RT Journal Article
SR Electronic
T1 Alternative splice variants and germline polymorphisms in human immunoglobulin light chain genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.05.429934
DO 10.1101/2021.02.05.429934
A1 Mikocziova, Ivana
A1 Peres, Ayelet
A1 Gidoni, Moriah
A1 Greiff, Victor
A1 Yaari, Gur
A1 Sollid, Ludvig M.
YR 2021
UL http://biorxiv.org/content/early/2021/02/06/2021.02.05.429934.abstract
AB Immunoglobulin loci are rich in germline polymorphisms and identification of novel polymorphic variants can be facilitated by germline inference of B cell receptor repertoires. Germline gene inference is complicated by somatic hypermutations, errors arising from PCR amplification, and DNA sequencing as well as from the varying length of reference alleles. Inference of light chain genes is even more challenging than inference of heavy chain genes due to large gene duplication events on the kappa locus as well as absence of D genes in the rearranged light chain transcripts. Here, we analyzed the light chain cDNA sequences from naïve BCR repertoires of a Norwegian cohort of 100 individuals. We optimized light chain allele inference by tweaking parameters within TIgGER functions, extending the germline reference sequences, and establishing mismatch frequency patterns at polymorphic positions to filter out false positive candidates. As a result, we identified 48 previously unreported variants of light chain variable genes. Altogether, we selected 14 candidates for novel light chain polymorphisms for validation and successfully validated 11 by Sanger sequencing. Additional clustering of light chain 5’UTR, L-PART1 and L-PART2 revealed partial intron retention in alternative splice variants in 11 kappa and 9 lambda V alleles. The alternatively spliced transcripts were only observed in genes with low expression levels, suggesting a possible role in expression regulation. Our results provide novel insight into germline variation in human light chain immunoglobulin loci.Competing Interest StatementThe authors have declared no competing interest.