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HLA-G genetic diversity and evolutive aspects in worldwide populations.

Published version
Peer-reviewed

Type

Article

Change log

Authors

de Almeida, Bibiana S 
Muniz, Yara CN 
Silva, Nayane SB 
Passos, Marília RS 

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.

Description

Keywords

3' Untranslated Regions, Alleles, Computational Biology, Dimerization, Evolution, Molecular, Gene Frequency, Genes, MHC Class I, Genetic Variation, Genetics, Population, Genotype, Global Health, HLA-G Antigens, Haplotypes, High-Throughput Nucleotide Sequencing, Humans, Immune Checkpoint Proteins, Immunogenetics, Introns, Linkage Disequilibrium, Polymorphism, Genetic, Polymorphism, Single Nucleotide

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

11

Publisher

Springer Science and Business Media LLC