HLA-G genetic diversity and evolutive aspects in worldwide populations
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2021-12-01
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Castelli, Erick C. [UNESP]
de Almeida, Bibiana S.
Muniz, Yara C. N.
Silva, Nayane S. B. [UNESP]
Passos, Marília R. S. [UNESP]
Souza, Andreia S. [UNESP]
Page, Abigail E.
Dyble, Mark
Smith, Daniel
Aguileta, Gabriela
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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.
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Scientific Reports, v. 11, n. 1, 2021.