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52. Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds

Author

European Commission, Naval-Sánchez, Marina, Nguyen, Quan, McWilliam, Sean, Porto-Neto, Laercio, Tellam, Ross, Vuocolo, Tony, Reverter, Antonio, Pérez-Enciso, Miguel, Brauning, Rudiger, Clarke, Shannon, McCulloch, Alan, Zamani, Wahid, Naderi, Saeid, Reza Rezaei, Hamid, Pompanon, François, Taberlet, Pierre, Worley, Kim C., Gibbs, Richard A., Muzny, Donna, Jhangiani, Shalini N., Cockett, Noelle, Daetwyler, Hans, Kijas, James, European Commission, Naval-Sánchez, Marina, Nguyen, Quan, McWilliam, Sean, Porto-Neto, Laercio, Tellam, Ross, Vuocolo, Tony, Reverter, Antonio, Pérez-Enciso, Miguel, Brauning, Rudiger, Clarke, Shannon, McCulloch, Alan, Zamani, Wahid, Naderi, Saeid, Reza Rezaei, Hamid, Pompanon, François, Taberlet, Pierre, Worley, Kim C., Gibbs, Richard A., Muzny, Donna, Jhangiani, Shalini N., Cockett, Noelle, Daetwyler, Hans, and Kijas, James

Abstract

Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species.

Published
2018

54. Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds

Author

Naval-Sanchez, Marina, primary, Nguyen, Quan, additional, McWilliam, Sean, additional, Porto-Neto, Laercio R., additional, Tellam, Ross, additional, Vuocolo, Tony, additional, Reverter, Antonio, additional, Perez-Enciso, Miguel, additional, Brauning, Rudiger, additional, Clarke, Shannon, additional, McCulloch, Alan, additional, Zamani, Wahid, additional, Naderi, Saeid, additional, Rezaei, Hamid Reza, additional, Pompanon, Francois, additional, Taberlet, Pierre, additional, Worley, Kim C., additional, Gibbs, Richard A., additional, Muzny, Donna M., additional, Jhangiani, Shalini N., additional, Cockett, Noelle, additional, Daetwyler, Hans, additional, and Kijas, James, additional

Published
2018
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59. Additional file 2: Table S2. of Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight

Author

Hawlader Al-Mamun, Kwan, Paul, Clark, Samuel, Ferdosi, Mohammad, Tellam, Ross, and Gondro, Cedric

Abstract

The 39 SNPs that have a significant association with body weight in 1743 Merino sheep. This table presents the chromosomal positions of 39 genome-wide significant SNPs with MAF, P-values as well as the proportion of genetic variance and allele substitution effects that can be attributed to each SNP. (DOCX 23 kb)

Published
2015
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60. Additional file 3: Table S3. of Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight

Author

Hawlader Al-Mamun, Kwan, Paul, Clark, Samuel, Ferdosi, Mohammad, Tellam, Ross, and Gondro, Cedric

Abstract

Percentages of genetic variance explained by each chromosome. This table presents the percentages of genetic variance explained by each chromosome obtained by fitting all chromosomes simultaneously in the GCTA software. (DOCX 19 kb)

Published
2015
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63. Identification of genes directly responding to <italic>DLK1</italic> signaling in Callipyge sheep.

Author

Yu, Hui, Waddell, Jolena N., Kuang, Shihuan, Tellam, Ross L., Cockett, Noelle E., and Bidwell, Christopher A.

Subjects
GENES, FOOD animals, MUSCLE growth, MUSCULAR hypertrophy, LUCIFERASES, MYOBLASTS
Abstract

Background: In food animal agriculture, there is a need to identify the mechanisms that can improve the efficiency of muscle growth and protein accretion. Callipyge sheep provide excellent machinery since the up-regulation of DLK1 and RTL1 results in extreme postnatal muscle hypertrophy in distinct muscles. The aim of this study is to distinguish the genes that directly respond to DLK1 and RTL1 signaling from the genes that change as the result of muscle specific effects. Results: The quantitative PCR results indicated that DLK1 expression was significantly increased in hypertrophied muscles but not in non-hypertrophied muscles. However, RTL1 was up-regulated in both hypertrophied and non-hypertrophied muscles. Five genes, including PARK7, DNTTIP1, SLC22A3, METTL21E and PDE4D, were consistently co-expressed with DLK1, and therefore were possible transcriptional target genes responding to DLK1 signaling. Treatment of myoblast and myotubes with DLK1 protein induced an average of 1.6-fold and 1.4-fold increase in Dnttip1 and Pde4d expression respectively. Myh4 expression was significantly elevated in DLK1-treated myotubes, whereas the expression of Mettl21e was significantly increased in the DLK1-treated myoblasts but reduced in DLK1-treated myotubes. DLK1 treatment had no impact on Park7 expression. In addition, Park7 and Dnttip1 increased Myh4 and decreased Myh7 promoter activity, resemble to the effects of Dlk1. In contrast, expression of Mettl21e increased Myh7 and decreased Myh4 luciferase activity. Conclusion: The study provided additional supports that RTL1 alone was insufficient to induce muscle hypertrophy and concluded that DLK1 was likely the primary effector of the hypertrophy phenotype. The results also suggested that DNTTIP1 and PDE4D were secondary effector genes responding to DLK1 signaling resulting in muscle fiber switch and muscular hypertrophy in callipyge lamb. [ABSTRACT FROM AUTHOR]

Published
2018
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69. The Imprinted Retrotransposon-Like Gene PEG11 (RTL1) Is Expressed as a Full-Length Protein in Skeletal Muscle from Callipyge Sheep

Author

Byrne, Keren, Colgrave, Michelle, Vuocolo, Tony, Pearson, Roger, Bidwell, Christopher, Cockett , Noelle, Lynn, David, Fleming-Waddell, Jolena, and Tellam, Ross

Abstract

Members of the Ty3-Gypsy retrotransposon family are rare in mammalian genomes despite their abundance in invertebrates and some vertebrates. These elements contain a gag-pol-like structure characteristic of retroviruses but have lost their ability to retrotranspose into the mammalian genome and are thought to be inactive relics of ancient retrotransposition events. One of these retrotransposon-like elements, PEG11 (also called RTL1) is located at the distal end of ovine chromosome 18 within an imprinted gene cluster that is highly conserved in placental mammals. The region contains several conserved imprinted genes including BEGAIN, DLK1, DAT, GTL2 (MEG3), PEG11 (RTL1), PEG11as, MEG8, MIRG and DIO3. An intergenic point mutation between DLK1 and GTL2 causes muscle hypertrophy in callipyge sheep and is associated with large changes in expression of the genes linked in cis between DLK1 and MEG8. It has been suggested that over-expression of DLK1 is the effector of the callipyge phenotype; however, PEG11 gene expression is also strongly correlated with the emergence of the muscling phenotype as a function of genotype, muscle type and developmental stage. To date, there has been no direct evidence that PEG11 encodes a protein, especially as its anti-sense transcript (PEG11as) contains six miRNA that cause cleavage of the PEG11 transcript. Using immunological and mass spectrometry approaches we have directly identified the full-length PEG11 protein from postnatal nuclear preparations of callipyge skeletal muscle and conclude that its over-expression may be involved in inducing muscle hypertrophy. The developmental expression pattern of the PEG11 gene is consistent with the callipyge mutation causing recapitulation of the normal fetal-like gene expression program during postnatal development. Analysis of the PEG11 sequence indicates strong conservation of the regions encoding the antisense microRNA and in at least two cases these correspond with structural or functional domains of the protein suggesting co-evolution of the sense and antisense genes.

Published
2010

72. Genetic architecture of gene expression in ovine skeletal muscle

Author

Kogelman, Lisette Johanna Antonia, Byrne, Keren, Vuocolo, Tony, Watson-Haigh, Nathan S., Kadarmideen, Haja, Kijas, James W., Oddy, Hutton V., Gardiner, Graham E., Gondro, Cedric, Tellam, Ross L., Kogelman, Lisette Johanna Antonia, Byrne, Keren, Vuocolo, Tony, Watson-Haigh, Nathan S., Kadarmideen, Haja, Kijas, James W., Oddy, Hutton V., Gardiner, Graham E., Gondro, Cedric, and Tellam, Ross L.

Abstract

Background: In livestock populations the genetic contribution to muscling is intensively monitored in the progeny of industry sires and used as a tool in selective breeding programs. The genes and pathways conferring this genetic merit are largely undefined. Genetic variation within a population has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle.Results: The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing and expressed as an Estimated Breeding Value by comparison with contemporary sires. Microarray gene expression data were obtained for longissimus lumborum samples taken from forty progeny of the six sires (4-8 progeny/sire). Initial unsupervised hierarchical clustering analysis revealed strong genetic architecture to the gene expression data, which also discriminated the sire-based Estimated Breeding Value for the trait. An integrated systems biology approach was then used to identify the major functional pathways contributing to the genetics of enhanced muscling by using both Estimated Breeding Value weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing, mitochondrial function and transcriptional regulation.Conclusions: This study has revealed strong genetic structure in the gene expression program within ovine longissimus lumborum m

Published
2011

73. The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

Author

Elsik, Christine, Elsik, Christine G, Tellam, Ross L., Worley, Kim C., Gibbs, Richard A., Muzny, Donna M., Weinstock, George M., Adelson, David L., Eichler, Evan E., Elnitski, Laura, Guigó, Roderic, Hamernik, Debora L., Kappes, Steve M., Lewin, Harris A., Lynn, David J., Nicholas, Frank W., Reymond, Alexandre, Rijnkels, Monique, Skow, Loren C., Zdobnov, Evgeny M, Schook, Lawrence, Womack, James, Alioto, Tyler, Antonarakis, Stylianos E., Astashyn, Alex, Chapple, Charles E., Chen, Hsui-Chuan, Chrast, Jacqueline, Câmara, Francisco, Waardenberg, Ashley, Al, et, Elsik, Christine, Elsik, Christine G, Tellam, Ross L., Worley, Kim C., Gibbs, Richard A., Muzny, Donna M., Weinstock, George M., Adelson, David L., Eichler, Evan E., Elnitski, Laura, Guigó, Roderic, Hamernik, Debora L., Kappes, Steve M., Lewin, Harris A., Lynn, David J., Nicholas, Frank W., Reymond, Alexandre, Rijnkels, Monique, Skow, Loren C., Zdobnov, Evgeny M, Schook, Lawrence, Womack, James, Alioto, Tyler, Antonarakis, Stylianos E., Astashyn, Alex, Chapple, Charles E., Chen, Hsui-Chuan, Chrast, Jacqueline, Câmara, Francisco, Waardenberg, Ashley, and Al, et

Abstract

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production., Yes.

Published
2009

83. Unlocking the bovine genome

Author

Tellam, Ross L, primary, Lemay, Danielle G, additional, Van Tassell, Curtis P, additional, Lewin, Harris A, additional, Worley, Kim C, additional, and Elsik, Christine G, additional

Published
2009
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88. A physical map of the bovine genome

Author

Snelling, Warren M, primary, Chiu, Readman, additional, Schein, Jacqueline E, additional, Hobbs, Matthew, additional, Abbey, Colette A, additional, Adelson, David L, additional, Aerts, Jan, additional, Bennett, Gary L, additional, Bosdet, Ian E, additional, Boussaha, Mekki, additional, Brauning, Rudiger, additional, Caetano, Alexandre R, additional, Costa, Marcos M, additional, Crawford, Allan M, additional, Dalrymple, Brian P, additional, Eggen, André, additional, Everts-van der Wind, Annelie, additional, Floriot, Sandrine, additional, Gautier, Mathieu, additional, Gill, Clare A, additional, Green, Ronnie D, additional, Holt, Robert, additional, Jann, Oliver, additional, Jones, Steven JM, additional, Kappes, Steven M, additional, Keele, John W, additional, de Jong, Pieter J, additional, Larkin, Denis M, additional, Lewin, Harris A, additional, McEwan, John C, additional, McKay, Stephanie, additional, Marra, Marco A, additional, Mathewson, Carrie A, additional, Matukumalli, Lakshmi K, additional, Moore, Stephen S, additional, Murdoch, Brenda, additional, Nicholas, Frank W, additional, Osoegawa, Kazutoyo, additional, Roy, Alice, additional, Salih, Hanni, additional, Schibler, Laurent, additional, Schnabel, Robert D, additional, Silveri, Licia, additional, Skow, Loren C, additional, Smith, Timothy PL, additional, Sonstegard, Tad S, additional, Taylor, Jeremy F, additional, Tellam, Ross, additional, Van Tassell, Curtis P, additional, Williams, John L, additional, Womack, James E, additional, Wye, Natasja H, additional, Yang, George, additional, and Zhao, Shaying, additional

Published
2007
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91. Insect chitin synthase

Author

Tellam, Ross L., primary, Vuocolo, Tony, additional, Johnson, Samuel E., additional, Jarmey, Janine, additional, and Pearson, Roger D., additional

Published
2000
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92. mRNA Structural Constraints on EBNA1 Synthesis Impact on In Vivo Antigen Presentation and Early Priming of CD8+ T Cells.

Author

Tellam, Judy T., Zhong, Jie, Lekieffre, Lea, Bhat, Purnima, Martinez, Michelle, Croft, Nathan P., Kaplan, Warren, Tellam, Ross L., and Khanna, Rajiv

Subjects
MESSENGER RNA, ANTIGENS, CD8 antigen, T cells
Abstract

Recent studies have shown that virally encoded mRNA sequences of genome maintenance proteins from herpesviruses contain clusters of unusual structural elements, G-quadruplexes, which modulate viral protein synthesis. Destabilization of these G-quadruplexes can override the inhibitory effect on self-synthesis of these proteins. Here we show that the purine-rich repetitive mRNA sequence of Epstein-Barr virus encoded nuclear antigen 1 (EBNA1) comprising G-quadruplex structures, limits both the presentation of MHC class I-restricted CD8+ T cell epitopes by CD11c+ dendritic cells in draining lymph nodes and early priming of antigen-specific CD8+ T-cells. Destabilization of the G-quadruplex structures through codon-modification significantly enhanced in vivo antigen presentation and activation of virus-specific T cells. Ex vivo imaging of draining lymph nodes by confocal microscopy revealed enhanced antigen-specific T-cell trafficking and APC-CD8+ T-cell interactions in mice primed with viral vectors encoding a codon-modified EBNA1 protein. More importantly, these antigen-specific T cells displayed enhanced expression of the T-box transcription factor and superior polyfunctionality consistent with the qualitative impact of translation efficiency. These results provide an important insight into how viruses exploit mRNA structure to down regulate synthesis of their viral maintenance proteins and delay priming of antigen-specific T cells, thereby establishing a successful latent infection in vivo. Furthermore, targeting EBNA1 mRNA rather than protein by small molecules or antisense oligonucleotides will enhance EBNA1 synthesis and the early priming of effector T cells, to establish a more rapid immune response and prevent persistent infection. [ABSTRACT FROM AUTHOR]

Published
2014
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96. An Always Correlated gene expression landscape for ovine skeletal muscle, lessons learnt from comparison with an "equivalent" bovine landscape.

Author

Wei Sun, Hudson, Nicholas J., Reverter, Antonio, Waardenberg, Ashley J., Tellam, Ross L., Vuocolo, Tony, Byrne, Keren, and Dalrymple, Brian P.

Subjects
GENE expression, GENETIC regulation, BIOSYNTHESIS, MOLECULAR genetics, PHENOTYPES, GENETICS
Abstract

Background: We have recently described a method for the construction of an informative gene expression correlation landscape for a single tissue, longissimus muscle (LM) of cattle, using a small number (less than a hundred) of diverse samples. Does this approach facilitate interspecies comparison of networks? Findings: Using gene expression datasets from LM samples from a single postnatal time point for high and low muscling sheep, and from a developmental time course (prenatal to postnatal) for normal sheep and sheep exhibiting the Callipyge muscling phenotype gene expression correlations were calculated across subsets of the data comparable to the bovine analysis. An "Always Correlated" gene expression landscape was constructed by integrating the correlations from the subsets of data and was compared to the equivalent landscape for bovine LM muscle. Whilst at the high level apparently equivalent modules were identified in the two species, at the detailed level overlap between genes in the equivalent modules was limited and generally not significant. Indeed, only 395 genes and 18 edges were in common between the two landscapes. Conclusions: Since it is unlikely that the equivalent muscles of two closely related species are as different as this analysis suggests, within tissue gene expression correlations appear to be very sensitive to the samples chosen for their construction, compounded by the different platforms used. Thus users need to be very cautious in interpretation of the differences. In future experiments, attention will be required to ensure equivalent experimental designs and use cross-species gene expression platform to enable the identification of true differences between different species. [ABSTRACT FROM AUTHOR]

Published
2012
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99. Lipids from Plasmodium vinckei-infected erythrocytes and their susceptibility to oxidative damage.

Author

Stocker, Roland, Cowden, William, Tellam, Ross, Weidemann, Maurice, and Hunt, Nicholas

Abstract

The constituent lipids of plasma and red blood cells (RBC) from mice late in infection with the malarial parasite Plasmodium vinckei were analyzed and compared with those obtained from uninfected animals. On a dry weight basis, the total extractable lipids of RBC increased three-fold during infection, while those of the plasma did not change significantly. In general, changes in individual plasma lipid constituents paralleled those found in RBC of infected mice but were of smaller magnitude. While the increase in the total lipids of parasitized RBC was largely attributable to an increase of more than fourfold in total phospholipids, a significant increase in neutral lipids was also observed. Phosphatidylcholine and phosphatidylethanolamine were the major phospholipids present within RBC, and their total and relative concentrations increased as a result of the infection. A parallel increase occurred in the ratio of unsaturated to saturated fatty acids in the parasitized RBC phospholipids. Infection was also associated with decreases in the relative amount of cholesterol present in RBC and in the ratio of cholesterol to phospholipid. Consistent with this, the fluorescence polarization of 1[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene within parasitized RBC plasma membranes was decreased in comparison with its value in noninfected RBC, indicating that malarial infection decreases the 'order' of membrane lipids. These modifications, in conjunction with the increased levels of vitamin E and malonyldialdehyde reported elsewhere, are important determinants of the susceptibility of the different membrane compartments within infected RBC to peroxidative damage. [ABSTRACT FROM AUTHOR]

Published
1987
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100. Intrauterine Growth Restriction and the Sex Specific Programming of Leptin and Peroxisome Proliferator-Activated Receptor ? (PPAR?) mRNA Expression in Visceral Fat in the Lamb

Author

Duffield, Jaime A, Vuocolo, Tony, Tellam, Ross, McFarlane, Jim R, Kauter, Kate G, Muhlhausler, Beverly S, and McMillen, I Caroline

Abstract

Being born small is associated with an increased risk of visceral obesity and insulin resistance in adult life. We have investigated the effect of IUGR on adipogenic and lipogenic gene expression in visceral fat in the lamb at 3 wk of age. Perirenal fat mass, but not adipocyte size was greater in females than males, independent of birth weight. Plasma insulin concentrations during the first 24 h after birth predicted the size of the adipocytes and expression of adiponectin in visceral adipose tissue in both males and females. In females, plasma nonesterified fatty acids (NEFA) concentrations during the first 24 h after birth were directly related to peroxisome proliferator-activated receptor ? (PPAR?) mRNA expression in the perirenal fat depot at 3 wk of age. In the males, in contrast to the females, PPAR? and leptin expression in perirenal visceral fat were significantly lower in IUGR compared with control lambs. Thus, the early nutritional environment programs adipocyte growth and gene expression in visceral adipose tissue. The differential effect of sex and IUGR on PPAR? and leptin expression in visceral fat may be important in the subsequent development of visceral obesity and the insulin resistant phenotype in later life.

Published
2009
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