Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions...Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions （Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution）. Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms （SNPs） in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Prol2Ala in Yin-deficiency and PPARD rs2076167, APMI rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotypel3 （Hapl3） of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hapl4 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes ofPPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.展开更多
The association of polymorphisms in exon 1 of the WNK1 gene with essential hypertension in the minority groups of Hani and Yi of China was investigated in the case-control study.The sequence of 1257 bp containing the ...The association of polymorphisms in exon 1 of the WNK1 gene with essential hypertension in the minority groups of Hani and Yi of China was investigated in the case-control study.The sequence of 1257 bp containing the WNK1 gene exon 1 was determined in 1307 individuals（649 essential hypertension subjects and 658 controls）to identify SNPs in Hani and Yi minority groups.Four of eleven previously known SNPs （rs3168640,rs11885,rs11554421 and rs34880640）were identified.The SNP analysis indicated that SNPs rs11885 and rs11554421 were significantly associated with hypertension in both Hani and Yi populations,and rs34880640 was significantly associated with hypertension in Hani but not in Yi population,adjusted for covariates.Haplotype analysis indicated that the haplotype H1 significantly decreased the risk of hypertension in both populations.These results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population specificity.This finding supported the importance of population specificity in determining the genetic factors associated with diseases and thus disease treatment.展开更多
Mutations in mitochondrial 12S rRNA gene are one of the most important causes of aminoglycoside-induced and nonsyndromic hearing loss. Here we report the characterization of one Han Chinese pedigree with aminoglycosid...Mutations in mitochondrial 12S rRNA gene are one of the most important causes of aminoglycoside-induced and nonsyndromic hearing loss. Here we report the characterization of one Han Chinese pedigree with aminoglycoside-induced and nonsyndromic hearing loss. This Chinese family carrying the 12S rRNA A1555G mutation exhibited high penetrance and expressivity of heating impairment. In particular, penetrances of hearing loss in this family pedigree were 43.8% and 25%, respectively, when aminoglycoside-induced heating loss was included or excluded. Mutational analysis of entire mitochondrial genomes in this family showed the homoplasmic A1555G mutation and a set of variants belonging to haplogroup Y2. Of these, the A14693G variant occurred at the extremely conserved nucleotide （conventional position 54） of the TψC-loop of tRNA^Clu and was absent in 156 Chinese controls. Nucleotides at position 54 of tRNAs are often modified, thereby contributing to the structural formation and stabilization of functional tRNAs. Thus, the structural alteration of tRNA by the A14693G variant may lead to a failure in tRNA metabolism and impair mitochondrial protein synthesis, thereby worsening mitochondrial dysfunctions altered by the A1555G mutation. Therefore, the tRNA^Glu A14693G variant may have a potential modifier role in increasing the penetrance and expressivity of the deafness-associated A1555G mutation in this Chinese pedigree.展开更多
To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory ...To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory hearing loss patients were tested for 1555A→G mutation using a new compact testing kit, which allows clear distinction between wild type and 1555 A→G mutated mtDNAs. Results Nineteen subjects among the 546 patients (3.48%) were found to carry mtDNA A1555G mutation. The results were confirmed by sequencing in an ABI 3100 Avant sequencer. Conclusions Maternal inherited deafness families are a frequently seen in outpatient group. The detection of mtDNA 1555 A→G mutation with a low cost, ready to use detection kit is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.展开更多
For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bron...For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus （AIBV） antigenic domain of a vaccine serotype （DE072） and a virulent viral strain （GA98） to better understand adaptive evolution of AIBV. In addition, the SARS Coronavirus （SARS-CoV） was also analyzed in the same way. It is interesting to find that extreme comparability exists between AIBV and SARS in amino acid substitution pattern. It suggests that amino acid changes that result in overall shift of residue charge and polarity should be paid special attention to during the development of vaccines.展开更多
Enzyme cascade reactions play significant roles in bioelectrochemical processes because they permit more complex reactions. Co-immobilization of multienzyme on the electrode could help to facilitate substrate/intermed...Enzyme cascade reactions play significant roles in bioelectrochemical processes because they permit more complex reactions. Co-immobilization of multienzyme on the electrode could help to facilitate substrate/intermediate transfer among different enzymes and electron transfer from enzyme active sites to the electrode with high stability and retrievability. Different co-immobilization strategies to construct multienzyme bioelectrodes have been widely reported, however, up to now, they have barely been reviewed. In this review, we focus on recent state-of-the-art techniques for constructing co-immobilized multienzyme electrodes including random and positional co-immobilization. Particular attention is given to strategies such as multienzyme complex and surface display. Cofactor co-immobilization on the electrode is also crucial for the enhancement of catalytic reaction and electron transfer, yet, few studies have been reported. The up-to-date advances in bioelectrochemical applications of multienzyme bioelectrodes are also presented. Finally, key challenges and future perspectives are discussed.展开更多
AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chrom...AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.展开更多
Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and stat...Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and statistical analyses of blood pressure （BP） across various pedigrees, it has been estimated that 30%--50% of the variability in blood pressure among the general population is genetically determined （Garcia et al., 2003）. Although the genetic mechanisms of essential hyper- tension have not been studied well, investigations for the genes that constitute the renin-angiotensin system （RAS） appear to be particularly promising, since this system plays a central role in the regulation of blood pressure （Ferrario, 2010）.展开更多
The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIP...The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.展开更多
Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalas- semia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA2 and normal HbF ...Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalas- semia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA2 and normal HbF level. On the other hand carriers of severe alpha-thalassemia also have similar CBC parameters to that of β-thalassemia with normal HbA2 level. Co-presence of mutations in the β-globin and delta-globin genes (point mutations or deletions) usually give normal HbA2 and elevated HbF level. We report a β-thal carrier with normal level of HbA2 and increased level of HbF who had a point mutation in CD39 on the beta-globin gene and a point mutation in CD27 on the δ-globin gene named Hb-Yialousa. Materials & Methods: An individual with low hematological indices, normal HbA2 and elevated HbF was referred to our center as routine premarital screening program. Mutations in the β-globin and δ-globin genes were screened using ARMS and sequencing methods. Results: The mutation in β- and δ-globin genes were identified as CD39 and CD27 (HbYialousa) respectively. No point mutation or deletion in α-globin gene was identified. Discussion: We showed that normal HBA2 with elevated HbF level is due to co-inheritance of delta-globin gene mutation with mutation in the β-globin gene. When screening for β-thalassemia, one has to either rule out presence of α-globin gene mutation of mutation in the delta-globin gene.展开更多
文摘对浙江瑞安、福建宁德、福建东张水库3个地理群体共31例香鱼(Plecoglossus altivelis)的线粒体细胞色素b(Cyt b)基因和线粒体D-loop区序列进行了PCR扩增、序列测定、核苷酸组成和多态性分析。Cytb基因中,A、T、C和G4种核苷酸的比例分别为19.72%、29.71%、32.25%和18.32%,A+T含量为49.43%,G+C含量为50.57%。D-loop区序列中,A、T、C和G4种核苷酸的比例分别为29.99%、29.29%、23.80%和16.92%,A+T含量为59.28%,G+C含量为40.72%。在长度为1141bp的Cytb基因序列中,仅存在1个变异位点,核苷酸多样性指数(π值)为0.00028,31个样本中仅出现两种单倍型;857 bp 长的D-loop区序列中,仅存在5个变异位点,核苷酸多样性指数(π值)为0.00199,仅出现5种单倍型。这表明闽浙地区香鱼的遗传多样性水平很低,应当加大对香鱼的保护力度。
基金supported by the National Basic Research Program of China (973 Program) (No. 2005CB523501)
文摘Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions （Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution）. Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms （SNPs） in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Prol2Ala in Yin-deficiency and PPARD rs2076167, APMI rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotypel3 （Hapl3） of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hapl4 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes ofPPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.
基金financially supported by the National Nature Science Foundation of China (Nos. U0932603 and 3091112048)the Natural Science Foundation of Yunnan Province (No. 2009CC001).
文摘The association of polymorphisms in exon 1 of the WNK1 gene with essential hypertension in the minority groups of Hani and Yi of China was investigated in the case-control study.The sequence of 1257 bp containing the WNK1 gene exon 1 was determined in 1307 individuals（649 essential hypertension subjects and 658 controls）to identify SNPs in Hani and Yi minority groups.Four of eleven previously known SNPs （rs3168640,rs11885,rs11554421 and rs34880640）were identified.The SNP analysis indicated that SNPs rs11885 and rs11554421 were significantly associated with hypertension in both Hani and Yi populations,and rs34880640 was significantly associated with hypertension in Hani but not in Yi population,adjusted for covariates.Haplotype analysis indicated that the haplotype H1 significantly decreased the risk of hypertension in both populations.These results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population specificity.This finding supported the importance of population specificity in determining the genetic factors associated with diseases and thus disease treatment.
基金supported by the Public Health Service grants (No. RO1DC05230 and RO1DC07696) from the National Institute on Deafness and Other Communication Disordersgrants from the National Basic Research Priorities Program of China (No. 2004CCA02200)the Ministry of Science and Technology of Zhejiang Province (No. 2007G50G2090026)
文摘Mutations in mitochondrial 12S rRNA gene are one of the most important causes of aminoglycoside-induced and nonsyndromic hearing loss. Here we report the characterization of one Han Chinese pedigree with aminoglycoside-induced and nonsyndromic hearing loss. This Chinese family carrying the 12S rRNA A1555G mutation exhibited high penetrance and expressivity of heating impairment. In particular, penetrances of hearing loss in this family pedigree were 43.8% and 25%, respectively, when aminoglycoside-induced heating loss was included or excluded. Mutational analysis of entire mitochondrial genomes in this family showed the homoplasmic A1555G mutation and a set of variants belonging to haplogroup Y2. Of these, the A14693G variant occurred at the extremely conserved nucleotide （conventional position 54） of the TψC-loop of tRNA^Clu and was absent in 156 Chinese controls. Nucleotides at position 54 of tRNAs are often modified, thereby contributing to the structural formation and stabilization of functional tRNAs. Thus, the structural alteration of tRNA by the A14693G variant may lead to a failure in tRNA metabolism and impair mitochondrial protein synthesis, thereby worsening mitochondrial dysfunctions altered by the A1555G mutation. Therefore, the tRNA^Glu A14693G variant may have a potential modifier role in increasing the penetrance and expressivity of the deafness-associated A1555G mutation in this Chinese pedigree.
文摘To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory hearing loss patients were tested for 1555A→G mutation using a new compact testing kit, which allows clear distinction between wild type and 1555 A→G mutated mtDNAs. Results Nineteen subjects among the 546 patients (3.48%) were found to carry mtDNA A1555G mutation. The results were confirmed by sequencing in an ABI 3100 Avant sequencer. Conclusions Maternal inherited deafness families are a frequently seen in outpatient group. The detection of mtDNA 1555 A→G mutation with a low cost, ready to use detection kit is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.
文摘For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus （AIBV） antigenic domain of a vaccine serotype （DE072） and a virulent viral strain （GA98） to better understand adaptive evolution of AIBV. In addition, the SARS Coronavirus （SARS-CoV） was also analyzed in the same way. It is interesting to find that extreme comparability exists between AIBV and SARS in amino acid substitution pattern. It suggests that amino acid changes that result in overall shift of residue charge and polarity should be paid special attention to during the development of vaccines.
基金supported by the National Natural Science Foundation of China(21878324,21706273)the CAS Pioneer Hundred Talent Program(Type C,reference#2016-081)。
文摘Enzyme cascade reactions play significant roles in bioelectrochemical processes because they permit more complex reactions. Co-immobilization of multienzyme on the electrode could help to facilitate substrate/intermediate transfer among different enzymes and electron transfer from enzyme active sites to the electrode with high stability and retrievability. Different co-immobilization strategies to construct multienzyme bioelectrodes have been widely reported, however, up to now, they have barely been reviewed. In this review, we focus on recent state-of-the-art techniques for constructing co-immobilized multienzyme electrodes including random and positional co-immobilization. Particular attention is given to strategies such as multienzyme complex and surface display. Cofactor co-immobilization on the electrode is also crucial for the enhancement of catalytic reaction and electron transfer, yet, few studies have been reported. The up-to-date advances in bioelectrochemical applications of multienzyme bioelectrodes are also presented. Finally, key challenges and future perspectives are discussed.
基金Risbin-Iptekdok 2007/2008,Ministry of Health Republic of IndonesiaExcellent Scholarship(Beasiswa Unggulan Program),Foreign Scholarship(Beasiswa Luar Negeri),Directorate of Higher Education(DGHE)+1 种基金Ministry of National Education Republic of Indonesiathe PhD-fellowship Program of the Radboud University(RU-fellowship)
文摘AIM: To investigate the prevalence of fragile X syndrome(FXS) in intellectually disabled male and female Indonesians.METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability(ID). In this previous study,87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples(162 females and 283 males).RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527(1.7%). The prevalence in males and females is 1.5%(5/329) and 2%(4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited.CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.
基金supported by the grants from the National Nature Science Foundation of China(No.U0932603)the Natural Science Foundation of Yunnan Province(No.2009CC001)the Science and Technology Project of Yunnan Provincial Science and Technology Department(No.2011FZ005)
文摘Essential hypertension is one of the most common multi- factorial diseases, affecting 20%--30% of the human popula- tion （Ibrahim and Damasceno, 2012）. Based on the results of twin studies, adoption studies and statistical analyses of blood pressure （BP） across various pedigrees, it has been estimated that 30%--50% of the variability in blood pressure among the general population is genetically determined （Garcia et al., 2003）. Although the genetic mechanisms of essential hyper- tension have not been studied well, investigations for the genes that constitute the renin-angiotensin system （RAS） appear to be particularly promising, since this system plays a central role in the regulation of blood pressure （Ferrario, 2010）.
基金supported by the National Key Research and Development Program of China 2016YFC1000307The sub-project of National Key Research and Development Program of China 2016YFC1000307-10the Program of National Research Institute for Family Planning(2017GJM04,2018CNV).
文摘The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.
文摘Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalas- semia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA2 and normal HbF level. On the other hand carriers of severe alpha-thalassemia also have similar CBC parameters to that of β-thalassemia with normal HbA2 level. Co-presence of mutations in the β-globin and delta-globin genes (point mutations or deletions) usually give normal HbA2 and elevated HbF level. We report a β-thal carrier with normal level of HbA2 and increased level of HbF who had a point mutation in CD39 on the beta-globin gene and a point mutation in CD27 on the δ-globin gene named Hb-Yialousa. Materials & Methods: An individual with low hematological indices, normal HbA2 and elevated HbF was referred to our center as routine premarital screening program. Mutations in the β-globin and δ-globin genes were screened using ARMS and sequencing methods. Results: The mutation in β- and δ-globin genes were identified as CD39 and CD27 (HbYialousa) respectively. No point mutation or deletion in α-globin gene was identified. Discussion: We showed that normal HBA2 with elevated HbF level is due to co-inheritance of delta-globin gene mutation with mutation in the β-globin gene. When screening for β-thalassemia, one has to either rule out presence of α-globin gene mutation of mutation in the delta-globin gene.
