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At least 595 records · Page 33Linked to original sources
PubMed1999

Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus.

The short arm of chromosome 8 is frequently lost in many human carcinomas including breast cancer, suggesting the presence of a tumor suppressor gene(s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L hereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOHs of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by linkage analysis. We further performed LOH analysis in 8p12-p21 in 34 breast cancers and identified a 5-cM region of common allelic loss that overlapped with the locus for positive lod score in familial breast cancer. We further analyzed genomic alterations of hEXT1L in tumors in which frequent LOHs of 8p were reported. A total of 327 cancers (313 primary tumors and 14 cancer cell lines) including 22 primary breast cancers were analyzed, but none of the tumors had somatic mutations: only one thyroid cancer patient without any family history of cancer had a 9-bp insertion in the constitutional DNA. These results suggest that mutations of hEXT1L do not play a major role in the development of sporadic cancers including breast cancer, and that other tumor suppressor gene(s) exists in the 5-cM region identified in this study.

Alleles↗
PubMed2002

Genomic analysis of the aromatic catabolic pathways from Pseudomonas putida KT2440.

Analysis of the catabolic potential of Pseudomonas putida KT2440 against a wide range of natural aromatic compounds and sequence comparisons with the entire genome of this microorganism predicted the existence of at least four main pathways for the catabolism of central aromatic intermediates, that is, the protocatechuate (pca genes) and catechol (cat genes) branches of the beta-ketoadipate pathway, the homogentisate pathway (hmg/fah/mai genes) and the phenylacetate pathway (pha genes). Two additional gene clusters that might be involved in the catabolism of N-heterocyclic aromatic compounds (nic cluster) and in a central meta-cleavage pathway (pcm genes) were also identified. Furthermore, the genes encoding the peripheral pathways for the catabolism of p-hydroxybenzoate (pob), benzoate (ben), quinate (qui), phenylpropenoid compounds (fcs, ech, vdh, cal, van, acd and acs), phenylalanine and tyrosine (phh, hpd) and n-phenylalkanoic acids (fad) were mapped in the chromosome of P. putida KT2440. Although a repetitive extragenic palindromic (REP) element is usually associated with the gene clusters, a supraoperonic clustering of catabolic genes that channel different aromatic compounds into a common central pathway (catabolic island) was not observed in P. putida KT2440. The global view on the mineralization of aromatic compounds by P. putida KT2440 will facilitate the rational manipulation of this strain for improving biodegradation/biotransformation processes, and reveals this bacterium as a useful model system for studying biochemical, genetic, evolutionary and ecological aspects of the catabolism of aromatic compounds.

Adipates↗
PubMed1982

Molecular cloning, genomic analysis, and biological properties of rat leukemia virus and the onc sequences of Rasheed rat sarcoma virus.

Rasheed rat sarcoma virus (RaSV) has been shown to code for a protein of 29,000 Mr not present in replication-competent rat type C helper virus (RaLV)-infected cells. This protein is a fused gene product consisting of a portion of the RaLV p15 gag protein and the transformation-specific 21,000 Mr (p21) ras protein, which is also found in Harvey murine sarcoma virus. We now report the molecular cloning of both the SD-1 (Sprague-Dawley) strain of RaLV and the transforming ras sequences of RaSV. Heteroduplex analysis of these cloned DNAs demonstrated that the RaSV ras gene (v-Ra-ras) was inserted into the rat type C viral genome with a small deletion of RaLV genetic information in the 5' region of the gag gene and that the v-Ra-ras gene (0.72 kilobase pair) is homologous to and colinear with the p21 ras gene of Harvey murine sarcoma virus (v-Ha-ras). Restriction enzyme mapping confirmed the homology demonstrated by heteroduplex mapping, showing strong site conservation of restriction endonucleases known to cleave v-Ha-ras. Cloned v-Ra-ras DNA transformed NIH 3T3 cells, inducing the synthesis of the p29 RaSVgag-ras protein.

Base Sequence↗
PubMed2006

Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis.

Human T-lymphotropic virus type 3 (HTLV-3) is a new virus recently identified in two primate hunters in Central Africa. Limited sequence analysis shows that HTLV-3 is distinct from HTLV-1 and HTLV-2 but is genetically similar to simian T-lymphotropic virus type 3 (STLV-3). We report here the first complete HTLV-3 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocytes from an HTLV-3-infected person. The HTLV-3(2026ND) genome is 8,917 bp long and is genetically equidistant from HTLV-1 and HTLV-2, sharing about 62% identity. Phylogenetic analysis of all gene regions confirms this relationship and shows that HTLV-3 falls within the diversity of STLV-3, suggesting a primate origin. However, HTLV-3(2026ND) is unique, sharing only 87% to 92% sequence identity with STLV-3. SimPlot and phylogenetic analysis did not reveal any evidence of genetic recombination with either HTLV-1, HTLV-2, or STLV-3. Molecular dating estimates that the ancestor of HTLV-3 is as old as HTLV-1 and HTLV-2, with an inferred divergence time of 36,087 to 54,067 years ago. HTLV-3 has a prototypic genomic structure, with all enzymatic, regulatory, and structural proteins preserved. Like STLV-3, HTLV-3 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains a unique activator protein-1 transcription factor upstream of the 21-bp repeat elements. A PDZ motif, like that in HTLV-1, which is important for cellular signal transduction and transformation, is present in the C terminus of the HTLV-3 Tax protein. A basic leucine zipper region located in the antisense strand of HTLV-1, believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-3. The ancient origin of HTLV-3, the broad distribution of STLV-3 in Africa, and the propensity of STLVs to cross species into humans all suggest that HTLV-3 may be prevalent and support the need for expanded surveillance for this virus.

Amino Acid Sequence↗
PubMed2005

Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion.

BACKGROUND: The malaria parasite Plasmodium must complete a complex developmental life cycle within Anopheles mosquitoes before it can be transmitted into the human host. One day after mosquito infection, motile ookinetes traverse the midgut epithelium and, after exiting to its basal site facing the hemolymph, develop into oocysts. Previously, we have identified hemolymph factors that can antagonize or promote parasite development. RESULTS: We profiled on a genomic scale the transcriptional responses of the A. gambiae midgut to P. berghei and showed that more than 7% of the assessed mosquito transcriptome is differentially regulated during invasion. The profiles suggested that actin- and microtubule-cytoskeleton remodeling is a major response of the epithelium to ookinete penetration. Other responses encompass components of innate immunity, extracellular-matrix remodeling, and apoptosis. RNAi-dependent gene silencing identified both parasite antagonists and agonists among regulators of actin dynamics and revealed that actin polymerization is inhibitory to the invading parasite. Combined transcriptional and reverse-genetic analysis further identified an unexpected dual role of the lipid-trafficking machinery of the hemolymph for both parasite and mosquito-egg development. CONCLUSIONS: We conclude that the determinants of malaria-parasite development in Anopheles include components not only of systemic humoral immunity but also of intracellular, local epithelial reactions. These results provide novel mechanistic insights for understanding malaria transmission in the mosquito vector.

Actins↗
PubMed2004

Characterisation of a new Leishmania META gene and genomic analysis of the META cluster.

The META1 gene of Leishmania is upregulated in metacyclic promastigotes and encodes a 12 kDa virulence-related protein, conserved in all Leishmania species analysed. In this study, the genomic region adjacent to the Leishmania amazonensis META1 gene was characterised and compared to the Leishmania major META1 locus as well as to syntenic loci identified in Trypanosoma brucei and Trypanosoma cruzi. Three new genes expressed with increased abundance of steady state mRNA in L. amazonensis promastigotes were identified, two of which are upregulated in stationary phase promastigotes, sharing the pattern of expression previously described for the META1 mRNA. One of these new genes, named META2, encodes a polypeptide of 444 amino acid residues with a repetitive structure showing three repeats of the META domain (defined as a small domain family found in the Leishmania META1 protein and in bacterial proteins hypothetically secreted and/or implicated in motility) and a carboxyl-terminal region similar to several putative calpain-like proteins of Trypanosoma and Leishmania.

Amino Acid Sequence↗
PubMed1992

Genomic analysis of Theileria sergenti stocks in Japan with DNA probes.

Restriction fragment length polymorphisms of Theileria sergenti DNA from 18 different infections of cattle in 14 locations in Japan were analyzed by Southern blotting using T. sergenti genomic DNA fragments as probes. Probe pTs 2 hybridized with four fragments in BamHI digested piroplasm DNA, at 8.0, 7.3, 6.0 and 3.4 kb. Probe pTs 11-D1 hybridized with multiple fragments. With each probe, polymorphisms were observed among stocks from different locations. However, there was no correlation between the patterns of hybridization bands and the locations where parasites were collected. Analysis of the hybridization patterns of stocks obtained from individual cattle in the same grazing areas showed an almost identical pattern.

Animals↗
PubMed1999

Sequences of European wheat mosaic virus and oat golden stripe virus and genome analysis of the genus furovirus.

The complete nucleotide sequences of both RNAs of oat golden stripe virus (OGSV) and a wheat-infecting furovirus isolate from France, previously thought to be soil-borne wheat mosaic virus (SBWMV), have been determined. Both viruses had a similar genomic organisation to SBWMV and Chinese wheat mosaic virus, the two other furoviruses previously sequenced but had <70% nucleotides identical to them. The French isolate has been named European wheat mosaic virus (EWMV). Phylogenetic analyses supported the recognition of these isolates as distinct viruses in the genus Furovirus. Analysis of the coat protein readthrough domain on RNA2 of all furoviruses strongly predicts two mutually compatible conserved transmembrane domains that may be significant for fungus transmission. The second of these regions is eliminated by a deletion in the isolate of OGSV studied. Leaky opal (UGA) stop codons occur on both RNAs of all four furoviruses characterised and, in common with most other leaky opal codons identified in plant viruses, they are followed by a CGG codon.

Amino Acid Sequence↗
PubMed1992

Effects of ionizing radiation on a plant genome: analysis of two Arabidopsis transparent testa mutations.

Ionizing radiation is known to cause chromosomal alterations such as inversions and deletions and has been used extensively for inducing mutations. In Arabidopsis, two methods for the isolation of genes identified on the basis of mutant phenotypes--genomic subtraction and chromosome walking--either rely on or are greatly facilitated by the availability of these types of mutations. This article gives a detailed characterization of ionizing radiation-induced mutations in plants. The Arabidopsis genes encoding chalcone flavanone isomerase (CHI) and dihydroflavonol 4-reductase (DFR) were cloned and found to correspond to two transparent testa loci. A CHI allele, generated by fast-neutron irradiation, consisted of an inversion within the gene. A 272-bp fragment from 38 centimorgans away on the same chromosome was transferred to one end of this inversion. A DFR allele, induced by x-irradiation, contained two deletions and an inversion of the 2.8-centimorgan intervening region. Sequence analysis of the break points in both mutants indicate that repair of radiation-induced damage involves mechanisms similar or identical to those that mediate the integration of foreign sequences into the genome. The chromosome rearrangements found in these mutants have important implications for the use of ionizing radiation-induced alleles in classical and molecular genetic experiments in plants.

Alcohol Oxidoreductases↗
PubMed2005

Identifying sigma factors in Mycobacterium smegmatis by comparative genomic analysis.

Mycobacterium smegmatis is a saprophytic species that has been used for 15 years as a model to perform heterologous regulation and virulence studies of Mycobacterium tuberculosis. Members of the extracytoplasmic sigma factors family, which are required for adaptive responses to various environmental stresses, are responsible for some of the virulence traits of M. tuberculosis. A bioinformatic search on the genome of M. smegmatis has predicted the existence of 26 sigma factors, which is twice the number that are present in M. tuberculosis. A phylogenetic analysis has shown that despite this high number of sigma factors the orthologs of the genes sigC, sigI and sigK of M. tuberculosis are absent in the M. smegmatis genome. Several sigma factors are specific for M. smegmatis, with a special enrichment in the sigH and, to a lesser extent, in the sigJ and sigL subfamily, pinpointing the potential variability of the repertoire of adaptive response in this saprophytic species.

Adaptation, Physiological↗
PubMed2001

Genome analysis of Agrobacterium tumefaciens: linkage map and genetic features of the left region of the linear chromosome.

In addition to a unique tumor-inducing (Ti) plasmid, the plant pathogenic bacterium Agrobacterium tumefaciens has an unconventional chromosomal organization. Our previous studies on A. tumefaciens MAFF301001 revealed that it possesses a 2 Mb linear and a 2.8 Mb circular chromosome plus a 206.479 kbp Ti plasmid (pTi-SAKURA). In this study, a linkage map for the left half of its linear chromosome covering a 900 kbp region was constructed and the number of potential genes existing in the region was estimated. The linkage map consists of 31 BAC and 8 lambda phage recombinants without any gaps. It confirmed the size and all the structural landmarks indicated in the corresponding region of our previously constructed physical map for the linear chromosome. Sequencing analysis of the end-regions of each linking clone led to the identification of 6 genes and another 27 potential genes or ORFs, including genes and/or gene clusters responsible for homologous recombination (ruvB), trehalose/maltose sugar transport (thuR, thuG) and alanine catabolism (dadR). Two virulence-related gene homologues (attK and celB), previously reported in the circular chromosome of a different strain of A. tumefaciens were found in this region. These findings will provide a ready-to-use linkage map for further functional analysis of the linear chromosome.

Agrobacterium tumefaciens↗
PubMed1998

Quantitative whole-genome analysis of DNA-protein interactions by in vivo methylase protection in E. coli.

A global methylation-based technique was used to identify, display, and quantitate the in vivo occupancy of numerous protein-binding sites within the Escherichia coli genome. The protein occupancy profiles of these sites showed variation across different growth conditions and genetic backgrounds. Of the 25 sites identified in this study, 24 occurred within 5' noncoding regions. Protein occupancy at 13 of these sites was supported by independent biochemical and genetic evidence. Most of the remaining 12 sites fell upstream of genes with no previously known function. A multivariate statistical analysis was utilized to group such uncharacterized genes with well-characterized ones, providing insights into their function based on a common pattern of transcriptional regulation.

DNA Modification Methylases↗
PubMedDate not supplied

Array-based genomic analysis of screen-detected Gleason score 6 and 7 prostatic adenocarcinomas.

BACKGROUND: Prostate cancer is known for its heterogeneous histological appearance. It is currently not clear whether this histological heterogeneity is also reflected in the genomic composition of a tumor. MATERIALS AND METHODS: The cancer DNA's were retrieved from the European Randomized Study of Screening for Prostate Cancer section Rotterdam (ERSPC). Tumors with volumes 1.0-1.5 ml and a Gleason score of 3+3 or 3+4 were selected. Comparative genomic hybridization with a 3500-element BAC array was used to detect differences in the genetic content of Gleason patterns 3 and 4. RESULTS: A total of 1155 gains and 583 losses were discriminated in 10 G3 areas; 768 gains and 497 losses were detected in 7 G4 regions. Frequent losses included chromosome arms 6q, 8p and 13q, while frequent gains were seen on 7q and 8q. There were no significant differences between Gleason patterns 3 and 4, or between Gleason grades within one cancer. CONCLUSION: Histological heterogeneity, defined by Gleason grades 3 and 4, does not have a genomic counterpart. Furthermore, these asymptomatic screen-detected prostate carcinomas have genetic signatures comparable with those commonly seen in symptomatic cancers.

Adenocarcinoma↗
PubMedDate not supplied

[Comparative genome analysis of Helicobacter pylori strains].

DNA macroarrays were used to characterize 17 Helicobacter pylori strains isolated in four geographic regions of Russia (Moscow, St. Petersburg, Kazan, and Novosibirsk). Of all genes, 1272 (81%) proved to occur in all strains and to constitute a functional core of the genome, and 293 (18.7%) were strain-specific and greatly varied among the H. pylori strains. Most (71%) of the latter had unknown functions; the remainder included restriction-modification genes (3-9%), transposition genes (2-4%), and genes coding for outer membrane proteins (2-4%). The Russian H. pylori strains did not differ in genome organization or in the number and distribution of strain-specific genes from strains isolated in other countries.

Bacterial Proteins↗
PubMed1997

Neural network prediction of translation initiation sites in eukaryotes: perspectives for EST and genome analysis.

Translation in eukaryotes does not always start at the first AUG in an mRNA, implying that context information also plays a role. This makes prediction of translation initiation sites a non-trivial task, especially when analysing EST and genome data where the entire mature mRNA sequence is not known. In this paper, we employ artificial neural networks to predict which AUG triplet in an mRNA sequence is the start codon. The trained networks correctly classified 88% of Arabidopsis and 85% of vertebrate AUG triplets. We find that our trained neural networks use a combination of local start codon context and global sequence information. Furthermore, analysis of false predictions shows that AUGs in frame with the actual start codon are more frequently selected than out-of-frame AUGs, suggesting that our networks use reading frame detection. A number of conflicts between neural network predictions and database annotations are analysed in detail, leading to identification of possible database errors.

Amino Acid Sequence↗
PubMed2002

Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease.

Historically, the first six recorded cholera pandemics occurred between 1817 and 1923 and were caused by Vibrio cholerae O1 serogroup strains of the classical biotype. Although strains of the El Tor biotype caused sporadic infections and cholera epidemics as early as 1910, it was not until 1961 that this biotype emerged to cause the 7th pandemic, eventually resulting in the global elimination of classical biotype strains as a cause of disease. The completed genome sequence of 7th pandemic El Tor O1 strain N16961 has provided an important tool to begin addressing questions about the evolution of V. cholerae as a human pathogen and environmental organism. To facilitate such studies, we constructed a V. cholerae genomic microarray that displays over 93% of the predicted genes of strain N16961 as spotted features. Hybridization of labeled genomic DNA from different strains to this microarray allowed us to compare the gene content of N16961 to that of other V. cholerae isolates. Surprisingly, the results reveal a high degree of conservation among the strains tested. However, genes unique to all pandemic strains as well as genes specific to 7th pandemic El Tor and related O139 serogroup strains were identified. These latter genes may encode gain-of-function traits specifically associated with displacement of the preexisting classical strains in South Asia and may also promote the establishment of endemic disease in previously cholera-free locations.

Cholera↗