A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity

Abstract

BackgroundAs genetic genetic factors are important in SLE, so screening causative genes is of great significance for the prediction and early prevention in people who may develop SLE. At present, it is very difficult to screen causative genes through pedigrees. The analytical method described herein can be used to screen causative genes for SLE and other complex diseases through pedigrees.MethodsFor the first time, 24 lupus pedigrees were analyzed by combining whole exon sequencing and a variety of biological information tools including common-specific analysis, pVAAST (pedigree variant annotation, analysis and search tool), Exomiser (Combining phenotype and PPI associated analysis), and FARVAT (family based gene burden), and the causative genes of these families with lupus identified. Selected causative genes in peripheral-blood mononuclear cells (PBMCs) were evaluated by quantitative polymerase chain reaction (qPCR).ResultsCell division cycle 27 (CDC27) was screened out by common-specific analysis and Exomiser causative gene screening. FARVAT analysis on these families detected only CDC27 at the extremely significant level (false discovery rate <0.05) by three family-based burden analyses (BURDEN, CALPHA, and SKATO). QPCR was performed to detect for CDC27 in the PBMCs of the SLE family patients, sporadic lupus patients, and healthy people. Compared with the healthy control group, CDC27 expression was low in lupus patients (familial and sporadic patients) (P<0.05) and correlated with lupus activity indicators: negatively with C-reactive protein (CRP) (P<0.05) and erythrocyte sedimentation rate (P<0.05) and positively with complement C3 and C4 (P<0.05). The CDC27 expression was upregulated in PBMCs from SLE patients with reduced lupus activity after immunotherapy (P<0.05). Based on Receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of CDC27 in diagnosing SLE were 82.30% and 94.40%.ConclusionThe CDC27 gene, as found through WES combined with multiple analytical method may be a causative gene of lupus. CDC27 may serve as a marker for the diagnosis of SLE and is closely related to the lupus activity. We hope that the analytical method in this study will be used to screen causative genes for other diseases through small pedigrees, especially among non-close relatives.

The genetic architecture of complete blood counts in lactating Holstein dairy cows

“…Lastly, CDC27 is located in the region identified. This gene has been linked to several diseases including lupus ( Shang et al, 2022 ), pulmonary fibrosis ( Qi et al, 2020 ), and numerous cancers ( Ahn et al, 2014 ; Guo et al, 2015 ; Xin et al, 2018 ). Due to the connection of these genes with regulation of immune cells, genes related to immune response, and autoimmune diseases and cancer in humans, it may be worthwhile further investigating their relationship to WBC in cattle.…”

Next generation sequencing based exploration of potential candidate variants and microRNAs in patients with idiopathic Hypospermatogenesis sub-type of Non-Obstructive Azoozpermia

“…The highest levels of CDC27 expression are observed in thyroid and testicular tissue, which makes it an important gene to be searched for the presence of mutations in patients with cell cycle-associated pathogenic mechanisms responsible for the disease. For instance, the association of CDC27 variants with cell proliferation-related diseases such as systemic lupus erythematosus and cancer has been demonstrated in earlier studies (Kazemi-Sefat et al, 2021) (Shang et al, 2022). The TUBB8 gene is a primate speci c beta tubulin isotype which speci cally plays role in spindle assembly in oocytes.…”

Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

“…Recent studies have described several novel genes associated with SLE following WES analysis in an Asian population, such as the decreased expression of cell division cycle 27 (CDC27) in patients ( Shang et al, 2022 ), and novel variants in genes encoding for complement receptor 2 (CR2) ( Tang and Luo, 2022 ), C1R ( Demirkaya et al, 2017 ), NRAS, TNFAIP3 and PIK3CD ( Li et al, 2020 ), WNT16 and ERVW-1 ( Chen et al, 2022 ), ACP5 and SAMHD1 ( Hong et al, 2022 ). This list of genes contributing to monogenic SLE continues to grow with increased usage of WES over the past few years, further enriching our knowledge about the genetic contribution to SLE.…”