Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis

Raheleh Rahbari, Luciana Zuccherato, German Tischler, Belinda Chihota, Eduardo Tarazona-Santos, Lee Machado, Edward J Hollox

Research output: Contribution to conference typesAbstractResearch

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 (IgG). In humans, five low affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B, which are located in a 82.5kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy number variation. Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemnic lupus erythematosus and rheumatoid arthritis. In this study we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous Native American populations, and show that some but not all alleles are likely to be identical-by descent. We also localise a duplication breakpoint, confirming that the mechanism of CNV generation is non-allelic 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 aCGH data, and confirm association of FCGR3B deletion with increased risk rheumatoid arthritis in a large cohort of 1982 cases and 3271 controls (Odds Ratio 1.61, p=2.9x10-3).
Original languageEnglish
DOIs
Publication statusPublished - 6 Dec 2016
EventBritish Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016 - Liverpool
Duration: 6 Dec 2016 → …
http://bsicongress.com/

Conference

ConferenceBritish Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016
Period6/12/16 → …
Internet address

Fingerprint

Fc Receptors
Rheumatoid Arthritis
Alleles
Genomic Segmental Duplications
Immunoglobulin Fc Fragments
Gene Conversion
North American Indians
Homologous Recombination
Cell Surface Receptors
Population
Immunoglobulin G
Chromosomes
Odds Ratio
Genome
Genes

Cite this

Rahbari, R., Zuccherato, L., Tischler, G., Chihota, B., Tarazona-Santos, E., Machado, L., & Hollox, E. J. (2016). Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis. Abstract from British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016, . https://doi.org/10.1002/humu.23159
Rahbari, Raheleh ; Zuccherato, Luciana ; Tischler, German ; Chihota, Belinda ; Tarazona-Santos, Eduardo ; Machado, Lee ; Hollox, Edward J. / Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis. Abstract from British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016, .
@conference{eea9edfbc1dd44cabed096a884b98b77,
title = "Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis",
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 (IgG). In humans, five low affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B, which are located in a 82.5kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy number variation. Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemnic lupus erythematosus and rheumatoid arthritis. In this study we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous Native American populations, and show that some but not all alleles are likely to be identical-by descent. We also localise a duplication breakpoint, confirming that the mechanism of CNV generation is non-allelic 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 aCGH data, and confirm association of FCGR3B deletion with increased risk rheumatoid arthritis in a large cohort of 1982 cases and 3271 controls (Odds Ratio 1.61, p=2.9x10-3).",
author = "Raheleh Rahbari and Luciana Zuccherato and German Tischler and Belinda Chihota and Eduardo Tarazona-Santos and Lee Machado and Hollox, {Edward J}",
year = "2016",
month = "12",
day = "6",
doi = "10.1002/humu.23159",
language = "English",
note = "British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016 ; Conference date: 06-12-2016",
url = "http://bsicongress.com/",

}

Rahbari, R, Zuccherato, L, Tischler, G, Chihota, B, Tarazona-Santos, E, Machado, L & Hollox, EJ 2016, 'Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis' British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016, 6/12/16, . https://doi.org/10.1002/humu.23159

Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis. / Rahbari, Raheleh; Zuccherato, Luciana; Tischler, German; Chihota, Belinda; Tarazona-Santos, Eduardo; Machado, Lee; Hollox, Edward J.

2016. Abstract from British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016, .

Research output: Contribution to conference typesAbstractResearch

TY - CONF

T1 - Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis

AU - Rahbari, Raheleh

AU - Zuccherato, Luciana

AU - Tischler, German

AU - Chihota, Belinda

AU - Tarazona-Santos, Eduardo

AU - Machado, Lee

AU - Hollox, Edward J

PY - 2016/12/6

Y1 - 2016/12/6

N2 - 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 (IgG). In humans, five low affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B, which are located in a 82.5kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy number variation. Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemnic lupus erythematosus and rheumatoid arthritis. In this study we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous Native American populations, and show that some but not all alleles are likely to be identical-by descent. We also localise a duplication breakpoint, confirming that the mechanism of CNV generation is non-allelic 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 aCGH data, and confirm association of FCGR3B deletion with increased risk rheumatoid arthritis in a large cohort of 1982 cases and 3271 controls (Odds Ratio 1.61, p=2.9x10-3).

AB - 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 (IgG). In humans, five low affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B, which are located in a 82.5kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy number variation. Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemnic lupus erythematosus and rheumatoid arthritis. In this study we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous Native American populations, and show that some but not all alleles are likely to be identical-by descent. We also localise a duplication breakpoint, confirming that the mechanism of CNV generation is non-allelic 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 aCGH data, and confirm association of FCGR3B deletion with increased risk rheumatoid arthritis in a large cohort of 1982 cases and 3271 controls (Odds Ratio 1.61, p=2.9x10-3).

UR - http://bsicongress.com/

U2 - 10.1002/humu.23159

DO - 10.1002/humu.23159

M3 - Abstract

ER -

Rahbari R, Zuccherato L, Tischler G, Chihota B, Tarazona-Santos E, Machado L et al. Understanding the genomic structure of copy number variants of the low-affinity Fcγ receptor region allows confirmation of the association of FCGR3B deletion with rheumatoid arthritis. 2016. Abstract from British Society for Immunology/Dutch Society for Immunology (BSI/NVVI) Annual Congress 2016, . https://doi.org/10.1002/humu.23159