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14 results on '"Julien Sarry"'

1. A single base pair duplication inSLC33A1gene causes fetal losses and neonatal lethality in Manech Tête Rousse dairy sheep

Author

Maxime Ben Braiek, Soline Szymczak, Céline André, Philippe Bardou, Francis Fidelle, Itsasne Granado-Tajada, Florence Plisson-Petit, Julien Sarry, Florent Woloszyn, Carole Moreno-Romieux, Stéphane Fabre, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Départemental de l'Elevage Ovin (CDEO), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), NEIKER-Basque Institute for Agricultural Research and Development, CASDAR n°20ART1532777, PRESAGE, APISGENE, HOMLET, Région OCCITANIE, HOMLET, PRESAGE, HOMLET, European Project: 772787,H2020-EU.3.2.1.1., and H2020-EU.3.2.,SMARTER(2018)

Subjects
Ovis aries, acetyl-CoA transporter, neonatal mortality, [SDV]Life Sciences [q-bio], lethal variant, MTRDHH2, abortion, SLC33A1, Ovis aries homozygous haplotype deficiency MTRDHH2 lethal variant abortion neonatal mortality SLC33A1 acetyl-CoA transporter, homozygous haplotype deficiency
Abstract

Recently, we evidenced that the Manech Tête Rousse (MTR) deficient homozygous haplotype 2 (MTRDHH2) was likely to harbor a recessive lethal variant in ovine. In the present study, we fine mapped this region by analyzing the whole genome sequence of five MTRDHH2 heterozygous carriers compared to 95 sequences of non-carrier animals from MTR and others ovine breeds. We successfully identified a single base pair duplication in theSLC33A1gene, resulting in a frameshift leading to a premature stop codon (p.Arg246Alafs*3). SLC33A1 acts as a transmembrane transporter of acetyl-Coenzyme A, essential for cellular metabolism. In order to assess for the lethal phenotype in homozygous MTR sheep, we generated at-risk matings by artificial insemination (AI) between rams and ewes heterozygous for theSLC33A1variant namedSLC33A1_dupG. Gestation status was checked 15 days post-AI by a molecular test from blood expression of the interferon Tau-stimulatedMX1gene, and by ultrasonography performed between 45 days and 60 days post-AI. Based on ultrasonography, the AI success was reduced by 12% compared to safe matings suggesting embryonic/fetal losses further confirmed by the molecular test based onMX1differential expression. Forty-nine lambs were born from at-risk matings with a mortality rate of 34.7% observed before weaning. HomozygousSLC33A1_dupG lambs contributed to 47% of this mortality occurring mainly in the first five days after lambing with no obvious clinical signs. Thus, an appropriate management ofSLC33A1_dupG (allele frequency of 0.04) in the MTR selection scheme should increase the overall fertility and lamb survival.

Published
2023
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2. Homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant inMMUTgene affecting newborn lamb viability

Author

Maxime Ben Braiek, Carole Moreno-Romieux, Céline André, Jean-Michel Astruc, Philippe Bardou, Arnaud Bordes, Frédéric Debat, Francis Fidelle, Itsasne Granado–Tajada, Chris Hozé, Florence Plisson-Petit, François Rivemale, Julien Sarry, Némuel Tadi, Florent Woloszyn, Stéphane Fabre, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Départemental de l'Elevage Ovin (CDEO), Institut de l'élevage, Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), NEIKER-Basque Institute for Agricultural Research and Development, Eliance, CASDAR n°20ART1532777 PRESAGE, PRESAGE, European Project: 772787,H2020-EU.3.2.1.1., and H2020-EU.3.2.,SMARTER(2018)

Subjects
Ovis aries, Methylmalonic aciduria, neonatal mortality, MTRDHH1, [SDV]Life Sciences [q-bio], lethal variant, MMUT, homozygous haplotype deficiency
Abstract

Recessive deleterious variants are known to segregate in livestock populations as in human, and some may cause lethality when homozygous. By scanning the genome of 6,845 Manech Tête Rousse dairy sheep using phased 50k SNP genotypes and pedigree data, we searched for deficiency in homozygous haplotype (DHH). Five Manech Tête Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified with a homozygous deficiency ranging from 84% to 100%. These haplotypes are located on OAR1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5) and OAR20 (MTRDHH1), and have frequencies ranging from 7.8% to 16.6%. When comparing at-risk mating between DHH carriers to safe mating between non-carriers, two DHH (MTRDHH1 and 2) showed significant effects on decreasing artificial insemination success and/or increasing stillbirth rate. We particularly investigated the MTRDHH1 haplotype highly increasing stillbirth rate, and we identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in theMMUTgene (methylmalonyl-CoA mutase) by using a whole genome sequencing (WGS) approach. We generated homozygous lambs for theMMUTmutation by oriented mating, and most of them died within the first 24h after birth without any obvious clinical defect. RT-qPCR and western blotting performed on post-mortem liver and kidney biological samples showed a decreased expression ofMMUTmRNA in the liver and absence of a full-length MMUT protein in mutated homozygous lambs. In parallel, MTRDHH4 and MTRDHH5 showed partial association with variants inRXFP2andASIPgenes, respectively, already known to control horned/polled and coat color phenotypes in sheep, two morphological traits accounting in the MTR breed standard. Further investigations are needed to identified the supposed recessive deleterious variant hosted by MTRDHH2 and MTRDHH3. Anyway, an appropriate management of these haplotypes/variants in the MTR dairy sheep selection program should increase the overall fertility and lamb survival.Author SummaryIn this article, we used reverse genetics screen in ovine using large genotype data available in the framework of genomic selection program in Manech Tête Rousse dairy sheep. We identified five genomic regions with a highly significant deficit in homozygous animal. These regions are thus supposed to host recessive deleterious mutations. In one of these genomic regions, we identified a nonsense mutation inMMUTthat alters the functioning of this essential gene of cell metabolism, causing perinatal mortality of homozygous lambs. In this work, we also identified other regions possibly associated with morphological appearance part of the breed standard such as polledness and coat color. Increasing knowledge in these genomic regions will help the future genetic management of the Manech Tête Rousse breed, particularly to reduce lamb mortality.

Published
2023
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3. A validation study of loci associated with mastitis resistance in two French dairy sheep breeds

Author

Charlotte Allain, Claire Oget, David Portes, Gilles Foucras, Rachel Rupp, Alessandra Stella, Julien Sarry, J. M. Astruc, Gwenola Tosser-Klopp, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Domaine expérimental de La Fage (LA FAGE), Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), PTP Science Park, Institut de l'élevage (IDELE), This work was supported by grants from the EU 3SR project (FP7-KBBE, Project ID: 245140) and the French National Research Agency (ANR) REIDSOCS project (ANR 2016, Project ID: ANR-16-CE20-0010)., ANR-16-CE20-0010,REIDSOCS,Robustesse, Efficacité, Inflammation et Maladies sous le contrôle de SOCS-2(2016), European Project: 245140,EC:FP7:KBBE,FP7-KBBE-2009-3,3SR(2010), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), and Université de Toulouse (UT)-Université de Toulouse (UT)

Subjects
sheep, lcsh:QH426-470, 040301 veterinary sciences, Short Communication, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Sheep Diseases, Single-nucleotide polymorphism, Mastitis, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, goat, mastitis resistance, 0403 veterinary science, resistance, 03 medical and health sciences, Polymorphism (computer science), genomics, Genetics, medicine, Animals, SNP, Udder, Ovis, Ecology, Evolution, Behavior and Systematics, Disease Resistance, lcsh:SF1-1100, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, snp, 04 agricultural and veterinary sciences, General Medicine, parameter, genetic, biology.organism_classification, medicine.disease, lcsh:Genetics, medicine.anatomical_structure, Backcrossing, Female, Animal Science and Zoology, lcsh:Animal culture, Autre (Sciences du Vivant)
Abstract

BACKGROUND: The identification of loci associated with resistance to mastitis or of the causative mutations may be helpful in breeding programs for dairy sheep as it is for cattle worldwide. Seven genomic regions that control milk somatic cell counts, an indirect indicator of udder infection, have already been identified in sheep (Spanish Churra, French Lacaune and Italian Sardinian-Lacaune backcross populations). In this study, we used a 960 custom-designed ovine single nucleotide polymorphism (SNP) chip in Lacaune and Manech Tête Rousse dairy sheep to validate these seven genomic regions associated with mastitis.RESULTS: The most significant SNP (rs868996547) on Ovis aries chromosome (OAR) 3 was a previously described mutation in the suppressor of cytokine signalling 2 (SOCS2) gene. An antagonist effect of this causal candidate between health and growth in Lacaune sheep was confirmed. Effects of the mutation on the infectious status of the udder, i.e. increases in milk somatic cell counts and bacteria shedding, were also identified. This SNP was not present in the data available on Manech Tête Rousse. Three other regions associated with mastitis were also confirmed on OAR16 (Manech Tête Rousse), 19 (Lacaune) and 2 (both breeds). For the OAR2 region, we validated previously detected SNPs in several other breeds (Sarda, Churra, and Chios). For significant SNPs in the four mastitis regions, the effect varied from 0.24 to 0.67 phenotypic standard deviation of the traits. Two of the mastitis quantitative trait loci (QTL) regions (OAR2 and 16) that we validated here were also associated in opposite ways with milk production traits in both populations.CONCLUSIONS: These results indicate, at least in part, a genomic basis for the trade-off between milk production and mastitis resistance. Four of the seven mastitis QTL regions that were previously identified in independent populations, were confirmed in this study, which demonstrates partial sharing of mastitis-related genetic mechanisms between different distant dairy sheep populations.

Published
2019
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4. The high prolificacy of D’man sheep is associated with the segregation of the FecLL mutation in the B4GALNT2 gene

Author

Stéphane Fabre, Florent Woloszyn, N. Lassoued, Slim Ben Jemaa, Julien Sarry, Julien Ruesche, Université de Carthage - University of Carthage, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique de Tunisie (INRAT), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the International Foundation for Science (IFS grant B/5478‐2) and by the Tunisian Livestock and Pasture Office (OEP)., and European Project: 244356,EC:FP7:KBBE,FP7-KBBE-2009-3,NEXTGEN(2010)

Subjects
D'man sheep, [SDV]Life Sciences [q-bio], Locus (genetics), Biology, Genetic determinism, prolificacy, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Animal science, Genotype, B4GALNT2, [INFO]Computer Science [cs], Allele, Genotyping, major gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, 030219 obstetrics & reproductive medicine, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Fecundity, 040201 dairy & animal science, Major gene, Breed, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Animal Science and Zoology, Biotechnology
Abstract

International audience; Mutations in the FecL locus are associated with large variation in ovulation rate and litter size in the French Lacaune sheep breed. It has been shown that the B4GALNT2 gene within the FecL locus is most likely responsible for the high fecundity in the French breed. In this study, we have highlighted the segregation of the FecLL mutation within the B4GALNT2 gene in North African sheep breeds and notably in the highly prolific D'man breed. Genotyping of a sample of 183 Tunisian D'man individuals revealed a high frequency (0.65) of the prolific allele FecLLwhich was attributed to the adoption of a decades‐old breeding strategy based on the selection of ewe lambs born from large litter size. Homozygous LL ewes showed a significantly increased litter size compared to heterozygous and non‐carrier ewes (FecLL/FecLL = 2.47 ± 0.09 vs. FecLL/FecL+ = 2.23 ± 0.09, p < 0.05 and FecL+/FecL+ = 1.93 ± 0.18, p < 0.01). The presence of the FecLLpolymorphism in both D'man and Lacaune breeds argues for an ancestral origin of this mutation and brings an answer to the old question of the genetic determinism of the extreme prolificacy of the D'man ewes. The results of this study can help to establish planned genotype‐based mating allowing both higher profit for the breeders and an optimal management of the FecLL mutation in D'man sheep populations.

Published
2019
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5. Author correction : A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content

Author

Justine Bertrand-Michel, Philippe Bardou, Gwenola Tosser-Klopp, Ines Racke, P. Martin, Kamila Canale-Tabet, Florent Woloszyn, Julien Sarry, Isabelle Palhiere, Hüseyin Besir, Rachel Rupp, Cyrielle Maroteau, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT), University of Dundee, SIGENAE, Institut National de la Recherche Agronomique (INRA), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Molecular Biology Laboratory (EMBL), French organizations through 'PhenoFinlait', Region Midi-PyreneesRegion OccitanieRegion Provence-Alpes-Cote d'Azur, ALLICE, European Project: 245140,EC:FP7:KBBE,FP7-KBBE-2009-3,3SR(2010), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ProdInra, Migration, Sustainable Solutions for Small Ruminants - 3SR - - EC:FP7:KBBE2010-05-01 - 2013-10-31 - 245140 - VALID, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]

Subjects
0301 basic medicine, Science, [SDV]Life Sciences [q-bio], Genome Scan, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, [INFO] Computer Science [cs], 03 medical and health sciences, [INFO]Computer Science [cs], Food science, Author Correction, ComputingMilieux_MISCELLANEOUS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Milk production, 040201 dairy & animal science, [SDV] Life Sciences [q-bio], [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Milk fat, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Medicine
Abstract

The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits. For a major region on chromosome 14 closely associated with fat content, the Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively. The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%. Both mutations were associated with a notable decrease in milk fat content. Their causality was then demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk synthesis and will help improve the management of the French dairy goat breeding program.

Published
2018
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6. Detection of single nucleotide polymorphisms at major prolificacy genes in the Mehraban sheep and association with litter size

Author

Fazlollah Afraz, Stéphane Fabre, Florent Woloszyn, Julien Sarry, A. Ahmadi, Reza Talebi, Dept Anim Sci, Fac Agr, University of Peradeniya, Agr Biotechnol Res Inst North Reg, Partenaires INRAE, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, 2. Zero hunger, Genetics, Litter (animal), [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV]Life Sciences [q-bio], polymorphism, mehraban sheep, major gene, prolificacy, 0402 animal and dairy science, Single-nucleotide polymorphism, 04 agricultural and veterinary sciences, Biology, 040201 dairy & animal science, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 03 medical and health sciences, 030104 developmental biology, [INFO]Computer Science [cs], Gene
Abstract

The present study aimed to investigate the presence of polymorphisms at four known genes controlling ovine prolificacy i.e. BMP15, GDF9, BMPR1B and B4GALNT2 in a sample of 115 Iranian Mehraban ewes and their association with litter size (LS) and lambs’ birth weight (BW) traits. Using Sanger sequencing of exons and polymorphism specific genotyping, ten SNPs (Single Nucleotide Polymorphisms) were observed in only two genes, GDF9 and BMPR1B. Seven SNPs were found in the GDF9 gene on the chromosome 5. Among them, six were already described in the coding sequence, and a new one (g.41840985C>T) was found in the 3’UTR. In the BMPR1B gene on the chromosome 6, three novel SNPs were detected in the exon 7 (g.29382184G>A; g.29382337G>A and g.29382340G>A). Allelic frequencies were established for six SNPs among the ten identified and they were in Hardy-Weinberg equilibrium. A significant association was found between the novel SNPs found in the exon 7 of BMPR1B and LS. Present results indicate the potential role of the BMPR1B locus in controlling prolificacy of Mehraban sheep and provide genetic markers for further exploitation in selection to improve reproductive efficiency.

Published
2018
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7. Genome-wide identification of the mutation uderlying fleece variation and discriminating ancestral hairy species from modern woolly sheep

Author

Julie Demars, Stéphane Fabre, Florent Woloszyn, Gwenola Tosser-Klopp, Fabien Carrière, Didier Foulquier, Philippe Mulsant, D. Allain, Florence Plisson-Petit, Olivier Bouchez, Maarten Pirson, Nathalie Rodde, Bertrand Servin, L. Drouilhet, Mathias Aletru, Philippe Bardou, Margarita Cano, Julien Sarry, Stéphane Cauet, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Instituto Nacional de Tecnología Agropecuaria, Domaine expérimental de La Fage (LA FAGE), Institut National de la Recherche Agronomique (INRA), Centre National de Ressources Génomiques Végétales (CNRGV), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], UE 0321 LA FAGE Domaine Expérimental de La Fage., GeT PlaGe, Genotoul, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), GenPhySE - UMR 1388 ( Génétique Physiologie et Systèmes d'Elevage ), Institut National de la Recherche Agronomique ( INRA ) -École nationale supérieure agronomique de Toulouse [ENSAT]-ENVT, Institut National de la Recherche Agronomique ( INRA ), Domaine expérimental de La Fage ( LA FAGE ), and Centre National de Ressources Génomiques Végétales ( CNRGV )

Subjects
0301 basic medicine, Untranslated region, breed, merino, [SDV]Life Sciences [q-bio], Population, Biology, Genome, Ovinos, 03 medical and health sciences, domestication, Genetic variation, Genetics, Animals, DNA, Ancient, Allele, education, Domestication, gene, Molecular Biology, Sheep, Domestic, Discoveries, Ecology, Evolution, Behavior and Systematics, 2. Zero hunger, education.field_of_study, Sheep, [ SDV ] Life Sciences [q-bio], Mutación, Wool, Genetic Variation, RNA, mouse oocyte, Biological Evolution, Phenotype, Genética, 030104 developmental biology, Mutation, Carrier Proteins, Genome-Wide Association Study, Transcription Factors
Abstract

The composition and structure of fleece variation observedin mammals is a consequence of a strong selective pressure for fiber production after domestication. In sheep, fleece variation discriminates ancestral species carrying a long and hairy fleece from modern domestic sheep (Ovis aries) owning a short and woolly fleece.Here, we report that the “woolly” allele results from the insertion of an antisenseEIF2S2retrogene (calledasEIF2S2)intothe3 0 UTR of theIRF2BP2 gene leading to an abnormal IRF2BP2 transcript. We provide evidence that this chimeric IRF2BP2/asEIF2S2 messenger 1) targets the genuine sense EIF2S2 RNA and 2) creates a long endogenous double-stranded RNA which alters the expression of both EIF2S2 and IRF2BP2 mRNA. This represents a unique example of a phenotype arising via a RNA-RNA hybrid, itself generated through a retroposition mechanism. Our results bring new insights on the sheep population history thanks to the identification of the molecular origin of an evolutionary phenotypic variation. Instituto de Genética Fil: Demars, Julie. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Cano, Ema Margarita. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina Fil: Drouilhet, Laurence. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Plisson-Petit, Florence. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Bardou, Philippe. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Fabre, Stéphane. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Servin, Bertrand. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Sarry, Julien. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Woloszyn, Florent. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Mulsant, Philippe. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Foulquier, Didier. Institut National de la Recherche Agronomique; Francia Fil: Carriere, Fabien. Institut National de la Recherche Agronomique; Francia Fil: Aletru, Mathias. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Rodde, Nathalie. Institut National de la Recherche Agronomique; Francia Fil: Cauet, Stéphane. Institut National de la Recherche Agronomique; Francia Fil: Bouchez, Olivier. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Pirson, Maarten. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Tosser-Klopp, Gwenola. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia Fil: Allain, Daniel. Université de Toulouse. GenPhySE; Francia. Institut National de la Recherche Agronomique; Francia

Published
2017
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8. A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content

Author

Gwenola Tosser-Klopp, Ines Racke, Philippe Bardou, Justine Bertrand-Michel, Isabelle Palhiere, Florent Woloszyn, Rachel Rupp, Hüseyin Besir, Julien Sarry, P. Martin, Kamila Canale-Tabet, Cyrielle Maroteau, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Division of Molecular and Clinical Medecine, University of Dundee, SIGENAE, MetaToul-Lipidomic Core Facility, MetaboHUB, Institut National de la Santé et de la Recherche Médicale (INSERM), Protein Expression and Purification Core Facility, European Molecular Biology Laboratory, PhénoFinLait, Région Midi-Pyrénées, École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ProdInra, Archive Ouverte, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT)

Subjects
0301 basic medicine, microsatellite, Animal breeding, milk, production, genome, dairy goat, mutation, Science, [SDV]Life Sciences [q-bio], Genome-wide association study, Biology, somatic cell score, coa diacylglycerol, medicine.disease_cause, Article, 03 medical and health sciences, Genetic variation, acyltransferase, medicine, genetic polymorphism, Gene, acid composition, 2. Zero hunger, Genetics, marker, Mutation, Multidisciplinary, 0402 animal and dairy science, 04 agricultural and veterinary sciences, 040201 dairy & animal science, Breed, [SDV] Life Sciences [q-bio], 030104 developmental biology, protein percentage, Medicine, Microsatellite, false discovery rate, linkage disequilibrium, Reference genome
Abstract

Un corrigendum de cet article a été publié dans le vol.8, Article 4060 avec la clé UT (WOS) 000426355200007 et le DOI : 10.1038/s41598-018-22118-x; The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock.However, little is known about the regions of the genome that influence these traits in goats. Weconducted a genome wide association study in French goats and identified 109 regions associatedwith dairy traits. For a major region on chromosome 14 closely associated with fat content, theDiacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidategene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found inthe gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutionsin the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% andthe R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively.The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%.Both mutations were associated with a notable decrease in milk fat content. Their causality was thendemonstrated by a functional test. These results provide new knowledge on the genetic basis of milksynthesis and will help improve the management of the French dairy goat breeding program.

Published
2017
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9. Correction : Design and Characterization of a 52K SNP Chip for Goats

Author

Gwenola Tosser-Klopp, Philippe Bardou, Olivier Bouchez, Cédric Cabau, Richard Crooijmans, Yang Dong, Cécile Donnadieu-Tonon, André Eggen, Henri C M Heuven, Saadiah Jamli, Abdullah Johari Jiken, Christophe Klopp, Cynthia T Lawley, John McEwan, Patrice Martin, Carole R Moreno, Philippe Mulsant, Ibouniyamine Nabihoudine, Eric Pailhoux, Isabelle Palhière, Rachel Rupp, Julien Sarry, Brian L Sayre, Aurélie Tircazes, Jun Wang, Wen Wang, Wenguang Zhang, International Goat Genome Consortium, GenPhySE - UMR 1388 ( Génétique Physiologie et Systèmes d'Elevage ), Institut National de la Recherche Agronomique ( INRA ) -École nationale supérieure agronomique de Toulouse [ENSAT]-ENVT, GeT PlaGe, Genotoul, Institut National de la Recherche Agronomique ( INRA ), Biotechnologie, Wageningen University and Research Center ( WUR ), Unité de Mathématiques et Informatique Appliquées de Toulouse ( MIAT INRA ), Biologie du développement et reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Wageningen University and Research [Wageningen] (WUR), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Wageningen University and Research Center (WUR), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0106 biological sciences, 0301 basic medicine, Computer science, [SDV]Life Sciences [q-bio], Section (typography), lcsh:Medicine, Breeding, computer.software_genre, Bioinformatics, 010603 evolutionary biology, 01 natural sciences, Polymorphism, Single Nucleotide, 03 medical and health sciences, Animals, lcsh:Science, Oligonucleotide Array Sequence Analysis, Multidisciplinary, Genome, [ SDV ] Life Sciences [q-bio], business.industry, Published Erratum, Goats, lcsh:R, Correction, Reproducibility of Results, Genomics, SNP genotyping, 030104 developmental biology, lcsh:Q, Artificial intelligence, business, computer, Natural language processing
Abstract

The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.

Published
2016
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10. A point mutation in suppressor of cytokine signalling 2 (Socs2) increases the susceptibility to inflammation of the mammary gland while associated with higher body weight and size and higher milk production in a sheep model

Author

Olivier Bouchez, Charlotte Allain, Guillaume Tabouret, Cécile Caubet, David Portes, Laeticia Ligat, Mathieu Lebastard, Rachel Rupp, Florent Woloszyn, Christian Tasca, Pavel Senin, Julien Sarry, Gilles Foucras, Gwenola Tosser-Klopp, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Domaine expérimental de La Fage (LA FAGE), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
Male, Cancer Research, [SDV]Life Sciences [q-bio], Genome-wide association study, Suppressor of Cytokine Signaling Proteins, Growth hormone receptor, Mastitis, [MATH] Mathematics [math], qtl, somatic cell count, mastitis resistance, dairy cattle, genome, gene, selection, [MATH]Mathematics [math], SOCS2, Genetics (clinical), Genetics, 0303 health sciences, 04 agricultural and veterinary sciences, [SDV] Life Sciences [q-bio], Female, Research Article, Protein Binding, lcsh:QH426-470, Molecular Sequence Data, Quantitative Trait Loci, Biology, [INFO] Computer Science [cs], Suppressor of cytokine signalling, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, Animals, Humans, Lactation, Point Mutation, [INFO]Computer Science [cs], Amino Acid Sequence, Mammary Glands, Human, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Sheep, Base Sequence, Point mutation, Body Weight, 0402 animal and dairy science, Wild type, medicine.disease, 040201 dairy & animal science, lcsh:Genetics, Somatic cell count
Abstract

Mastitis is an infectious disease mainly caused by bacteria invading the mammary gland. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but the genetic basis and underlying mechanisms are still largely unknown. We describe the discovery, fine mapping and functional characterization of a genetic variant associated with elevated milk leukocytes count, or SCC, as a proxy for mastitis. After implementing genome-wide association studies, we identified a major QTL associated with SCC on ovine chromosome 3. Fine mapping of the region, using full sequencing with 12X coverage in three animals, provided one strong candidate SNP that mapped to the coding sequence of a highly conserved gene, suppressor of cytokine signalling 2 (Socs2). The frequency of the SNP associated with increased SCC was 21.7% and the Socs2 genotype explained 12% of the variance of the trait. The point mutation induces the p.R96C substitution in the SH2 functional domain of SOCS2 i.e. the binding site of the protein to various ligands, as well-established for the growth hormone receptor GHR. Using surface plasmon resonance we showed that the p.R96C point mutation completely abrogates SOCS2 binding affinity for the phosphopeptide of GHR. Additionally, the size, weight and milk production in p.R96C homozygote sheep, were significantly increased by 24%, 18%, and 4.4%, respectively, when compared to wild type sheep, supporting the view that the point mutation causes a loss of SOCS2 functional activity. Altogether these results provide strong evidence for a causal mutation controlling SCC in sheep and highlight the major role of SOCS2 as a tradeoff between the host’s inflammatory response to mammary infections, and body growth and milk production, which are all mediated by the JAK/STAT signaling pathway., Author Summary Mastitis is an inflammation of the mammary gland mainly caused by invading bacteria. Ruminants show natural variability in their predisposition to mastitis, and therefore provide unique models for study of the genetics and physiology of host response to bacterial infection. A genome-wide association study was conducted in a dairy sheep population for milk somatic cell counts as a proxy for mastitis. Fine mapping, using whole genome sequencing, led to the identification of a mutation in the Suppressor of Cytokine Signaling 2 gene (socs2). This mutation was shown to cause a loss of functional activity of the SOCS2 protein, which suggested impairment of feedback control of the JAK/STAT signaling pathways in susceptible animals. Additionally, size, weight and milk production were increased in animals carrying the susceptible variant suggesting a pleiotropic effect of the gene on production versus health traits. Results gave strong evidence of the role of SOCS2 in the host’s inflammation of the udder and provided new insights into the key mechanisms underlying the genetic control of mastitis.

Published
2015
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11. Novel BMP15 mutations responsible for an atypical hyperprolificacy phenotype in sheep

Author

Julie Demars, Stéphane Fabre, Julien Sarry, Rossetti, R., Hélène Gilbert, Persani, L., Gwenola Tosser-Klopp, Philippe Mulsant, Nowak, Z., Drobik, D., Martyniuk, E., Loys Bodin, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), Warsaw University of Life Sciences (SGGW), Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)

Subjects
reproduction, marker, sheep, snp50, phenotype, [SDV]Life Sciences [q-bio], bmp15, [INFO]Computer Science [cs], genetic, mutation, hyperprolificacy, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2013

12. The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the B4GALNT2 Gene within the Ovary

Author

Florent Woloszyn, Julien Sarry, Catherine Viguié, Jérôme Lluch, Stéphane Fabre, Laurence Drouilhet, Danielle Monniaux, Philippe Mulsant, Kamila Canale Tabet, Loys Bodin, Camille Mansanet, Philippe Bardou, Grégoire Harichaux, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Ecole Nationale Vétérinaire de Toulouse (ENVT), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Laboratoire de Génétique Cellulaire ( LGC ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire de Toulouse, Physiologie de la reproduction et des comportements [Nouzilly] ( PRC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Toxicologie Alimentaire ( UTA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Station d'Amélioration Génétique des Animaux ( SAGA ), Institut National de la Recherche Agronomique ( INRA ), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ovulation, Cancer Research, Glycosylation, lcsh:QH426-470, Granulosa cell, [SDV]Life Sciences [q-bio], Locus (genetics), Biology, 03 medical and health sciences, Ovarian Follicle, Gene expression, Genetics, Animals, Humans, RNA, Messenger, Allele, Molecular Biology, Gene, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Sheep, Domestic, 030304 developmental biology, 2. Zero hunger, Regulation of gene expression, 0303 health sciences, Granulosa Cells, [ SDV ] Life Sciences [q-bio], 0402 animal and dairy science, 04 agricultural and veterinary sciences, Luteinizing Hormone, 040201 dairy & animal science, Major gene, Molecular biology, lcsh:Genetics, Fertility, Gene Expression Regulation, N-Acetylgalactosaminyltransferases, Ectopic expression, Female, Infertility, Female, Research Article
Abstract

Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecLL. Our previous work localized FecL on sheep chromosome 11 within a locus of 1.1 Mb encompassing 20 genes. With the aim to identify the FecL gene, we developed a high throughput sequencing strategy of long-range PCR fragments spanning the locus of FecLL carrier and non-carrier ewes. Resulting informative markers defined a new 194.6 kb minimal interval. The reduced FecL locus contained only two genes, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and beta-1,4-N-acetyl-galactosaminyl transferase 2 (B4GALNT2), and we identified two SNP in complete linkage disequilibrium with FecLL. B4GALNT2 appeared as the best positional and expressional candidate for FecL, since it showed an ectopic expression in the ovarian follicles of FecLL/FecLL ewes at mRNA and protein levels. In FecLL carrier ewes only, B4GALNT2 transferase activity was localized in granulosa cells and specifically glycosylated proteins were detected in granulosa cell extracts and follicular fluids. The identification of these glycoproteins by mass spectrometry revealed at least 10 proteins, including inhibin alpha and betaA subunits, as potential targets of B4GALNT2 activity. Specific ovarian protein glycosylation by B4GALNT2 is proposed as a new mechanism of ovulation rate regulation in sheep, and could contribute to open new fields of investigation to understand female infertility pathogenesis., Author Summary Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in ovarian function and female fertility. Indeed, fecundity genes of the Bone Morphogenetic Protein (BMP) family discovered in sheep was evidenced as genetic candidates to explain female infertility pathologies. Studying French Lacaune sheep breed, we discovered another fecundity gene named B4GALNT2, encoding a glycosylation enzyme that is not related to the BMP family. The high prolificacy of Lacaune sheep was explained by overexpression of B4GALNT2 in the ovary leading to atypical glycosylation of inhibin, an important hormone regulating ovarian function. Our findings open promising fields of investigation to better understand female fertility disorders.

Published
2013
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13. Transcriptome profiling of sheep granulosa cells and oocytes during early follicular development obtained by Laser Capture Microdissection

Author

Patrice Martin, Gwenola Tosser-Klopp, Corinne Cotinot, Elena Terenina, Claudia Bevilacqua, Beatrice Mandon-Pepin, Francis Benne, Julien Sarry, Agnès Bonnet, Loys Bodin, Magali SanCristobal, Laurence Liaubet, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Biologie du Développement et Reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Bonnet, Agnes

Subjects
[SDV]Life Sciences [q-bio], Cell Separation, MESH: Animals, Newborn, Transcriptome, 0302 clinical medicine, folliculogenesis, Follicular phase, MESH: Animals, Laser capture microdissection, Oligonucleotide Array Sequence Analysis, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Real-Time Polymerase Chain Reaction, MESH: Laser Capture Microdissection, female reproductive function, Cell biology, MESH: Reproducibility of Results, MESH: Cattle, medicine.anatomical_structure, Female, Folliculogenesis, Research Article, Biotechnology, endocrine system, sheep, lcsh:QH426-470, lcsh:Biotechnology, Granulosa cell, MESH: Sheep, Laser Capture Microdissection, Biology, Real-Time Polymerase Chain Reaction, Follicular cell, MESH: Cell Separation, MESH: Oocytes, 03 medical and health sciences, MESH: Gene Expression Profiling, granulosa, MESH: RNA, lcsh:TP248.13-248.65, medicine, Genetics, Animals, 030304 developmental biology, Granulosa Cells, Microarray analysis techniques, Gene Expression Profiling, Reproducibility of Results, cell, MESH: Granulosa Cells, Oocyte, Molecular biology, lcsh:Genetics, Animals, Newborn, MESH: Oligonucleotide Array Sequence Analysis, Oocytes, RNA, Cattle, transcriptome, MESH: Female
Abstract

Background Successful achievement of early folliculogenesis is crucial for female reproductive function. The process is finely regulated by cell-cell interactions and by the coordinated expression of genes in both the oocyte and in granulosa cells. Despite many studies, little is known about the cell-specific gene expression driving early folliculogenesis. The very small size of these follicles and the mixture of types of follicles within the developing ovary make the experimental study of isolated follicular components very difficult. The recently developed laser capture microdissection (LCM) technique coupled with microarray experiments is a promising way to address the molecular profile of pure cell populations. However, one main challenge was to preserve the RNA quality during the isolation of single cells or groups of cells and also to obtain sufficient amounts of RNA. Using a new LCM method, we describe here the separate expression profiles of oocytes and follicular cells during the first stages of sheep folliculogenesis. Results We developed a new tissue fixation protocol ensuring efficient single cell capture and RNA integrity during the microdissection procedure. Enrichment in specific cell types was controlled by qRT-PCR analysis of known genes: six oocyte-specific genes (SOHLH2, MAEL, MATER, VASA, GDF9, BMP15) and three granulosa cell-specific genes (KL, GATA4, AMH). A global gene expression profile for each follicular compartment during early developmental stages was identified here for the first time, using a bovine Affymetrix chip. Most notably, the granulosa cell dataset is unique to date. The comparison of oocyte vs. follicular cell transcriptomes revealed 1050 transcripts specific to the granulosa cell and 759 specific to the oocyte. Functional analyses allowed the characterization of the three main cellular events involved in early folliculogenesis and confirmed the relevance and potential of LCM-derived RNA. Conclusions The ovary is a complex mixture of different cell types. Distinct cell populations need therefore to be analyzed for a better understanding of their potential interactions. LCM and microarray analysis allowed us to identify novel gene expression patterns in follicular cells at different stages and in oocyte populations.

Published
2011
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14. Genome-Wide Association Studies Identify Two Novel BMP15 Mutations Responsible for an Atypical Hyperprolificacy Phenotype in Sheep

Author

Wioleta Drobik, Julie Demars, Raffaella Rossetti, Stéphane Fabre, Julien Sarry, Gwenola Tosser-Klopp, Hélène Gilbert, E. Martyniuk, Zuzanna Nowak, Philippe Mulsant, Luca Persani, Loys Bodin, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National de la Recherche Agronomique (INRA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Francois Rabelais [Tours], Institut Français du Cheval et de l'Equitation, Università degli Studi di Milano [Milano] (UNIMI), Warsaw University of Life Sciences (SGGW), Station d'Amélioration Génétique des Animaux (SAGA), This work was supported by grants from France via Agence National pour la Recherche (http://www.agence-nationale-recherche.fr /) (ANR 2010 BLANC grant 160801, MONOPOLY) and EC (FP7/2007–2013), grant 245140, '3SR', Sustainable Solutions for Small Ruminants (http://www.3srbreeding.eu/), WP4 (this publication reflects only the authors' views and the EC is not liable for any use that may be made of the information contained herein), and the DEGERAM Program (FNADT, FEDER, CR Midi Pyrénées, Auvergne et Limousin). This work was partially supported by Telethon Foundation, Italy (grant GGP09126 to LP)., Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Demars, Julie

Subjects
rasa aragonesa sheep, Cancer Research, Candidate gene, Anatomy and Physiology, Litter Size, [SDV]Life Sciences [q-bio], Genome-wide association study, medicine.disease_cause, Genetic analysis, Genotype, Genetics (clinical), Genetics, 0303 health sciences, Mutation, 04 agricultural and veterinary sciences, Phenotype, Medicine, Bone Morphogenetic Protein 15, increased prolificacy, Research Article, Ovulation, statistical method, lcsh:QH426-470, premature ovarian failure, Biology, haplotype reconstruction, 03 medical and health sciences, granulosa, Genetic Mutation, Genetic variation, Genome-Wide Association Studies, medicine, Animals, Humans, increased ovulation rate, bone morphogenetic protein 15, growth differentiation factor 9, cell function, phenotype, Allele, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Sheep, Reproductive System, 0402 animal and dairy science, 040201 dairy & animal science, lcsh:Genetics, Haplotypes, Genetic marker, Genetic Polymorphism, Animal Genetics, Population Genetics, Genome-Wide Association Study
Abstract

Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E−05 and 1E−07. The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecXGr and FecXO were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (pFecXGr = 5.98E−06 and pFecXO = 2.55E−08). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecXGr/FecXGr, LS = 2.50±0.65 versus FecX+/FecXGr, LS = 1.93±0.42, p, Author Summary Although causes altering reproductive function and leading to several fertility syndromes in women are various, a clear association between mutations in some members of the TGFβ family (BMP15 and GDF9) and abnormal ovarian phenotype has established the importance of these factors for normal female fertility. Some sheep breeds are naturally prolific since they carry major genes affecting ovulation rate and litter size. These species are therefore unique informative models for the study of reproductive genetics and physiology. Through a GWAS conducted in two sheep breeds using highly prolific ewes as cases and normal prolific ewes as controls, we identified an X chromosome locus close to the BMP15 gene in both breeds. Two novel non-conservative BMP15 mutations, one in each population, located in very well conserved domains of the protein were associated with the phenotype at heterozygous and homozygous status. Moreover, we showed that both mutations altered the BMP15 signaling activity, suggesting a novel kind of BMP15 variant responsible for an atypical high prolificacy, in contrast to all other BMP15 variants described so far. Our findings suggest an additional role of the BMP15 protein in folliculogenesis and could contribute to a better understanding of the pathogenesis of women′s fertility disorders.

Published
2013
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