New evidence for balancing selection at the HLA-G locus in South Amerindians

Abstract

HLA-G is a non-classical HLA (Human Leukocyte Antigen) molecule characterized by limited tissue distribution under normal physiological conditions and low variability at both DNA and protein levels. Several studies suggest that HLA-G could play a role, as an immunoregulatory molecule, in situations as diverse as transplantation, cancer, viral infections and inflammatory diseases. A total of 237 individuals from 21 South American tribes speaking nine different linguistic families were studied in relation to the 14 bp insertion/deletion polymorphism at the HLA-G gene. A consistent (seven in nine) excess of heterozygosity in samples classified by language was obtained. Our data supply evidences for balancing selection acting at the HLA-G 14 bp INDEL region. Enhanced fetal survival in a pathogen-rich environment may account for these findings.

Exceeding Hrdlička's aims: 100 Years of genetics in anthropology

“…The evidence for balanced selection increased with the number of alleles at each locus. Balancing selection has also been indicated at HLA‐G in South American Indians (Veit, Cazarolli, Salzano, Schiengold, & Chies, ). Among indigenous North Americans, very strong balancing selection was also proposed to explain a great excess of heterozygotes at the HLA‐A and HLA‐B loci among the Havasupai people of Arizona (Markow et al, ).…”

Role of 14-Bp HLA-G, INDEL Polymorphism in Recurrent Miscarriage

“…3) HLA-G is involved in immune modulation and not in antigen presentation, on the opposite to the classical HLA class Ia molecules (Veit et al, 2012). 4) HLA-G has a unique promoter region, which is not observed in other HLA-encoding genes.…”

Co-infecção Plasmodium falciparum e Schistosoma haematobium: papel dos genes HLA não-clássicos de classe I (HLA-G, -E e -F) na suscetibilidade à malária

“…The HLA-G 3' UTR evaluated here revealed well-documented haplotypes (Tan et al 2005;Hviid et al 2006;Castelli et al 2010Castelli et al , 2011Castelli et al , 2014aCastelli et al , 2017Consiglio et al 2011;Lucena-Silva et al 2012Sizzano et al 2012;Veit et al 2012Veit et al , 2014Carlini et al 2013;Martelli-Palomino et al 2013;Santos et al 2013;Courtin et al 2013;Garcia et al 2013;Sabbagh et al 2014;Catamo et al 2014Catamo et al , 2015Garziera et al 2015;Gineau et al 2015;Porto et al 2015;Nilsson et al 2016;Zambra et al 2016;de Albuquerque et al 2016) (Table 8).…”

“…Up to date, approximately 14 variabe sites are frequently observed at the 3' UTR segment in worldwide populations, which are rearranged into several 3' UTR haplotypes, with UTR-01 to -07 the most frequent (minimum frequency of 4%) (Castelli et al 2010(Castelli et al , 2014a(Castelli et al , 2017Lucena-Silva et al 2012;Sabbagh et al 2014;de Albuquerque et al 2016;Nilsson et al 2016). Many studies conducted in several worldwide populations have evaluated HLA-G variability at the 5' upstream regulatory region (promoter), coding and/or 3' UTR segments (Tan et al 2005;Hviid et al 2006;Castelli et al 2010Castelli et al , 2011Consiglio et al 2011;Lucena-Silva et al 2012Sizzano et al 2012;Veit et al 2012Veit et al , 2014Carlini et al 2013;Martelli-Palomino et al 2013;Santos et al 2013;Courtin et al 2013;Garcia et al 2013;Sabbagh et al 2014;Catamo et al 2014Catamo et al , 2015Gineau et al 2015;Porto et al 2015;Garziera et al 2015;Nilsson et al 2016;Zambra et al 2016;de Albuquerque et al 2016). But, with the exception of a study reporting HLA-G variability based on the 1000 Genomes phase I data (Castelli et al 2014a), which is characterized by low depth of coverage, the complete HLA-G gene variability has not yet been characterized in African population samples.…”