References of "Ahariz, Naïma"
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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 ▲]

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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 ▲]

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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 ▲]

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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)

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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)

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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 ▲]

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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 ▲]

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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 ▲]

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