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A Cambon-Thomsen

Publications and source records attributed to A Cambon-Thomsen.

At least 19 recordsLinked to original sources
PubMed2006

Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes.

First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1*03 and DRB1*04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.

Chromosome Mapping↗
PubMed2006

The dbMHC microsatellite portal: a public resource for the storage and display of MHC microsatellite information.

Major histocompatibility complex (MHC) region Microsatellites (Msat) have been extensively used in various applications, such as disease mapping, forensics, and population genetics. A comprehensive review of HLA Msat primers has been previously published based on literature and sequence analysis, but electronic tools are lacking to make it easily accessible and actually used by the community. We have integrated data from this review, with an overlapping set of 31 Msat markers used in the 13th International Histocompatibility and Immunogenetics Workshop (IHIWS) to create a public archive that will synchronize published descriptions to a common framework. http://www.ncbi.nlm.nih.gov/projects/mhc. Currently, the dbMHC contains 389 primer pairs across the extended MHC targeting 281 distinct repeat regions (approximately 1/45 kb). Literature review and analysis of the primers reveal that over 200 synonymous names have been published for these markers. Users may view or download specific Msat data sets using the portal. Query options include name or partial name, primer sequence, neighboring genes, and/or position. Query results include locus name(s), a graphic showing of the relative location of the marker in relation to the classical HLA genes, a listing of the constituent primer pairs and name, a link to UniSTS, aliases, allele range (bp), overlapping single nucleotide polymorphisms, a link to e-polymerase chain reaction, and physical mapping information. To increase the utility of this resource, researchers using Msat markers in the HLA region are encouraged by the authors to submit new primers to the dbMHC. The minimal Msat submission consists of primers sequences, a submitter's name and contact information. Additional information recommended but not required is the laboratory protocol(s), known allele size range (bp), known aliases, and an exemplar sequence. Assigned UniSTS numbers can be used for primer pair standard identification.

Animals↗
PubMed2006

Microsatellite typing of the human leucocyte antigen region: analytical approach and contribution to rheumatoid arthritis immunogenetic studies.

Within the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-DRB1 locus is clearly associated with rheumatoid arthritis (RA). Using a microsatellite (MSat) typing approach, we aimed to identify other loci associated with RA susceptibility and/or severity within the MHC. A panel of nine MSat HLA loci [D6S291, D6S2876 (G51152), D6S1666 (DQCAR II), D6S273, D6S2789 (TNFd), D6S2810 (MIB), D6S265, D6S2222, D6S2239], and HLA-A, -B and -DRB1 genes were typed in 170 RA cases and 282 controls. For susceptibility analysis, MSat and HLA allele distribution were compared between cases and controls, before and after stratification on HLA-DRB1*04. Haplotype frequencies were estimated using an expectation-maximization algorithm in a permutation test procedure. For severity analysis, we compared the distribution of structural damage score at onset and after 4 years of follow-up in RA cases carrying susceptibility alleles. Two MSat polymorphisms were positively associated with RA susceptibility: allele*136 of D6S265 [odds ratio, OR (confidence interval, CI) = 1.55 (1.11-2.17), P= 0.007], allele*116 of D6S2239 [OR = 1.34 (1-1.79), P= 0.03] and HLA-A2 [OR = 1.46 (1.08-1.98), P= 0.01]. Two MSat polymorphisms were negatively associated with RA susceptibility: allele*133 of D6S273 [OR = 0.3 (0.1-0.75), P= 0.005] and allele*177 of D6S291 [OR = 0.72 (0.53-0.96), P= 0.02]. The association between allele*136 of D6S265 and RA susceptibility remained unchanged after stratification on HLA-DRB1*04. The haplotypic analysis showed an overrepresentation of D6S265*136/HLA-A*02 haplotype, which suggests an effect independent of HLA-DRB1 locus in RA susceptibility. While HLA-A2 and HLA-DR4 were associated with RA severity, no MSat polymorphism was associated with structural damage score.

Arthritis, Rheumatoid↗
PubMed2004

Integration of microsatellite characteristics in the MHC region: a literature and sequence based analysis.

Reviews of microsatellite markers in the human leukocyte antigen region have been very useful in addressing the needs of the immunogenetics community. Nevertheless, characterization of the same microsatellite loci in different laboratories can lead to seemingly contradictory results, particularly in terms of nomenclature. Here we provide an update of previous reports, as well as a standardized characterization of primers for microsatellites located within the major histocompatibility complex (MHC). A uniform and extended inventory of 378 primer pairs from published reports was performed as well as a standardized characterization of the corresponding microsatellite loci according to the extended full-length consensus sequence of MHC region. The literature-based approach was complemented by a sequence-based analysis of each reported microsatellite locus. Iterative electronic polymerase chain reaction runs and an original algorithm that characterizes patterns of repeats within sequence were used. The sequence of primers was corrected according to the consensus sequence. Table of synonymous names for individual microsatellite loci is provided.

DNA Primers↗
PubMed2003

Cost-effectiveness analysis of two strategies for typing unrelated donors for bone marrow transplantation in France.

Large Registries of HLA-typed potential volunteer donors have been set up in numerous countries to find HLA-matched unrelated bone marrow donors. This study compared two strategies medicoeconomically for HLA typing in the context of a bone marrow volunteer donor Registry. It investigated the cost-effectiveness of strategies before and after the French Registry was modified in January 1999: HLA- A, B typing only at registration and secondary HLA-DR typing on part of the Registry (AB strategy) vs. typing at once for HLA- A, B, and DR (ABDR strategy). The point of view considered was that of payers, French typing tariffs with a 5% discount rate were used, effectiveness was defined as identification of at least one donor with no HLA-A, B, DR incompatibilities for a given recipient (compatible potential donor), the observation period was 9 months, and the judgement criterion was the differential cost-effectiveness ratio. The ABDR strategy identified 94.7% (142/150) of compatible potential donors. The differential cost-effectiveness ratio between the two strategies was 387,005 francs (Euro 58,995) for one supplementary compatible potential donor. Compared with a "do nothing" policy, the ratio was 3,744,087 francs (Euro 570,745) for the AB strategy vs. 576,136 francs (Euro 87,826) for the ABDR strategy. The ABDR strategy is thus more effective but also more costly than the AB strategy. Nevertheless, because of its lower effectiveness and the size of available ABDR Registries, the AB strategy will become obsolete.

Journal Article↗
PubMed2003

HLA associations in type 1 diabetes: DPB1 alleles may act as markers of other HLA-complex susceptibility genes.

Alleles at the HLA-DQB1, -DQA1 and -DRB1 loci are major determinants for susceptibility to develop type 1 diabetes (T1D). Increasing evidence supports that also other genes in, or near, the HLA complex contribute to the HLA-encoded risk. Alleles at the DPB1 locus have been suggested to directly influence the risk conferred by DQB1, DQA1 and DRB1 alleles, but the results are conflicting. We therefore genotyped 217 families from Norway, Denmark, Sweden and southern France to address the role of DPB1 alleles in T1D. After taking into account linkage disequilibrium (LD) with DQB1, DQA1 and DRB1 alleles, we found evidence that some DPB1 alleles are associated with modulating the risk of developing T1D. However, we show that the strong LD in the HLA complex, and the presence of extended haplotypes complicate the interpretation of the results. On DQ2-DR3 haplotypes, both allele 3 at microsatellite D6S2223 located 5.3-Mb telomeric of DPB1 and the extended DQ2-DR3-B18 haplotype display much stronger association than DPB1 alleles. When we exclude these effects, most of the apparent association of DPB1 alleles on DQ2-DR3 haplotypes disappear. Taken together, although we cannot completely rule out an effect of some DPB1 alleles, we propose that the statistically significant, albeit weak, DPB1 associations found are most likely the result of LD with another unidentified disease-susceptibility gene(s) in this region.

Alleles↗
PubMed2003

Evidence of at least two type 1 diabetes susceptibility genes in the HLA complex distinct from HLA-DQB1, -DQA1 and -DRB1.

Susceptibility to, and protection against development of type 1 diabetes (T1D) are primarily associated with the highly polymorphic exon 2 sequences of the HLA class II genes: DQB1, DQA1 and DRB1. However, several studies have also suggested that additional genes in the HLA complex influence T1D risk, albeit to a lesser degree than the class II genes. We have previously shown that allele 3 of microsatellite marker D6S2223, 4.9 Mb telomeric of DQ in the extended class I region, is associated with a reduction in risk conferred by the DQ2-DR3 haplotype. Here we replicate this finding in two populations from Sweden and France. We also show that markers in the HLA class II, III and centromeric class I regions contribute to the DQ2-DR3 associated risk of T1D, independently of linkage disequilibrium (LD) with both the DQ/DR genes and the D6S2223 associated gene. The associated marker alleles are carried on the DQ2-DR3-B18 haplotype in a region of strong LD. By haplotype mapping, we have located the most likely location for this second DQ2-DR3 haplotype-modifying locus to the 2.35 Mb region between HLA-DOB and marker D6S2702, located 970 kb telomeric of HLA-B.

Chi-Square Distribution↗
PubMed2003

[Ethical aspects of biological sample banks].

Numerous activities in the domain of epidemiology require the constitution or the use of biological sample banks. Such biobanks raise ethical issues. A number of recommendations are applicable to this field, in France and elsewhere. Major principles applicable to biobanks include the respect of person's autonomy, the respect of human body, the respect of confidentiality. These principles are translated into practices through the following procedures: relevant information to the persons regarding their sample management prior to informed consent, opinion of an independent ethics committee, actual implementation of conditions for protecting samples and data. However, although those principles may appear quite simple and obvious, in the context of a largely international practice of research and given the large variety of biobanks, it is not always obvious for researchers to find their way. The attitudes vary between countries, there are numerous texts for various types of biobanks, the same texts raise different interpretations in different institutions, there are new ethical opinions expressed, and mainly the novelty of questions raised by the uses of samples that are possible today, especially in genetics, and were not foreseeable at the time of sampling make the field difficult in practice. This article reviews the types of biobanks, the relevant ethical issues. It also underlines the still unclear or ambiguous situations using some examples of practical situations.

Bioethical Issues↗
PubMed2003

[Ethical and legal aspects of biological sample banks: synthesis, practical questions and proposals].

The overview of the numerous ethical questions and complex legal framework regarding biological sample collections leads to present in this synthesis 1) tables of the principal ethical recommendations and French or supranational reglementary texts in this domain, with their internet access; 2) to detail the procedures to follow in some practical situations; 3) to underline the still open questions and current debates, as the ethical and legal framework of human biobanks is in deep evolution.

Bioethical Issues↗
PubMed2001

Interferon gamma gene polymorphism and susceptibility to, and severity of, rheumatoid arthritis.

A strong association between an interferon gamma (IFN-gamma) gene polymorphism and rheumatoid arthritis susceptibility and severity has been reported in a case-control study. We investigated this polymorphism in 103 patients with early rheumatoid arthritis and 130 controls. Severity of rheumatoid arthritis was measured after 4-year follow-up with a validated radiographic score. The median radiographic score in patients increased from 1 (IQR 0-4) to 11.5 (2-35) over the 4-year follow up. The distribution of IFN-gamma alleles did not differ between patients and controls, and the distribution of radiographic scores did not differ among patients carrying the different IFN-gamma alleles. We have failed to confirm the association between the IFN-gamma gene polymorphism and rheumatoid arthritis susceptibility or severity.

Alleles↗
PubMed2001

West Mediterranean islands (Corsica, Balearic islands, Sardinia) and the Basque population: contribution of HLA class I molecular markers to their evolutionary history.

The genetic structure of Balearic islands (Corsica and Sardinia), situated on the same trans-Mediterranean maritime routes and having very similar histories, were compared and their position among the neighbouring Caucasian populations was inferred. For this purpose, three HLA loci (HLA-A, -B and -Cw) were typed at the DNA level in these populations and the allelic and haplotypic frequencies were estimated. Because previous studies have shown common genetic features in the Sardinians and Basques, HLA-Cw molecular typing was also performed in a sample of French Basques in order to establish the haplotypic structure of this population for a more accurate comparison with the three others. By its allelic composition, the Corsican population has an intermediate position between the two other islander populations. Its close relationship with the Sardinian population, however, was clearly revealed by the phylogenetic analysis which also suggests a proximity with eastern Mediterranean peoples, whereas the Balearic islands are more narrowly related to Spain and western Europe. Peculiarities were observed in the distributions of some common haplotypes in the populations of the islands that confirm the results of the phylogenetic analysis and could be related to their history. Noteworthy is the presence of the HLA-A30-Cw*0501-B18 haplotype at frequencies approximately 2% in Corsica and the Balearic islands, yet the estimated frequencies of this haplotype are much lower than in the Sardinian and Basque populations.

Evolution, Molecular↗
PubMed2000

Microsatellites in the HLA region: 1999 update.

In this third update of a series of reviews on microsatellites in the HLA region or close to it we report 155 microsatellites, corresponding to 51 newly described markers, in addition to the 103 reported in the 1997 and 1998 reviews. This work is based both on a literature review and on data publicly available in molecular databases on the internet (http://www.gdb.org; http://bioinfo.weizmann.ac.il/cards/; http://cedar.genetics.soton.ac.uk/) up to September 1999. Thanks to numerous studies involving major histocompatibility complex (MHC) microsatellites, documentation on HLA region is proposed, including information on microsatellites described through MHC sequence projects and presenting documented location, polymorphism and amplification condition, together with additional information on previously described microsatellites when available and information on data in the literature regarding gametic associations between HLA region loci and alleles and microsatellite alleles. As basic information are presented various documents: i) a table showing the following characteristics of the 155 microsatellites: name, localisation, polymorphism, primer sequences, reference; ii) an integrated map of some HLA region genes and the 155 microsatellites considered; and iii) a summary table on HLA and microsatellites association patterns. In addition, an overview on HLA microsatellite analysis application is presented, with a special focus on disease genetics studies in the form of recent references where the use of microsatellites of the HLA region was a key tool. This review aims at providing the human immunogenetics community with a tool for helping optimal choice of microsatellites to be used in various studies.

Evolution, Molecular↗
PubMed2000

Genetic structure of north-west Africa revealed by STR analysis.

We have analysed a large set of autosomal short tandem repeat (STR) loci in several Arabic and Berber-speaking groups from north-west Africa (ie Moroccan Arabs, northern-central and southern Moroccan Berbers, Saharawis, and Mozabites). Two levels of analysis have been devised using two sets of 12STR loci, (D3S1358, vWA, FGA, THO1, TPOX, CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820) and 21 (the former set plus D9S926, D11S2010, D13S767, D14S306, D18S848, D2S1328, D4S243, F13A1, and FES/FPS). For each set, data for a number of external reference populations were gathered from the literature. Several methods of analysis based on genetic distances (neighbour-joining trees, principal coordinate analysis, boundary detection), as well as AMOVA, showed that genetic differentiation among NW African populations was very low and devoid of any spatial pattern. When the NW African populations were grouped according to cultural or linguistic differences, the partition was not associated with genetic differentiation. Thus, it is likely that Arabisation was mainly a cultural process. A clear genetic difference was found between NW African populations and Iberians, which underscores the Gilbraltar Straits as a strong barrier to genetic exchange; nonetheless, some degree of gene flow into Southern Iberia may have existed. NW Africans were genetically closer to Iberians and to other Europeans than to African Americans.

Africa, Northern↗
PubMed1999

Recent male-mediated gene flow over a linguistic barrier in Iberia, suggested by analysis of a Y-chromosomal DNA polymorphism.

We have examined the worldwide distribution of a Y-chromosomal base-substitution polymorphism, the T/C transition at SRY-2627, where the T allele defines haplogroup 22; sequencing of primate homologues shows that the ancestral state cannot be determined unambiguously but is probably the C allele. Of 1,191 human Y chromosomes analyzed, 33 belong to haplogroup 22. Twenty-nine come from Iberia, and the highest frequencies are in Basques (11%; n=117) and Catalans (22%; n=32). Microsatellite and minisatellite (MSY1) diversity analysis shows that non-Iberian haplogroup-22 chromosomes are not significantly different from Iberian ones. The simplest interpretation of these data is that haplogroup 22 arose in Iberia and that non-Iberian cases reflect Iberian emigrants. Several different methods were used to date the origin of the polymorphism: microsatellite data gave ages of 1,650, 2,700, 3,100, or 3,450 years, and MSY1 gave ages of 1,000, 2,300, or 2,650 years, although 95% confidence intervals on all of these figures are wide. The age of the split between Basque and Catalan haplogroup-22 chromosomes was calculated as only 20% of the age of the lineage as a whole. This study thus provides evidence for direct or indirect gene flow over the substantial linguistic barrier between the Indo-European and non-Indo-European-speaking populations of the Catalans and the Basques, during the past few thousand years.

Base Sequence↗
PubMed1998

HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations.

HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three-locus haplotypes was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.

Alleles↗
PubMed1998

Microsatellites in the HLA region: 1998 update.

In order to update the review published in Tissue Antigens in 1997, we present here a new overview on microsatellites in the HLA region, including additional information, with focus on the following points: * Description of 103 microsatellite characteristics in the HLA region, 50 markers having been newly described since 1996. * An integrated map of the HLA region, including microsatellites and some HLA genes, revealing an important microsatellite density in the MHC (Class I, Class II and Class III regions). * A synthesis of microsatellite analysis in disease studies, summarizing results of microsatellite approaches in 24 pathologies, including autoimmune diseases, HLA-associated or HLA-linked diseases and cancers. * Other applications of HLA region microsatellites in population or transplantation studies.

Chromosome Mapping↗