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Sem Genini,
Bouabid Badaoui,
Gert Sclep,
Stephen C Bishop,
Dave Waddington,
Marie-Hélène Pinard van der Laan,
Christophe Klopp,
Cédric Cabau,
Hans-Martin Seyfert,
Wolfram Petzl, [......],
Guro M Boman,
Giuliano Pisoni,
Paolo Moroni,
Bianca Castiglioni,
Paola Cremonesi,
Marcello Del Corvo,
Eliane Foulon,
Gilles Foucras,
Rachel Rupp,
Elisabetta Giuffra
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ABSTRACT: Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged in vivo with S. aureus, E. coli, and S. uberis, samples from goats challenged in vivo with S. aureus, as well as cattle macrophages and ovine dendritic cells infected in vitro with S. aureus. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific.
Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e.g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including XBP1 and SREBF1.The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of E. coli and S. aureus infections in cattle in vivo revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that E. coli caused a stronger host response.
This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources.
BMC Genomics 01/2011; 12(1):225. · 4.07 Impact Factor
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Christine G Elsik,
Ross L Tellam,
Kim C Worley,
Richard A Gibbs,
Donna M Muzny,
George M Weinstock,
David L Adelson,
Evan E Eichler,
Laura Elnitski,
Roderic Guigó, [......],
Ashley J Waardenberg,
Zhiquan Wang,
Robert Ward,
Rosemarie Weikard,
Thomas H Welsh,
Stephen N White,
Laurens G Wilming,
Kris R Wunderlich,
Jianqi Yang,
Feng-Qi Zhao
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ABSTRACT: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
Science 05/2009; 324(5926):522-8. · 31.20 Impact Factor
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ABSTRACT: A method to measure genomic response to natural and artificial selection by means of genetic markers in livestock is proposed. Genomic response through several levels of selection was measured using sequential testing for distorted segregation of alleles among selected and nonselected sons, single-sperm typing, and a test with records for growth performance. Statistical power at a significance level of 0.05 was >0.5 for a marker linked to a QTL with recombination fractions 0, 0.10, and 0.20 for detecting genomic responses for gene effects of 0.6, 0.7, and 1.0 phenotypic standard deviations, respectively. Genomic response to artificial selection in six commercial bull sire families comprising 285 half-sib sons selected for growth performance was measured using 282 genetic markers evenly distributed over the cattle genome. A genome-wide test using selected sons was significant (P < 0.001), indicating that selection induces changes in the genetic makeup of commercial cattle populations. Markers located in chromosomes 6, 10, and 16 identified regions in those chromosomes that are changing due to artificial selection as revealed by the association of records of performance with alleles at specific markers. Either natural selection or genetic drift may cause the observed genomic response for markers in chromosomes 1, 7, and 17.
Genetics 12/2002; 162(3):1381-8. · 4.01 Impact Factor
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ABSTRACT: A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.
Genetics 05/2002; 161(1):373-9. · 4.01 Impact Factor
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Helge Klungland,
Ayman Sabry,
Bjørg Heringstad,
Hanne Gro Olsen,
Luis Gomez-Raya,
Dag Inge Våge, Ingrid Olsaker,
Jørgen Ødegård,
Gunnar Klemetsdal,
Nina Schulman,
Johanna Vilkki,
John Ruane,
Monica Aasland,
Knut Rønningen,
Sigbjørn Lien
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ABSTRACT: Norway has a field recording system for dairy cattle that includes recording of all veterinary treatments on an individual
animal basis from 1978 onwards. Application of these data in a genome search for quantitative trait loci (QTL) verified genome-wise
significant QTL affecting clinical mastitis on Chromosome (Chr) 6. Additional putative QTL for clinical mastitis were localized
to Chrs. 3, 4, 14, and 27. The comprehensive field recording system includes information on somatic cell count as well. This
trait is often used in selection against mastitis when direct information on clinical mastitis is not available. The absence
of common QTL positions for the two traits in our study indicates that the use of somatic cell count data in QTL studies aimed
for reducing the incidence of mastitis should be carefully evaluated.
Mammalian Genome 01/2001; 12(11):837-842. · 2.89 Impact Factor
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ABSTRACT: An autosomal genome scan for quantitative trait loci (QTL) affecting twinning rate was carried out in the Norwegian Cattle
population. Suggestive QTL were detected on Chromosomes (Chr) 5, 7, 12, and 23. Among these, the QTL positions on both Chr
5 and Chr 23 are strongly supported by literature in the field. Our results also confirm previous mapping of a QTL for twinning
to Chr 7, but definitely suggest a different location of the QTL on this chromosome. The most convincing QTL peak was observed
for a region in the middle part of Chr 5 close to the insulin-like growth factor 1 (IGF1) gene. Since IGF1 plays an important role in the regulation of folliculogenesis, a mutation search was performed by sequencing more than 3.5
kb of the gene in actual families. The sequencing revealed three polymorphisms in noncoding regions of the gene that will
be important in fine structure mapping and characterization of the QTL.
Mammalian Genome 01/2000; 11(10):877-882. · 2.89 Impact Factor
