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Results for “full genomic sequence”

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At least 127 records · Page 7Linked to original sources

PubMed2002

Mother-to-child HIV type 1 transmission in Argentina: BF recombinants have predominated in infected children since the mid-1980s.

The molecular epidemiology of HIV-1 in Argentina is more complex than was previously appreciated. One circulating recombinant form, CRF12_BF, and many related BF recombinant forms predominate in the capital city, Buenos Aires. This study of HIV-1 subtypes acquired perinatally between 1984 and 2000 has permitted, for the first time, a reconstruction of the history of BF recombination in Argentina. Sequencing of a partial genome region from the beginning of vpu to the beginning of env(gp120), which spans a breakpoint common in most contemporary Argentine BF recombinants, enabled samples to be rapidly screened. Among 23 children born between 1984 and 2000, 15 including 1 child born in 1986, harbored a BF recombinant. Thirteen of the 15 recombinants shared a common breakpoint at the 5' end of env(gp120). Full genome sequencing of two viruses, from 1986 and 1987, respectively, revealed them to be genetically related but not identical to CRF12_BF. Both contained more subtype B sequence than did CRF12_BF. BF recombinants related to CRF12_BF have been in circulation in Buenos Aires since 1986 and continue to predominate in perinatal transmissions.

Adolescent↗

PubMed2003

From genes to genomes: universal scale-invariant properties of microbial chromosome organisation.

The availability of complete genome sequences for a large variety of organisms is a major advance in understanding genome structure and function. One attribute of genome structure is chromosome organisation in terms of gene localisation and orientation. For example, bacterial operons, i.e. clusters of co-oriented genes that form transcription units, enable functionally related genes to be expressed simultaneously. The description of genome organisation was pioneered with the study of the distribution of genes of the Escherichia coli partial genetic map before the full genome sequence was known. Deploying powerful techniques from circular statistics and signal processing, we revisit the issue of gene localisation and orientation using 89 complete microbial chromosomes from the eubacterial and archaeal domains. We demonstrate that there is no characteristic size pertinent to the description of chromosome structure, e.g. there does not exist any single length appropriate to describe gene clustering. Our results show that, for all 89 chromosomes, gene positions and gene orientations share a common form of scale-invariant correlations known as "long-range correlations" that we can reveal for distances from the gene length, up to the chromosome size. This observation indicates that genes tend to assemble and to co-orient over any scale of observation greater than a few kilobases. This unexpected property of chromosome structure can be portrayed as an operon-like organisation at all scales and implies that a complete scale range extending over more than three orders of magnitudes of chromosome segment lengths is necessary to properly describe prokaryotic genome organisation. We propose that this pattern results from the effects of the superhelical context on gene expression coupled with the structure and dynamics of the nucleoid, possibly accommodating the diverse gene expression profiles needed during the different stages of cellular life.

Archaea↗

PubMed1998

Short-sequence DNA repeats in prokaryotic genomes.

Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneous. SSRs are encountered in many different branches of the prokaryote kingdom. They are found in genes encoding products as diverse as microbial surface components recognizing adhesive matrix molecules and specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs function at various levels of gene expression regulation. Variations in the number of repeat units per locus or changes in the nature of the individual repeat sequences may result from recombination processes or polymerase inadequacy such as slipped-strand mispairing (SSM), either alone or in combination with DNA repair deficiencies. These rather complex phenomena can occur with relative ease, with SSM approaching a frequency of 10(-4) per bacterial cell division and allowing high-frequency genetic switching. Bacteria use this random strategy to adapt their genetic repertoire in response to selective environmental pressure. SSR-mediated variation has important implications for bacterial pathogenesis and evolutionary fitness. Molecular analysis of changes in SSRs allows epidemiological studies on the spread of pathogenic bacteria. The occurrence, evolution and function of SSRs, and the molecular methods used to analyze them are discussed in the context of responsiveness to environmental factors, bacterial pathogenicity, epidemiology, and the availability of full-genome sequences for increasing numbers of microorganisms, especially those that are medically relevant.

Adhesins, Bacterial↗

PubMed2001

GeneOrder: comparing the order of genes in small genomes.

MOTIVATION: The recent rapid rise in the availability of whole genome DNA sequence data has led to bottlenecks in their complete analysis. Specifically, there is a need for software tools that will allow mining of gene and putative gene data at a whole genome level. These new tools will complement the current set already in use for studying specific aspects of individual genes and putative genes in detail. A key software challenge is to make them user-friendly, without losing their flexibility and capability for use in research. RESULTS: The creation of GeneOrder-a web-based interactive, computational tool-allows researchers to compare the order of genes in two genomes. It has been tested on full genome sequence data for viruses, mitochondria and chloroplasts that were obtained from the NCBI GenBank database. It is accessible at http://www.bif.atcc.org/GENEOrder/index.html. GeneOrder prepares the comparison in table form, listing the order of similar genes. Hyperlinks are provided from this output; these lead to the 'Protein Coding Regions' in the NCBI database.

Animals↗

PubMed2006

Identification of hepatitis B virus subgenotype A3 in rural Gabon.

An hepatitis B virus (HBV) molecular survey was conducted in five remote villages in the equatorial forest in Gabon, Central Africa. Two hundred seventy out of 311 inhabitants (86.8%) were HBV-infected or had evidence of past HBV infection. Chronic hepatitis corresponding to hepatitis B surface antigen (HBsAg) positivity was suspected in 27 (8.6%) of the HBV-infected subjects. High HBV viral loads were detected mainly in children aged 4-7 years. The pre-S/S domains were sequenced in 13 cases and 12 strains belonged to HBV-A genotype. In one case we found evidence for recombination between genotypes A and E. Phylogenetic analysis revealed that Gabonese HBV strains were distinct from HBV-A subgenotypes (A1 and A2). These new HBV strains from Gabon clustered with previously reported HBV-A3 subgenotype strains from Cameroon and Democratic Republic of Congo. The analysis of the pre-S2 domain allowed us to determine two amino acid substitutions (N/152/S and N/174/T) specific to the Central African HBV-A3 subgenotype strains and one amino acid substitution (P/155/Q) unique to these new Gabonese HBV-A3 subgenotype isolates. Two full genome sequences of two new Gabonese HBV isolates are also presented and confirm the distinctive HBV-Gab-A3 cluster.

Adolescent↗

PubMed2000

Human mutations in glucose 6-phosphate dehydrogenase reflect evolutionary history.

Glucose 6-phosphate dehydrogenase (G6PD) is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. Inherited G6PD deficiency is associated with either episodic hemolytic anemia (triggered by fava beans or other agents) or life-long hemolytic anemia. We show here that an evolutionary analysis is a key to understanding the biology of a housekeeping gene. From the alignment of the amino acid (aa) sequence of 52 glucose 6-phosphate dehydrogenase (G6PD) species from 42 different organisms, we found a striking correlation between the aa replacements that cause G6PD deficiency in humans and the sequence conservation of G6PD: two-thirds of such replacements are in highly and moderately conserved (50-99%) aa; relatively few are in fully conserved aa (where they might be lethal) or in poorly conserved aa, where presumably they simply would not cause G6PD deficiency. This is consistent with the notion that all human mutants have residual enzyme activity and that null mutations are lethal at some stage of development. Comparing the distribution of mutations in a human housekeeping gene with evolutionary conservation is a useful tool for pinpointing amino acid residues important for the stability or the function of the corresponding protein. In view of the current explosive increase in full genome sequencing projects, this tool will become rapidly available for numerous other genes.

Amino Acid Sequence↗

PubMed2003

[Genome-wide non-sequencing strategies for bacterial genome comparison: the necessity and an analysis of the variable bacterial world].

A tremendous success in bacterial genome sequencing has been achieved during the recent years; it resulted in making available, for analysis, multiple sequences of different bacterial genomes, including such pathogens as causative agents of syphilis, typhus, and tuberculosis as well as such organisms like archaebacterias living under extreme conditions. A comparative analysis of bacterial genomes leads to conclusions, which have a general biological value, and, in particular, to the conclusions about mechanisms and evolution rate as well as about the variability of genomes and interrelation between organisms and their habitat. On the other hand, the analysis reveals specific features of separate bacterial species responsible for their pathogenicity and ability to avoid the destruction of the host immune system as well as for adaptation to exist within a certain ecological niche. However, the variability of bacterial genomes is so high that methods, which enable to evaluate the variability without full genome sequencing, are needed to depict adequately the evolution and ecological characteristics of the prokaryotic world and to develop new effective therapeutics and diagnostic tools. The survey covers two approaches to such comparative analysis, i.e. DNA arrays and subtractive hybridization. The advantages and disadvantages of each approach are discussed and the necessity in a new approach combining the positive features of the two mentioned approaches is substantiated.

DNA, Bacterial↗

PubMed2001

The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species.

Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a vast number of signals in metazoans. The importance of the Tec family of kinases was immediately recognized when, in 1993, mutations in the gene encoding Bruton's tyrosine kinase (Btk) were reported to cause the human disease X-linked agammaglobulinemia (XLA). Since then, additional kinases belonging to this family have been isolated, and the availability of full genome sequences allows identification of all members in selected species enabling phylogenetic considerations. Tec kinases are endowed with Pleckstrin homology (PH) and Tec homology (TH) domains and are involved in diverse biological processes related to the control of survival and differentiation fate. Membrane translocation resulting in the activation of Tec kinases with subsequent Ca2+ release seems to be a general feature. However, nuclear translocation may also be of importance. The purpose of this essay is to characterize members of the Tec family and discuss their involvement in signaling. The three-dimensional structure, expression pattern and evolutionary aspects will also be considered.

Amino Acid Sequence↗

PubMed2005

Nucleotide mutations associated with hepatitis B e antigen negativity.

One hundred and forty four patients with chronic hepatitis B were tested to identify new mutations associated with hepatitis B e antigen (HBeAg) negativity, using a full genome sequence analysis. All the patients were Chinese and had hepatitis B virus infection of genotype C. Patients with none of the pre-core or core promoter mutations were significantly (P < 0.001) less common in the group with anti-HBe (13%) than in the group with HBeAg (56%). The complete nucleotide sequence was determined in four anti-HBe-positive patients who had neither pre-core nor core promoter mutations and in five HBeAg-positive patients who also had neither of these mutations (the groups were matched for age and sex). Six mutations were found to be significantly more common in the former group than in the latter: G529A (3/4 vs. 0/5), C934A (4/4 vs. 1/5), A1053G (4/4 vs. 1/5), G1915T/A (4/4 vs. 0/5), T2005C/A (4/4 vs. 0/5), and C3026T (3/4 vs. 0/5). Three of the six mutations were significantly more common in the four anti-HBe-positive patients who had neither pre-core nor core promoter mutations, compared to 11 HBeAg-positive patients who had pre-core and core promoter mutations, and also compared to 15 anti-HBe-positive patients who had pre-core and core promoter mutations, suggesting further the specificity of these mutations. Of the six mutations, two resulted in amino acid substitution in the polymerase protein, and one is located near the enhancer I region. The results suggest that the six newly discovered mutations are associated with HBeAg negativity.

Adolescent↗

PubMed2006

Tracing the history of hepatitis B virus genotype D in western Japan.

The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D (HBV/D), however, is widespread in a small area of Western Japan, where the Gianotti-Crosti syndrome caused by HBV subtype ayw, which is suspected to be HBV/D, was endemic in the 1970s. The aim of the study was to elucidate its origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was done in 363 patients with HBV infection. The year of birth was checked in patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which were obtained from a single carrier with a 19-year-interval, were analyzed. An evolutionary rate, the date of the most recent common ancestor, and the effective number of HBV/D infections were calculated. Fifty-two of 363 patients were infected with HBV/D, and 39 were born in 1970s. In a phylogenetic tree, the 20 HBV/D strains produced a definite cluster, and the evolutionary rate was calculated to be 5.4 x 10(-5) nucleotide substitutions/site/year. The root of the tree was estimated to be in approximately 1,900 and began to spread from the 1940s, leading to a rapid increase of infected patients in the 1970s. From these results, it is suspected that HBV/D was likely transmitted to the area investigated approximately 100 years ago and then spread widely in the 1970s. From the history of the area and the genetic analysis, HBV/D in this area was speculated to be of Russian origin.

Acrodermatitis↗

PubMed2006

Proteomic and bioinformatic analysis of iron- and sulfur-oxidizing Acidithiobacillus ferrooxidans using immobilized pH gradients and mass spectrometry.

A comparative analysis of the protein composition of Acidithiobacillus ferrooxidans cells grown on elemental sulfur and ferrous iron was performed. A newly developed protocol involving immobilized pH gradients, improved protein reduction, mass spectrometry protein identification and full genome sequence information was applied. This approach resulted in more than 1300 protein spots displayed in broad and basic pH ranges, the best A. ferrooxidans proteome resolution to date. A comparative image analysis revealed that the proteome was significantly influenced by the growth type, and allowed for the detection of many physiologically important proteins. Among them were sulfate adenylyltransferase and sulfide dehydrogenase, which are involved in sulfate assimilation and sulfide metabolism, respectively. Many other proteins were related to important processes like cell attachment and electron transport. Co-migration of phosphate and sulfate transport proteins was also observed.

Acidithiobacillus↗

PubMed2006

The proteome of Mannheimia succiniciproducens, a capnophilic rumen bacterium.

Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is an industrially important bacterium as an efficient succinic acid producer. Recently, its full genome sequence was determined. In the present study, we analyzed the M. succiniciproducens proteome based on the genome information using 2-DE and MS. We established proteome reference map of M. succiniciproducens by analyzing whole cellular proteins, membrane proteins, and secreted proteins. More than 200 proteins were identified and characterized by MS/MS supported by various bioinformatic tools. The presence of proteins previously annotated as hypothetical proteins or proteins having putative functions were also confirmed. Based on the proteome reference map, cells in the different growth phases were analyzed at the proteome level. Comparative proteome profiling revealed valuable information to understand physiological changes during growth, and subsequently suggested target genes to be manipulated for the strain improvement.

Animals↗

PubMed2002

Prospects for functional genomics in Schizosaccharomyces pombe.

Schizosaccharomyces pombe is well established as an experimental organism for basic research, with well developed technologies for molecular biology, genetics and cell biology. Its full genome sequence has recently been published. Here, the prerequisites for functional genomics studies in Sch. pombe are examined and compared with those of some established prominent functional genomics model organisms, especially Saccharomyces cerevisiae. It is argued that functional genomics studies in certain areas of cellular and molecular biology could potentially be more efficiently performed in Sch. pombe than in most other experimental organisms.

Drug Evaluation, Preclinical↗

PubMed2006

Natural synchronisation for the study of cell division in the green unicellular alga Ostreococcus tauri.

Ostreococcus tauri (Prasinophyceae) is a marine unicellular green alga which diverged early in the green lineage. The interest of O. tauri as a potential model to study plant cell division is based on its key phylogenetic position, its simple binary division, a very simple cellular organisation and now the availability of the full genome sequence. In addition O. tauri has a minimal yet complete set of cell cycle control genes. Here we show that division can be naturally synchronised by light/dark cycles and that organelles divide before the nucleus. This natural synchronisation, although being only partial, enables the study of the expression of CDKs throughout the cell cycle. The expression patterns of OtCDKA and OtCDKB were determined both at the mRNA and protein levels. The single OtCDKA gene is constantly expressed throughout the cell cycle, whereas OtCDKB is highly regulated and expressed only in S/G2/M phases. More surprisingly, OtCDKA is not phosphorylated at the tyrosine residue, in contrast to OtCDKB which is strongly phosphorylated during cell division. OtCDKA kinase activity appears before the S phase, indicating a possible role of this protein in the G1/S transition. OtCDKB kinase activity occurs later than OtCDKA, and its tyrosine phosphorylation is correlated to G2/M, suggesting a possible control of the mitotic activity. To our knowledge this is the first organism in the green lineage which showed CDKB tyrosine phosphorylation during cell cycle progression.

Base Sequence↗

PubMed2005

Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). We demonstrated PAH mutational spectrum from patients with PKU, including 10 novel and 3 tetrahydrobiopterin (BH(4))-responsive mutations. In this study, 11 PAH missense mutations, including 6 novel mutations (P69S, G103S, L293M, G332V, S391I, A447P) found in our previous study, 2 mutations common in east Asian patients with PKU (R243Q, R413P), and 3 tetrahydrobiopterin (BH(4))-responsive mutations (R53H, R241C, R408Q) have been functionally and structurally analyzed. METHODS: A transient protein overexpression system and an in vitro BH(4)-responsiveness study were used. The effects of PAH missense mutations on the PAH protein structure were also analyzed. To determine the conservation of 12 mutated residues, PAH was aligned using BLAST against full genomic sequences of 221 different species. Model structures of PAH protein and the composite tetramer were constructed using the software program, SHEBA. RESULTS: No PAH activity was detected for some mutants. However, the residual activities associated with other mutants ranged over a wide spectrum. The missense mutations responsive to BH(4) were not highly conserved throughout the 43 species in the multiple sequence alignment that encode PAH. The composite model structure of PAH revealed that dimer stability was reduced in the BH(4)-responsive mutants, whereas tetramer stability remained normal. CONCLUSION: This expression study analyzed PAH mutations and model structures of mutant PAH proteins are proposed. Correlation between the proposed mutant PAH structures and functions are suggested.

Amino Acid Sequence↗

PubMed2006

Family of Tc1-like elements from fish genomes and horizontal transfer.

The involvement of horizontal transfer (HT) in the evolution of vertebrate transposable elements (TEs) is a matter of an ongoing debate. The phylogenetic relationships between Tc1 TEs, based on limited dataset have been previously used to infer a case of Tc1 HT between the genomes of fish and frogs. Here this hypothesis has been critically evaluated by the experimental approach including comparative data on the range of fish species available today. The distribution of a Tc1 subfamily of TE in selected fish species was investigated by PCR with a single primer complementary to ITRs and showed that they are widespread in the studied 17 fish species. They belong to five different subfamilies of Tc1 TEs, as revealed by the comparison with current genomic data for fish and amphibians. The original hypothesis would get much weaker support from the current data, although at least one novel potential and more convincing case of HT was identified between genomes of Perciformes fish. An interesting case of recombination-driven mobilisation of a degenerated TE by distantly related TE from different subfamily was discovered in the genome of pike. The occurrence of such cases widens the range of TE elements identifiable with the employed experimental approach. Further similar studies would help to explain the evolution of the multiple Tc1 lineages including species for which full genome sequences will not be available soon.

Animals↗

PubMed2025

Reversible phenotypic resistance to phage infection via capsule downregulation in Klebsiella pneumoniae.

Capsule loss is a major mechanism by which bacteria evade phage infection. This has traditionally been attributed to mutations in capsule biosynthesis genes. Here, we investigated phage resistance in Klebsiella pneumoniae, a medically relevant encapsulated bacterium. Phage infection rapidly selected for resistant acapsular cells. As expected, transcriptomic analysis revealed a marked downregulation of capsule biosynthesis genes. However, full genome sequencing showed that capsule loss occurred without evidence of mutations, and acapsular phage-resistant cells were able to rapidly restore their capsule once phage pressure was removed. These findings highlight that phage-driven selective pressure can act on non-heritable variation in gene expression, providing a faster and more flexible resistance mechanism compared to the traditional mutation-selection process. This reversible resistance may complicate predictability and limit the long-term efficacy of phage therapy.

Cell biology↗

PubMed2004

Pernicious plans revealed: Plasmodium falciparum genome wide expression analysis.

The asexual intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum is responsible for the majority of the clinical manifestations of malaria in humans. Although malaria has been studied for over a century, the elucidation of the full genome sequence of P. falciparum has now allowed for in-depth studies of gene expression throughout the entire intraerythrocytic stage. As the mainstays of anti-malarial chemotherapy become increasingly ineffective, we need a deeper understanding of fundamental plasmodial bioregulatory mechanisms to successfully subvert them. Recent gene expression studies have begun to examine different aspects of the IDC and are providing key insights into the basic mechanisms of Plasmodium gene regulation and are helping to define gene functions. However, to date, no transcription factor has been fully characterized from Plasmodium and the definitive identification of cis-acting regulatory elements along with their corresponding trans-acting partners is still lacking. The characterization of the transcriptome of P. falciparum is the first major step towards the understanding of the genome wide regulation of gene expression in this parasite. IDC expression data for almost every gene in the P. falciparum genome can now be publicly queried at and. The results of these studies suggest promising leads for identifying novel targets for anti-malarial therapeutics and vaccines in addition to providing a solid foundation for the ongoing elucidation of plasmodial gene expression.

Animals↗