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ABSTRACT: Depression is a mental disorder characterized by emotional and cognitive dysfunction, which is related to the abnormal activity in brain regions involving emotion processing such as amygdala (AMYG). The laterality of AMYG during emotional information processing has always been a controversial issue in any depression study, however, the dynamic characteristic of laterality in the AMYG has been ignored. In this paper, we proposed to explore the time-varying functional coupling between the anterior cingulate cortex (ACC) and the bilateral AMYG in the time-frequency domain. As a result, an emotional facial expression paradigm was undertaken in this study. Using magnetoencephalogram (MEG) data acquired from 16 patients with major depression disorder and 16 matched healthy controls, we calculated the wavelet coherence. The research led to the conclusion that, after sad facial stimuli, the ACC-bilateral AMYG connectivity in depressive patients showed a significant decrease in the beta band during the first 100ms. In addition, the ACC-left AMYG connectivity led to a significant increase in the gamma band around 400ms and in beta band around 700ms. Our work suggests a lack of sufficient inhibition of the ACC on the bilateral AMYG in the early period and the lateralized dysregulation of the ACC on the left AMYG in late period during the sad facial information processing task. We hypothesised that the clinical manifestations of depression may partly result from it.
Neuroscience Letters 05/2013; · 2.11 Impact Factor
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ABSTRACT: Magnetoencephalography (MEG) power topography may be useful for obtaining discriminative brain activity patterns that can distinguish depressed patients from healthy control subjects at the individual level. However, the application is still limited due to the lack of adequate analysis strategies to remove artifacts from the MEG signals. In this study, the Multichannel Matching Pursuit (MMP) method was designed; in this technique, a linear decomposition method that provides components by iteratively reanalysing a residual signal after removing previously found components,. Forty-four subjects, half depressed patients and half healthy subjects, were recruited for MEG scanning while watching a video of sad faces. MMP was implemented to manage multichannel, multi-trial MEG signals. The representative post-MMP analysis signals were utilised to calculate the power topography over the whole brain and designed as inputs for a Support Vector Machine (SVM) classifier. A statistically significant discriminative accuracy of 86% (p= 0.002) after a permutation test was achieved. Comparing the system classification performance to that of the ensemble averaging method and the established Independent Component Analysis (ICA), we demonstrated the ability of MMP to represent critical MEG information and, in turn, to mark the abnormality of oscillatory activities under negative stimuli using images of sad faces.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 04/2013; · 3.05 Impact Factor
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Journal of Magnetic Resonance Imaging 12/2012; · 2.70 Impact Factor
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ABSTRACT: Depression is proved to be associated with the dysfunction of prefrontal-limbic neural circuit, especially during emotion processing procedure. Related explorations have been undertaken from the aspects of abnormal activation and functional connectivity. However, the mechanism of the dysfunction of coordinated interactions remains unknown and is still a matter of debate. The present study gave direct evidence of this issue from the aspect of effective connectivity via dynamic causal modeling (DCM). 20 major depressive disorder (MDD) patients and 20 healthy controls were recruited to attend facial emotional stimulus during MEG recording. Bayesian model selection (BMS) was applied to choose the best model. Results under the optimal model showed that top-down endogenous effective connectivity from the dorsolateral prefrontal cortex (DLPFC) to the amygdala was greatly impaired in patients relative to health controls; while bottom-up endogenous effective connectivity from the amygdala to the anterior cingulate cortex (ACC) as well as modulatory effective connectivity from ACC to DLPFC was significantly increased. We inferred the incapable DLPFC failed to exert influence on amygdala, and finally lead to enhanced amygdala-ACC and ACC-DLPFC bottom-up effects. Such impaired prefrontal-amygdala connectivity was supposed to be responsible for the dysfunction in MDD when dealing with emotional stimuli.
Neuroscience Letters 06/2012; 523(2):125-30. · 2.11 Impact Factor
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ABSTRACT: This paper aimed to develop a method for depression detection using blood-oxygen-level-dependent (BOLD) response estimated from event-related signals and resting-state functional magnetic resonance imaging (fMRI) signals together.
Thirteen patients with unipolar depression and matched healthy subjects were recruited. Resting state data of each subject were collected. Thereafter, event-related paradigm was undertaken using sad facial stimuli. The resting-state fMRI signal was deemed as the baseline of each subject's activity. Coefficient marks were designed to sort and select temporal independent components of event-related signals. Thereafter, stimulus-evoked BOLD response components inside event-related signal were extracted and taken as features to discriminate depressive patients from healthy controls.
Accuracy rate for depression recognition was 77.27% with P value of .017 for whole-brain analysis and 81.82% with P value of .009 for region-of-interest analysis. The effectiveness and the superiority of the proposed method for disease recognition were demonstrated via the performance comparison with three other typical methods.
The proposed model was effective in depression recognition.
Magnetic Resonance Imaging 04/2012; 30(3):347-55. · 1.99 Impact Factor
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Guohong Deng,
Gangqiao Zhou,
Rong Zhang,
Yun Zhai,
Wenli Zhao,
Zehui Yan,
Chunqing Deng,
Xiaoyan Yuan,
Baoyan Xu,
Xiaojia Dong,
Xiumei Zhang,
Xuqing Zhang, Zhijian Yao,
Yan Shen,
Boqing Qiang,
Yuming Wang,
Fuchu He
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ABSTRACT: The importance of expression of interferon gamma-inducible protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV) infection has been recently emphasized. In this report, we investigated whether the naturally occurred sequence variations in the CXCL10 gene impact liver damage and disease progression of chronic HBV infection.
A hospital-based case-control study was conducted, and a total of 613 and 1787 unrelated Han Chinese HBV carriers were recruited from Beijing and Chongqing, respectively. We systematically screened sequence variations in the CXCL10 gene and examined the association between the variations in this gene and susceptibility to disease progression of chronic HBV infection in Chinese populations from Beijing and Chongqing. Functional analyses were conducted to verify the biological significances of the associated genetic variation.
We identified that the polymorphism G-201A, located in the promoter region of CXCL10, was associated with susceptibility to disease progression in male HBV carriers (dominant model; odds ratio, 1.53; P = .001). Functional analyses show that the G-201A polymorphism alters the binding affinity of nuclear protein and regulates CXCL10 expression. We observed higher CXCL10 transcription in interferon gamma-stimulated peripheral blood mononuclear cells with the disease-susceptible genotypes. Enzyme-linked immunosorbent assay and immunohistochemical analysis showed augmented CXCL10 production in serum and liver tissues of progressed HBV carriers.
The novel regulatory polymorphism G-201A [corrected] in the promoter of CXCL10 gene could be a part of the genetic variation underlying the susceptibility of individuals to disease progression of chronic HBV infection.
Gastroenterology 04/2008; 134(3):716-26. · 11.68 Impact Factor
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Kelly A Frazer,
Dennis G Ballinger,
David R Cox,
David A Hinds,
Laura L Stuve,
Richard A Gibbs,
John W Belmont,
Andrew Boudreau,
Paul Hardenbol,
Suzanne M Leal, [......],
Vivian Ota Wang,
Jane L Peterson,
Michael Shi,
Jack Spiegel,
Lawrence M Sung,
Lynn F Zacharia,
Francis S Collins,
Karen Kennedy,
Ruth Jamieson,
John Stewart
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ABSTRACT: We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.
Nature 11/2007; 449(7164):851-61. · 36.28 Impact Factor
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Pardis C Sabeti,
Patrick Varilly,
Ben Fry,
Jason Lohmueller,
Elizabeth Hostetter,
Chris Cotsapas,
Xiaohui Xie,
Elizabeth H Byrne,
Steven A McCarroll,
Rachelle Gaudet, [......],
Vivian Ota Wang,
Jane L Peterson,
Michael Shi,
Jack Spiegel,
Lawrence M Sung,
Lynn F Zacharia,
Francis S Collins,
Karen Kennedy,
Ruth Jamieson,
John Stewart
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ABSTRACT: With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.
Nature 11/2007; 449(7164):913-8. · 36.28 Impact Factor
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Pardis C. Sabeti,
Patrick Varilly,
Ben Fry,
Jason Lohmueller,
Elizabeth Hostetter,
Chris Cotsapas,
Xiaohui Xie,
Elizabeth H. Byrne,
Steven A. McCarroll,
Rachelle Gaudet, [......],
Vivian Ota Wang,
Jane L. Peterson,
Michael Shi,
Jack Spiegel,
Lawrence M. Sung,
Lynn F. Zacharia,
Francis S. Collins,
Karen Kennedy,
Ruth Jamieson,
John Stewart
[show abstract]
[hide abstract]
ABSTRACT: With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2)
Nature 10/2007; 449(7164):913-918. · 36.28 Impact Factor
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Yun Zhai,
Gangqiao Zhou,
Guohong Deng,
Weimin Xie,
Xiaojia Dong,
Xiumei Zhang,
Ling Yu,
Hao Yang,
Xiaoyan Yuan,
Hongxin Zhang,
Lianteng Zhi, Zhijian Yao,
Yan Shen,
Boqing Qiang,
Fuchu He
[show abstract]
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ABSTRACT: Overexpression of estrogen receptors (ESRs) is implicated in the development of hepatocellular carcinoma (HCC) in both animal models and humans. We examined whether the ESR1 polymorphisms were related to HCC risk among chronic hepatitis B virus carriers.
Six ESR1 polymorphisms, which are (TA)n repeat in the promoter, T29C at codon 10 in exon 1, PvuII and XbaI site in intron 1, C136474G at codon 325 in exon 4, and A252966G in intron 5, were genotyped in 248 patients with HCC and 239 controls. The associations with the susceptibility to HCC were estimated by logistic regression. Allele-specific transcription difference of ESR1 messenger RNA was performed by real-time quantitative polymerase chain reaction.
We observed a statistically significant increased susceptibility to HCC associated with the homozygous alleles with a high number of TA repeats (assigned as H/H genotype; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.44-4.94; P = .0018), T29C C/C genotype (OR, 2.31; 95% CI, 1.25-4.26; P = .0076), and PvuII C/C genotype (OR, 2.19; 95% CI, 1.27-3.78; P = .0048) compared with the homozygous alleles with a low number of TA repeats (assigned as L/L genotype), T29C T/T, and PvuII T/T genotype, respectively. In accordance, the relative messenger RNA levels of the at-risk C allele of T29C were consistently higher than those of the T allele in heterozygous cells.
Our findings suggest that the genetic polymorphism in ESR1 may play a role in mediating susceptibility to HCC in Chinese hepatitis B virus carriers.
Gastroenterology 07/2006; 130(7):2001-9. · 11.68 Impact Factor
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Donna M Muzny,
Steven E Scherer,
Rajinder Kaul,
Jing Wang,
Jun Yu,
Ralf Sudbrak,
Christian J Buhay,
Rui Chen,
Andrew Cree,
Yan Ding, [......],
Jianling Zhou,
Yang Zhou,
David Nelson,
Hans Lehrach,
Richard Reinhardt,
Susan L Naylor,
Huanming Yang,
Maynard Olson,
George Weinstock,
Richard A Gibbs
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ABSTRACT: After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
Nature 05/2006; 440(7088):1194-8. · 36.28 Impact Factor
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Donna M. Muzny,
Steven E. Scherer,
Rajinder Kaul,
Jing Wang,
Jun Yu,
Ralf Sudbrak,
Christian J. Buhay,
Rui Chen,
Andrew Cree,
Yan Ding, [......],
Yang Zhou,
further contributors,
David Nelson,
Hans Lehrach,
Richard Reinhardt,
Susan L. Naylor,
Huanming Yang,
Maynard Olson,
George Weinstock,
Richard A. Gibbs
[show abstract]
[hide abstract]
ABSTRACT: After the completion of a draft human genome sequence1, the International Human Genome Sequencing Consortium has proceeded to finish2 and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B3. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
Nature 04/2006; 440(7088):1194-1198. · 36.28 Impact Factor
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Huan Nie,
Fan Yang,
Xiaobing Zhang,
Jian Yang,
Lihong Chen,
Jing Wang,
Zhaohui Xiong,
Junping Peng,
Lilian Sun,
Jie Dong,
Ying Xue,
Xingye Xu,
Shuxia Chen, Zhijian Yao,
Yan Shen,
Qi Jin
[show abstract]
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ABSTRACT: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).
The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes.
Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.
BMC Genomics 02/2006; 7:173. · 4.07 Impact Factor
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Yongliang Yan,
Jian Yang,
Lihong Chen,
Fan Yang,
Jie Dong,
Ying Xue,
Xingye Xu,
Yafang Zhu, Zhijian Yao,
Min Lin,
Yiping Wang,
Qi Jin
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ABSTRACT: Four gene clusters associated with denitrification were identified in the genome of A1501 strain, nar, nir, nor and nos, including 40 genes totally, which encode proteins for substance transportation, gene regulation and reductases. The three gene clusters, nir, nor and nos are adjacent on chromosome and are far from nar gene cluster. Compared with other denitrifying bacteria, the 40 denitrification genes in A1501 strain compose a complete denitrification catalysis system. In A1501 strain, this system has the following characteristics: (i) only one copy of narK gene is found in nar gene cluster; (ii) a narM gene is present between narK and narG; (iii) two genes, dnarE and orfl are identified at downstream of narX and narL genes, of which dnrE perhaps is a transcriptional factor belonging to FNR family; (iv) there are 16 nir genes in A1501, the most in the known denitrifying bacteria; (v) it is for the first time that norR gene has been found in A1501 and also in Pseudomonas; (vi) nos gene cluster is relatively conservative, with a completely identical composition and arrangement of genome to the reference bacteria strain.
Science in China Series C Life Sciences 01/2006; 48(6):585-92. · 1.61 Impact Factor
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Wei Qian,
Yantao Jia,
Shuang-Xi Ren,
Yong-Qiang He,
Jia-Xun Feng,
Ling-Feng Lu,
Qihong Sun,
Ge Ying,
Dong-Jie Tang,
Hua Tang, [......],
Yingchuan Tian, Zhijian Yao,
Gang Fu,
Baoshan Chen,
Rongxiang Fang,
Boqin Qiang,
Zhu Chen,
Guo-Ping Zhao,
Ji-Liang Tang,
Chaozu He
[show abstract]
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ABSTRACT: Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.
Genome Research 07/2005; 15(6):757-67. · 13.61 Impact Factor
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Fan Yang,
Jian Yang,
Xiaobing Zhang,
Lihong Chen,
Yan Jiang,
Yongliang Yan,
Xudong Tang,
Jing Wang,
Zhaohui Xiong,
Jie Dong, [......],
Jianguo Xu,
Yu Wang,
Zhenghong Yuan,
Yumei Wen, Zhijian Yao,
Yan Shen,
Boqin Qiang,
Yunde Hou,
Jun Yu,
Qi Jin
[show abstract]
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ABSTRACT: The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
Nucleic Acids Research 02/2005; 33(19):6445-58. · 8.03 Impact Factor
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ABSTRACT: Bacterial pathogens continue to impose a major threat to public health worldwide in the 21st century. Intensified studies on bacterial pathogenesis have greatly expanded our knowledge about the mechanisms of the disease processes at the molecular level over the last decades. To facilitate future research, it becomes necessary to form a database collectively presenting the virulence factors (VFs) of various medical significant bacterial pathogens. The aim of virulence factor database (VFDB) (http://www.mgc.ac.cn/VFs/) is to provide such a source for scientists to rapidly access to current knowledge about VFs from various bacterial pathogens. VFDB is comprehensive and user-friendly. One can search VFDB by browsing each genus or by typing keywords. Furthermore, a BLAST search tool against all known VF-related genes is also available. VFDB provides a unified gateway to store, search, retrieve and update information about VFs from various bacterial pathogens.
Nucleic Acids Research 02/2005; 33(Database issue):D325-8. · 8.03 Impact Factor
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Guohong Deng,
Gangqiao Zhou,
Yun Zhai,
Shuqing Li,
Xuhong Li,
Ya Li,
Ruifang Zhang, Zhijian Yao,
Yan Shen,
Boqing Qiang,
Yuming Wang,
Fuchu He
[show abstract]
[hide abstract]
ABSTRACT: Several studies have demonstrated that estrogen receptor alpha (ESR1) participates in the pathogenesis of persistent hepatitis B virus (HBV) infection. To examine whether polymorphisms at the ESR1 gene locus are associated with persistent HBV infection, we resequenced ESR1 genomic region for single nucleotide polymorphisms (SNPs) in 27 unrelated Chinese. Two haplotype-tagged SNPs (htSNP), T29C and A252966G, were selected for genotyping in 1,277 persistent HBV-infected cases, 748 spontaneously recovered controls, and 293 nuclear families using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. We observed that the subjects bearing ESR1 29T/T genotype had an increased susceptibility to persistent HBV infection compared to those bearing at least one 29C allele (odds ratio 1.41; 95% CI, 1.17-1.71, P < .001). Consistent with the results of population-based association study, a significantly greater than expected transmission of the 29T allele (56.4%) from heterozygous parents to offspring with persistent HBV infection was observed (chi2 = 4.60, P = .033) using the transmission-disequilibrium test (TDT) in 293 nuclear families. Linkage disequilibrium (LD) mapping analysis indicated that the T29C polymorphism contained within a LD block located from promoter region to intron 3 of ESR1, suggesting that the strong association detected with T29C in ESR1 originated from ESR1 itself. In conclusion, our results suggest that the genetic variation at the ESR1 locus influences susceptibility to persistent HBV infection in a Chinese population.
Hepatology 08/2004; 40(2):318-26. · 11.66 Impact Factor
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Gangqiao Zhou,
Yun Zhai,
Xiaojia Dong,
Xiumei Zhang,
Fengying He,
Kaixin Zhou,
Yunping Zhu,
Handong Wei, Zhijian Yao,
Shaofei Zhong,
Yan Shen,
Boqing Qiang,
Fuchu He
[show abstract]
[hide abstract]
ABSTRACT: Interleukin-13 (IL13) is believed to play an important role in the pathogenesis of atopy and allergic asthma. To better understand genetic variation at the IL13 locus, we resequenced a 5.1-kb genomic region spanning the entire locus and identified 26 single-nucleotide polymorphisms (SNPs) in 74 individuals from three major populations-Chinese, Caucasian, and African. Our survey suggests exceptionally high and significant geographic structure at the IL13 locus between African and outside Africa populations. This unusual pattern suggests that positive selection that acts in some local populations may have played a role on the IL13 locus. In support of this suggestion, we found a significant excess of high frequency-derived SNPs in the Chinese population and Caucasian population, respectively, as expected after a recent episode of positive selection. Further, the unusual haplotype structure indicates that different scenarios of the action of positive selection on the IL13 locus in different populations may exist. In the Caucasian population, the skewed haplotype distribution dominated by one common haplotype supports the hypothesis of simple directional selection. Whereas, in the Chinese population, the two-round hitchhiking hypothesis may explain the skewed haplotype structure with three dominant ones. These findings may provide insight into the likely relative roles of selection and population history in establishing present-day variation at the IL13 locus, and, motivate further studies of this locus as an important candidate in common diseases association studies.
Molecular Biology and Evolution 02/2004; 21(1):29-35. · 5.55 Impact Factor
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Gangqiao Zhou,
Yun Zhai,
Xiaojia Dong,
Ya Li,
Xiumei Zhang,
Ruifang Zhang,
Shuqing Li,
Xuhong Li,
Fengying He,
Handong Wei,
Xiaoping Chen, Zhijian Yao,
Yan Shen,
Boqing Qiang,
Fuchu He
[show abstract]
[hide abstract]
ABSTRACT: Human TNFRSF5, a key signaling molecule expressed by antigen-presenting cells of the immune system, might have associations with autoimmune diseases and various infectious diseases. In the present study, we screened single-nucleotide polymorphisms (SNPs) in TNFRSF5 and examined whether they are risk factors for persistent HBV infection or disease severity. We resequenced all 9 exons, the promoter and splicing regions of all introns for 186 Chinese individuals, and identified 11 SNPs. Haplotypes and their frequencies were estimated. The linkage disequilibrium (LD) pattern was also evaluated. Neutrality tests indicated that the variation pattern at TNFRSF5 locus departs from neutrality and may be maintained by positive selection or demography factors such as population growth. Three SNPs (g.53031T>C, g.54068T>C and g.64493A>G) were determined as haplotype-tag SNPs (htSNPs). Furthermore, computer analyses indicated that sequences surrounding g.53031T>C and g.53824T>C were potential binding sites for transcription factors Sp1 and H4TF-2, respectively. We then genotyped these four SNPs for 603 persistent HBV infection patients and 384 spontaneously recovered subjects by PCR direct sequencing. No statistically significant associations were observed between any of the SNPs or haplotypes and persistent HBV infection or disease severity. The information from this study of the TNFRSF5 would be useful for genetic studies of other common diseases.
Human Mutation 01/2004; 23(1):99-100. · 5.69 Impact Factor
