References of "Coppieters, Wouter"
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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-mediated gene regulation: contribution to phenotypic variation and disease.
Georges, Michel ULg; Coppieters, Wouter ULg; Charlier, Carole ULg

in Current opinion in genetics & development (2007), 17(3), 166-76

The expression of at least a third of mammalian genes is post-transcriptionally fine-tuned by approximately 1000 microRNAs (miRNAs), assisted by the RNA silencing machinery, comprising tens of components ... [more ▼]

The expression of at least a third of mammalian genes is post-transcriptionally fine-tuned by approximately 1000 microRNAs (miRNAs), assisted by the RNA silencing machinery, comprising tens of components. Polymorphisms and mutations in the corresponding sequence space (machinery, miRNA precursors and target sites) are likely to make a significant contribution to phenotypic variation, including disease susceptibility. Here we review basic miRNA biology in animals, survey the available evidence for DNA sequence polymorphisms affecting miRNA-mediated gene regulation and thus phenotype, and discuss their possible importance in the determination of complex traits. [less ▲]

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See detailA 2.5-Mb contig constructed from Angus, Longhorn and horned Hereford DNA spanning the polled interval on bovine chromosome 1
Wunderlich, K. R.; Abbey, C. A.; Clayton, D. R. et al

in Animal Genetics (2006), 37(6), 592-594

The polled locus has been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. As an intermediate step in our efforts to identify the polled locus and the underlying causative ... [more ▼]

The polled locus has been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. As an intermediate step in our efforts to identify the polled locus and the underlying causative mutation for the polled phenotype, we have constructed a BAC-based physical map of the interval containing the polled locus. Clones containing genes and markers in the critical interval were isolated from the TAMBT (constructed from Angus and Longhorn genomic DNA) and CHORI-240 (constructed from horned Hereford genomic DNA) BAC libraries and ordered based on fingerprinting and the presence or absence of 80 STS markers. A single contig spanning 2.5 Mb was assembled. Comparison of the physical order of STSs to the corresponding region of human chromosome 21 revealed the same order of genes within the polled critical interval. This contig of overlapping BAC clones from horned and polled breeds is a useful resource for SNP discovery and characterization of positional candidate genes. [less ▲]

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See detailGenetic identification of distinct loci controlling mammary tumor multiplicity, latency and aggressiveness in the rat
Quan, X.; Laes, Jean-François; Stieber, D. et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (2006), 17(4), 310-321

The rat is considered an excellent model for studying human breast cancer. Therefore, understanding the genetic basis of susceptibility to mammary cancer in this species is of great interest. Previous ... [more ▼]

The rat is considered an excellent model for studying human breast cancer. Therefore, understanding the genetic basis of susceptibility to mammary cancer in this species is of great interest. Previous studies based on crosses involving the susceptible strain WF (crossed with the resistant strains COP or WKY) and focusing on tumor multiplicity as the susceptibility phenotype led to the identification of several loci that control chemically induced mammary cancer. The present study was aimed to determine whether other loci can be identified by analyzing crosses derived from another susceptible strain on the one hand, and by including phenotypes other than tumor multiplicity on the other hand. A backcross was generated between the susceptible SPRD-Cu3 strain and the resistant WKY strain. Female progeny were genotyped with microsatellite markers covering all rat autosomes, treated with a single dose of DMBA, and phenotyped with respect to tumor latency, tumor multiplicity, and tumor aggressiveness. Seven loci controlling mammary tumor development were detected. Different loci control tumor multiplicity, latency, and aggressiveness. While some of these loci colocalize with loci identified in crosses involving the susceptible strain WF, new loci have been uncovered, indicating that the use of distinct susceptible and resistant strain pairs will help in establishing a comprehensive inventory of mammary cancer susceptibility loci [less ▲]

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See detailResults of a whole-genome quantitative trait locus scan for growth, carcass composition and meat quality in a porcine four-way cross.
Harmegnies, N.; DAVIN, Fabienne ULg; DE SMET, Samantha ULg et al

in Animal Genetics (2006), 37(6), 543-53

A whole-genome quantitative trait locus (QTL) scan for 31 phenotypes related to growth, carcass composition and meat quality was conducted using 1187 progeny of a commercial four-way cross. Animals were ... [more ▼]

A whole-genome quantitative trait locus (QTL) scan for 31 phenotypes related to growth, carcass composition and meat quality was conducted using 1187 progeny of a commercial four-way cross. Animals were genotyped for 198 microsatellite markers that spanned the entire porcine genome. QTL analysis was conducted to extract information from paternal and maternal meioses separately using a rank-based nonparametric approach for half-sib designs. Nine QTL exceeded genome-wide significance: one QTL affecting growth (average daily gain on SSC1), two QTL influencing carcass composition (fatness on SSC3 and muscle mass on SSC15) and six QTL influencing meat quality (tenderness on SSC4 and SSC14; colour on SSC5, SSC6 and SSCX; and conductivity on SSC16). All but one of these coincided with previously reported QTL. In addition, we present evidence for 78 suggestive QTL with a combined false discovery rate of 40%. [less ▲]

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See detailGenetical metabolomics of flavonoid biosynthesis in Populus: a case study.
Morreel, Kris; Goeminne, Geert; Storme, Veronique et al

in Plant Journal (The) (2006), 47(2), 224-37

Genetical metabolomics [metabolite profiling combined with quantitative trait locus (QTL) analysis] has been proposed as a new tool to identify loci that control metabolite abundances. This concept was ... [more ▼]

Genetical metabolomics [metabolite profiling combined with quantitative trait locus (QTL) analysis] has been proposed as a new tool to identify loci that control metabolite abundances. This concept was evaluated in a case study with the model tree Populus. Using HPLC, the peak abundances were analyzed of 15 closely related flavonoids present in apical tissues of two full-sib poplar families, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24, and correlation and QTL analysis were used to detect flux control points in flavonoid biosynthesis. Four robust metabolite quantitative trait loci (mQTL), associated with rate-limiting steps in flavonoid biosynthesis, were mapped. Each mQTL was involved in the flux control to one or two flavonoids. Based on the identities of the affected metabolites and the flavonoid pathway structure, a tentative function was assigned to three of these mQTL, and the corresponding candidate genes were mapped. The data indicate that the combination of metabolite profiling with QTL analysis is a valuable tool to identify control points in a complex metabolic pathway of closely related compounds. [less ▲]

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See detailMeasuring the extent of linkage disequilibrium in commercial pig populations
Harmegnies, N.; Farnir, Frédéric ULg; DAVIN, Fabienne ULg et al

in Animal Genetics (2006), 37(3), 225-231

To evaluate the extent of linkage disequilibrium in domestic pigs, we genotyped 33 and 44 unrelated individuals from two commercial populations for 29 and five microsatellite markers located on ... [more ▼]

To evaluate the extent of linkage disequilibrium in domestic pigs, we genotyped 33 and 44 unrelated individuals from two commercial populations for 29 and five microsatellite markers located on chromosomes 15 and 2 respectively. A high proportion of marker pairs up to 40 cM apart exhibited significant linkage disequilibrium in both populations. Pair-wise r(2) values averaged between 0.15 and 0.50 (depending on chromosome and population) for markers < 1 cM apart and declined to values of 0.05 for more distant syntenic markers. Our results suggest that both populations underwent a bottleneck approximately 20 generations ago, which reduced the effective population size from thousands to < 200 animals. [less ▲]

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See detailLinkage disequilibrium on the bovine X chromosome: Characterization and use in quantitative trait locus mapping
Sandor, Cynthia ULg; Farnir, Frédéric ULg; Hansoul, Sarah ULg et al

in Genetics (2006), 173(3), 1777-1786

We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between ... [more ▼]

We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. [less ▲]

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See detailGenetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition
Grisart, B.; Farnir, Frédéric ULg; Karim, Latifa ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2004), 101(8), 2398-2403

We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait ... [more ▼]

We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait nucleotide underlying a quantitative trait locus (QTL) affecting milk fat composition, previously mapped to the centromeric end of bovine chromosome 14. We herein generate genetic and functional data that confirm the causality of the DGAT1 K232A mutation. We have constructed a high-density single-nucleotide polymorphism map of the 3.8-centimorgan BULGE30-BULGE9 interval containing the QTL and show that the association with milk fat percentage maximizes at the DGAT1 gene. We provide evidence that the K allele has undergone a selective sweep. By using a baculovirus expression system, we have expressed both DGAT1 alleles in Sf9 cells and show that the K allele, causing an increase in milk fat percentage in the live animal, is characterized by a higher V-max in producing triglycerides than the A allele. [less ▲]

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See detailMolecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition.
Blott, Sarah; Kim, Jong-Joo; Moisio, Sirja et al

in Genetics (2003), 163(1), 253-66

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome ... [more ▼]

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome 20 marker map and by exploiting linkage disequilibrium using two distinct approaches, we provide strong evidence that a chromosome segment including the gene coding for the growth hormone receptor accounts for at least part of the chromosome 20 QTL effect. By sequencing individuals with known QTL genotype, we identify an F to Y substitution in the transmembrane domain of the growth hormone receptor gene that is associated with a strong effect on milk yield and composition in the general population. [less ▲]

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See detailPositional candidate cloning of a QTL in dairy cattle: Identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition
Grisart, B.; Coppieters, Wouter ULg; Farnir, Frédéric ULg et al

in Genome Research (2002), 12(2), 222-231

We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition-particularly fat content-to the centromeric end of bovine chromosome 14. We subsequently exploited linkage ... [more ▼]

We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition-particularly fat content-to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (I) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGATf), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics. [less ▲]

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See detailSimultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: Revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14
Farnir, Frédéric ULg; Grisart, B.; Coppieters, Wouter ULg et al

in Genetics (2002), 161(1), 275-287

A maximum-likelihood QTL mapping method that simultaneously exploits linkage and linkage disequilibrium and that is applicable in outbred half-sib pedigrees is described. The method is applied to fine map ... [more ▼]

A maximum-likelihood QTL mapping method that simultaneously exploits linkage and linkage disequilibrium and that is applicable in outbred half-sib pedigrees is described. The method is applied to fine map a QTL with major effect on milk fat content in a 3-cM marker interval on proximal BTA14. This proximal location is confirmed by applying a haplotype-based association method referred to as recombinant ancestral haplotype analysis. The origin of the discrepancy between the QTL position derived in this work and that of a previous analysis is examined and shown to be due to the existence of distinct marker haplotypes associated with QTL alleles having large substitution effects. [less ▲]

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See detailExtensive Genome-Wide Linkage Disequilibrium in Cattle
Farnir, Frédéric ULg; Coppieters, Wouter ULg; Arranz, J. J. et al

in Genome Research (2000), 10(2), 220-7

A genome-wide linkage disequilibrium (LD) map was generated using microsatellite genotypes (284 autosomal microsatellite loci) of 581 gametes sampled from the dutch black-and-white dairy cattle population ... [more ▼]

A genome-wide linkage disequilibrium (LD) map was generated using microsatellite genotypes (284 autosomal microsatellite loci) of 581 gametes sampled from the dutch black-and-white dairy cattle population. LD was measured between all marker pairs, both syntenic and nonsyntenic. Analysis of syntenic pairs revealed surprisingly high levels of LD that, although more pronounced for closely linked marker pairs, extended over several tens of centimorgan. In addition, significant gametic associations were also shown to be very common between nonsyntenic loci. Simulations using the known genealogies of the studied sample indicate that random drift alone is likely to account for most of the observed disequilibrium. No clear evidence was obtained for a direct effect of selection ("Bulmer effect"). The observation of long range disequilibrium between syntenic loci using low-density marker maps indicates that LD mapping has the potential to be very effective in livestock populations. The frequent occurrence of gametic associations between nonsyntenic loci, however, encourages the combined use of linkage and linkage disequilibrium methods to avoid false positive results when mapping genes in livestock. [less ▲]

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See detailConvenient Genotyping of Six Myostatin Mutations Causing Double-Muscling in Cattle Using a Multiplex Oligonucleotide Ligation Assay
Karim, Latifa ULg; Coppieters, Wouter ULg; Grobet, Luc ULg et al

in Animal Genetics (2000), 31(6), 396-9

We herein describe a procedure that allows for simultaneous genotyping of six loss-of-function mutations in the bovine myostatin gene associated with the double-muscling phenotype. The proposed method ... [more ▼]

We herein describe a procedure that allows for simultaneous genotyping of six loss-of-function mutations in the bovine myostatin gene associated with the double-muscling phenotype. The proposed method relies on a multiplex oligonucleotide ligation assay and detection of the fluorescently labelled products using automatic sequencers. [less ▲]

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See detailMapping QTL influencing muscularity in a Texel x Romanov intercross
Marcq, Fabienne ULg; Elsen, J.-M.; Marot, V. et al

(2000)

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See detailFine-Mapping of Quantitative Trait Loci by Identity by Descent in Outbred Populations: Application to Milk Production in Dairy Cattle
Riquet, J.; Coppieters, Wouter ULg; Cambisano, Nadine ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (1999), 96(16), 9252-9257

We previously mapped a quantitative trait locus (QTL) affecting milk production to bovine chromosome 14. To refine the map position of this QTL, we have increased the density of the genetic map of ... [more ▼]

We previously mapped a quantitative trait locus (QTL) affecting milk production to bovine chromosome 14. To refine the map position of this QTL, we have increased the density of the genetic map of BTA14q11-16 by addition of nine microsatellites and three single nucleotide polymorphisms. Fine-mapping of the QTL was accomplished by a two-tiered approach. In the first phase, we identified seven sires heterozygous "Qq" for the QTL by marker-assisted segregation analysis in a Holstein-Friesian pedigree comprising 1,158 individuals. In a second phase, we genotyped the seven selected sires for the newly developed high-density marker map and searched for a shared haplotype flanking an hypothetical, identical-by-descent QTL allele with large substitution effect. The seven chromosomes increasing milk fat percentage were indeed shown to carry a common chromosome segment with an estimated size of 5 cM predicted to contain the studied QTL. The same haplotype was shown to be associated with increased fat percentage in the general population as well, providing additional support in favor of the location of the QTL within the corresponding interval. [less ▲]

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See detailAn imprinted QTL with major effect on muscle mass and fat deposition maps to the IgfII locus in pigs
Nezer, C.; Moreau, L.; Brouwers, B. et al

in Nature Genetics (1999), 21

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See detailThe great-grand-daughter design: a simple strategy to increase the power of a grand-daughter design for QTL mapping
Coppieters, Wouter ULg; Kvasz, A.; Arranz, J. J. et al

in Genetical Research (1999), 74

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See detailMapping quantitative trait loci causing the muscular hypertrophy of Belgian Texel sheep
Marcq, Fabienne ULg; Elsen, J.-M.; Marot, V. et al

(1999)

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