13 research outputs found

    Contribution à l'étude des facteurs évolutifs déterminant les profils moléculaires des gènes HLA des populations humaines

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    Cette thèse porte sur l'étude des facteurs évolutifs contribuant à la distribution du polymorphisme du complexe des antigènes leucocytaires humains (HLA). Utilisant des données moléculaires HLA issues de séquençages ADN, il vise à apporter des éléments de réponse sur l'importance de tels facteurs, selon trois niveaux d'analyse. Le premier niveau concerne les mécanismes susceptibles de générer de la diversité HLA au sein des populations, conduisant, par exemple, à l'apparition de nouveaux allèles. Le second niveau se concentre sur la façon dont s'est distribuée cette diversité entre les différentes populations humaines, au travers de l'histoire du peuplement et de ses mécanismes, à savoir les migrations et la dérive génétique mais aussi la sélection naturelle. Le troisième niveau s'intéresse aux mécanismes qui ont pu faire varier ce polymorphisme au sein de diverses espèces (humain et chimpanzé) sur une échelle de temps plus longue, conduisant, par exemple, à l'apparition de nouveaux gènes

    HLA-DQA1 AND-DQB1 HIGH-THROUGHPUT SEQUENCING OF MORE THAN 1,500 INDIVIDUALS FROM 26 AFRICAN POPULATIONS: A MOLECULAR POPULATION GENETICS APPROACH

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    HLA-DQA1 AND-DQB1 HIGH-THROUGHPUT SEQUENCING OF MORE THAN 1,500 INDIVIDUALS FROM 26 AFRICAN POPULATIONS: A MOLECULAR POPULATION GENETICS APPROACH. 30. European Immunogenetics and Histocompatibility Conferenc

    Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa

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    With the aim to understand how next-generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well-documented population from sub-Saharan Africa (Mandenka). The results of full-gene NGS-MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide-presentation function, a lower diversity of HLA-C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA-A exon 2, revealing demographic signals. Based on full-length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population, DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors and DRB1*11:02:01 as recipient. Finally, our analysis revealed a high occurrence of the DRB1*13:04-DQA1*05:05:01-DQB1*03:19 haplotype, possibly resulting from a selective sweep due to protection to Onchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments
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