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Dive into the research topics where Christoph W. Sensen is active.

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Featured researches published by Christoph W. Sensen.


Nature Genetics | 1999

Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

Angela Brooks-Wilson; Michel Marcil; Susanne M. Clee; Lin-Hua Zhang; Kirsten Rump; M van Dam; Lu Yu; C. Brewer; Jennifer A. Collins; H.O. Molhuizen; O. Loubser; B.F. Ouelette; Keith Fichter; K.J. Ashbourne-Excoffon; Christoph W. Sensen; Steve Scherer; Stephanie Mott; Maxime Denis; D. Martindale; J. Frohlich; Kenneth Morgan; Ben F. Koop; Simon N. Pimstone; John J. P. Kastelein; Jacques Genest; Michael R. Hayden

Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).


Proceedings of the National Academy of Sciences of the United States of America | 2001

The complete genome of the crenarchaeon Sulfolobus solfataricus P2

Qunxin She; Rama K. Singh; Fabrice Confalonieri; Yvan Zivanovic; Ghislaine Allard; Mariana J. Awayez; Christina C.-Y. Chan-Weiher; Ib Groth Clausen; Bruce A. Curtis; Anick De Moors; G. Erauso; Cynthia Fletcher; Paul M. K. Gordon; Ineke Heikamp-de Jong; Alex C. Jeffries; Catherine Kozera; Nadine Medina; Xu Peng; Hoa Phan Thi-Ngoc; Peter Redder; Margaret E. Schenk; Cynthia Theriault; Niels Tolstrup; Robert L. Charlebois; W. Ford Doolittle; Michel Duguet; Terry Gaasterland; Roger A. Garrett; Mark A. Ragan; Christoph W. Sensen

The genome of the crenarchaeon Sulfolobus solfataricus P2 contains 2,992,245 bp on a single chromosome and encodes 2,977 proteins and many RNAs. One-third of the encoded proteins have no detectable homologs in other sequenced genomes. Moreover, 40% appear to be archaeal-specific, and only 12% and 2.3% are shared exclusively with bacteria and eukarya, respectively. The genome shows a high level of plasticity with 200 diverse insertion sequence elements, many putative nonautonomous mobile elements, and evidence of integrase-mediated insertion events. There are also long clusters of regularly spaced tandem repeats. Different transfer systems are used for the uptake of inorganic and organic solutes, and a wealth of intracellular and extracellular proteases, sugar, and sulfur metabolizing enzymes are encoded, as well as enzymes of the central metabolic pathways and motility proteins. The major metabolic electron carrier is not NADH as in bacteria and eukarya but probably ferredoxin. The essential components required for DNA replication, DNA repair and recombination, the cell cycle, transcriptional initiation and translation, but not DNA folding, show a strong eukaryal character with many archaeal-specific features. The results illustrate major differences between crenarchaea and euryarchaea, especially for their DNA replication mechanism and cell cycle processes and their translational apparatus.


Proceedings of the National Academy of Sciences of the United States of America | 2002

The analysis of 100 genes supports the grouping of three highly divergent amoebae: Dictyostelium, Entamoeba, and Mastigamoeba

Eric Bapteste; Henner Brinkmann; Jennifer A. Lee; Dorothy V. Moore; Christoph W. Sensen; Paul M. K. Gordon; Laure Duruflé; Terry Gaasterland; Philippe Lopez; Miklós Müller; Hervé Philippe

The phylogenetic relationships of amoebae are poorly resolved. To address this difficult question, we have sequenced 1,280 expressed sequence tags from Mastigamoeba balamuthi and assembled a large data set containing 123 genes for representatives of three phenotypically highly divergent major amoeboid lineages: Pelobionta, Entamoebidae, and Mycetozoa. Phylogenetic reconstruction was performed on ≈25,000 aa positions for 30 species by using maximum-likelihood approaches. All well-established eukaryotic groups were recovered with high statistical support, validating our approach. Interestingly, the three amoeboid lineages strongly clustered together in agreement with the Conosa hypothesis [as defined by T. Cavalier-Smith (1998) Biol. Rev. Cambridge Philos. Soc. 73, 203–266]. Two amitochondriate amoebae, the free-living Mastigamoeba and the human parasite Entamoeba, formed a significant sister group to the exclusion of the mycetozoan Dictyostelium. This result suggested that a part of the reductive process in the evolution of Entamoeba (e.g., loss of typical mitochondria) occurred in its free-living ancestors. Applying this inexpensive expressed sequence tag approach to many other lineages will surely improve our understanding of eukaryotic evolution.


The Lancet | 1999

Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux

Michel Marcil; Angela Brooks-Wilson; Susanne M. Clee; Kirsten Roomp; Lin-Hua Zhang; Lu Yu; Jennifer A. Collins; Marjel van Dam; Odell Loubster; B. F. Francis Ouellette; Christoph W. Sensen; Keith Fichter; Stephanie Mott; Maxime Denis; Betsie Boucher; Simon N. Pimstone; Jacques Genest; John J. P. Kastelein; Michael R. Hayden

BACKGROUND A low concentration of HDL cholesterol is the most common lipoprotein abnormality in patients with premature atherosclerosis. We have shown that Tangier disease, a rare and severe form of HDL deficiency characterised by a biochemical defect in cellular cholesterol efflux, is caused by mutations in the ATP-binding-cassette (ABC1) gene. This gene codes for the cholesterol-efflux regulatory protein (CERP). We investigated the presence of mutations in this gene in patients with familial HDL deficiency. METHODS Three French-Canadian families and one Dutch family with familial HDL deficiency were studied. Fibroblasts from the proband of each family were defective in cellular cholesterol efflux. Genomic DNA of each proband was used for mutation detection with primers flanking each exon of the ABC1 gene, and for sequencing of the entire coding region of the gene. PCR and restriction-fragment length polymorphism assays specific to each mutation were used to investigate segregation of the mutation in each family, and to test for absence of the mutation in DNA from normal controls. FINDINGS A different mutation was detected in ABC1 in each family studied. Each mutation either created a stop codon predicted to result in truncation of CERP, or altered a conserved aminoacid residue. Each mutation segregated with low concentrations of HDL-cholesterol in the family, and was not observed in more than 500 control chromosomes tested. INTERPRETATION These data show that mutations in ABC1 are the major cause of familial HDL deficiency associated with defective cholesterol efflux, and that CERP has an essential role in the formation of HDL. Our findings highlight the potential of modulation of ABC1 as a new route for increasing HDL concentrations.


Nature | 2009

Prepublication data sharing.

Ewan Birney; Thomas J. Hudson; Eric D. Green; Chris Gunter; Sean R. Eddy; John A. Rogers; Jennifer R. Harris; S D Ehrlich; Rolf Apweiler; C P Austin; L Berglund; Martin Bobrow; C. Bountra; Anthony J. Brookes; Anne Cambon-Thomsen; Nigel P. Carter; Rex L. Chisholm; Jorge L. Contreras; R M Cooke; William L. Crosby; Ken Dewar; Richard Durbin; Dyke Som.; Joseph R. Ecker; K El Emam; Lars Feuk; Stacey Gabriel; John Gallacher; William M. Gelbart; Antonio Granell

Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.


Nucleic Acids Research | 2015

BRENDA in 2015: exciting developments in its 25th year of existence

Antje Chang; Ida Schomburg; Sandra Placzek; Lisa Jeske; Marcus Ulbrich; Mei Xiao; Christoph W. Sensen; Dietmar Schomburg

The BRENDA enzyme information system (http://www.brenda-enzymes.org/) has developed into an elaborate system of enzyme and enzyme-ligand information obtained from different sources, combined with flexible query systems and evaluation tools. The information is obtained by manual extraction from primary literature, text and data mining, data integration, and prediction algorithms. Approximately 300 million data include enzyme function and molecular data from more than 30 000 organisms. The manually derived core contains 3 million data from 77 000 enzymes annotated from 135 000 literature references. Each entry is connected to the literature reference and the source organism. They are complemented by information on occurrence, enzyme/disease relationships from text mining, sequences and 3D structures from other databases, and predicted enzyme location and genome annotation. Functional and structural data of more than 190 000 enzyme ligands are stored in BRENDA. New features improving the functionality and analysis tools were implemented. The human anatomy atlas CAVEman is linked to the BRENDA Tissue Ontology terms providing a connection between anatomical and functional enzyme data. Word Maps for enzymes obtained from PubMed abstracts highlight application and scientific relevance of enzymes. The EnzymeDetector genome annotation tool and the reaction database BKM-react including reactions from BRENDA, KEGG and MetaCyc were improved. The website was redesigned providing new query options.


Environmental Science & Technology | 2011

Carbon and Sulfur Cycling by Microbial Communities in a Gypsum-Treated Oil Sands Tailings Pond

Esther Ramos-Padrón; Sylvain Bordenave; Shiping Lin; Iyswarya Mani Bhaskar; Xiaoli Dong; Christoph W. Sensen; Joseph Fournier; Gerrit Voordouw; Lisa M. Gieg

Oil sands tailings ponds receive and store the solid and liquid waste from bitumen extraction and are managed to promote solids densification and water recycling. The ponds are highly stratified due to increasing solids content as a function of depth but can be impacted by tailings addition and removal and by convection due to microbial gas production. We characterized the microbial communities in relation to microbial activities as a function of depth in an active tailings pond routinely treated with gypsum (CaSO(4)·2H(2)O) to accelerate densification. Pyrosequencing of 16S rDNA gene sequences indicated that the aerobic surface layer, where the highest level of sulfate (6 mM) but no sulfide was detected, had a very different community profile than the rest of the pond. Deeper anaerobic layers were dominated by syntrophs (Pelotomaculum, Syntrophus, and Smithella spp.), sulfate- and sulfur-reducing bacteria (SRB, Desulfocapsa and Desulfurivibrio spp.), acetate- and H(2)-using methanogens, and a variety of other anaerobes that have been implicated in hydrocarbon utilization or iron and sulfur cycling. The SRB were most abundant from 10 to 14 mbs, bracketing the zone where the sulfate reduction rate was highest. Similarly, the most abundant methanogens and syntrophs identified as a function of depth closely mirrored the fluctuating methanogenesis rates. Methanogenesis was inhibited in laboratory incubations by nearly 50% when sulfate was supplied at pond-level concentrations suggesting that in situ sulfate reduction can substantially minimize methane emissions. Based on our data, we hypothesize that the emission of sulfide due to SRB activity in the gypsum treated pond is also limited due to its high solubility and oxidation in surface waters.


Extremophiles | 2000

Two different and highly organized mechanisms of translation initiation in the archaeon Sulfolobus solfataricus

Niels Tolstrup; Christoph W. Sensen; Roger A. Garrett; Ib Groth Clausen

Abstract The translational starts of 144 Sulfolobus solfataricus genes have been determined by database comparison. Half the genes lie inside operons and the other half are at the start of an operon or single genes. A Shine–Dalgarno sequence is found upstream of the genes inside operons, but not for the first gene in an operon or isolated genes; this indicates that two different mechanisms are used for translation initiation in S. solfataricus. A box A transcriptional signal is found for the genes starting an operon or isolated genes, but not for the genes inside an operon. The box A signal is located about 27 nt upstream of the start codon, which implies that little or no upstream sequence is available for translation initiation for this group of genes. This finding is discussed.


Journal of Biotechnology | 2013

Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest.

Mei Xiao; Ye Zhang; Xue Chen; Eun-Jeong Lee; Carla J. S. Barber; Romit Chakrabarty; Isabel Desgagné-Penix; Tegan M. Haslam; Yeon-bok Kim; Enwu Liu; Gillian MacNevin; Sayaka Masada-Atsumi; Darwin W. Reed; Jake Stout; Philipp Zerbe; Yansheng Zhang; Joerg Bohlmann; Patrick S. Covello; Vincenzo De Luca; Jonathan E. Page; Dae-Kyun Ro; Peter J. Facchini; Christoph W. Sensen

Plants produce a vast array of specialized metabolites, many of which are used as pharmaceuticals, flavors, fragrances, and other high-value fine chemicals. However, most of these compounds occur in non-model plants for which genomic sequence information is not yet available. The production of a large amount of nucleotide sequence data using next-generation technologies is now relatively fast and cost-effective, especially when using the latest Roche-454 and Illumina sequencers with enhanced base-calling accuracy. To investigate specialized metabolite biosynthesis in non-model plants we have established a data-mining framework, employing next-generation sequencing and computational algorithms, to construct and analyze the transcriptomes of 75 non-model plants that produce compounds of interest for biotechnological applications. After sequence assembly an extensive annotation approach was applied to assign functional information to over 800,000 putative transcripts. The annotation is based on direct searches against public databases, including RefSeq and InterPro. Gene Ontology (GO), Enzyme Commission (EC) annotations and associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps are also collected. As a proof-of-concept, the selection of biosynthetic gene candidates associated with six specialized metabolic pathways is described. A web-based BLAST server has been established to allow public access to assembled transcriptome databases for all 75 plant species of the PhytoMetaSyn Project (www.phytometasyn.ca).


Biochimie | 1996

Fully automated genome analysis that reflects user needs and preferences. A detailed introduction to the MAGPIE system architecture

Terry Gaasterland; Christoph W. Sensen

A system called MAGPIE (Multipurpose Automated Genome Project Investigation Environment) has been designed and implemented to meet the challenges of automated whole genome analysis. The system initiates large numbers of remote and local transactions, each depending on evolving criteria and on changing remote and local conditions. Transactions are requested from different types of remote and local resources. The remote request load is fairly balanced with other community demands on server resources. Local decision modules monitor and obey user preferences and combine evidence from multiple sources to formulate credible hypotheses about sequence function. Consistency checks from multiple types of data are integrated into the ongoing local analysis. The system performs reliably on local UNIX workstations and communicates with remote resources through standard networking protocols.

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Paul M. K. Gordon

Alberta Children's Hospital

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Jung Soh

University of Calgary

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Mei Xiao

University of Calgary

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