References of "Georges, Michel"
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See detailPhenotyping Belgian Blue cattle for their susceptibility to psoroptic mange
Abos, Romain ULg; Coussé, Annelies; Sarre, Charlotte et al

Poster (2014, October 17)

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See detailPedigree-based haplotype reconstruction, identification of cross-overs and detection of map and genotyping errors using PHASEBOOK
Druet, Tom ULg; Georges, Michel ULg

Conference (2014, August 22)

Haplotype reconstruction is important in many applications in animal genomics. In livestock species, thanks to the availability of large half-sibs families and genotyped relatives, phasing methods can ... [more ▼]

Haplotype reconstruction is important in many applications in animal genomics. In livestock species, thanks to the availability of large half-sibs families and genotyped relatives, phasing methods can rely on strong familial information and results in families with more than 10 offspring are very accurate. However, most methods are sensitive to genotyping and map errors which will be more common with next generation sequencing data. Such problems are particularly important when studying recombination rate as we plan to do in the near future. We herein describe a novel algorithm which is robust to genotyping errors and which can identify errors in marker maps. Using a large dairy cattle data set genotyped with high-density genotyping arrays, we show that the novel algorithm strongly reduces the occurrence of spurious cross-overs due to different sources of errors, and identifies map errors for most of the bovine autosomes. The implemented version is still experimental and further research will be conducted to characterize the novel method (including simulations) and to fully describe the identified map errors. [less ▲]

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See detailA 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock
Kumar Kadri, Naveen; Sahana, Goutam; Charlier, Carole ULg et al

in PLoS Genetics (2014), 10(1), 1004049

In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has ... [more ▼]

In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated. [less ▲]

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See detailGigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation.
Trivellin, Giampaolo; Daly, Adrian ULg; Faucz, Fabio R. et al

in The New England journal of medicine (2014)

Background Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. Methods We performed ... [more ▼]

Background Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. Methods We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. Results We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. Conclusions We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.). [less ▲]

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See detailSelection in action: dissecting the molecular underpinnings of the increasing muscle mass of Belgian Blue Cattle.
Druet, Tom ULg; Ahariz, Naima; Cambisano, Nadine et al

in BMC genomics (2014), 15(1), 796

BACKGROUND: Belgian Blue cattle are famous for their exceptional muscular development or "double-muscling". This defining feature emerged following the fixation of a loss-of-function variant in the ... [more ▼]

BACKGROUND: Belgian Blue cattle are famous for their exceptional muscular development or "double-muscling". This defining feature emerged following the fixation of a loss-of-function variant in the myostatin gene in the eighties. Since then, sustained selection has further increased muscle mass of Belgian Blue animals to a comparable extent. In the present paper, we study the genetic determinants of this second wave of muscle growth. RESULTS: A scan for selective sweeps did not reveal the recent fixation of another allele with major effect on muscularity. However, a genome-wide association study identified two genome-wide significant and three suggestive quantitative trait loci (QTL) affecting specific muscle groups and jointly explaining 8-21% of the heritability. The top two QTL are caused by presumably recent mutations on unique haplotypes that have rapidly risen in frequency in the population. While one appears on its way to fixation, the ascent of the other is compromised as the likely underlying MRC2 mutation causes crooked tail syndrome in homozygotes. Genomic prediction models indicate that the residual additive variance is largely polygenic. CONCLUSIONS: Contrary to complex traits in humans which have a near-exclusive polygenic architecture, muscle mass in beef cattle (as other production traits under directional selection), appears to be controlled by (i) a handful of recent mutations with large effect that rapidly sweep through the population, and (ii) a large number of presumably older variants with very small effects that rise slowly in the population (polygenic adaptation). [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 detailA splice-acceptor site variant in the bovine PIGH gene causes glycosylphosphatidyl inositol deficiency and lethal arthrogryposis syndrome.
Sartelet, Arnaud ULg; Li, Wanbo; Pailhoux Eric et al

in Bayrou, Calixte; Cabaraux, Jean-François; Delguste, Catherine (Eds.) et al Proccedings of the 3rd Scientific Meetingof the Faculty of Veterinary Medecine (2013, October 11)

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See detailMethod for identifying cows with mastitis by bulk genotyping of tank milk.
Georges, Michel ULg; Coppieters, Wouter ULg; Blard, Grégoire

Patent (2013)

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See detailA triad of highly divergent polymeric immunoglobulin receptor (PIGR) haplotypes with major effect on IgA concentration in bovine milk.
Berry, Sarah; Coppieters, Wouter ULg; Davis, Stephen et al

in PloS one (2013), 8(3), 57219

The aim of this study was to determine a genetic basis for IgA concentration in milk of Bos taurus. We used a Holstein-Friesian x Jersey F2 crossbred pedigree to undertake a genome-wide search for QTL ... [more ▼]

The aim of this study was to determine a genetic basis for IgA concentration in milk of Bos taurus. We used a Holstein-Friesian x Jersey F2 crossbred pedigree to undertake a genome-wide search for QTL influencing IgA concentration and yield in colostrum and milk. We identified a single genome-wide significant QTL on chromosome 16, maximising at 4.8 Mbp. The polymeric immunoglobulin receptor gene (PIGR) was within the confidence interval of the QTL. In addition, mRNA expression analysis revealed a liver PIGR expression QTL mapping to the same locus as the IgA quantitative trait locus. Sequencing and subsequent genotyping of the PIGR gene revealed three divergent haplotypes that explained the variance of both the IgA QTL and the PIGR expression QTL. Genetic selection based on these markers will facilitate the production of bovine herds producing milk with higher concentrations of IgA. [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 detailDeep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma
Rosewick, Nicolas; Momont, Mélanie ULg; Durkin, Keith ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2013)

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy however remains poorly understood, especially as viral ... [more ▼]

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy however remains poorly understood, especially as viral mRNA/protein are tightly silenced in tumors. Here, using deep sequencing of broad windows of small RNA sizes in the Bovine Leukemia Virus ovine model of leukemia/lymphoma, we provide in vivo evidence of the production of non-canonical Pol IIItranscribed viral microRNAs in leukemic B-cells in the complete absence of Pol II 5’ LTR-driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, BLV microRNAs represent ~ 40 % of all microRNAs in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and/or viral targets. BLV microRNAs are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent microRNAs subvert cellular and viral pathways will contribute in deciphering the intricate perturbations that underlie malignant transformation. [less ▲]

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See detailDetection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy
Dupuis, Marie-Capucine; Zhang, Zhiyan ULg; Durkin, Keith ULg et al

in Animal Genetics (2013)

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with ... [more ▼]

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN), an important equine upper airway disease compromising performance. A total of 2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs, particularly deletions, were shown to be significantly depleted in genes. Fifty-two of the 67 common CNVRs (frequency ! 1%) were validated by association mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67 common CNVRs were significantly associated with RLN when accounting for multiple testing. However, a duplication on chromosome 10 was detected in 10 cases (representing three breeds) and two unphenotyped parents but in none of the controls. The duplication was embedded in an 8-Mb haplotype shared across breeds. [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 detailAllelic heterogeneity of Crooked Tail Syndrome: result of balancing selection?
Sartelet, Arnaud ULg; Klingbeil, Pamela; Franklin, Chris et al

in Animal Genetics (2012), 43(5), 604-607

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See detailGenetic variation in PLAG1 associates with early life body weight and peripubertal weight and growth in Bos taurus.
Littlejohn, M.; Grala, T.; Sanders, K. et al

in Animal Genetics (2012), 43(5), 591-4

Variation at the pleiomorphic adenoma gene 1 (PLAG1) locus has recently been implicated in the regulation of stature and weight in Bos taurus. Using a population of 942 outbred Holstein-Friesian dairy ... [more ▼]

Variation at the pleiomorphic adenoma gene 1 (PLAG1) locus has recently been implicated in the regulation of stature and weight in Bos taurus. Using a population of 942 outbred Holstein-Friesian dairy calves, we report confirmation of this effect, demonstrating strong association of early life body weight with PLAG1 genotype. Peripubertal body weight and growth rate were also significantly associated with PLAG1 genotype. Growth rate per kilogram of body weight, daily feed intake, gross feed efficiency and residual feed intake were not significantly associated with PLAG1 genotype. This study supports the status of PLAG1 as a key regulator of mammalian growth. Further, the data indicate the utility of PLAG1 polymorphisms for the selection of animals to achieve enhanced weight gain or conversely to aid the selection of animals with lower mature body weight and thus lower maintenance energy requirements. [less ▲]

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See detailHost-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
Jostins, Luke; Ripke, Stephan; Weersma, Rinse K. et al

in Nature (2012), 491(7422), 119-24

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome ... [more ▼]

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD. [less ▲]

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