References of "Coppieters, Wouter"
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See detailTowards positional identification of susceptibility loci for White Heifer disease in Belgian Blue Cattle (poster)
Sartelet, Arnaud ULg; Druet, Tom ULg; Coppieters, Wouter ULg et al

in New Biotechnology (2010, April), 27(Supplement 1), 79

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See detailPatrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates
Hiard, Samuel ULg; Charlier, Carole ULg; Coppieters, Wouter ULg et al

in Nucleic Acids Research (2010), 38(Database), 640-651

The Patrocles database (http://www.patrocles.org/) compiles DNA sequence polymorphisms (DSPs) that are predicted to perturb miRNA-mediated gene regulation. Distinctive features include: (i) the coverage ... [more ▼]

The Patrocles database (http://www.patrocles.org/) compiles DNA sequence polymorphisms (DSPs) that are predicted to perturb miRNA-mediated gene regulation. Distinctive features include: (i) the coverage of seven vertebrate species in its present release, aiming for more when information becomes available, (ii) the coverage of the three compartments involved in the silencing process (i.e. targets, miRNA precursors and silencing machinery), (iii) contextual information that enables users to prioritize candidate ‘Patrocles DSPs’, including graphical information on miRNA-target coexpression and eQTL effect of genotype on target expression levels, (iv) the inclusion of Copy Number Variants and eQTL information that affect miRNA precursors as well as genes encoding components of the silencing machinery and (v) a tool (Patrocles finder) that allows the user to determine whether her favorite DSP may perturb miRNA-mediated gene regulation of custom target sequences. To support the biological relevance of Patrocles' content, we searched for signatures of selection acting on ‘Patrocles single nucleotide polymorphisms (pSNPs)’ in human and mice. As expected, we found a strong signature of purifying selection against not only SNPs that destroy conserved target sites but also against SNPs that create novel, illegitimate target sites, which is reminiscent of the Texel mutation in sheep. [less ▲]

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See detailGenotyping panels available in cattle and their properties
Druet, Tom ULg; Zhang, Zhiyan; Coppieters, Wouter ULg et al

in Book of Abstracts of the 61st Annual Meeting of the European Association for Animal Production (2010)

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

Scientific conference (2009, September 29)

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See detailMarker assisted selection of bovine for improved milk production using diacylglycerol acyltransferase gene DGAT1.
Georges, Michel ULg; Coppieters, Wouter ULg; Grisart, Bernard et al

Patent (2009)

The present invention provides a method of genotyping bovine for improved milk production traits by determining the DGAT1 genotypic state of said bovine, wherein the DGAT1 gene and polymorphisms within ... [more ▼]

The present invention provides a method of genotyping bovine for improved milk production traits by determining the DGAT1 genotypic state of said bovine, wherein the DGAT1 gene and polymorphisms within said gene have been found to be associated with such improved milk production traits. [less ▲]

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See detailBalancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle.
Fasquelle, Corinne ULg; Sartelet, Arnaud ULg; Li, Wanbo et al

in PLoS Genetics (2009), 5(9), 1000666

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals ... [more ▼]

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. [less ▲]

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See detailA nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle.
Koltes, James E; Mishra, Bishnu P; Kumar, Dinesh et al

in Proceedings of the National Academy of Sciences of the United States of America (2009), 106(46), 19250-5

Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a ... [more ▼]

Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle. [less ▲]

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See detailMapping QTL influencing gastrointestinal nematode burden in Dutch Holstein-Friesian dairy cattle.
Coppieters, Wouter ULg; Mes, Ted H M; Druet, Tom ULg et al

in BMC Genomics (2009), 10

BACKGROUND: Parasitic gastroenteritis caused by nematodes is only second to mastitis in terms of health costs to dairy farmers in developed countries. Sustainable control strategies complementing ... [more ▼]

BACKGROUND: Parasitic gastroenteritis caused by nematodes is only second to mastitis in terms of health costs to dairy farmers in developed countries. Sustainable control strategies complementing anthelmintics are desired, including selective breeding for enhanced resistance. RESULTS AND CONCLUSION: To quantify and characterize the genetic contribution to variation in resistance to gastro-intestinal parasites, we measured the heritability of faecal egg and larval counts in the Dutch Holstein-Friesian dairy cattle population. The heritability of faecal egg counts ranged from 7 to 21% and was generally higher than for larval counts. We performed a whole genome scan in 12 paternal half-daughter groups for a total of 768 cows, corresponding to the approximately 10% most and least infected daughters within each family (selective genotyping). Two genome-wide significant QTL were identified in an across-family analysis, respectively on chromosomes 9 and 19, coinciding with previous findings in orthologous chromosomal regions in sheep. We identified six more suggestive QTL by within-family analysis. An additional 73 informative SNPs were genotyped on chromosome 19 and the ensuing high density map used in a variance component approach to simultaneously exploit linkage and linkage disequilibrium in an initial inconclusive attempt to refine the QTL map position. [less ▲]

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See detailMarker assisted selection of bovine for improved milk composition.
Blott, Sarah; Kim; Schmidt-Kuntzel, Anne et al

Patent (2008)

The present invention provides a method of genotyping bovine for improved milk production traits by determining the GHR genotypic state of said bovine, wherein the GHR gene and polymorphisms within said ... [more ▼]

The present invention provides a method of genotyping bovine for improved milk production traits by determining the GHR genotypic state of said bovine, wherein the GHR gene and polymorphisms within said gene have been found to be associated with such improved milk production traits. [less ▲]

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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 detailCharacterization of the bovine pseudoautosomal boundary: Documenting the evolutionary history of mammalian sex chromosomes.
Van Laere, Anne-Sophie ULg; Coppieters, Wouter ULg; Georges, Michel ULg

in Genome Research (2008), 18(12), 1884-95

Here, we report the sequence characterization of the bovine pseudoautosomal boundary (PAB) and its neighborhood. We demonstrate that it maps to the 5' end of the GPR143 gene, which has concomitantly lost ... [more ▼]

Here, we report the sequence characterization of the bovine pseudoautosomal boundary (PAB) and its neighborhood. We demonstrate that it maps to the 5' end of the GPR143 gene, which has concomitantly lost upstream noncoding exons on the Y chromosome. We show that the bovine PAB was created approximately 20.7 million years ago by illegitimate intrachromatid recombination between inverted, ruminant-specific Bov-tA repeats. Accordingly, we demonstrate that cattle share their PAB with all other examined ruminants including sheep, but not with cetaceans or more distantly related mammals. We provide evidence that, since its creation, the ancestral ruminant PAB has been displaced by attrition, which occurs at variable rates in different species, and that it is capable of retreat by attrition erasure. We have estimated the ratio of male to female mutation rates in the Bovidae family as approximately 1.7, and we provide evidence that the mutation rate is higher in the recombining pseudoautosomal region than in the adjacent, nonrecombining gonosome-specific sequences. [less ▲]

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See detailHighly effective SNP-based association mapping and management of recessive defects in livestock.
Charlier, Carole ULg; Coppieters, Wouter ULg; Rollin, Frédéric ULg et al

in Nature Genetics (2008), 40(4), 449-54

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal ... [more ▼]

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings. [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, 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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