TY - JOUR
T1 - Polymorphisms in human immunoglobulin heavy chain variable genes and their upstream regions
AU - Mikocziova, Ivana
AU - Gidoni, Moriah
AU - Lindeman, Ida
AU - Peres, Ayelet
AU - Snir, Omri
AU - Yaari, Gur
AU - Sollid, Ludvig M.
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2020/6/4
Y1 - 2020/6/4
N2 - 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=85085904028&partnerID=8YFLogxK
U2 - 10.1093/NAR/GKAA310
DO - 10.1093/NAR/GKAA310
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C2 - 32365177
AN - SCOPUS:85085904028
SN - 0305-1048
VL - 48
SP - 5499
EP - 5510
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 10
ER -