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

Martin M. Corcoran (), Ganesh E. Phad, Néstor Vázquez Bernat, Christiane Stahl-Hennig, Noriyuki Sumida, Mats A.A. Persson, Marcel Martin () and Gunilla B. Karlsson Hedestam ()
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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

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13642

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