HLA-G genetic diversity and evolutive aspects in worldwide populations
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 individua...
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Nature Portfolio
2021
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oai:doaj.org-article:4aa35f18b2a3467d92010afb84f174e12021-12-05T12:14:22ZHLA-G genetic diversity and evolutive aspects in worldwide populations10.1038/s41598-021-02106-42045-2322https://doaj.org/article/4aa35f18b2a3467d92010afb84f174e12021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02106-4https://doaj.org/toc/2045-2322Abstract 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.Erick C. CastelliBibiana S. de AlmeidaYara C. N. MunizNayane S. B. SilvaMarília R. S. PassosAndreia S. SouzaAbigail E. PageMark DybleDaniel SmithGabriela AguiletaJaume BertranpetitAndrea B. MiglianoYeda A. O. DuarteMarília O. ScliarJaqueline WangMaria Rita Passos-BuenoMichel S. NaslavskyMayana ZatzCelso Teixeira Mendes-JuniorEduardo A. DonadiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
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Medicine R Science Q |
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Medicine R Science Q 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 HLA-G genetic diversity and evolutive aspects in worldwide populations |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Erick C. Castelli |
| title |
HLA-G genetic diversity and evolutive aspects in worldwide populations |
| title_short |
HLA-G genetic diversity and evolutive aspects in worldwide populations |
| title_full |
HLA-G genetic diversity and evolutive aspects in worldwide populations |
| title_fullStr |
HLA-G genetic diversity and evolutive aspects in worldwide populations |
| title_full_unstemmed |
HLA-G genetic diversity and evolutive aspects in worldwide populations |
| title_sort |
hla-g genetic diversity and evolutive aspects in worldwide populations |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/4aa35f18b2a3467d92010afb84f174e1 |
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