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, MarkSmith, DanielAguileta, GabrielaBertranpetit, JaumeMigliano, Andrea B.Duarte, Yeda A. O.Scliar, Marília O.Wang, JaquelinePassos-Bueno, Maria RitaNaslavsky, Michel S.Zatz, MayanaMendes-Junior, Celso TeixeiraDonadi, Eduardo A.2022-04-292022-04-292021-12-01Scientific Reports, v. 11, n. 1, 2021.2045-2322http://hdl.handle.net/11449/231561HLA-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.engArtigo10.1038/s41598-021-02106-42-s2.0-85120087641