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Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions

View ORCID ProfileIvana Mikocziova, Moriah Gidoni, View ORCID ProfileIda Lindeman, Ayelet Peres, View ORCID ProfileOmri Snir, View ORCID ProfileGur Yaari, View ORCID ProfileLudvig M. Sollid
doi: https://doi.org/10.1101/2020.01.27.921197
Ivana Mikocziova
1K.G.Jebsen Centre for Celiac Disease Research and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
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  • For correspondence: ivana.mikocziova@medisin.uio.no
Moriah Gidoni
2Faculty of Engineering, Bar Ilan University, Ramat Gan 5290002, Israel
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Ida Lindeman
1K.G.Jebsen Centre for Celiac Disease Research and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
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Ayelet Peres
2Faculty of Engineering, Bar Ilan University, Ramat Gan 5290002, Israel
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Omri Snir
1K.G.Jebsen Centre for Celiac Disease Research and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
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Gur Yaari
2Faculty of Engineering, Bar Ilan University, Ramat Gan 5290002, Israel
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Ludvig M. Sollid
1K.G.Jebsen Centre for Celiac Disease Research and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
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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 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 28, 2020.
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Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions
Ivana Mikocziova, Moriah Gidoni, Ida Lindeman, Ayelet Peres, Omri Snir, Gur Yaari, Ludvig M. Sollid
bioRxiv 2020.01.27.921197; doi: https://doi.org/10.1101/2020.01.27.921197
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Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions
Ivana Mikocziova, Moriah Gidoni, Ida Lindeman, Ayelet Peres, Omri Snir, Gur Yaari, Ludvig M. Sollid
bioRxiv 2020.01.27.921197; doi: https://doi.org/10.1101/2020.01.27.921197

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