Genetic diversity of HLA class II genes in worldwide populations and detection of variants that influence the expression profile of these genes

• Grant number: 21/02815-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2021
• Status: Discontinued
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Erick da Cruz Castelli
• Grantee: Nayane dos Santos Brito Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The HLA class II genes encode molecules that have a pivotal role in the process of antigenic presentation and therefore, they are important in several physiological and pathological conditions, such as infections, graft-host reactions, neoplasms, and autoimmune diseases. Variability is an important characteristic of HLA class II genes, which allows them to present thousands of different peptides. Polymorphisms in introns and regulatory regions may have a significant impact on the biological function of these genes, such as changes in their expression levels and alternative editing of the primary transcript. In this context, we will evaluate the genetic diversity (SNPs and haplotypes) of the main genes of the MHC class II region, HLA-DRA, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1, TAP1, TAP2, HLA- DMA, HLA-DMB, HLA-DOA, and HLA-DOB, in 4507 samples from 84 different populations, through new generation sequencing and computational methods developed for this project. The expression profile of these genes will be evaluated in 460 samples from the previous step, looking for variants that influence the expression and editing profile of the primary transcript. The variability data will constitute the profile of the studied populations, which can be useful in further population and disease association studies, especially autoimmune diseases. (AU)