High-resolution analysis of DNA copy number variations in Systemic Lupus Erythematosus patients. F. B. Barbosa1, M. Simioni2, E. A. Donadi3, V. L. Gil-da-Silva-Lopes2, A. L. Simões1 1) Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; 2) Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil; 3) Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Advances in molecular-based techniques for DNA investigation enabled the detection of an important type of genomic variation named copy number variations (CNVs). CNVs are defined as genomic segments, usually greater than 1 kilobase (kb) in size, ranging in copy number when compared to a reference genome. They can contribute to risk variability among individuals in complex diseases etiology. Systemic Lupus Erythematosus (SLE) is an autoimmune disease with strong genetic component characterized by chronic inflammation and autoantibodies production. To date, several loci have been associated with SLE pathogenesis by genome-wide association studies (GWAS). However, there are few analyses about CNVs in SLE patients. The purpose of this study was to determine the role of CNVs in 23 SLE patients. To screen the CNVs, high-resolution array Genomic Hybridization Assay was performed using the Affymetrix CytoScan HD platform. To calculate copy numbers, the data were normalized to baseline reference intensities using 366 samples (270 HapMap samples and 96 healthy normal individuals). Data was analyzed by Chromosome Analysis Suite v.1.2.2 (ChAS) software, which includes the Hidden Markov Model (HMM) algorithm used to determine the copy number states. At total, 406 CNVs were identified (CNV average number per patient was 18), distributed across all chromosomes, except Y. Deletions were more frequent than duplications, 311 and 95, respectively. CNV profile showed 269 CNVs were overlapped by genes, 152 unique CNVs and 59 CNV regions (CNVRs). From all, 39 CNVs detected have not been described in the main database of healthy subjects, the Database of Genomic Variants (DGV). Nine of these have not been described in any structural variants databases. CNVs were found in ten genes previously related with autoimmunity: deletion-type CNVs in STAT4, HLA-DPB2, CFHR4, CFHR5, SNTG1, IL3RA, UGT2B15, ADAM3A and duplication-type CNVs in MECP2 and KIAA1267. This is the first report of CNVs in these genes in SLE patients. The identification of CNV in SLE suggests a possible contribution of these variations to development of autoimmunity or the onset of the disease. This is consistent with the observed overlap between CNVs and genes implicated in the development of autoimmunity. The action of these genes in determining SLE or any other autoimmune disease should be investigated in future studies. Support: FAEPA, CAPES and FAPESP.
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