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pmTR Database: Population Matched (PM) Germline Allelic Variants of T-Cell Receptor ( TR) Loci
57 Pages Posted: 28 Jan 2021
More...Abstract
T-cell receptor (TR) germline alleles are arranged, organized and made available to the research community by the IMGT database. This state-of-the-art database, however, does not provide information regarding population specificity and allelic frequencies of the genes all four human TR loci (TRA, TRB, TRG and TRD). The specificity of allelic variants to different human populations can, however, be a rich source of information when studying the genetic basis of population-specific immune responses in vaccination and disease. To make TR germline alleles available for such population-specific studies, we meticulously identified true germline alleles enriched with complete TR allele sequences and their frequencies across 26 different human populations, profiled by “1,000 Genomes data”. We identified 205TRAV, 249TRBV, 16 TRGV and 5 TRDV germline alleles supported by at least four haplotypes (= minimum of two individuals). The diversity of germline allelic variants in the TR loci is highest in Africans followed by Non-African populations. A majority of the Non-African alleles are specific to the Asian populations, suggesting a diverse profile of TR germline alleles in different human populations. Interestingly, the alleles known in the IMGT database are frequent and common across all the superpopulations. We believe that this new set of genuine germline TR sequences represents a valuable new resource which we have made available through the new population-matchedTR (pmTR) database, accessible via https://pmtrig.lumc.nl/ .
Funding Statement: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 707404.
This project has also received funding from the PERISCOPE program. PERISCOPE has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115910. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA) and Bill and Melinda Gates Foundation (BMGF).
Declaration of Interests: JJMvD is the founder of the EuroClonality Consortium and one of the inventors on the EuroClonality-owned patents and EuroFlow-owned patents, which are licensed to Invivoscribe, BD Biosciences or Cytognos; these companies pay royalties to the EuroClonality and EuroFlow Consortia, respectively, which are exclusively used for sustainability of these consortia. JJMvD reports an Educational Services Agreement with BD Biosciences and a Scientific Advisory Agreement with Cytognos to LUMC. The rest of the authors declare that they have no other relevant conflicts of interest.
Keywords: population, germline, allelic variants, TR loci, diversity
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