The advent of DNA microarray technology has offered the promise of casting new insights onto deciphering secrets of life by monitoring activities of thousands of genes simulta-neously. Current analyses of microarray d...The advent of DNA microarray technology has offered the promise of casting new insights onto deciphering secrets of life by monitoring activities of thousands of genes simulta-neously. Current analyses of microarray data focus on precise classification of biological types, for example, tumor versus normal tissues. A further scientific challenging task is to extract dis-ease-relevant genes from the bewildering amounts of raw data, which is one of the most critical themes in the post-genomic era, but it is generally ignored due to lack of an efficient approach. In this paper, we present a novel ensemble method for gene extraction that can be tailored to fulfill multiple biological tasks including (i) precise classification of biological types; (ii) disease gene mining; and (iii) target-driven gene networking. We also give a numerical application for (i) and (ii) using a public microarrary data set and set aside a separate paper to address (iii).展开更多
Brugada syndrome(BrS)is a life-threatening cardiac rhythm disorder characterized by persistent STsegment elevation in leads V1–V3 and right bundle branch block on electrocardiograms(ECG),and by syncope and sudden dea...Brugada syndrome(BrS)is a life-threatening cardiac rhythm disorder characterized by persistent STsegment elevation in leads V1–V3 and right bundle branch block on electrocardiograms(ECG),and by syncope and sudden death from ventricular tachycardia(VT)and ventricular fibrillation(VF).BrS is responsible for nearly 4%of sudden cardiac deaths and considered to be the most common cause of natural death in males younger than 50 years in some Asian countries.Since the first diseasecausing gene for BrS(the cardiac sodium channel gene SCN5A)was identified in 1998,extensive investigations on both clinical and basic aspects of BrS have occurred rapidly.SCN5A mutations remain the most common cause of BrS;nearly 300 SCN5A mutations have been identified and are responsible for 20%–30%of BrS cases.Commercial genetic testing is available for SCN5A.Recently,seven other disease-causing genes for BrS have been identified and include GPD1L(BrS2),CACNA1C(Cav1.2,BrS3),CACNB2(Cavβ2,BrS4),SCN1B(Navβ1,BrS5),KCNE3(MiRP2,BrS6),SCN3B(Navβ3,BrS7),and HCN4(BrS8).This article will briefly review the progress made over the past decade in our understanding of the clinical,genetic and molecular aspects of BrS.展开更多
目的在27例儿茶酚胺介导的多形性室速患者及家庭成员中寻找CASQ2基因突变。方法应用直接DNA序列分析对临床诊断为家族性多形性室速27例患者及家庭成员进行进行基因突变分析。应用Taqman基因分型检测在以1400名正常人群中确定CASQ2变异...目的在27例儿茶酚胺介导的多形性室速患者及家庭成员中寻找CASQ2基因突变。方法应用直接DNA序列分析对临床诊断为家族性多形性室速27例患者及家庭成员进行进行基因突变分析。应用Taqman基因分型检测在以1400名正常人群中确定CASQ2变异的频率。结果在一个多形性室速家系中发现了1个新的杂合子改变F189L。通过与多种生物比对，证实该改变发生于在第2结构域一个高度保守的氨基酸上，位于第5外显子的F189L的改变，使编码蛋白的第189位氨基酸由苯丙氨酸改变为亮氨酸。应用Taqman SNP genotyping assay分析方法证实正常人群1400名中未发现同样改变。在CASQ2基因中未发现其他引起疾病的基因突变。结论发现了CASQ2基因的1个新F189L突变。展开更多
Objective To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.Methods Thirty-one Chinese LQTS pedigrees were characterized for mutations in ...Objective To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.Methods Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing.Results Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 +18C >T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients.Conclusions The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.展开更多
基金This work was supported in part by the National Natural Science Foundation of China(Grant Nos.30170515 and 30370798)the Chinese 863 Program(Grant No.2003AA2Z2051 and 2002AA2Z2052)+2 种基金the 211 Projectthe Tenth'Five-year'PlanHarbin Medical University.
文摘The advent of DNA microarray technology has offered the promise of casting new insights onto deciphering secrets of life by monitoring activities of thousands of genes simulta-neously. Current analyses of microarray data focus on precise classification of biological types, for example, tumor versus normal tissues. A further scientific challenging task is to extract dis-ease-relevant genes from the bewildering amounts of raw data, which is one of the most critical themes in the post-genomic era, but it is generally ignored due to lack of an efficient approach. In this paper, we present a novel ensemble method for gene extraction that can be tailored to fulfill multiple biological tasks including (i) precise classification of biological types; (ii) disease gene mining; and (iii) target-driven gene networking. We also give a numerical application for (i) and (ii) using a public microarrary data set and set aside a separate paper to address (iii).
基金This work was supported by the China National Basic Research Program(973 program)(No.2007CB512002)a grant from the National Natural Science Foundation of China(Grant No.30700455)a Wuhan City Academic Leadership award,and the Hubei Natural Science Key Program.
文摘Brugada syndrome(BrS)is a life-threatening cardiac rhythm disorder characterized by persistent STsegment elevation in leads V1–V3 and right bundle branch block on electrocardiograms(ECG),and by syncope and sudden death from ventricular tachycardia(VT)and ventricular fibrillation(VF).BrS is responsible for nearly 4%of sudden cardiac deaths and considered to be the most common cause of natural death in males younger than 50 years in some Asian countries.Since the first diseasecausing gene for BrS(the cardiac sodium channel gene SCN5A)was identified in 1998,extensive investigations on both clinical and basic aspects of BrS have occurred rapidly.SCN5A mutations remain the most common cause of BrS;nearly 300 SCN5A mutations have been identified and are responsible for 20%–30%of BrS cases.Commercial genetic testing is available for SCN5A.Recently,seven other disease-causing genes for BrS have been identified and include GPD1L(BrS2),CACNA1C(Cav1.2,BrS3),CACNB2(Cavβ2,BrS4),SCN1B(Navβ1,BrS5),KCNE3(MiRP2,BrS6),SCN3B(Navβ3,BrS7),and HCN4(BrS8).This article will briefly review the progress made over the past decade in our understanding of the clinical,genetic and molecular aspects of BrS.
文摘目的在27例儿茶酚胺介导的多形性室速患者及家庭成员中寻找CASQ2基因突变。方法应用直接DNA序列分析对临床诊断为家族性多形性室速27例患者及家庭成员进行进行基因突变分析。应用Taqman基因分型检测在以1400名正常人群中确定CASQ2变异的频率。结果在一个多形性室速家系中发现了1个新的杂合子改变F189L。通过与多种生物比对，证实该改变发生于在第2结构域一个高度保守的氨基酸上，位于第5外显子的F189L的改变，使编码蛋白的第189位氨基酸由苯丙氨酸改变为亮氨酸。应用Taqman SNP genotyping assay分析方法证实正常人群1400名中未发现同样改变。在CASQ2基因中未发现其他引起疾病的基因突变。结论发现了CASQ2基因的1个新F189L突变。
基金This study was supported by grants from the National Natural Science Foundation of China (No.30170381) the American Heart Association Ohio-Affiliate (No. AHA 0051205B).
文摘Objective To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.Methods Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing.Results Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 +18C >T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients.Conclusions The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.
