- PBI, and PBII) are given in Fig. 2. In the same manner, Fig. 3 shows ject (http://www.ncbi.nlm.nih.gov/gene/). These achievements re- the amino acid sequences encoded by OPRPN and MUC7. STATH, vealed that alternative splicing causes multiple exon combinations, HTN3, and HTN1 are composed of six exons that are thought to be including coding- and non-coding DNA sequences, thereby many derived
Recommended publications
  • Computational Analysis of DNA Methylation and Gene Expression Patterns in Prostate Cancer

    Computational Analysis of DNA Methylation and Gene Expression Patterns in Prostate Cancer

    Ieva Rauluševičiūtė Computational Analysis of DNA Methylation and Gene Expression Patterns in Prostate Cancer Master’s thesis in Molecular Medicine Trondheim, June 2018 Supervisors: dr. Morten Beck Rye and prof. Finn Drabløs Norwegian University of Science and Technology Faculty of Medicine and Health Sciences Department of Clinical and Molecular Medicine ABSTRACT DNA methylation is an important contributor for prostate cancer development and progression. It has been studied experimentally for years, but, lately, high-throughput technologies are able to produce genome-wide DNA methylation data that can be analyzed using various computational approaches. Thus, this study aims to bioinformatically investigate different DNA methylation and gene expression patterns in prostate cancer. DNA methylation data from three datasets (TCGA, Absher and Kirby) was correlated with gene expression data in order to distinguish different regulation patterns. Classically, increased DNA methylation in promoter regions is being associated with gene expression downregulation. Although, results of the present project demonstrate another robust pattern, where DNA hypermethylation in promoter regions of 1,058 common genes is accompanied by upregulated expression. After analyzing expression and methylation values in the same samples from TCGA dataset, expression overcompensation in a dataset as an explanation for upregulation was excluded. Further reasons behind the pattern were investigated using TCGA DNA methylation data with extended list of probes and includes the presence of methylated positions in CpG islands, distance to transcription start sites and alternative TSSs. As compared with the downregulated genes in the classical pattern, upregulated genes were shown to have more positions in CpG islands and closer to TSSs. Moreover, the presence of alternative TSS in prostate was demonstrated, also disclosing the limitations of methylation detection systems.
  • Cow's Milk Allergy in Dutch Children

    Cow's Milk Allergy in Dutch Children

    Petrus et al. Clin Transl Allergy (2016) 6:16 DOI 10.1186/s13601-016-0105-z Clinical and Translational Allergy RESEARCH Open Access Cow’s milk allergy in Dutch children: an epigenetic pilot survey Nicole C. M. Petrus1*†, Peter Henneman2†, Andrea Venema2, Adri Mul2, Femke van Sinderen2, Martin Haagmans2, Olaf Mook2, Raoul C. Hennekam1,2, Aline B. Sprikkelman1‡ and Marcel Mannens2‡ Abstract Background: Cow’s milk allergy (CMA) is a common disease in infancy. Early environmental factors are likely to con- tribute to CMA. It is known that epigenetic gene regulation can be altered by environmental factors. We have set up a proof of concept study, aiming to detect epigenetic associations specific with CMA. Methods: We studied children from the Dutch EuroPrevall birth cohort study (N 20 CMA, N 23 controls, N 10 tolerant boys), age and gender matched. CMA was challenge proven. Bisulfite converted= DNA =(blood) was analyzed= using the 450K infinium DNA-methylation array. Four groups (combined, girls, boys and tolerant boys) were analysed between CMA and controls. Statistical analysis and pathway-analysis were performed in “R” using IMA, Minfi and the global-test package. Differentially methylated regions in DHX58, ZNF281, EIF42A and HTRA2 genes were validated by quantitative amplicon sequencing (ROCHE 454®). Results: General hypermethylation was found in the CMA group compared to control children, while this effect was absent in the tolerant group. Methylation differences were, among others, found in regions of DHX58, ZNF281, EIF42A and HTRA2 genes. Several of these genes are known to be involved in immunological pathways and associated with other allergies. Conclusion: We show that epigenetic associations are involved in CMA.
  • Identification of ROBO2 As a Potential Locus Associated with Inhaled

    Identification of ROBO2 As a Potential Locus Associated with Inhaled

    Journal of Personalized Medicine Article Identification of ROBO2 as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma Natalia Hernandez-Pacheco 1,2,3,*,†, Mario Gorenjak 4 , Jiang Li 5 , Katja Repnik 4,6, Susanne J. Vijverberg 7,8,9, Vojko Berce 4,10 , Andrea Jorgensen 11, Leila Karimi 12 , Maximilian Schieck 13,14, Lesly-Anne Samedy-Bates 15,16, Roger Tavendale 17, Jesús Villar 3,18,19 , Somnath Mukhopadhyay 17,20, Munir Pirmohamed 21 , Katia M. C. Verhamme 12, Michael Kabesch 13, Daniel B. Hawcutt 22,23, Steve Turner 24 , Colin N. Palmer 17, Kelan G. Tantisira 5,25, Esteban G. Burchard 15,16, Anke H. Maitland-van der Zee 7,8,9 , Carlos Flores 1,3,26,27 , Uroš Potoˇcnik 4,6,*,‡ and Maria Pino-Yanes 2,3,27,‡ 1 Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Carretera General del Rosario 145, 38010 Santa Cruz de Tenerife, Spain; cfl[email protected] 2 Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez s/n, Faculty of Science, Apartado 456, 38200 San Cristóbal de La Laguna, Spain; [email protected] 3 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Avenida de Monforte de Lemos, 5, 28029 Madrid, Spain; [email protected] 4 Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia; [email protected] (M.G.); [email protected] (K.R.); [email protected]
  • Supplementary Data

    Supplementary Data

    Supplementary Fig. 1 A B Responder_Xenograft_ Responder_Xenograft_ NON- NON- Lu7336, Vehicle vs Lu7466, Vehicle vs Responder_Xenograft_ Responder_Xenograft_ Sagopilone, Welch- Sagopilone, Welch- Lu7187, Vehicle vs Lu7406, Vehicle vs Test: 638 Test: 600 Sagopilone, Welch- Sagopilone, Welch- Test: 468 Test: 482 Responder_Xenograft_ NON- Lu7860, Vehicle vs Responder_Xenograft_ Sagopilone, Welch - Lu7558, Vehicle vs Test: 605 Sagopilone, Welch- Test: 333 Supplementary Fig. 2 Supplementary Fig. 3 Supplementary Figure S1. Venn diagrams comparing probe sets regulated by Sagopilone treatment (10mg/kg for 24h) between individual models (Welsh Test ellipse p-value<0.001 or 5-fold change). A Sagopilone responder models, B Sagopilone non-responder models. Supplementary Figure S2. Pathway analysis of genes regulated by Sagopilone treatment in responder xenograft models 24h after Sagopilone treatment by GeneGo Metacore; the most significant pathway map representing cell cycle/spindle assembly and chromosome separation is shown, genes upregulated by Sagopilone treatment are marked with red thermometers. Supplementary Figure S3. GeneGo Metacore pathway analysis of genes differentially expressed between Sagopilone Responder and Non-Responder models displaying –log(p-Values) of most significant pathway maps. Supplementary Tables Supplementary Table 1. Response and activity in 22 non-small-cell lung cancer (NSCLC) xenograft models after treatment with Sagopilone and other cytotoxic agents commonly used in the management of NSCLC Tumor Model Response type
  • Region Based Gene Expression Via Reanalysis of Publicly Available Microarray Data Sets

    Region Based Gene Expression Via Reanalysis of Publicly Available Microarray Data Sets

    University of Louisville ThinkIR: The University of Louisville's Institutional Repository Electronic Theses and Dissertations 5-2018 Region based gene expression via reanalysis of publicly available microarray data sets. Ernur Saka University of Louisville Follow this and additional works at: https://ir.library.louisville.edu/etd Part of the Bioinformatics Commons, Computational Biology Commons, and the Other Computer Sciences Commons Recommended Citation Saka, Ernur, "Region based gene expression via reanalysis of publicly available microarray data sets." (2018). Electronic Theses and Dissertations. Paper 2902. https://doi.org/10.18297/etd/2902 This Doctoral Dissertation is brought to you for free and open access by ThinkIR: The University of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The University of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact [email protected]. REGION BASED GENE EXPRESSION VIA REANALYSIS OF PUBLICLY AVAILABLE MICROARRAY DATA SETS By Ernur Saka B.S. (CEng), University of Dokuz Eylul, Turkey, 2008 M.S., University of Louisville, USA, 2011 A Dissertation Submitted To the J. B. Speed School of Engineering in Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Computer Science and Engineering Department of Computer Engineering and Computer Science University of Louisville Louisville, Kentucky May 2018 Copyright 2018 by Ernur Saka All rights reserved REGION BASED GENE EXPRESSION VIA REANALYSIS OF PUBLICLY AVAILABLE MICROARRAY DATA SETS By Ernur Saka B.S. (CEng), University of Dokuz Eylul, Turkey, 2008 M.S., University of Louisville, USA, 2011 A Dissertation Approved On April 20, 2018 by the following Committee __________________________________ Dissertation Director Dr.
  • Bivariate Genome-Wide Association Analysis Strengthens the Role of Bitter Receptor Clusters on Chromosomes 7 and 12 in Human Bitter Taste

    Bivariate Genome-Wide Association Analysis Strengthens the Role of Bitter Receptor Clusters on Chromosomes 7 and 12 in Human Bitter Taste

    bioRxiv preprint doi: https://doi.org/10.1101/296269; this version posted April 6, 2018. 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. Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste Liang-Dar Hwang1,2,3,4, Puya Gharahkhani1, Paul A. S. Breslin5,6, Scott D. Gordon1, Gu Zhu1, Nicholas G. Martin1, Danielle R. Reed5, and Margaret J. Wright2,7 1 QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia 2 Queensland Brain Institute, University of Queensland, St Lucia, Queensland 4072, Australia 3 Faculty of Medicine, University of Queensland, Herston, Queensland 4006, Australia 4 University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Woolloongabba, Queensland 4102, Australia 5 Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA 6 Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick NJ, 08901 USA 7 Centre for Advanced Imaging, University of Queensland, St Lucia, Queensland 4072, Australia Correspondence to be sent to: Liang-Dar Hwang University of Queensland Diamantina Institute Wolloongabba QLD 4102, Australia Email: [email protected] Telephone: +61 7 3443 7976 Fax: +61 7 3443 6966 1 bioRxiv preprint doi: https://doi.org/10.1101/296269; this version posted April 6, 2018. 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.
  • Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

    Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

    UCSF UC San Francisco Previously Published Works Title Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Permalink https://escholarship.org/uc/item/95h5g8mq Journal Cell reports, 33(7) ISSN 2211-1247 Authors Saitou, Marie Gaylord, Eliza A Xu, Erica et al. Publication Date 2020-11-01 DOI 10.1016/j.celrep.2020.108402 Peer reviewed eScholarship.org Powered by the California Digital Library University of California HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Cell Rep Manuscript Author . Author manuscript; Manuscript Author available in PMC 2020 November 30. Published in final edited form as: Cell Rep. 2020 November 17; 33(7): 108402. doi:10.1016/j.celrep.2020.108402. Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva Marie Saitou1,2,3, Eliza A. Gaylord4, Erica Xu1,7, Alison J. May4, Lubov Neznanova5, Sara Nathan4, Anissa Grawe4, Jolie Chang6, William Ryan6, Stefan Ruhl5,*, Sarah M. Knox4,*, Omer Gokcumen1,8,* 1Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A 2Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, U.S.A 3Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Viken, Norway 4Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A 5Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A 6Department of Otolaryngology, School of Medicine, University of California, San Francisco, CA, U.S.A 7Present address: Weill-Cornell Medical College, Physiology and Biophysics Department 8Lead Contact SUMMARY Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease.
  • The Genome-Wide Landscape of Copy Number Variations in the MUSGEN Study Provides Evidence for a Founder Effect in the Isolated Finnish Population

    The Genome-Wide Landscape of Copy Number Variations in the MUSGEN Study Provides Evidence for a Founder Effect in the Isolated Finnish Population

    European Journal of Human Genetics (2013) 21, 1411–1416 & 2013 Macmillan Publishers Limited All rights reserved 1018-4813/13 www.nature.com/ejhg ARTICLE The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population Chakravarthi Kanduri1, Liisa Ukkola-Vuoti1, Jaana Oikkonen1, Gemma Buck2, Christine Blancher2, Pirre Raijas3, Kai Karma4, Harri La¨hdesma¨ki5 and Irma Ja¨rvela¨*,1 Here we characterized the genome-wide architecture of copy number variations (CNVs) in 286 healthy, unrelated Finnish individuals belonging to the MUSGEN study, where molecular background underlying musical aptitude and related traits are studied. By using Illumina HumanOmniExpress-12v.1.0 beadchip, we identified 5493 CNVs that were spread across 467 different cytogenetic regions, spanning a total size of 287.83 Mb (B9.6% of the human genome). Merging the overlapping CNVs across samples resulted in 999 discrete copy number variable regions (CNVRs), of which B6.9% were putatively novel. The average number of CNVs per person was 20, whereas the average size of CNV per locus was 52.39 kb. Large CNVs (41 Mb) were present in 4% of the samples. The proportion of homozygous deletions in this data set (B12.4%) seemed to be higher when compared with three other populations. Interestingly, several CNVRs were significantly enriched in this sample set, whereas several others were totally depleted. For example, a CNVR at chr2p22.1 intersecting GALM was more common in this population (P ¼ 3.3706 Â 10 À44) than in African and other European populations. The enriched CNVRs, however, showed no significant association with music-related phenotypes.
  • 1 Proteins of the XMRV Retrovirus Implicated in Chronic Fatigue

    1 Proteins of the XMRV Retrovirus Implicated in Chronic Fatigue

    1 Proteins of the XMRV retrovirus implicated in chronic fatigue syndrome and prostate cancer are homologous to human proteins relevant to both conditions. C.J.Carter Flat 4, 20 Upper Maze Hill, Saint-Leonards on Sea , East Sussex, TN38 OLG [email protected] The XMRV retrovirus has been implicated in chronic fatigue syndrome and prostate cancer. A homology search comparing retroviral with human proteins revealed short contiguous amino acid strings (typically 5-8 aa) matching human proteins whose dysfunction might be expected to cause fatigue, including mitochondrial proteins related to oxidative phosphorylation, glutamate receptors and their synaptic scaffolds, muscular acetylcholine receptor scaffolds and structural proteins, components of the immune system, and phosphatidylinositol signalling inter alia. Viral proteins are also homologous to members of the oestrogen, peroxisome proliferator, and CREB activated receptor networks, all of which are implicated in prostate cancer, and to a protein, SRCAP, that controls the expression of the prostate- specific antigen. These short matches are often predicted to be antigenic, and antibodies to XMRV proteins may target their human homologues. This is supported by the presence of autoantibodies to muscarinic receptors , vimentin and LAMINB1 (all XMRV homologues) in chronic fatigue syndrome sufferers. Homologous XMRV proteins might also interfere with the protein interactomes of their human homologues. Viral mimicry of human proteins is extensive and often relevant to disease. For example Epstein-Barr viral proteins aligns with multiple sclerosis autoantigens, while HIV-1 proteins align with several components of the immune system. Mutant proteins in Huntington’s disease and cystic fibrosis also align with proteins from common phages or viruses.
  • Genome-Wide Postnatal Changes in Immunity Following Fetal Inflammatory Response

    Genome-Wide Postnatal Changes in Immunity Following Fetal Inflammatory Response

    medRxiv preprint doi: https://doi.org/10.1101/19000109; this version posted September 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Genome-wide postnatal changes in immunity following fetal inflammatory response Daniel Costa1,2, Núria Bonet3, Amanda Solé2,4,5, José Manuel González de Aledo-Castillo6, Eduard Sabidó2,4,5, Ferran Casals3, Carlota Rovira7, Alfons Nadal8, Jose Luis Marin9, Teresa Cobo9,*, Robert Castelo2,10,* 1Department of Pediatrics, Hospital de Figueres, Figueres, Spain; 2Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain; 3Genomics Core Facility, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain; 4Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona, Spain; 5Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 6Inborn Errors of Metabolism Section, Laboratory of Biochemistry and Molecular Genetics, Hospital Clínic, Barcelona, Spain; 7Hospital Sant Joan de Déu, Barcelona, Spain; 8Department of Pathology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; 9Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; 10Research Programme on Biomedical Informatics, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain; *Correspondence: Robert Castelo ([email protected]), Teresa Cobo ([email protected]) NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
  • Atlas Journal

    Atlas Journal

    Atlas of Genetics and Cytogenetics in Oncology and Haematology Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Portal Teaching X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA Atlas Journal Atlas Journal versus Atlas Database: the accumulation of the issues of the Journal constitutes the body of the Database/Text-Book. TABLE OF CONTENTS Volume 12, Number 5, Sep-Oct 2008 Previous Issue / Next Issue Genes XAF1 (XIAP associated factor-1) (17p13.2). Stéphanie Plenchette, Wai Gin Fong, Robert G Korneluk. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 668-673. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/XAF1ID44095ch17p13.html WWP1 (WW domain containing E3 ubiquitin protein ligase 1) (8q21.3). Ceshi Chen. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 674-680. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/WWP1ID42993ch8q21.html TSPAN1 (tetraspanin 1) (1p34.1). David Murray, Peter Doran. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 681-683. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/TSPAN1ID44178ch1p34.html TCL1B (T-cell leukemia/lymphoma 1B) (14q32.13). Herbert Eradat, Michael A Teitell. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 684-686. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/TCL1BID354ch14q32.html PVRL4 (poliovirus receptor-related 4) (1q23.3). Marc Lopez. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 687-690. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/PVRL4ID44141ch1q23.html PTTG1IP (pituitary tumor-transforming 1 interacting protein) (21q22.3). Vicki Smith, Chris McCabe. Atlas Genet Cytogenet Oncol Haematol 2008; 12 (5): 691-694.
  • (12) Patent Application Publication (10) Pub. No.: US 2003/0198970 A1 Roberts (43) Pub

    (12) Patent Application Publication (10) Pub. No.: US 2003/0198970 A1 Roberts (43) Pub

    US 2003O19897OA1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0198970 A1 Roberts (43) Pub. Date: Oct. 23, 2003 (54) GENOSTICS clinical trials on groups or cohorts of patients. This group data is used to derive a Standardised method of treatment (75) Inventor: Gareth Wyn Roberts, Cambs (GB) which is Subsequently applied on an individual basis. There is considerable evidence that a significant factor underlying Correspondence Address: the individual variability in response to disease, therapy and FINNEGAN, HENDERSON, FARABOW, prognosis lies in a person's genetic make-up. There have GARRETT & DUNNER been numerous examples relating that polymorphisms LLP within a given gene can alter the functionality of the protein 1300 ISTREET, NW encoded by that gene thus leading to a variable physiological WASHINGTON, DC 20005 (US) response. In order to bring about the integration of genomics into medical practice and enable design and building of a (73) Assignee: GENOSTIC PHARMA LIMITED technology platform which will enable the everyday practice (21) Appl. No.: 10/206,568 of molecular medicine a way must be invented for the DNA Sequence data to be aligned with the identification of genes (22) Filed: Jul. 29, 2002 central to the induction, development, progression and out come of disease or physiological States of interest. Accord Related U.S. Application Data ing to the invention, the number of genes and their configu rations (mutations and polymorphisms) needed to be (63) Continuation of application No. 09/325,123, filed on identified in order to provide critical clinical information Jun. 3, 1999, now abandoned. concerning individual prognosis is considerably less than the 100,000 thought to comprise the human genome.