1. HLA-G genetic diversity and evolutive aspects in worldwide populations
- Author
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Nayane S. B. Silva, Eduardo Antônio Donadi, Gabriela Aguileta, Bibiana Sgorla de Almeida, Marília R S Passos, Daniel J. Smith, Mayana Zatz, Andrea Bamberg Migliano, Yara Costa Netto Muniz, Jaqueline Wang, Abigail E. Page, Jaume Bertranpetit, Michel S Naslavsky, Marilia O. Scliar, Celso T. Mendes-Junior, Andreia S. Souza, Yeda Aparecida de Oliveira Duarte, Mark Dyble, Maria Rita Passos-Bueno, Erick C. Castelli, Universidade Estadual Paulista (UNESP), Universidade de São Paulo (USP), Universidade Federal de Santa Catarina (UFSC), London School of Hygiene and Tropical Medicine, University College London (UCL), University of Bristol, Universitat Pompeu Fabra, Unversity of Zurich, Hospital Israelita Albert Einstein, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Fundação de Amparo à Pesquisa do Estado de São Paulo, University of Zurich, Castelli, Erick C, Donadi, Eduardo A, Castelli, Erick C [0000-0003-2142-7196], and Apollo - University of Cambridge Repository
- Subjects
10207 Department of Anthropology ,Linkage disequilibrium ,Genotype ,Bioinformatics ,Population genetics ,Science ,Population ,Genes, MHC Class I ,Human leukocyte antigen ,Biology ,Balancing selection ,Global Health ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,Evolution, Molecular ,Gene Frequency ,Immunogenetics ,Humans ,Genetic variability ,education ,3' Untranslated Regions ,ANTÍGENOS HLA ,Alleles ,Genetic association ,HLA-G Antigens ,1000 Multidisciplinary ,education.field_of_study ,Genetic diversity ,Multidisciplinary ,Polymorphism, Genetic ,300 Social sciences, sociology & anthropology ,Haplotype ,Computational Biology ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Immune Checkpoint Proteins ,Introns ,Genetics, Population ,Haplotypes ,Evolutionary biology ,Medicine ,Dimerization - Abstract
HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies., We acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil, #302060/2019-7), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil, Finance code: 001), INCTC/FAPESP (Grant #465539/2014-9) for financial support, and FAPESP/Brazil (#Grant 2017/19223-0).
- Published
- 2021
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