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.

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) )

Association between individual proportion of African, Native American and European genomic ancestry levels with <i>Trypanosoma cruzi</i> infection (The Bambui-Epigen Cohort Study of Aging).

<p>Association between individual proportion of African, Native American and European genomic ancestry levels with <i>Trypanosoma cruzi</i> infection (The Bambui-Epigen Cohort Study of Aging).</p

Selected baseline characteristics of study participants, and by <i>Trypanosoma cruzi</i> infection (The Bambui Cohort Study of Ageing).

<p>Selected baseline characteristics of study participants, and by <i>Trypanosoma cruzi</i> infection (The Bambui Cohort Study of Ageing).</p

Hazard ratio for 15-year mortality by the presence of any major electrocardiogram abnormalities among infected with <i>Trypanosoma cruzi</i> and stratified by individual proportion of African, Native American and European ancestry levels (The Bambui-Epigen Cohort Study of Aging).

<p>Hazard ratio for 15-year mortality by the presence of any major electrocardiogram abnormalities among infected with <i>Trypanosoma cruzi</i> and stratified by individual proportion of African, Native American and European ancestry levels (The Bambui-Epigen Cohort Study of Aging).</p

Association between individual proportion of Western African sub-continental genomic ancestry levels relative to total African ancestry with <i>Trypanosoma cruzi</i> infection and any major electrocardiogram abnormalities among infected (The Bambui-Epigen Cohort Study of Aging).

<p>Association between individual proportion of Western African sub-continental genomic ancestry levels relative to total African ancestry with <i>Trypanosoma cruzi</i> infection and any major electrocardiogram abnormalities among infected (The Bambui-Epigen Cohort Study of Aging).</p

Baseline characteristics of study participants significantly associated with African, Native American and/or European genomic ancestry (The Bambui Cohort Study of Ageing).

<p>Baseline characteristics of study participants significantly associated with African, Native American and/or European genomic ancestry (The Bambui Cohort Study of Ageing).</p

Association between individual proportion of African, Native American and European genomic ancestry levels with any major electrocardiogram abnormalities among infected with <i>Trypanosoma cruzi</i> (The Bambui-Epigen Cohort Study of Aging).

<p>Association between individual proportion of African, Native American and European genomic ancestry levels with any major electrocardiogram abnormalities among infected with <i>Trypanosoma cruzi</i> (The Bambui-Epigen Cohort Study of Aging).</p

Tabular_kinship_AllAnimals

This file contains the Kinship values between each pair of individuals present in the All animals sample. Theses kinship values were used in each resampling approach applied in the present study

Tabular_Gmatrix_All_animals

This file contains the G matrix (VanRaden, 2009) values between each pair of individuals present in the All animals sample. Theses kinship values were used in each resampling approach applied in the present study

Supplementary_file1

This file contains the R script used to perform the threshold resampling applied in this study