HLA-G genetic diversity and evolutive aspects in worldwide populations

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.

Bibliographic Details

Main Authors:	Castelli, Erick C., Almeida, Bibiana S. de, Muniz, Yara C. N., Silva, Nayane, S. B., Passos, Marília R. S., Souza, Andreia S., Page, Abigail E., Dyble, Mark, Smith, Daniel, Aguileta, Gabriela, Bertranpetit, Jaume, Migliano, Andrea B., Duarte, Yeda A. O., Scliar, Marília O., Wang, Jacqueline, Passos-Bueno, Maria Rita, Naslavsky, Michel S., Zatz, Mayana, Teixeira Mendes-Junior, Celso, Donadi, Aduardo A.
Other Authors:	Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil)
Format:	artículo biblioteca
Language:	English
Published:	Springer Nature 2021-11-29
Online Access:	http://hdl.handle.net/10261/269030 http://dx.doi.org/10.13039/501100003593 http://dx.doi.org/10.13039/501100002322 http://dx.doi.org/10.13039/501100001807
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