title: Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Corcoran
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
authors.forename: Ganesh E
authors.initials: GE
authors.lastname: Phad
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
authors.forename: Néstor
authors.lastname: Vázquez Bernat
authors.affiliation: Deutsches Primatenzentrum GmbH (DPZ), Leibniz-Institute for Primate Research, Göttingen D-37077, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
authors.forename: Noriyuki
authors.identifier: 0000-0001-6121-4553
authors.initials: N
authors.lastname: Sumida
authors.affiliation: Department of Clinical Neuroscience, Stockholm University, Box 1031, Solna SE-17121, Sweden.
authors.forename: Mats A A
authors.initials: MA
authors.lastname: Persson
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Box 1031, Solna SE-17121, Sweden.
authors.forename: Marcel
authors.identifier: 0000-0002-0680-200X
authors.initials: M
authors.lastname: Martin
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D020121:5' Untranslated Regions; D000483:Alleles; D000818:Animals; D000916:Antibody Diversity; D030541:Databases, Genetic; D015723:Gene Library; D005803:Genes, Immunoglobulin; D056726:Genetic Association Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010802:Phylogeny; D013045:Species Specificity
chemical_list: D020121:5' Untranslated Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region