An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the ...An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the two key histidine residues were replaced, WRN1 may not be active as RNase. Southern blotting analysis showed that WRN1 exists as one of a small gene family in common wheat genome.展开更多
Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simpl...Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability. Methods:Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing. Results:We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC)of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay. Conclusions:In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.展开更多
The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
目的探讨中国汉族人群中DNA修复基因的拷贝数多态性(copy number variations,CNV)与年龄相关性白内障(age-related cataract,ARC)易感性的关系。方法研究对象来自"江苏眼病研究"流行病学人群,包括ARC组780例和对照组525人。...目的探讨中国汉族人群中DNA修复基因的拷贝数多态性(copy number variations,CNV)与年龄相关性白内障(age-related cataract,ARC)易感性的关系。方法研究对象来自"江苏眼病研究"流行病学人群,包括ARC组780例和对照组525人。采集受试者外周静脉血,提取全血基因组DNA。通过实时荧光定量PCR方法检测四种DNA修复基因的拷贝数(copy number,CN),分析ARC组和对照组基因CN的差异以及相对危险度(odds ratio,OR)。结果在WRN基因中发现了新的CNV。WRN基因高拷贝(CN=3+)与ARC的易感性有关(OR=1.88,P=0.02);HSF4基因低拷贝(CN=1)的人群对ARC易感(OR=4.09,P=0.004)。WRN基因高拷贝与核性以及后囊下性ARC的易感性有关(OR=2.06、3.72,均为P=0.02)。HSF4基因低拷贝与核性以及后囊下性ARC的易感性有关(OR=5.73,P=0.001;OR=6.80,P=0.01)。WRN和HSF4基因的联合作用显著增加了ARC的易感性。经过多重校正以后,仅有HSF4的CNV与ARC的易感性有关,尤其与核性和后囊下性ARC的易感性有关。结论 HSF4基因与WRN基因的CNV可能与中国汉族人群ARC的易感性有关。DNA修复基因对ARC易感性有一定的作用,并且对不同亚型ARC产生不同的影响。展开更多
文摘An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the two key histidine residues were replaced, WRN1 may not be active as RNase. Southern blotting analysis showed that WRN1 exists as one of a small gene family in common wheat genome.
文摘Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability. Methods:Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing. Results:We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC)of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay. Conclusions:In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
