Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/39573
Title: Understanding the Genomic Structure of Copy-Number Variation of the Low-Affinity Fcγ Receptor Region Allows Confirmation of the Association of FCGR3B Deletion with Rheumatoid Arthritis.
Authors: Rahbari, Raheleh
Zuccherato, Luciana W.
Tischler, German
Chihota, Belinda
Ozturk, Hasret
Saleem, Sara
Tarazona-Santos, Eduardo
Machado, Lee R.
Hollox, Edward J.
First Published: 20-Dec-2016
Publisher: Wiley for Human Genome Variation Society
Citation: Human Mutation, 2016, 38, pp. 390–399.
Abstract: Fcγ receptors are a family of cell-surface receptors that are expressed by a host of different innate and adaptive immune cells, and mediate inflammatory responses by binding the Fc portion of immunoglobulin G. In humans, five low-affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, which are located in an 82.5-kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy-number variation (CNV). Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA). In this study, we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous native American population, and show that some but not all alleles are likely to be identical-by-descent. We also localize a duplication breakpoint, confirming that the mechanism of CNV generation is nonallelic homologous recombination, and identify several alleles with gene conversion events using fosmid sequencing data. We use information on the structure of the deletion alleles to distinguish FCGR3B deletions from FCGR3A deletions in whole-genome array comparative genomic hybridization (aCGH) data. Reanalysis of published aCGH data using this approach supports association of FCGR3B deletion with increased risk of RA in a large cohort of 1,982 cases and 3,271 controls (odds ratio 1.61, P = 2.9×10(-3) ).
DOI Link: 10.1002/humu.23159
ISSN: 1059-7794
eISSN: 1098-1004
Links: http://onlinelibrary.wiley.com/doi/10.1002/humu.23159/abstract
http://hdl.handle.net/2381/39573
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Novel variants have been submitted to dbVAR (accession number nstd142) (https://www.ncbi.nlm.nih.gov/dbvar).
Appears in Collections:Published Articles, Dept. of Genetics

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