Polymorphisms in human immunoglobulin heavy chain variable genes and their upstream regions

Ivana Mikocziova, Moriah Gidoni, Ida Lindeman, Ayelet Peres, Omri Snir, Gur Yaari, Ludvig M. Sollid

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, and such polymorphisms may impact disease susceptibility. However, the knowledge of the genomic variation of the immunoglobulin loci is scarce. Here, we report 25 potential novel germline IGHV alleles as inferred from rearranged naive B cell cDNA repertoires of 98 individuals. Thirteen novel alleles were selected for validation, out of which ten were successfully confirmed by targeted amplification and Sanger sequencing of non-B cell DNA. Moreover, we detected a high degree of variability upstream of the V-REGION in the 5_UTR, L-PART1 and L-PART2 sequences, and found that identical V-REGION alleles can differ in upstream sequences. Thus, we have identified a large genetic variation not only in the V-REGION but also in the upstream sequences of IGHV genes. Our findings provide a new perspective for annotating immunoglobulin repertoire sequencing data.

Original languageEnglish
Pages (from-to)5499-5510
Number of pages12
JournalNucleic Acids Research
Volume48
Issue number10
DOIs
StatePublished - 4 Jun 2020

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© The Author(s) 2020.

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