Abstract
The current SARS-CoV-2 pandemic era launched an immediate and broad response of the research community with studies both about the virus and host genetics. Research in genetics investigated HLA association with COVID-19 based on in silico, population, and individual data. However, they were conducted with variable scale and success; convincing results were mostly obtained with broader whole-genome association studies. Here, we propose a technical review of HLA analysis, including basic HLA knowledge as well as available tools and advice. We notably describe recent algorithms to infer and call HLA genotypes from GWAS SNPs and NGS data, respectively, which opens the possibility to investigate HLA from large datasets without a specific initial focus on this region. We thus hope this overview will empower geneticists who were unfamiliar with HLA to run MHC-focused analyses following the footsteps of the Covid-19|HLA & Immunogenetics Consortium.
Highlights
INTRODUCTIONThe classical HLA proteins are expressed on the surface of human cells. their primary role is to present exogenous and endogenous peptides, they were first described as “antigens” due to their interaction with T-cells in transplant rejection (Dausset, 1958)
TO HUMAN LEUKOCYTE ANTIGENS: CREATING IMMUNITY FROM DIVERSITYThe classical HLA proteins are expressed on the surface of human cells
We notably describe recent algorithms to infer and call HLA genotypes from genome-wide association studies (GWAS) SNPs and next-generation sequencing (NGS) data, respectively, which opens the possibility to investigate HLA from large datasets without a specific initial focus on this region
Summary
The classical HLA proteins are expressed on the surface of human cells. their primary role is to present exogenous and endogenous peptides, they were first described as “antigens” due to their interaction with T-cells in transplant rejection (Dausset, 1958). There are other important non-HLA genes in the MHC, such as TAP1 and TAP2, both related to peptide pumping from the cytoplasm to the endoplasmic reticulum (Praest et al, 2018), MICA and MICB, both induced in viral infections and tumors and activate NK-mediate killing (Ghadially et al, 2017), the tripartite motif (TRIM) family, related to cell cycle progression, autophagy, and viral replication restriction (van Tol et al, 2017), PSORS1C1, conferring susceptibility to psoriasis and systemic sclerosis (Allanore et al, 2011), and others In addition to their large number and potential for many combinations, the HLA genes display unparalleled genetic diversity, with more than 27,000 alleles and almost 17,000 unique proteins (June 03, 2021, https://www.ebi.ac.uk/ipd/ imgt/hla/stats.html) identified for the five most polymorphic loci (HLA-A, -C, -B, -DRB and -DQB1). We hope this work will empower researchers to include HLA-focused investigations in their palette and will contribute to promote efforts for in-depth explorations of the relationship between HLA and immunerelated outcomes in this pandemic era
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
