Biomedical subjects

Dawei Li

Publications and source records attributed to Dawei Li.

At least 19 recordsLinked to original sources

PubMed2026

A conserved COBL3-like protein promotes PDLP5-dependent callose accumulation to confer broad-spectrum plasmodesmata-mediated antiviral defense.

Plasmodesmata (PDs) play vital roles in plant growth and defense by controlling the symplastic transport of important molecules. Here we report that a conserved COBRA-like protein, COBL3, positively regulates callose accumulation and is required for PD-mediated antiviral defense (PMAD) against divergent plant RNA viruses in wheat (Triticum aestivum) and tobacco (Nicotiana benthamiana). The wheat COBL3 protein, TaCOBL3, interacts with the 17K movement protein (MP) of barley yellow dwarf virus-GAV (BYDV-GAV). TaCOBL3 is associated with the plasma membrane and co-localizes with 17K MP at PDs. Genetic analysis with overexpression and knockout lines revealed that TaCOBL3 positively regulates wheat defense against BYDV-GAV by modulating callose accumulation at PDs. Interestingly, TaCOBL3 interacts with the wheat homolog of PDLP5, a conserved key regulator of PD permeability in higher plants. Silencing TaPDLP5 attenuates the elevated BYDV-GAV defense conferred by overexpression of TaCOBL3 in wheat. Furthermore, transient expression of TaCOBL3 promotes callose accumulation and lowers PD permeability in tobacco cells, and these effects are largely compromised when tobacco PDLP5 is silenced. Notably, BYDV 17K MP weakens the interaction between TaCOBL3 and TaPDLP5 and inhibits their callose-binding activities. Finally, silencing of tobacco NbCOBL3 reduces callose content and attenuates host defense against two tobraviruses, one potexvirus, and one hordeivirus. Overall, our study reveals a previously unknown role of COBRA-like proteins in PMAD and provides insight into how a plant viral MP sabotages PMAD by perturbing the COBL3-PDLP5 interaction to facilitate virus spread through PDs. The conserved COBL3 gene may be a valuable target for engineering of broad-spectrum antiviral resistance in crop plants.

COBRA-like protein↗

PubMed2007

Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: a HuGE review and meta-analysis.

Schizophrenia is a severe mental illness to which hypofunction of the N-methyl-D-aspartate receptors has been linked. Association studies have implicated the N-methyl-D-aspartate receptor 2B subunit gene (GRIN2B) as a candidate for schizophrenia. Subsequent studies have attempted to replicate the association, but the results have been mixed and thus inconclusive. It is necessary to explain the inconsistency of these results and to clarify the contribution of the GRIN2B gene to schizophrenia. The current meta-analysis covers all published association studies up to January 2006 using systematic allelic and genotypic analyses involving five polymorphisms. The results show evidence of a statistically significant association for GRIN2B. The association seems weaker, but nonetheless interesting. The meta-analysis supports the involvement of the glutamate system of the brain in the pathogenesis of schizophrenia. This may be the first systematic meta-analysis study focusing on GRIN2B.

Case-Control Studies↗

PubMed2006

G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies.

Schizophrenia may result from a neurotransmission hypofunction of glutamatergic and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has identified several promising and novel positional candidates, including the G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive association report, many subsequent studies have attempted to replicate the association but the results have been mixed. To try to resolve this inconsistency and to elucidate the relationship between the important glutamate-related genes and schizophrenia, the current meta-analysis has combined samples involving 16 polymorphisms covering all published case-control and family-based association studies up to October 2005. The results suggest that there is weak evidence of association between the G72/G30 genes and schizophrenia.

Carrier Proteins↗

PubMed2006

Analysis of the association between Apolipoprotein D and schizophrenia.

Schizophrenia is a severe, chronic and common complex debilitating mental illness with a large genetic component. Evidence to date suggests that apolipoprotein D protein may be closely related to schizophrenia. To investigate the role of the APOD gene in the etiology of schizophrenia, we genotyped three genetic polymorphisms (rs7659, rs2280520 and rs4677695) in a case-control study using subjects from the Chinese population, and altogether 425 cases and 473 controls were analyzed in the study. However, we found no significant discrepancies in allele and genotype frequencies of the three polymorphisms nor in the haplotype distribution between the cases and the controls. Our data indicate no direct evidence of association between schizophrenia and the APOD gene, and the results suggest that the three genetic polymorphisms within the APOD gene are unlikely to confer increased susceptibility to the illness in the Chinese population.

Adolescent↗

PubMed2006

Association study of the G-protein signaling 4 (RGS4) and proline dehydrogenase (PRODH) genes with schizophrenia: a meta-analysis.

Schizophrenia is a devastating psychiatric disease that affects up to 1% of the population worldwide. Recent studies suggested that schizophrenia might result from the hypofunction of glutamatergic neurotransmission. Systematic positional, expression and functional studies have implicated the regulator of G-protein signaling 4 (RGS4) and proline dehydrogenase (PRODH) genes as promising and novel candidates for explaining schizophrenia. However, the findings of association studies tend to vary depending on the different populations on which they have been conducted. To reconcile this conflict of evidence, we combined all available population-based and family-based studies up to July 2005 involving eight polymorphisms. However, this meta-analysis did not find statistically significant evidence for association between the two glutamate-related genes and schizophrenia on the basis of either allelic or genotypic analysis. This may be the first systematic meta-analysis study based on RGS4 and PRODH.

Humans↗

PubMed2006

Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD).

Molecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3'-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4) and a microsatellite polymorphism located at 18.5 kb from the 5' end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR=1.34, 95% CI 1.23-1.45, P= 2 x 10(-12)) and 5-repeat (OR=1.68, 95% CI 1.17-2.41, P=0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P= 8 x 10(-8)) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR=0.90, 95% CI 0.84-0.97, P=0.004) and DRD5 136-bp (OR=0.57, 95% CI 0.34-0.96, P=0.022) alleles have protective effects. In contrast, we found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P=0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD.

3' Untranslated Regions↗

PubMed2006

Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia.

A number of studies have suggested an association between schizophrenia and the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent in schizophrenia. In an attempt to clarify this inconsistency our meta-analysis has combined all the studies using multiple research methods published up to February 2006 to give a comprehensive picture of the role of three hydroxylase-related genes. The TPH A218C/A779C (OR = 1.18, 95% C.I. 1.06-1.33, P = 0.004) revealed a significant association with schizophrenia. However, the evidence for the TH and phenylalanine hydroxylase (PAH) genes was weak. No publication bias was detected in current studies. The findings, which may implicate the involvement of TPH in the pathogenesis of schizophrenia, have potentially important clinical, scientific and public health implications as well as providing a putative basis for the study of hydroxylase-related drugs. To our knowledge, this is the first meta-analysis of association between the three genes and schizophrenia.

Gene Frequency↗

PubMed2006

Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.

Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans and confirmed by meta-analysis of published linkage data. Systematic fine mapping using extended Icelandic pedigrees identified an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAP(ICE)), defined by five SNPs and two microsatellite polymorphisms was found to be associated with schizophrenia in the Icelandic and Scottish populations. A number of subsequent independent studies have attempted to replicate the association, and while some have been successful, the associated haplotype is not always HAP(ICE). Furthermore, no obviously functional or pathogenic variants have been identified, and the relationship between the gene and schizophrenia has remained inconclusive. To reconcile these conflicting findings and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 13 published population-based and family-based association studies up to November 2005. We analysed data from the SNP markers SNP8NRG241930, SNP8NRG243177, SNP8NRG221132 and SNP8NRG221533, and the microsatellite markers 478B14-848, 420M9-1395. Across these studies, strong positive association was found for all six polymorphisms. The haplotype analysis also showed significant association in the pooled international populations (OR=1.22, 95% CI 1.15-1.3, P=8 x 10(-10)). In Asian populations, the risk haplotype was focused around the two microsatellite markers, 478B14-848, 420M9-1395 (haplotype block B), and in Caucasian populations with the remaining four SNP markers (haplotype block A). This meta-analysis supports the involvement of NRG1 in the pathogenesis of schizophrenia, but with association between two different but adjacent haplotypes blocks in the Caucasian and Asian populations.

Asian People↗

PubMed2006

Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses.

Suicide is a major public health issue, especially in western countries, accounting for approximately 1 million deaths every year throughout the world. The tryptophan hydroxylase (TPH) gene has been extensively studied as a candidate for suicidal behavior due to its role in serotonergic neurotransmission. Since the first study associating the gene with schizophrenia, there have been many attempts to replicate it. However, a number of these studies have produced contrary results, possibly reflecting inadequate statistical power and the use of different populations. Association data relating European and, more particularly, Asian populations has become increasingly available in recent years. To examine whether the aggregate data provide evidence of statistical significance, the current meta-analysis has combined all the published studies up to July 2005, and examined the polymorphisms (A779C, A218C, A-6526G) in the context of varied suicidal behaviors by analyzing the studies in total and in subsets. Compared with the inconsistent results of previous studies, the current results (22 references) confirm a strong overall association between suicidal behavior and the A779C/A218C polymorphisms, supporting the involvement of TPH in the pathogenesis of suicidal behavior.

Gene Frequency↗

PubMed2006

Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis.

Serotonin 2A receptor (5-HT2A) gene was implicated to be associated with both schizophrenia and suicidal behavior due to its role of key neurotransmitter in many physiologic processes. Association studies were reported in different populations, however, a great number of subsequent studies have produced contrary results, possibly reflecting inadequate statistical power. With the cumulative data in recent years in both European and Asian populations, particularly in Asian populations, it was necessary to carry out a comprehensive analysis of previous findings. The meta-analysis, therefore, combined all English and Chinese studies using multiple research methods published up to July 2005 to give a new picture of the role of the 5-HT2A gene. Compared with significant results reported previously, the current large samples (73 studies in all) failed to find significant association of the T102C polymorphism with either schizophrenia or suicidal behavior. Evidence of significant association was only detected between A-1438G and suicidal behavior. The current study did not support the association of the 5-HT2A gene with either schizophrenia or suicidal behavior.

Alleles↗

PubMed2006

Analysis of the subgenomic RNAs and the small open reading frames of Beet black scorch virus.

A full-length cDNA of the genome of Beet black scorch virus (BBSV), isolate Ningxia, was constructed and modified by site-directed mutagenesis to permit in vitro transcription of mutant viral RNAs. Two subgenomic (sg) RNAs (sgRNA1 and sgRNA2) appeared during BBSV replication. Mutagenesis revealed that sgRNA1 transcription was initiated at G2209 within the P82 polymerase subunit open reading frame (ORF) and that transcription of sgRNA2 began at G2526 within the nested p7b/p5' ORF. Initiation-codon shifting or premature termination of translation of the three ORFs (P7a, P7b and P5') encoded by sgRNA1 indicated that each of the genes was required for localized movement, accumulation of viral RNAs and formation of local lesions on the leaves of Chenopodium amaranticolor. Microscopic observations of the distribution of green fluorescent protein fused to the N-terminal portion of the capsid protein provided additional evidence that the P7a, P7b and P5' proteins are each required for cell-to-cell movement. In contrast, elimination of sgRNA2 showed that the BBSV coat protein was not required for viral RNA accumulation or the appearance of local lesions on C. amaranticolor. In addition, disruption of the small P5 ORF previously predicted by computer analysis to originate at the C terminus of the P82 ORF had no effect on disease phenotype, suggesting that this ORF may represent a cryptic, non-essential gene. These results show that BBSV has a novel cell-to-cell movement protein organization that differs in size and sequence from that of other viruses.

Base Sequence↗

PubMed2005

Positive association of the human GABA-A-receptor beta 2 subunit gene haplotype with schizophrenia in the Chinese Han population.

A converging body of evidence implicates the gamma-amino butyric acid neurotransmitter system in the pathogenesis of schizophrenia. Recently, Lo et al. reported strong positive association between schizophrenia and GABRB2, demonstrated by single markers and haplotypes of five markers in introns of GABRB2, rs6556547, rs1816071, rs194072, rs252944, and rs187269. To validate this linkage disequilibrium report, we genotyped these five SNPs and additional rs1816072 in 352 Chinese Han family trios. Though we failed to detect any positive results in single markers, we did find a significant haplotypic association (global p = 0.00157-0.00588) which had not been identified in Lo's study. Our data indicated that the haplotype 'GACTCT' (p = 0.00215, frequency = 53.6%) was overtransmitted which suggests that GABRB2 is in linkage disequilibrium with schizophrenia in the Chinese Han population. The difference between the two studies may be due to the respective analytic power of the two designs. These two independent studies highlighting linkage disequilibrium support the potential involvement of GABRB2 or a nearby gene in the genetic etiology of schizophrenia.

Asian People↗

PubMed2005

Tools and strategies for physiological genomics: the Rat Genome Database.

The broad goal of physiological genomics research is to link genes to their functions using appropriate experimental and computational techniques. Modern genomics experiments enable the generation of vast quantities of data, and interpretation of this data requires the integration of information derived from many diverse sources. Computational biology and bioinformatics offer the ability to manage and channel this information torrent. The Rat Genome Database (RGD; http://rgd.mcw.edu) has developed computational tools and strategies specifically supporting the goal of linking genes to their functional roles in rat and, using comparative genomics, to human and mouse. We present an overview of the database with a focus on these unique computational tools and describe strategies for the use of these resources in the area of physiological genomics.

Animals↗

PubMed2005

A family-based association study of the MOG gene with schizophrenia in the Chinese population.

Recently the expression of human myelin/oligodendrocyte glycoprotein (MOG) has been found to be significantly downregulated in the brain tissue of subjects with schizophrenia, suggesting that the MOG gene resides within a high-susceptibility locus for schizophrenia. In order to test this prediction, we analyzed three microsatellites from MOG in the Han Chinese population using a sample of 532 trios. Analysis of allele, genotype and haplotype frequencies showed weak positive association between the markers and the disease (p=0.01982). Our results would indicate that the MOG gene may play a significant role in schizophrenia in the Han Chinese. However, further study is required using other methods and involving other populations.

Asian People↗

PubMed2005

The Genomes of Oryza sativa: a history of duplications.

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.

Base Sequence↗

PubMed2005

The Rat Genome Database (RGD): developments towards a phenome database.

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.

Animals↗

PubMed2005

Nuclear magnetic resonance solution structure of the Escherichia coli DNA polymerase III theta subunit.

The catalytic core of Escherichia coli DNA polymerase III holoenzyme contains three subunits: alpha, epsilon, and theta. The alpha subunit contains the polymerase, and the epsilon subunit contains the exonucleolytic proofreading function. The small (8-kDa) theta subunit binds only to epsilon. Its function is not well understood, although it was shown to exert a small stabilizing effect on the epsilon proofreading function. In order to help elucidate its function, we undertook a determination of its solution structure. In aqueous solution, theta yielded poor-quality nuclear magnetic resonance spectra, presumably due to conformational exchange and/or protein aggregation. Based on our recently determined structure of the theta homolog from bacteriophage P1, named HOT, we constructed a homology model of theta. This model suggested that the unfavorable behavior of theta might arise from exposed hydrophobic residues, particularly toward the end of alpha-helix 3. In gel filtration studies, theta elutes later than expected, indicating that aggregation is potentially responsible for these problems. To address this issue, we recorded 1H-15N heteronuclear single quantum correlation (HSQC) spectra in water-alcohol mixed solvents and observed substantially improved dispersion and uniformity of peak intensities, facilitating a structural determination under these conditions. The structure of theta in 60/40 (vol/vol) water-methanol is similar to that of HOT but differs significantly from a previously reported theta structure. The new theta structure is expected to provide additional insight into its physiological role and its effect on the epsilon proofreading subunit.

Alcohols↗

PubMed2005

[Study on chitosan-DNA nanoparticles as gene carriers].

The preparation and cell transfection of chitosan-DNA nanoparticles were studied. The TFPI (tissue factor pathway inhibitor) or EGFP (enhanced green fluorescent protein) plasmid DNA was encapsulated with chitosan to form gene nanoparticles. The results with TEM showed that the nanoparticles were of sphere shape. The mean diameter of the nanoparticles was 149 nm and the diameter ranged from 80-250 nm, which were measured by the photo related spectrometry (PCS). The encapsulation efficiency of DNA was 96% +/- 1.38% and the DNA content in the nanoparticles was 37% +/- 3.0%. The encapsulated DNA could be protected from the degradation by DNase I. The transfection efficiency of chitosan nanoparticles were about equivalent to that of the LipofectAMINETM reagent. Our results also showed that chitosan nanoparticles were nontoxic to cultured cells.

Cells, Cultured↗