References of "Georges, Michel"
     in
Bookmark and Share    
Full Text
See detailSequence-based association analysis identifies coding and non-coding variants in HFM1, MLH3, MSH4, MSH5, RNF212 and RNF212B with large effects on male and female recombination rate in cattle
Kadri, Naveen Kumar ULg; Harland, Chad ULg; Faux, Pierre ULg et al

Poster (2016, June 15)

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We identify 2,395,177 crossover (CO) events in sperm cells transmitted by 2,940 sires ... [more ▼]

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We identify 2,395,177 crossover (CO) events in sperm cells transmitted by 2,940 sires to 94,516 offspring, and 579,996 CO events in oocytes transmitted by 11,461 cows to 25,332 offspring. When measured in identical family structures, the average number of CO in males (23.3) was found to be larger than in females (21.4). The heritability of global recombination rate (GRR) was estimated at 0.13 in males and 0.08 in females. The genetic correlation was equal to 0.66, indicating that shared variants are influencing GRR in both genders. Haplotype-based genome-wide association studies revealed seven genome-wide significant QTL. Variants identified by next-generating sequencing in 5 Mb windows encompassing the QTL peaks were imputed in order to perform a sequence-based association analysis. For four QTLs, we identified missense mutations in genes known to be involved in meiotic recombination among the most significantly associated variants. Most of the identified mutations had significant effects in both genders with three of them accounting each for approximately 10% of the genetic variance in males (the allelic substitution effect being approximately equal to one additional CO per genome). Thus, a large fraction of the genetic variance is associated with missense mutations in genes known to be involved in meiotic recombination. Our results are very different from reports of recombination in other species. For instance, in human, recombination rate is higher in females, distinct variants affect recombination rate in males and females, and the genetic correlation is close to 0, whereas in cattle, we observed a higher recombination rate in males controlled by shared variants effective in both sexes. [less ▲]

Detailed reference viewed: 56 (3 ULg)
Peer Reviewed
See detailIdentification and characterization of novel bovine leukemia virus (BLV) antisense transcripts in leukemic and pre-leukemic clones
Durkin, Keith ULg; Rosewick, Nicolas; Artesi, Maria ULg et al

Conference (2016, May 21)

The deltaretrovirus Bovine Leukemia Virus (BLV) is closely related to the Human T-cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, produces a lifelong ... [more ▼]

The deltaretrovirus Bovine Leukemia Virus (BLV) is closely related to the Human T-cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, produces a lifelong infection. Most infected animals remain asymptomatic but following a protracted latency period about ~5% develop an aggressive leukemia/lymphoma, mirroring the disease trajectory of HTLV-1. Like the case in HTLV-1 the 5’LTR BLV provirus is transcriptionally silent in tumors, however the provirus is not entirely quiescent, constitutively express the BLV microRNAs in tumors. Using RNA-seq, we found that in addition to microRNAs, the BLV provirus also constitutively expresses two antisense transcripts in all BLV infected samples examined. The first transcript (AS1) has alternate potential polyadenylation sites generating a short transcript of ~600bp (AS1-S) and a less abundant longer transcript of ~2200bp (AS1-L). Alternative splicing also creates a second transcript of ~400bp (AS2) utilizing the first exon of AS1. Production of AS transcripts from the 3’LTR was supported by reporter assays demonstrating that the BLV LTR has substantial and Tax-independent antisense promoter activity. BLV AS transcripts predominantly localize in the nucleus. Examination of protein coding potential showed AS2 to be non-coding, while the AS1-S/L transcripts coding potential is ambiguous, with a small potential open reading frame (ORF) of 264bp present. The AS1-L transcript overlaps the BLV microRNAs transcribed in the sense direction. Using high throughput sequencing of RNA-ligase-mediated (RLM) 5' RACE products, we show that the perfect complementary between the transcripts leads to RNA-induced silencing complex (RISC) mediated cleavage of AS1-L. Furthermore, experiments using BLV proviruses where the microRNAs were removed or inverted point to additional transcriptional interactions between the two viral RNA species. Knock down of AS1-S/L using locked nucleic acids (LNAs) showed no obvious effect on the cells phenotype. While a detailed elucidation of the BLV antisense transcripts function remains in the future, the constitutive expression in all samples examined, points to a vital role for the transcripts in the life cycle and oncogenic potential of BLV. [less ▲]

Detailed reference viewed: 25 (1 ULg)
See detailHIGHER MALE THAN FEMALE RECOMBINATION RATE LARGELY CONTROLLED BY MISSENSE VARIANTS IN RNF212, MLH3, HFM1, MSH5 AND MSH4 IN CATTLE
Kadri, Naveen Kumar ULg; Harland, Chad ULg; Faux, Pierre ULg et al

Poster (2016, May 11)

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We identify 2,395,177 crossover (CO) events in sperm cells transmitted by 2,940 sires ... [more ▼]

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We identify 2,395,177 crossover (CO) events in sperm cells transmitted by 2,940 sires to 94,516 offspring, and 579,996 CO events in oocytes transmitted by 11,461 cows to 25,332 offspring. When measured in identical family structures, the average number of CO in males (23.3) was found to be larger than in females (21.4). The heritability of global recombination rate (GRR) was estimated at 0.13 in males and 0.08 in females. The genetic correlation was equal to 0.66, indicating that shared variants are influencing GRR in both genders. Haplotype-based genome-wide association studies revealed seven genome-wide significant QTL. Variants identified by next-generating sequencing in 5 Mb windows encompassing the QTL peaks were imputed in order to perform a sequence-based association analysis. For four QTLs, we identified missense mutations in genes known to be involved in meiotic recombination among the most significantly associated variants. The P259S variant identified in RNF212 had already been reported, whereas missense mutations in MLH3 (N408S), HFM1 (S1189L), MSH5 (R631Q), MSH4 (C342Y) and a second in RNF212 (A77T) are new. Surprisingly, variants previously identified in REC8 were not associated with a QTL detected on BTA10 whereas variants in RNF212B, a paralog of RNF212, showed much stronger association with the phenotype in this region. This suggests that RNF212B might be involved in the recombination process. Most of the identified mutations had significant effects in both genders with three of them accounting each for approximately 10% of the genetic variance in males (the allelic substitution effect being approximately equal to one additional CO per genome). Thus, a large fraction of the genetic variance is associated with missense mutations in genes known to be involved in meiotic recombination. Our results are very different from reports of recombination in other species. For instance, in human, recombination rate is higher in females, distinct variants affect recombination rate in males and females, and the genetic correlation is close to 0, whereas in cattle, we observed a higher recombination rate in males controlled by shared variants effective in both sexes. [less ▲]

Detailed reference viewed: 32 (0 ULg)
Peer Reviewed
See detailThe impact of dopaminergic genes on inhibitory processes and cognitive control.
Jaspar, Mathieu ULg; Muto, Vincenzo ULg; Meyer, Christelle et al

Poster (2016, March 18)

Detailed reference viewed: 29 (5 ULg)
Full Text
Peer Reviewed
See detailCoding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle.
Kadri, Naveen Kumar ULg; Harland, Chad ULg; Faux, Pierre ULg et al

in Genome Research (2016)

We herein study genetic recombination in three cattle populations from France, New Zealand, and the Netherlands. We identify 2,395,177 crossover (CO) events in 94,516 male gametes, and 579,996 CO events ... [more ▼]

We herein study genetic recombination in three cattle populations from France, New Zealand, and the Netherlands. We identify 2,395,177 crossover (CO) events in 94,516 male gametes, and 579,996 CO events in 25,332 female gametes. The average number of COs was found to be larger in males (23.3) than in females (21.4). The heritability of global recombination rate (GRR) was estimated at 0.13 in males and 0.08 in females, with a genetic correlation of 0.66 indicating that shared variants are influencing GRR in both sexes. A genome-wide association study identified seven quantitative trait loci (QTL) for GRR. Fine-mapping following sequence-based imputation in 14,401 animals pinpointed likely causative coding (5) and noncoding (1) variants in genes known to be involved in meiotic recombination (HFM1, MSH4, RNF212, MLH3, MSH5) for 5/7 QTL, and noncoding variants (3) in RNF212B for 1/7 QTL. This suggests that this RNF212 paralog might also be involved in recombination. Most of the identified mutations had significant effects in both sexes, with three of them each accounting for approximately 10% of the genetic variance in males. [less ▲]

Detailed reference viewed: 25 (3 ULg)
Full Text
Peer Reviewed
See detailGenome-wide association study of acute renal graft rejection.
Ghisdal, L.; Baron, C.; Lebranchu, Y. et al

in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (2016)

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T ... [more ▼]

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls, on Illumina 2.5 M arrays. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant SNPs from the discovery cohort. In the discovery cohort, we found 5 candidate loci tagged by a number of contiguous SNPs (>5) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signalling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium. This article is protected by copyright. All rights reserved. [less ▲]

Detailed reference viewed: 9 (1 ULg)
Full Text
Peer Reviewed
See detailCharacterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs.
Durkin, Keith ULg; Rosewick, Nicolas; Artesi, Maria ULg et al

in Retrovirology (2016), 13(1), 33

BACKGROUND: Bovine Leukemia Virus (BLV) is a deltaretrovirus closely related to the Human T cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, producing a ... [more ▼]

BACKGROUND: Bovine Leukemia Virus (BLV) is a deltaretrovirus closely related to the Human T cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, producing a lifelong infection. Most infected animals remain asymptomatic but following a protracted latency period about 5 % develop an aggressive leukemia/lymphoma, mirroring the disease trajectory of HTLV-1. The mechanisms by which these viruses provoke cellular transformation remain opaque. In both viruses little or no transcription is observed from the 5'LTR in tumors, however the proviruses are not transcriptionally silent. In the case of BLV a cluster of RNA polymerase III transcribed microRNAs are highly expressed, while the HTLV-1 antisense transcript HBZ is consistently found in all tumors examined. RESULTS: Here, using RNA-seq, we demonstrate that the BLV provirus also constitutively expresses antisense transcripts in all leukemic and asymptomatic samples examined. The first transcript (AS1) can be alternately polyadenylated, generating a transcript of ~600 bp (AS1-S) and a less abundant transcript of ~2200 bp (AS1-L). Alternative splicing creates a second transcript of ~400 bp (AS2). The coding potential of AS1-S/L is ambiguous, with a small open reading frame of 264 bp, however the transcripts are primarily retained in the nucleus, hinting at a lncRNA-like role. The AS1-L transcript overlaps the BLV microRNAs and using high throughput sequencing of RNA-ligase-mediated (RLM) 5'RACE, we show that the RNA-induced silencing complex (RISC) cleaves AS1-L. Furthermore, experiments using altered BLV proviruses with the microRNAs either deleted or inverted point to additional transcriptional interference between the two viral RNA species. CONCLUSIONS: The identification of novel viral antisense transcripts shows the BLV provirus to be far from silent in tumors. Furthermore, the consistent expression of these transcripts in both leukemic and nonmalignant clones points to a vital role in the life cycle of the virus and its tumorigenic potential. Additionally, the cleavage of the AS1-L transcript by the BLV encoded microRNAs and the transcriptional interference between the two viral RNA species suggest a shared role in the regulation of BLV. [less ▲]

Detailed reference viewed: 16 (2 ULg)
Full Text
Peer Reviewed
See detailEctopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy.
Xu, Xuewen; Ectors, Fabien ULg; Davis, Erica E. et al

in PloS one (2015), 10(10), 0140594

The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype ... [more ▼]

The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep. [less ▲]

Detailed reference viewed: 52 (18 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 69 (13 ULg)
Full Text
Peer Reviewed
See detailImproving the methodology for the detection of proviral integration sites in the host genome via high throughput sequencing.
Durkin, Keith ULg; Artesi, Maria ULg; Rosewick, Nicolas et al

in Retrovirology (2015, August 28), 12(1),

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailOn the use of the transmission disequilibrium test to detect pseudo-autosomal variants affecting traits with sex-limited expression
Elansary, Mahmoud ULg; Stinckens, Anneleen; Ahariz, Naïma ULg et al

in Animal Genetics (2015)

We herein describe the realization of a genome-wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission ... [more ▼]

We herein describe the realization of a genome-wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission disequilibrium test to avoid spurious associations due to population stratification. By doing so, we obtained genome-wide significant signals for both diseases with SNPs located in the pseudo-autosomal region in the vicinity of the pseudo-autosomal boundary. By further analyzing these signals, we demonstrate that the observed transmission disequilibria are artifactual. We determine that transmission bias at pseudo-autosomal markers will occur (i) when analyzing traits with sex-limited expression and (ii) when the allelic frequencies at the marker locus differ between X and Y chromosomes. We show that the bias is due to the fact that (i) sires will preferentially transmit the allele enriched on the Y (respectively X) chromosome to affected sons (respectively daughters) and (ii) dams will appear to preferentially transmit the allele enriched on the Y (respectively X) to affected sons (respectively daughters), as offspring inheriting the other allele are more likely to be non-informative. We define the conditions to mitigate these issues, namely by (i) extracting information from maternal meiosis only and (ii) ignoring trios for which sire and dam have the same heterozygous genotype. We show that by applying these rules to scrotal hernia and cryptorchidism, the pseudo-autosomal signals disappear, confirming their spurious nature. [less ▲]

Detailed reference viewed: 38 (5 ULg)
See detailPrioritizing likely causative genes in GWAS identified risk loci for immune-mediated inflammatory disorders using cell-type specific eQTL information.
Docampo Martínez, Elisa ULg; Fang, Ming ULg; Dmitrieva, Joelia Borisnova ULg et al

Poster (2015, May 05)

Background/Purpose: Immune-mediated inflammatory disorders (IMIDs) share many genetic risk factors. Pleiotropy may exist at different levels and most of the underlying mechanisms are still to be uncovered ... [more ▼]

Background/Purpose: Immune-mediated inflammatory disorders (IMIDs) share many genetic risk factors. Pleiotropy may exist at different levels and most of the underlying mechanisms are still to be uncovered. GWAS have identified hundreds of risk loci for IMIDs but causative genes have been identified in only a handful of cases. Recent fine-mapping efforts indicate that only a minority of risk variants are coding. This suggests that most risk variants will be regulatory hence affecting disease risk via eQTL effects. Methods: To aid in the identification of causative genes for IMIDs, we generated transcriptome information (HT12 arrays) for six blood cell types (CD4, CD8, CD19, CD14, CD15 and platelets) and intestinal biopsies at three anatomical locations (ileum, colon, rectum) for 350 healthy Caucasians. The same individuals were genotyped with SNP arrays interrogating > 700K variants, augmented by imputation from the 1KG project. To detect cis-eQTL we tested variants within 0.5 megabase windows centered on the tested probe. The nominal p-value of the best SNP within a cis-window was Sidak-corrected for the window-specific number of independent tests. The corresponding best, Sidak-corrected p-values for each probe were jointly used to estimate their respective false discovery rate.To identify likely causative genes in GWAS identified risk loci variants and also better understand pleiotropic effects, we (i) developed a method that quantifies the correlation between “disease association pattern” (DAP) and “eQTL association pattern” (EAP) and provides an empirical estimate of its significance, and (ii) evaluated the effect of fitting known risk variants as covariates in the eQTL analysis following Nica et al. (2010). We applied both approaches to celiac disease (CE) and rheumatoid arthritis (RA) and the second one to type one diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and psoriasis (PSO). Results: We detected > 16000 significant cis-eQTL, with a degree of sharing between cell types ranging from 38 to 90% highlighting the utility of our multi-tissue panel. GWAS variants were drivers of ciseQTL effects across the different tissues in 399 tests (23.6%), mostly in CD4 cells, and pinpointing 64 new gene-disease associations (3.7%). The number of shared loci and shared eQTL were highly correlated (rho=0.66).RA and SLE showed the highest degree of sharing. Conclusions: We identified new potential candidate genes for IMIDs and characterized pleiotropic effects through ciseQTL mapping in GWAS loci. These findings could shed a light on IMIDs pathogenesis and co-occurrence. Latest results will be presented. [less ▲]

Detailed reference viewed: 105 (12 ULg)
Full Text
See detailHigher male than female recombination rate in cattle is controlled by genetic variants effective in both sexes
Kadri, Naveen Kumar ULg; Harland, Chad ULg; Coppieters, Wouter ULg et al

Poster (2015, May 05)

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We apply a new phasing algorithm extracting familial information suited for large half ... [more ▼]

We herein study genetic recombination in three dairy cattle populations from France, New-Zealand and the Netherlands. We apply a new phasing algorithm extracting familial information suited for large half-sib families to reconstruct haplotypes and detect cross-overs (CO). The software is robust to genotyping and map errors. We identify more than 2,000,000 CO events in sperm cells transmitted by 3008 sires to 94,603 offspring, and more than 500,000 CO events in oocytes transmitted by 11,497 cows to 25,390 offspring. When measured in identical family structures, the average number of CO in males (24.0) was found to be larger than in females (21.8). In males, recombination rates were higher closer to telomeres whereas in females, recombination rates dropped at both centromeres and telomeres (probably as a result of lower informativity). The heritability of the global recombination rate (GRR) was close to 0.20 in males and to 0.08 in females. Genetic correlation ranged from 0.38 to 0.69 depending on the population, indicating that shared variants are influencing GRR in both genders. Haplotype-based genome-wide association studies revealed four genome-wide significant QTL, including two previously identified ones (involving REC8 and RNF212). For all QTLs, there was a positive correlation between haplotype effects across sexes, ranging from 0.35 to 0.68. We selected two reference panels of respectively 122 and 215 bulls sequenced at cover > 15x to impute variants in the New-Zealand and French populations. All variants identified by next-generating sequencing in 5 Mb windows encompassing the QTL peaks were imputed with Beagle in order to perform a sequence-based association study. For three QTLs, we identified missense mutations in genes known to be involved in meiosis among the most significantly associated variants. These variants were perfectly associated with the haplotypes underlying the QTL effects. The variant identified in RNF212 had already been reported, whereas missense mutations in MLH3 (N408S) and HFM1 (S1189L) are new findings. Surprisingly, variants previously identified in REC8 did not capture the QTL effect whereas variants in RNF212B, PPP1R3E, BCL2L2, HOMEZ and PABPN1 had much stronger association with the phenotype. The three missense mutations were significant in both genders with two of them accounting for approximately 10% of the genetic variance in males (the allelic substitution effect being approximately equal to one additional CO per genome). Our results are very different from reports of recombination in other species. For instance, in human, recombination rate is higher in females, distinct variants affect recombination rate in males and females and the genetic correlation is close to 0 whereas in cattle, we observed a higher recombination rate in males controlled by shared variants effective in both sexes. [less ▲]

Detailed reference viewed: 111 (12 ULg)
Full Text
See detailX-Linked acro-gigantism (X-LAG) due to microduplications of chromosome Xq26 : A new disorder and implications for acromegaly
Trivellin, G; Daly, AF; Faucz, FR et al

in Abstract book - ENDO 2015 (2015, March)

Detailed reference viewed: 31 (8 ULg)
Full Text
See detailScanning the genome for QTL affecting the recombination process in the male and female cattle germline
Kadri, Naveen Kumar ULg; Harland, Chad ULg; Coppieters, Wouter ULg et al

Poster (2015, February)

We herein study genetic recombination in three dairy cattle population from France, New-Zealand and The Netherlands. We apply a new phasing algorithm extracting familial information suited for large half ... [more ▼]

We herein study genetic recombination in three dairy cattle population from France, New-Zealand and The Netherlands. We apply a new phasing algorithm extracting familial information suited for large half-sib families to reconstruct haplotypes and detect cross-overs. The software is robust to genotyping errors and map errors (genome builts still contain errors for non-model organisms). We identify more than 2,000,000 cross-over events in sperm cells transmitted by 2942 sires to 94,049 offspring, and more than 500,000 cross-over events in oocytes transmitted by 10,943 cows to 23,850 offspring. The estimated number of cross-overs per gamete and its accuracy were influenced by the family structure (number of offsprings, parents and grand-parents genotyped). The average number of cross-overs in males (24.0) was larger than in females (21.8), even after correction for family structure. In males, recombination rates were higher closer to telomeres whereas in females, recombination rates dropped at both centromeres and telomeres (probably as a result of lower informativity). The heritability of the global recombination rate was close to 0.20 in males and to 0.10 in females and the genetic correlation was ~0.70, indicating that common genes are influencing both traits. Genome-wide association studies clearly confirmed QTL located close to REC8 and RNF212 in males. The QTL associated to REC8 was also detected in females and there was a positive correlation between QTL effects in males and females. The QTL associated to REC8 accounted for ~10% of the genetic variance in both males and females. [less ▲]

Detailed reference viewed: 91 (9 ULg)
Peer Reviewed
See detailLordose et/ou xyphose chez le porc : mise à l’épreuve de l’hypothèse héréditaire
Laitat, Martine ULg; Veillat, Emilie; Van Cauwenberge, Henry et al

Poster (2015, February)

Lordosis and/or kyphosis, also called ”dipped shoulder” or ”humpy‐back” is sporadically observed in growing pigs. This condition is characterized by a thoracic and/or lumbar spinal deformity ... [more ▼]

Lordosis and/or kyphosis, also called ”dipped shoulder” or ”humpy‐back” is sporadically observed in growing pigs. This condition is characterized by a thoracic and/or lumbar spinal deformity. Pathomorphologically, it may be comparable with Scheuermann’s kyphosis in man and so constitutes a spontaneous model for this humane kyphosis of the thoracic or thoracolumbar spine. In pigs, this condition may decrease the value of carcasses, making deboning efforts challenging. Three major and non‐exclusive hypotheses formulated to explain these back deformations are nutrition, intrauterine viral infection and inherited predisposition. The objective of the present study was to test the latter and, if possible, to identify a locus (some loci) associated with the affection. Forty‐eight pigs were included in this case‐control study. Based on a clinical examination and/or on a measure of the degree of spinal deformity, 25 pigs classified as affected were compared to 23 pigs considered as normal. A whole genome Single Nucleotide Polymorphism (SNP) analysis was performed using a 50,000 SNP array. DNA from forty‐seven samples (tail tissue or blood) was extracted while one sample was eliminated because of its poor quality. After applying quality controls, 40 pigs and 57,838 SNPs (on a total of 62,163) remained for further analysis. One SNP (ASGA0090747) located on Sus scrofa chromosome SSC8 crossed the genome‐wide significant threshold and is thus suspected of being associated with the lordosis and/or kyphosis phenotype. These results seem to confirm the hereditary hypothesis. Further investigations are however needed to confirm the suspected association. [less ▲]

Detailed reference viewed: 115 (12 ULg)
Full Text
Peer Reviewed
See detailHigh-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis.
Goyette, Philippe; Boucher, Gabrielle; Mallon, Dermot et al

in Nature Genetics (2015), 47(2), 172-9

Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major ... [more ▼]

Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD. [less ▲]

Detailed reference viewed: 77 (18 ULg)