References of "Karim, Latifa"
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See detailA stop-gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle
Sartelet, Arnaud ULg; Harland, Chad ULg; Tamma, Nico ULg et al

in Animal Genetics (2015), 46(5), 566-570

Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity ... [more ▼]

Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3-Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected calf, (ii) transcriptomic data from a panel of tissues and (iii) a list of functionally ranked positional candidates pinpointed a private G to A nucleotide substitution in the LAMA3 gene that creates a premature stop codon (p.Arg2609*) in exon 60, truncating 22% of the corresponding protein. The LAMA3 gene encodes the alpha 3 subunit of the heterotrimeric laminin-332, a key constituent of the lamina lucida that is part of the skin basement membrane connecting epidermis and dermis layers. Homozygous loss-of-function mutations in this gene are known to cause severe junctional epidermolysis bullosa in human, mice, horse, sheep and dog. Overall, our data strongly support the causality of the identified gene and mutation. [less ▲]

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See detailIdentification of molecular components of the host-microbiota-connectome by using "Omics Approaches"
Mariman, Rob ULg; Coppieters, Wouter ULg; Elansary, Mahmoud ULg et al

Poster (2014, April 24)

The host immune system plays an critical role in maintaining homeostasis with resident microbial communities, therefore ensuring that the complex symbiotic relationship is maintained. At the same time ... [more ▼]

The host immune system plays an critical role in maintaining homeostasis with resident microbial communities, therefore ensuring that the complex symbiotic relationship is maintained. At the same time, resident microbiota contribute to host nutrition and energy balance and to the development or maintenance of a robust immune system. Dysbiosis of the microbiota is associated with various immunological disorders, including inflammatory bowel diseases (IBD). Both genetic and environmental factors are implicated in this disturbance; however, the relative contributions of these two factors, and the mechanism by which they interact remain unclear. Recently, we started a project that aims to identify molecular components of the hostmicrobiota-connectome by taking advantage of common variation in – on the one hand – the genome, transcriptome and metabolome of the host, and – on the other hand – the composition of its gut microbiota. We will take advantage of the already established CEDAR cohort that provides integrated genetic (SNP genotypes) and transcriptome data (circulating immune cells subset, as well as samples from various anatomical locations in the intestine). We will further enrich the dataset in this cohort with metabolome (plasma), and gut microbiota data (16srRNA sampled at the ileum, colon, and rectum). The CEDAR cohort is composed of healthy individuals and is therefore more suitable to study effect of common risk variants than (IBD) patients, since analysis of samples from patients suffering from active inflammation may only give insight in ongoing patho-physiological processes, that are likely to mask the primum movens events. Next, we will study the overlap between the identified components of the HMC network identified and the ~160 GWAS-identified risk loci for IBD. We anticipate to reveal novel connections between the microbiota and IBD by this integrative “omics” approach, thereby shedding new light on the pathogenesis of IBD. Latest results will be presented with respect to the microbiota composition of from different anatomical locations in the intestine using the V2 and V5-6 regions of the bacterial 16S rRNA. [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 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 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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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 ▲]

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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 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 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 detailThe callipyge (CLPG) mutation enhances the expression of the coregulated DLK1, GTL2, PEG11 and MEG8 genes in cis without affecting their imprinting status
Charlier, Carole ULg; SEGERS, Karin ULg; Karim, Latifa ULg et al

in Nature Genetics (2001), 27

The callipyge (CLPG) phenotype (from kappa(alpha)lambda(iota), "beautiful," and pi(iota)gamma(epsilon), "buttocks") described in sheep is an inherited muscular hypertrophy that is subject to an unusual ... [more ▼]

The callipyge (CLPG) phenotype (from kappa(alpha)lambda(iota), "beautiful," and pi(iota)gamma(epsilon), "buttocks") described in sheep is an inherited muscular hypertrophy that is subject to an unusual parent-of-origin effect referred to as polar overdominance: only heterozygous individuals having inherited the CLPG mutation from their sire exhibit the muscular hypertrophy. The callipyge (clpg) locus was mapped to a chromosome segment of approximately 400 kb (refs. 2-4), which was shown to contain four genes (DLK1, GTL2, PEG11 and MEG8) that are preferentially expressed in skeletal muscle and subject to parental imprinting in this tissue. Here we describe the effect of the CLPG mutation on the expression of these four genes, and demonstrate that callipyge individuals have a unique expression profile that may account for the observed polar overdominance. [less ▲]

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