RT Journal Article
SR Electronic
T1 Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.27.921197
DO 10.1101/2020.01.27.921197
A1 Ivana Mikocziova
A1 Moriah Gidoni
A1 Ida Lindeman
A1 Ayelet Peres
A1 Omri Snir
A1 Gur Yaari
A1 Ludvig M. Sollid
YR 2020
UL http://biorxiv.org/content/early/2020/01/28/2020.01.27.921197.abstract
AB 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 novel germline IGHV alleles as inferred from rearranged naïve 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, leader 1, and leader 2 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 challenge current approaches used for annotating immunoglobulin repertoire sequencing data.