Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
| Autor: | Kozyrev, Sergey V, Abelson, Anna-Karin, Wojcik, Jerome, Zaghlool, Ammar, Linga Reddy, M V Prasad, Sanchez, Elena, Gunnarsson, Iva, Svenungsson, Elisabet, Sturfelt, Gunnar, Jönsen, Andreas, Truedsson, Lennart, Pons-Estel, Bernardo A, Witte, Torsten, D'Alfonso, Sandra, Barizzone, Nadia, Barrizzone, Nadia, Danieli, Maria Giovanna, Gutierrez, Carmen, Suarez, Ana, Junker, Peter, Laustrup, Helle, González-Escribano, Maria Francisca, Martin, Javier, Abderrahim, Hadi, Alarcón-Riquelme, Marta E |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Nonsynonymous substitution
Linkage disequilibrium DNA Complementary Amino Acid Motifs Molecular Sequence Data Variation (Genetics) Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium Cohort Studies Exon Gene Frequency Genetics medicine Ankyrin Chromosomes Human Humans Lupus Erythematosus Systemic Protein Isoforms Genetic Predisposition to Disease Histidine Amino Acid Sequence Gene Alleles Adaptor Proteins Signal Transducing chemistry.chemical_classification Sweden B-Lymphocytes Lupus erythematosus Genome Human Membrane Proteins Exons Sequence Analysis DNA medicine.disease Physical Chromosome Mapping Introns Ankyrin Repeat Protein Structure Tertiary Alternative Splicing Logistic Models chemistry Amino Acid Substitution Haplotypes Case-Control Studies Ankyrin repeat Gene Deletion |
| Zdroj: | Kozyrev, S V, Abelson, A-K, Wojcik, J, Zaghlool, A, Linga Reddy, M V P, Sanchez, E, Gunnarsson, I, Svenungsson, E, Sturfelt, G, Jönsen, A, Truedsson, L, Pons-Estel, B A, Witte, T, D'Alfonso, S, Barizzone, N, Barrizzone, N, Danieli, M G, Gutierrez, C, Suarez, A, Junker, P, Laustrup, H, González-Escribano, M F, Martin, J, Abderrahim, H & Alarcón-Riquelme, M E 2008, ' Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus ', Nature Genetics, vol. 40, no. 2, pp. 211-216 . https://doi.org/10.1038/ng.79 |
| DOI: | 10.1038/ng.79 |
| Popis: | Udgivelsesdato: Feb Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance. In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease. |
| Databáze: | OpenAIRE |
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