References of "Cambisano, Nadine"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailA missense mutation accelerating the gating of the lysosomal Cl-/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle.
Sartelet, Arnaud ULg; Stauber, Tobias; Coppieters, Wouter ULg et al

in Disease Models & Mechanisms (2014), 7

Chloride/proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal ... [more ▼]

Chloride/proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mutations accelerate the usually slow voltage-dependent gating of ClC-7/Ostm1. However, it has remained unclear whether the fastened kinetics is indeed causative for the disease. Here we identified and characterized a new deleterious ClC-7 mutation in Belgian Blue Cattle with a severe symptomatology including peri-natal lethality and in most cases gingival hamartomas. By autozygosity mapping and genome-wide sequencing we found a handful of candidate variants, including a cluster of three private SNPs causing the substitution of a conserved tyrosine in the CBS2 domain of ClC-7 by glutamine. The case for ClC-7 was strengthened by subsequent examination of affected calves that revealed severe osteopetrosis. The Y750Q mutation largely preserved the lysosomal localization and assembly of ClC-7/Ostm1, but drastically accelerated its activation by membrane depolarization. These data provide first evidence that accelerated ClC-7/Ostm1 gating per se is deleterious, highlighting a physiological importance of the slow voltage-activation of ClC-7/Ostm1 in lysosomal function and bone resorption. [less ▲]

Detailed reference viewed: 43 (5 ULg)
Full Text
Peer Reviewed
See detailA genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.
GEORGES, Anouk ULg; Cambisano, Nadine ULg; Ahariz, Naïma ULg et al

in PloS one (2013), 8(12), 83574

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree ... [more ▼]

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree. [less ▲]

Detailed reference viewed: 26 (2 ULg)
See detailScan for selective sweeps associated with muscular devolpment in Belgian Blue beef cattle
Druet, Tom ULg; Ahariz, Naïma ULg; Cambisano, Nadine ULg et al

Poster (2013, February)

The Belgian Blue beef cattle is well known for its double muscling phenotype resulting from fixation of a deletion in the myostatin gene. Since this fixation, further intensive selection for muscular ... [more ▼]

The Belgian Blue beef cattle is well known for its double muscling phenotype resulting from fixation of a deletion in the myostatin gene. Since this fixation, further intensive selection for muscular development has been particularly succesful. This response to selection might be due to fixation of more genetic variants increasing muscular development. In the present study, we search for selective sweeps in the Belgian Blue genome which might result from the fixation of such variants. To that end we used data from 593 sires genotyped with the BovineHD SNP array. In addition, we used the Belgian Blue dual purpose and the Holstein breeds as controls. We first performed scans for regions of complete homozygosity resulting from fixation. Large fixed regions were found around major genes known to be fixed in the Belgian Blue cattle breed (MSTN, PLAG1 and MC1R) but no other regions of the same magnitude was found. Among the smaller identified regions, only few of them were unique to the Belgian Blue breed. Statistical tests based on long range haplotype information were also implemented, revealing large regions in the genome of reduced haplotype homozygosity specific to the Belgian Blue breed. Some of these regions corresponded to known major genes (MSTN, roan locus, PLAG1 or MC1R) while other regions were new. To determine whether these regions might be the result of selection for muscular development, we performed association studies for muscular development. None of the identified QTL matched with the regions of reduced haplotype homozygosity and the largest QTLs did not presented evidence of strong selective sweeps. These results suggest that the response to selection for muscular development in Belgian Blue beef cattle is probably the result of polygenic selection. [less ▲]

Detailed reference viewed: 55 (1 ULg)
Full Text
See detailA missense mutation in the ClC-7 chloride channel causes hamartomas with osteopetrosis in cattle.
Sartelet, Arnaud ULg; Stauber, Tobias; Coppieters, Wouter ULg et al

Conference (2012, October 19)

Detailed reference viewed: 51 (15 ULg)
Full Text
See detailA missense mutation in the ClC-7 chloride channel causes hamartomas with osteopetrosis in cattle.
Sartelet, Arnaud ULg; Stauber, Tobias; Druet, Tom ULg et al

Conference (2012, June 05)

Detailed reference viewed: 23 (3 ULg)
Full Text
Peer Reviewed
See detailSerial translocation by means of circular intermediates underlies colour sidedness in cattle.
Durkin, Keith ULg; Coppieters, Wouter ULg; Drogemuller, Cord et al

in Nature (2012), 482(7383), 81-4

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik ... [more ▼]

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism. [less ▲]

Detailed reference viewed: 104 (58 ULg)
Full Text
Peer Reviewed
See detailA deletion in the bovine FANCI gene compromises fertility by causing fetal death and brachyspina.
Charlier, Carole ULg; Agerholm, Jorgen Steen; Coppieters, Wouter ULg et al

in PLoS ONE (2012), 7(8), 43085

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping ... [more ▼]

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that despite the very low incidence of BS (<1/100,000), carrier frequency is as high as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is likely due to the fact that a large proportion of homozygous mutant calves die during pregnancy. We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility, and propose a genotype-driven screening strategy to detect the corresponding deleterious mutations. [less ▲]

Detailed reference viewed: 11 (1 ULg)
Full Text
Peer Reviewed
See detailMolecular dissection of the color-sided phenotype in cattle reveals a novel mechanism of chromosome evolution involving circular shuttling intermediates.
Durkin, Keith ULg; Cambisano, Nadine ULg; Ahariz, Naïma ULg et al

in Chromosome Research : An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology (2011, May), 19(S1), 18

The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC ... [more ▼]

The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC unambiguously positioned the Cs locus on chromo- some 29 (BTA29); however, SNP arrays and CGH detected an equally perfectly associated <480 kb duplication encompassing the KIT gene on chromo- some 6 (BTA6). FISH analysis reconciled these results by revealing an intrachromosomal duplication, which transposed a fragment of BTA6 to BTA29. The organization of the duplicated segment, including breakpoint definition, was determined by high-throughput resequencing and revealed that the transpo- sition occurred via a circular intermediate. The trans- posed KIT copy was shown to be transcriptionally competent, suggesting that dominant color-sidedness results from dysregulated expression of KIT. Similar analyses of the color-sided phenotype conducted in BS revealed linkage on BTA6, a <120- kb-BTA6 duplication (which overlaps with the BBC duplication), and a <414-kb-BTA29 duplication adja- cent to the BTA29 breakpoint defined in BBC. FISH analysis showed the duplicated portion of BTA29 was located on BTA6 and adjacent to the KIT gene. SNP genotyping indicated that the BTA6 and BTA29 haplotypes associated with color-sidedness in BS and BBC were near identical, demonstrating the non-independence of the two chromosomal events. High-throughput resequencing of a color-sided BS animal defined the corresponding breakpoints and suggests that the BS Cs allele is derived from the BBC duplication [less ▲]

Detailed reference viewed: 56 (17 ULg)
Full Text
Peer Reviewed
See detailVariants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature.
Karim, Latifa ULg; Takeda, Haruko ULg; Lin, Li et al

in Nature Genetics (2011), 43(5), 405-13

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits ... [more ▼]

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the approximately 780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene. [less ▲]

Detailed reference viewed: 80 (31 ULg)
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 ▲]

Detailed reference viewed: 15 (3 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 54 (3 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 9 (0 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 29 (7 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 15 (0 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 8 (1 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 109 (14 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 30 (5 ULg)
Full Text
Peer Reviewed
See detailA Qtl with Major Effect on Milk Yield and Composition Maps to Bovine Chromosome 14
Coppieters, Wouter ULg; Riquet, J.; Arranz, J. J. et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1998), 9(7), 540-4

A whole genome scan was undertaken in a granddaughter design comprising 1158 progeny-tested bulls in order to map QTL influencing milk yield and composition. In this paper we report the identification of ... [more ▼]

A whole genome scan was undertaken in a granddaughter design comprising 1158 progeny-tested bulls in order to map QTL influencing milk yield and composition. In this paper we report the identification of a locus on the centromeric end of bovine Chromosome (Chr) 14, with major effect on fat and protein percentage as well as milk yield. The genuine nature of this QTL was verified using the grand2-daughter design, that is, by tracing the segregating QTL alleles from heterozygous grandsires to their maternal grandsons and confirming the predicted QTL allele substitution effect. [less ▲]

Detailed reference viewed: 17 (2 ULg)
Full Text
Peer Reviewed
See detailA Qtl Affecting Milk Yield and Composition Maps to Bovine Chromosome 20: A Confirmation
Arranz, J. J.; Coppieters, Wouter ULg; Berzi, P. et al

in Animal Genetics (1998), 29(2), 107-15

As part of a whole genome scan undertaken to detect quantitative trait loci (QTL) affecting milk yield and composition, we have genotyped a granddaughter design comprising 1152 sons for six microsatellite ... [more ▼]

As part of a whole genome scan undertaken to detect quantitative trait loci (QTL) affecting milk yield and composition, we have genotyped a granddaughter design comprising 1152 sons for six microsatellite markers spanning bovine chromosome 20. An analysis performed across families provided strong evidence (experiment-wise P-values < 0.01) for the presence of a QTL affecting primarily protein percentage towards the telomeric end of the chromosome. A founder sire, shown in a previous study to segregate for a similar QTL in the corresponding chromosome region, was characterized by 29 and 57 sons and maternal grandsons, respectively, in the present design. Sorting corresponding sons and grandsons by paternal or grandpaternal allele provided significant evidence for the segregation of a QTL on chromosome 20. Altogether these results confirm the location of a QTL affecting milk production on bovine chromosome 20. [less ▲]

Detailed reference viewed: 26 (2 ULg)