Biomedical subjects

Zhijian Yao

Publications and source records attributed to Zhijian Yao.

15 recordsLinked to original sources

PubMed2006

Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a.

BACKGROUND: 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). RESULTS: 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. CONCLUSION: 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.

Chromosome Aberrations↗

PubMed2006

Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest that the genetic polymorphism in ESR1 may play a role in mediating susceptibility to HCC in Chinese hepatitis B virus carriers.

Adult↗

PubMed2005

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery.

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.

DNA Transposable Elements↗

PubMed2005

Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris.

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.

Bacterial Proteins↗

PubMed2005

VFDB: a reference database for bacterial virulence factors.

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.

Bacteria↗

PubMed2005

Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response.

We have been studying the pharmacogenetic correlates of side effects and early response to antipsychotic treatment in a series of Chinese Han first-episode drug-naive patients with schizophrenia. Here, we report the association of three functional polymorphisms of receptor genes on initial symptom severity and outcome in these patients. We studied the dopamine D3 receptor ser9gly, the dopamine D2 receptor Taq IA and the 5-HT2C receptor promoter -759C/T polymorphisms in 117 patients who had symptoms assessed by Positive and Negative Syndrome Scale (PANSS) on admission and following 10-week antipsychotic treatment, primarily with risperidone or chlorpromazine. The D2 polymorphism was found not to be significantly associated with baseline levels or changes in total PANSS in these patients. The D3 genotype is associated with the change in total PANSS (p<0.01), an effect reflecting positive and general (each p<0.01) but not negative symptom improvement. However, symptom improvement at 10 weeks strongly correlates with total PANSS score on admission, in which the greater improvement is seen with the more severe initial symptom score. The D3 genotype is also related to severity on admission, i.e. to total baseline PANSS (p<0.05), including baseline PANSS score as a covariate, the association of the genotype to change over 10 weeks remains significant for total PANSS (p<0.05) and for positive and general, but not negative, symptom scores. The 5-HT2C promoter polymorphism was also associated with improvement in PANSS (p<0.05), but reflecting effects on negative and general, but not positive, symptom scores. This polymorphism was not associated with PANSS score on admission, although after controlling for the effect of this parameter on 10-week outcome, a stronger association with change in total PANSS (p<0.01) was apparent, again reflecting improvements in negative and general symptoms but not changes in positive symptoms.

Alleles↗

PubMed2005

Structural and functional analysis of denitrification genes in Pseudomonas stutzeri A1501.

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.

Escherichia coli↗

PubMed2004

Association of estrogen receptor alpha polymorphisms with susceptibility to chronic hepatitis B virus infection.

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.

Adult↗

PubMed2004

Variants in TNFRSF5 locus and association analysis with Hepatitis B virus (HBV) infection.

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.

Adult↗

PubMed2003

Haplotype structure and evidence for positive selection at the human IL13 locus.

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.

Asian People↗

PubMed2003

Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population.

OBJECTIVE: An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. METHODS AND RESULTS: Thirty polymorphisms of PON1, PON2, and PON3 gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients. Twelve polymorphisms were additionally investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele, and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P=0.0054 and P=0.0002). Haplotype analyses for various polymorphism combinations additionally confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher, whereas only the frequencies of haplotypes containing 160G allele were significantly lower in cases than in controls in various polymorphism combinations. CONCLUSIONS: This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population and warrants additional study to elucidate the biological mechanism.

Alleles↗

PubMed2003

Association between genetic variation of CACNA1H and childhood absence epilepsy.

Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and, among the variations identified, 12 were missense mutations and only found in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy.

Age of Onset↗

PubMed2003

Linkage analysis of 2q14-q23 and 5q32 with blood pressure quantitative traits in Chinese sib pairs.

OBJECTIVES: Several genome-wide scans recently accomplished in the ethnic Chinese revealed a number of candidate loci possibly contributing to essential hypertension, and some appeared to be replicable in 2q14-q23 and 5q32. The current study aimed to examine the linkage of qualitative and blood pressure quantitative traits in essential hypertension with these genomic regions in a large sample of Chinese hypertensive families. METHODS: We performed a genetic analysis on 148 randomly ascertained families containing 328 affected sib pairs, grouped into two geographically distinct subsets. Five highly informative microsatellite markers (D2S151, D2S142, D5S2090, D5S413 and D5S2013) were genotyped, and linkage analyses were performed with different genetic models. RESULTS: We did not observe consistent evidence for excess allele sharing identity by descent in either of the qualitative or the quantitative test. However, higher LOD scores were found at D5S2013 in North Group subset with Haseman-Elston and maximum likelihood (ML) variance (no dominance variance, NDV) algorithms. With the ML (NDV) algorithm, the LOD was 1.410 for diastolic blood pressure at this locus, although this was not statistically significant. CONCLUSIONS: These findings provide no evidence to support a significant linkage of 2q14-q23 or 5q32 with essential hypertension or blood pressure quantitative traits in the ethnic Chinese, and indicate the aetiologic diversity and complexity of hypertension. Previous reports implied 2q14-q23 or beta 2- adrenergic receptor gene potentially linked to essential hypertension in the ethnic Chinese. To replicate these results and perform quantitative linkage analysis, we genotyped members of 148 hypertensive families with five highly informative microsatellite markers. We observed no evidence of excess allele sharing identity by descent in sib pairs, revealing a lack of linkage between 2q14-q23 or 5q32 (chromosome region harboring the gene encoding beta 2 adrenergic receptor) and hypertension in our study sample.

Adult↗

PubMed2002

Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157.

We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.

Amino Acid Sequence↗

PubMed2002

[Association of antipsychotic agent-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene].

OBJECTIVE: To determine whether 5-hydroxytryptamine 2C (5-HT2C) receptor gene 759C/T polymorphism influences the weight gain following antipsychotic agents (APS) treatment in patient with schizophrenia. METHODS: DNA was extracted from the peripheral blood of 117 Chinese first-episode patients of Han nationality with schizophrenia diagnosed according to CCMD-II-R criteria. PCR-RELP technique was used to analyse the frequencies of 5-HTR2C receptor gene 759C/T hemizygote (male) and genotype (female). Monotherapy with APS (chlorpromazine or rispperidone) was given for 10 weeks. The body weight was taken and body mass index (BMI) was calculated on admission and every week subsequently for each patient. The correlation of hemizygote or genotype and the BMI was analyzed. RESULTS: Ten weeks after treatment, there was an average increase in body weight of (3.2 +/- 3.5) kg or (5.7 +/- 6.2)% of the baseline weight with a range of -7 kg approximately 12 kg or -7.8% approximately 32%. The frequency of mutant hemizygote was 58% among the 58 male subjects; the frequency of mutant homozygote was 0%, and the frequency of mutant heterozygote was 27.0% among the 59 female subjects. The body weight gain > 7% occurred in 53% of wild type hemizygote males and 47% of wild type homozygote females; and only 18% of mutant hemizygote males and 13% of mutant heterozygote females. The proportions of 759T hemizygote males or heterozygote females in those with body weight gain > 7% and those with body weight < 7% were significantly different (chi(2) = 22.35, v1, P = 0.000 1; chi(2) = 12.36, v1, P = 0.000 1). Patients without mutant allele were five to six times more likely to develop substantial weight gain (OR = 5.11, 6.68). CONCLUSION: The 5-HT2C-receptor gene -759C/T polymorphism is associated with APS-induced weight gain. 759C-->T may be a protective factor for the development of weight gain in Chinese schizophrenic patients of Han nationality.

Adolescent↗