RT Journal Article
SR Electronic
T1 Computational inference, validation, and analysis of 5’UTR-leader sequences of alleles of immunoglobulin heavy chain variable genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.10.447679
DO 10.1101/2021.06.10.447679
A1 Yixun Huang
A1 Linnea Thörnqvist
A1 Mats Ohlin
YR 2021
UL http://biorxiv.org/content/early/2021/06/10/2021.06.10.447679.abstract
AB Upstream and downstream sequences of immunoglobulin genes may affect the expression of such genes. However, these sequences are rarely studied or characterized in most studies of immunoglobulin repertoires. Inference from large, rearranged immunoglobulin transcriptome data sets offers an opportunity to define the upstream regions (5’-untranslated regions and leader sequences). We have now established a new data pre-processing procedure to eliminate artifacts caused by a 5’-RACE library generation process, reanalyzed a previously studied data set defining human immunoglobulin heavy chain genes, and identified novel upstream regions, as well as previously identified upstream regions that may have been identified in error. Upstream sequences were also identified for a set of previously uncharacterized germline gene alleles. Several novel upstream region variants were validated, for instance by their segregation to a single haplotype in heterozygotic subjects. SNPs representing several sequence variants were identified from population data. Finally, based on the outcomes of the analysis, we define a set of testable hypotheses with respect to the placement of particular alleles in complex IGHV locus haplotypes, and discuss the evolutionary relatedness of particular heavy chain variable genes based on sequences of their upstream regions.Competing Interest StatementThe authors have declared no competing interest.