HLA-G genetic diversity and evolutive aspects in worldwide populations

Author(s):Show less -

Castelli, Erick C. ^{[1, 2]} ; de Almeida, Bibiana S. ^{[3, 4]} ; Muniz, Yara C. N. ^[5] ; Silva, Nayane S. B. ^[2] ; Passos, Marilia R. S. ^[2] ; Souza, Andreia S. ^[2] ; Page, Abigail E. ^[6] ; Dyble, Mark ^[7] ; Smith, Daniel ^[8] ; Aguileta, Gabriela ^[9] ; Bertranpetit, Jaume ^[9] ; Migliano, Andrea B. ^[10] ; Duarte, Yeda A. O. ^{[11, 12]} ; Scliar, Marilia O. ^[13] ; Wang, Jaqueline ^[13] ; Passos-Bueno, Maria Rita ^{[14, 13]} ; Naslavsky, Michel S. ^{[15, 14, 13]} ; Zatz, Mayana ^{[14, 13]} ; Mendes-Junior, Celso Teixeira ^[16] ; Donadi, Eduardo A. ^[3]

Affiliation:Show less -

^[1] Sao Paulo State Univ, UNESP, Dept Pathol, Sch Med, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ, UNESP, Mol Genet & Bioinformat Lab, Expt Res Unit, Sch Med, Botucatu, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, Div Clin Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Fed Santa Catarina UFSC, Ctr Ciencias Biol, Lab Multiusuario Estudos Biol, Florianopolis, SC - Brazil

^[5] Univ Fed Santa Catarina UFSC, Ctr Ciencias Biol, Dept Biol Celular Embriol & Genet, Florianopolis, SC - Brazil

^[6] London Sch Hyg & Trop Med, Dept Populat Hlth, London - England

^[7] Univ Coll London UCL, Dept Anthropol, London - England

^[8] Univ Bristol, Bristol Med Sch PHS, Bristol, Avon - England

^[9] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona - Spain

^[10] Univ Zurich, Dept Anthropol, Zurich - Switzerland

^[11] Univ Sao Paulo, Escola Enfermagem, Sao Paulo, SP - Brazil

^[12] Univ Sao Paulo, Fac Saude Publ, Sao Paulo, SP - Brazil

^[13] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Biosci Inst, Sao Paulo, SP - Brazil

^[14] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil

^[15] Hosp Israelita Albert Einstein, Sao Paulo, SP - Brazil

^[16] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 NOV 29 2021.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 17/19223-0 - KIR2DL4, KIR3DL2, KIR3DL3, LILRB1 (ILT2) and LILRB2 (ILT4) variability and haplotypes in a Brazilian population sample from the São Paulo state
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants