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PubMedDate not supplied

Molecular cloning and characterization of a novel human kinase gene, PDIK1L.

We isolated a 4301-bp cDNA from a human foetal brain cDNA library by high-throughput cDNA sequencing. It encodes a protein of 341 amino acids, which shows 69% identity with the human kinase CLIK1 (AAL99353), which was suggested to be the CLP-36 interacting kinase. Bioinformatics analysis suggests that the putative kinase may interact with PDZ and LIM domain proteins. Therefore the protein and its cDNA were named 'PDLIM1 interacting kinase 1 like' (PDIK1L; nomenclature approved by the HUGO Gene Nomenclature Committee). Ensembl Genome Browser located PDIK1L to human chromosome 1p35.3. It spans about 13.7 kb and consists of four exons and three introns. Multiple-tissue cDNA panel PCR revealed that the gene is expressed widely in human tissues: liver, kidney, pancreas, spleen, thymus and prostate. The protein appears to be localized to the nucleus.

Amino Acid Sequence↗

PubMed2006

Overlapping transcripts, double-stranded RNA and antisense regulation: a genomic perspective.

Bioinformatic analysis of the transcriptomes of diverse eukaryotes has demonstrated the ubiquity and structural diversity of complementary antisense RNAs. These include both trans-encoded microRNAs and a large population of cis-encoded antisense RNAs that encompasses both coding and non-coding RNAs. Antisense regulation has previously been characterized primarily as a post-transcriptional response affecting RNA stability, nuclear processing, export, or translation. However, the formation of double-stranded (ds) RNAs by base-pairing between complementary RNAs may elicit regulatory responses at the transcriptional level as well. Analysis of antisense transcription at several imprinted loci has suggested a number of other mechanisms that may not require formation of dsRNA. Understanding the integration of transcriptional and post-transcriptional regulatory mechanisms represents a major challenge for understanding antisense regulation in eukaryotes. Such insight is also essential for understanding general principles of genetic regulation within the complex genomes characteristic of mouse and man as well as those of other eukaryotes.

Animals↗

PubMed2005

Genetic and physical mapping of Pi37(t), a new gene conferring resistance to rice blast in the famous cultivar St. No. 1.

The famous rice cultivar (cv.), St. No. 1, confers complete resistance to many isolates collected from the South China region. To effectively utilize the resistance, a linkage assay using microsatellite markers (SSR) was performed in the three F2 populations derived from crosses between the donor cv. St. No. 1 and each of the three susceptible cvs. C101PKT, CO39 and AS20-1, which segregated into 3R:1S (resistant/susceptible) ratio, respectively. A total of 180 SSR markers selected from each chromosome equally were screened. The result showed that the two markers RM128 and RM486 located on chromosome 1 were linked to the resistance gene in the respective populations above. This result is not consistent with those previously reported, in which a well-known resistance gene Pif in the St. No. 1 is located on chromosome 11. To confirm this result, additional four SSR markers, which located in the region lanked by RM128 and RM486, were tested. The results showed that markers RM543 and RM319 were closer to, and RM302 and RM212 completely co-segregated with the resistance locus detected in the present study. These results indicated that another resistance gene involved in the St. No. 1, which is located on chromosome 1, and therefore tentatively designated as Pi37(t). To narrow down genomic region of the Pi37(t) locus, eight markers were newly developed in the target region through bioinformatics analysis (BIA) using the publicly available sequences. The linkage analysis with these markers showed that the Pi37(t) locus was mapped to a approximately 0.8 centimorgans (cM) interval flanked by RM543 and FPSM1, where a total of seven markers co-segregated with it. To physically map the locus, the Pi37(t)-linked markers were landed on the reference sequence of cv. Nipponbare through BIA. A contig map corresponding to the locus was constructed based on the reference sequence aligned by the Pi37(t)-linked markers. Consequently, the Pi37(t) locus was defined to 374 kb interval flanking markers RM543 and FPSM1, where only four candidate genes with the resistance gene conserved structure (NBS-LRR) were further identified to a DNA fragment of 60 kb in length by BIA.

China↗

PubMed2005

Fine mapping of f5-Du, a gene conferring wide-compatibility for pollen fertility in inter-subspecific hybrids of rice (Oryza sativa L.).

Wide-compatibility varieties (WCVs), comprising a special class of rice germplasm, are able to produce fertile hybrids when crossed with both indica and japonica varieties. Dular, a landrace variety from India, has both a wide spectrum and high level of wide-compatibility when crossed with a range of indica and japonica varieties. In previous studies, an allele at the f5 locus from Dular (f5-Du) was identified as a neutral allele conferring wide-compatibility with a large effect on both pollen and spikelet fertility. Using a population of 1993 hybrid plants derived from a cross between ZS(f5-Du/f5-ZS) (F1 of near isogenic line of Zhenshan 97 containing f5-Du) and Balilla (a japonica tester), f5-Du was genetically mapped to an interval of about 1.6 cM, with 0.8 cM from both SSR markers WFPM3 and WFPR1. Combined with bioinformatic analysis, a contig map was constructed for the f5 region, consisting of five bacterial artificial chromosome (BAC) or P1 artificial chromosome (PAC) clones and spanning approximately 437 kb in length. By assaying the recombinant events in the region with markers developed using the sequence information, the f5 locus was further narrowed down to a 70 kb fragment containing nine predicted genes. The result will be very useful for cloning this gene and marker-assisted transferring of the neutral allele in rice breeding programs.

Chromosomes↗

PubMed2005

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes. METHODS: We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions. RESULTS: We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic-euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects. CONCLUSIONS/INTERPRETATION: Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

Amino Acid Sequence↗

PubMed2006

Thrombin-like effect of an important green pit viper toxin, albolabrin: a bioinformatic study.

The green pit viper venom has a major effect on the hematological system. Clinical features of venomous snakebites vary from asymptomatic to fatal bleeding. The venom is found to have a thrombin-like effect in vitro. Here, the author performs a bioinformatic analysis on the green pit viper venom focusing on its thrombin-like effect. Sequence comparison between green pit viper venom, albolabrin and thrombin was performed. In addition, the author performed a search for other human proteins closely relating to the thrombin and created a multiple sequence alignment phylogenetic tree to present the family tree of the thrombin, albolabrin and those proteins recorded in the genomic database. In conclusion, the comparative sequence analysis between green pit viper venom and thrombin gives several identities. The reported relationship on the phylogenetic tree can match with the reported in vivo function of green pit viper. Explanations on the effect of green pit viper toxin on the hemostasis can be derived from this study. Furthermore, future researches based on the reported identities can be expected.

Amino Acid Sequence↗

PubMed2005

Functional genomics of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1.

Nitrate-reducing bacteria of the recently recognized Azoarcus/Thauera group within the Betaproteobacteria contribute significantly to the biodegradation of aromatic and other refractory compounds in anoxic waters and soils. Strain EbN1 belongs to a distinct cluster (new genus) and is the first member of this phylogenetic group, the genome of which has been determined (4.7 Mb; one chromosome, two plasmids) by [Rabus R, Kube M, Heider J, Beck A, Heitmann K, Widdel F, Reinhardt R (2005) The genome sequence of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1. Arch Microbiol 183:27-36]. Ten anaerobic and four aerobic aromatic-degradation pathways were recognized on the chromosome, with the coding genes mostly forming clusters. Presence of paralogous gene clusters (e.g. for anaerobic ethylbenzene degradation) suggests an even broader degradation spectrum than previously known. Metabolic versatility is also reflected by the presence of multiple respiratory complexes and is apparently controlled by an extensive regulatory network. Strain EbN1 is unique for its capacity to degrade toluene and ethylbenzene anaerobically via completely different pathways. Bioinformatical analysis of their genetic blueprints and global expression analysis (DNA-microarray and proteomics) of substrate-adapted cells [Kühner S, Wöhlbrand L, Fritz I, Wruck W, Hultschig C, Hufnagel P, Kube M, Reinhardt R, Rabus R (2005) Substrate-dependent regulation of anaerobic degradation pathways for toluene and ethylbenzene in a denitrifying bacterium, strain EbN1. J Bacteriol 187:1493-1503] indicated coordinated vs sequential modes of regulation for the toluene and ethylbenzene pathways, respectively.

Anaerobiosis↗

PubMed2005

Tissue distribution of the secretory protein, SPLUNC1, in the human fetus.

We previously identified a tissue-specific gene, short palate, lung, and nasal epithelium clone 1 (SPLUNC1), in nasopharyngeal epithelial tissues. SPLUNC1 was differentially expressed in nasopharyngeal carcinoma. Bioinformatic analysis revealed that SPLUNC1 has the bactericidal permeability-increasing protein/lipid-binding protein (BPI/LBP) domain and a 19 amino acid signal peptide, which suggest that it is a secretory protein. Its precise cellular localization in the respiratory tract is mainly in mucous cells and ducts of submucosal glands. However, little is known about its expression pattern in various human tissues. We generated a highly specific antibody and analyzed its distribution in the human fetus by immunohistochemistry to more precisely determine SPLUNC1 protein localization in human tissues. The results were further validated by RT-PCR. Our results showed that SPLUNC1 protein is expressed at not only the serous glands and epithelium of the upper respiratory tract and digestive tract, but also in the oculi of human embryos. Interestingly, we also found positive staining in fetus adipose tissue, a result not previously reported in studies of adult human tissues. Western blot analysis detected a 24 kDa SPLUNC1 protein in the compounds of nasopharyngeal secretions. This secretory protein was also detected in saliva and tears. Our research suggests that SPLUNC1 protein may not only be an antimicrobial peptide that plays an important role in the maintenance of homeostasis in the upper respiratory tract, oculi, and alimentary tract, it may also be important in the development and lipid metabolism of the adipose tissue.

Adipose Tissue↗

PubMed2006

Developmental expression and phylogenetic conservation of alternatively spliced forms of the C-terminal binding protein corepressor.

The C-terminal binding protein (CtBP) is an evolutionarily conserved transcriptional corepressor found in multicellular eukaryotes. Multiple forms of the protein are typically found in animal cells, produced from separate genes and by alternative splicing. CtBP isoforms have also been implicated in cytoplasmic functions, including Golgi fission and vesicular trafficking. All forms of CtBP contain a conserved core domain that is homologous to alpha-hydroxyacid dehydrogenases, and a subset of isoforms (CtBP(L)) contain extensions at the C terminus. Despite distinct developmental profiles and knockout phenotypes in the mouse, the properties of different isoforms of the protein are found to be similar in many transcriptional assays. We have investigated the expression and conservation of distinct isoforms of the CtBP protein in insects and found that the expression of multiple, developmentally regulated isoforms is widely conserved. In a variety of Drosophila species, the relative abundance of CtBP(L) to CtBP(S) drops sharply after embryogenesis, revealing a conserved developmental shift. Despite the overall lower levels of this isoform, bioinformatic analysis reveals that exons encoding the C-terminal extension in CtBP(L) are conserved from Diptera to Coleoptera, suggesting that the CtBP(L) isoform contributes an important, evolutionarily conserved function.

Alcohol Oxidoreductases↗

PubMed2002

Identification of a 118-kb DNA fragment containing the locus of blast resistance gene Pi-2(t) in rice.

Rice blast disease, caused by the fungal pathogen Pyricularia grisea Sacc., is one of the most devastating crop diseases worldwide. Previous studies have shown that the dominant blast resistance gene Pi-2(t) confers resistance to a broad spectrum of pathogenic strains. Using a population of 292 recombinant inbred lines combined with bioinformatic analysis, we mapped Pi-2(t) between the SSR (simple-sequence repeat) marker SSR140 and the RFLP (restriction fragment length polymorphism) marker JSH12, 0.9 cM from both SSR140 and JSH12. A physical map consisting of six overlapping BAC (bacterial artificial chromosome) clones was anchored to the region containing the Pi-2(t) locus. By analyzing recombination events in this region, the Pi-2(t) locus was localized to a DNA fragment of 118 kb in length. The detailed genetic and physical maps of the Pi-2(t) locus will facilitate both molecular isolation of the gene and marker-assisted transfer of the gene in breeding programs.

Genes, Plant↗

PubMed2003

Shigella flexneri 2a strain 2457T expresses three members of the H-NS-like protein family: characterization of the Sfh protein.

Shigella flexneri 2a is known to express the H-NS nucleoid-structuring protein and the paralogous protein StpA. Using bioinformatic analysis we have now discovered a third member of the H-NS protein family, Sfh (Shigella flexneri H-NS-like protein), in strain 2457T. This protein is encoded by the sfh gene, which is located on a high-molecular-mass plasmid that is closely related to the self-transmissible plasmid R27. When expressed in Escherichia coli, the Sfh protein can complement an hns null mutation, restoring wild-type Bgl, porin protein, and mucoidy phenotypes, and wild-type expression of the fliC and proU genes. While a knockout mutation in the sfh gene alone had no effect on the expression of virulence genes in S. flexneri, an additive effect on virulence gene derepression was seen when the sfh lesion was combined with a mutation in hns. Over-expression of the sfh gene repressed expression of the VirB virulence regulatory protein and transcription of a VirB-dependent structural gene promoter. The purified Sfh protein bound specifically to DNA sequences containing the promoters of the virF and virB virulence regulatory genes. These findings show that Sfh has the ability to influence genetic events beyond the genetic element that encodes it, including the expression of the S. flexneri virulence genes. They raise the possibility of a triangular relationship among three closely related proteins with broad consequences for genetic events in the bacterium that harbours them.

Bacterial Proteins↗

PubMed2002

Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.

Base Sequence↗

PubMed2002

Experimental and bioinformatics comparison of gene expression between T cells from TIL of liver cancer and T cells from UniGene.

BACKGROUND: The major difficulty of mapping parallel gene expression obtained from solid tumors is mainly due to contaminating cells. In this study, by applying a strategy of parallel gene expression at a cell-cluster or colony level, we have identified the gene expression pattern of T cells within tumor-infiltrating lymphocytes (TJLs) obtained from two liver cancer patients. METHODS: Here a new method was utilized to analyze the parallel gene expression. By using bioinformatics analysis, the data were also compared with T-cell gene expression present in UniGene. RESULTS: Our results demonstrated that 18 genes in specimen A and 13 genes in specimen B were highly expressed after the removal of a nonspecific TIL cDNA library, by pairing gene hybridization; the genes were expressed in CD3+ cells from peripheral blood mononuclear cells (PBMC). By using BlastN search, 17 of the 18, and 12 of the 13 sequences were exhibited, respectively, in Homo sapiens, with a range of BlastN E values of 0 to 4 x 10(-13). The LocusLink distribution in chromosomes obtained from both specimens was not significantly different; 17 of 19 putative genes (both specimen A and specimen B) were observed in the UniGene cluster in Homo sapiens, except for dihydropyrimidinase-related protein-3 and diacyglycerol kinase alpha. Interestingly, only 4 of 19 (21%) putative genes were displayed in the T-cell UniGene database (i.e., LD-78 in Hs. 73817, IL-8 in Hs. 624, TRAIL in Hs. 83429, and Fas ligand in Hs. 2007). CONCLUSIONS: By comparison with the reported data and UniGene, the parallel gene expression of T cells obtained from TIL can provide essential new insights into T-cell activity, T-cell extravasation into tumor tissues, and T-cell cytotoxicity against tumor cells.

Adult↗

PubMed2006

Ligand specificity of odorant receptors.

Odorant receptors belong to class A of the G protein-coupled receptors (GPCRs) and detect a large number of structurally diverse odorant molecules. A recent structural bioinformatic analysis suggests that structural features are conserved across class A of GPCRs in spite of their low sequence identity. Based on this work, we have aligned the sequences of 29 ORs for which ligand binding data are available. Recent site-directed mutagenesis experiments on one such receptor (MOR174-9) provide information that helped to identify nine amino-acid residues involved in ligand binding. Our modeling provides a rationale for amino acids in equivalent positions in most of the odorant receptors considered and helps to identify other amino acids that could be important for ligand binding. Our findings are consistent with most of the previous models and allow predictions for site-directed mutagenesis experiments, which could also validate our model.

Amino Acid Sequence↗

PubMed2002

Molecular cloning and characterization of a novel human cAMP response element-binding ( CREB) gene ( CREB4).

Cyclic adenosine monophosphate (cAMP) response element-binding (CREB) proteins are a family of mammalian transcription activators. We identified a novel human CREB gene ( CREB4) that was 1592 bp long and encoded a protein of 395 amino acid residues. The protein shared high homology to mouse CREB3 (identity 62%, similarity 72%). The expression pattern of the human CREB4 gene showed transcripts in prostate, brain, pancreas, skeletal muscle, small intestine, testis, leukocyte, and thymus, whereas in heart, lung, liver, kidney, placenta, spleen, ovary, and colon, specific bands of the transcript could not be detected. The CREB4 gene consisted of ten exons and nine introns and was mapped to chromosome 1q21.3 by means of a bioinformatics analysis.

Amino Acid Sequence↗

PubMed2002

Molecular cloning and characterization of a novel human Rab ( Rab2B) gene.

Rab proteins are small-molecular-weight guanosine triphosphatases (GTPases) that control vesicular traffic in eukaryotic cells. The small GTPase Rab2 is a resident of pre-Golgi intermediates and is required for protein transport from the endoplasmic reticulum to the Golgi complex. We identified a novel human Rab (Rab2B) gene that was 2312 bp in length and encoded a protein of 216 amino acid residues. The protein shared high homology with mouse Rab2 (identity 83%, similarity 91%). The expression pattern of the human Rab2B gene showed that there is a transcript in kidney, prostate, lung, liver, thymus, colon, pancreas, and skeletal muscle, and low levels in placenta, whereas specific bands of the transcript could not be detected in heart, brain, spleen, testis, ovary, small intestine, and leukocyte. Overexpression has been observed in colon adenocarcinoma CX-1. The Rab2B gene consists of nine exons and eight introns and is mapped to chromosome 14q11.1-14q11.2 by bioinformatics analysis.

Aged↗

PubMed2003

Isolation and characterization of a novel human NM23-H1B gene, a different transcript of NM23-H1.

The NM23 gene is a conspicuous metastasis-suppressor gene. Eight human genes of the NM23/nucleoside diphosphate kinase family have been discovered. From our large cDNA cloning and sequencing project, we cloned a different transcript ( NM23-H1B) of human NM23-H1 from 18-week-old human fetal brain. The 987-bp cDNA encodes a protein of 177 amino acid residues. Compared with NM23H1, the cDNA contained an additional NH(2)-terminal region (25 amino acid residues). It was mapped to chromosome 17q21.3 using bioinformatics analysis, which shows that the second exon does not exist in NM23-H1. The expression pattern of NM23-H1B showed that it was ubiquitously expressed in normal tissues (15 tissues except colon) at different levels. Our data also indicated that the expression of the transcript in tumors related to tumor differentiation: in poorly differentiated breast carcinoma GI-101, pancreatic adenocarcinoma GI-103, and undifferentiated ovarian carcinoma GI-102, there was no expression. In poorly differentiated lung carcinoma LX-1, lung carcinoma GI-117, the expression level was very low. The transcript band in well-differentiated colon adenocarcinoma CX-1 was significantly higher than that in poorly differentiated colon adenocarcinoma GI-112. A high transcription level was also found in grade IV prostatic adenocarcinoma PC3.

Adenocarcinoma↗

PubMed2003

Molecular cloning and characterization of the protein 4.1O gene, a novel member of the protein 4.1 family with focal expression in ovary.

Protein 4.1 is an important structural protein that is expressed in erythroid and in a variety of nonerythroid tissues. In mammalian erythrocytes, it plays a key role in regulating the physical properties of mechanical stability and deformability in membranes by stabilizing the spectrin-actin interaction. The protein 4.1 family mainly comprises 4.1R, 4.1G (general type), 4.1B (brain type), and 4.1N (neuron type). We identified a novel human 4.1 ( 4.1O) gene that is 2312 bp in length and encodes a protein of 553 amino acid residues. The protein shared homology with mouse protein 4.1B (identity 38%, similarity 55%) with a FERM domain. The expression pattern of the human 4.1O gene in 16 tissues showed that there was a transcript only in ovary, whereas in the remaining 15 tissues, specific bands of the transcript could not be detected. In eight human fetal tissues, the specific bands of the transcript could be detected in skeletal muscle, with lower levels detected in thymus and brain. The 4.1O gene consists of 14 exons and 13 introns and was mapped to Chromosome 9q21-9q22 by bioinformatics analysis.

Amino Acid Sequence↗