Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration,...Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has ad- vanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.展开更多
The copy number of 5S rDNA and centromerie sequence RCS2 was determined by extended DNA fiber based fluorescence in situ hybridization (Fiber-FISH) in rice (Oryza sativa ssp. indica cv. Guangluai No. 4) genome. In ord...The copy number of 5S rDNA and centromerie sequence RCS2 was determined by extended DNA fiber based fluorescence in situ hybridization (Fiber-FISH) in rice (Oryza sativa ssp. indica cv. Guangluai No. 4) genome. In order to determine the copy number, it is necessary to know the basepair number that a given length DNA fiber contains under a microscope. Therefore, the length of two DNA frag-ments, in which the basepair number had been already known, was measured. The insert sequence of the tested BAC 38D17 was 136 kb and its extended DNA was 56.4 μm long, 2.41 kb/μm on average, while that of the tested BAC 44B4 was 144.5 kb in total and 55.7 μm long, 2.60 kb/μm on average under the microscope. They were very close to the theoretical value of B-DNA in the Watson-Crick DNA model, which is 2.97 kb/μm. According to the average value of basepair number per μm of the two samples mentioned above, that is, 2.51 kb/μm, it could be estimated that the copy number was about 686 for 5S rDNA and 286-1121 for the展开更多
Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma.However,whether CDKN2A SCNVs are useful b...Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma.However,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is unknown.This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)ESCdys.Methods:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to 2019.Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy number.The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.Results:A total of 205 patients with baseline m/M ESCdys were enrolled.The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion.CDKN2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable analysis.Conclusion:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.展开更多
目的利用孟德尔随机化(Mendelian randomization,MR)方法探讨DNA拷贝数与阿尔茨海默病风险之间的因果关系及免疫细胞的潜在中介效应。方法从全基因组关联分析数据库中获取了731种免疫细胞、DNA拷贝数、阿尔茨海默病的相关数据,主要采用...目的利用孟德尔随机化(Mendelian randomization,MR)方法探讨DNA拷贝数与阿尔茨海默病风险之间的因果关系及免疫细胞的潜在中介效应。方法从全基因组关联分析数据库中获取了731种免疫细胞、DNA拷贝数、阿尔茨海默病的相关数据,主要采用逆方差加权方法及MR-Egger法,对DNA拷贝数与阿尔茨海默病的因果关系进行双向MR分析。此外,通过两步中介分析识别出可能的中介免疫细胞。结果筛选后共纳入134个SNP进行双向MR分析。MR分析结果显示,DNA拷贝数与阿尔茨海默病风险之间存在负向因果关系(P<0.05),而反向分析无统计学意义(P>0.05),敏感性分析验证了结果的稳定性。中介分析显示免疫细胞表型HVEM on CD45RA-CD4^(+)在DNA拷贝数与阿尔茨海默病风险之间的因果关系中起到部分中介作用(中介效应比为4.6%)。结论DNA拷贝数的增加可能会降低阿尔茨海默病风险,免疫细胞在这一因果联系中存在部分中介作用。展开更多
目的揭示乳腺癌组织中跨膜蛋白81（TMEM81）的表达变化及其与预后的关系。方法使用TCGA数据库的门户网站cBioPortal、UALCAN以及癌症多组学和临床数据库LinkedOmics分析TMEM81在乳腺癌组织中的变化及其与临床预后的关系。结果 c BioPor...目的揭示乳腺癌组织中跨膜蛋白81（TMEM81）的表达变化及其与预后的关系。方法使用TCGA数据库的门户网站cBioPortal、UALCAN以及癌症多组学和临床数据库LinkedOmics分析TMEM81在乳腺癌组织中的变化及其与临床预后的关系。结果 c BioPortal分析结果显示26%乳腺癌患者癌组织中TMEM81基因发生了改变,包括突变、拷贝数畸变和mRNA水平上调,mRNA水平上调超过默认阈值（EXP≥2）的比例为18%,且TMEM81 mRNA水平上调不利于患者预后（P〈0.05）;UALCAN分析结果显示乳腺癌组织中TMEM81 mRNA水平显著高于正常组织（P〈0.01）;LinkedOmics分析结果显示癌组织TMEM81 mRNA水平分别受到乳腺癌PAM50分型、雌激素受体、孕激素受体、病理分期、病理T分期、组织学类型、种族和年龄的影响（P〈0.01, P〈0.01,P〈0.01,P〈0.01,P〈0.01,P〈0.01,P〈0.01,P〈0.05）。最后,TMEM81 mRNA水平与其基因拷贝数畸变正相关（P〈0.01）,而与其DNA甲基化水平负相关（P〈0.01）。结论乳腺癌组织中TMEM81基因拷贝数增加和甲基化水平降低促进其表达,TMEM81高表达不利于预后,可作为乳腺癌预后的候选标志物。展开更多
基金supported by the National Institute of Aging/National Institution of Health, USA (No. AG025223 and AG024640) to YB.
文摘Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has ad- vanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39900083) the Research Fund of the Doctoral Program of Higher Education (Grant No. 207980112).
文摘The copy number of 5S rDNA and centromerie sequence RCS2 was determined by extended DNA fiber based fluorescence in situ hybridization (Fiber-FISH) in rice (Oryza sativa ssp. indica cv. Guangluai No. 4) genome. In order to determine the copy number, it is necessary to know the basepair number that a given length DNA fiber contains under a microscope. Therefore, the length of two DNA frag-ments, in which the basepair number had been already known, was measured. The insert sequence of the tested BAC 38D17 was 136 kb and its extended DNA was 56.4 μm long, 2.41 kb/μm on average, while that of the tested BAC 44B4 was 144.5 kb in total and 55.7 μm long, 2.60 kb/μm on average under the microscope. They were very close to the theoretical value of B-DNA in the Watson-Crick DNA model, which is 2.97 kb/μm. According to the average value of basepair number per μm of the two samples mentioned above, that is, 2.51 kb/μm, it could be estimated that the copy number was about 686 for 5S rDNA and 286-1121 for the
基金Beijing Natural Science Foundation(No.7181002)Capital’s Funds for Health Improvement and Research(No.2018-1-1021)National Key Research&Development Program of China(No.2016YFC0901404)
文摘Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma.However,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is unknown.This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)ESCdys.Methods:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to 2019.Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy number.The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.Results:A total of 205 patients with baseline m/M ESCdys were enrolled.The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion.CDKN2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable analysis.Conclusion:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.
文摘目的利用孟德尔随机化(Mendelian randomization,MR)方法探讨DNA拷贝数与阿尔茨海默病风险之间的因果关系及免疫细胞的潜在中介效应。方法从全基因组关联分析数据库中获取了731种免疫细胞、DNA拷贝数、阿尔茨海默病的相关数据,主要采用逆方差加权方法及MR-Egger法,对DNA拷贝数与阿尔茨海默病的因果关系进行双向MR分析。此外,通过两步中介分析识别出可能的中介免疫细胞。结果筛选后共纳入134个SNP进行双向MR分析。MR分析结果显示,DNA拷贝数与阿尔茨海默病风险之间存在负向因果关系(P<0.05),而反向分析无统计学意义(P>0.05),敏感性分析验证了结果的稳定性。中介分析显示免疫细胞表型HVEM on CD45RA-CD4^(+)在DNA拷贝数与阿尔茨海默病风险之间的因果关系中起到部分中介作用(中介效应比为4.6%)。结论DNA拷贝数的增加可能会降低阿尔茨海默病风险,免疫细胞在这一因果联系中存在部分中介作用。
