title: Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases.
abstract: Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases.
authors.affiliation: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Steiman-Shimony
authors.forename: Hanna
authors.initials: H
authors.lastname: Edelman
authors.forename: Michal
authors.initials: M
authors.lastname: Barak
authors.forename: Gitit
authors.initials: G
authors.lastname: Shahaf
authors.forename: Deborah
authors.initials: D
authors.lastname: Dunn-Walters
authors.forename: David I
authors.initials: DI
authors.lastname: Stott
authors.forename: Roshini S
authors.initials: RS
authors.lastname: Abraham
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005803:Genes, Immunoglobulin / Q000235:genetics / Q000276:immunology; D005821:Genetic Techniques; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology*; D009154:Mutation; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology; D010375:Pedigree; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology
chemical_list: D007135:Immunoglobulin Variable Region