المؤلفون: Mark E Engel, Taariq Salie

مصطلحات موضوعية: Immunology not elsewhere classified, Medical microbiology not elsewhere classified, Group A streptococci, immunology/genetics of the immune system, Vaccinology, Longitudinal analyses, Pharyngitis

الوصف: Supplementary materials to the following publication: Salie MT, et al. Serum immune responses to group A streptococcal antigens following pharyngeal acquisitions among children in Cape Town, South Africa. mSphere 2023 . This document contains additional information with respect to the symptoms from participants enrolled into the longitudinal study evaluating immune responses in Cape Town children. Also, GAS isolates' characteristics are provided.

العلاقة: https://figshare.com/articles/journal_contribution/Serum_immune_responses_to_group_A_streptococcal_antigens_following_pharyngeal_acquisitions_among_children_in_Cape_Town_South_Africa_Supplementary_data_/21510186Test

الإتاحة: https://doi.org/10.25375/uct.21510186.v3Test
https://figshare.com/articles/journal_contribution/Serum_immune_responses_to_group_A_streptococcal_antigens_following_pharyngeal_acquisitions_among_children_in_Cape_Town_South_Africa_Supplementary_data_/21510186Test

المؤلفون: Engel, Mark, Salie, Taariq

مصطلحات موضوعية: Vaccinology, 320499 Immunology not elsewhere classified, Longitudinal analyses, Medical microbiology not elsewhere classified, Group A streptococci, immunology/genetics of the immune system, 320799 Medical microbiology not elsewhere classified, Pharyngitis, Immunology not elsewhere classified

الوصف: Supplementary materials to the following publication: Salie MT, et al. Serum immune responses to group A streptococcal antigens following pharyngeal acquisitions among children in Cape Town, South Africa. mSphere 2023 . This document contains additional information with respect to the symptoms from participants enrolled into the longitudinal study evaluating immune responses in Cape Town children. Also, GAS isolates' characteristics are provided.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80d38ffcd8237a77ec901db4ec7aa5e9Test

المؤلفون: G Fernandez (8983853)

مصطلحات موضوعية: Immunology, congenic mouse strains, immunology/genetics of the immune system, Sexual dimorphism, QTL mapping

الوصف: Source data for 10.21203/rs.3.rs-337166/v1

العلاقة: https://figshare.com/articles/dataset/NCOMMS-21-10552A/14685906Test

الإتاحة: https://doi.org/10.6084/m9.figshare.14685906.v4Test

المؤلفون: Zimmerman, Mary, Yang, Dafeng, Hu, Xiaolin, Liu, Feiyan, Singh, Nagendra, Browning, Darren, Ganapathy, Vadivel, Chandler, Phillip, Choubey, Divaker, Abrams, Scott I., Liu, Kebin

المساهمون: Department of Biochemistry and Molecular Biology, Immunotherapy Center

مصطلحات موضوعية: Research Article, Immunology, Immunology/Genetics of the Immune System, Immunology/Immune Response, Immunology/Immunomodulation, Immunology/Leukocyte Activation, Immunology/Leukocyte Development, Animals, Antibodies, Monoclonal, Antigens, CD3, Apoptosis, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Cell Survival, Female, Gene Expression Profiling, Immunotherapy, Adoptive, Inhibitor of Apoptosis Proteins, Interferon-gamma, Intracellular Signaling Peptides and Proteins, Mice, Inbred BALB C, Neoplasms, Experimental

الوصف: Background: A common procedure in human cytotoxic T lymphocyte (CTL) adoptive transfer immunotherapy is to expand tumor-specific CTLs ex vivo using CD3 mAb prior to transfer. One of the major obstacles of CTL adoptive immunotherapy is a lack of CTL persistence in the tumor-bearing host after transfer. The aim of this study is to elucidate the molecular mechanisms underlying the effects of stimulation conditions on proliferation and survival of tumor-specific CTLs. ; Methodology/Principal Findings: Tumor-specific CTLs were stimulated with either CD3 mAb or cognate Ag and analyzed for their proliferation and survival ex vivo and persistence in tumor-bearing mice. Although both Ag and CD3 mAb effectively induced the cytotoxic effecter molecules of the CTLs, we observed that Ag stimulation is essential for sustained CTL proliferation and survival. Further analysis revealed that Ag stimulation leads to greater proliferation rates and less apoptosis than CD3 mAb stimulation. Re-stimulation of the CD3 mAb-stimulated CTLs with Ag resulted in restored CTL proliferative potential, suggesting that CD3 mAb-induced loss of proliferative potential is reversible. Using DNA microarray technology, we identified that survivin and ifi202, two genes with known functions in T cell apoptosis and proliferation, are differentially induced between Ag- and CD3 mAb-stimulated CTLs. Analysis of the IFN-γ signaling pathway activation revealed that Ag stimulation resulted in rapid phosphorylation of STAT1 (pSTAT1), whereas CD3 mAb stimulation failed to activate STAT1. Chromatin immunoprecipitation revealed that pSTAT1 is associated with the promoters of both survivin and ifi202 in T cells and electrophoresis mobility shift assay indicated that pSTAT1 directly binds to the gamma activation sequence element in the survivin and ifi202 promoters. Finally, silencing ifi202 expression significantly decreased T cell proliferation. ; Conclusions/Significance: Our findings delineate a new role of the IFN-γ signaling pathway in regulating T cell ...

العلاقة: PLoS One. 2010 Nov 22; 5(11):e14076; http://hdl.handle.net/10675.2/610Test; PMC2989915

الإتاحة: https://doi.org/10.1371/journal.pone.0014076Test
http://hdl.handle.net/10675.2/610Test

المؤلفون: Deng, Ya-jun, Ye, Shi-hui, Yan, Jiang-wei, Yang, Guang, Wang, Hong-dan, Qin, Hai-xia, Huang, Qi-zhao, Zhang, Jing-Jing, Shen, Chun-mei, Zhu, Bo-feng

المساهمون: Vascular Biology Center, Institute of Molecular Medicine and Genetics

مصطلحات موضوعية: Research Article, Genetics and Genomics/Population Genetics, Immunology/Genetics of the Immune System, Evolutionary Biology/Human Evolution, Alleles, Asian Continental Ancestry Group, China, Gene Frequency, Genetic Variation, Genotype, HLA-A Antigens, HLA-B Antigens, HLA-DR Antigens, HLA-DRB1 Chains, Haplotypes, Humans, Linkage Disequilibrium, Phylogeny, Polymorphism, Genetic

الوصف: Background: Previous studies indicate that the frequency distributions of HLA alleles and haplotypes vary from one ethnic group to another or between the members of the same ethnic group living in different geographic areas. It is necessary and meaningful to study the high-resolution allelic and haplotypic distributions of HLA loci in different groups. ; Methodology/Principal Findings: High-resolution HLA typing for the Uyghur ethnic minority group using polymerase chain reaction-sequence-based-typing method was first reported. HLA-A, -B and -DRB1 allelic distributions were determined in 104 unrelated healthy Uyghur individuals and haplotypic frequencies and linkage disequilibrium parameters for HLA loci were estimated using the maximum-likelihood method. A total of 35 HLA-A, 51 HLA-B and 33 HLA-DRB1 alleles were identified at the four-digit level in the population. High frequency alleles were HLA-A*1101 (13.46%), A*0201 (12.50%), A*0301 (10.10%); HLA-B*5101(8.17%), B*3501(6.73%), B*5001 (6.25%); HLA-DRB1*0701 (16.35%), DRB1*1501 (8.65%) and DRB1*0301 (7.69%). The two-locus haplotypes at the highest frequency were HLA-A*3001-B*1302 (2.88%), A*2402-B*5101 (2.86%); HLA-B*5001-DRB1*0701 (4.14%) and B*0702-DRB1*1501 (3.37%). The three-locus haplotype at the highest frequency was HLA-A*3001-B*1302-DRB1*0701(2.40%). Significantly high linkage disequilibrium was observed in six two-locus haplotypes, with their corresponding relative linkage disequilibrium parameters equal to 1. Neighbor-joining phylogenetic tree between the Uyghur group and other previously reported populations was constructed on the basis of standard genetic distances among the populations calculated using the four-digit sequence-level allelic frequencies at HLA-A, HLA-B and HLA-DRB1 loci. The phylogenetic analyses reveal that the Uyghur group belongs to the northwestern Chinese populations and is most closely related to the Xibe group, and then to Kirgiz, Hui, Mongolian and Northern Han. ; Conclusions/Significance: The present findings could be ...

العلاقة: PLoS One. 2010 Nov 4; 5(11):e13458; http://hdl.handle.net/10675.2/607Test; PMC2973946

الإتاحة: https://doi.org/10.1371/journal.pone.0013458Test
http://hdl.handle.net/10675.2/607Test

المؤلفون: Christian B. Willberg, Keith E. Garrison, R. Brad Jones, Duncan A. Meiklejohn, Gerald Spotts, Teri J. Liegler, Mario A. Ostrowski, Annika C. Karlsson, Frederick M. Hecht, Douglas F. Nixon

المصدر: PloS one, vol 11, iss 7
PLoS ONE
PLoS ONE, Vol 11, Iss 7, p e0160293 (2016)

مصطلحات موضوعية: General Science & Technology, lcsh:Medicine, Epitopes, T-Lymphocyte, HIV Infections, T-Cell Antigen Receptor Specificity, CD8-Positive T-Lymphocytes, Immunology/Immunity to Infections, Humans, Longitudinal Studies, lcsh:Science, Alleles, Multidisciplinary, lcsh:R, Correction, Genetic Variation, Infectious Diseases/HIV Infection and AIDS, Viral Load, CD4 Lymphocyte Count, Immunology/Immune Response, Disease Progression, HIV-1, lcsh:Q, HLA-B35 Antigen, Immunology/Genetics of the Immune System, Research Article, T-Lymphocytes, Cytotoxic

الوصف: Background The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele. Methodology/Principal Findings Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals. Conclusions/Significance This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2c4b8835b3eaba7e537f91a1cf2a6d1Test
https://escholarship.org/uc/item/99p2x3chTest

المؤلفون: Shunichi Takeda, Ben Buelow, Marcia Paddock, Andrew M. Scharenberg

المصدر: PLoS Biology, Vol 16, Iss 3, p e1002621 (2018)
PLoS Biology

مصطلحات موضوعية: 0301 basic medicine, Immunoglobulin gene, Biochemistry/Replication and Repair, Mutation, General Immunology and Microbiology, QH301-705.5, DNA repair, General Neuroscience, Protein domain, Biology, medicine.disease_cause, Biochemistry, DNA-binding protein, General Biochemistry, Genetics and Molecular Biology, Protein–protein interaction, Cell biology, 03 medical and health sciences, 030104 developmental biology, BRCT domain, medicine, Gene conversion, Biology (General), Immunology/Genetics of the Immune System, General Agricultural and Biological Sciences, Research Article

الوصف: During affinity maturation, genomic integrity is maintained through specific targeting of DNA mutations. The DNA damage sensor PARP-1 helps determine whether a DNA lesion results in faithful or mutagenic repair.
Genetic variation at immunoglobulin (Ig) gene variable regions in B-cells is created through a multi-step process involving deamination of cytosine bases by activation-induced cytidine deaminase (AID) and their subsequent mutagenic repair. To protect the genome from dangerous, potentially oncogenic effects of off-target mutations, both AID activity and mutagenic repair are targeted specifically to the Ig genes. However, the mechanisms of targeting are unknown and recent data have highlighted the role of regulating mutagenic repair to limit the accumulation of somatic mutations resulting from the more widely distributed AID-induced lesions to the Ig genes. Here we investigated the role of the DNA damage sensor poly-(ADPribose)-polymerase-1 (PARP-1) in the repair of AID-induced DNA lesions. We show through sequencing of the diversifying Ig genes in PARP-1−/− DT40 B-cells that PARP-1 deficiency results in a marked reduction in gene conversion events and enhanced high-fidelity repair of AID-induced lesions at both Ig heavy and light chains. To further characterize the role of PARP-1 in the mutagenic repair of AID-induced lesions, we performed functional analyses comparing the role of engineered PARP-1 variants in high-fidelity repair of DNA damage induced by methyl methane sulfonate (MMS) and the mutagenic repair of lesions at the Ig genes induced by AID. This revealed a requirement for the previously uncharacterized BRCT domain of PARP-1 to reconstitute both gene conversion and a normal rate of somatic mutation at Ig genes, while being dispensable for the high-fidelity base excision repair. From these data we conclude that the BRCT domain of PARP-1 is required to initiate a significant proportion of the mutagenic repair specific to diversifying antibody genes. This role is distinct from the known roles of PARP-1 in high-fidelity DNA repair, suggesting that the PARP-1 BRCT domain has a specialized role in assembling mutagenic DNA repair complexes involved in antibody diversification.
Author Summary To produce a limitless diversity of antibodies within the constraints of a finite genome, activated B cells introduce random mutations into antibody genes through a process of targeted DNA damage and subsequent mutagenic repair. At the same time, the rest of the genome must be protected from mutagenesis to prevent off-target mutations which can lead to the development of lymphoma or leukemia. How antibody genes are specifically targeted is still largely unknown. A potential player in this process is the DNA-damage-sensing enzyme PARP-1, which recruits DNA repair enzymes to sites of damage. Using a chicken B cell lymphoma cell line because it has only a single PARP isoform and constitutively mutates its antibody genes, we compared the types of mutations accumulated in PARP-1−/− cells to wild type. We found that in cells lacking PARP-1, the major pathway of mutagenic repair was disrupted and fewer mutations than normal were introduced into their antibody genes. To identify what might be important for mutagenesis, we tested different factors for their ability to rescue this mutagenic deficiency and found a role for the BRCT (BRCA1 C-terminal) domain of PARP-1, a consensus protein domain known to be involved in directing protein-protein interactions. Our evidence suggests that PARP-1 may be interacting with another hypothetical protein via its BRCT domain that is required for the mutagenic rather than faithful repair of DNA lesions in the antibody genes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::207764a0100f030f35d9ded47339ea47Test
https://doi.org/10.1371/journal.pbio.1002621Test

المؤلفون: Stefan Schreiber, Gesa M. Richter, Birte Groessner-Schreiber, Bruno G. Loos, Barbara Noack, Arne S. Schaefer, Michael Nothnagel, Nour-Eddine El Mokhtari, Søren Jepsen

المساهمون: Parodontologie (OUD, ACTA)

المصدر: PLoS Genetics, Vol 5, Iss 2, p e1000378 (2009)
PLoS Genetics
Schaefer, A S, Richter, G M, Groessner-Schreiber, B, Noack, D, Nothnagel, M, El Mokhtari, N E, Loos, B G, Jepsen, S & Schreiber, S 2009, ' Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis ', PLoS Genetics, vol. 5, pp. 1-8 . https://doi.org/10.1371/journal.pgen.1000378Test
PLOS Genetics, 5, 1-8. Public Library of Science
PLoS Genetics, 5, 1-8. Public Library of Science
PLoS Genetics, 5 (2).

مصطلحات موضوعية: Male, Cancer Research, Linkage disequilibrium, Coronary Disease, Genome-wide association study, Bioinformatics, Linkage Disequilibrium, 0302 clinical medicine, Germany, Aggressive periodontitis, Genetics and Genomics/Genetics of Disease, Genetics (clinical), Genetics and Genomics/Medical Genetics, Genetics, 0303 health sciences, Middle Aged, 3. Good health, Female, Genetics and Genomics/Gene Discovery, Genetics and Genomics/Genetics of the Immune System, Chromosomes, Human, Pair 9, Research Article, Adult, Genotype, lcsh:QH426-470, Single-nucleotide polymorphism, Locus (genetics), Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, RNA, Antisense, Periodontitis, Molecular Biology, Cyclin-Dependent Kinase Inhibitor p16, Ecology, Evolution, Behavior and Systematics, Aged, Cyclin-Dependent Kinase Inhibitor p15, 030304 developmental biology, Haplotype, 030206 dentistry, medicine.disease, lcsh:Genetics, Diabetes Mellitus, Type 2, Immunology/Genetics of the Immune System

الوصف: Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33–2.94; P = 6.9×10−4) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6×10−2) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases.
Author Summary Coronary heart disease (CHD) and periodontitis are the most widespread diseases in the Western industrialized world and pose a substantial health threat to populations worldwide. CHD is a leading cause for premature death, and periodontitis is the major cause for tooth loss in adults over 40 years. Both diseases are associated with similar risk factors such as smoking, diabetes, and gender, and both diseases are further characterized by a chronic inflammatory process. In the last year, several genome studies have identified a region of the human genome near the CDKN2A and CDKN2B genes as having an influence on CHD. We show that this genetic region, being the most important susceptibility locus for CHD to date, is also associated with a substantial risk increase of aggressive periodontitis. The associated genetic region maps to a genomic region that codes for an “antisense RNA,” which partly overlaps regulatory and coding sequences of genes CDKN2A/CDKN2B. The interplay between these common inflammatory complex diseases could be partially due to the shared genetic risk variants of this antisense RNA.

وصف الملف: application/pdf; text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c835cdcefdfa557b8157dda1551be8f6Test
https://hdl.handle.net/11245/1.314037Test

المؤلفون: Madjou Sacko, Boubacar Coulibaly, Michelle M. Riehle, Susan M. Rottschaefer, Oumou Niaré, Isabelle Morlais, Sekou F. Traore, Brian P. Lazzaro, Kenneth D. Vernick

المساهمون: Cornell University [New York], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, University of Bamako [Mali], Institut de Recherche pour le Développement [Yaoundé, Cameroun] (IRD-OCEAC), Génétique et Génomique des Insectes vecteurs, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

المصدر: PLoS Biology
PLoS Biology, Public Library of Science, 2011, 9 (3), pp.e1000600. ⟨10.1371/journal.pbio.1000600⟩
PLoS Biology, 2011, 9 (3), pp.e1000600. ⟨10.1371/journal.pbio.1000600⟩
PLoS Biology, Vol 9, Iss 3, p e1000600 (2011)

مصطلحات موضوعية: MESH: Geography, Plasmodium falciparum/*immunology, Anopheles gambiae, MESH: Selection, Genetic, Adaptation, Biological, Population genetics, Innate/genetics, 0302 clinical medicine, MESH: Insect Proteins, MESH: Animals, Biology (General), MESH: Evolution, Molecular, MESH: Plasmodium falciparum, Genetics, 0303 health sciences, education.field_of_study, biology, Geography, General Neuroscience, Anopheles/*genetics/immunology/parasitology, Insect Vectors/*genetics/parasitology, 3. Good health, Insect Proteins, MESH: Immunity, Innate, Seasons, General Agricultural and Biological Sciences, Polymorphism, Research Article, QH301-705.5, Evolution, 030231 tropical medicine, Population, Plasmodium falciparum, Locus (genetics), MESH: Insect Vectors, Quantitative trait locus, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, MESH: Anopheles, 03 medical and health sciences, Insect Proteins/chemistry/*genetics, Genetic, Genetic variation, Anopheles, parasitic diseases, MESH: Polymorphism, Genetic, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Selection, Genetic, Adaptation, education, 030304 developmental biology, Polymorphism, Genetic, General Immunology and Microbiology, Evolutionary Biology/Evolutionary and Comparative Genetics, MESH: Adaptation, Biological, Immunity, Molecular, biology.organism_classification, Biological, Immunity, Innate, Insect Vectors, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Evolutionary biology, Selection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Selective sweep, Immunology/Genetics of the Immune System, MESH: Seasons

الوصف: The three-gene APL1 locus encodes essential components of the mosquito immune defense against malaria parasites. APL1 was originally identified because it lies within a mapped QTL conferring the vector mosquito Anopheles gambiae natural resistance to the human malaria parasite, Plasmodium falciparum, and APL1 genes have subsequently been shown to be involved in defense against several species of Plasmodium. Here, we examine molecular population genetic variation at the APL1 gene cluster in spatially and temporally diverse West African collections of A. gambiae. The locus is extremely polymorphic, showing evidence of adaptive evolutionary maintenance of genetic variation. We hypothesize that this variability aids in defense against genetically diverse pathogens, including Plasmodium. Variation at APL1 is highly structured across geographic and temporal subpopulations. In particular, diversity is exceptionally high during the rainy season, when malaria transmission rates are at their peak. Much less allelic diversity is observed during the dry season when mosquito population sizes and malaria transmission rates are low. APL1 diversity is weakly stratified by the polymorphic 2La chromosomal inversion but is very strongly subdivided between the M and S “molecular forms.” We find evidence that a recent selective sweep has occurred at the APL1 locus in M form mosquitoes only. The independently reported observation of a similar M-form restricted sweep at the Tep1 locus, whose product physically interacts with APL1C, suggests that epistatic selection may act on these two loci causing them to sweep coordinately.
Author Summary Immune defense genes are sometimes highly variable in host populations, reflecting selective pressure to combat diverse pathogens. In other instances, where there are only a few dominant pathogens, natural selection may favor only one or a few defense alleles. Here, we show that both adaptive strategies can occur in the same genes under different circumstances. We examined diversity in the APL1 genes of the human malaria vector mosquito Anophleles gambiae, which play a role in defense against malaria parasites. We found that the APL1 genes are exceptionally polymorphic, being 10-fold more diverse than typical A. gambiae genes. The distribution of APL1 allelic diversity, however, is strongly structured depending on whether the genes are carried by the M or S “molecular forms” of the vector, which are thought to constitute newly forming species. We show that despite the evolutionary maintenance of APL1 diversity in the S form of A. gambiae, there is evidence of strong recent directional selection on APL1 genes in the M form. Independent research has shown that Tep1, a gene which encodes a protein that physically interacts with the APL1C protein, also harbors high allelic diversity in the S form and shows evidence of recent directional selection in the M form, suggesting that the evolutionary trajectories of the Tep1 and APL1 defense loci may be correlated.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2750bc43a80da2c411880a8e1b1f2788Test
https://hal-pasteur.archives-ouvertes.fr/pasteur-02008334/documentTest

المؤلفون: Maja Barbalić, Paul M. Ridker, Alex Parker, Daniel I. Chasman, Joshua C. Bis, Dov Shiffman, Guillaume Paré, Josée Dupuis, Emelia J. Benjamin, Lynda M. Rose, Abbas Dehghan

المصدر: PLoS Genetics, Vol 7, Iss 4, p e1001374 (2011)
PLoS Genetics

مصطلحات موضوعية: Cancer Research, medicine.medical_specialty, Multifactorial Inheritance, Genotype, lcsh:QH426-470, Transcription Factor RelA, Cardiovascular Disorders/Coronary Artery Disease, Genome-wide association study, ICAM-1, GWAS, Disease, Biology, Genetics and Genomics/Complex Traits, Polymorphism, Single Nucleotide, ABO Blood-Group System, Cohort Studies, Gene Frequency, Molecular genetics, ABO blood group system, Genetics, medicine, Humans, Molecular Biology, Allele frequency, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Genetic association, Adaptor Proteins, Signal Transducing, Models, Genetic, Genome, Human, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Proteins, Lipase, Intercellular Adhesion Molecule-1, I-kappa B Kinase, lcsh:Genetics, Genetic Loci, Female, Immunology/Genetics of the Immune System, Genome-Wide Association Study, Research Article

الوصف: Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.
Author Summary Soluble Intercellular Adhesion Molecule 1 (sICAM-1) is an inflammatory marker that has been associated with several common diseases such as diabetes, heart disease, stroke, and malaria. While it is known that blood concentrations of sICAM-1 are at least partially genetically determined, our current knowledge of which genes mediate this effect is limited. Taking advantage of technologies allowing us to interrogate genetic variation on a whole-genome basis, we found that variation in the NFKBIK, PNPLA3, RELA, and SH2B3 genes are important determinant of sICAM-1 blood concentrations. The NFKBIB and RELA genes are involved in regulation of inflammation. These observations are significant because this is the first report of genetic association within these extensively studied inflammation genes. The PNPLA3 gene has previously been associated with liver disease, and the SH2B3 gene has been associated with a multitude of traits including cardiovascular disease. Extension of these associations to sICAM-1 adds to the intriguing diversity of effects of these genes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4090913610b8ae5bcd0a11f9598490bTest
https://doi.org/10.1371/journal.pgen.1001374Test