187 results on '"Archibald AL"'
Search Results
52. Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project.
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Andersson L, Archibald AL, Bottema CD, Brauning R, Burgess SC, Burt DW, Casas E, Cheng HH, Clarke L, Couldrey C, Dalrymple BP, Elsik CG, Foissac S, Giuffra E, Groenen MA, Hayes BJ, Huang LS, Khatib H, Kijas JW, Kim H, Lunney JK, McCarthy FM, McEwan JC, Moore S, Nanduri B, Notredame C, Palti Y, Plastow GS, Reecy JM, Rohrer GA, Sarropoulou E, Schmidt CJ, Silverstein J, Tellam RL, Tixier-Boichard M, Tosser-Klopp G, Tuggle CK, Vilkki J, White SN, Zhao S, and Zhou H
- Subjects
- Animals, Databases, Genetic, Genomics, Software, Animals, Domestic genetics, Genome, Molecular Sequence Annotation
- Abstract
We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species.
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- 2015
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53. Third Report on Chicken Genes and Chromosomes 2015.
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Schmid M, Smith J, Burt DW, Aken BL, Antin PB, Archibald AL, Ashwell C, Blackshear PJ, Boschiero C, Brown CT, Burgess SC, Cheng HH, Chow W, Coble DJ, Cooksey A, Crooijmans RP, Damas J, Davis RV, de Koning DJ, Delany ME, Derrien T, Desta TT, Dunn IC, Dunn M, Ellegren H, Eöry L, Erb I, Farré M, Fasold M, Fleming D, Flicek P, Fowler KE, Frésard L, Froman DP, Garceau V, Gardner PP, Gheyas AA, Griffin DK, Groenen MA, Haaf T, Hanotte O, Hart A, Häsler J, Hedges SB, Hertel J, Howe K, Hubbard A, Hume DA, Kaiser P, Kedra D, Kemp SJ, Klopp C, Kniel KE, Kuo R, Lagarrigue S, Lamont SJ, Larkin DM, Lawal RA, Markland SM, McCarthy F, McCormack HA, McPherson MC, Motegi A, Muljo SA, Münsterberg A, Nag R, Nanda I, Neuberger M, Nitsche A, Notredame C, Noyes H, O'Connor R, O'Hare EA, Oler AJ, Ommeh SC, Pais H, Persia M, Pitel F, Preeyanon L, Prieto Barja P, Pritchett EM, Rhoads DD, Robinson CM, Romanov MN, Rothschild M, Roux PF, Schmidt CJ, Schneider AS, Schwartz MG, Searle SM, Skinner MA, Smith CA, Stadler PF, Steeves TE, Steinlein C, Sun L, Takata M, Ulitsky I, Wang Q, Wang Y, Warren WC, Wood JM, Wragg D, and Zhou H
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- Animals, Chickens classification, Chickens physiology, Chromosome Mapping, DNA Methylation, Evolution, Molecular, Female, Gene Expression Profiling, Genetic Variation, Genomics methods, In Situ Hybridization, Fluorescence methods, Male, Molecular Sequence Annotation, Phylogeny, Chickens genetics, Chromosomes genetics
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- 2015
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54. Beyond the whole genome consensus: unravelling of PRRSV phylogenomics using next generation sequencing technologies.
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Lu ZH, Archibald AL, and Ait-Ali T
- Subjects
- Animals, Evolution, Molecular, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus isolation & purification, Swine, Genetic Variation, Genome, Viral, High-Throughput Nucleotide Sequencing, Phylogeny, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics
- Abstract
The highly heterogeneous porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent responsible for an economically important pig disease with the characteristic symptoms of reproductive losses in breeding sows and respiratory illnesses in young piglets. The virus can be broadly divided into the European and North American-like genotype 1 and 2 respectively. In addition to this intra-strains variability, the impact of coexisting viral quasispecies on disease development has recently gained much attention; owing very much to the advent of the next-generation sequencing (NGS) technologies. Genomic data produced from the massive sequencing capacities of NGS have enabled the study of PRRSV at an unprecedented rate and details. Unlike conventional sequencing methods which require knowledge of conserved regions, NGS allows de novo assembly of the full viral genomes. Evolutionary variations gained from different genotypic strains provide valuable insights into functionally important regions of the virus. Together with the advancement of sophisticated bioinformatics tools, ultra-deep NGS technologies make the detection of low frequency co-evolving quasispecies possible. This short review gives an overview, including a proposed workflow, on the use of NGS to explore the genetic diversity of PRRSV at both macro- and micro-evolutionary levels., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
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55. Design and development of exome capture sequencing for the domestic pig (Sus scrofa).
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Robert C, Fuentes-Utrilla P, Troup K, Loecherbach J, Turner F, Talbot R, Archibald AL, Mileham A, Deeb N, Hume DA, and Watson M
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- Amino Acid Substitution, Animals, Expressed Sequence Tags, Haplotypes, Insulin-Like Growth Factor II genetics, Molecular Sequence Annotation, Phosphatidylinositol 3-Kinases genetics, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled genetics, Sus scrofa metabolism, Exome, Sequence Analysis, DNA, Sus scrofa genetics
- Abstract
Background: The domestic pig (Sus scrofa) is both an important livestock species and a model for biomedical research. Exome sequencing has accelerated identification of protein-coding variants underlying phenotypic traits in human and mouse. We aimed to develop and validate a similar resource for the pig., Results: We developed probe sets to capture pig exonic sequences based upon the current Ensembl pig gene annotation supplemented with mapped expressed sequence tags (ESTs) and demonstrated proof-of-principle capture and sequencing of the pig exome in 96 pigs, encompassing 24 capture experiments. For most of the samples at least 10x sequence coverage was achieved for more than 90% of the target bases. Bioinformatic analysis of the data revealed over 236,000 high confidence predicted SNPs and over 28,000 predicted indels., Conclusions: We have achieved coverage statistics similar to those seen with commercially available human and mouse exome kits. Exome capture in pigs provides a tool to identify coding region variation associated with production traits, including loss of function mutations which may explain embryonic and neonatal losses, and to improve genomic assemblies in the vicinity of protein coding genes in the pig.
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- 2014
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56. The sheep genome illuminates biology of the rumen and lipid metabolism.
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Jiang Y, Xie M, Chen W, Talbot R, Maddox JF, Faraut T, Wu C, Muzny DM, Li Y, Zhang W, Stanton JA, Brauning R, Barris WC, Hourlier T, Aken BL, Searle SMJ, Adelson DL, Bian C, Cam GR, Chen Y, Cheng S, DeSilva U, Dixen K, Dong Y, Fan G, Franklin IR, Fu S, Guan R, Highland MA, Holder ME, Huang G, Ingham AB, Jhangiani SN, Kalra D, Kovar CL, Lee SL, Liu W, Liu X, Lu C, Lv T, Mathew T, McWilliam S, Menzies M, Pan S, Robelin D, Servin B, Townley D, Wang W, Wei B, White SN, Yang X, Ye C, Yue Y, Zeng P, Zhou Q, Hansen JB, Kristensen K, Gibbs RA, Flicek P, Warkup CC, Jones HE, Oddy VH, Nicholas FW, McEwan JC, Kijas J, Wang J, Worley KC, Archibald AL, Cockett N, Xu X, Wang W, and Dalrymple BP
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- Amino Acid Sequence, Animals, Fatty Acids, Volatile metabolism, Fatty Acids, Volatile physiology, Gene Expression Regulation, Genome, Keratins, Hair-Specific genetics, Lipid Metabolism genetics, Molecular Sequence Data, Phylogeny, Rumen metabolism, Sheep, Domestic classification, Transcriptome, Wool growth & development, Lipid Metabolism physiology, Rumen physiology, Sheep, Domestic genetics, Sheep, Domestic metabolism
- Abstract
Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals., (Copyright © 2014, American Association for the Advancement of Science.)
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- 2014
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57. Analysis of the genetics of boar taint reveals both single SNPs and regional effects.
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Rowe SJ, Karacaören B, de Koning DJ, Lukic B, Hastings-Clark N, Velander I, Haley CS, and Archibald AL
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- Androstenes metabolism, Animals, Chromosomes, Mammalian, Cytochrome P-450 CYP2E1 metabolism, Genetic Variation, Genome-Wide Association Study, Male, Orchiectomy, Phenotype, Skatole metabolism, Cytochrome P-450 CYP2E1 genetics, Fat Body chemistry, Meat analysis, Odorants analysis, Polymorphism, Single Nucleotide, Sus scrofa genetics
- Abstract
Background: Boar taint is an offensive urine or faecal-like odour, affecting the smell and taste of cooked pork from some mature non-castrated male pigs. Androstenone and skatole in fat are the molecules responsible. In most pig production systems, males, which are not required for breeding, are castrated shortly after birth to reduce the risk of boar taint. There is evidence for genetic variation in the predisposition to boar taint.A genome-wide association study (GWAS) was performed to identify loci with effects on boar taint. Five hundred Danish Landrace boars with high levels of skatole in fat (>0.3 μg/g), were each matched with a litter mate with low levels of skatole and measured for androstenone. DNA from these 1,000 non-castrated boars was genotyped using the Illumina PorcineSNP60 Beadchip. After quality control, tests for SNPs associated with boar taint were performed on 938 phenotyped individuals and 44,648 SNPs. Empirical significance thresholds were set by permutation (100,000). For androstenone, a 'regional heritability approach' combining information from multiple SNPs was used to estimate the genetic variation attributable to individual autosomes., Results: A highly significant association was found between variation in skatole levels and SNPs within the CYP2E1 gene on chromosome 14 (SSC14), which encodes an enzyme involved in degradation of skatole. Nominal significance was found for effects on skatole associated with 4 other SNPs including a region of SSC6 reported previously. Genome-wide significance was found for an association between SNPs on SSC5 and androstenone levels and nominal significance for associations with SNPs on SSC13 and SSC17. The regional analyses confirmed large effects on SSC5 for androstenone and suggest that SSC5 explains 23% of the genetic variation in androstenone. The autosomal heritability analyses also suggest that there is a large effect associated with androstenone on SSC2, not detected using GWAS., Conclusions: Significant SNP associations were found for skatole on SSC14 and for androstenone on SSC5 in Landrace pigs. The study agrees with evidence that the CYP2E1 gene has effects on skatole breakdown in the liver. Autosomal heritability estimates can uncover clusters of smaller genetic effects that individually do not exceed the threshold for GWAS significance.
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- 2014
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58. Down-regulation of mechanisms involved in cell transport and maintenance of mucosal integrity in pigs infected with Lawsonia intracellularis.
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Smith SH, Wilson AD, Van Ettinger I, MacIntyre N, Archibald AL, and Ait-Ali T
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- Animals, Desulfovibrionaceae Infections genetics, Desulfovibrionaceae Infections microbiology, Ileum, Immunohistochemistry veterinary, Intestinal Mucosa cytology, Intestinal Mucosa microbiology, Oligonucleotide Array Sequence Analysis veterinary, Real-Time Polymerase Chain Reaction veterinary, Swine, Swine Diseases microbiology, Desulfovibrionaceae Infections veterinary, Gene Expression Regulation, Intestinal Mucosa physiology, Lawsonia Bacteria physiology, Swine Diseases genetics
- Abstract
Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated transcripts, CD163 and CDK1 were novel findings and considered to be important, due to their respective roles in innate immunity and cellular proliferation. Overall, targeted cellular mechanisms included those that are important in epithelial restitution, migration and protection; maintenance of stable inter-epithelial cell relationships; cell transport of nutrients and electrolytes; innate immunity; and cell cycle.
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- 2014
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59. A genome-wide linkage analysis for reproductive traits in F2 Large White × Meishan cross gilts.
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Hernandez SC, Finlayson HA, Ashworth CJ, Haley CS, and Archibald AL
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- Animals, Chromosome Mapping veterinary, Genetic Linkage, Genetic Markers, Genome, Microsatellite Repeats, Quantitative Trait Loci, Reproduction genetics, Swine genetics
- Abstract
Female reproductive performance traits in pigs have low heritabilities thus limiting improvement through traditional selective breeding programmes. However, there is substantial genetic variation found between pig breeds with the Chinese Meishan being one of the most prolific pig breeds known. In this study, three cohorts of Large White × Meishan F2 cross-bred pigs were analysed to identify quantitative trait loci (QTL) with effects on reproductive traits, including ovulation rate, teat number, litter size, total born alive and prenatal survival. A total of 307 individuals were genotyped for 174 genetic markers across the genome. The genome-wide analysis of the trait-recorded F2 gilts in their first parity/litter revealed one QTL for teat number significant at the genome level and a total of 12 QTL, which are significant at the chromosome-wide level, for: litter size (three QTL), total born alive (two QTL), ovulation rate (four QTL), prenatal survival (one QTL) and teat number (two QTL). Further support for eight of these QTL is provided by results from other studies. Four of these 12 QTL were mapped for the first time in this study: on SSC15 for ovulation rate and on SSC18 for teat number, ovulation rate and litter size., (© 2014 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)
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- 2014
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60. Genomic variation in macrophage-cultured European porcine reproductive and respiratory syndrome virus Olot/91 revealed using ultra-deep next generation sequencing.
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Lu ZH, Brown A, Wilson AD, Calvert JG, Balasch M, Fuentes-Utrilla P, Loecherbach J, Turner F, Talbot R, Archibald AL, and Ait-Ali T
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- Animals, Cluster Analysis, Evolution, Molecular, Genotype, High-Throughput Nucleotide Sequencing, Molecular Sequence Data, Phylogeny, Porcine respiratory and reproductive syndrome virus growth & development, Porcine respiratory and reproductive syndrome virus isolation & purification, Sequence Analysis, DNA, Swine, Virus Cultivation, Genetic Variation, Genome, Viral, Macrophages virology, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics, RNA, Viral genetics
- Abstract
Background: Porcine Reproductive and Respiratory Syndrome (PRRS) is a disease of major economic impact worldwide. The etiologic agent of this disease is the PRRS virus (PRRSV). Increasing evidence suggest that microevolution within a coexisting quasispecies population can give rise to high sequence heterogeneity in PRRSV., Findings: We developed a pipeline based on the ultra-deep next generation sequencing approach to first construct the complete genome of a European PRRSV, strain Olot/9, cultured on macrophages and then capture the rare variants representative of the mixed quasispecies population. Olot/91 differs from the reference Lelystad strain by about 5% and a total of 88 variants, with frequencies as low as 1%, were detected in the mixed population. These variants included 16 non-synonymous variants concentrated in the genes encoding structural and nonstructural proteins; including Glycoprotein 2a and 5., Conclusion: Using an ultra-deep sequencing methodology, the complete genome of Olot/91 was constructed without any prior knowledge of the sequence. Rare variants that constitute minor fractions of the heterogeneous PRRSV population could successfully be detected to allow further exploration of microevolutionary events.
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- 2014
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61. Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar).
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Houston RD, Taggart JB, Cézard T, Bekaert M, Lowe NR, Downing A, Talbot R, Bishop SC, Archibald AL, Bron JE, Penman DJ, Davassi A, Brew F, Tinch AE, Gharbi K, and Hamilton A
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- Alleles, Animals, Cluster Analysis, Contig Mapping, Gene Frequency, Gene Library, Genetic Linkage, Genotype, Haploidy, High-Throughput Nucleotide Sequencing, Male, Genome, Polymorphism, Single Nucleotide, Salmo salar genetics
- Abstract
Background: Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array., Results: SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex., Conclusions: This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection.
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- 2014
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62. The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide.
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Kapetanovic R, Fairbairn L, Downing A, Beraldi D, Sester DP, Freeman TC, Tuggle CK, Archibald AL, and Hume DA
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- Animals, Bone Marrow Cells immunology, Bone Marrow Cells metabolism, Gene Expression Regulation immunology, Homeostasis immunology, Immunity, Innate genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lipopolysaccharides pharmacology, Macrophages, Alveolar metabolism, Multigene Family, Oligonucleotide Array Sequence Analysis, Organ Specificity, Principal Component Analysis, Species Specificity, Sus scrofa genetics, Sus scrofa metabolism, Transcriptome, Macrophages, Alveolar immunology, Sus scrofa immunology
- Abstract
Background: The draft genome of the domestic pig (Sus scrofa) has recently been published permitting refined analysis of the transcriptome. Pig breeds have been reported to differ in their resistance to infectious disease. In this study we examine whether there are corresponding differences in gene expression in innate immune cells, Results: We demonstrate that macrophages can be harvested from three different compartments of the pig (lungs, blood and bone-marrow), cryopreserved and subsequently recovered and differentiated in CSF-1. We have performed surface marker analysis and gene expression profiling on macrophages from these compartments, comparing twenty-five animals from five different breeds and their response to lipopolysaccharide. The results provide a clear distinction between alveolar macrophages (AM) and monocyte-derived (MDM) and bone-marrow-derived macrophages (BMDM). In particular, the lung macrophages express the growth factor, FLT1 and its ligand, VEGFA at high levels, suggesting a distinct pathway of growth regulation. Relatively few genes showed breed-specific differential expression, notably CXCR2 and CD302 in alveolar macrophages. In contrast, there was substantial inter-individual variation between pigs within breeds, mostly affecting genes annotated as being involved in immune responses., Conclusions: Pig macrophages more closely resemble human, than mouse, in their set of macrophage-expressed and LPS-inducible genes. Future research will address whether inter-individual variation in macrophage gene expression is heritable, and might form the basis for selective breeding for disease resistance.
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- 2013
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63. Comparative analysis of monocyte subsets in the pig.
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Fairbairn L, Kapetanovic R, Beraldi D, Sester DP, Tuggle CK, Archibald AL, and Hume DA
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- Animals, Flow Cytometry, Humans, Immunophenotyping, Monocytes metabolism, Oligonucleotide Array Sequence Analysis, Swine, Transcriptome, Monocytes cytology, Monocytes immunology, Sus scrofa immunology
- Abstract
Human and mouse monocyte can be divided into two different subpopulations based on surface marker expression: CD14/16 and Ly6C/CX3CR1, respectively. Monocyte subpopulations in the pig were identified based on reciprocal expression of CD14 and the scavenger receptor CD163. The two populations, CD14(hi)-CD163(low) and CD14(low)-CD163(hi), show approximately equal abundance in the steady-state. Culture of pig PBMCs in CSF1 indicates that the two populations are a maturation series controlled by this growth factor. Gene expression in pig monocyte subpopulations was profiled using the newly developed and annotated pig whole genome snowball microarray. Previous studies have suggested a functional equivalence between human and mouse subsets, but certain genes such as CD36, CLEC4E, or TREM-1 showed human-specific expression. The same genes were expressed selectively in pig monocyte subsets. However, the profiles suggest that the pig CD14(low)-CD163(high) cells are actually equivalent to intermediate human monocytes, and there is no CD14(-) CD16(+) "nonclassical" population. The results are discussed in terms of the relevance of the pig as a model for understanding human monocyte function.
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- 2013
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64. Secreted phosphoprotein 1 expression in endometrium and placental tissues of hyperprolific large white and meishan gilts.
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Hernandez SC, Hogg CO, Billon Y, Sanchez MP, Bidanel JP, Haley CS, Archibald AL, and Ashworth CJ
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- Animals, Epithelial Cells metabolism, Female, Fetal Development, Fetus metabolism, Litter Size genetics, Osteopontin genetics, Pregnancy, Species Specificity, Endometrium metabolism, Osteopontin metabolism, Placenta metabolism, Swine metabolism
- Abstract
Increased litter size and within-litter uniformity in birth weight would improve pig reproductive efficiency. This study compared the location and gene and protein expression of secreted phosphoprotein 1 in placental and uterine tissues supplying a normally sized and the smallest fetus carried by hyperprolific Large White and Meishan gilts on Days 41-42 of pregnancy. Immunohistochemistry and in situ hybridization showed that the protein and gene encoding secreted phosphoprotein 1 were located in the glandular and luminal epithelium of the endometrium and in the placenta. Secreted phosphoprotein 1 protein levels were higher in glandular epithelium, luminal epithelium, and placenta from Meishan gilts compared to corresponding tissues from hyperprolific Large White gilts. Reverse transcription quantitative PCR demonstrated secreted phosphoprotein 1 mRNA levels were higher in endometrium, but not placenta, from Meishan compared to hyperprolific Large White gilts. In hyperprolific Large White gilts, secreted phosphoprotein 1 protein levels were higher in glandular epithelium and placenta surrounding small fetuses than corresponding tissues supplying normal-sized fetuses. Similarly, in Meishan gilts, secreted phosphoprotein 1 protein levels were higher in luminal epithelium surrounding small compared to normal-sized fetuses. Within hyperprolific Large White, but not Meishan, gilts secreted phosphoprotein 1 mRNA was higher in endometrium surrounding the normal-sized fetus than the control fetus. The contradictory relationship between fetal size and secreted phosphoprotein 1 protein and mRNA in the hyperprolific Large White is intriguing and may reflect breed differences in posttranslational modification. The striking breed differences in secreted phospoprotein 1 expression suggest that SPP1 may be associated with placental efficiency.
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- 2013
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65. Structural and functional annotation of the porcine immunome.
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Dawson HD, Loveland JE, Pascal G, Gilbert JG, Uenishi H, Mann KM, Sang Y, Zhang J, Carvalho-Silva D, Hunt T, Hardy M, Hu Z, Zhao SH, Anselmo A, Shinkai H, Chen C, Badaoui B, Berman D, Amid C, Kay M, Lloyd D, Snow C, Morozumi T, Cheng RP, Bystrom M, Kapetanovic R, Schwartz JC, Kataria R, Astley M, Fritz E, Steward C, Thomas M, Wilming L, Toki D, Archibald AL, Bed'Hom B, Beraldi D, Huang TH, Ait-Ali T, Blecha F, Botti S, Freeman TC, Giuffra E, Hume DA, Lunney JK, Murtaugh MP, Reecy JM, Harrow JL, Rogel-Gaillard C, and Tuggle CK
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- Animals, Cattle, Evolution, Molecular, Gene Duplication, Humans, Immunoglobulins genetics, Mice, Models, Molecular, Protein Conformation, Receptors, Antigen, T-Cell genetics, Receptors, KIR genetics, Selection, Genetic, Species Specificity, Genomics, Immunity genetics, Molecular Sequence Annotation, Swine genetics, Swine immunology
- Abstract
Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems., Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome., Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.
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- 2013
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66. Signatures of diversifying selection in European pig breeds.
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Wilkinson S, Lu ZH, Megens HJ, Archibald AL, Haley C, Jackson IJ, Groenen MA, Crooijmans RP, Ogden R, and Wiener P
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- Animals, Genome, Genomics, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Selection, Genetic, Swine, Breeding, Sus scrofa genetics
- Abstract
Following domestication, livestock breeds have experienced intense selection pressures for the development of desirable traits. This has resulted in a large diversity of breeds that display variation in many phenotypic traits, such as coat colour, muscle composition, early maturity, growth rate, body size, reproduction, and behaviour. To better understand the relationship between genomic composition and phenotypic diversity arising from breed development, the genomes of 13 traditional and commercial European pig breeds were scanned for signatures of diversifying selection using the Porcine60K SNP chip, applying a between-population (differentiation) approach. Signatures of diversifying selection between breeds were found in genomic regions associated with traits related to breed standard criteria, such as coat colour and ear morphology. Amino acid differences in the EDNRB gene appear to be associated with one of these signatures, and variation in the KITLG gene may be associated with another. Other selection signals were found in genomic regions including QTLs and genes associated with production traits such as reproduction, growth, and fat deposition. Some selection signatures were associated with regions showing evidence of introgression from Asian breeds. When the European breeds were compared with wild boar, genomic regions with high levels of differentiation harboured genes related to bone formation, growth, and fat deposition., Competing Interests: The authors have declared that no competing interests exist.
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- 2013
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67. Genome sequencing reveals fine scale diversification and reticulation history during speciation in Sus.
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Frantz LA, Schraiber JG, Madsen O, Megens HJ, Bosse M, Paudel Y, Semiadi G, Meijaard E, Li N, Crooijmans RP, Archibald AL, Slatkin M, Schook LB, Larson G, and Groenen MA
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- Africa, Animal Distribution, Animals, Asia, Southeastern, Chromosome Mapping, Climate, Gene Flow, Genetics, Population, Phylogeography, Sequence Analysis, DNA, Genetic Speciation, Genetic Variation, Genome, Phylogeny, Swine classification, Swine genetics
- Abstract
Background: Elucidating the process of speciation requires an in-depth understanding of the evolutionary history of the species in question. Studies that rely upon a limited number of genetic loci do not always reveal actual evolutionary history, and often confuse inferences related to phylogeny and speciation. Whole-genome data, however, can overcome this issue by providing a nearly unbiased window into the patterns and processes of speciation. In order to reveal the complexity of the speciation process, we sequenced and analyzed the genomes of 10 wild pigs, representing morphologically or geographically well-defined species and subspecies of the genus Sus from insular and mainland Southeast Asia, and one African common warthog., Results: Our data highlight the importance of past cyclical climatic fluctuations in facilitating the dispersal and isolation of populations, thus leading to the diversification of suids in one of the most species-rich regions of the world. Moreover, admixture analyses revealed extensive, intra- and inter-specific gene-flow that explains previous conflicting results obtained from a limited number of loci. We show that these multiple episodes of gene-flow resulted from both natural and human-mediated dispersal., Conclusions: Our results demonstrate the importance of past climatic fluctuations and human mediated translocations in driving and complicating the process of speciation in island Southeast Asia. This case study demonstrates that genomics is a powerful tool to decipher the evolutionary history of a genus, and reveals the complexity of the process of speciation.
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- 2013
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68. Strong signatures of selection in the domestic pig genome.
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Rubin CJ, Megens HJ, Martinez Barrio A, Maqbool K, Sayyab S, Schwochow D, Wang C, Carlborg Ö, Jern P, Jørgensen CB, Archibald AL, Fredholm M, Groenen MA, and Andersson L
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- Amino Acid Sequence, Animals, DNA Copy Number Variations, Homozygote, Molecular Sequence Data, Quantitative Trait Loci, Sequence Homology, Amino Acid, Animals, Domestic genetics, Genome, Selection, Genetic, Swine genetics
- Abstract
Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig--the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.
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- 2012
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69. Analyses of pig genomes provide insight into porcine demography and evolution.
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Groenen MA, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, Rogel-Gaillard C, Park C, Milan D, Megens HJ, Li S, Larkin DM, Kim H, Frantz LA, Caccamo M, Ahn H, Aken BL, Anselmo A, Anthon C, Auvil L, Badaoui B, Beattie CW, Bendixen C, Berman D, Blecha F, Blomberg J, Bolund L, Bosse M, Botti S, Bujie Z, Bystrom M, Capitanu B, Carvalho-Silva D, Chardon P, Chen C, Cheng R, Choi SH, Chow W, Clark RC, Clee C, Crooijmans RP, Dawson HD, Dehais P, De Sapio F, Dibbits B, Drou N, Du ZQ, Eversole K, Fadista J, Fairley S, Faraut T, Faulkner GJ, Fowler KE, Fredholm M, Fritz E, Gilbert JG, Giuffra E, Gorodkin J, Griffin DK, Harrow JL, Hayward A, Howe K, Hu ZL, Humphray SJ, Hunt T, Hornshøj H, Jeon JT, Jern P, Jones M, Jurka J, Kanamori H, Kapetanovic R, Kim J, Kim JH, Kim KW, Kim TH, Larson G, Lee K, Lee KT, Leggett R, Lewin HA, Li Y, Liu W, Loveland JE, Lu Y, Lunney JK, Ma J, Madsen O, Mann K, Matthews L, McLaren S, Morozumi T, Murtaugh MP, Narayan J, Nguyen DT, Ni P, Oh SJ, Onteru S, Panitz F, Park EW, Park HS, Pascal G, Paudel Y, Perez-Enciso M, Ramirez-Gonzalez R, Reecy JM, Rodriguez-Zas S, Rohrer GA, Rund L, Sang Y, Schachtschneider K, Schraiber JG, Schwartz J, Scobie L, Scott C, Searle S, Servin B, Southey BR, Sperber G, Stadler P, Sweedler JV, Tafer H, Thomsen B, Wali R, Wang J, Wang J, White S, Xu X, Yerle M, Zhang G, Zhang J, Zhang J, Zhao S, Rogers J, Churcher C, and Schook LB
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- Animals, Demography, Models, Animal, Molecular Sequence Data, Population Dynamics, Genome genetics, Phylogeny, Sus scrofa classification, Sus scrofa genetics
- Abstract
For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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- 2012
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70. USP18 restricts PRRSV growth through alteration of nuclear translocation of NF-κB p65 and p50 in MARC-145 cells.
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Xu D, Lillico SG, Barnett MW, Whitelaw CB, Archibald AL, and Ait-Ali T
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- Animals, Cell Line, Haplorhini, Immunity, Innate, Protein Transport, Endopeptidases metabolism, NF-kappa B p50 Subunit metabolism, Porcine respiratory and reproductive syndrome virus growth & development, Porcine respiratory and reproductive syndrome virus immunology, Transcription Factor RelA metabolism, Ubiquitins metabolism
- Abstract
Although the functions of porcine respiratory and reproductive syndrome virus (PRRSV) proteins are increasingly understood, the roles of host factors in modifying infection are less well understood. Growing evidence places deubiquitination at the core of a multitude of regulatory processes, ranging from cell growth to innate immune response and health, such as cancer, degenerative and infectious diseases. This report provides further information on the functional role of the porcine ubiquitin-specific peptidase 18 (USP18) during innate immune responses to PRRSV. We have shown that constitutive overexpression of the porcine USP18 in MARC-145 cells restricts PRRSV growth, at least in part via early activation of NF-κB. Viral growth of PRRSV may be perturbed by increasing and decreasing nuclear translocation of p65 and p50, respectively. Our data highlight USP18 as a host restriction factor during innate immune response to PRRSV., (Copyright © 2012 Elsevier B.V. All rights reserved.)
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- 2012
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71. Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.
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Kapetanovic R, Fairbairn L, Beraldi D, Sester DP, Archibald AL, Tuggle CK, and Hume DA
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- Animals, Bone Marrow Cells drug effects, Cell Differentiation drug effects, Gene Expression Profiling, Gene Expression Regulation immunology, Gene Regulatory Networks, Humans, Macrophage Colony-Stimulating Factor pharmacology, Macrophages metabolism, Male, Mice, Molecular Sequence Data, Nitric Oxide analysis, Oligonucleotide Array Sequence Analysis, Phagocytosis drug effects, Promoter Regions, Genetic genetics, Recombinant Proteins pharmacology, Salmonella enterica, Sequence Alignment, Sequence Homology, Nucleic Acid, Species Specificity, Sus scrofa anatomy & histology, Bone Marrow Cells physiology, Lipopolysaccharides pharmacology, Macrophage Activation drug effects, Macrophages drug effects, Sus scrofa immunology
- Abstract
Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely in studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from the domestic pig using human rCSF-1 and whether porcine macrophages might represent a better model of human macrophage biology. Cultivation of pig bone marrow cells for 5-7 d in presence of human rCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells, and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow cells that had been stored frozen and thawed so that multiple experiments can be performed on samples from a single animal. Gene expression in pig BMDM from outbred animals responding to LPS was profiled using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely resembled the known responses of human than mouse macrophages, sharing with humans the regulation of genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3-converting enzyme, Cyp27B1. Conversely, in common with published studies of human macrophages, pig BMDM did not strongly induce genes involved in arginine metabolism, nor did they produce NO. These results establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control.
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- 2012
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72. Reprogramming pig fetal fibroblasts reveals a functional LIF signaling pathway.
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Thomson AJ, Pierart H, Meek S, Bogerman A, Sutherland L, Murray H, Mountjoy E, Downing A, Talbot R, Sartori C, Whitelaw CB, Freeman TC, Archibald AL, and Burdon T
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- Animals, Cell Differentiation drug effects, Cell Differentiation genetics, Cell Differentiation physiology, Cells, Cultured, Cellular Reprogramming drug effects, Cellular Reprogramming genetics, Embryonic Stem Cells drug effects, Embryonic Stem Cells physiology, Fetus cytology, Fetus metabolism, Fetus physiology, Fibroblasts drug effects, Fibroblasts physiology, Gene Expression Profiling, HEK293 Cells, Humans, Kruppel-Like Factor 4, Leukemia Inhibitory Factor genetics, Leukemia Inhibitory Factor pharmacology, Leukemia Inhibitory Factor physiology, Mice, Mice, Inbred NOD, Mice, SCID, Microarray Analysis, Signal Transduction drug effects, Signal Transduction genetics, Signal Transduction physiology, Swine, Transfection, Cellular Reprogramming physiology, Embryonic Stem Cells metabolism, Fibroblasts metabolism, Leukemia Inhibitory Factor metabolism
- Abstract
Distinct signaling pathways are reported to maintain pluripotency in embryo-derived stem cells. Mouse embryonic stem cells (ESCs) respond to leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP)-mediated activity, whereas human ESCs depend upon Fibroblast growth factor (FGF) and activin signaling. In the majority of mammals investigated, however, the signals that support stem cell pluripotency are not well defined, as is evident by the persistent difficulties in maintaining authentic stable ESC lines. Induction of pluripotency by transcription factor-mediated reprogramming could provide an alternative way to produce ESC-like cells from nonpermissive species, and facilitate identification of core ESC signaling requirements. To evaluate the effectiveness of this approach in pigs, we transduced porcine foetal fibroblasts with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc, and maintained the resulting cultures in medium containing either LIF or FGF2. Alkaline phosphatase positive colonies with compact, mouse ESC-like morphology were preferentially recovered using serum-free medium supplemented with LIF. These cell lines expressed the endogenous stem cell transcription factors, OCT4, NANOG, and SOX2, and the cell surface marker SSEA-4, consistent with acquisition of an undifferentiated state. However, restricted differentiation potential, and persistent expression of retroviral transgenes indicated that reprogramming was incomplete. Interestingly, LIF activated both the transcription factor STAT3 and its target gene SOCS3, and stimulated cell growth, indicating functional coupling of the signaling pathway in these cells. This demonstration of LIF-dependence in reprogrammed pig cells supports the notion that the connection between LIF/STAT3 signaling and the core regulatory network of pluripotent stem cells is a conserved pathway in mammals.
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- 2012
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73. Detection of a quantitative trait locus associated with resistance to Ascaris suum infection in pigs.
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Skallerup P, Nejsum P, Jørgensen CB, Göring HH, Karlskov-Mortensen P, Archibald AL, Fredholm M, and Thamsborg SM
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- Animals, Ascariasis genetics, Ascariasis immunology, Ascariasis parasitology, Ascaris suum isolation & purification, Chromosomes, Mammalian, Female, Gene Frequency, Genome, Genotype, Male, Parasite Load, Polymorphism, Single Nucleotide, Swine, Swine Diseases parasitology, Ascariasis veterinary, Ascaris suum immunology, Disease Resistance, Quantitative Trait Loci, Swine Diseases genetics, Swine Diseases immunology
- Abstract
Helminths almost invariably have an over-dispersed distribution in the host population. Human and animal studies have provided evidence suggesting that a large part of this variation is due to host genetic factors. Recently, the heritability for roundworm (Ascaris suum) infection levels in pigs was estimated to be 0.45. We used single nucleotide polymorphism markers to perform a whole-genome scan on 195 pigs experimentally infected with A. suum. A putative quantitative trait locus for worm burden on chromosome 4 covering 2.5 Mbp was identified by measured genotype analysis, although none of the SNPs reached genome-wide significance. To validate the putative quantitative trait locus, we genotyped two of the SNPs within the region in unrelated, informative animals exposed to experimental or natural infections and from which we had worm counts and/or faecal egg counts; the validation studies showed that one of the SNPs (TXNIP) was associated with total worm burden (P < 0.001) and adult worm burden(P < 0.0001), whereas the other SNP (ARNT) was associated with adult worm burden (P < 0.025) in these populations. We were thus able to confirm the existence of the quantitative trait locus on chromosome 4.This is to our knowledge the first report of a quantitative trait locus associated with helminth burden in pigs.
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- 2012
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74. An intronic polymorphism in the porcine IRF7 gene is associated with better health and immunity of the host during Sarcocystis infection, and affects interferon signalling.
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Brock AJ, Matika O, Wilson AD, Anderson J, Morin AC, Finlayson HA, Reiner G, Willems H, Bishop SC, Archibald AL, and Ait-Ali T
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- Animals, Base Sequence, Cloning, Molecular, DNA Primers genetics, Gene Frequency, Genome-Wide Association Study, Introns genetics, Linear Models, Molecular Sequence Data, Reverse Transcriptase Polymerase Chain Reaction, Sarcocystosis genetics, Sequence Analysis, DNA, Signal Transduction genetics, Sus scrofa immunology, Swine, Interferon Regulatory Factor-7 genetics, Phenotype, Sarcocystosis veterinary, Signal Transduction immunology, Sus scrofa genetics, Swine Diseases genetics, Swine Diseases parasitology
- Abstract
Interferon regulatory factor 7 (IRF7), as a key regulator of type I interferon response, plays an important role during innate response against viral infection. Although well conserved across species, the structure of IRF7 and its function during parasite infection are not well documented in farm animals, such as the pig. To bridge this gap, we have determined the porcine IRF7 gene structure and identified two intronic single nucleotide polymorphisms (SNPs), SNP g.748G>C and SNP g.761A>G, in commercial pig breeds. The distribution of SNP g.761A>G in multiple breeds suggested that it was in Hardy-Weinberg equilibrium and allowed us to map it at the top of SSC2. We found that during Sarcocystis miescheriana infection, the G allele was associated with high lymphocyte levels (P < 0.02), reduced drop in platelet levels (P < 0.002) and IgG1-Th2-dominated response (P < 0.05). This suggests that the G allele was associated with better health and immunity of the host during Sarcocystis infection. Furthermore, we have also provided suggestive evidence that the G allele of SNPc.761A>G enhances the transactivation activity of IRF7, possibly by improving IRF7 transcript splicing of intron-3. These findings would suggest that IRF7, as a transcriptional regulator, is involved in the defence mechanism against a larger spectrum of pathogens, and in more host species, than initially anticipated., (© 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.)
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- 2011
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75. Host inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response.
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Ait-Ali T, Wilson AD, Carré W, Westcott DG, Frossard JP, Mellencamp MA, Mouzaki D, Matika O, Waddington D, Drew TW, Bishop SC, and Archibald AL
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- Animals, Gene Expression Regulation, Immunity, Innate genetics, Macrophages, Alveolar virology, Porcine Reproductive and Respiratory Syndrome genetics, Swine, Host-Pathogen Interactions genetics, Interferon Type I genetics, Macrophages, Alveolar immunology, Porcine Reproductive and Respiratory Syndrome immunology, Porcine respiratory and reproductive syndrome virus physiology, Transcription, Genetic, Virus Replication
- Abstract
Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by a positive RNA strand arterivirus. PRRS virus (PRRSV) interacts primarily with lung macrophages. Little is known how the virus subverts the innate immune response to initiate its replication in alveolar macrophages. Large-scale transcriptional responses of macrophages with different levels of susceptibility to PRRSV infection were compared over 30 h of infection. This study demonstrates a rapid and intense host transcriptional remodelling during the early phase of the replication of the virus which correlates with transient repression of type-I interferon transcript as early as 8 h post-infection. These results support the suggestion from previous studies that host innate immune response inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response.
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- 2011
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76. Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs.
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Jacobsen M, Cirera S, Joller D, Esteso G, Kracht SS, Edfors I, Bendixen C, Archibald AL, Vogeli P, Neuenschwander S, Bertschinger HU, Rampoldi A, Andersson L, Fredholm M, and Jørgensen CB
- Abstract
Background: Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes., Findings: The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues., Conclusions: None of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.
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- 2011
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77. Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection.
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Noyes H, Brass A, Obara I, Anderson S, Archibald AL, Bradley DG, Fisher P, Freeman A, Gibson J, Gicheru M, Hall L, Hanotte O, Hulme H, McKeever D, Murray C, Oh SJ, Tate C, Smith K, Tapio M, Wambugu J, Williams DJ, Agaba M, and Kemp SJ
- Subjects
- Alleles, Animals, Cattle, Cloning, Molecular, Expressed Sequence Tags, Gene Expression Profiling, Genotype, Models, Genetic, Molecular Sequence Data, Mutation, Polymorphism, Genetic, Quantitative Trait Loci, Tissue Distribution, Gene Expression Regulation, Trypanosoma congolense metabolism, Trypanosomiasis, Bovine genetics, Trypanosomiasis, Bovine parasitology
- Abstract
African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. Some African Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. We used three strategies to obtain short lists of candidate genes within QTL that were previously shown to regulate response to infection. We analyzed the transcriptomes of trypanotolerant N'Dama and susceptible Boran cattle after infection with Trypanosoma congolense. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for evidence of selective sweeps. The scan of the EST sequences identified a previously undescribed polymorphism in ARHGAP15 in the Bta2 trypanotolerance QTL. The polymorphism affects gene function in vitro and could contribute to the observed differences in expression of the MAPK pathway in vivo. The expression data showed that TLR and MAPK pathways responded to infection, and the former contained TICAM1, which is within a QTL on Bta7. Genetic analyses showed that selective sweeps had occurred at TICAM1 and ARHGAP15 loci in African taurine cattle, making them strong candidates for the genes underlying the QTL. Candidate QTL genes were identified in other QTL by their expression profile and the pathways in which they participate.
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- 2011
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78. Evaluation of approaches for identifying population informative markers from high density SNP chips.
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Wilkinson S, Wiener P, Archibald AL, Law A, Schnabel RD, McKay SD, Taylor JF, and Ogden R
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- Animals, Gene Frequency, Genotype, Animal Identification Systems methods, Cattle genetics, Genetic Markers, Polymorphism, Single Nucleotide
- Abstract
Background: Genetic markers can be used to identify and verify the origin of individuals. Motivation for the inference of ancestry ranges from conservation genetics to forensic analysis. High density assays featuring Single Nucleotide Polymorphism (SNP) markers can be exploited to create a reduced panel containing the most informative markers for these purposes. The objectives of this study were to evaluate methods of marker selection and determine the minimum number of markers from the BovineSNP50 BeadChip required to verify the origin of individuals in European cattle breeds. Delta, Wright's FST, Weir & Cockerham's FST and PCA methods for population differentiation were compared. The level of informativeness of each SNP was estimated from the breed specific allele frequencies. Individual assignment analysis was performed using the ranked informative markers. Stringency levels were applied by log-likelihood ratio to assess the confidence of the assignment test., Results: A 95% assignment success rate for the 384 individually genotyped animals was achieved with <80, <100, <140 and <200 SNP markers (with increasing stringency threshold levels) across all the examined methods for marker selection. No further gain in power of assignment was achieved by sampling in excess of 200 SNP markers. The marker selection method that required the lowest number of SNP markers to verify the animal's breed origin was Wright's FST (60 to 140 SNPs depending on the chosen degree of confidence). Certain breeds required fewer markers (<100) to achieve 100% assignment success. In contrast, closely related breeds require more markers (~200) to achieve>95% assignment success. The power of assignment success, and therefore the number of SNP markers required, is dependent on the levels of genetic heterogeneity and pool of samples considered., Conclusions: While all SNP selection methods produced marker panels capable of breed identification, the power of assignment varied markedly among analysis methods. Thus, with effective exploration of available high density genetic markers, a diagnostic panel of highly informative markers can be produced.
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- 2011
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79. Mapping QTL in the porcine MHC region affecting fatness and growth traits in a Meishan/Large White composite population.
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Wei WH, Skinner TM, Anderson JA, Southwood OI, Plastow G, Archibald AL, and Haley CS
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- Adipose Tissue growth & development, Animals, Breeding, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Major Histocompatibility Complex, Meat, Quantitative Trait Loci, Sus scrofa genetics, Sus scrofa growth & development
- Abstract
A number of studies have mapped QTL regulating porcine fatness and growth traits to the region of the major histocompatibility complex (MHC) on porcine chromosome 7 using various experimental crosses. The QTL results from crosses using the Chinese Meishan (MS) (slow growing and fat) are particularly interesting because the MS alleles have been found to be associated with increased growth rate and reduced backfat depth. We investigated these QTL further in a composite population derived previously over eight generations by intercrossing Meishan and the European Large White breeds. Genotype information from 32 markers in a 15cM target region was used in linkage and association analyses. A two-step variance component analysis identified QTL for three growth-related traits, explaining 19 ∼ 24% of the phenotypic variance with a confidence interval of 4 cM in the target region. SNP association analyses found that ss181128966 and ss181128924 within the QTL interval were strongly associated with the growth traits. Only weak signals for an effect on backfat depth were found in the association and linkage analyses, possibly because of past directional selection in the composite population., (© 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.)
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- 2011
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80. The receptor locus for Escherichia coli F4ab/F4ac in the pig maps distal to the MUC4-LMLN region.
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Rampoldi A, Jacobsen MJ, Bertschinger HU, Joller D, Bürgi E, Vögeli P, Andersson L, Archibald AL, Fredholm M, Jørgensen CB, and Neuenschwander S
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- Animals, Bacterial Adhesion, Base Sequence, Chromosome Mapping, Enterotoxigenic Escherichia coli genetics, Escherichia coli Infections genetics, Escherichia coli Infections immunology, Escherichia coli Infections microbiology, Female, Fimbriae, Bacterial immunology, Linkage Disequilibrium, Male, Molecular Sequence Data, Mucin-4 immunology, Polymorphism, Single Nucleotide, Receptors, Cell Surface immunology, Swine immunology, Swine microbiology, Swine Diseases immunology, Swine Diseases microbiology, Enterotoxigenic Escherichia coli immunology, Escherichia coli Infections veterinary, Fimbriae, Bacterial genetics, Mucin-4 genetics, Receptors, Cell Surface genetics, Swine genetics, Swine Diseases genetics
- Abstract
Enterotoxigenic Escherichia coli (ETEC) with fimbriae of the F4 family are one of the major causes of diarrhea and death among neonatal and young piglets. Bacteria use the F4 fimbriae to adhere to specific receptors expressed on the surface of the enterocytes. F4 fimbriae exist in three different antigenic variants, F4ab, F4ac, and F4ad, of which F4ac is the most common. Resistance to ETEC F4ab/F4ac adhesion in pigs has been shown to be inherited as an autosomal recessive trait. In previous studies the ETEC F4ab/F4ac receptor locus (F4bcR) was mapped to the q41 region on pig chromosome 13. A polymorphism within an intron of the mucin 4 (MUC4) gene, which is one of the possible candidate genes located in this region, was shown earlier to cosegregate with the F4bcR alleles. Recently, we discovered a Large White boar from a Swiss experimental herd with a recombination between F4bcR and MUC4. A three-generation pedigree including 45 offspring was generated with the aim to use this recombination event to refine the localization of the F4bcR locus. All pigs were phenotyped using the microscopic adhesion test and genotyped for a total of 59 markers. The recombination event was mapped to a 220-kb region between a newly detected SNP in the leishmanolysin-like gene (LMLN g.15920) and SNP ALGA0072075. In this study the six SNPs ALGA0072075, ALGA0106330, MUC13-226, MUC13-813, DIA0000584, and MARC0006918 were in complete linkage disequilibrium with F4bcR. Based on this finding and earlier investigations, we suggest that the locus for F4bcR is located between the LMLN locus and microsatellite S0283.
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- 2011
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81. The sheep genome reference sequence: a work in progress.
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Archibald AL, Cockett NE, Dalrymple BP, Faraut T, Kijas JW, Maddox JF, McEwan JC, Hutton Oddy V, Raadsma HW, Wade C, Wang J, Wang W, and Xun X
- Subjects
- Animals, Cattle, Genomics standards, Molecular Sequence Annotation, Physical Chromosome Mapping veterinary, Reference Standards, Genome, Sheep, Domestic genetics
- Abstract
Until recently, the construction of a reference genome was performed using Sanger sequencing alone. The emergence of next-generation sequencing platforms now means reference genomes may incorporate sequence data generated from a range of sequencing platforms, each of which have different read length, systematic biases and mate-pair characteristics. The objective of this review is to inform the mammalian genomics community about the experimental strategy being pursued by the International Sheep Genomics Consortium (ISGC) to construct the draft reference genome of sheep (Ovis aries). Component activities such as data generation, sequence assembly and annotation are described, along with information concerning the key researchers performing the work. This aims to foster future participation from across the research community through the coordinated activities of the consortium. The review also serves as a 'marker paper' by providing information concerning the pre-publication release of the reference genome. This ensures the ISGC adheres to the framework for data sharing established at the recent Toronto International Data Release Workshop and provides guidelines for data users., (© 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.)
- Published
- 2010
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82. Pig genome sequence--analysis and publication strategy.
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Archibald AL, Bolund L, Churcher C, Fredholm M, Groenen MA, Harlizius B, Lee KT, Milan D, Rogers J, Rothschild MF, Uenishi H, Wang J, and Schook LB
- Subjects
- Animals, Publications, Sequence Analysis, DNA, Genome, Sus scrofa genetics
- Abstract
Background: The pig genome is being sequenced and characterised under the auspices of the Swine Genome Sequencing Consortium. The sequencing strategy followed a hybrid approach combining hierarchical shotgun sequencing of BAC clones and whole genome shotgun sequencing., Results: Assemblies of the BAC clone derived genome sequence have been annotated using the Pre-Ensembl and Ensembl automated pipelines and made accessible through the Pre-Ensembl/Ensembl browsers. The current annotated genome assembly (Sscrofa9) was released with Ensembl 56 in September 2009. A revised assembly (Sscrofa10) is under construction and will incorporate whole genome shotgun sequence (WGS) data providing > 30x genome coverage. The WGS sequence, most of which comprise short Illumina/Solexa reads, were generated from DNA from the same single Duroc sow as the source of the BAC library from which clones were preferentially selected for sequencing. In accordance with the Bermuda and Fort Lauderdale agreements and the more recent Toronto Statement the data have been released into public sequence repositories (Genbank/EMBL, NCBI/Ensembl trace repositories) in a timely manner and in advance of publication., Conclusions: In this marker paper, the Swine Genome Sequencing Consortium (SGSC) sets outs its plans for analysis of the pig genome sequence, for the application and publication of the results.
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- 2010
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83. Genotype and expression analysis of two inbred mouse strains and two derived congenic strains suggest that most gene expression is trans regulated and sensitive to genetic background.
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Noyes HA, Agaba M, Anderson S, Archibald AL, Brass A, Gibson J, Hall L, Hulme H, Oh SJ, and Kemp S
- Subjects
- Animals, Female, Genetic Loci genetics, Genotype, Inbreeding, Male, Mice, Mice, Congenic, Polymorphism, Single Nucleotide, Probability, Gene Expression Profiling, Gene Expression Regulation genetics, Transcription Factors metabolism
- Abstract
Background: Differences in gene expression may be caused by nearby DNA polymorphisms (cis regulation) or by interactions of gene control regions with polymorphic transcription factors (trans regulation). Trans acting loci are much harder to detect than cis acting loci and their effects are much more sensitive to genetic background., Results: To quantify cis and trans regulation we correlated haplotype data with gene expression in two inbred mouse strains and two derived congenic lines. Upstream haplotype differences between the parental strains suggested that 30-43% of differentially expressed genes were differentially expressed because of cis haplotype differences. These cis regulated genes displayed consistent and relatively tissue-independent differential expression. We independently estimated from the congenic mice that 71-85% of genes were trans regulated. Cis regulated genes were associated with low p values (p < 0.005) for differential expression, whereas trans regulated genes were associated with values 0.005 < p < 0.05. The genes differentially expressed between congenics and controls were not a subset of those that were differentially expressed between the founder lines, showing that these were dependent on genetic background. For example, the cholesterol synthesis pathway was strongly differentially expressed in the congenic mice by indirect trans regulation but this was not observable in the parental mice., Conclusions: The evidence that most gene regulation is trans and strongly influenced by genetic background, suggests that pathways that are modified by an allelic variant, may only exhibit differential expression in the specific genetic backgrounds in which they were identified. This has significant implications for the interpretation of any QTL mapping study.
- Published
- 2010
- Full Text
- View/download PDF
84. Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs.
- Author
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Jacobsen M, Kracht SS, Esteso G, Cirera S, Edfors I, Archibald AL, Bendixen C, Andersson L, Fredholm M, and Jørgensen CB
- Subjects
- Animals, Enterotoxigenic Escherichia coli classification, Escherichia coli Infections genetics, Escherichia coli Infections microbiology, Female, Haplotypes, Male, Microsatellite Repeats, Sus scrofa, Swine, Swine Diseases microbiology, Enterotoxigenic Escherichia coli physiology, Escherichia coli Infections veterinary, Genetic Predisposition to Disease, Swine Diseases genetics
- Abstract
Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.
- Published
- 2010
- Full Text
- View/download PDF
85. Refined localization of the Escherichia coli F4ab/F4ac receptor locus on pig chromosome 13.
- Author
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Joller D, Jørgensen CB, Bertschinger HU, Python P, Edfors I, Cirera S, Archibald AL, Bürgi E, Karlskov-Mortensen P, Andersson L, Fredholm M, and Vögeli P
- Subjects
- Animals, Chromosome Mapping veterinary, Chromosomes genetics, Chromosomes metabolism, Escherichia coli Infections genetics, Escherichia coli Proteins metabolism, Fimbriae Proteins metabolism, Genetic Markers genetics, Swine, Bacterial Adhesion genetics, Escherichia coli Infections veterinary, Escherichia coli Proteins genetics, Fimbriae Proteins genetics, Fimbriae, Bacterial metabolism, Swine Diseases genetics, Swine Diseases microbiology
- Abstract
Diarrhoea in newborn and weaned pigs caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbriae leads to considerable losses in pig production. In this study, we refined the mapping of the receptor locus for ETEC F4ab/F4ac adhesion (F4bcR) by joint analysis of Nordic and Swiss data. A total of 236 pigs from a Nordic experimental herd, 331 pigs from a Swiss experimental herd and 143 pigs from the Swiss performing station were used for linkage analysis. Genotyping data of six known microsatellite markers, two newly developed markers (MUC4gt and HSA125gt) and an intronic SNP in MUC4 (MUC4-8227) were used to create the linkage map. The region for F4bcR was refined to the interval SW207-S0075 on pig chromosome 13. The most probable position of F4bcR was in the SW207-MUC4 region. The order of six markers was supported by physical mapping on the BAC fingerprint contig from the Wellcome Trust Sanger Institute. Thus, the region for F4bcR could be reduced from 26 to 14 Mb.
- Published
- 2009
- Full Text
- View/download PDF
86. Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology.
- Author
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Ramos AM, Crooijmans RP, Affara NA, Amaral AJ, Archibald AL, Beever JE, Bendixen C, Churcher C, Clark R, Dehais P, Hansen MS, Hedegaard J, Hu ZL, Kerstens HH, Law AS, Megens HJ, Milan D, Nonneman DJ, Rohrer GA, Rothschild MF, Smith TP, Schnabel RD, Van Tassell CP, Taylor JF, Wiedmann RT, Schook LB, and Groenen MA
- Subjects
- Animals, Genotype, Species Specificity, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods, Swine genetics
- Abstract
Background: The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay., Methodology/principal Findings: A total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274., Conclusions/significance: Overall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs.
- Published
- 2009
- Full Text
- View/download PDF
87. Functional analysis of the porcine USP18 and its role during porcine arterivirus replication.
- Author
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Ait-Ali T, Wilson AW, Finlayson H, Carré W, Ramaiahgari SC, Westcott DG, Waterfall M, Frossard JP, Baek KH, Drew TW, Bishop SC, and Archibald AL
- Subjects
- Amino Acid Sequence, Animals, Cells, Cultured, Chlorocebus aethiops, Endopeptidases genetics, Humans, Immunity, Innate, Macrophages, Alveolar metabolism, Macrophages, Alveolar virology, Mice, Molecular Sequence Data, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome virology, Promoter Regions, Genetic, Sus scrofa, Ubiquitin Thiolesterase, Ubiquitination, Virus Replication, Endopeptidases physiology, Porcine respiratory and reproductive syndrome virus physiology
- Abstract
Emerging evidence places deubiquitylation at the core of a multitude of regulatory processes, ranging from cell growth to innate immune response and health, such as cancer, degenerative and infectious diseases. Little is known about deubiquitylation in pig and arterivirus infection. This report provides information on the biochemical and functional role of the porcine USP18 during innate immune response to the porcine respiratory and reproductive syndrome virus (PRRSV). We have shown that UBP gene is the ortholog of the murine USP18 (Ubp43) gene and the human ubiquitin specific protease 18 (USP18) gene and encodes a biochemically functional de-ubiquitin enzyme which inhibits signalling pathways that lead to IFN-stimulating response element (ISRE) promotor regulation. Furthermore we have demonstrated that overexpression of the porcine USP18 leads to reduced replication and/or growth of PRRSV. Our data contrast with the conclusion of numerous reports demonstrating that USP18-deficient mice are highly resistant to viral and bacterial infections and to oncogenic transformation by BCR-ABL, and highlight USP18 as a potential target gene that promotes reduced replication of PRRSV.
- Published
- 2009
- Full Text
- View/download PDF
88. Comparative genomics of Toll-like receptor signalling in five species.
- Author
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Jann OC, King A, Corrales NL, Anderson SI, Jensen K, Ait-Ali T, Tang H, Wu C, Cockett NE, Archibald AL, and Glass EJ
- Subjects
- Animals, Cattle, Chromosomes, Mammalian, Disease Susceptibility, Genomics methods, Humans, Immunity, Innate genetics, Mice, Radiation Hybrid Mapping, Sheep genetics, Swine genetics, Comparative Genomic Hybridization, Quantitative Trait Loci, Toll-Like Receptors genetics
- Abstract
Background: Over the last decade, several studies have identified quantitative trait loci (QTL) affecting variation of immune related traits in mammals. Recent studies in humans and mice suggest that part of this variation may be caused by polymorphisms in genes involved in Toll-like receptor (TLR) signalling. In this project, we used a comparative approach to investigate the importance of TLR-related genes in comparison with other immunologically relevant genes for resistance traits in five species by associating their genomic location with previously published immune-related QTL regions., Results: We report the genomic localisation of TLR1-10 and ten associated signalling molecules in sheep and pig using in-silico and/or radiation hybrid (RH) mapping techniques and compare their positions with their annotated homologues in the human, cattle and mouse whole genome sequences. We also report medium-density RH maps for porcine chromosomes 8 and 13. A comparative analysis of the positions of previously published relevant QTLs allowed the identification of homologous regions that are associated with similar health traits in several species and which contain TLR related and other immunologically relevant genes. Additional evidence was gathered by examining relevant gene expression and association studies., Conclusion: This comparative genomic approach identified eight genes as potentially causative genes for variations of health related traits. These include susceptibility to clinical mastitis in dairy cattle, general disease resistance in sheep, cattle, humans and mice, and tolerance to protozoan infection in cattle and mice. Four TLR-related genes (TLR1, 6, MyD88, IRF3) appear to be the most likely candidate genes underlying QTL regions which control the resistance to the same or similar pathogens in several species. Further studies are required to investigate the potential role of polymorphisms within these genes.
- Published
- 2009
- Full Text
- View/download PDF
89. Mapping quantitative trait loci for reproduction in pigs.
- Author
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Hernandez SC, Finlayson HA, Ashworth CJ, Haley CS, and Archibald AL
- Subjects
- Animals, Breeding methods, Chromosome Mapping methods, Embryo Loss genetics, Female, Litter Size genetics, Ovulation genetics, Chromosome Mapping veterinary, Quantitative Trait Loci genetics, Reproduction genetics, Swine genetics
- Published
- 2009
90. Quantitative trait loci for production traits in pigs: a combined analysis of two Meishan x Large White populations.
- Author
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Guo YM, Lee GJ, Archibald AL, and Haley CS
- Subjects
- Animals, Crosses, Genetic, Female, Genome, Male, Quantitative Trait, Heritable, Quantitative Trait Loci, Sus scrofa genetics
- Abstract
Combined analysis of data from two or more resource populations can improve the power and accuracy of QTL mapping and allow some cross-validation of results. In this study, we performed a genome-wide scan using combined data from two F(2) populations derived from a cross between Large White and Chinese Meishan pigs. A total of 739 pigs were included in the analysis. In total 187 markers were genotyped in the two populations, including 115 markers genotyped in both populations, and these markers covered 2282 cM of the pig genome with an average of 13.58 cM between markers. Seven traits (teat number, birth weight, weaning weight, test-end weight, fat depth at shoulder, fat depth at mid back and fat depth at loin) were analysed for both individual populations and the combined population. There were 9 (2, 10), 1 (4, 4) and 14 (5, 18) QTL that achieved 1% genome-wide, 5% genome-wide and suggestive significance levels respectively in population 1 (population 2, combined population). Additive effects of QTL detected in the two populations at all significance levels were largely consistent suggesting that the QTL represent real genetic effects, but this was not the case for dominance or imprinting effects. There were also a number of significant interactions between detected QTL effects and population.
- Published
- 2008
- Full Text
- View/download PDF
91. An animal model to evaluate the function and regulation of the adaptively evolving stress protein SEP53 in oesophageal bile damage responses.
- Author
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Nelson L, Anderson S, Archibald AL, Rhind S, Lu ZH, Condie A, McIntyre N, Thompson J, Nenutil R, Vojtesek B, Whitelaw CB, Little TJ, and Hupp T
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Tumor, Epithelium metabolism, Esophagus metabolism, Humans, Membrane Proteins genetics, Molecular Sequence Data, Neoplasm Proteins genetics, Sequence Alignment, Sequence Homology, Amino Acid, Swine, Bile metabolism, Disease Models, Animal, Epithelium pathology, Esophagus anatomy & histology, Esophagus pathology, Membrane Proteins metabolism, Neoplasm Proteins metabolism
- Abstract
Squamous epithelium in mammals has evolved an atypical stress response involving down-regulation of the classic HSP70 protein and induction of sets of proteins including one named SEP53. This atypical stress response might be due to the unusual environmental pressures placed on squamous tissue. In fact, SEP53 plays a role as an anti-apoptotic factor in response to DNA damage induced by deoxycholic acid stresses implicated in oesophageal reflux disease. SEP53 also has a genetic signature characteristic of an adaptively and rapidly evolving gene, and this observation has been used to imply a role for SEP53 in immunity. Physiological models of squamous tissue are required to further define the regulation and function of SEP53. We examined whether porcine squamous epithelium would be a good model to study SEP53, since this animal suffers from a bile-reflux disease in squamous oesophageal tissue. We have (1) cloned and sequenced the porcine SEP53 locus from porcine bacterial artificial chromosome genomic DNA, (2) confirmed the strikingly divergent nature of the C-terminal portion of the SEP53 gene amongst mammals, (3) discovered that a function of the conserved N-terminal domain of the gene is to maintain cytoplasmic localisation, and (4) examined SEP53 expression in normal and diseased porcine pars oesophagea. SEP53 expression in porcine tissue was relatively confined to gastric squamous epithelium, consistent with its expression in normal human squamous epithelium. Immunohistochemical staining for SEP53 protein in normal and damaged pars oesophagea demonstrated significant stabilisation of SEP53 protein in the injured tissue. These results suggest that porcine squamous epithelium would be a robust physiological model to examine the evolution and function of the SEP53 stress pathway in modulating stress-induced responses in squamous tissue.
- Published
- 2008
- Full Text
- View/download PDF
92. Characterization of the porcine KIT ligand gene: expression analysis, genomic structure, polymorphism detection and association with coat colour traits.
- Author
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Hadjiconstantouras C, Sargent CA, Skinner TM, Archibald AL, Haley CS, and Plastow GS
- Subjects
- Alternative Splicing, Animals, Base Sequence, Exons, Genetic Linkage, Genome, Introns, Molecular Sequence Data, Open Reading Frames, Physical Chromosome Mapping, Quantitative Trait Loci, Gene Expression, Hair Color genetics, Polymorphism, Genetic, Stem Cell Factor genetics, Sus scrofa genetics
- Abstract
Kit ligand (KITLG) is the ligand for the type III receptor tyrosine kinase KIT. Studies of the KIT/KITLG pathway in a number of mammalian species have shown that it is important for the development of stem cell populations in haematopoietic tissues, germ cells in reproductive organs and the embryonic migrating melanoblasts that give rise to melanocytes. Consequently, mutations in the pathway may result in a range of defects including anaemia, sterility and de-pigmentation. The cDNA sequence of the porcine KITLG gene has been reported previously, and is an attractive candidate locus for moderating coat colour in pigs. In this paper we report the gene structure and physical mapping of the porcine gene. We also report the identification of polymorphisms in the gene, one of which was used to confirm linkage to chromosome 5. Preliminary RNA expression studies using a panel of tissues have shown that in addition to the known variant lacking exon 6, there is alternative splicing of exon 4. However, little evidence was found for the KITLG gene being linked to variation in colour in a Meishan x Large White cross.
- Published
- 2008
- Full Text
- View/download PDF
93. The cholecystokinin type A receptor g.179A>G polymorphism affects feeding rate.
- Author
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Houston RD, Rance KA, Sutcliffe E, Archibald AL, and Haley CS
- Subjects
- Animals, Crosses, Genetic, Satiety Response physiology, Swine growth & development, 5' Untranslated Regions genetics, Energy Intake, Feeding Behavior physiology, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Receptor, Cholecystokinin A genetics, Swine genetics
- Abstract
A polymorphism within the 5' untranslated region of the cholecystokinin type A receptor (CCKAR) gene has been shown to affect feed intake and growth in commercial pig lines. To further investigate the phenotype of animals carrying alternative alleles at this polymorphism, we genotyped animals from a distinct segregating commercial line and an experimental cross F(2) population, both with electronically recorded feeding pattern data. The data indicate that the daily feed intake increasing effect of the DQ496228:g.179G allele is mediated through a faster rate of feed intake, without evidence for an effect on other feeding behaviour traits.
- Published
- 2008
- Full Text
- View/download PDF
94. Structural analysis and haplotype diversity in swine LEP and MC4R genes.
- Author
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D'Andrea M, Pilla F, Giuffra E, Waddington D, and Archibald AL
- Subjects
- Animals, Animals, Wild genetics, Base Sequence, Body Weight genetics, Breeding, Chromosome Inversion, DNA genetics, Female, Genetic Variation, Haplotypes, Male, Molecular Sequence Data, Phylogeny, Polymorphism, Single Nucleotide, Species Specificity, Sus scrofa anatomy & histology, Sus scrofa classification, Swine genetics, Leptin genetics, Receptor, Melanocortin, Type 4 genetics, Sus scrofa genetics
- Abstract
Knowledge about structural variation of candidate genes could be important to improve breeding selection scheme and preserve genetic variability in livestock species. Leptin (LEP) and melanocortin-4 receptor (MC4R) genes are involved in the energetic pathway and are obvious candidate genes for fatness. By sequencing LEP and MC4R genes in 72 pigs belonging to lean (Large White and Duroc), fat (Meishan and Casertana) breeds and also Wild Boar, 98 polymorphic sites, of which 91 were novel, were found in the Leptin sequence while only the previously described mutation was found in the MC4R gene. A total of 18 LEP haplotypes were observed and their distribution was unequal among the breeds. The phylogenetic analysis showed two haplotype branches distinguishing between lean and fat breeds.
- Published
- 2008
- Full Text
- View/download PDF
95. Dynamic differential regulation of innate immune transcripts during the infection of alveolar macrophages by the porcine reproductive and respiratory syndrome virus.
- Author
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Ait-Ali T, Wilson AD, Westcott DG, Frossard JP, Mellencamp MA, Drew TW, Bishop SC, and Archibald AL
- Subjects
- Animals, Base Sequence, DNA Primers, Swine, Virus Replication, Immunity, Innate genetics, Macrophages, Alveolar virology, Porcine respiratory and reproductive syndrome virus physiology, RNA, Messenger genetics
- Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, is the etiologic agent of an infectious disease of that name, characterized by respiratory disorders, abortion in pregnant sows and high mortality in piglets, resulting in significant economic losses in the pig industry worldwide. In order to identify whether genetic differences in PRRSV response may exist in pigs, alveolar macrophages were used to assess the progression of the type-I interferon (IFN) transcript response in porcine alveolar macrophages infected by PRRSV. Our results suggest that a dynamic differential regulation of the type-I IFN and chemokine transcripts may operate during the first hours of infection with and entry of the virus in alveolar macrophages, and provide a compelling mechanism for the establishment of PRRSV replication in susceptible cells.
- Published
- 2008
- Full Text
- View/download PDF
96. Genetic perspectives on host responses to porcine reproductive and respiratory syndrome (PRRS).
- Author
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Lewis CR, Ait-Ali T, Clapperton M, Archibald AL, and Bishop S
- Subjects
- Animals, Immunity, Innate genetics, Porcine Reproductive and Respiratory Syndrome physiopathology, Swine, Swine Diseases physiopathology, Genetic Variation, Porcine Reproductive and Respiratory Syndrome genetics, Swine Diseases genetics
- Abstract
Porcine reproductive and respiratory syndrome (PRRS) is the most economically important disease in pig populations, worldwide. Current research, both in vitro and in vivo, has failed to provide industry with a reliable or effective method to combat the disease. In this paper the present knowledge of the genetics of the host response to porcine reproductive and respiratory syndrome virus (PRRSV) is reviewed. Special reference is made to clinical signs of disease, in vitro and in vivo studies, and evidence of genetic variation in host response to the disease. It is concluded that although clinical signs are numerous, and in vitro and in vivo studies often fail to yield comparable results, there is sufficient evidence of genetic variation in host responses to infection to examine the possibility of breeding for enhanced resistance or tolerance. Advances in genomics have allowed examination of changes in gene expression in response to infection to be examined in tandem with genomewide linkage disequilibrium scans. These advances could allow the possibility for commercial breeding programs to be established, selecting for PRRS resistance or tolerance. When breeding for resistance to one disease, such as PRRS, it could be postulated that the viral control mechanism being exploited could have beneficial effects on resistance to other viral diseases in pigs if, for example, the mechanisms act on primary immune pathways associated with viral replication. Conversely, however, selection for disease resistance could facilitate an increase in susceptibility to other diseases or a reduction in overall productivity. Extensive data recording may be required to guard against such possibilities. Overall, breeding for disease control in pigs is an underutilized tool that could have desirable long-term effects in breeding programs. More research is needed to examine the possible pathways of PRRS resistance so that viable control methods can be found to ease the disease burden and thus increase animal welfare and economic viability.
- Published
- 2007
- Full Text
- View/download PDF
97. QTL modulating ear size and erectness in pigs.
- Author
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Wei WH, de Koning DJ, Penman JC, Finlayson HA, Archibald AL, and Haley CS
- Subjects
- Animals, Chromosome Mapping, Crosses, Genetic, Ear physiology, Genomics methods, Organ Size, Ear anatomy & histology, Quantitative Trait Loci, Sus scrofa genetics
- Abstract
Ear size and erectness are important conformation measurements in pigs. An F(2) population established by crossing European Large White (small, erect ears) with Chinese Meishan (large, flop ears) was used to study the genetic influence of the two ear traits for the first time. A linkage map incorporating 152 markers on 18 autosomal chromosomes was utilised in a genome scan for QTL. Significant QTL were found on SSC1, 5, 7, 9 and 12 for the two traits. The QTL on SSC5 and SSC7 had major effects and were significant at the genome-wide level (P < 0.01). The QTL on SSC1 for ear erectness also had a major effect and was genome-wide significant (P < 0.01). The 95% confidence interval (CI) of the ear size QTL on SSC5 spanned only 4 cM. The QTL on SSC7 for the two ear traits each had a CI of <20 cM, and their positions overlapped with those of the major QTL affecting subcutaneous fat depths on the same chromosome. This study provides insights on the complex genetic influences underlying pig ear traits and will facilitate positional candidate gene analysis to identify causative DNA variants.
- Published
- 2007
- Full Text
- View/download PDF
98. Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated Swine alveolar macrophages.
- Author
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Ait-Ali T, Wilson AD, Westcott DG, Clapperton M, Waterfall M, Mellencamp MA, Drew TW, Bishop SC, and Archibald AL
- Subjects
- Animals, Bronchoalveolar Lavage Fluid cytology, Immunity, Innate, Interleukin-8 genetics, Porcine respiratory and reproductive syndrome virus physiology, RNA, Messenger analysis, Receptors, Virus analysis, Swine, Tumor Necrosis Factor-alpha genetics, Macrophages, Alveolar virology, Porcine respiratory and reproductive syndrome virus immunology, Virus Replication
- Abstract
Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by a positive RNA strand arterivirus. PRRS virus (PRRSV) interacts primarily with lung macrophages. Identifying the genetic components involved in host resistance/susceptibility would represent an important step forward in the design of disease control programs. In this study, alveolar macrophages derived from five commercial pig lines were used to study the innate immune response to PRRSV infection in vitro. Analysis by flow cytometry has demonstrated that bronchial alveolar lavage fluid (BALF) preparations were almost exclusively composed of alveolar macrophages and that the pigs tested were free from infection. Macrophages from the Landrace line showed significantly reduced virus replication and poor growth of PRRSV during 30 h of infection. By 72 h, PRRSV viral load was down to 2.5 log(10) TCID(50) compared with an average of 5 log(10) TCID(50) for the other breeds tested. These observations suggest that factors intrinsic to the Landrace breed may be responsible for this reduced or delayed response to PRRSV. Preliminary investigation suggests that the PRRSV coreceptor, sialoadhesin, may not be responsible for the Landrace macrophage phenotype as its abundance and localisation were comparable in all the breeds. Strikingly, we found that the reduced or delayed growth of PRRSV was temporally associated with high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-8 mRNA accumulation and substantial reduction of secretion of IL-8, suggesting a key contributory role for cytokine synthesis and secretion during the innate immune response to PRRSV infection.
- Published
- 2007
- Full Text
- View/download PDF
99. A polymorphism in the 5'-untranslated region of the porcine cholecystokinin type a receptor gene affects feed intake and growth.
- Author
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Houston RD, Haley CS, Archibald AL, Cameron ND, Plastow GS, and Rance KA
- Subjects
- Alleles, Animals, Base Sequence, Female, Gene Frequency, Male, Molecular Sequence Data, Selection, Genetic, Sus scrofa, 5' Untranslated Regions, Eating genetics, Growth genetics, Polymorphism, Genetic, Receptor, Cholecystokinin A genetics
- Abstract
The location and utilization of quantitative trait loci (QTL) and candidate genes with significant effects on economically important traits are becoming increasingly important in livestock breeding programs. The porcine cholecystokinin type A receptor (CCKAR) is a candidate gene for performance traits, due to its known role in the physiological control of feed intake, satiety, and obesity. We investigated the association of CCKAR polymorphisms with feeding, growth, and efficiency traits in an F2 population derived from a cross between Meishan and Large White founder animals and in lines of Large White pigs that had been divergently selected on the basis of lean growth efficiency traits. In the F2 population, CCKAR genotype was significantly associated with daily feed intake and average daily gain. The effects of the polymorphisms were then assessed in a larger-scale analysis of segregating commercial lines. A newly discovered single-nucleotide polymorphism (SNP) within the 5'-untranslated region (5'-UTR) had highly significant effects on feed intake, average daily gain, and days to 110 kg, which were not seen for a previously reported SNP within the CCKAR gene. Furthermore, we provide evidence that the novel SNP disrupts the binding of the YY1 transcription factor, which raises the possibility that it is the causal variant. The 5'-UTR SNP could be utilized as a molecular genetic test for increased feed intake, faster lean growth, and reduced days to market weight in segregating commercial lines.
- Published
- 2006
- Full Text
- View/download PDF
100. Assessment of SULT1A1, CYP2A6 and CYP2C18 as candidate genes for elevated backfat skatole levels in commercial and experimental pig populations.
- Author
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Skinner TM, Anderson JA, Haley CS, and Archibald AL
- Subjects
- Alleles, Animals, Body Composition genetics, Chromosome Mapping, Cytochrome P-450 CYP2A6, Genetic Linkage, Genetic Markers, Genotype, Microsatellite Repeats, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Swine anatomy & histology, Swine metabolism, Adipose Tissue metabolism, Aryl Hydrocarbon Hydroxylases genetics, Arylsulfotransferase genetics, Mixed Function Oxygenases genetics, Skatole metabolism, Swine genetics
- Published
- 2006
- Full Text
- View/download PDF
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