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

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Castelli, Erick C. ; Mendes-Junior, Celso T. ; Sabbagh, Audrey ; Porto, Iane O. P. ; Garcia, Andre ; Ramalho, Jaqueline ; Lima, Thalitta H. A. ; Massaro, Juliana D. ; Dias, Fabricio C. ; Collares, Cristhianna V. A. ; Jamonneau, Vincent ; Bucheton, Bruno ; Camara, Mamadou ; Donadi, Eduardo A.

• Document type: Journal article
• Source: HUMAN IMMUNOLOGY; v. 76, n. 12, p. 9-pg., 2015-12-01.

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. (C) 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/17084-2 - Evaluation of MHC Class I genes variability, regulation and evolutive history
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants