15 results on '"Giffon, T."'
Search Results
2. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids
- Author
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Alcala, N, Leblay, N, Gabriel, A A G, Mangiante, L, Hervas, D, Giffon, T, Sertier, A S, Ferrari, A, Derks, J, Ghantous, A, Delhomme, T M, Chabrier, A, Cuenin, C, Abedi-Ardekani, B, Boland, A, Olaso, R, Meyer, V, Altmuller, J, Le Calvez-Kelm, F, Durand, G, Voegele, C, Boyault, S, Moonen, L, Lemaitre, N, Lorimier, P, Toffart, A C, Soltermann, A, Clement, J H, Saenger, J, Field, J K, et al, and University of Zurich
- Subjects
1300 General Biochemistry, Genetics and Molecular Biology ,10049 Institute of Pathology and Molecular Pathology ,610 Medicine & health ,1600 General Chemistry ,3100 General Physics and Astronomy - Published
- 2019
3. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids
- Author
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Alcala, N; https://orcid.org/0000-0002-5961-5064, Leblay, N, Gabriel, A A G, Mangiante, L, Hervas, D, Giffon, T; https://orcid.org/0000-0001-8133-6507, Sertier, A S, Ferrari, A, Derks, J; https://orcid.org/0000-0002-0442-1879, Ghantous, A, Delhomme, T M; https://orcid.org/0000-0003-0265-4246, Chabrier, A, Cuenin, C, Abedi-Ardekani, B, Boland, A, Olaso, R, Meyer, V, Altmuller, J, Le Calvez-Kelm, F, Durand, G, Voegele, C, Boyault, S; https://orcid.org/0000-0002-2297-6894, Moonen, L, Lemaitre, N, Lorimier, P, Toffart, A C, Soltermann, A, Clement, J H; https://orcid.org/0000-0002-6601-2456, Saenger, J, Field, J K; https://orcid.org/0000-0003-3951-6365, et al, Alcala, N; https://orcid.org/0000-0002-5961-5064, Leblay, N, Gabriel, A A G, Mangiante, L, Hervas, D, Giffon, T; https://orcid.org/0000-0001-8133-6507, Sertier, A S, Ferrari, A, Derks, J; https://orcid.org/0000-0002-0442-1879, Ghantous, A, Delhomme, T M; https://orcid.org/0000-0003-0265-4246, Chabrier, A, Cuenin, C, Abedi-Ardekani, B, Boland, A, Olaso, R, Meyer, V, Altmuller, J, Le Calvez-Kelm, F, Durand, G, Voegele, C, Boyault, S; https://orcid.org/0000-0002-2297-6894, Moonen, L, Lemaitre, N, Lorimier, P, Toffart, A C, Soltermann, A, Clement, J H; https://orcid.org/0000-0002-6601-2456, Saenger, J, Field, J K; https://orcid.org/0000-0003-3951-6365, and et al
- Abstract
The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.
- Published
- 2019
4. Multi-omics comparative analyses of pulmonary typical carcinoids, atypical carcinoids, and large-cell neuroendocrine carcinoma
- Author
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Leblay, N., Alcala, N., Marin, D.H., Delhomme, T.M., Giffon, T., Ghantous, A., Chabrier, A., Cuenin, C., Altmueller, J., Durand, G., Voegele, C., Lorimier, P., Toffart, A.C., Derks, J., Brustugun, O.T., Clement, J.H., Saenger, J., Field, J.K., Soltermann, A., Wright, G.M., Roz, L., Muscarella, L.A., Graziano, P., Herceg, Z., Speel, E.J., Nuernberg, P., McKay, J., Girard, N., Lantuejoul, S., Sandoval, J., Brambilla, E., Foll, M., Fernandez-Cuesta, L., MUMC+: MA Med Staf Artsass Longziekten (9), RS: GROW - R2 - Basic and Translational Cancer Biology, and Pathologie
- Abstract
Pulmonary grade-1 typical (TC) and grade-2 atypical (AC) carcinoids share molecular characteristics with grade-3 large-cell neuroendocrine carcinoma (LCNEC) despite the distinct clinical behaviors. Most carcinoids can be surgically resected, however, limited treatment options exist for metastatic disease, present in 10-23% of TC and 40-50% of AC. Comprehensive genomic studies could help identify better therapeutic opportunities, novel diagnostic markers, and provide insight on the mechanisms responsible for the increased aggressiveness of AC versus TC. Such studies are rare due to the limited availability of suitable material. We have established a multi-center collaboration that has given us access to a unique collection of samples. We have already characterized 40 TC and 60 LCNEC genomes/exomes, and 61 TC, 8 AC and 69 LCNEC trancriptomes (published data). In the present study, we have performed whole-exome and transcriptome sequencing on 20 AC patients. Methylation data from 850K Illumina arrays were also generated for these samples, and for a subset of 20 TC and 20 LCNEC previously mentioned. When comparing the mutational data on AC with that of TC and LCNEC, we have found that similar to TC, AC harbor recurrent alterations in chromatin remodeling genes (such as MEN1 and ARID1A). They also carry alterations in genes involved in other cancer-related pathways (based on STRING), such as cell motility and cell death explaining their more aggressive phenotype. Integrative clustering analysis (MOFA and iCLUSTER) based on expression and methylation data tends to classify carcinoids into four groups: groups 1 and 2 are mostly composed of females with TC, and differ by their age composition and smoking status (Fisher's exact test p=0.008 and 0.03, respectively). Groups 3 and 4 are mostly composed of males with AC (Fisher's exact test for tumor type p=8x10-5). When including the LCNEC data, the samples from group 3 cluster with LCNEC, suggesting that AC can display a variety of expression and methylation patterns that may be linked to aggressiveness. This result was supported by the better survival of groups 1 and 2 compared to groups 3 and 4 (log-rank p=0.02), for which survival was similar to that of patients with LCNEC. Here, we present for the first time: (i) a multi-omics study on AC; (ii) the methylome characterization of TC, AC, and LCNEC; and (iii) the results of a comparative analysis of TC, AC, and LCNEC based on their molecular characteristics. We have identified the genes and pathways that might explain the progression from low-grade TC to intermediate-grade AC. Our expression and methylation data also supports the existence of a “super-AC” group, which clusters with LCNEC. Finally, we have identified a panel of molecular alterations that may help pathologist distinguishing between these three entities. NL and NA contributed equally. LFC and MF jointly supervised this work. Citation Format: Noémie Leblay, Nicolas Alcala, David Hervás Marin, Tiffany M. Delhomme, Théo Giffon, Akram Ghantous, Amélie Chabrier, Cyrille Cuenin, Janine Altmueller, Geoffroy Durand, Catherine Voegele, Philippe Lorimier, Anne-Claire Toffart, Jules Derks, Odd Terje Brustugun, Joachim H. Clement, Joerg Saenger, John K. Field, Alex Soltermann, Gavin M. Wright, Luca Roz, Lucia Anna Muscarella, Paolo Graziano, Zdenko Herceg, Ernst-Jan Speel, Peter Nuernberg, James McKay, Nicolas Girard, Sylvie Lantuejoul, Juan Sandoval, Elisabeth Brambilla, Matthieu Foll, Lynnette Fernandez-Cuesta. Multi-omics comparative analyses of pulmonary typical carcinoids, atypical carcinoids, and large-cell neuroendocrine carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5358.
- Published
- 2018
5. Influenza A virus elevates active cathepsin B in primary murine DC
- Author
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Burster, T., primary, Giffon, T., additional, Dahl, M. E., additional, Bjorck, P., additional, Bogyo, M., additional, Weber, E., additional, Mahmood, K., additional, Lewis, D. B., additional, and Mellins, E. D., additional
- Published
- 2007
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6. La région HLA de classe I du CMH : une des régions les plus complexes du génome humain ?
- Author
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Pichon, L, primary, Giffon, T, additional, Chauvel, B, additional, Le Gall, JY, additional, and David, V, additional
- Published
- 1996
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7. Retinoic acid hypersensitivity promotes peripheral tolerance in recent thymic emigrants.
- Author
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Bhaumik S, Giffon T, Bolinger D, Kirkman R, Lewis DB, Weaver CT, and Randolph DA
- Subjects
- Animals, Animals, Newborn, Autoantigens immunology, Autoantigens metabolism, Forkhead Transcription Factors antagonists & inhibitors, Forkhead Transcription Factors biosynthesis, Hypersensitivity metabolism, Hypersensitivity pathology, Interferon-gamma antagonists & inhibitors, Interferon-gamma biosynthesis, Lymph Nodes cytology, Lymph Nodes immunology, Lymph Nodes metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Spleen cytology, Spleen immunology, Spleen metabolism, Thymus Gland cytology, Thymus Gland immunology, Thymus Gland metabolism, Time Factors, Tretinoin metabolism, Cell Movement immunology, Hypersensitivity immunology, Immune Tolerance, Tretinoin physiology
- Abstract
Whereas thymic education eliminates most self-reactive T cells, additional mechanisms to promote tolerance in the periphery are critical to prevent excessive immune responses against benign environmental Ags and some self-Ags. In this study we show that murine CD4(+) recent thymic emigrants (RTEs) are programmed to facilitate tolerance in the periphery. Both in vitro and in vivo, naive RTEs more readily upregulate Foxp3 than do mature naive cells after stimulation under tolerogenic conditions. In RTEs, a relatively high sensitivity to retinoic acid contributes to decreased IFN-γ production, permitting the expression of Foxp3. Conversely, mature naive CD4 cells have a lower sensitivity to retinoic acid, resulting in increased IFN-γ production and subsequent IFN-γ-mediated silencing of Foxp3 expression. Enhanced retinoic acid signaling and Foxp3 induction in RTEs upon Ag encounter in the periphery may serve as form of secondary education that complements thymic education and helps avoid inappropriate immune responses. This mechanism for tolerance may be particularly important in settings where RTEs comprise a large fraction of the peripheral T cell pool, such as in newborns or after umbilical cord blood transplant.
- Published
- 2013
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8. Immunotherapy with MVA-BN®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells.
- Author
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Mandl SJ, Rountree RB, Dalpozzo K, Do L, Lombardo JR, Schoonmaker PL, Dirmeier U, Steigerwald R, Giffon T, Laus R, and Delcayre A
- Subjects
- Adenocarcinoma immunology, Adenocarcinoma pathology, Animals, B-Lymphocyte Subsets enzymology, B-Lymphocyte Subsets pathology, Cancer Vaccines immunology, Cell Line, Tumor, Colonic Neoplasms enzymology, Colonic Neoplasms pathology, Disease Models, Animal, Female, Humans, Immunophenotyping, Lung Neoplasms immunology, Lung Neoplasms secondary, Lung Neoplasms therapy, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, T-Lymphocytes, Regulatory enzymology, T-Lymphocytes, Regulatory pathology, Adenocarcinoma therapy, B-Lymphocyte Subsets immunology, Cancer Vaccines pharmacology, Colonic Neoplasms therapy, Immunotherapy methods, Receptor, ErbB-2 immunology, T-Lymphocytes, Regulatory immunology
- Abstract
MVA-BN®-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN®-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (T(reg)) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN®-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN®-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8+CD11c+ T cells accompanied by a decrease in the frequency of T(reg) cells in the lung, resulting in a significantly increased ratio of effector T cells to T(reg) cells. In contrast, administration of HER2 protein formulated in Complete Freund's Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8+ T cells or the decrease in the frequency of T(reg) cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8+ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN®-HER2. Furthermore, depletion of CD4+ or CD25+ cells demonstrated that tumor-induced T(reg) cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN®-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN®-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression.
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- 2012
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9. Impaired accumulation and function of memory CD4 T cells in human IL-12 receptor beta 1 deficiency.
- Author
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Cleary AM, Tu W, Enright A, Giffon T, Dewaal-Malefyt R, Gutierrez K, and Lewis DB
- Subjects
- Adolescent, CD4-Positive T-Lymphocytes metabolism, Cell Membrane genetics, Cell Membrane immunology, Child, Child, Preschool, Exons genetics, Humans, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes immunology, Interferon-gamma biosynthesis, Interleukin-12 deficiency, Interleukin-12 genetics, Interleukin-12 physiology, Interleukin-12 Subunit p40, Interleukin-23, Interleukin-23 Subunit p19, Interleukins deficiency, Interleukins genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation genetics, Male, Point Mutation, Protein Subunits deficiency, Protein Subunits genetics, Protein Subunits physiology, RNA Splicing genetics, RNA, Messenger biosynthesis, RNA, Messenger blood, Receptors, Interleukin biosynthesis, Receptors, Interleukin physiology, Receptors, Interleukin-12, Salmonella Infections genetics, Salmonella Infections immunology, T-Lymphocyte Subsets metabolism, Th1 Cells immunology, Th1 Cells metabolism, CD4-Positive T-Lymphocytes immunology, Cell Movement genetics, Cell Movement immunology, Immunologic Memory genetics, Interleukin-12 metabolism, Receptors, Interleukin deficiency, Receptors, Interleukin genetics, T-Lymphocyte Subsets immunology
- Abstract
Defects in IL-12 production or IL-12 responsiveness result in a vulnerability to infection with non-viral intracellular organisms, but the immunological mechanisms responsible for this susceptibility remain poorly understood. We present an immunological analysis of a patient with disseminated Salmonella enteritidis and a homozygous splice acceptor mutation in the IL-12Rbeta1-chain gene. This mutation resulted in the absence of IL-12Rbeta1 protein on PBMC and an inability of T cells to specifically bind IL-12 or produce IFN-gamma in response to either IL-12 or IL-23. The accumulation of memory (CD45R0(high)) CD4 T cells that were CCR7(high) (putative central memory cells) was normal or increased for age. Central memory CD4 T cells of the patient and age-matched controls were similar in having a low to undetectable capacity to produce IFN-gamma after polyclonal stimulation. In contrast, the patient had a substantial decrease in the number of CCR7(neg/dull) CD45R0(high) memory CD4 T cells (putative effector memory cells), and these differed from control cells in having a minimal ability to produce IFN-gamma after polyclonal stimulation. Importantly, tetanus toxoid-specific IFN-gamma production by PBMC from the patient was also significantly reduced compared with that in age-matched controls, indicating that signaling via the IL-12Rbeta1-chain is generally necessary for the in vivo accumulation of human memory CD4 T cells with Th1 function. These results are also consistent with a model in which the IL-12Rbeta1 subunit is necessary for the conversion of central memory CD4 T cells into effector memory cells.
- Published
- 2003
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10. Systematic sequencing of the human HLA-A/HLA-F region: establishment of a cosmid contig and identification of a new gene cluster within 37 kb of sequence.
- Author
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Lepourcelet M, Andrieux N, Giffon T, Pichon L, Hampe A, Galibert F, and Mosser J
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- Amino Acid Sequence, Animals, Base Sequence, Dyneins, Evolution, Molecular, Hemochromatosis genetics, Humans, Male, Mice, Molecular Sequence Data, Sequence Alignment, Sequence Homology, Species Specificity, Testis metabolism, Ubiquitin-Protein Ligases, Zinc Fingers genetics, t-Complex Genome Region, Chromosome Walking, Chromosomes, Human, Pair 6 genetics, Cosmids genetics, DNA-Binding Proteins genetics, Genes, Genes, MHC Class I, HLA Antigens genetics, HLA-A Antigens genetics, Histocompatibility Antigens Class I genetics, Intracellular Signaling Peptides and Proteins, Microtubule-Associated Proteins, Nuclear Proteins genetics
- Abstract
The class I region of the human histocompatibility complex is characterized by a high density of genes and pseudogenes and a complex structural organization. To elucidate the complete structure of the HLA-A/HLA-F region with a view to defining its contents in genes and pseudogenes, we developed a strategy of systematic sequencing. This report describes the establishment of a cosmid contig spanning most of the region and the analysis of a 37-kb sequence from one of the cosmids. Four new genes, organized with the HCG-V gene in a clustered structure, have been identified. Two of these contain a zinc finger motif characteristic of DNA-binding proteins. The former, a member of the C3HC4 protein family, is highly expressed in prostate and contains a B30-2-like sequence identified in several genes mapped within the class I region. The latter, which is ubiquitously expressed, is the human equivalent of the yeast polymerase IA12.2 subunit and of the murine tctex6 gene. Of the two other genes, one remains an anonymous gene with no particular feature, while the fourth, specifically expressed in testis, is the human equivalent of the murine tctex4 gene. This cluster, located in a region corresponding to a syntenic unit between mouse and human, appears to be highly conserved.
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- 1996
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11. Structural analysis of the HLA-A/HLA-F subregion: precise localization of two new multigene families closely associated with the HLA class I sequences.
- Author
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Pichon L, Carn G, Bouric P, Giffon T, Chauvel B, Lepourcelet M, Mosser J, Legall JY, and David V
- Subjects
- Cell Line, Chromosome Mapping, Chromosomes, Artificial, Yeast, Cloning, Molecular, Cosmids, DNA Fingerprinting, Hemochromatosis genetics, Humans, HLA Antigens genetics, HLA-A Antigens genetics, Histocompatibility Antigens Class I genetics, Multigene Family
- Abstract
Positional cloning strategies for the hemochromatosis gene have previously concentrated on a target area restricted to a maximum genomic expanse of 400 kb around the HLA-A and HLA-F loci. Recently, the candidate region has been extended to 2-3 Mb on the distal side of the MHC. In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion. Two of these (HCG II and HCG IV) belong to multigene families, as well as other sequences already described in this region, i.e., P5, pMC 6.7, and HLA class 1. Fingerprinting of the four YACs overlapping the region was performed and allowed partial localization of the different multigene family sequences on each YAC without defining their exact positions. Fingerprinting on cosmids isolated from the ICRF chromosome 6-specific cosmid library allowed more precise localization of the redundant sequences in all of the multigene families and revealed their apparent organization in clusters. Further examination of these intertwined sequences demonstrated that this structural organization resulted from a succession of complex phenomena, including duplications and contractions. This study presents a precise description of the structural organization of the HLA-A/HLA-F region and a determination of the sequences involved in the megabase size polymorphism observed among the A3, A24, and A31 haplotypes.
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- 1996
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12. Physical map of the HLA-A/HLA-F subregion and identification of two new coding sequences.
- Author
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Pichon L, Giffon T, Chauvel B, Carn G, Bouric P, El Kahloun A, Legall JY, and David V
- Subjects
- Blotting, Northern, Chromosomes, Artificial, Yeast, Cloning, Molecular, DNA Fingerprinting, DNA, Complementary genetics, Electrophoresis, Gel, Pulsed-Field, Gene Library, HLA Antigens genetics, HLA-A Antigens genetics, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Transcription, Genetic, Chromosomes, Human, Pair 6, Hemochromatosis genetics, Histocompatibility Antigens Class I genetics, Open Reading Frames, Restriction Mapping
- Abstract
As part of an effort to characterize the hemochromatosis gene, we selected three non-chimeric yeast artificial chromosomes (YACs) overlapping with the YAC B30 previously described and forming an 800 kilobase contig covering the HLA-A/HLA-F region. The precise physical map of these YACs and of the corresponding genomic region were established. Nine concentrated sites of CpG cutter elements, potentially HTF islands, were mapped. In addition, several probes have been generated as tools for mapping and examining transcripts produced in the region. This allowed for the characterization and localization of two new coding sequences, provisionally named HCG (for hemochromatosis candidate gene) and numbered VIII and IX.
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- 1996
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13. A new non-HLA multigene family associated with the PERB11 family within the MHC class I region.
- Author
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Pichon L, Hampe A, Giffon T, Carn G, Legall JY, and David V
- Subjects
- Base Sequence, Blotting, Northern, Blotting, Southern, Cell Line, Chromosomes, Artificial, Yeast, Cosmids, Databases, Factual, Duodenum chemistry, Gene Expression Regulation, Humans, Lymphocytes chemistry, Molecular Sequence Data, Muscles chemistry, RNA analysis, Repetitive Sequences, Nucleic Acid, Chromosome Mapping, Genes, MHC Class I, Multigene Family
- Abstract
In an effort to initiate steps designed to characterize the idiopathic hemochromatosis disease gene, the HLA-A/HLA-F region where this gene is in disequilibrium linkage with some polymorphic markers has been overlapped by a yeast artificial chromosome (YAC) contig. In order to achieve the physical mapping of these YACs and of the corresponding genomic region, we subcloned one of the YACs involved. A computer-assisted analysis of the sequence of one subclone led to the isolation of a potential exon that proved to belong to a new expressed messenger named HCGIX. After Southern blot analysis, the corresponding cDNA clone was found to belong to a new multigene family whose members are dispersed throughout the HLA class I region and are closely associated with members of another recently described multigene family designated PERB11. The data reported here suggest that these two multigene families form a cluster that have been dispersed together throughout the telomeric part of the major histocompatibility complex and have been involved in the genesis of this human class I region.
- Published
- 1996
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14. Cloning of a human homologue of the mouse Tctex-5 gene within the MHC class I region.
- Author
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Giffon T, Lepourcelet M, Pichon L, Jezequel P, Bouric P, Carn G, Pontarotti P, Gall JY, and David V
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- Amino Acid Sequence, Animals, Base Sequence, Centromere genetics, Cloning, Molecular, DNA, Complementary genetics, Hemochromatosis genetics, Humans, Linkage Disequilibrium, Mice genetics, Molecular Sequence Data, Open Reading Frames, Sequence Homology, Amino Acid, Species Specificity, Ubiquitin-Protein Ligases, t-Complex Genome Region, Chromosomes, Human, Pair 6 genetics, Genes, MHC Class I, Intracellular Signaling Peptides and Proteins, Microtubule-Associated Proteins, Nuclear Proteins genetics
- Abstract
Using a positional cloning strategy to identify the hemochromatosis gene (HFE), we isolated seven cDNAs by cDNA selection from a region of 400 kilobases (kb) located near the HLA-A and HLA-F loci. In this paper, we report the study of one of the corresponding genes, referred to as HCG V (hemochromatosis candidate gene), localized 150 kb centromeric to HLA-A. This gene was found to be expressed ubiquitously in the form of a 1.8 kb transcript, and to be apparently well conserved during evolution. The gene spanned 3.1 kb and is organized in three exons and two introns. The cDNA of 1620 base pairs (bp) showed an open reading frame of 378 bp, encoding for a 126 amino acid polypeptide which displayed a strong identity with the predicted product of a mouse Tctex-5 gene (t complex, testis expressed) localized in the t complex on chromosome 17. The HCG V gene was assessed as a potential candidate for hemochromatosis in regard to its localization in the linkage disequilibrium area between HFE and polymorphic markers. The study of deletions and point mutations in hemochromatosis patients revealed a single bp polymorphism within the coding region; however, no associated disease changes were found. Therefore we conclude that HCG V is unlikely to be involved in the pathogenesis of hemochromatosis.
- Published
- 1996
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15. A human homologue to the yeast omnipotent suppressor 45 maps 100 kb centromeric to HLA-A.
- Author
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Chauvel B, Dorval I, Fergelot P, Pichon L, Giffon T, Gicquel I, Le Gall JY, and David V
- Subjects
- Base Sequence, Chromosome Mapping, Fungal Proteins genetics, Gene Expression, Humans, Molecular Sequence Data, Protein Biosynthesis, RNA, Messenger genetics, Restriction Mapping, Chromosomes, Human, Pair 6, Genes, Suppressor, HLA-A Antigens genetics, Hemochromatosis genetics, Peptide Termination Factors, Saccharomyces cerevisiae Proteins
- Published
- 1995
- Full Text
- View/download PDF
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