collaborateurs

André Langaney

Professeur(e) honoraire chez Anthropologie & Immunogénétique

  • T: +41 22 379 63 24
  • office 4-415 (Sciences II)
  • Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa. HLA 2017 Nov;():. 10.1111/tan.13180.

    résumé

    With the aim to understand how 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 to 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 to 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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  • Genetic evidence for complexity in ethnic differentiation and history in East Africa. Ann. Hum. Genet. 2009 Nov;73(Pt 6):582-600. AHG541. 10.1111/j.1469-1809.2009.00541.x.

    résumé

    The Afro-Asiatic and Nilo-Saharan language families come into contact in Western Ethiopia. Ethnic diversity is particularly high in the South, where the Nilo-Saharan Nyangatom and the Afro-Asiatic Daasanach dwell. Despite their linguistic differentiation, both populations rely on a similar agripastoralist mode of subsistence. Analysis of mitochondrial DNA extracted from Nyangatom and Daasanach archival sera revealed high levels of diversity, with most sequences belonging to the L haplogroups, the basal branches of the mitochondrial phylogeny. However, in sharp contrast with other Ethiopian populations, only 5% of the Nyangatom and Daasanach sequences belong to haplogroups M and N. The Nyangatom and Daasanach were found to be significantly differentiated, while each of them displays close affinities with some Tanzanian populations. The strong genetic structure found over East Africa was neither associated with geography nor with language, a result confirmed by the analysis of 6711 HVS-I sequences of 136 populations mainly from Africa. Processes of migration, language shift and group absorption are documented by linguists and ethnographers for the Nyangatom and Daasanach, thus pointing to the probably transient and plastic nature of these ethnic groups. These processes, associated with periods of isolation, could explain the high diversity and strong genetic structure found in East Africa.

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  • Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history. BMC Genet. 2008 ;9():21. 1471-2156-9-21. 10.1186/1471-2156-9-21. PMC2292740.

    résumé

    The N-acetyltransferase 2 (NAT2) gene plays a crucial role in the metabolism of many drugs and xenobiotics. As it represents a likely target of population-specific selection pressures, we fully sequenced the NAT2 coding region in 97 Mandenka individuals from Senegal, and compared these sequences to extant data on other African populations. The Mandenka data were further included in a worldwide dataset composed of 41 published population samples (6,727 individuals) from four continental regions that were adequately genotyped for all common NAT2 variants so as to provide further insights into the worldwide haplotype diversity and population structure at NAT2.

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  • Haplotype tagging efficiency and tagSNP sets portability in worldwide populations in NAT2 gene (Marquage d'haplotypes du gène NAT2 : efficacité dans différentes régions du monde) Bull. et Mém. Soc. d'Anthropologie de Paris 19(3-4):233-241 (2007)

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  • Génétique, linguistique et histoire des peuplements humains Langages 146:80-90 (2002)

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  • Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation. Am. J. Hum. Genet. 2002 Jan;70(1):207-23. S0002-9297(07)61294-4. 10.1086/338304. PMC384889.

    résumé

    A large and ethnically well-defined Mandenka sample from eastern Senegal was analyzed for the polymorphism of the beta-globin gene cluster on chromosome 11. Five RFLP sites of the 5' region were investigated in 193 individuals revealing the presence of 10 different haplotypes. The frequency of the sickle-cell anemia causing mutation (beta(S)) in the Mandenka estimated from this sample is 11.7%. This mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the beta-globin gene were sequenced for a subset of 94 chromosomes, showing the presence of four transversions, five transitions, and a composite microsatellite polymorphism. The sequence of 22 beta(S) chromosomes was also identical to the previously defined Senegal haplotype, suggesting that this mutation is very recent. Monte Carlo simulations (allowing for a specific balancing selection model, a logistic growth of the population, and variable initial frequencies of the Senegal haplotype) were used to estimate the age of the beta(S) mutation. Resulting maximum-likelihood estimates are 45-70 generations (1,350-2,100 years) for very different demographic scenarios. Smallest confidence intervals (25-690 generations) are obtained under the hypothesis that the Mandenka population is large (N(e) >5,000) and stationary or that it has undergone a rapid demographic expansion to a current size of >5,000 reproducing individuals, which is quite likely in view of the great diversity found on beta(A) chromosomes.

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  • La langue paternelle Sciences et Avenir, Hors-série (Quelle langue parlait-on il y a 100 000 ans?: la langue d'Homo erectus) 125:42-49 (2000-2001)

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  • The molecular diversity of the Niokholo Mandenkalu from Eastern Senegal: An insight into West Africa genetic history In: Boyce AJ and Mascie-Taylor CGN, eds. Molecular Biology and Human Diversity. Cambridge: Cambridge University Press, p.141-155 (1996)

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  • L'Homme descend du sexe La Recherche 20:994-1007 (1989)

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