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  1 / 2449 MEDLINE  
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[PMID]:28695282
[Au] Autor:Naranbhai V; Carrington M
[Ad] Endereço:Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA. vnaranbhai@mgh.harvard.edu.
[Ti] Título:Host genetic variation and HIV disease: from mapping to mechanism.
[So] Source:Immunogenetics;69(8-9):489-498, 2017 Aug.
[Is] ISSN:1432-1211
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This review aims to provide a summary of current knowledge of host genetic effects on human immunodeficiency virus (HIV) disease. Mapping of simple single nucleotide polymorphisms (SNP) has been largely successful in HIV, but more complex genetic associations involving haplotypic or epigenetic variation, for example, remain elusive. Mechanistic insights explaining SNP associations are incomplete, but continue to be forthcoming. The number of robust immunogenetic correlates of HIV is modest and their discovery mostly predates the genome-wide era. Nevertheless, genome-wide evaluations have nicely validated the impact of HLA and CCR5 variants on HIV disease, and importantly, made clear the many false positive associations that were previously suggested by studies using the candidate gene approach. We describe how multiple HIV outcome measures such as acquisition, viral control, and immune decline have been studied in adults and in children, but that collectively these identify only the two replicable loci responsible for modifying HIV disease, CCR5, and HLA. Recent heritability estimates in this disease corroborate the modest impact of genetic determinants and their oligogenic nature. While the mechanism of protection afforded by genetic variants that diminish CCR5 expression is clear, new aspects of HLA class I-mediated protection continue to be uncovered. We describe how these genetic findings have enhanced insights into immunobiology, been clinically translated into CCR5 antagonists, allowed prioritization of antigens for vaccination efforts, and identified targets for genome-editing interventions. Finally, we describe how studies of genetically complex parts of the genome using new tools may begin revealing additional correlates.
[Mh] Termos MeSH primário: Infecções por HIV/genética
[Mh] Termos MeSH secundário: Genes MHC Classe I
Variação Genética
Seres Humanos
Imunogenética
Polimorfismo de Nucleotídeo Único
Receptores CCR5/genética
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (CCR5 protein, human); 0 (Receptors, CCR5)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1007/s00251-017-1000-z


  2 / 2449 MEDLINE  
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[PMID]:28416603
[Au] Autor:Langerak AW; Brüggemann M; Davi F; Darzentas N; van Dongen JJM; Gonzalez D; Cazzaniga G; Giudicelli V; Lefranc MP; Giraud M; Macintyre EA; Hummel M; Pott C; Groenen PJTA; Stamatopoulos K; EuroClonality-NGS Consortium
[Ad] Endereço:Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands; a.langerak@erasmusmc.nl.
[Ti] Título:High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges.
[So] Source:J Immunol;198(10):3765-3774, 2017 May 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis. This concerns the preanalytical (sample preparation, target choice), analytical (amplification, NGS), and postanalytical (immunoinformatics) phases. Here we critically discuss pitfalls and challenges of IG/TR NGS methodology and its applications in hemato-oncology and immunology.
[Mh] Termos MeSH primário: Hematologia/métodos
Sequenciamento de Nucleotídeos em Larga Escala
Imunogenética/métodos
Técnicas Imunológicas
[Mh] Termos MeSH secundário: Alelos
Biologia Computacional/métodos
Rearranjo Gênico
Genes de Imunoglobulinas
Genes Codificadores dos Receptores de Linfócitos T/genética
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Seres Humanos
Imunogenética/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1602050


  3 / 2449 MEDLINE  
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[PMID]:28187283
[Au] Autor:Liu XS; Mardis ER
[Ad] Endereço:Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, 450 Brookline Ave, Boston MA 02215, USA. Electronic address: xsliu@jimmy.harvard.edu.
[Ti] Título:Applications of Immunogenomics to Cancer.
[So] Source:Cell;168(4):600-612, 2017 Feb 09.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/imunologia
Neoplasias/genética
Neoplasias/imunologia
[Mh] Termos MeSH secundário: Animais
Vacinas Anticâncer/imunologia
Genoma Humano
Antígenos HLA/imunologia
Seres Humanos
Imunogenética
Linfócitos do Interstício Tumoral/imunologia
Mutação
Análise de Sequência de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Cancer Vaccines); 0 (HLA Antigens)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE


  4 / 2449 MEDLINE  
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[PMID]:27888301
[Au] Autor:Antonides J; Ricklefs R; DeWoody JA
[Ad] Endereço:Department of Forestry and Natural Resources, Purdue University, West Lafayette, IN, USA. jantonid@purdue.edu.
[Ti] Título:The genome sequence and insights into the immunogenetics of the bananaquit (Passeriformes: Coereba flaveola).
[So] Source:Immunogenetics;69(3):175-186, 2017 03.
[Is] ISSN:1432-1211
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Avian genomics, especially of non-model species, is in its infancy relative to mammalian genomics. Here, we describe the sequencing, assembly, and annotation of a new avian genome, that of the bananaquit Coereba flaveola (Passeriformes: Thraupidae). We produced ∼30-fold coverage of the genome with an assembly size of ca. 1.2 Gb, including approximately 16,500 annotated genes. Passerine birds, such as the bananaquit, are commonly infected by avian malarial parasites (Haemosporida), which presumably drive adaptive evolution of immunogenetic loci within the host genome. In the context of our research on the distribution of avian Haemosporida, we specifically characterized immune loci, including toll-like receptor (TLR) and major histocompatibility complex (MHC) genes. Additionally, we identified novel molecular markers in the form of single nucleotide polymorphisms (SNPs), both genome-wide and within identified immune loci. We discovered nine TLR genes and four MHC genes and identified five other TLR- or MHC- associated genes. Genome-wide, over 6 million high-quality SNPs were annotated, including 568 within TLR genes and 102 in MHC genes. This newly described genome and immune characterization expands the knowledge base for avian genomics and phylogenetics and allows for immune genotyping in the bananaquit, providing tools for the investigation of host-parasite coevolution.
[Mh] Termos MeSH primário: Variação Genética/genética
Genoma
Imunogenética
Complexo Principal de Histocompatibilidade/genética
Passeriformes/genética
Passeriformes/imunologia
Receptores Toll-Like/genética
[Mh] Termos MeSH secundário: Animais
Evolução Biológica
Genômica
Genótipo
Anotação de Sequência Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Toll-Like Receptors)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161127
[St] Status:MEDLINE
[do] DOI:10.1007/s00251-016-0960-8


  5 / 2449 MEDLINE  
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[PMID]:27859681
[Au] Autor:Gödel P; Fischer J; Scheid C; Gathof BS; Wolf J; Rybniker J
[Ad] Endereço:1st Department of Internal Medicine, University of Cologne, Cologne, Germany.
[Ti] Título:Familial acquired thrombotic thrombocytopenic purpura in siblings - no immunogenetic link with associated human leucocyte antigens.
[So] Source:Eur J Haematol;98(3):311-313, 2017 Mar.
[Is] ISSN:1600-0609
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acquired immunoglobulin G (IgG)-mediated thrombotic thrombocytopenic purpura (TTP) has not yet been described in non-twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life-threatening disease. However, human leucocyte antigen (HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members.
[Mh] Termos MeSH primário: Púrpura Trombocitopênica Trombótica/diagnóstico
Púrpura Trombocitopênica Trombótica/etiologia
[Mh] Termos MeSH secundário: Proteína ADAMTS13/imunologia
Proteína ADAMTS13/metabolismo
Adulto
Autoanticorpos/imunologia
Suscetibilidade a Doenças
Feminino
Antígenos HLA/genética
Antígenos HLA/imunologia
Seres Humanos
Imunogenética
Masculino
Meia-Idade
Fenótipo
Irmãos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (HLA Antigens); EC 3.4.24.87 (ADAMTS13 Protein)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170223
[Lr] Data última revisão:
170223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1111/ejh.12831


  6 / 2449 MEDLINE  
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[PMID]:27832379
[Au] Autor:Ota M; Umemura T; Kawa S
[Ad] Endereço:Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. otamasao@shinshu-u.ac.jp.
[Ti] Título:Immunogenetics of IgG4-Related AIP.
[So] Source:Curr Top Microbiol Immunol;401:35-44, 2017.
[Is] ISSN:0070-217X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. AIP has the features of a complex disease that is caused by multifactorial genes. However, the genetic factors underlying AIP have not been elucidated conclusively. Association studies by the candidate-gene approach and genome-wide association studies (GWAS) have revealed several susceptibility genes for AIP, including HLA DRB1*04:05-DQB1*04:01, FCRL3, CTLA4, and KCNA3, albeit in small-scale analyses. Thus, GWAS of large sample sizes and multinational collaborative meta-analyses are needed to identify the precise genetic variants that are associated with AIP onset. Systems genetics approaches that integrate DNA sequencing, expression quantitative trait locus (eQTL) mapping, proteomics, and metabolomics will also be useful in clarifying the pathogenesis of AIP.
[Mh] Termos MeSH primário: Doenças Autoimunes/genética
Imunoglobulina G/imunologia
Pancreatite Crônica/genética
[Mh] Termos MeSH secundário: Animais
Doenças Autoimunes/imunologia
Predisposição Genética para Doença
Seres Humanos
Imunogenética
Pancreatite Crônica/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunoglobulin G)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161111
[St] Status:MEDLINE
[do] DOI:10.1007/82_2016_37


  7 / 2449 MEDLINE  
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[PMID]:27587690
[Au] Autor:Voitenko OS; Dhroso A; Feldmann A; Korkin D; Kalinina OV
[Ad] Endereço:Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, Saarbrücken 66123, Germany, Graduate School for Computer Science, Saarland University, Campus E1 3, Saarbrücken 66123, Germany.
[Ti] Título:Patterns of amino acid conservation in human and animal immunodeficiency viruses.
[So] Source:Bioinformatics;32(17):i685-i692, 2016 Sep 01.
[Is] ISSN:1367-4811
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:MOTIVATION: Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity. RESULTS: We propose a method for identification of two types of surface residues clusters with abnormal conservation: extremely conserved and extremely variable clusters. We identify them on the surface of proteins from HIV and other animal immunodeficiency viruses. Both types of clusters are overrepresented on the interaction interfaces of viral proteins with other proteins, nucleic acids or low molecular-weight ligands, both in the viral particle and between the virus and its host. In the immunodeficiency viruses, the interaction interfaces are not more conserved than the corresponding proteins on an average, and we show that extremely conserved clusters coincide with protein-protein interaction hotspots, predicted as the residues with the largest energetic contribution to the interaction. Extremely variable clusters have been identified here for the first time. In the HIV-1 envelope protein gp120, they overlap with known antigenic sites. These antigenic sites also contain many residues from extremely conserved clusters, hence representing a unique interacting interface enriched both in extremely conserved and in extremely variable clusters of residues. This observation may have important implication for antiretroviral vaccine development. AVAILABILITY AND IMPLEMENTATION: A Python package is available at https://bioinf.mpi-inf.mpg.de/publications/viral-ppi-pred/ CONTACT: voitenko@mpi-inf.mpg.de or kalinina@mpi-inf.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
[Mh] Termos MeSH primário: Aminoácidos
Sequência Conservada
Evolução Molecular
Imunogenética
Proteínas Virais
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
HIV-1
Seres Humanos
Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Viral Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1093/bioinformatics/btw441


  8 / 2449 MEDLINE  
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[PMID]:27402904
[Au] Autor:Sheikh QM; Gatherer D; Reche PA; Flower DR
[Ad] Endereço:School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
[Ti] Título:Towards the knowledge-based design of universal influenza epitope ensemble vaccines.
[So] Source:Bioinformatics;32(21):3233-3239, 2016 Nov 01.
[Is] ISSN:1367-4811
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:MOTIVATION: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. RESULTS: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes. AVAILABILITY AND IMPLEMENTATION: http://imed.med.ucm.es/Tools/episopt.html CONTACT: d.r.flower@aston.ac.uk.
[Mh] Termos MeSH primário: Simulação por Computador
Vírus da Influenza A/imunologia
Vacinas contra Influenza
Influenza Humana/prevenção & controle
[Mh] Termos MeSH secundário: Linfócitos T CD4-Positivos
Epitopos de Linfócito T
Seres Humanos
Imunogenética
Influenza Humana/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epitopes, T-Lymphocyte); 0 (Influenza Vaccines)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE


  9 / 2449 MEDLINE  
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[PMID]:27399422
[Au] Autor:Johanns TM; Ward J; Wilson C; Kobayashi DK; Bender D; Fu Y; Alexandrov A; Artyomov MN; Miller CA; Mardis ER; Dunn GP
[Ti] Título:143 Identification of Neoantigen-specific CD8+ T Cells in Two Murine Orthotopic Glioblastoma Models Using Cancer Immunogenomics.
[So] Source:Neurosurgery;63 Suppl 1:158, 2016 Aug.
[Is] ISSN:1524-4040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Our understanding of how immune-based strategies designed to enhance T-cell activation might effectively control glioblastoma progression has been limited by our ability to identify and monitor tumor-specific T cells. The "cancer immunogenomics" approach has facilitated the search for tumor-specific antigens over the past 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in preclinical brain tumor models susceptible to checkpoint immunotherapy. METHODS: The C57BL/6-derived GL-261 and VM/Dk-derived SMA-560 H-2b haplotype brain tumors underwent DNA whole exome and RNA sequencing. High-affinity candidate neoepitopes were predicted by using in silico computational approaches. Tumor-specific T-cell recognition was assessed using enzyme-linked immunospot (ELISPOT) and mutant-specific tetramer analyses of tumor-infiltrating lymphocytes from tumors injected subcutaneously and intracranially. RESULTS: The GL-261 and SMA-560 tumors harbored 4644 and 2066 nonsynonymoous exome mutations, respectively, of which half were expressed. We applied H-2Db- and H-2Kb-specific neoantigen prediction algorithms to identify candidate tumor antigens. To validate the immunogenicity of these candidate neoantigens, we assessed tumor-specific T-cell responses of tumor-infiltrating lymphocytes harvested from GL-261 and SMA-560 tumors transplanted heterotopically and orthotopically into their respective syngeneic hosts. Using interferon-γ ELISPOT and tetramer analysis, we confirmed H2-Db-restricted IMP3-D81N (GL-261) and ODC1-Q129L (SMA-560) as endogenous neoantigens that were functionally immunogenic. Neoantigen-specific T cells were detected within intracranial tumors as well as draining lymph nodes. CONCLUSION: We credentialed the immunogenicity of 2 predicted high-affinity neoepitopes in well-studied orthotopic syngeneic preclinical brain tumor models, GL-261 and SMA-560. Furthermore, we identified tetramer-positive, antigen-specific T-cell populations within transplanted brain tumors and draining lymph nodes. We therefore extend cancer immunogenomics-based neoantigen discovery to glioblastoma models and establish a foundation to expand studies of the tumor-specific mutanome and explore fundamental mechanisms of T-cell activation in central nervous system immunobiology.
[Mh] Termos MeSH primário: Antígenos de Neoplasias
Linfócitos T CD8-Positivos/imunologia
Glioblastoma
Imunoterapia
[Mh] Termos MeSH secundário: Animais
Antígenos de Neoplasias/genética
Antígenos de Neoplasias/imunologia
Glioblastoma/genética
Glioblastoma/imunologia
Glioblastoma/terapia
Imunogenética
Camundongos
Camundongos Endogâmicos C57BL
Neoplasias Experimentais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160712
[St] Status:MEDLINE
[do] DOI:10.1227/01.neu.0000489713.52326.9a


  10 / 2449 MEDLINE  
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[PMID]:27337483
[Au] Autor:Abi-Rached L; Raoult D
[Ti] Título:Paleogenetics and Past Infections: the Two Faces of the Coin of Human Immune Evolution.
[So] Source:Microbiol Spectr;4(3), 2016 Jun.
[Is] ISSN:2165-0497
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. These paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and to approximately 0.2% of modern Asian genomes. Although these contributions are modest, they played a major role in shaping immune gene families, such as the HLA class I genes, for which the archaic alleles now represent more than 50% of the alleles in Europe and Asia. Such a high frequency is consistent with these archaic HLA class I variants having been positively selected because of their protective effect against contagious and devastating epidemics, such as those due to the plague agent Yersinia pestis or to Mycobacterium tuberculosis, which is responsible for deadly tuberculosis. While the exact nature of the infectious agents that contributed to the selection of the archaic variants is unknown, we are entering an exciting period in which paleogenetics and paleomicrobiology data can be integrated to generate a clearer picture of how the immune system of modern populations was shaped and the role admixture and epidemics have played in such evolutions.
[Mh] Termos MeSH primário: Doenças Transmissíveis/epidemiologia
Doenças Transmissíveis/imunologia
Evolução Molecular
Fósseis
Sistema Imunitário
Imunogenética/métodos
Paleopatologia/métodos
[Mh] Termos MeSH secundário: Seres Humanos
Seleção Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160624
[St] Status:MEDLINE
[do] DOI:10.1128/microbiolspec.PoH-0018-2015



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