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D Charron

Publications and source records attributed to D Charron.

At least 91 records · Page 5Linked to original sources
PubMed1999

Mitochondrial DNA polymorphism in the Vietnamese population.

The mitochondrial DNA variation was screened in a sample of 50 unrelated individuals of the Vietnamese population originating from Hanoi. A combination of long and standard PCR and restriction endonuclease digests with the enzymes HpaI, BamHI, HaeII, MspI, AvaII and HincII were used to reveal mtDNA variation. Twenty enzyme morphs were detected, three of which (HaeII-13Viet, MspI-19Viet and MspI-20Viet) are new and are produced by a single mutational event in already known enzyme morphs. Ten already known and four new mitotypes [93Viet (1-1-2-4-1), 94Viet (2-1-13Viet-1-1), 95Viet (2-1-13Viet-19Viet-1) and 96Viet (1-1-2-20Viet-12)] were found in the Vietnamese population. The 9-bp deletion occurring in the COII/tRNALys region of the mitochondrial genome was also analysed and 10 samples were found to have this deletion. The comparison of the Vietnamese with other East Asian populations showed a close genetic relationship of the population under investigation with other Orientals. However, the Vietnamese population can be differentiated by the significantly higher frequency of the enzyme morph HincII-5 and by seven new markers. These results strongly support the hypothesis of a dual ethnic origin of the Vietnamese population from the Chinese and Thai-Indonesian populations based on HLA markers and linguistic evidence.

China↗
PubMed1999

Disassembly of nuclear inclusions in the dividing cell--a novel insight into neurodegeneration.

Spinocerebellar ataxias and Huntington's disease are examples of neurodegenerative diseases caused by a trinucleotide repeat expansion. One hallmark of such diseases is the formation of inclusion bodies (IBs) within neuronal tissue. Although these inclusions may play a pivotal role in the disease process, the reasons underlying their specific accumulation remain obscure. By studying intranuclear IBs in dividing cells we demonstrate for the first time that inclusions such as those of ataxin-1 disperse during mitosis, thus reducing the nuclear aggregate burden. IBs reform in the interphase nucleus. By high-resolution confocal microscopy we also show that inclusions comprise ordered structures capable of homotypic interactions. Unlike those of a non-pathologic protein, ataxin-1 inclusions were shown to be capable of non-specific protein sequestration. Our studies indicate that the specific accumulation of inclusions in terminally differentiated cells such as neurons is a direct consequence of their inability to divide and therefore provides a key to explaining their persistence in neurodegenerative disease.

Amino Acid Sequence↗
PubMed1999

[HLA-C allele recognition using DNA sequencing].

The HLA-C locus was sequenced in 106 normal unrelated members of the French CEPH families. Following generic PCR amplification, exons 2 and 3 were amplified separately then sequenced using the ALF Expres sequencer. The Sequi Typer program was used for data analysis. Of the 72 alleles identified to date, 20 were recognized in the panel studied. Results were compared to those provided by the lymphocytotoxicity test, which had a 13.5% error rate and failed to reach the level of specific recognition. Sequencing preceded by amplification allowed immediate unambiguous allele assignment in 96% of cases. In four cases, a complementary method was required to resolve ambiguities. Reproducibility was high. The sequencing strategy described herein is a significant advance and may be particularly valuable for achieving perfect donor/recipient matching for allogeneic stem cell transplants.

Alleles↗
PubMed1998

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Arthritis, Rheumatoid↗
PubMed1998

Mitochondrial DNA sequence variation in human leukemic cells.

The Long PCR followed by the RFLP technique has been used to search for abnormally structured mitochondrial DNA (mtDNA) and specific sequence differences implicated in the pathogenesis of acute lymphoblastic leukaemia (ALL). We have studied 54 specific sites whose combinations define groups of mtDNA types, in 30 leukemic patients of French Caucasian origin. Results were compared with those in 100 French healthy individuals. Nucleotide substitutions have been defined in 11 patients. This polymorphism is expressed by single base substitution at 6 sites which corresponds to 5 morphs, 2 of which were not found in the reference group. Combining the 11 observed morphs, we have identified 7 different mtDNA types, defined in 30 patients with ALL. Two of the morphs (MspI-2 and AvaII-3) and 3 of the types (17-2, 55-2, NewFr150) were not found in the group of healthy individuals. We have observed significant statistical changes in type 28-2 in ALL patients compared with the controls.

Adult↗
PubMed1998

The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire.

Umbilical cord blood (CB) constitutes a promising alternative to bone marrow for allogeneic transplantation and is increasingly used because of the reduced severity of graft-versus-host disease after CB transplantation. We have compared the T-cell receptor beta chain (TCRB) diversity of CB lymphocytes with that of adult lymphocytes by analyzing the complementarity determining region 3 (CDR3) size heterogeneity. In marked contrast to adult samples, we observed bell-shaped profiles in all of the 22 functional beta-chain variable (BV) subfamilies that reflect the lack of prior antigenic stimulation in CB samples. However, the mean CDR3 size and BV usage were comparable between CB and adult samples. BJ2 (65%) segments were used preferentially to BJ1 (35%), especially BJ2S7, BJ2S5, BJ2S3, and BJ2S1, in both CB and in adult lymphocytes. We therefore conclude that although naive as reflected by the heterogeneity of the CDR3 size, the TCRBV repertoire appears fully constituted at birth. The ability to expand TCRB subfamilies was confirmed by stimulation with staphylococcal superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxin A. This study provides the basis for future analysis of the T-cell repertoire reconstitution following umbilical CB transplantation.

Adult↗
PubMed1998

Naturally processed peptides from HLA-DQ7 (alpha1*0501-beta1*0301): influence of both alpha and beta chain polymorphism in the HLA-DQ peptide binding specificity.

Self peptides bound to HLA-DQ7 (alpha1*0501-beta1*0301), one of the HLA molecules associated with protection against insulin-dependent diabetes mellitus, were characterized after their acid elution from immunoaffinity-purified HLA-DQ7 (alpha1*0501-beta1*0301) molecules. The majority of these self peptides derived from membrane-associated proteins including HLA class I, class II, class II-associated invariant chain peptide and the transferrin-receptor (TfR). By in vitro binding assays, the specificity of these endogenous peptides for HLA-DQ7 (alpha1*0501-beta1*0301) molecules was confirmed. Among these peptides, the binding specificity of the TfR 215-230 self peptide was further examined on a variety of HLA-DQ and DR dimers. Several findings emerged from this analysis: (1) this peptide displayed HLA-DQ allelic specificity, binding only to HLA-DQ7 (alpha1*0501-beta1*0301); (2) when either the DQalpha or DQbeta chain was exchanged, little or no binding was observed, indicating that specificity of HLA-DQ peptide binding was determined by polymorphic residues of both the alpha and beta chains. (3) Unexpectedly, the TfR 215-230 self peptide, eluted from DQ, was promiscuous with regard to HLA-DR binding. This distinct DR and DQ binding pattern could reflect the structure of these two molecules as recently evidenced by crystallography.

Alleles↗
PubMed1998

HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity.

In an effort to reassess the contribution of HLA-DRB1 polymorphisms to inter-individual variations of human longevity, we have compared their genotypic distributions between longevous and adult control groups in the French population. The longevous groups included two independent cohorts totalling 533 centenarians, and 163 nonagenarian siblings. Allelic distributions were significantly different between controls and longevous groups. Three individual alleles were mostly responsible for these differences: DR7, DR11 and DR13. Multivariate logistic analyses were performed in order to sort out interactions between gender- and age-specific genetic effects. DR7 frequency was elevated in longevous men, in centenarians as well as nonagenarian siblings [OR = 1.72 (1.2-2.5)]. DR11's influence on longevity displayed a significant interaction with sex, with an increase in women from longevous sibships [OR = 2.03 (1.4-3.0)]. DR13's frequency was increased in centenarians of both genders [OR = 1.46 (1.2-1.75)]. These results are discussed in the context of other pathophysiological effects of the implicated alleles. Our data support the direct involvement of three HLA-DR alleles in survival at very old ages. Two allele-specific effects on longevity appear to depend on gender and one on familial status for aggregation of this trait. The latter is an original finding for humans.

Adult↗
PubMed1998

Sequencing-based typing reveals six novel MHC class I chain-related gene B (MICB) alleles.

The MHC class I chain-related gene A (MICA) is highly polymorphic. In this paper we demonstrate polymorphism in the other expressing member of the MIC family of genes: MICB. Using a sequencing-based typing approach on cDNA, analysis of exons 2 through 6 revealed eight polymorphic sites resulting in six unique MICB sequences. Although MICB has high nucleotide homology with MICA, its polymorphism is restricted and at different sites compared to those in MICA.

Alleles↗
PubMed1998

Description of a new DRB1*11 allele (DRB1*1132).

We describe a new DRB1*11 allele which is similar to DRB1*11011 except at codon 74, where a GCG is changed for a GTG leading to an alanine/valine substitution. This new allele was carried by a Caucasian patient suffering from rheumatoid arthritis and by her healthy daughter. The motif at codon 74 of the new DRB1*11 is not found in any other known DRB alleles, nor among the published DQA1, DQB1, DPA1 or DPB1 alleles, and therefore suggests a mechanism of point mutation.

Alleles↗
PubMed1998

Alteration of HLA-B27 peptide presentation after infection of transfected murine L cells by Shigella flexneri.

Shigella flexneri is a triggering agent for reactive arthritis in HLA-B27-susceptible individuals. Considering the intracellular multiplication of bacteria, it seems likely that bacterial peptides may be presented by the major histocompatibility complex (MHC) class I pathway. To examine this hypothesis, we infected HLA-B*2705- and/or human beta2-microglobulin-transfected murine L-cell lines with M90T, an invasive strain of S. flexneri. Bacterial infection induced no detectable modifications in the biosynthesis and expression level of HLA-B27, as assessed by immunoprecipitation, Northern blot analysis, and flow cytometry. Using confocal microscopy, we observed that bacterial infection induced a clustering of HLA-B27 molecules during macropinocytosis and before bacterial dissemination from cell to cell. Peptides naturally bound to HLA-B27 molecules were acid eluted from infected cells and separated by high-performance liquid chromatography. Major differences were observed in high-performance liquid chromatography profiles and in the nature of peptides presented following bacterial infection. Although most of the antigens presented were not accessed by Edman degradation, we obtained two sequences partially homologous to bacterial proteins. These peptides lacked the major HLA-B27 peptide anchor (Arg) at position 2, and one had an unusual length of 14 amino acids. These data suggest that alterations in the peptide presentation by HLA-B27 occur during infection, which could be relevant to the pathogenesis of HLA-B27-related arthritis.

Animals↗