HLA-G genetic diversity and evolutive aspects in worldwide populations.
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Authors
de Almeida, Bibiana S
Muniz, Yara CN
Silva, Nayane SB
Passos, Marília RS
Souza, Andreia S
Page, Abigail E
Dyble, Mark
Smith, Daniel
Aguileta, Gabriela
Bertranpetit, Jaume
Migliano, Andrea B
Duarte, Yeda AO
Scliar, Marília O
Wang, Jaqueline
Passos-Bueno, Maria Rita
Naslavsky, Michel S
Zatz, Mayana
Mendes-Junior, Celso Teixeira
Donadi, Eduardo A
Publication Date
2021-11-29Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Number
ARTN 23070
Pages
23070
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Castelli, E. C., de Almeida, B. S., Muniz, Y. C., Silva, N. S., Passos, M. R., Souza, A. S., Page, A. E., et al. (2021). HLA-G genetic diversity and evolutive aspects in worldwide populations.. Sci Rep, 11 (1. ARTN 23070), 23070. https://doi.org/10.1038/s41598-021-02106-4
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.
Identifiers
External DOI: https://doi.org/10.1038/s41598-021-02106-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332982
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