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Biomedical subjects

G Fu

Publications and source records attributed to G Fu.

At least 19 recordsLinked to original sources
PubMed2006

Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes.

The BXSB mouse strain is an important model of glomerulonephritis observed in systemic lupus erythematosus (SLE). Linkage studies have successfully identified disease-susceptibility intervals; however, extracting the identity of the susceptibility gene(s) in such regions is the crucial next step. Congenic mouse strains present a defined genetic resource that is highly amenable to microarray analysis. We have performed microarray analysis using a series of chromosome 1 BXSB congenic mice with partially overlapping disease-susceptibility intervals. Simultaneous comparison of the four congenic lines allowed the identification of expression differences associated with both the initiation and progression of disease. Thus, we have identified a number of novel SLE disease gene candidates and have confirmed the identity of Ifi202 as a disease candidate in the BXSB strain. Sequencing of the promoter regions of Gas5 has revealed polymorphisms in the BXSB strain, which may account for the differential expression profile. Furthermore, the combination of the microarray results with the different phenotypes of these mice has allowed the identification of a number of expression differences that do not necessarily map to the congenic interval, but may be implicated in disease pathways.

Animals↗
PubMed2004

DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

Animals↗
PubMed2001

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗
PubMed2001

Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene.

The human homologue of the Drosophila melanogaster orphan nuclear receptor fushi tarazu factor 1 (Ftz-F1), NR5A2 (hB1F), was initially identified as a regulatory factor that binds and activates enhancer II of hepatitis B virus. NR5A2 (hB1F) is expressed specifically in pancreas and liver, playing important roles in the regulation of several liver-specific genes. A detailed analysis on the genomic structure and promoter activity will greatly promote future studies on the function of the NR5A2 (hB1F) gene. In this report, a bacterial artificial chromosome clone and several phage clones covering the NR5A2 (hB1F) gene were isolated and the complete genomic sequence was obtained. Alignment of different cDNAs of the NR5A2 (hB1F) gene with the genomic sequence facilitated the delineation of its structural organization, which spans over 150 kb and consists of eight exons interrupted by seven introns. RT-PCR and 3'-RACE revealed that utilization of two polyadenylation signals results in the 3.8 and 5.2 kb transcripts that were observed previously. The transcription start site of the NR5A2 (hB1F) gene was mapped downstream of a canonical TATA box. An upstream fragment containing binding sites for several liver-specific and ubiquitous transcription factors exhibits hepatocyte-specific promoter activity. Transient transfections indicated that hepatocyte nuclear factors HNF1 and HNF3beta could activate NR5A2 (hB1F) promoter.

3T3 Cells↗
PubMed2001

Genomic sequence and expression analyses of human chromatin assembly factor 1 p150 gene.

Chromatin assembly factor-1 (CAF-1) plays essential roles in eukaryotic chromatin assembly during DNA replication (Smith and Stillman, 1989. Cell 58, 15-25), (Krude, 1999. Eur. J. Biochem. 263, 1-5). Its p150 subunit, involved in interaction with histone H3 and H4, is critical to the CAF-1 nucleosome assembly activity. In this study, we sequenced a 96-kb genomic DNA region that includes a 42.8-kb CAF-1 p150 subunit gene (CHAF1A), and a 41.1-kb EEN gene. A scripted bioinformatics analysis pipeline (research agent) has been set up to annotate the BAC sequence with a set of integrated algorithms. The CAF-1 p150 subunit gene contains 15 exons and 14 introns. The promoter region is characterized by deletional analyses, revealing a potential repressor. Tissue-correlated alternative splicing forms of the transcript was initially identified by EST clustering analysis, then confirmed by RT-PCR which resulted more splicing forms than computational prediction.

3T3 Cells↗
PubMed2001

Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP.

Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DGI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.

Asian People↗
PubMed2001

Map position and expression of the genes in the 38 region of Drosophila.

With the completion of the Drosophila genome sequence, an important next step is to extract its biological information by systematic functional analysis of genes. We have produced a high-resolution genetic map of cytological region 38 of Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints within the region. Of a total of 45 independent P-element lines that mapped by in situ hybridization to the region, 14 targeted 7 complementation groups within the 38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17 complementation groups. Because these two pools partially overlap, the completed analysis revealed 21 distinct complementation groups defined by point mutations. Seven additional functions were defined by trans-heterozygous combinations of deficiencies, resulting in a total of 28 distinct functions. We further produced a developmental expression profile for the 760 kb from 38B to 38E. Of 135 transcription units predicted by GENSCAN, 22 have at least partial homology to mobile genetic elements such as transposons and retroviruses and 17 correspond to previously characterized genes. We analyzed the developmental expression pattern of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos, larvae, males, and females. We discuss the correlation between GENSCAN predictions and experimentally confirmed transcription units, the high number of male-specific transcripts, and the alignment of the genetic and physical maps in cytological region 38.

Animals↗
PubMed2001

[Total water pollution load determining on Tianxi catchment area in Shenyang city].

This paper analysed and determined the total water pollution load of Tianxi catchment area in Shenyang city systematically; by giving the reliability measurement to the total pollution load, put forward the suggestions to improve the system information reliability. It was found that to strengthen monitoring and investigation for the pumping station is of great advantage to control the pollutants of heavy metals, moreover, by adding monitoring to the Huanglatuozi section of Xi river, not only can the pollution load be identified clearly but also organic pollutants can be controlled more accurately and timely.

China↗
PubMed2001

[The influence of hydraulic characteristics on wastewater purifying efficiency in vertical flow constructed wetlands].

The hydraulic characteristics of vertical flow constructed wetlands was investigated, and the influence of these characteristics on wastewater purifying efficiency was studied as an emphasis. The results of the experiments in small scale plots and medium scale plots showed the plant roots, with the physical and biological effects, play a significant role in hydraulics and the wastewater purifying efficiency. The other characteristics such as retention time, effluent velocity and influent load also directly affect the wastewater purifying efficiency of constructed wetland. To get a better understanding of the hydraulics will be crucial to the improvement of purifying efficiency and facilitate the practical use of constructed wetland.

Sewage↗
PubMed2001

[Experimental study on effect of zenggu-I, -II, -III on osteoblast in vitro].

OBJECTIVE: To investigate the effect of Zenggu (ZG)-I, -II and -III on osteoblast (OB) cultured in vitro. METHODS: OB was isolated from calvaria of 22-day-old fetal SD rats by means of modified sequential collagenase digestion and incubated in RM1640 medium and the cell morphology was observed by alkaline phosphatase (ALP) staining. Different concentrations of ZG-I, -II and -III were added to the OB and incubated. The effect of ZG on the proliferation and osteogenesis of OB was monitored by MTT analysis, BGP content radioimmunoassay, ALP activity and calcium contents determination. RESULTS: The BGP, ALP, and calcium contents of the cultured OB cells as well as the cell proliferation were higher in ZG-III group than those in the other groups (P < 0.05) in a dose-dependent manner. It suggested that ZG-III could promote the proliferation and osteogenesis of OB, but ZG-I and ZG-II had insignificant influence on OB cultured in vitro. CONCLUSION: ZG-III could promote the OB proliferation and bone formation, ZG-I, -II, -III sequential therapy could effectively prevent and treat osteoporosis and promote the bone formation.

Animals↗
PubMed2000

Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.

Alternative Splicing↗
PubMed2000

Gene expression in CD34(+) cells from normal bone marrow and leukemic origins.

INTRODUCTION: To address the molecular regulation of hematopoiesis and the complex mechanism in leukemogenesis, we established the first catalogs of genes expressed in normal bone marrow and leukemia CD34(+) cells. MATERIALS AND METHODS: CD34(+) cell cDNA libraries were constructed using mRNA from adult bone marrow and from a case of acute myeloid leukemia-M5 transformed from myelodysplastic syndrome (MDS-AML). Expressed sequence tags (ESTs) and full-length cDNAs were generated by sequencing and were annotated using bioinformatic tools. RESULTS: From a total of 4142 ESTs obtained from normal bone marrow, 3424 meaningful tags were integrated into 1630 clusters, representing 622 known genes, 522 dbEST entries and 486 novel sequences. Out of 5382 ESTs from MDS-AML, 1985 clusters were produced based on the analysis of 4321 useful ESTs, including 711 known genes, 657 known ESTs and 617 novel sequences. Among 251 transcripts found in both bone marrow and MDS-AML EST datasets and those present in only one dataset, 58 showed statistically significant differences in EST copy numbers between the two tissues (P<0.05). Twenty putative full-length cDNAs for novel genes were also cloned from the MDS-AML library. CONCLUSION: The distinct gene expression patterns in MDS-AML-CD34(+) cells as compared to normal control cells may contribute to the development and/or maintenance of the malignant phenotypes of leukemia cells.

Adult↗
PubMed2000

Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.

Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.

Alternative Splicing↗
PubMed2000

[The relationship between angiotensin converting enzyme gene polymorphism and risk factors for coronary heart disease].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene polymorphism and risk factors for coronary heart disease (CHD). METHODS: 148 patients with CHD and 159 unrelated healthy individuals were studied using polymerase chain reaction (PCR) and genetic methods. Risk factors of CHD were assessed by standard questionnaire, physical examination and blood tests. RESULTS: (1) There were no significant differences among genotypes in terms of years, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL), HDL(2), HDL(3), apolipoprotein (Apo) AI, ApoB, and lipoprotein (a) [Lp (a)]. The prevalence rates of hyperlipidemia, hypertension (HT), cigarette smoking, diabetes mellitus (DM) and obesity were similar in the ACE genotypes (P > 0.05). (2) The DD genotype frequencies in low CHD risk groups, as defined by ApoB < 125 mg/dl and BMI <or= 24 kg/m(2), or TC < 230 mg/dl, TG < 200 mg/dl, LDL < 160 mg/dl and BMI <or=24 kg/m(2) without HT and DM were significantly higher than that in normal subjects (0.257, 0.315, 0.273 vs 0.157, chi(2) = 3.98, 7.80, 4.01, P < 0.05). CONCLUSION: There was no correlations between ACE gene polymorphism and the classic CHD risk factors noticed. ACE DD genotype seemed to be an independent risk factor for CHD in the Chinese population.

Asian People↗
PubMed2000

[The changes in serum antibody level after immunization with HFRS vaccine].

OBJECTIVES: To observe the changes in serum antibody level after mass immunization with vaccine against hemorrhagic fever with renal syndrome (HFRS) and to evaluate its efficacy and effectiveness in the prevalent areas. METHODS: Healthy people aged 16 to 60 years in the villages were recruited as study subjects, excluding those suffered from HFRS previously, going out for more than nine months and those with contraindications, and were randomly allocated into immunization and control groups with 10,460 and 16,159 persons, respectively. Specific IgG antibody was determined with indirect immunofluorescent assay (IFA) and neutralizing antibody (NA) was determined with micro CPE method. RESULTS: Two weeks after the full-course immunization, sero-conversion rate for IFA reached 100% in those sero-negative before immunization, with a 95% confidence interval of 96.3 - 100.0%, and that for NA 44.4%, with a 95% CI of 22.0% - 69.0%. Geometric mean titer (GMT) were 72.1 and 4.6 for IFA and NA, respectively. Booster immunization was provided for them one year later. Positivity of IFA and NA was 28.6%, 83.3%, 75.0%, 53.1%, 22.6% and 14.8%, 55.6%, 35.0%, 31.3%, 26.0%, before booster immunization, two weeks, one year, one and a half years, two years after booster immunization, respectively. CONCLUSION: HFRS vaccine had good immunogenicity, but its duration of serum antibody sustenance was relatively short.

Adolescent↗
PubMed2000

[Exploration of gene expression profiles of CD(34)(+) hematopoietic stem/progenitor cells based on large scale sequencing].

OBJECTIVE: To set up a large scale sequencing system and explore the gene expression profiles of CD(34)(+) hematopoietic stem/progenitor cells (HSPCs). METHODS: CD(34)(+) cells were isolated from umbilical cord blood and subjected to cDNA library construction. A primary profile of gene expression in HSPCs was emerged by EST sequencing and bioinformatics analyzing. RESULTS: Among 9,866 ESTs thus obtained, 7 476 meaningful ESTs were clustered into 2,060 unique sequence species (USSs), representing 1,054 known gene species and 1,006 unknown gene fragments. The 1054 known genes were divided into 8 categories: (1) hematopoiesis associated: 73, (2) chromatin structure and cell division/apoptosis: 91, (3) signal transduction and receptors: 111, (4) cell structure/mobility: 48, (5) cell/organism defense/homeostasis: 41; (6) Gene expression (transcription, translation and modification): 265, (7) metabolism: 192; and (8) unclassified: 233. CONCLUSION: A gene expression profile including 1,054 known genes and 1006 new gene fragments of HSPCs was primarily obtained, which may lay a basis for the further study on the molecular mechanism of hematopoiesis regulation and provide candidates for new gene cloning.

Antigens, CD34↗