HLA-G genetic diversity and evolutive aspects in worldwide populations

Autor: Erick C. Castelli, Bibiana S. de Almeida, Yara C. N. Muniz, Nayane S. B. Silva, Marília R. S. Passos, Andreia S. Souza, Abigail E. Page, Mark Dyble, Daniel Smith, Gabriela Aguileta, Jaume Bertranpetit, Andrea B. Migliano, Yeda A. O. Duarte, Marília O. Scliar, Jaqueline Wang, Maria Rita Passos-Bueno, Michel S. Naslavsky, Mayana Zatz, Celso Teixeira Mendes-Junior, Eduardo A. Donadi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-02106-4
Popis: 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.
Databáze: Directory of Open Access Journals
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