HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples.

Abstract

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.

• Authors: Erick C Castelli, Celso T Mendes-Junior, Audrey Sabbagh, Iane O P Porto, André Garcia, Jaqueline Ramalho, Thálitta H A Lima, Juliana D Massaro, Fabrício C Dias, Cristhianna V A Collares, Vincent Jamonneau, Bruno Bucheton, Mamadou Camara, Eduardo A Donadi
• Journal: Human immunology (Hum Immunol) Vol. 76 Issue 12 Pg. 945-53 (Dec 2015) ISSN: 1879-1166 [Electronic] United States
• PMID: 26187162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• 3' Untranslated Regions
• HLA-E antigen
• Histocompatibility Antigens Class I

Topics

• 3' Untranslated Regions
• Africa, Western
• Alleles
• Black People (genetics)
• Gene Frequency
• Genetic Variation
• Genetics, Population
• Haplotypes
• High-Throughput Nucleotide Sequencing (methods)
• Histocompatibility Antigens Class I (genetics)
• Histocompatibility Testing
• Humans
• Linkage Disequilibrium
• Open Reading Frames
• Polymorphism, Single Nucleotide
• Sequence Analysis, DNA