Association of HLA-A and Non-Classical HLA Class I Alleles

Abstract

The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region.

Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios

“…Traditionally, the HLA super-locus has been divided in five genomic sub-regions [ 10 ]. Within the encoded genes, further distinction is made between the so-called classical MHC genes, which encode the functional, epitope presenting molecules; and much less polymorphic, accessory non-classical genes [ 11 , 12 ] . The class I classical MHC genes HLA-A, HLA-B and HLA-C, are expressed in all nucleated cells and are known to bind proteins from intracellular invading pathogens [ 13 , 14 ].…”

“…There are two additional regions, extended class I and extended class II, whose contributions to the gene count are minimal and are often disregarded [ 10 ]. Typically, for transplantation purposes only the classical genes are tested, there is an ongoing discussion on the role of non-classical genes in transplantation failure [ 11 , 12 ] .…”

Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF

“…For allelic and two or more loci frequency estimations, all putative homozygotes were considered either true homozygotes or heterozygotes for the observed allele, and an undefined or undetectable ('blank') allele as previously described. [16] Based on this haplotype estimation, main haplotypes, with a cumulated frequency higher than 98%, were a priori encoded for each gene and genotype data were reanalyzed according to this new nomenclature. Using an in-house computer program, data output files (.txt) were formatted into files readable by the "Phenotype" application of the Gene[rate] computer tool package.…”

Characterisation of major histocompatibility complex class I transcripts in an Australian dragon lizard

“…This is not surprising given that MHC loci arise by periodic gene duplication and rearrangement events (Nei and Rooney, 2005). It is also possible that these transcripts are naturally truncated and encode non-classical MHC I molecules that are secreted and undertake peptide presentation away from the cell surface, given the lack of Tm/Cyt domains and the presence of conserved sites associated with peptide presentation (Carlini et al, 2016;Donadi et al, 2011;Glaberman et al, 2009). Given that Ctde-UA*007 and Ctde-UA*008 are likely truncated due to incomplete transcriptome assembly they were not assigned to a new locus group and were included in the 'UA' MHC I locus group.…”