A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity
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...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.876963/full |
| _version_ | 1818312689977393152 |
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| author | Shunlai Shang Shunlai Shang Yena Zhou Keng Chen Lang Chen Ping Li Diangeng Li Shaoyuan Cui Mei-Jun Zhang Xiangmei Chen Xiangmei Chen Qinggang Li |
| author_facet | Shunlai Shang Shunlai Shang Yena Zhou Keng Chen Lang Chen Ping Li Diangeng Li Shaoyuan Cui Mei-Jun Zhang Xiangmei Chen Xiangmei Chen Qinggang Li |
| author_sort | Shunlai Shang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T08:21:51Z |
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| id | doaj.art-cd3c6701f0f14198b51dd02e6057453d |
| institution | Directory Open Access Journal |
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| last_indexed | 2024-12-13T08:21:51Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-cd3c6701f0f14198b51dd02e6057453d2022-12-21T23:53:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.876963876963A Novel Gene CDC27 Causes SLE and Is Associated With the Disease ActivityShunlai Shang0Shunlai Shang1Yena Zhou2Keng Chen3Lang Chen4Ping Li5Diangeng Li6Shaoyuan Cui7Mei-Jun Zhang8Xiangmei Chen9Xiangmei Chen10Qinggang Li11School of Medicine, Nankai University, Tianjin, ChinaDepartment of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaClinical Medical School, Guangdong Pharmaceutical University, Guangzhou, ChinaMedical Technology & Bioinformatics Department, Beijing Mygenostics co., LTD, Beijing, ChinaDepartment of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, ChinaDepartment of Academic Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, ChinaBioinformation Department, Geneis (Beijing) Co., Ltd., Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, ChinaDepartment of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, ChinaBackgroundAs 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.876963/fulllupus familymultiple bioinformatics analysisCDC27whole exone sequencingmarker |
| spellingShingle | Shunlai Shang Shunlai Shang Yena Zhou Keng Chen Lang Chen Ping Li Diangeng Li Shaoyuan Cui Mei-Jun Zhang Xiangmei Chen Xiangmei Chen Qinggang Li A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity Frontiers in Immunology lupus family multiple bioinformatics analysis CDC27 whole exone sequencing marker |
| title | A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity |
| title_full | A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity |
| title_fullStr | A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity |
| title_full_unstemmed | A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity |
| title_short | A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity |
| title_sort | novel gene cdc27 causes sle and is associated with the disease activity |
| topic | lupus family multiple bioinformatics analysis CDC27 whole exone sequencing marker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.876963/full |
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