Descrição
Made available in DSpace on 2022-04-29T08:46:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01
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.
Molecular Genetics and Bioinformatics Laboratory Experimental Research Unit School of Medicine São Paulo State University (UNESP)
Department of Pathology School of Medicine São Paulo State University (UNESP)
Division of Clinical Immunology Department of Medicine Ribeirão Preto Medical School University of São Paulo (USP)
Laboratório Multiusuário de Estudos em Biologia Centro de Ciências Biológicas Universidade Federal de Santa Catarina (UFSC)
Departamento de Biologia Celular Embriologia e Genética Centro de Ciências Biológicas Universidade Federal de Santa Catarina (UFSC)
Department of Population Health London School of Hygiene and Tropical Medicine
Departament of Anthropology University College London (UCL)
Bristol Medical School (PHS) University of Bristol
Department of Experimental and Health Sciences Universitat Pompeu Fabra
Departament of Anthropology Unversity of Zurich
Escola de Enfermagem e Faculdade de Saúde Pública Universidade de São Paulo (USP)
Human Genome and Stem Cell Research Center Biosciences Institute University of São Paulo (USP)
Department of Genetics and Evolutionary Biology Biosciences Institute University of São Paulo (USP)
Hospital Israelita Albert Einstein
Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo
Molecular Genetics and Bioinformatics Laboratory Experimental Research Unit School of Medicine São Paulo State University (UNESP)
Department of Pathology School of Medicine São Paulo State University (UNESP)
