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Flora J Logan-Klumpler,
Nishadi De Silva,
Ulrike Boehme,
Matthew B Rogers,
Giles Velarde,
Jacqueline A McQuillan,
Tim Carver,
Martin Aslett,
Christian Olsen, Sandhya Subramanian, [......],
Julian Parkhill,
Matthew Holden,
Omar S Harb,
Brian P Brunk,
Peter J Myler,
David Roos,
Mark Carrington,
Deborah F Smith,
Christiane Hertz-Fowler,
Matthew Berriman
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ABSTRACT: GeneDB (http://www.genedb.org) is a genome database for prokaryotic and eukaryotic pathogens and closely related organisms. The resource provides a portal to genome sequence and annotation data, which is primarily generated by the Pathogen Genomics group at the Wellcome Trust Sanger Institute. It combines data from completed and ongoing genome projects with curated annotation, which is readily accessible from a web based resource. The development of the database in recent years has focused on providing database-driven annotation tools and pipelines, as well as catering for increasingly frequent assembly updates. The website has been significantly redesigned to take advantage of current web technologies, and improve usability. The current release stores 41 data sets, of which 17 are manually curated and maintained by biologists, who review and incorporate data from the scientific literature, as well as other sources. GeneDB is primarily a production and annotation database for the genomes of predominantly pathogenic organisms.
Nucleic Acids Research 11/2011; 40(Database issue):D98-108. · 8.03 Impact Factor
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ABSTRACT: Rickettsiae are obligate intracellular parasites of eukaryotic cells that are the causative agents responsible for spotted fever and typhus. Their small genome (about 800 protein-coding genes) is highly conserved across species and has been postulated as the ancestor of the mitochondria. No genes that are required for glycolysis are found in the Rickettsia prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in both. A 2.4 Å resolution crystal structure of R. prowazekii fumarate hydratase, an enzyme catalyzing the third step of the tricarboxylic acid cycle pathway that ultimately converts phosphoenolpyruvate into succinyl-CoA, has been solved. A structure alignment with human mitochondrial fumarate hydratase highlights the close similarity between R. prowazekii and mitochondrial enzymes.
Acta Crystallographica Section F Structural Biology and Crystallization Communications 09/2011; 67(Pt 9):1123-8. · 0.51 Impact Factor
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ABSTRACT: Rickettsia prowazekii, a parasitic Gram-negative bacterium, is in the second-highest biodefense category of pathogens of the National Institute of Allergy and Infectious Diseases, but only a handful of structures have been deposited in the PDB for this bacterium; to date, all of these have been solved by the SSGCID. Owing to its small genome (about 800 protein-coding genes), it relies on the host for many basic biosynthetic processes, hindering the identification of potential antipathogenic drug targets. However, like many bacteria and plants, its metabolism does depend upon the type II fatty-acid synthesis (FAS) pathway for lipogenesis, whereas the predominant form of fatty-acid biosynthesis in humans is via the type I pathway. Here, the structure of the third enzyme in the FAS pathway, 3-ketoacyl-(acyl-carrier-protein) reductase, is reported at a resolution of 2.25 Å. Its fold is highly similar to those of the existing structures from some well characterized pathogens, such as Mycobacterium tuberculosis and Burkholderia pseudomallei, but differs significantly from the analogous mammalian structure. Hence, drugs known to target the enzymes of pathogenic bacteria may serve as potential leads against Rickettsia, which is responsible for spotted fever and typhus and is found throughout the world.
Acta Crystallographica Section F Structural Biology and Crystallization Communications 09/2011; 67(Pt 9):1118-22. · 0.51 Impact Factor
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Martin Aslett,
Cristina Aurrecoechea,
Matthew Berriman,
John Brestelli,
Brian P. Brunk,
Mark Carrington,
Daniel P. Depledge,
Steve Fischer,
Bindu Gajria,
Xin Gao, [......],
Dhileep Sivam,
Deborah F. Smith,
Ganesh Srinivasamoorthy,
Christian J. Stoeckert Jr, Sandhya Subramanian,
Ryan Thibodeau,
Adrian Tivey,
Charles Treatman,
Giles Velarde,
Haiming Wang
Nucleic Acids Research. 01/2010; 38:457-462.
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Martin Aslett,
Cristina Aurrecoechea,
Matthew Berriman,
John Brestelli,
Brian P Brunk,
Mark Carrington,
Daniel P Depledge,
Steve Fischer,
Bindu Gajria,
Xin Gao, [......],
Dhileep Sivam,
Deborah F Smith,
Ganesh Srinivasamoorthy,
Christian J Stoeckert, Sandhya Subramanian,
Ryan Thibodeau,
Adrian Tivey,
Charles Treatman,
Giles Velarde,
Haiming Wang
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ABSTRACT: TriTrypDB (http://tritrypdb.org) is an integrated database providing access to genome-scale datasets for kinetoplastid parasites, and supporting a variety of complex queries driven by research and development needs. TriTrypDB is a collaborative project, utilizing the GUS/WDK computational infrastructure developed by the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.org) to integrate genome annotation and analyses from GeneDB and elsewhere with a wide variety of functional genomics datasets made available by members of the global research community, often pre-publication. Currently, TriTrypDB integrates datasets from Leishmania braziliensis, L. infantum, L. major, L. tarentolae, Trypanosoma brucei and T. cruzi. Users may examine individual genes or chromosomal spans in their genomic context, including syntenic alignments with other kinetoplastid organisms. Data within TriTrypDB can be interrogated utilizing a sophisticated search strategy system that enables a user to construct complex queries combining multiple data types. All search strategies are stored, allowing future access and integrated searches. 'User Comments' may be added to any gene page, enhancing available annotation; such comments become immediately searchable via the text search, and are forwarded to curators for incorporation into the reference annotation when appropriate.
Nucleic Acids Research 10/2009; 38(Database issue):D457-62. · 8.03 Impact Factor
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Donna M Muzny,
Steven E Scherer,
Rajinder Kaul,
Jing Wang,
Jun Yu,
Ralf Sudbrak,
Christian J Buhay,
Rui Chen,
Andrew Cree,
Yan Ding, [......],
Jianling Zhou,
Yang Zhou,
David Nelson,
Hans Lehrach,
Richard Reinhardt,
Susan L Naylor,
Huanming Yang,
Maynard Olson,
George Weinstock,
Richard A Gibbs
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ABSTRACT: After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
Nature 05/2006; 440(7088):1194-8. · 36.28 Impact Factor
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Donna M. Muzny,
Steven E. Scherer,
Rajinder Kaul,
Jing Wang,
Jun Yu,
Ralf Sudbrak,
Christian J. Buhay,
Rui Chen,
Andrew Cree,
Yan Ding, [......],
Yang Zhou,
further contributors,
David Nelson,
Hans Lehrach,
Richard Reinhardt,
Susan L. Naylor,
Huanming Yang,
Maynard Olson,
George Weinstock,
Richard A. Gibbs
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ABSTRACT: After the completion of a draft human genome sequence1, the International Human Genome Sequencing Consortium has proceeded to finish2 and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B3. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
Nature 04/2006; 440(7088):1194-1198. · 36.28 Impact Factor
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Christopher K Raymond, Sandhya Subramanian,
Marcia Paddock,
Ruolan Qiu,
Chloe Deodato,
Anthony Palmieri,
Jean Chang,
Tana Radke,
Eric Haugen,
Arnie Kas,
David Waring,
Donald Bovee,
Robin Stacy,
Rajinder Kaul,
Maynard V Olson
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ABSTRACT: Currently, challenges exist to acquire long-range (hundreds of kilobase pairs) phase-discriminated sequence across substantial numbers of individuals. We have developed a straightforward method for isolating and characterizing specific genomic regions in a haplospecific manner. Real-time PCR is carried out to STS content map and genotype pools of fosmid clones arrayed in 384-well microtiter plates. Single-nucleotide polymorphisms, microsatellite markers, and insertion-deletion polymorphisms are used to differentiate the target region into haplotype-specific tiling paths. DNA of clones from these tiling paths is retrieved from the library and either sequenced by standard shotgun methods or amplified in vitro and sequenced by a primer-based, directed method. This approach provides convenient access to complete, haplotype-resolved resequencing data from multiple individuals across tens to hundreds of thousands of basepairs. We illustrate its implementation with a detailed example of more than 400 kbp from the human CFTR region, across 15 individuals, and summarize our experience applying it to many other human loci.
Genomics 01/2006; 86(6):759-66. · 3.02 Impact Factor
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Christopher K Raymond,
Arnold Kas,
Marcia Paddock,
Ruolan Qiu,
Yang Zhou, Sandhya Subramanian,
Jean Chang,
Anthony Palmieri,
Eric Haugen,
Rajinder Kaul,
Maynard V Olson
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ABSTRACT: Allelic variation in codons that specify amino acids that line the peptide-binding pockets of HLA's Class II antigen-presenting proteins is superimposed on strikingly few deeply diverged haplotypes. These haplotypes appear to have been evolving almost independently for tens of millions of years. By complete resequencing of 20 haplotypes across the approximately 100-kbp region that spans the HLA-DQA1, -DQB1, and -DRB1 genes, we provide a detailed view of the way in which the genome structure at this locus has been shaped by the interplay of selection, gene-gene interaction, and recombination.
Genome Research 10/2005; 15(9):1250-7. · 13.61 Impact Factor
