Scholarship 16/10306-8 - Autoimunidade, Lúpus eritematoso sistêmico - BV FAPESP
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Impact of C4 copy number variation in the susceptibility to systemic lupus erythematosus

Grant number: 16/10306-8
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date: August 02, 2016
End date: December 21, 2016
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Aguinaldo Luiz Simões
Grantee:Fernanda Bueno Barbosa
Supervisor: Bernardo Lemos Ferreira da Silva
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Institution abroad: Harvard University, Cambridge, United States  
Associated to the scholarship:13/17062-9 - CNV Analysis in Systemic Lupus Erythematosus patients, BP.DR

Abstract

Molecular approaches have been applied to understanding the role of genomic structural variation in systemic lupus erythematosus (SLE), an autoimmune disease with a strong genetic background. Copy number variations (CNVs), deletions or duplications usually greater than 1 Kb in genomic DNA, can contribute to the variability of the risk among individuals in complex diseases etiology. Low copy number of complement component 4 (C4) gene has been associated with susceptibility to SLE in European and Asian populations. However, few studies focus on CNVs associated with SLE in admixed population as the Brazilian one. Considering the heterogeneity of the disease and the fact that the frequencies of risk alleles may change according to the geographic region and ancestry, different association results can be identified depending on the population studied. The aim of this proposal is to perform a case-control study investigating the association of the C4 CNV with SLE in the Brazilian population. The C4 copy number state will be determined by TaqMan-based quantitative PCR (qPCR) in 140 unrelated SLE patients and 160 healthy individuals. Independent replication analysis of C4 copy number genotyping will be performed by droplet digital PCR (ddPCR). Due the disease heterogeneity, the logistic regression model for evaluating the association of C4 copy number changes with SLE will be adjusted for the confounding effect of population stratification and sex. In silico analysis will be performed to predict possible functional consequences of changes in the C4 copy number state on splicing. The coupled qPCR-ddPCR approach can be an effective way to elucidate the impact of C4 dosage changes in susceptibility to SLE. The findings from this research will contribute to a better understanding of how CNVs can act as potential modulators in SLE etiology. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BARBOSA, FERNANDA BUENO; SIMIONI, MILENA; VIEIRA WIEZEL, CLAUDIA EMILIA; TORRES, FABIO ROSSI; MOLCK, MIRIAM COELHO; BONILLA, MELVIN M.; DE ARAUJO, TABIA KAWASAKI; DONADI, EDUARDO ANTONIO; GIL-DA-SILVA-LOPES, VERA LUCIA; LEMOS, BERNARDO; et al. Copy number variation in the susceptibility to systemic lupus erythematosus. PLoS One, v. 13, n. 11, . (11/23794-7, 13/17062-9, 16/10306-8)
BARBOSA, F. B.; SIMIONI, M.; BONILLA, M. M.; TORRES, F. R.; MOLCK, M. C.; ARAUJO, T. K.; DONADI, E. A.; GIL-DA-SILVA-LOPES, V. L.; LEMOS, B.; SIMOES, A. L.. Rare copy number variations in patients with systemic lupus erythematosus. European Journal of Human Genetics, v. 26, p. 1-pg., . (13/17062-9, 11/23794-7, 16/10306-8)