目的以中国汉族偏执型精神分裂症患者为研究对象,重复验证RELN(Reelin)基因单核苷酸多态性与精神分裂症的关联性。方法以美国精神障碍诊断与统计手册第四版为诊断标准(Diagnostic and StatisticalManual of Mental Disorders-Fourth Edi...目的以中国汉族偏执型精神分裂症患者为研究对象,重复验证RELN(Reelin)基因单核苷酸多态性与精神分裂症的关联性。方法以美国精神障碍诊断与统计手册第四版为诊断标准(Diagnostic and StatisticalManual of Mental Disorders-Fourth Edition,DSM-Ⅳ)在河南省北部地区收集326例偏执型精神分裂症患者(男女各半),在同一地域招募健康体检者334名(男女各半)作为对照,检测RELN基因rs12705169、rs11764507和rs17157643单核苷酸多态性位点。结果仅发现患者组和对照组之间rs12705169位点的基因型和等位基因频率差异有统计学意义(P<0.01)。按性别分层后进一步分析,rs12705169在女性患者和对照之间基因型和基因频率分布差异具有统计学意义(CC:OR=0.27,95%CI=0.18～0.45;AC:OR=0.43,95%CI=0.29～0.63,P<0.01)。结论RELN基因多态性与中国女性偏执型汉族精神分裂症存在关联,RELN基因可能是精神分裂症的易感基因。展开更多
Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations.Based on the reported down-regulation of RELN in schizophrenia patient...Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations.Based on the reported down-regulation of RELN in schizophrenia patients compared with normal subjects,we speculated that variants in the RELN promoter region may confer risk for schizophrenia.In this study,we investigated the associations of three SNPs in the promoter region of RELN with schizophrenia in a case-control sample from southwestern China（940 cases and 13 69 controls）.The results suggested that none of the SNPs showed significant associations in our sample,indicating the risk variants for schizophrenia in RELN may not be located in the promoter region.We also performed meta-analysis by combining our data with previously reported data on the Chinese population with a total sample size of 2 843 individuals,and the result remained nonsignificant.Collectively,our results suggested variants in the RELN promoter may not harbor risk SNPs associated with schizophrenia in the Chinese population.展开更多
Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal ...Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy(ADLTE).However,this mutation is not frequently discovered in the Chinese population.Additionally,there are few clinical studies regarding the connection between RELN and glioma.Case presentation The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures(GTCS)during sleep for 7 years were retrospectively analyzed.In addition to experiencing his first seizure at the age of one,his mother also suffered from GTCS during her pregnancy,and a glioma was discovered.An investigation involving gene sequencing was conducted on the proband and his parents.He was diagnosed with ADLTE once a missense mutation in RELN(c.1799 C>T)was identified as the causal factor.The mutation was inherited from his mother.He was taking levetiracetam(500 mg twice a day)to avoid seizures,but his mother died of status epilepticus caused by glioma recurrence two years earlier.Conclusions Genetic issues should be given more consideration in cases of temporal lobe epilepsy.If the source of the seizures is determined to be inherited,anti-seizure medications should be used for prolonged periods.Furthermore,more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.展开更多
RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtai...RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.展开更多
文摘目的以中国汉族偏执型精神分裂症患者为研究对象,重复验证RELN(Reelin)基因单核苷酸多态性与精神分裂症的关联性。方法以美国精神障碍诊断与统计手册第四版为诊断标准(Diagnostic and StatisticalManual of Mental Disorders-Fourth Edition,DSM-Ⅳ)在河南省北部地区收集326例偏执型精神分裂症患者(男女各半),在同一地域招募健康体检者334名(男女各半)作为对照,检测RELN基因rs12705169、rs11764507和rs17157643单核苷酸多态性位点。结果仅发现患者组和对照组之间rs12705169位点的基因型和等位基因频率差异有统计学意义(P<0.01)。按性别分层后进一步分析,rs12705169在女性患者和对照之间基因型和基因频率分布差异具有统计学意义(CC:OR=0.27,95%CI=0.18～0.45;AC:OR=0.43,95%CI=0.29～0.63,P<0.01)。结论RELN基因多态性与中国女性偏执型汉族精神分裂症存在关联,RELN基因可能是精神分裂症的易感基因。
文摘Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations.Based on the reported down-regulation of RELN in schizophrenia patients compared with normal subjects,we speculated that variants in the RELN promoter region may confer risk for schizophrenia.In this study,we investigated the associations of three SNPs in the promoter region of RELN with schizophrenia in a case-control sample from southwestern China（940 cases and 13 69 controls）.The results suggested that none of the SNPs showed significant associations in our sample,indicating the risk variants for schizophrenia in RELN may not be located in the promoter region.We also performed meta-analysis by combining our data with previously reported data on the Chinese population with a total sample size of 2 843 individuals,and the result remained nonsignificant.Collectively,our results suggested variants in the RELN promoter may not harbor risk SNPs associated with schizophrenia in the Chinese population.
文摘Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy(ADLTE).However,this mutation is not frequently discovered in the Chinese population.Additionally,there are few clinical studies regarding the connection between RELN and glioma.Case presentation The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures(GTCS)during sleep for 7 years were retrospectively analyzed.In addition to experiencing his first seizure at the age of one,his mother also suffered from GTCS during her pregnancy,and a glioma was discovered.An investigation involving gene sequencing was conducted on the proband and his parents.He was diagnosed with ADLTE once a missense mutation in RELN(c.1799 C>T)was identified as the causal factor.The mutation was inherited from his mother.He was taking levetiracetam(500 mg twice a day)to avoid seizures,but his mother died of status epilepticus caused by glioma recurrence two years earlier.Conclusions Genetic issues should be given more consideration in cases of temporal lobe epilepsy.If the source of the seizures is determined to be inherited,anti-seizure medications should be used for prolonged periods.Furthermore,more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.
基金This work was supported by the National Key Research and Development Program of China (2018YFA0107001)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010100)+5 种基金the National Key Research and Development Program of China (2018YFC2000100,2018YFA0107203,2017YFA0103304,2017 YFA0102802,2015CB964800,2014CB910503)the National Natural Science Foundation of China (81625009,81330008,91749202, 91749123,31671429,81671377,81771515,31601109,31601158, 81701388,81422017,81601233,81471414,81870228,81822018, 81801399,31801010,81801370 and 81861168034)Program of Beijing Mun icipal Science and Technology Commission (Z151100003915072)Key Research Program of the Chinese Academy of Sciences (KJZDEWTZ-L05)Beijing Municipal Commission of Health and Family Planning (PXM2018_026283_ 000002)Advanced Innovation Center for Human Brain Protection (117212) and the State Key Laboratory of Membrane Biology.
文摘RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.
