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See detailPatrocles: a database of polymorphic miRNA-mediated gene regulation
Hiard, Samuel ULg; Baurain, Denis ULg; Coppieters, Wouter ULg et al

Conference (2008, March 03)

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See detailCompiling polymorphic miRNA-target interactions: the Patrocles database.
Hiard, Samuel ULg; Tordoir, Xavier ULg; Coppieters, Wouter ULg et al

Poster (2007, November 12)

Using positional cloning, we have recently identified the mutation responsible for muscular phenotype of the Texel sheep. It is located in the 3’UTR of the GDF8 gene - a known developmental repressor of ... [more ▼]

Using positional cloning, we have recently identified the mutation responsible for muscular phenotype of the Texel sheep. It is located in the 3’UTR of the GDF8 gene - a known developmental repressor of muscle growth - and creates an illegitimate target site for miRNA expressed in the same tissue. This causes miRNA-mediated translation inhibition of mutant GDF8 transcripts which leads to muscle hypertrophy. We followed up on this finding by searching for common polymorphisms and mutations that affect either (i) RNAi silencing machinery components, (ii) miRNA precursors or (iii) target sites. These might likewise alter miRNA-target interaction and could be responsible for substantial differences in gene expression level. They have been compiled in a public database (“Patrocles”: www.patrocles.org), where they are classified in (i) DNA sequence polymorphisms (DSP) affecting the silencing machinery, (ii) DSP affecting miRNA structure or expression and (iii) DSP affecting miRNA target sites. DSP from the last category were organized in four classes: destroying a target site conserved between mammals (DC), destroying a non-conserved target site (DNC), creating a non-conserved target site (CNC), or shifting a target site (S). To aid in the identification of the most relevant DSP (such as those were a target site is created in an antitarget gene), we have quantified the level of coexpression for all miRNA-gene pairs. Analysis of the numbers of Patrocles-DSP as well as their allelic frequency distribution indicates that a substantial proportion of them undergo purifying selection. The signature of selection was most pronounced for the DC class but was significant for the DNC and CNC class as well, suggesting that a significant proportion of non-conserved targets is truly functional. The Patrocles database allowed for the selection of DSP that are likely to affect gene function and possibly disease susceptibility. The effect of these DSP is being studied both in vitro and in vivo. In conclusion, Patrocles-DSP could be widespread and underlie an appreciable amount of phenotypic variation, including common disease susceptibility. [less ▲]

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See detailCompiling polymorphic miRNA-target interactions: the Patrocles database.
Hiard, Samuel ULg; Tordoir, Xavier ULg; Coppieters, Wouter ULg et al

Poster (2007, February 15)

Using positional cloning, we have recently identified the mutation responsible for muscular phenotype of the Texel sheep. It is located in the 3’UTR of the GDF8 gene - a known developmental repressor of ... [more ▼]

Using positional cloning, we have recently identified the mutation responsible for muscular phenotype of the Texel sheep. It is located in the 3’UTR of the GDF8 gene - a known developmental repressor of muscle growth - and creates an illegitimate target site for miRNA expressed in the same tissue. This causes miRNA-mediated translation inhibition of mutant GDF8 transcripts which leads to muscle hypertrophy. We followed up on this finding by searching for common polymorphisms and mutations that affect either (i) RNAi silencing machinery components, (ii) miRNA precursors or (iii) target sites. These might likewise alter miRNA-target interaction and could be responsible for substantial differences in gene expression level. They have been compiled in a public database (“Patrocles”: www.patrocles.org), where they are classified in (i) DNA sequence polymorphisms (DSP) affecting the silencing machinery, (ii) DSP affecting miRNA structure or expression and (iii) DSP affecting miRNA target sites. DSP from the last category were organized in four classes: destroying a target site conserved between mammals (DC), destroying a non-conserved target site (DNC), creating a non-conserved target site (CNC), or shifting a target site (S). To aid in the identification of the most relevant DSP (such as those were a target site is created in an antitarget gene), we have quantified the level of coexpression for all miRNA-gene pairs. Analysis of the numbers of Patrocles-DSP as well as their allelic frequency distribution indicates that a substantial proportion of them undergo purifying selection. The signature of selection was most pronounced for the DC class but was significant for the DNC and CNC class as well, suggesting that a significant proportion of non-conserved targets is truly functional. The Patrocles database allowed for the selection of DSP that are likely to affect gene function and possibly disease susceptibility. The effect of these DSP is being studied both in vitro and in vivo. In conclusion, Patrocles-DSP could be widespread and underlie an appreciable amount of phenotypic variation, including common disease susceptibility. [less ▲]

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See detailPolymorphic miRNA-target interactions : A Novel Source of Phenotypic Variation
Georges, Michel ULg; Clop, Alex; Marcq, Fabienne ULg et al

in Cold Spring Harbor Symposia on Quantitative Biology (2006, June), 71

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and ... [more ▼]

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and miR-206 that are highly expressed in skeletal muscle. This causes the down-regulation of this muscle-specific chalone and hence contributes to the muscular hypertrophyof Texel sheep. We demonstrate that polymorphisms which alter the content of putative miRNA target sites are commonin human and mice, and provide evidence that both conserved and nonconserved target sites are selectively constrained. Wespeculate that these polymorphisms might be important mediators of phenotypic variation including disease. To facilitatestudies along those lines, we have constructed a database (www.patrocles.org) listing putative polymorphic microRNA–targetinteractions. [less ▲]

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See detailThe callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis
Takeda, Haruko ULg; Caiment, Florian ULg; Smit, Maria et al

in Proceedings of the National Academy of Sciences USA (2006), 103(21), 8119-8124

The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic ... [more ▼]

The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy and its non-Mendelian inheritance pattern known as polar overdominance. We herein demonstrate that the CLPG mutation alters the muscular epigenotype of the DLK1-GTL2 IG region in cis, including hypomethylation, acquisition of novel DNase-I hypersentivite sites, and, most strikingly, strongly enhanced bidirectional, long-range IG transcription. The callipyge phenotype thus emerges as a unique model to study the functional significance of IG transcription, which recently has proven to be a widespread, yet elusive, feature of the mammalian genome. [less ▲]

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See detailA mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep.
Clop, Alex; Marcq, Fabienne ULg; Takeda, Haruko ULg et al

in Nature Genetics (2006), 38(7), 813-8

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We ... [more ▼]

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation. [less ▲]

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See detailBEGAIN: a novel imprinted gene that generates paternally expressed transcripts in a tissue- and promoter-specific manner in sheep.
Smit, Maria A; Tordoir, Xavier ULg; Gyapay, Gabor et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (2005), 16(10), 801-14

In this article we describe the organization of the ovine BEGAIN gene, located 138 kb proximally from the imprinted DLK1 gene and 203 kb from the CLPG mutation that causes the callipyge phenotype. We have ... [more ▼]

In this article we describe the organization of the ovine BEGAIN gene, located 138 kb proximally from the imprinted DLK1 gene and 203 kb from the CLPG mutation that causes the callipyge phenotype. We have shown that in sheep BEGAIN is ubiquitously expressed, including in skeletal muscle, throughout development. We have identified four major BEGAIN transcripts resulting from a combination of alternate promoter usage and alternative splicing. In ovine brain, kidney, liver, and skeletal muscle, these four BEGAIN transcripts exhibited paternal or biallelic expression in a tissue- and promoter-specific manner. Our results indicate that the CLPG mutation does not alter transcript levels of BEGAIN, contrary to its effect on a core cluster of genes in the DLK1-GTL2 domain. Thus, although the BEGAIN gene represents another paternally expressed gene in the ovine DLK1-GTL2 imprinted domain, its expression is not governed by the long-range regulatory element that contains the CLPG mutation. [less ▲]

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See detailM1/E2 transition rates in Fe x through Fe XIII measured at a heavy-ion storage ring
Trabert, E.; Gwinner, G.; Wolf, A. et al

in Journal of Physics B-Atomic Molecular and Optical Physics (2002), 35(3), 671-689

The rates of several electric-dipole forbidden decays of 3p and 3d levels in Cl-, S-, P- and Si-like ions of Fe have been measured optically at a heavy-ion storage ring. In several cases, more than one ... [more ▼]

The rates of several electric-dipole forbidden decays of 3p and 3d levels in Cl-, S-, P- and Si-like ions of Fe have been measured optically at a heavy-ion storage ring. In several cases, more than one decay contributes to a given decay curve, which complicates the analysis. The lifetime results, with a precision range from 0.6 to 20%, compare well with some theoretical predictions, but are more precise. They are also more precise than some experimental data from an electrostatic ion trap. [less ▲]

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See detailEquilibrium charge-state distributions of sodium ions in carbon foil
Tordoir, Xavier ULg; Bastin, Thierry ULg; Dumont, Paul-Dominique ULg et al

in Nuclear Instruments & Methods in Physics Research. Section B, Beam Interactions with Materials and Atoms (2001), 173

The equilibrium charge-state distributions have been measured for sodium ions at the exit of a carbon foil for energies ranging from 0.43 to 1.66 Me V. A comparison of our results with available models is ... [more ▼]

The equilibrium charge-state distributions have been measured for sodium ions at the exit of a carbon foil for energies ranging from 0.43 to 1.66 Me V. A comparison of our results with available models is performed and an empirical formula for calculating the charge-state fractions of sodium ions is deduced. [less ▲]

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See detailLifetimes of metastable state in Sr II
Biémont, Emile ULg; Lidberg, J.; Mannervik, S. et al

in European Physical Journal D -- Atoms, Molecules, Clusters & Optical Physics (2000), 11

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See detailHyperfine structure and lifetimes of metastable states studied by means of laser excitation of stored ions
Norlin, L.-O.; Biémont, Emile ULg; Lidberg, J. et al

in Hyperfine Interactions (1999), 120-121

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See detailLifetime measurements in Yb II with time-resolved laser spectroscopy
Li, Z. S.; Svanberg, S.; Quinet, Pascal ULg et al

in Journal of Physics : B Atomic Molecular & Optical Physics (1999), 32

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See detailAtomic Lifetimes and Transition Probabilities in Boron-like (Na VII) and Beryllium-like (Na VIII) Sodium Ions
Tordoir, Xavier ULg; Biémont, Emile ULg; Garnir, Henri-Pierre ULg et al

in European Physical Journal D -- Atoms, Molecules, Clusters & Optical Physics (1999), 6

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See detailAtomic Lifetimes of n=2 Levels of Boron-like Na
Tordoir, Xavier ULg; Biémont, Emile ULg; Garnir, Henri-Pierre ULg et al

Conference (1998, August)

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