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Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

Author

Listed:
  • Martin M. Corcoran

    (Tumor and Cell Biology, Karolinska Institutet)

  • Ganesh E. Phad

    (Tumor and Cell Biology, Karolinska Institutet)

  • Néstor Vázquez Bernat

    (Tumor and Cell Biology, Karolinska Institutet)

  • Christiane Stahl-Hennig

    (Deutsches Primatenzentrum GmbH (DPZ), Leibniz-Institute for Primate Research)

  • Noriyuki Sumida

    (Tumor and Cell Biology, Karolinska Institutet)

  • Mats A.A. Persson

    (Stockholm University)

  • Marcel Martin

    (Science for Life Laboratory, Stockholm University)

  • Gunilla B. Karlsson Hedestam

    (Tumor and Cell Biology, Karolinska Institutet)

Abstract

Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.

Suggested Citation

  • Martin M. Corcoran & Ganesh E. Phad & Néstor Vázquez Bernat & Christiane Stahl-Hennig & Noriyuki Sumida & Mats A.A. Persson & Marcel Martin & Gunilla B. Karlsson Hedestam, 2016. "Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13642
    DOI: 10.1038/ncomms13642
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    1. Fredrika Hellgren & Alberto Cagigi & Rodrigo Arcoverde Cerveira & Sebastian Ols & Theresa Kern & Ang Lin & Bengt Eriksson & Michael G. Dodds & Edith Jasny & Kim Schwendt & Conrad Freuling & Thomas Mül, 2023. "Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Mark Chernyshev & Mrunal Sakharkar & Ruth I. Connor & Haley L. Dugan & Daniel J. Sheward & C. G. Rappazzo & Aron Stålmarck & Mattias N. E. Forsell & Peter F. Wright & Martin Corcoran & Ben Murrell & L, 2023. "Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Marco Mandolesi & Hrishikesh Das & Liset Vries & Yiqiu Yang & Changil Kim & Manojj Dhinakaran & Xaquin Castro Dopico & Julian Fischbach & Sungyong Kim & Mariia V. Guryleva & Monika Àdori & Mark Cherny, 2024. "Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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