scholarly journals Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Li ◽  
Jun Zhang ◽  
Dan Liao ◽  
Lu Yang ◽  
Yingxiong Wang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Meta Analysis ◽  
Significant Risk ◽  
Gene Copy Number ◽  
Significant Risk Factor ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Case Control Studies

Abstract Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE.

scholarly journals Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Danlei Zhou ◽  
Michael Rudnicki ◽  
Gilbert T. Chua ◽  
Simon K. Lawrance ◽  
Bi Zhou ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Copy Number ◽  
Inflammatory Diseases ◽  
Stop Codon ◽  
Case Series ◽  
Gene Copy Number ◽  
Genetic Mutation ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Human Complement

Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a deficiency of C4B protein caused by genetic mutation in addition to gene copy-number variation. Those variants and mutants were characterized, sequenced and specific techniques for detection developed. Novel findings were made in four case series. First, the amino acid sequence determinant for C4B7 was likely the R729Q variation at the anaphylatoxin-like region. Second, in healthy White subject MS630, a C-nucleotide deletion at codon-755 led to frameshift mutations in his single C4B gene, which was a private mutation. Third, in European family E94 with multiplex lupus-related mortality and low serum C4 levels, the culprit was a recurrent haplotype with HLA-A30, B18 and DR7 that segregated with two defective C4B genes and identical mutations at the donor splice site of intron-28. Fourth, in East-Asian subject E133P with anti-NMDA receptor encephalitis, the C4B gene had a mutation that changed tryptophan-660 to a stop-codon (W660x), which was present in a haplotype with HLA-DRB1*04:06 and B*15:27. The W660x mutation is recurrent among East-Asians with a frequency of 1.5% but not detectable among patients with SLE. A meticulous annotation of C4 sequences revealed clusters of variations proximal to sites for protein processing, activation and inactivation, and binding of interacting molecules.

scholarly journals Systematic identification of mutations and copy number alterations associated with cancer patient prognosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Joan C Smith ◽  
Jason M Sheltzer
Keyword(s):  
Copy Number ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Driver Genes ◽  
Cancer Driver ◽  
Molecular Alterations ◽  
Patient Prognosis ◽  
Almost All ◽  
Systematic Identification

Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almost all cancer driver genes contain remarkably little information on patient prognosis. However, CNAs in these same driver genes harbor significant prognostic power. Focal CNAs are associated with worse outcomes than broad alterations, and CNAs in many driver genes remain prognostic when controlling for stage, grade, TP53 status, and total aneuploidy. By performing a meta-analysis across independent patient cohorts, we identify robust prognostic biomarkers in specific cancer types, and we demonstrate that a subset of these alterations also confer specific therapeutic vulnerabilities. In total, our analysis establishes a comprehensive resource for cancer biomarker identification and underscores the importance of gene copy number profiling in assessing clinical risk.

Abstract 3098: ERCC1 gene copy number variations in resected non-small cell lung cancer

2012 ◽  
Author(s):  
Luc Friboulet ◽  
Ken A. Olaussen ◽  
Alexander Valent ◽  
Ximing Tang ◽  
Tao Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Copy Number Variations ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung
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