Germline polymorphisms and alternative splicing of human immunoglobulin light chain genes.
Genetics
Genomics
Immunology
Molecular genetics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Oct 2021
22 Oct 2021
Historique:
received:
06
04
2021
revised:
17
07
2021
accepted:
27
09
2021
entrez:
25
10
2021
pubmed:
26
10
2021
medline:
26
10
2021
Statut:
epublish
Résumé
Inference of germline polymorphisms in immunoglobulin genes from B cell receptor repertoires is complicated by somatic hypermutations, sequencing/PCR errors, and by varying length of reference alleles. The light chain inference is particularly challenging owing to large gene duplications and absence of D genes. We analyzed the light chain cDNA sequences from naïve B cell receptor repertoires from 100 individuals. We optimized light chain allele inference by tweaking parameters of the TIgGER functions, extending the germline reference sequences, and establishing mismatch frequency patterns at polymorphic positions to filter out false-positive candidates. We identified 48 previously unreported variants of light chain variable genes. We selected 14 variants for validation and successfully validated 11 by Sanger sequencing. Clustering of light chain 5'UTR, L-PART1, and L-PART2 revealed partial intron retention in 11 kappa and 9 lambda V alleles. Our results provide insight into germline variation in human light chain immunoglobulin loci.
Identifiants
pubmed: 34693229
doi: 10.1016/j.isci.2021.103192
pii: S2589-0042(21)01160-3
pmc: PMC8517844
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103192Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
V.G. declares advisory board positions in aiNET GmbH and Enpicom B.V. V.G. is also a consultant for Roche/Genentech. All remaining authors declare no conflict of interests.
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