Shiyi Zhou - Academia.edu (original) (raw)

Papers by Shiyi Zhou

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 21, 2016

The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an import... more The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). The strongest SNP, rs2070600C>T (P = 1.21 × 10(-52)), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10(-10)). Both SNPs were...

Human Mutation, 2010

To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in ... more To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co-segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation. ©2010 Wiley-Liss, Inc.

Molecular vision, Jan 21, 2010

To identify the genetic defects in a three-generation Chinese family with congenital nuclear cata... more To identify the genetic defects in a three-generation Chinese family with congenital nuclear cataract. Four patients and three healthy members from the family underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from peripheral blood leukocytes of the family members as well as from 100 healthy normal controls. Polymerase chain reaction (PCR) amplification and direct sequencing of all coding exons of candidate genes were performed. The functional consequences of the mutation were analyzed with biology softwares. A novel mutation (c.130G>A) was identified in the connexin 46 gene (GJA3), which resulted in the substitution of valine by methionine at the highly conserved codon 44 of connexin 46. This mutation co-segregated among the affected members of the family and was not observed in either unaffected members or the 100 normal controls. This is a novel missense mutation identified in the first extracellular loop of connexin 46; this expands the mutatio...

Background: Microbiome residing in the respiratory tract has emerged as an important player in th... more Background: Microbiome residing in the respiratory tract has emerged as an important player in the etiology and progression of COPD, but results are conflicting regarding the features of respiratory tract microbiome in COPD and at exacerbations and it is unknown whether these features differ by ethnicity and geography. Method: To address these questions, we enrolled healthy individuals and patients with COPD, including healthy-COPD pairs from same households, from four geographical regions of Yunan province, representative of different ethnicities and/or environmental exposures. Sputum and oropharyngeal swabs were collected from these healthy individuals and from COPD patients at stable state (COPD) or exacerbations (AECOPD) and subjected to 16S microbiome profiling. Results: Both COPD disease status and region had an impact on alpha-diversity of sputum and oropharyngeal microbiomes, with AECOPD having the lowest microbiome diversity. Shifts in the relative abundance (≥ 1.5 fold, ad...

Molecular vision, Jan 16, 2009

To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in ... more To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. Family history and clinical data were recorded. The genomic DNA was extracted from peripheral blood leukocytes. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point logarithm of odds (LOD) scores were calculated by using the Linkage software after genotyping. Mutations were detected by DNA sequence analysis of the candidate genes. Effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis. Evidence of a linkage was obtained at markers D1S514 (LOD score [Z]=3.48, recombination fraction [theta]=0.0) and D1S1595 (Z=2.49, theta=0.0). Haplotype analysis indicated that the cataract gene was close to these two markers. Sequencing of the connexin 50 (GJA8) gene revealed a T>C transition at nucleotide position c.92. This nucleotide change resulted in the ...

International Journal of Cardiology, 2011

Congenital heart malformations are the most common birth defects in humans and occur in about 1% ... more Congenital heart malformations are the most common birth defects in humans and occur in about 1% of infants [1]. Nevertheless, the genetic alterations underlying these disorders have only partially been unraveled. Some scientists have had shown that in mice loss of the hairy-related transcription factor 2 (HEY2), which functions as a repressor through the bHLH domain, results in a high incidence of fatal ventricular and atrial septal defects, combined with tricuspid stenosis or atresia in some cases [2]. The HEY2 gene spans about 12 kb on human chromosome 6q22, comprises 5 exons, and encodes a 337 amino acid protein. The basic helix-loop-helix transcriptional repressor HEY2 is expressed in ventricular, but not atrial, cardiomyocytes, and in endothelial and vascular smooth cell. HEY2 is an important determinant of mammalian heart development and functions as a repressor through the bHLH domain which DNA binding and protein dimerization were relied on [3,4] and one of the few known mediators of Notch signaling [5]. HEY2 is characterized by three conserved domains: a bHLH domain, an orange domain and a four-amino-acid motif, YRPW. HEY2 may underlie a broader spectrum of diseases in humans than previously anticipated,

Reproductive Toxicology, 2014

Two-cell arrest plays a principal role in the elevated levels of embryo loss during the first wee... more Two-cell arrest plays a principal role in the elevated levels of embryo loss during the first week of development in mouse. Previously, we have shown that arsenic can apparently induce 2-cell arrest in mouse preimplantation embryo and the expression of oxidative stress adaptor protein p66(Shc) is up-regulated in this process. In the present study, we demonstrated that microinjection of p66(Shc) siRNA into the pronucleus of zygotes resulted in a markedly decrease in both mRNA and protein levels of p66(Shc). The arsenite-induced 2-cell arrests, along with a reduction in the levels of reactive oxygen species (ROS), were significantly inhibited and the number of embryos developing to morula stage concurrently increased upon p66(shc) siRNA microinjection. These findings indicate that knockdown of p66(shc) improves the developmental competence of arsenite-exposed embryos in vitro by increasing the resistance to oxidative stress. In addition, we highlight the utility of single-embryo analysis in preimplantation embryos.

Epilepsy Research, 2011

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is partly caused by mutations in the ... more Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is partly caused by mutations in the nicotinic acetylcholine receptor (nAChR) genes CHRNA4, CHRNB2, and CHRNA2. Cases of non-familial nocturnal frontal lobe epilepsy (NFLE) are more common than the familial type and the phenotypes of the two are similar. CHRNA4 mutations have been found in sporadic NFLE, but no mutation in CHRNB2 or CHRNA2 have been reported. To analyze the genetic features of sporadic NFLE, we designed mutation screening of exon 5 of CHRNA4, exon 5 of CHRNB2, and exon 6 of CHRNA2, mutations in which are associated with ADFLE. We screened a group of 105 Chinese sporadic NFLE cases and identified a novel CHRNB2 mutation, V337G, in an evolutionary conserved region of the intracellular loop between transmembrane domains M3 and M4 in one patient. This mutation was not observed in the control group of 200 subjects. Bioinformatics analysis indicated that the mutation altered the hydrophobicity and secondary structure of the protein. To the best of our knowledge, this study established for the first time that CHRNB2 is potentially associated with non-familial NFLE patient. No mutations in CHRNA4 or CHRNA2 were revealed by our screening method.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 21, 2016

The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an import... more The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). The strongest SNP, rs2070600C>T (P = 1.21 × 10(-52)), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10(-10)). Both SNPs were...

Human Mutation, 2010

To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in ... more To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co-segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation. ©2010 Wiley-Liss, Inc.

Molecular vision, Jan 21, 2010

To identify the genetic defects in a three-generation Chinese family with congenital nuclear cata... more To identify the genetic defects in a three-generation Chinese family with congenital nuclear cataract. Four patients and three healthy members from the family underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from peripheral blood leukocytes of the family members as well as from 100 healthy normal controls. Polymerase chain reaction (PCR) amplification and direct sequencing of all coding exons of candidate genes were performed. The functional consequences of the mutation were analyzed with biology softwares. A novel mutation (c.130G>A) was identified in the connexin 46 gene (GJA3), which resulted in the substitution of valine by methionine at the highly conserved codon 44 of connexin 46. This mutation co-segregated among the affected members of the family and was not observed in either unaffected members or the 100 normal controls. This is a novel missense mutation identified in the first extracellular loop of connexin 46; this expands the mutatio...

Background: Microbiome residing in the respiratory tract has emerged as an important player in th... more Background: Microbiome residing in the respiratory tract has emerged as an important player in the etiology and progression of COPD, but results are conflicting regarding the features of respiratory tract microbiome in COPD and at exacerbations and it is unknown whether these features differ by ethnicity and geography. Method: To address these questions, we enrolled healthy individuals and patients with COPD, including healthy-COPD pairs from same households, from four geographical regions of Yunan province, representative of different ethnicities and/or environmental exposures. Sputum and oropharyngeal swabs were collected from these healthy individuals and from COPD patients at stable state (COPD) or exacerbations (AECOPD) and subjected to 16S microbiome profiling. Results: Both COPD disease status and region had an impact on alpha-diversity of sputum and oropharyngeal microbiomes, with AECOPD having the lowest microbiome diversity. Shifts in the relative abundance (≥ 1.5 fold, ad...

Molecular vision, Jan 16, 2009

To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in ... more To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. Family history and clinical data were recorded. The genomic DNA was extracted from peripheral blood leukocytes. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point logarithm of odds (LOD) scores were calculated by using the Linkage software after genotyping. Mutations were detected by DNA sequence analysis of the candidate genes. Effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis. Evidence of a linkage was obtained at markers D1S514 (LOD score [Z]=3.48, recombination fraction [theta]=0.0) and D1S1595 (Z=2.49, theta=0.0). Haplotype analysis indicated that the cataract gene was close to these two markers. Sequencing of the connexin 50 (GJA8) gene revealed a T>C transition at nucleotide position c.92. This nucleotide change resulted in the ...

International Journal of Cardiology, 2011

Congenital heart malformations are the most common birth defects in humans and occur in about 1% ... more Congenital heart malformations are the most common birth defects in humans and occur in about 1% of infants [1]. Nevertheless, the genetic alterations underlying these disorders have only partially been unraveled. Some scientists have had shown that in mice loss of the hairy-related transcription factor 2 (HEY2), which functions as a repressor through the bHLH domain, results in a high incidence of fatal ventricular and atrial septal defects, combined with tricuspid stenosis or atresia in some cases [2]. The HEY2 gene spans about 12 kb on human chromosome 6q22, comprises 5 exons, and encodes a 337 amino acid protein. The basic helix-loop-helix transcriptional repressor HEY2 is expressed in ventricular, but not atrial, cardiomyocytes, and in endothelial and vascular smooth cell. HEY2 is an important determinant of mammalian heart development and functions as a repressor through the bHLH domain which DNA binding and protein dimerization were relied on [3,4] and one of the few known mediators of Notch signaling [5]. HEY2 is characterized by three conserved domains: a bHLH domain, an orange domain and a four-amino-acid motif, YRPW. HEY2 may underlie a broader spectrum of diseases in humans than previously anticipated,

Reproductive Toxicology, 2014

Two-cell arrest plays a principal role in the elevated levels of embryo loss during the first wee... more Two-cell arrest plays a principal role in the elevated levels of embryo loss during the first week of development in mouse. Previously, we have shown that arsenic can apparently induce 2-cell arrest in mouse preimplantation embryo and the expression of oxidative stress adaptor protein p66(Shc) is up-regulated in this process. In the present study, we demonstrated that microinjection of p66(Shc) siRNA into the pronucleus of zygotes resulted in a markedly decrease in both mRNA and protein levels of p66(Shc). The arsenite-induced 2-cell arrests, along with a reduction in the levels of reactive oxygen species (ROS), were significantly inhibited and the number of embryos developing to morula stage concurrently increased upon p66(shc) siRNA microinjection. These findings indicate that knockdown of p66(shc) improves the developmental competence of arsenite-exposed embryos in vitro by increasing the resistance to oxidative stress. In addition, we highlight the utility of single-embryo analysis in preimplantation embryos.

Epilepsy Research, 2011

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is partly caused by mutations in the ... more Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is partly caused by mutations in the nicotinic acetylcholine receptor (nAChR) genes CHRNA4, CHRNB2, and CHRNA2. Cases of non-familial nocturnal frontal lobe epilepsy (NFLE) are more common than the familial type and the phenotypes of the two are similar. CHRNA4 mutations have been found in sporadic NFLE, but no mutation in CHRNB2 or CHRNA2 have been reported. To analyze the genetic features of sporadic NFLE, we designed mutation screening of exon 5 of CHRNA4, exon 5 of CHRNB2, and exon 6 of CHRNA2, mutations in which are associated with ADFLE. We screened a group of 105 Chinese sporadic NFLE cases and identified a novel CHRNB2 mutation, V337G, in an evolutionary conserved region of the intracellular loop between transmembrane domains M3 and M4 in one patient. This mutation was not observed in the control group of 200 subjects. Bioinformatics analysis indicated that the mutation altered the hydrophobicity and secondary structure of the protein. To the best of our knowledge, this study established for the first time that CHRNB2 is potentially associated with non-familial NFLE patient. No mutations in CHRNA4 or CHRNA2 were revealed by our screening method.