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

Article Article scientifique Article Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa eng 2018 author Goeury Thomas 0009-0006-2938-6033 831700 author Creary L E author Brunet Lydie 656435 author Galan M author Pasquier Maeva 746455 author Kervaire Barbara Nelly 26220 author Langaney André 25252 author Tiercy Jean-Marie 26423 author Fernández-Viña M A author Nunes Jose Manuel 122321 author Sanchez-Mazas Alicia 22545 36-51 10.1111/tan.13180 29160618 2059-2302 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767763/ 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. Allelic conversion Balancing selection Full‐length HLA genes HLA nucleotide diversity Onchocerciasis Population genetics Selective sweep West Africa Dewey 590 Swiss National Science Foundation Early human settlements in contrasting environments: HLA molecular variation and its link to population expansions and immune adaptation 144180 CH Project funding 23 Institut de génétique et de génomique 0DH 44 Département de génétique et évolution 162 false 824 Groupe Sanchez-Mazas 1056 Unité d'anthropologie HLA 91 1 3569edd7-f065-45b5-98b9-e948c5faa329 Article (Published version) Public Goeury_et_al-2018-HLA.pdf 1936138 application/pdf OA OTHER openAccess Centres et instituts / Institut de génétique et de génomique Faculté des sciences / Section de biologie / Département de génétique et évolution

Title	Published in	Year	Views	Downloads

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa	HLA	2018	580	372
Etude des polymorphismes HLA-DQA1 et HLA-DQB1 dans des populations africaines du Sahel		2016	115	6

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Pasquier, Maeva