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

Autor: Corcoran MM; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden., Phad GE; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden., Vázquez Bernat; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden., Stahl-Hennig C; Deutsches Primatenzentrum GmbH (DPZ), Leibniz-Institute for Primate Research, Göttingen D-37077, Germany., Sumida N; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden., Persson MA; Department of Clinical Neuroscience, Stockholm University, Box 1031, Solna SE-17121, Sweden., Martin M; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Box 1031, Solna SE-17121, Sweden., Karlsson Hedestam GB; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-17177, Sweden.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2016 Dec 20; Vol. 7, pp. 13642. Date of Electronic Publication: 2016 Dec 20.
DOI: 10.1038/ncomms13642
Abstrakt: 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.
Databáze: MEDLINE