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HLA-E transcription profile and MHC polymorphisms influencing its expression profile and isoforms

Grant number: 21/14213-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2022
Effective date (End): August 31, 2022
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Erick da Cruz Castelli
Grantee:Isabelle Mira da Silva
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The MHC complex presents several genes involved in the innate and adaptive immune responses. The HLA-E gene encodes cell surface proteins that act in inflammatory processes and modulates Natural Killer (NK) and T-cell responses through activating (CD94/NKG2C) and inhibitory receptors (CD94/NKG2A). Although the HLA-E gene is quite conserved in protein diversity, recent studies demonstrated that HLA-E regulatory regions and introns are more polymorphic. These polymorphisms may influence the HLA-E transcriptional profile quantitatively (higher or lower mRNA production) and qualitatively (isoform production). This project aims to update the hla-mapper methodology to optimize and correct alignments of reads from RNA-seq studies, allowing an accurate HLA-E genotype and accurate expression estimates, avoiding the alignment bias common with HLA genes due to their paralogous origins. Then, we correlate the HLA-E expression data with the genotypes from the MHC region in 460 samples from the GEUVADIS dataset. The project will allow us to detect which variants along the MHC are associated with differential HLA-E expression and the possible mechanisms underlying these associations. (AU)

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